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Volume 23, Number 7, December 2012

from the desk of group editor-in-chief 365 Meditation may Reduce Death, Heart Attack

and Stroke in Heart Patients

Dr Veena Aggarwal MD, Group Executive Editor

IJCP Editorial Board Obstetrics and Gynaecology Dr Alka Kriplani Dr Thankam Verma, Dr Kamala Selvaraj Cardiology Dr Praveen Chandra, Dr SK Parashar Paediatrics Dr Swati Y Bhave Dr Balraj Singh Yadav Dr Vishesh Kumar, Dr Satish Tiwari Diabetology Dr Vijay Viswanathan Dr CR Anand Moses, Dr Sidhartha Das Dr A Ramachandran, Dr Samith A Shetty

original article 366 Personality Characteristics in the Patients of

Obsessive Compulsive Disorder

Gastroenterology Dr Ajay Kumar Dermatology Dr Hasmukh J Shroff Nephrology Dr Georgi Abraham

373 Role of Cystone Tablet, a Polyherbal Formulation

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Meditation may Reduce Death, Heart Attack and Stroke in Heart Patients

411 Cyanosis in an Older Woman

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medilaw 413 What should a Private Hospital do when a Patient

Needs an Intervention Cardiac Procedure but does not Pay for it?

MC Gupta

Around the globe

wice-a-day transcendental meditation helped African Americans with heart disease reduce their risk of death, heart attack and stroke. Meditation helped patients lower their blood pressure, stress and anger compared with those who attended a health education class.

African Americans with heart disease who practiced transcendental meditation regularly were 48% less likely to have a heart attack and stroke or die from all causes compared with African Americans who attended a health education class over more than five years, according to new research published in the American Heart Association journal Circulation: Cardiovascular Quality and Outcomes.

Those practicing meditation also lowered their blood pressure and reported less stress and anger. And the more regularly patients meditated, the greater their survival, said researchers who conducted the study at the Medical College of Wisconsin in Milwaukee.

414 News and Views

The National Heart, Lung and Blood Institute funded the study. (Medline)

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365

original article

Original article

Personality Characteristics in the Patients of Obsessive Compulsive Disorder Krishan Kumar*, Gurpreet Kaur**, Brahmdeep Sindhu†, Rajneesh Kumar‡, Sachin¶

Abstract The relationship between obsessional personality traits and obsessive compulsive disorder (OCD) has long been the subject of debate. Although clinicians have asserted for nearly a hundred years that such a relationship exists, empirical investigations have failed to provide consistent support; however, none of these empirical investigations have undertaken analyses that control for the effect of mood variables. Employing a non-clinical sample, some psychologists found that when mood variables are taken into account, a unique relationship between obsessional traits and obsessional symptoms emerges. A replication was undertaken on a large group of individuals with OCD. After the effects of depression and anxiety were removed from a correlational analysis, obsessional symptoms were found to be significantly associated with obsessional and passive aggressive traits. OCD was not associated with any other grouping of traits as specified in the DSM-1II-R (Axis II) classification system.

Keywords: Obsessive compulsive disorder, mood variable, obsessional traits

he relationship between obsessive compulsive disorder (OCD) and various forms of the ‘obsessional personality’ has been under discussion for nearly a hundred years (Janet, 1903). Opinions vary with respect to the exact nature of this relationship. Traditionally, the presence of a premorbid obsessional personality was thought to favor the development of obsessional symptoms (Freud, 1908); however, more recently, it has been suggested that obsessional personality features may develop after the onset of OCD as part of a general coping response (Berg, Rapoport, Whitaker et al, 1989). Theoretically, a mixture of these positions is also possible, whereby specific traits potentiate the emergence of particular symptoms and vice-versa. There have been virtually only a few researches examining the mechanisms that govern the relationship between obsessional traits and symptoms. This is largely because investigations have failed to move beyond repeated and unsatisfactory attempts at confirming that such a relationship exists at all. *Clinical Psychologist, National Brain Research Centre, Manesar **Scientist C, DIPR, DRDO, New Delhi †Senior Psychiatrist, General Hospital, Gurgaon ‡Neurologist, Paras Hospital, Gurgaon ¶Research Scholar, University of Rajasthan, Jaipur Address for correspondence Dr Krishan Kumar Clinical Psychologist, National Brain Research Centre, Manesar, Gurgaon E-mail: keshusony@rediffmail.com

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Indian Journal of Clinical Practice, Vol. 23, No. 7, December 2012

The first detailed description of a personality type thought to favor the development of obsessive compulsive symptoms was provided by Janet (1903) in his ‘Les Obsession et La Psychaesthenie.’ The ‘psychasthenic state’ was characterized by a broad range of personality features, many of which still appear in its contemporary successor, obsessive compulsive personality disorder (American Psychiatric Association, 1994). The full complement of psychasthenic features included feelings of incompleteness, doubt, an inner sense of imperfection, a need for uniformity and order, pedantry, a restricted range of emotional experience, excessive cleanliness, poor thought control and a fondness for collecting things. Some five years after Janet’s publication, Freud (1908) also endorsed the distinction between an obsessional personality and obsessional symptoms. For Freud, an ‘obsessional neurosis’ was more likely to arise in an individual showing features of the ‘anal erotic character’, which marked the coincidence of three traits: Obstinacy, parsimony and orderliness. Although, the theoretical framework employed by Freud to explain the development of both the ‘anal erotic character’ and ‘obsessional neurosis’ is widely recognized as weak, all three features of the ‘anal erotic character’ have survived to be included in the diagnostic criteria for obsessive compulsive personality disorder (OCPD). In Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) (American

Psychiatric Association, 1994), OCPD is described as ‘A pervasive pattern of preoccupation with orderliness, perfectionism and mental and interpersonal control, at the expense of flexibility, openness and efficiency’. The diagnostic criteria employed are very similar to those used in International Classification of Diseases, 10th Revision (ICD-10) (World Health Organization, 1992) for the Anankastic personality. A meaningful distinction between OCPD and the Anankastic personality cannot be made, as both sets of criteria are clearly designed to capture the same clinical entity. Although, the obsessional personality has been accepted as a clinical reality (cf. Pollak, 1979), its relationship with OCD remains contentious. Some studies suggest that the relationship exists (Black, 1974), while others do not (Steketee, 1990). After reviewing the literature, Baer and Jenike (1992) concluded that the majority of patients with OCD have at least one personality disorder; however, OCPD is in the minority, often occurring less frequently than mixed, dependent, avoidant and histrionic types. This failure to find a consistent relationship between obsessional traits and symptoms is rather perplexing to clinicians, who, on the whole, have tended to favor the idea that OCD is associated with ‘a certain type’ of character, be that the ‘obstinate’ or ‘vacillating’ types described by Lewis (1936) or the person of ‘strict conscience’ described by Rachman and Hodgson (1980). Moreover, principle component analyses of items included in measures of OCD tend to yield trait like factors. For example, Cooper and Keileher (1973) conducted several such analyses on the Leyton Obsessional Inventory (LOI) (Cooper, 1970). Common to all analyses were three components or factors. Two of these reflected the cardinal features of OCD, namely, washing and checking; however, a third reflected a ‘feeling of incompleteness’. It is interesting to note that the incompleteness component of the LOI bears a strong resemblance to Janet’s (1903) ‘sentiment d’ incompletud’. Rosen and Tallis (1995) have suggested that previous investigations failed to find a specific relationship between OCPD and OCD because the effects of mood were not taken into account. Controlling for mood effects in the analysis of data is of great importance insofar as anxiety and depression may obscure the specific relationship between OCPD and OCD. Employing a non-clinical population, significant correlations were found between obsessional symptoms, as measured by the Maudsley Obsessional-Compulsive Inventory (MOCI), and 10 out of 13 personality disorders as measured by the Personality Diagnostic Questionnaire-

Revised (PDQ-R) (Hyler & Rieder, 1987); however, once the effects of anxiety and depression were removed from the analysis, only one significant relationship remained. This was between OCPD and OCD. The results reported by Rosen and Tallis (1995) appear to support the view that OCPD and OCD are positively related; however, the data were collected from a nonclinical population. It is possible that the method of analysis employed, although capable of yielding promising results on a non-clinical population, would not yield similar results when applied to a large clinical group. Aim To examine the association between obsessional traits and symptoms. METHOD

Sample Seventy-seven individuals suffering from OCD were taken for the present study. Fifty-one were female and 26 were male. All had volunteered their names for entry onto a research data base; initial inclusion on this database was determined if they had scored 11 or above on the MOCI (Hodgson & Rachman, 1977). A subsample of 46 respondents was randomly selected for interview. All but one met DSM-III-R criteria for OCD. This suggests that 98% of the subjects participating in the present study would meet DSM-III-R criteria for a diagnosis of OCD. The mean age of the 77 respondents was 39 (SD = 10.017). The minimum age was 18, while the maximum age was 66.

Instruments PDQ-R (Hyler & Rieder, 1987) is a 151-item, selfadministered, forced-choice; true/false diagnostic instrument measuring all DSM-III-R (American Psychiatric Association, 1987) Axis-II personality disorders and also includes the provisional diagnoses of sadistic and self-defeating personality disorders. It yields a global PDQ-R score indicating overall personality pathology in addition to giving individual threshold scores on each of the Axis-II criteria. Its criteria are identical to DSM-III-R, Axis-II. MOCI (Hodgson & Rachman, 1977) is a 30-item, selfadministered, forced-choice, true/false measure of obsessional symptoms. The MOCI yields a total, global obsessionality score in addition to scores on four subscales: Checking, washing, slowness and doubting. It is stable psychometrically tool (Hodgson & Rachman,

Indian Journal of Clinical Practice, Vol. 23, No. 7, December 2012

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Original article

Original article 1977) and has been used in a variety of studies to assess obsessional symptomatology in both clinical and nonclinical samples (e.g. Sher, Frost, Kushner, Crews & Alexander, 1989; Salkovskis & Harrison, 1984). Beck Depression Inventory (BDI) (Beck, Ward, Mendelson, Mock & Erbaugh, 1961) was included as a measure of depression. It consists of 84 self-evaluative statements grouped into 21 categories that assess the cognitive, motivational and physiological symptoms of depression based on a one-week time frame. For each item there is a graded series of four alternative statements ranging from neutral to a maximum level of severity. The items are scored from 0 to 3 so that the total BDI score range is from 0 to 63. High test-retest values have been reported (Beck et al., 1961) and it has been found to have high levels of internal consistency (e.g. Strober et al., 1981). Spielberger State Trait Anxiety Inventory (STAI): Trait Scale, Form Y (STAI-Y) (Spielberger, Goruch, Lushene, Vagg & Jacobs, 1980) was used as a measure of trait anxiety and consists of a 20-item self-report measure developed to assess the separate concepts of state and trait anxiety. These are scored on a 4-point scale of intensity ranging from ‘almost never’ to ‘almost always’. The trait items are expected to be relatively stable and free from the influence of situational stresses. STAI has been found to possess high internal consistency, and the trait form has demonstrated good test-retest reliability for intervals upto three months (Spielberger et al., 1980).

RESULTS

Table 3. MOCI and Personality Disorder Correlation Coefficients with BDI and STAI Partial Out

The means and standard deviations for the MOCI, MOCI subscales, the BDI and the STAI-Y are shown in Table 1. All are in ranges suggesting clinical status. Pearson’s correlation coefficients were calculated for the data. All tests were two-tailed. Given the statistical problems associated with analyses employing multiple correlations, only those relationships significant at p < 0.01 and p < 0.001 are reported. MOCI total scores were significantly correlated with PDQ-R total scores and scores for nine out of 13 personality disorders (antisocial, avoidant, borderline, histrionic, narcissistic, obsessive compulsive, passive aggressive, sadistic and self-defeating). The washing subscale was significantly correlated with PDQ-R total scores, and scores for borderline, histrionic, obsessive compulsive, passive aggressive and self-defeating personality traits. The doubting subscale was significantly correlated

Personality disorder

Table 1. Mean and Standard Deviations (in Parentheses) for the MOCI, MOCI Subscales, BDI and the STAI-Y MOCI

Total

14.13

(5.59)

Slowness

2.83

(1.34)

Washing

3.82

(2.74)

Doubting

4.57

(1.84)

4.69

(2.27)

BDI

Checking

17.39

(11.43)

STAI-Y

54.04

(12.85)

Table 2. MOCI and Personality Disorder Bivariate Correlation Coefficients Personality disorder

PDQ-R total

MOCI total

Slowness

Washing

Doubting

Checking

0.288*

0.066

0.152

0.321*

0.169

Antisocial

0.195

0.149

0.097

0.045

0.180

Avoidant

0.047

-0.195

0.102

0.093

-0.013

Borderline

0.227

0.156

0.136

0.179

0.135

Dependent

0.009

-0.004

0.055

0.075

-0.091

Histrionic

0.252

0.111

0.167

0.169

0.120

Narcissistic Obsessive compulsive Paranoid Passive aggressive

0.102

-0.109

0.054

0.067

0.102

0.320*

0.176

0.216

0.413**

0.170

0.042

-0.069

-0.049

0.032

0.165

0.302*

0.184

0.149

0.471**

0.155

Sadistic

0.153

-0.020

0.106

0.039

0.146

Schizoid

-0.162

-0.216

-0.101

0.032

-0.210

Schizotypal

0.109

0.003

-0.005

0.109

0.094

Self-defeating

0.202

0.098

0.060

0.307*

0.120

*P < 0.01, **P < 0.001

with PDQ-R total scores, and scores for avoidant, borderline, dependent, histrionic, narcissistic, obsessive compulsive, passive aggressive and selfdefeating personality traits. The checking subscale was significantly correlated with PDQ-R total scores, and scores for borderline, histrionic, narcissistic, obsessive compulsive, passive aggressive, sadistic and selfdefeating personality traits. All these relationships are shown in Table 2. When partial correlations were calculated, controlling for the effects of depression and anxiety (as measured by the BDI and the STAI-Y), most of these significant relationships disappeared. The MOCI total scores remained significantly correlated with PDQ-R total scores (r = 0.288, p < 0.01) and scores for obsessive compulsive (r = 0.320, p < 0.01) and passive aggressive personality traits (r = 0.302, p < 0.01) only. Doubting subscale scores remained significantly correlated with PDQ-R total scores (r = 0.321, p < 0.01) and scores for obsessive compulsive (r = 0.413, p < 0.01), passive aggressive (r = 0.471, p < 0.01) and self-defeating (r = 0.301, p < 0.01) personality traits. These relationships are shown in Table 3.

MOCI total

Slowness

Washing

Doubting

Checking

PDQ-R total

0.568**

0.144

0.316*

0.589**

0.409**

Antisocial

0.288*

0.148

0.158

0.191

0.259

Avoidant

0.341*

-0.081

0.241

0.375*

0.232

Borderline

0.464**

0.235

0.273*

0.415**

0.332*

Dependent

0.260

0.025

0.185

0.325*

0.108

Histrionic

0.446**

0.152

0.281*

0.401**

0.290*

Narcissistic

0.350*

-0.044

0.197

0.338*

0.275*

Obsessive compulsive

0.514**

0.192

0.330*

0.591**

0.348*

0.169

-0.031

0.168

0.235

DISCUSSION

Passive aggressive

0.491**

0.213

0.266*

0.611**

0.336*

Sadistic

0.317*

0.034

0.199

0.222

0.276*

Schizoid

0.108

-0.096

0.033

0.237

0.007

Schizotypal

0.258

0.062

0.258

0.243

0.220

0.477**

0.167

0.477**

0.552**

0.339*

The present study demonstrated that obsessional symptoms, as measured by the MOCI, are associated with a wide range of personality traits, as measured by the PDQ-R. Significant associations were found between the MOCI and traits subsumed under the following DSM-III-R Axis-II headings: Antisocial, avoidant, borderline, histrionic, narcissistic, obsessive

Paranoid

Self-defeating *P < 0.01, **P < 0.001

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Indian Journal of Clinical Practice, Vol. 23, No. 7, December 2012

compulsive, passive aggressive, sadistic and selfdefeating. When subsequent analyses were undertaken controlling for the effects of depression and anxiety, only two significant relationships were preserved. That is between the MOCI and obsessive compulsive personality traits and between the MOCI and passive aggressive personality traits. The doubting subscale of the MOCI accounted for much of the relationship observed between MOCI total and PDQ-R total scores. The doubting subscale was also significantly correlated with self-defeating personality traits after partialling out the effects of anxiety and depression. In an initial investigation employing a non-clinical population (Rosen & Tallis, 1995), the same method of analysis demonstrated a significant association between obsessional symptoms and obsessive compulsive personality traits only. This suggests that increasing severity of obsessional symptoms captures a specific association with passive aggressive characteristics. The relationship between obsessional symptoms and passive aggressive personality traits will be considered before the main findings of the present study are discussed in detail. It should be noted that Passive Aggressive Personality Disorder (PAPD) is no longer listed in the Axis-II section of the DSM-IV. Evidence in favor of the construct was considered insufficient to warrant inclusion as an official diagnostic category; however, PAPD may appear in future editions of the DSM under a new heading, i.e. ‘Negativistic Personality Disorder’. Given that PAPD has been excluded from the current DSM and that the

Indian Journal of Clinical Practice, Vol. 23, No. 7, December 2012

369

Original article

Original article PDQ-R was based on the DSM-III-R system, DSM-III-R will be used as a basis for the present discussion. PAPD is described as: “A pervasive pattern of passive resistance to demands for adequate social and occupational performance.” Although individual criteria show some overlap with obsessional traits and symptoms (e.g. procrastination and slowness), the overlap is no more significant than can be found in several other personality disorders. For example, sensitivity to criticism is found in Avoidant Personality Disorder (Beck, Freeman, Pretzer, Davis, Fleming, Ottaviani, Beck, Simon, Padesky, Meyer & Trexler, 1990) and is also strongly associated with compulsive checking (Rachman, 1976). Overlapping criteria may be less relevant than the beliefs that are shared by individuals with OCD and PAPD. Central beliefs associated with PAPD include: “Being controlled or dominated by others is intolerable”, “I have to do things my own way” and “it is best not to express my anger directly but to show my displeasure by not conforming” (Beck et al., 1990). These reflect several common features found in OCD, namely, preoccupation with control (McFall & Wollersheim, 1979), rigidity (Guidano & Liotti, 1983) and difficulty expressing anger (Rachman, 1993; Tallis, 1994). It is interesting that the inadequate occupational performance described in PAPD is also a feature of OCD. For example, Rachman (1993) suggests that avoidance of excessive responsibility in individuals with OCD often leads to underachievement at work. Although some beliefs associated with PAPD may be relevant to OCD, the passive aggressive style of social interaction may represent a coping response. As such, traits associated with PAPD may develop as a consequence of existing obsessional problems. Many patients with OCD suffer a unique conflict that arises between rigidity and difficulty expressing anger. If an individual with OCD insists that significant others participate in certain rituals and anger cannot be employed to overcome resistance, then alternative strategies to gain compliance must be adopted. A passive aggressive attitude may provide the means of encouraging collusion without violating the selfimposed prohibition of the expression of anger. Shafran, Ralph and Tallis (1995) found that 60% of relatives are involved to some extent with the rituals of an affected family member. This suggests that individuals with OCD are able to develop sophisticated and effective methods of manipulating those who share their domestic environment. The main finding of the present study suggests that obsessional traits and symptoms are associated,

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consistent with some observations recorded in the clinical literature; however, it should be noted that the relationship between OCD and OCPD appears to be largely attributable to scores on the doubting subscale of the MOCI. This has important implications with respect to how the concept of the obsessional personality is interpreted. There is certainly some overlap between the items included in the doubting subscale of the MOCI and the obsessional trait items included in the PDQ-R, particularly those that appear to reflect constructs such as perfectionism and moral sensitivity. Nevertheless, the vast majority of items do not overlap. There are no specific ‘doubt’ items included in the PDQ-R, and the doubting subscale of the MOCI does not include any specific items that reflect rigidity, dedication to work, indecisiveness and restricted range of affect, parsimony and difficulty discarding possessions. In addition, although it might be argued that the doubtrelated items on the MOCI reflect a trait, Hodgson and Rachman (1977) underscore the efforts made during the development of the instrument to exclude items that might reflect traits. As such, all of the subscales of the MOCI should be regarded as measures of symptoms or complaints. Conclusion The main finding from the present study suggests that a relationship exists between a subset of obsessive compulsive symptoms and the personality traits that constitute OCPD. The doubting subscale of the MOCI includes items such as ‘I have a strict conscience’, “I tend to get behind in my work because I repeat things over and over again”, and “I usually have serious doubts about the simple everyday things I do.” These suggest that the obsessional patient with OCPD traits is likely to exhibit a symptom cluster characterized by unwanted intrusive thoughts (particularly those that violate a strict moral code), repetition (particularly when accompanied by a sense of incompletion) and doubts about everyday actions. This is consistent with Rachman and Hodgson (1980), who, although questioning the validity of the obsessional personality, suggested that specific obsessional traits might be related to specific obsessional symptoms. It is relatively easy to see how moral sensitivity will result in much of the ‘stream of consciousness’ being regarded as unwanted or intrusive. Similarly, a trait such as perfectionism will more than likely produce symptoms that reflect concern over detail; however, it is unclear why obsessional traits such as restricted affect or parsimony should be related to doubts about everyday actions or ‘repeating’. It seems plausible

therefore, to suggest that the diagnostic criteria of OCPD conceal a set of core personality features that relate very closely to the symptom subset captured by the doubting subscale of the MOCI. This set of core personality features might form the basis of a reformulated obsessional personality type. Although there is insufficient evidence to infer all the elements of such a personality type, moral sensitivity could certainly be granted a central position. The determinants of moral sensitivity may be closely associated with elements of the obsessional belief system already under investigation, most notably, exaggerated responsibility, thought action fusion and extended personal influence (Salkovskis, 1985; Rachman, 1993; Tallis, 1995). If the core features of a reformulated obsessional personality could be understood in terms of underlying beliefs, then such beliefs might serve as legitimate targets for modification in therapy. As such, the treatment of patients exhibiting doubt related symptoms might routinely include specific ‘schema focused’ components. Suggested Reading 1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders III (3rd edition Review), American Psychiatric Association: Washington, DC, 1987. 2. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders IV (4th edition), American Psychiatric Association: Washington, DC, 1994. 3. Baer L, Jenike MA. Personality disorders in obsessive compulsive disorder. Psychiatr Clin North Am 1992;15(4):803-12. 4. Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J. An inventory for measuring depression. Arch Gen Psychiatry 1961;4:561-71. 5. Beck AT, Freeman A, Pretzer J, Davis D, Fleming B, Ottaviani R, et al. Cognitive Therapy of Personality Disorders. Guilford: New York, 1990. 6. Berg CZ, Rapoport JL, Whitaker A, Davies M, Leonard H, Swedo SE, et al. Childhood obsessive compulsive disorder: a two-year prospective follow-up of a community sample. J Am Acad Child Adolesc Psychiatry 1989;28(4):528-33. 7. Black A. The natural history of obsessional neurosis. In: Obsessional States. Beech HR (Ed.), Methuen: London 1974:p.1-23. 8. Cooper J. The Leyton obsessional inventory. Psychol Med 1970;1(1):48-64. 9. Cooper J, Kelleher M. The Leyton Obsessional Inventory: a principal components analysis on normal subjects. Psychol Med 1973;3(2):204-8. 10. Freud S. Character and anal eroticism. In: Collected Papers. 2. Hogarth: London,1908. 11. Guidano VL, Liotti G. Cognitive Processes and Emotional Disorders. Guilford: New York, 1983.

12. Hodgson RJ, Rachman S. Obsessional-compulsive complaints. Behav Res Ther 1977;15(5):389-95. 13. Hyler SE, Rieder RO. Personality Diagnostic Questionnaire-Revised (PDQ-R). New York State Psychiatric Institute: New York, NY, 1987. 14. Janet P. Les Obsessions et la Psychaesthenie. Paris: Alcan, 1903. 15. Lewis A. Problems of Obsessional Illness: (Section of Psychiatry). Proc R Soc Med 1936;29(4):325-36. 16. McFall ME, Wollersheim JP. Obsessive-compulsive neurosis: a cognitive-behavioural formulation and approach to treatment. Cogn Ther Res 1979;3(4):333-48. 17. Pollak JM. Obsessive-compulsive personality: a review. Psychol Bull 1979;86(2):225-41. 18. Rachman S. Obsessional-compulsive checking. Behav Res Ther 1976;14(4):269-77. 19. Rachman S. Obsessions, responsibility and guilt. Behav Res Ther 1993;31(2):149-54. 20. Rachman SJ, Hodgson R. Obsessions and Compulsions. Englewood Cliffs, NJ: Prentice-Hall. International: Hemel Hempstead, 1980. 21. Rosen KV, Tallis F. Investigation into the relationship between personality traits and OCD. Behav Res Ther 1995;33(4):445-50. 22. Salkovskis PM. Obsessional-compulsive problems: a cognitive-behavioural analysis. Behav Res Ther 1985;23(5):571-83. 23. Salkovskis PM, Harrison J. Abnormal and normal obsessions - a replication. Behav Res Ther 1984;22(5):54952. 24. Shafran R, Ralph J, Tallis F. Obsessive-compulsive symptoms and the family. Bull Menninger Clin. 1995;59(4):472-9. 25. Sher KJ, Frost RO, Kushner M, Crews TM, Alexander JE. Memory deficits in compulsive checkers: replication and extension in a clinical sample. Behav Res Ther 1989;27(1):65-9. 26. Spielberger CD, Goruch RL, Lushene R, Vagg PR, Jacobs GA. Manual for the State-Trait Anxiety Inventory. Consulting Psychologists Press: Palo Alto, CA, 1980. 27. Steketee GS. Personality trait and disorders in obsessive compulsives. J Anx Dis 1990;4:351-64. 28. Strober M, Green J, Carlson G. Utility of the Beck Depression Inventory with psychiatrically hospitalized adolescents. J Consult Clin Psychol 1981;49(3):482-3. 29. Tallis F. Obsessions, responsibility and guilt: two case reports suggesting a common and specific aetiology. Behav Res Ther 1994;32(1):143-5. 30. Tallis F. Obsessive Compulsive Disorder: A Cognitive and Neuropsychological Perspective. New York: Wiley, 1995. 31. Tallis F. Compulsive washing in the absence of phobic and illness anxiety. Behav Res Ther 1996;34(4):361-2. 32. World Health Organization. The ICD-IO Classification of Mental and Behavioural Disorders: Clinical Descriptions and Diagnostic Guidelines. World Health Organization: Geneva, 1992.

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Role of Cystone Tablet, a Polyherbal Formulation in Urinary Disorders MG Desai

Abstract Herbal remedies for the treatment of urinary disorders are rising owing to their safe and effective relief of the condition, particularly for urinary stones and urinary tract infections (UTIs). Cystone is one such effective herbal preparation used in wide range of urinary conditions with well-accepted and documented results over a period of time. The present article reviews literature and clinical data available on Cystone tablet evaluated in clinical trials. Various clinical trials were carried out to evaluate the efficacy and safety of Cystone tablet in conditions like urinary calculi, renal colic and UTIs. Selected eight clinical trials amongst 85 trials including one meta-analysis on the product have been reviewed with respect to their study design, results and conclusions. Study of Cystone on pediatric urolithiasis with special reference to calculogenesis inhibitors showed significance in calcium oxalate, triple phosphate stones and stones in upper urinary tract. Meta-analysis of 50 clinical studies revealed efficacy of Cystone with calculi clearance and symptomatic relief. Another study compared Cystone over other advocated methods for urinary calculi and confirmed excellent efficacy of Cystone. A study on 43 cases of various renal disorders showed its efficacy in providing symptomatic and biochemical improvement. In another study, 18 healthy persons and 115 radiologically proven stone formers were selected. Cystone effectively decreased the mucoprotein excretion and urinary output. Promising effects of Cystone tablet in UTI were summarized for two studies. The review of various clinical trials on Cystone suggests that it has proven safety, in urinary disorders. It is safe for long-term use and has no contraindications.

Keywords: Cystone, urolithiasis, urinary tract infection, review

idney stones often result from a combination of factors, rather than a single, well-defined cause. Stones are more common in people whose diet is very high in animal protein or who do not consume enough water or calcium.1 They can also result from an underlying metabolic condition, such as distal renal tubular acidosis,2 Dentâ&#x20AC;&#x2122;s disease,3 hyperparathyroidism,4 primary hyperoxaluria5 or medullary sponge kidney. In fact, studies show about 3-20% of people who form kidney stones have medullary sponge kidney.6,7 The exact cause depends on the type of stone.8 Urinary stones can be classified according to the following aspects: Stone size, stone location, X-ray characteristics of stone, etiology of stone formation and stone composition and risk group for recurrent stone formation.

Associate Professor, Dept. of Urology Dr BR Ambedkar Medical College Bangalore, Karnataka Address for correspondence Dr MG Desai E-mail: drmgdesai@hotmail.com

Calcium stones are most common. Calcium can combine with other substances, such as oxalate (the most common substance), phosphate or carbonate, to form the stone.9 Cysteine stones can form in people who have cystinuria. This disorder runs in families and can affect both men and women.10 Struvite stones are mostly found in women who have a urinary tract infection (UTI). These stones can grow very large and can block the kidney, ureter or bladder (KUB). Uric acid stones are more common in men than in women.11 They can occur with gout or chemotherapy. Other substances also can form stones, including the medications, acyclovir, indinavir and triamterene.12 Review of epidemiological surveys suggests that in developed countries the prevalence rate is 4-20%.13 The rate in developing countries could be higher owing to the less reporting tendency. In 3% of nonsymptomatic subjects, kidney stones were diagnosed by renal ultrasonography.14 Patients with renal stone disease usually present with characteristic loin pain, vomiting and sometimes fever. Patients may also be asymptomatic. The standard evaluation of a patient includes taking a detailed medical history and physical examination. The clinical

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diagnosis should be supported by an appropriate imaging procedure.

pass on its own, or it has obstructed the flow leading to hydronephrosis or renal atrophy.

The safe (no risk of radiation), reproducible and inexpensive method of urinary stone detection is ultrasonography. It can identify stones located in the calices, pelvis, pyeloureteric junction and vesicoureteric junction, as well as dilatation of the upper urinary tract. Other methods are KUB and a noncontrast-enhanced computed tomography (NCCT).

Numerous indigenous drugs are in use for centuries in Asian countries, including India, to dissolve urinary stones in situ, or to prevent the onset/recurrence of urolithiasis. Cystone, an herbal formulation, is being widely used in India and elsewhere in the treatment of renal calculi and various renal disorders.

Pathophysiology Increased concentration of calculogenic substances in urine, a seed crystal may form through the process of nucleation.6 Heterogeneous nucleation i.e., mounting on hard, surface proceeds more rapidly than homogeneous nucleation i.e., growing in liquid medium, because it requires less energy. Adhering to cells on the surface of a renal papilla, a seed crystal can grow and aggregate into an organized mass. Depending on the chemical composition of the crystal, the lithogenesis may proceed more rapidly when the urine pH is unusually high or low.15 Inhibitors of stone formation Citrate in the urine inhibits the nucleation, growth, and aggregation of calcium-containing crystals. Other endogenous inhibitors include calgranulin, TammHorsfall protein, glycosaminoglycans, uropontin (a form of osteopontin), nephrocalcin (an acidic glycoprotein), prothrombin F1 peptide and bikunin (uronic acid-rich protein). Though, their actions are not thoroughly elucidated, when these substances fall below their normal proportions, stones can from an aggregation of crystals.16 Calcium binds with available oxalate in the gastrointestinal tract, thereby preventing its absorption into the bloodstream, and reducing oxalate absorption decreases kidney stone risk in susceptible people.17 The preferred calcium supplement for people at risk of stone formation is calcium citrate because it helps to increase urinary citrate excretion.11 Calcium citrate supplements can be taken with meals if dietary calcium cannot be increased by other means. Treatment depends on the type of stone and the severity of the symptoms. Conventional medical management includes controlling pain along with specific medications like allopurinol, antibiotics, diuretics, phosphate solutions, etc. All of these have limitations and several toxic side effects. Surgical intervention is needed if the stone is too large to

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Pharmacological Actions and Principal Herbs in Cystone Tablet Each Cystone tablet contains potential herbs like Didymocarpus pedicellata, Saxifraga ligulata, Rubia cordifolia, Cyperus scariosus, Achyranthes aspera, Onosma bracteatum and Vernonia cinerea. Didymocarpus pedicellata: The leaves contain a number of chalcones, quinochalcones and flavones. The leaf is well-known for its antilithic, lithotriptic, nephroprotective and antibiotic activities and is used for stones in kidney and bladder.18 It has also been shown that extracts significantly and dose dependently protect against ferric nitriloacetate-mediated damage to lipids and DNA. Saxifraga ligulata (Syn: Bergenia ciliata/Bergenia ligulata): The dried rhizome is astringent, tonic and spasmolytic and is used in dysuria, and other urinary disorders. Its richness in mucilage may be helpful for its antiprotective activity. Alcoholic extract of the rhizome is antilithic; whereas, acetone extract shows central nervous system (CNS)-depressant and antiinflammatory activities.19 Leaves have lithotripsy activities.20 Rubia cordifolia: The roots are rich in anthraquinones and their glycosides; the most important are purpurin, munjistin. The root has blood purifier, astringent, diuretic and antiseptic activities.21 It has some antimicrobial activities; emodin and physcion are the most active constituents isolated.22 Cyperus scariosus: The essential oil from tuber of C. scarious contains sesquiterpine, cyperenone and shows antibacterial, anti-inflammatory activities.23 The plant has diuretic and astringent activities.24 Achyranthes aspera: The herb contains alkaloid achyranthine and is used in kidney stone, minor hemorrhage. It also promotes wound healing.25 Aqueous extract of the plant shows antimicrobial activity. The plant is used in various clinical trials due to its diuretic, antispasmodic and anti-allergic activities.26

Onosma bracteatum: The plant has cooling, astringent and diuretic activities and is used in conditions like dysuria and urethral discharge.27 The plant has demulcent activity and is used for the management of urinary bladder irritation.28 Vernonia cinerea: The plant is used to relieve the spasm, dysuria and strangury in bladder.29 It is used in mild hemorrhage due to styptic activity.30 Results indicate that the extracts could possess analgesic, antipyretic and anti-inflammatory properties.31 In order to evaluate the safety and efficacy of Cystone tablet, several clinical trials have been conducted. For this review, we have summarized 8 clinical trials, which evaluated the safety and efficacy of Cystone tablets in various urinary disorders. CLINICAL TRIAL 1

Effect of Cystone on Pediatric Urolithiasis with Special Reference to Urinary Excretion of Calculogenesis Inhibitors32 Material and Methods Inclusion criteria: Eighty-seven children, below 12 years of age, diagnosed with renal or bladder stones, with or without any demonstrable metabolic abnormality, attending the Children’s Surgical OPD of the All India Institute of Medical Sciences, New Delhi, were included in this study. A written informed consent was obtained from parents of all patients. Exclusion criteria: Children who developed any complication like severe pain, hematuria or obstruction requiring immediate surgery with stones, secondary to other developmental abnormalities (e.g., posterior urethral valves, extrophy bladder, etc.), presenting with pyonephrosis and those whose parents refused to give informed consent, were excluded from the study. Study procedures: All included patients were stratified by diagnoses (renal or bladder calculi) and from each strata, patients were randomized to receive Cystone or placebo. A computer generated random number allocation program did the randomization. A baseline history was obtained in order to determine the child’s eligibility for enrolment in the trial, to compare the study groups and to describe the study population. The baseline assessment included personal data, a description of symptoms and details of past medical history, after which all patients underwent a complete clinical examination. All children were investigated for routine hemogram and blood urea, serum creatinine, sodium, potassium, calcium and

phosphorus and uric acid levels. In all children, routine and microscopic urine examination was done, which was followed by urine culture for three consecutive days. Furthermore, all children were monitored for 24-hour urinary excretion of albumin, creatinine, calcium, phosphorus, citric acid and magnesium levels. All children also underwent abdominal radio imaging and ultrasound examination. Dynamic renal scintigraphy with radiotracer imaging technique-using Tc-99m DTPA (Tecnenitum-99m diethylentriamine pentaacetic acid) was done to rule out renal malfunction. All these investigations were repeated at 120 days. All patients received the same dosage of Cystone or placebo (2 tablets, twice-daily) for a period of four months. Results Eighty-seven patients were enrolled in the study (69 males and 18 females), four patients were excluded from the study and 15 patients were lost to follow-up. Both the drug and placebo groups were statistically comparable on the parameters of age, blood urea and serum creatinine and serum calcium. On starting Cystone, 60 of the 87 patients (70.6%) reported symptomatic relief. Disappearance of stones (dissolution or spontaneous passage) was noted in 11 patients and out of these, four had a past history of stone passage. In the remaining seven patients, the stone had disappeared. There was a statistically significant difference in the 24-hour urinary excretion of calcium and magnesium in pre-treatment and post-treatment levels between the drug and placebo groups in relation to ‘calcium oxalate and triple phosphate stones’ and ‘upper tract stones (renal, ureteric or both renal and vesicular stones)’. There were no recurrences and adverse events reported during the study period. Conclusion This study indicates that in pediatric urolithiasis, Cystone appears to be an effective and safe treatment for long-term use. It also appears that Cystone has a favorable effect on inhibition of calculogenesis and seems to prevent recurrence in pediatric urolithiasis. CLINICAL TRIAL 2

Role of Cystone Tablets in Ureteric Calculi and Urinary Tract Infections (E. coli)33 Material and Methods A clinical trial was undertaken on 10 patients of ureteric calculi with 1.5 cm calculi treated with Cystone tablets 2 t.i.d. for three months.

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clinical Review Twenty cases of UTI, having Escherichia coli infection, were divided into three groups. ÂÂ

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Group A: Seven patients were given Cystone tablets 2 t.i.d. for 10-12 days or till the infection cleared. Group B: Seven patients were given Cystone tablets 2 t.i.d. for 10 days and co-trimoxazole 2 b.i.d. for five days. Group C: Six patients received nitrofurantoin 1 t.i.d. for 10 days with co-trimoxazole 2 b.i.d. for five days.

The patients were given Cystone two tablets t.i.d. for three months. Results and Conclusion All the patients of ureteric calculi passed out calculi with Cystone. Six patients passed out calculi in 30 days and the remaining four cases passed out their calculi within three months of treatment. Out of seven patients in Group A (UTI) six recovered. In Group B, all the patients recovered, i.e., 100% result, whereas in Group C, out of six patients, five patients responded to this combination. No adverse effects were recorded. In this series Cystone proved promising results in 10 cases of ureteric calculi and in 20 cases of UTIs. None of the patients reported any toxic effects with Cystone therapy. CLINICAL TRIAL 3

Role of Cystone in Management of Urolithiasis34 Material and Methods Inclusion criteria: All published studies, which evaluated the role of Cystone in urolithiasis, were included in the meta-analysis irrespective of the study design, as most of these researches were carried out in India, when randomized clinical trials were not being commonly carried out. The meta-analysis includes clinical trials, which were either controlled studies or open clinical studies. There were no restrictions regarding sex, age or duration of disease. The outcome variables included measurement data on changes in clinical symptoms and signs, laboratory results and incidence of adverse events during/after treatment. Exclusion criteria: Experimental, Phase I and Phase II studies were excluded from the study population. Study procedure: Fifty clinical studies carried out

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clinical Review between 1954 and 2004, with Cystone tablets were analyzed in the meta-analysis. From each study, the demographic data of patients on entry was tabulated. The duration of treatment varied from two weeks to 2 years and in most of the studies, except in pediatric patients, Cystone was used in the dose of 2 tablets t.i.d. Changes in the clinical and biochemical parameters were taken into account in addition to the calculi size, location of the calculi, urine volume and urinary excretion of oxalate, uric acid and calcium. Studies that considered parameters like burning micturition, bacteuria and the presence or absence of pus cells in the urine of urolithiasis patients, were also taken into account. Results and Conclusion The meta-analysis analyzed 50 clinical trials, which involved 3,037 patients (Cystone: 1,837, Others: 1,200) of either sex. The age range of patients included in all studies is 1-72 years and the duration of treatment is two weeks to 2 years. In 636 patients, data was available regarding the calculi size and analysis of this data indicates that there was a significant decrease in presence of renal calculi and the calculi size decreased from 6.21 ± 4.24 mm to 0.57 ± 0.79 mm (p < 0.0067). In one of the studies, antispasmodic medications, forced diuresis and intravenous (IV) fluids were used in 50 patients, which also showed significant decrease in renal calculi. Based on the location, it appears that Cystone, though effective in renal, ureteric and vesicle calculi, shows better results in ureteric calculi as compared to other sites. The clinical response in ureteric calculi was 89.96%; whereas, in renal calculi it was 73%. The results also indicate that in renal calculi, 27% of the patients required interventional surgery as compared to only 10% of patients in case of ureteric calculi. The meta-analysis also indicates that Cystone improves urinary volume to a significant level in eight weeks. It significantly decreases oxaluria, uric acid and calcium in the urine. The analysis also indicates that Cystone brings about significant symptomatic relief, as compared to other treatment group, in burning micturition and also reduces bacteuria and pus cells in patients with UTI. The outcome of 50 clinical studies indicated that Cystone is useful in the management of urolithiasis as revealed by the clearance of calculi, symptomatic relief, increased urine volume and reduction in the stone forming constituents in urine with negligible adverse

effects. CLINICAL TRIAL 4

Controlled Trial in 100 Cases with Nephroureterolithiasis by Cystone: An Indigenous Drug and Other Advocated Methods35 Material and Methods Hundred cases of nephroureterolithiasis were divided into four equal groups of 25 cases each for the purpose of treatment and to evaluate the effectiveness of these four methods in the treatment of small renal calculi and ureteric calculi. ÂÂ Group I: Cases (25) were given tablet Cystone in the dosage of two tablets, t.i.d. These patients were encouraged to take plenty of fluids by mouth. ÂÂ Group II: Cases (25) were given tablet Cystone in the dosage of 2 tablets, t.i.d. These patients were put on forced diuresis (Fluids viz. 5% dextrose and dextrose saline and furosemide intermittently during this period). ÂÂ Group III: Cases (25) were given antispasmodics (oral antispasmodic tablets). ÂÂ Group IV: Cases (25) were put on antispasmodics. These patients were put on forced diuresis. Duration of treatment in all the groups is 2-6 months. The cases were followed-up for the period of one year and repeated X-rays were taken at intervals of four weeks. Results and Conclusion In Group I, 19 cases (76%) including 16 cases of ureteric calculus and three cases of small renal calculi showed good response to treatment with Cystone and thereby could avert an operation. In Group II, 20 cases (80%) showed good response and expelled the stones and five cases (20%) were put to surgery. In Group III, only five cases (20%) passed out the stones and 20 cases (80%) had to undergo surgery. In Group IV, only seven cases (28%) responded to the treatment and 18 cases (72%) had to undergo surgery. No adverse effects were observed in any of the cases. Of the four different methods tried in the treatment of nephroureterolithiasis, Cystone tablets gave excellent results (76%) as compared to other methods (20-28%). Clinical Trial 5

Clinical Trial of Cystone in Various Renal Disorders36 Material and Methods

Forty-three cases of various renal disorders were the subjects of this controlled study. They were divided in two groups. The control group consisted of 17 patients of renal disorders (6 renal failures, 4 acute nephritis, 4 nephrotic syndromes and 3 UTI) who were treated by conventional therapy. In the study group of 26 cases, Cystone was given in the dosage of 6-9 tablets/day in addition to conventional therapy in 22 cases (8 renal failure, 6 acute nephritis, 3 nephrotic syndrome and 5 UTI) while in the remaining four cases (1 nephrotic syndrome and 3 UTI), Cystone was the only drug administered in the dosage of 6-9 tablets/day. Eight cases of renal failure put on Cystone therapy in addition to conventional therapy, showed satisfactory symptomatic improvement in the form of a feeling of well-being and increased urine output. No increase in albuminuria was observed in the study group on Cystone but was observed in one case of Control group. Increase in blood urea level was observed in 25% cases of study group on Cystone as compared to 66% cases of control group. Some symptomatic or biochemical changes were observed in patients of nephrotic syndrome and acute nephritis on Cystone therapy over conventional therapy. Results and Conclusion Symptomatic improvement was observed in all cases of Cystone treated group and in three cases in control group. Gradual reduction was observed in number of pus cells in urine in control and Cystone-treated group as well as in cases treated with only Cystone, where no other antibiotics were administered. None of the patients developed any adverse effects. The result from the clinical trial has provided the proof of significant efficacy of Cystone tablet in renal disorders. It is a polyherbal formulation with proven safety, consisting of drugs having multipharmacological properties and hence can be safely used in renal disorders. CLINICAL TRIAL 6

Urinary Mucoprotein Excretion in Stone Formers and the Effect of an Indigenous Formulation on its Excretion37 Material and Methods Eighteen healthy persons and 115 radiologically proven stone formers were selected. The normal men took their routine diet and patients were given standard hospital

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clinical Review diet. In the stone forming group, urine samples were collected before and after Cystone therapy. Cystone was given at a dose of 2 tablets t.i.d. for conservative treatment to all patients. The patients were advised to report back for further check-ups after a specified period unless they developed any serious complication requiring urgent attention. Two 24-hour urine samples were collected from all the normal subjects and seven stone formers who came for checkups after 12 weeks. A single 24-hour urine sample was collected from the other 38 stone formers who came for follow-ups after 4 and 8 weeks. Results and Conclusion The mucoprotein excretion in normal subjects ranged from 21.45 to 112.8 mg/24 hours with a mean excretion of 59.01 ± 5.20 mg/24 hours. In stone formers, the excretion ranged from 24.2 to 399.0 mg/24 hours with a mean excretion of 103.53 ± 11.72 mg/24 hours. The excretion in stone formers was significantly higher than that in normal subjects (p < 0.05). No significant difference was observed in urinary output of the two groups. These observations suggest that mucoprotein might be one of the etiological factors in stone formation in the local population. Cystone therapy decreased the mucoprotein excretion from 79.15 ± 8.04 to 55.40 ± 7.49 mg/24 hours (p < 0.05). Urinary output increased but it was not statistically significant.

clinical Review Seven patients expelled the stones spontaneously within 4-8 weeks of Cystone therapy. Cystone reduced the excretion and enhanced the phosphate excretion in all patients except in one case. The drug reduced the excretion significantly. None of the patients developed any adverse effects.

cases (26.6%), good in 11 cases (36.6%) and fair in 11 cases (36.6%), recording an overall favorable response in all the 30 cases in the group. No adverse effects was observed in any of the cases.

This study shows the usefulness of Cystone in urolithiasis, though it needs to be confirmed in a larger series and other populations as well. No effect was seen on magnesium excretion. The drug was well-tolerated by all the patients in this study.

The review of various clinical trials on Cystone suggests that it has proven safety in urinary disorders. It is safe for long-term use and has no contraindications. Its efficacy is proven in urinary stones at different locations of urinary system, UTIs and other renal dysfunctions. Clinical efficacy was confirmed clinically as well as ultrasonographically. The efficacy can be attributed to the synergistic activity of the herbs in the formulation. Cystone has direct protective action as it changes the crystalloid-colloid ratio so that protective colloids are increased. Cystone acts on the mucin that binds the particles of the calculus together and facilitates flushing out of the disintegrating particles along with the flow of urine. Cystone helps by flushing the urinary passage by virtue of its diuretic action. It relaxes smooth muscles of the urinary tract thereby relieving spasms, thus helpful in renal colic and pain. Its ingredients are devoid of any toxicity, even when given regularly and for prolonged periods. Thus, it can be summarized that Cystone is a herbomineral formulation having antilithic and lithotriptic, pH renormalizing, diuretic, antimicrobial, anti-inflammatory, demulcent, spasmolytic, antioxidant and tonic actions, and therefore it is a safe, effective, practical and affordable therapeutic modality for renal disorders like renal stones, UTI and renal colic.

CLINICAL TRIAL 8

Cystone in Urinary Tract Infections39 Material and Methods One hundred patients with UTIs were selected. In some cases, only Cystone was used, while in others it was used along with sulfa group of drugs and/or antibiotics. The cases were divided into three groups as follows: ÂÂ

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CLINICAL TRIAL 7

Indigenous Drugs in Modern Medicine: A Study on Cystone38 Material and Methods Fifty-five patients suffering from urinary stone disease were selected for the Cystone trial. Twenty-nine patients underwent immediate surgery; whereas, the second group of 26 patients having smaller stones and not requiring surgical intervention, were given two tablets of Cystone, t.i.d. These stones were analyzed by Kemlet’s wet chemical analysis method. Urine culture and sensitivity, calcium, oxalic acid, uric acid, inorganic phosphorus, sodium and potassium levels and blood chemistry for creatinine, calcium, magnesium, inorganic phosphorous, uric acid and alkaline phosphatase were studied before and after 4-8 weeks of Cystone treatment. Results and Conclusion

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ÂÂ

Group I: This group consisted of 53 cases. They were put on Cystone tablets two tablets t.i.d. with multivitamins and alkaline mixture in some cases. Vitamin C was given in three cases. In one case benzylpenicillin was administered for gonococcal and syphilitic affection. Group II: There were 17 cases. They were put on Cystone, two tablets t.i.d. either preceded or followed by antibiotics or sulfaphenazole group of drugs. Group III: There were 30 cases in this group and Cystone tablets were not used but antibiotics and/ or sulfa + trimethoprim group of drugs were used for comparing the therapeutic results with other groups. There were two unconscious patients to whom crushed Cystone tablets were given through nasal tubes.

Treatment was given for a period of two months. Results and Conclusion In Group I, results were excellent in nine cases (17%), good in 18 cases (34%) and fair in 16 cases (30%). The overall favorable response to Cystone was, thus, 81%. In Group II on Cystone along with antibiotics and/or sulfa, the response was excellent in five cases (29%), good in 4 cases (24%) and fair in seven cases (41%). Thus, the overall response in the group was favorable in 16 out 17 cases (94%). In Group III, 30 cases were treated only with antibiotics and sulfas, after bacterial sensitivity tests. The results were excellent in eight

CONCLUSION

References 1. Varma G, Nair N, Salim A, Marickar YM. Investigations for recognizing urinary stone. Urol Res 2009;37(6):349-52. 2. Moe OW. Kidney stones: pathophysiology and medical management. Lancet 2006;367(9507):333-44. 3. Thakker RV. Pathogenesis of Dent’s disease and related syndromes of X-linked nephrolithiasis. Kidney Int 2000;57(3):787-93.

6. Reilly RF Jr. Nephrolithiasis. Chapter 13. Reilly RF Jr., Perazella MA (Eds.) 2005:p.192-207. 7. National Kidney and Urologic Diseases Information Clearinghouse (2008). “Medullary Sponge Kidney (NIH Publication No. 08–6235)”. Kidney & Urologic Diseases: A-Z list of Topics and Titles. Bethesda, Maryland: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Public Health Service, US Department of Health and Human Services. Retrieved 2011-07-27. 8. Miller NL, Evan AP, Lingeman JE. Pathogenesis of renal calculi. Urol Clin North Am 2007;34(3):295-313. 9. Curhan GC. Nephrolithiasis. In: Cecil Medicine. 24th edition, Goldman L, Schafer AI, (Eds.), Saunders Elsevier: Philadelphia, PA 2011:chap.128. 10. Cameron MA, Sakhaee K. Uric acid nephrolithiasis. Urol Clin North Am 2007;34(3):335-46. 11. Finkielstein VA, Goldfarb DS. Strategies for preventing calcium oxalate stones. CMAJ 2006;174(10):1407-9. 12. Trinchieri A. Epidemiology of urolithiasis. Arch Ital Urol Androl 1996;68(4):203-49. 13. Buchholz NP, Abbas F, Afzal M, Khan R, Rizvi I, Talati J. The prevalence of silent kidney stones - an ultrasonographic screening study. J Pak Med Assoc 2003;53(1):24-5. 14. Pietrow PK, Preminger GM. Evaluation and medical management of urinary lithiasis. In: Campbell-Walsh Urology. 9th edition. Wein AJ, (Ed.), Saunders Elsevier: Philadelphia, PA 2007:chap 43. 15. Perazella MA. Urinalysis. Chapter 14. Reilly RF Jr., Perazella MA (Eds.) 2005:p.209-26. 16. Coe FL, Evan A, Worcester E. Kidney stone disease. J Clin Invest 2005;115(10):2598-608. 17. Heaney RP. Nutrition and chronic disease. Mayo Clin Proc 2006;81(3):297-9. 18. Singh AP. Didymocarpus pedicellata: the lithontriptic ethnomedicine. Short review. Ethnobotanical Leaflets 2007;11:73-5. 19. Asolkar LV, et al. Second supplement to glossary of Indian Medicinal Plants with active principles. CSIR, Govt. of India: New Delhi 1992a:p.122. 20. Prasad KVSRG, Sujatha D, Bharathi K. Herbal drugs in urolithiasis - A review. Pharmacogon Rev 2007;1(1):175-9. 21. Deshkar N, et al. A compressive review of Rubia cordifolia Linn. Review Article. Pharmacogn Rev 2008;2(3):124-34.

4. National Endocrine and Metabolic Diseases Information Service (2006). “Hyperparathyroidism (NIH Publication No. 6–3425)”. Information about Endocrine and Metabolic Diseases: A-Z list of Topics and Titles. Bethesda, Maryland: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Public Health Service, US Department of Health and Human Services. Retrieved 2011-07-27.

22. Khare CP. Indian Medicinal Plants: An Illustrative Dictionary. Springer: New Delhi 2007b:p.559-60.

5. Hoppe B, Langman CB. A United States survey on diagnosis, treatment, and outcome of primary hyperoxaluria. Pediatr Nephrol 2003;18(10):986-91.

25. Asolkar LV, et al. Second supplement to glossary of Indian Medicinal Plants with active principles. CSIR. Govt. of India: New Delhi 1992c:p.15-6.

23. Asolkar LV, et al. Second supplement to glossary of Indian Medicinal Plants with active principles. CSIR. Govt. of India: New Delhi 1992b:p.255. 24. Chopra RN, Nayar SL, Chopra IC. Glossary of Indian Medicinal Plants. National Institute of Science & Communication. New Delhi. 4th Reprint 1996a:p.89.

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to urinary excretion of calculogenesis inhibitors. Medicine Update 2004;11(11):47-54.

27. Khare CP. Indian Medicinal Plants: An Illustrative Dictionary. Springer: New Delhi 2007c:p.448.

33. Singh D. Role of Cystone tablets in ureteric calculi and urinary tract infections (E. coli). Probe 1984;XXIII(2):82-3.

28. Chopra RN, Nayar SL, Chopra IC. Glossary of Indian Medicinal Plants. National Institute of Science & Communication. New Delhi. 4th Reprint 1996b:p.180-1.

34. Marya SKS, Singla S. Role of Cystone in management of ureteric calculi-controlled clinical study. Med Surg 1983: p.21-3.

29. Chopra RN, Nayar SL, Chopra IC. Glossary of Indian Medicinal Plants. National Institute of Science & Communication. New Delhi. 4th Reprint 1996c: p.254.

35. Misgar MS. Controlled trial in 100 cases with nephroureterolithiasis by Cystone - an indigenous drug and other advocated methods. Med Surg 1993:p.21.

30. Khare CP. Indian Medicinal Plants: An Illustrative Dictionary. Springer: New Delhi 2007:p.699. 31. Iwalewa EO, Iwalewa OJ, Adeboye JO. Analgesic, antipyretic, anti-inflammatory effects of methanol, chloroform and ether extracts of Vernonia cinerea less leaf. J Ethnopharmacol 2003;86(2-3):229-34. 32. Bhatnagar V, Agarwal S, Gupta SK, Kolhapure SA. Effect of Cystone on pediatric urolithiasis with special reference

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36. Sharma BM, Panagariya A, Jain K. Clinical trial of Cystone in various renal disorders. Probe 1982;XXI(11):257-60. 37. Singh PP, Rathore V, Gochar BL, Pendse AK. Urinary mucoprotein excretion in stone formers and the effect of an indigenous formulation on its excretion. Asian Med J 1985;28(4):261-5. 38. Singh PP, Goyal A, Kumawat JL, Pendse AK, Ghosh R, Srivastava AK. Indigenous drugs in modern medicine - a study on Cystone. Arch Med Pract 1983;2:43-8.

Clinical study

Incidence of Medication Errors in Tertiary Care Center P Elango*, T Martha Mary**, K Balaji Singh†, J Damodharan‡

Abstract Introduction: Our organization is Sri Ramachandra Medical Centre located in Porur, Chennai, India. Pharmacy and Therapeutic Committee (PATC) and Medication Safety Team are formed and working in the medical center. Objective: To screen and analyse medication errors to ensure safe medication. Methods: Medication safety nurses and clinical pharmacists were deployed in patient care areas and the medication processes were closely monitored. Medication errors were collected through adverse drug reaction form and the errors were reported to PATC for remedial action. To ensure safe medication more than 20 policies were been framed and implemented. Medication errors are considered as five quality indicators. They are medication errors, ADR, delay in dispensing the drugs (DD), number of stock critical medicine (SCM) and rate of antibiotic usage (AU). Prescription errors, transcription errors, dispensing errors and administration errors are brought under medication errors. We considered medication errors and its quality indicator from January 2009 to December 2011 (36 months) were analysed. Results: There were 2,411 medication errors in these 36 months for 79,733 discharges and the quality indicator initially increased due to more screening and decreased towards the end of the period of observation and was always within the bench mark of 5. Conclusions: These observations showed increased incidence of errors, which finally decreased due to better awareness and strict auditing and education to medication personnels. Our hospital has been recognized with Joint Commission International Accreditation.

Keywords: Prescription, transcription, dispensing and administration errors, quality indicators

ur organization is a tertiary care level multispecialty hospital located at No. 1. Ramachandra Nagar, Porur, Chennai, India. It was instituted in 1985. It is now a 1,000 bedded hospital. Pharmacy and Therapeutic Committee (PATC) was organized in 2004. Since then, PATC started monitoring medication errors and adverse drug reactions (ADR). A Medication Safety Team (MST) was constituted from 2008 comprising Medication Safety Nurse, clinical pharmacists under clinical pharmacologist and it has obtained Joint Commission International Accreditation.

*Associate Professor Clinical Pharmacologist and Medication Safety Coordinator **Medication Safety Nurse †Professor in Surgery and Chairman, PATC ‡Professor in Medicine and Medical Director, Sri Ramachandra Medical Centre Sri Ramachandra University, Pour, Chennai Address for correspondence Dr P Elango C4, Golden Jubilee Apartments 208, Anna Main Road KK Nagar, Chennai - 600 078 E-mail: drpelango@yahoo.com

OBJECTIVES To screen and analyze the medication errors and evaluate the cause of the errors to ensure safe medication. All the observations were reported to PATC for remedial action. BACKGROUND OF THE ANALYSIS

What are Medication Errors? A medication error is defined by Cohen as “any preventable event that may cause or lead to inappropriate medication use or patient harm or which has the risk of being administered in a manner different from the prescribed norms while the medication is in the control of the healthcare professional, patient and consumer.” This definition explains the errors in the whole medication process like inventory of the drugs, storage, dispensing and administration. Cohen believes that the “Five rights of safe medication use namely the right patient, right drug, right time, right dose and right route of administration.” He emphasizes that “finding out who was involved is less important than learning what went wrong, how and why.”1 All the doctors,

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clinical study nurses and managers of the hospital intend to provide the best service to the patients, but unfortunately some harm can be done to the patient, if any one of their who is involved in the treatment process is not fully commitment. Types of Errors Medication errors are broadly classified as intercepted errors and actual errors. ÂÂ

Intercepted errors: These are errors that are corrected and prevented before reaching the patient by Safety Medication Team.

ÂÂ

Actual errors: These errors are on the basis of whether the drugs reach the patient or not, or when the drugs are administered in a manner different from the prescribed norms.

Medication errors can occur at different levels of the process and are divided into errors that occur at the prescription level, transcription, dispensing and administration levels. Prescription errors occur if the prescription has the wrong identity of the patient, wrong drug, wrong dose, wrong route, wrong timings and frequency, wrong duration of administration.2 Prescription faults can be explained as medication errors, which are based on decisionmaking in writing prescription. This error is simply knowledge-based and can produce severe harm to the patients.2 The Institute of Medicine in United States (IOM) says that illegible hand writing can share 7,000 of 98,000 deaths and it is very important and one of the dangerous procedures in the medication process and lead to risky outcome.1 Medication errors can be due to knowledge-based mistakes like prescribing a drug irrelevant to the indication, due to rule-based mistakes like deviating from prescription rules, due to action-based slips like administering drugs in a manner different from prescribed format and memory-based lapses like prescribing drugs with inadequate interpretation of laboratory reports or using wrong brand names.2 Drug administration is mainly carried out by nurses. Nurses should be responsible in their core duty of medication and have good nursing skills. Medication errors involve all the departments of a hospital and not just only pharmacists and pharmacy and doctors. If proper facility is not provided for drugs, this will lead to improper storage, which is considered as a medication error. Therefore, proper care must be taken to maintain all the departments with high-degree of standard.3

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A medication error will produce therapeutic failure in treatment process producing iatrogenic injuries, which are experienced by all people in all countries and incur not only more expenditure but also increases more morbidity and mortality.4,5 In 1910, Richard Clark published the first study that looked at error rates in clinical diagnosis.6 Since then, several studies have looked at the problem of medication errors. Incidence rates of adverse drug events (ADEs) amongst adults admitted to the hospital have ranged from 2 to 7/100 admissions.7,8 Approximately, 28% of ADEs are related to medication errors and are, therefore, judged to be preventable.9

ÂÂ

International patient safety goals

The goals are as follows:

Medication error commonly occurs one in every 5 doses even in reputed hospitals when medication is given by skilled nurses. It constitutes about 7% harmful effects. The defective medication system varies from place to place though widely prevalent.10 Over a period of time, there has been a transition from an era where medical practice and its practitioners are revered to a time when doubt and fear is expressed and legal suits are pursued by aggrieved patients.11 Therefore, there is a need of standard practice of medicine not only to prevent medication errors but also to upgrade the medical personnels in their methodology of execution of their skills without committing any medication errors inadvertently. Nowadays healthcare system is a team work, which includes many types of medical and paramedical personnels. The physician is always the team leader and he is supported by other workers. Computerized Physician Order Entry (COPE) and Clinical Decision Systems (CDSS) are supporting tools. Standard policies and guidelines associated with academic education will result in efficient patient care systems. Effective communication in between healthcare professionals should be overwhelmed and any break down will result in harm12 and these need to be addressed at several levels. In India, the healthcare system is very complex because of several sound-alike and look-alike drugs. Prescribing generic brands have considerable advantage of quality and less cost.13 A lot of hours have been spent on this to implement good quality and being done also to form a joint venture comprising of healthcare providers and patients to understand the risks and to reduce the harm. In order to set up a high standard medical care, we framed as many as 20 policies in the hospital. The policies are as follows:

ÂÂ

Identify patients by name and hospital

Improve effective communication

Do not store high alert medications in patient care areas

Extra precautions and double check should be undertaken to avoid choosing wrong site, wrong patient and wrong surgical procedures and also risk of infection should be kept in mind and strict aseptic precautions should be instituted.

Reduce the risk of healthcare-associated infections.

High-risk patients for example geriatric, pediatric and orthopedic patients who have tendency for fall should be screened, and policy should be made in handling these high risks cases.

Organization and management zz

We organize a system process to provide safe medication to the patients.

We have PATC and MST

hand written or communicated verbally they can cause confusion. Confusion regarding drug names is thought to account for 25% of all medication errors.14 Restricted drug policy

ÂÂ

METHODS Medication safety nurse and clinical pharmacists are deployed in patient care areas and the medication processes were closely monitored. The reports were collected through Reaction Form and the errors were forwarded to PATC for remedial action. In our hospital, medication errors are considered under five quality indicators. They are: 1) Medication errors, 2) ADRs, 3) delay in dispensing the drugs, 4) number of stock out critical medicine and 5) rate of antibiotic usage. Only medication errors were analyzed. Medication Errors Prescription errors, transcription errors, dispensing errors and administration errors are brought under medication errors. It is calculated as follows: =

Total no. of medication errors

x 100

Total no. of discharge

ÂÂ

Selection and procurement of drugs

ÂÂ

Prescription, transcription and dispensing of medication

Included population: Number of patients admitted in the Hospital.

ÂÂ

Drug administration

ÂÂ

Medication errors

ÂÂ

Monitoring of new drug

Excluded population: Outpatients and inpatients who want to buy the medicine during discharge by themselves.

ÂÂ

Storage of medication

ÂÂ

Usage and storage of narcotics

ÂÂ

High alert medications

ÂÂ

Medication management and use (MMU) monitoring

ÂÂ

Procurement of medication not available in the hospital

ÂÂ

Emergency medications

ÂÂ

Drug recall

ÂÂ

Investigational drugs

ÂÂ

Discharge medications

ÂÂ

ADR reporting

ÂÂ

Medication reconciliation

ÂÂ

Look-alike and sound-alike (LASA) policy: Some of the brand names may sound-alike when read out aloud or look-alike when in print, and when

We considered medication errors from January 2009 to December 2011 (36 months) for this study. The prescription errors were 231 for 26,832 discharges, 211 for 30,515 and 195 for 20,338 for the years 2009, 2010 and 2012, respectively. There is steady decline in the incidence of prescription errors due to good compliance of physicians over policies (Table 1 and Fig. 1).

350 300 250 200 150 100 50 0

2009 231

2010

2011

344 266

255 211 195 125

Prescription errors

Transcription errors

112 106

237

133

Dispensing Administration errors errors

Figure 1. Medication errors.

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clinical study

clinical study Table 1. Prescription Errors Years

2009

2010

2011

26,832

30,515

20,338

Wrong drug

Wrong strength

No. of discharges

Wrong dose

Wrong duration

Dose not mentioned

Wrong route

Illegible

Wrong frequency

No. of discharges

2009

2010

2011

26,832

30,515

20,338

Double entry

Symbol used

Small letter

Allergy drug written

Wrong drug

IVF discontinued

Wrong rate

Wrong documentation

Delayed administration

Wrong frequency

Omission

124

Wrong medication

Not labeled

Wrong route

Allergy drug given

Without order

Wrong dose

Wrong check

Wrong brand

Wrong formulation

Wrong dose

Wrong strength

Wrong brand

Wrong patient identity

Total

231

211

195

Wrong labeling

Wrong ward

125

256

The transcription errors also came down from 125 to 95 during the year 2009 and 2010, but started rising up in 2011. This rise is due to handing over transcription job from clinical pharmacists to nurses. The newly recruited nurses also were left in much difficulty in doing the job (Table 1 and Fig. 1).

Wrong formulations

Wrong strength

Wrong transport Omission

4.24 4.22 4.09 3.96 3.93

2.52

3.79

3.52

2.76

0.86

3.66

4.17 4.21 3.85

3.14

2.95 2.17 1.98 2.07 1.67 1.43 1.16

2.37

2.53

1.64

2.49 2.47 1.85

2.27

2.25

2.52 2.09 1.62 1.57 1.2

Dec 2011 Nov 2011 Oct 2011 Sep 2011 Aug 2011 Jul 2011 n Ju 2011 May 2011 Apr 2011 Mar 2011 Feb 2011 n Ja 2011 Dec 2010 Nov 2010 Oct 2010 Sep 2010 Aug 2010 Jul 2010 n Ju 2010 ay M 2010 Apr 2010 Mar 2010 Feb 2010 n Ja 2010 Dec 2009 Nov 2009 Oct 2009 Sep 2009 Aug 2009 Jul 2009 Jun 2009 ay M 2009 pr A 2009 Mar 2009 Feb 2009 Jan 2009 Bench mark

Figure 2. Quality indicators.

386

106

133

RESULTS AND DISCUSSION All the physicians were briefed about the policy of writing prescription. Delay in dispensing is the major part of dispensing errors. The drugs are transported from pharmacy to patient care areas through messenger girls who were allotted for this purpose alone. At times these workers turned up in poor numbers due to more transcription resulted in increased dispensing errors (Table 1 and Fig. 1).

Wrong formulation

Wrong time

Wrong strength

Excessive stock

266

237

Total

344

Indian Journal of Clinical Practice, Vol. 23, No. 7, December 2012

Quality indicators

2009

2010

2011

No. of discharges

MD Quality indicators

No. of discharges

MD Quality indicators

No. of discharges

MD Quality indicators

Jan

2,197

0.86

2,237

1.43

2,322

3.66

Feb

1,584

2.50

2,267

1.67

2,397

2.37

Mar

1,584

5.30

2,266

1.98

2,769

3.14

Apr

2,026

3.70

2,414

2.07

2,374

4.17

May

2,232

1.60

2,424

2.47

2,458

2.35

Jun

2,373

3.96

2,608

2.37

108

2,629

4.10

Jul

2,397

4.25

2,682

1.64

104

2,698

3.85

Aug

102

2,412

2.69

2,726

2.53

2,691

2.52

Sep

2,352

2.76

2,857

2.17

2,767

2.09

Oct

2,553

3.52

2,806

1.85

2,564

1.2

Nov

2542

2.95

2,648

2.49

2,769

1.62

Dec

2,580

1.16

2,580

3.79

3,048

1.57

Total

813

26,832

678

30,515

848

22,386

112

Months

5.3

Table 5. Quality Indicators

Less quantity

Total

1 22

8 35

Delay in documentation

Wrong quantity

No sign

1 89

Wrong medication

06 118

Wrong ward

Order by nurses

Self medication

No. of discharges

Wrong duration

20,338

Delay

30,515

Non availability

26,832

Frequency not mentioned

2011

Wrong patient

Order not in drug chart

2010

Not documented

Wrong frequency

2009

2011

Extra quantity

Route not mentioned

Years

2010

No. of discharges

Table 4. Administration Errors

2009

Without order

117

Order in wrong place in file

Years

Delay in repeating dose

Same generic - two brands

Table 3. Dispensing Errors

Double entry

Not repeated

Table 2. Transcription Errors

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Clinical Study

clinical study Administration errors were 344 in 2009 and gradually decreased to 237 in 2011. This was due to continued training program, decrease in patient and nurses ratio and frequently conducting medication safety week, an awareness program (Table 1 and Fig. 1). The quality indicator can be calculated according to the formula, as given page no. 385. To start with in January 2009, the indicator is very low and when the policies are implemented it gradually increased. The increase is due to more awareness and screening and effective reporting system. Thereafter, it started decreasing towards the end of December 2009 due to analysis of the basic cause of the errors and proper education given to all medical personnels. Afterwards in 2010 and 2011, there is up and down reasoning out to recruitment of new physicians and new nurses and others. However, it was brought to within benchmark of 5 because of repeated training and education programs on our safety medication policies (Table 2 and Fig. 2). CONCLUSIONS These observations showed increased incidence of errors, which finally reduced due to better awareness and strict auditing and education to medication personnels. Our hospital has been recognized with Joint Commission International Accreditation. REFERENCES 1. Aspden P, Wolcott JA, Bootman JL, Cronenwett LR. By the Committee on Identifying and Preventing Medication Errors and the Board on Health Care Services. New Engl J Med 2007;357:624-5. 2. Aronson JK. Medication errors: definitions and classification. Br J Clin Pharmacol 2009;67(6):599-604.

3. O’Shea E. Factors contributing to medication errors: a literature review. J Clin Nurs 1999;8(5):496-504. 4. Lesar TS, Lomaestro BM, Pohl H. Medication-prescribing errors in a teaching hospital. A 9-year experience. Arch Intern Med 1997;157(14):1569-76. 5. Classen DC, Pestotnik SL, Evans RS, Lloyd JF, Burke JP. Adverse drug events in hospitalized patients. Excess length of stay, extra costs, and attributable mortality. JAMA 1997;277(4):301-6. 6. Gore DC, Gregory SR. Historical perspective on medical errors: Richard Cabot and the Institute of Medicine. J Am Coll Surg 2003;197(4):609-11. 7. Bates DW, Boyle DL, Vander Vliet MB, Schneider J, Leape L. Relationship between medication errors and adverse drug events. J Gen Intern Med 1995;10(4):199-205. 8. Jha AK, Kuperman GJ, Teich JM, Leape L, Shea B, Rittenberg E, et al. Identifying adverse drug events: development of a computer-based monitor and comparison with chart review and stimulated voluntary report. J Am Med Inform Assoc 1998;5(3):305-14. 9. Bates DW, Cullen DJ, Laird N, Petersen LA, Small SD, Servi D, et al. Incidence of adverse drug events and potential adverse drug events. Implications for prevention. ADE Prevention Study Group. JAMA 1995;274(1):29-34. 10. Barker KN, Flynn EA, Pepper GA, Bates DW, Mikeal RL. Medication errors observed in 36 health care facilities. Arch Intern Med 2002;162(16):1897-903. 11. Ferner RE. Medication errors that have led to manslaughter charges. BMJ 2000;321(7270):1212-6. 12. Wilson T, Sheikh A. Enhancing public safety in primary care. BMJ 2002;324(7337):584-7. 13. Dyer O. New 20 year patents threaten to end AIDS drugs for developing countries. BMJ 2004;329(7478):1308. 14. Lambert BL, Lin SJ, Chang KY, Gandhi SK. Similarity as a risk factor in drug-name confusion errors: the look-alike (orthographic) and sound-alike (phonetic) model. Med Care 1999;37(12):1214-25.

A Study of Hyperinsulinemia and Waist-hip Ratio in Patients with Chronic Anovulation Aruna Verma*, Abhilasha Gupta**, A Sarup†

Abstract Introduction: Anovulation presents a variety of clinical problems like amenorrhea, irregular menses and hirsutism. When anovulation and android obesity are present, hyperinsulinemia may be an underlying disorder in most of cases. Aims and objectives: To study the markers of insulin resistance (IR) in women with chronic anovulation, which are waist-hip ratio (WHR), fasting plasma insulin (FPI) and fasting plasma glucose/Fasting plasma insulin (FPG/FPI). Material and methods: The present study was conducted in Dept. of Obstetrics and Gynecology, LLRM Medical College, Meerut from November 2003 to October 2004. Total 37 cases of anovulatory bleeding on the basis of history and clinical examination were included in the study and they were examined for following parameters: Body mass index (BMI) (kg/m2), waist circumference (WC), WHR, FPG/FPI (>4.8 = IR). The tests applied to see the distribution and significance were binomial, Chi-square, Fisher’s exact test. Observations and results: Out of 37 patients with chronic anovulation, 28 (75.5%) had WHR >0.85 (android obesity), 23 (62.2%) had fasting hyperinsulinemia and only 11 (29.11%) patients had IR. All the patients of IR, had android obesity; 90.9% of patients with IR had fasting hyperinsulinemia. Conclusion: There is strong association of android obesity and chronic anovulation and these patients are at risk of type 2 diabetes mellitus.

Keywords: Chronic anovulation, hyperinsulinemia, waist circumference, hip circumference, waist-hip ratio

n the present scenario, anovulation is a very common problem. It presents with a variety of clinical manifestation including amenorrhea, irregular menses hirsutism. Normal ovulation requires coordination of the menstrual system at all levels:

ÂÂ

The central hypothalamopituitary axis

ÂÂ

The feedback signals

ÂÂ

Focal response within ovary.

Obese anovulatory women have a characteristic distribution of body fat known as android obesity, which refers to fat located in the abdominal wall and visceral mesentric location. This fat distribution is associated with hyperinsulinemia, impaired glucose tolerance (IGT), diabetes mellitus and increased androgen production rates, decrease sex hormonebinding globulin (SHBG), increased free testosterone and estradiol levels. Waist-hip ratio (WHR) is a means

*Lecturer **Professor and Head †Ex-Resident Dept. of Obstetrics and Gynecology LLRM Medical College, Meerut, UP Address for correspondence Dr Aruna Verma C/o.: Dr Gyaneshwar Tonk R-18, Campus, LLRM Medical College, Meerut - 250 004 (UP) E-mail: arunatonk@yahoo.co.in

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Indian Journal of Clinical Practice, Vol. 23, No. 7, December 2012

to estimate the degree of upper and lower abdominal fat, which is increased in android obesity. Since, polycystic ovary syndrome (PCOS) is a state of chronic anovulation, it is reasonable to study the presence of insulin resistance (IR), body mass index (BMI) and WHR in patients with anovulatory dysfunctional uterine bleeding (DUB). AIMS and OBJECTIVES The aims and objectives of the study were to investigate markers of IR in women with chronic anovulation without features of PCOS. The markers studied were: ÂÂ

WHR

ÂÂ

Fasting plasma insulin (FPI) levels

ÂÂ

Ratio of fasting plasma glucose to fasting plasma insulin (FPG:FPI).

MATERIAL and METHODS This study was conducted in the Dept. of Obstetrics and Gynecology, SVBP Hospital, LLRM Medical College, Meerut, for period of one year (November 2003 to October 2004). Thirty-seven outdoor attending patients who were diagnosed as a case of anovulatory bleeding on the basis of history and clinical examination formed the subject of this study.

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389

clinical study

clinical study Inclusion Criteria ÂÂ

Postmenarchal adolescent two years after menarche.

ÂÂ

Perimenopausal women with anovulation as determined by clinical presentation of menstrual dysfunction ranging from irregular cycle to amenorrhea.

Every eugonadotrophic, amenorrhea were included.

nonhyperprolactenemic

Women were examined for the following parameters ÂÂ

BMI =

(if >27 = obesity)

ÂÂ

Wt. in Kg. Waist circumference (WC) (if >90 cm = obesity) Ht. in m2

ÂÂ

WHR (if >0.85 = android obesity)

ÂÂ

FPG and FPI ratio (if <4.5 = IR)

Table 4. Association between Hyperinsulinemia and Obesity

Characteristics

Obesity (Count % within hyperinsulinemia)

Frequency

P value

27.0

21-25

27.0

26-30

32.4

No.

31-35

13.5

Normal (≤27 kg/m2)

35.7

34.8

35.1

≤27 kg/m2

35.1

64.3

65.2

64.9

>27 kg/m2

64.9

Present (>27 kg/m2) Total

100.0

Normal <0.85

24.3

High ≥0.85

75.5

BMI (kg/m2)

37.8

Hip circumference was the circumference over the buttocks.

High ≥0.85

62.2

The statistical tests applied on the data determining the frequency distribution of obesity, WHR, FPG/FPI, hyperinsulinemia in general population is binomial test.

In the present study, the mean age of patient was 24.7 years. But, maximum number of patients belonged to 26-30 years of age. Out of total 37 cases, 64.9% had BMI >27, which is statistically significant. Among total cases, 75.7% had WHR >0.85, 62.2% had hyperinsulinemia and 29.1% had insulin resistance, which was statistically significant (Table 1). Out of 11 IR patients, 90.9% were obese and 9.1% were nonobese but this association was found insignificant (p = 0.33) (Table 2). All patients of IR had WHR >0.85 and this association was found statistically significant (p = 0.025) (Table 3). Among 11 IR patients, 90.9% had hyperinsulinemia and 9.1% had normal insulin level, which was statistically significant (p = 0.020) (Table 4). Out of 23 patients with fasting hyperinsulinemia, 65.2% were obese and 34.8% were nonobese. Association

Indian Journal of Clinical Practice, Vol. 23, No. 7, December 2012

p = 0.0495 (S)

WHR

OBSERVATIONS and RESULTS

Total

Normal <0.85

The statistical tests applied to determine the significant association between markers of IR and clinical features of anovulatory DUB were Chi-square test/Fisher exact test. A p value <0.05 was taken as statistically significant.

Increased insulin level (>10 MIU/ml) (n = 23)

15-20

FPI

maximal

Hyperinsulinemia Normal insulin level (≤10 MIU/ml (n = 14)

Age groups (years)

WC was the smallest circumference between rib cage and iliac crest.

390

Table 1. Baseline Data Distribution of Subjects according to Age, BMI, WHR, FPI, IR

p = 0.0012 (S)

p = 0.043 (S)

Table 5. Association between Fasting Hyperinsulinemia and WHR WHR (count % within hyperinsulinemia)

IR (FPG/FPI) Normal (absent) (>4.5)

70.3

IR (present) (<4.5)

29.7

p = 0.01003 (S)

Table 2. Association between Obesity and IR Obesity

FPG to FPI Ratio IR (<4.5) (n = 11)

Normal (≥ 4.5) (n = 26)

Total

No.

Absent (≤ 27 kg/m2)

9.1

46.2

35.1

Present (>27 kg/m2)

90.9

53.8

64.9

Total

100.0

Table 3. Association between WHR and IR WHR

FPG to FPI ratio IR (<4.5) (n = 11)

Normal (≥ 0.5) (n = 26)

Total

No.

Normal (<0.85)

0.0

34.6

24.3

High (>0.85)

100.0

65.4

75.7

Total

100.0

Hyperinsulinemia Normal (≤10 IU/ml) (n = 14)

Hyper insulinemia

Total

No.

Normal (<0.85)

42.9

13.0

24.3

High (≥ 0.85)

57.1

87.0

75.7

Total

100.0

between these entities was statistically insignificant (p = 0.613) (Table 5). Among all patients with fasting hyperinsulinemia 87% had android obesity (WHR >0.85) and 13% had WHR <0.85. This association between hyperinsulinemia and android obesity was statistically significant. DISCUSSION In the present prospective study, 37 patients with chronic anovulation without any clinical features of hyperandrogenism were evaluated. In terms of distribution of body fat, WHR >0.85 (i.e. android obesity), was found in 28 patients (75.5%). This observation was consistent with various studies, which showed that android obesity was related with metabolic disturbances.1-5 Intra-abdominal fat accumulation causes metabolic derangement, which results in altered physiology. The presence of IR was observed in 11 (29.7%) subjects from study group of 37 subject. Evidence of IR in PCOD subjects is available in literature. But, this significant association with chronic anovulation shows that IR is a feature not specific to PCOS but associated with

anovulation. Among 11 IR subjects 90.9% were obese and only 9.1% were nonobese. This observation was consistent with the previous observation on patient with chronic anovulation who concluded from their study that association between percentage body fat and FPG/FPI was not significant.6 WHR >0.85 i.e. android obesity was found in 75.5% of chronic anovulatory patients. All cases with increased WHR (>0.85) (75.5% of total), were found with IR. This is consistent with the previous studies, which show that it is the intra-abdominal fat accumulation, which is associated with metabolic abnormalities.1,7-9 Of 23 patients with fasting hyperinsulinemia, 65.2% were obese and 34.8% were nonobese. Previous study by McAuley, et al, showed plasma insulin concentration as a useful surrogate marker of IR.10 Out of 23 patients with fasting hyperinsulinemia, 87% had android obesity, thereby showing that derangement of insulin levels are associated with accumulation of intra-abdominal fat. This finding is consistent with the observation in which WHR was found to be a significant predictor of insulin concentration.3-5 CONCLUSION In chronic anovulatory patients, the carbohydrate metabolism is deranged, which may lead to development of type 2 diabetes mellitus in these patients. Although, percentage of patients with IR were less, it had the best association with other markers of IR. While presence of IR and markers of IR are hallmark of PCOS, the present study though involving small number of patients does indicate a similar biochemical derangement in non PCOS chronic anovulators. REFERENCES 1. Fujioka S, Matsuzawa Y, Tokunaga K, Tarui S. Contribution of intra-abdominal fat accumulation to the impairment of glucose and lipid metabolism in human obesity. Metabolism 1987;36(1):54-9. 2. Vague J. La differentiation sexuelle hymanic: ses ioncidences en pathologic. Paris Masson, 1953. 3. Kissebah AH, Vydelingum N, Murray R, Evans DJ, Hartz AJ, Kalkhoff RK, et al. Relation of body fat distribution to metabolic complications of obesity. J Clin Endocrinol Metab 1982;54(2):254-60. 4. Kalkhoff RK, Hartz AH, Rupley D, Kissebah AH, Kelber S. Relationship of body fat distribution to blood pressure, carbohydrate tolerance, and plasma lipids in healthy obese women. J Lab Clin Med 1983;102(4): 621-7.

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clinical study 5. Evans DJ, Hoffmann RG, Kalkhoff RK, Kissebah AH. Relationship of body fat topography to insulin sensitivity and metabolic profiles in premenopausal women. Metabolism 1984;33(1):68-75.

8. Randle PJ, Garland PB, Hales CN, Newsholme EA. The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet 1963;1(7285):785-9.

6. Vital Reyes VS, Mc Enriquez Miranda, Hartines E, et al. Relacion insulina-glucosa y composicion corporal grasa en paciewntes con enovulacion cronica y esteriudad. Ginecol obstet Mex., Feb 2002; Vol 70, No. 2. ISSN 0300-9041.

9. Cusin I, Rohner-Jeanrenaud F, Terrettaz J, Jeanrenaud B. Hyperinsulinemia and its impact on obesity and insulin resistance. Int J Obes Relat Metab Disord 1992;16 Suppl 4:S1-11.

7. Micheli H, Carlson LA, Hallberg D. Comparison of lipolysis in human subcutaneous and omental adipose tissue with regard to effects of noradrenaline, theophylline, prostaglandin E1 and age. Acta Chir Scand 1969;135(8):663-70.

10. McAuley KA, Williams SM, Mann JI, Walker RJ, LewisBarned NJ, Temple LA, et al. Diagnosing insulin resistance in the general population. Diabetes Care 2001;24(3):460-4.

Pleural Fluid Analysis in HIV-associated Tuberculosis Patients: A Retrospective Study Sunita H*, GB Doddamani**, Linganand L. Pujari†, CVB Prasad‡

Abstract Background: One of the most common opportunistic infection in human immunodeficiency virus (HIV)-infected patients is tuberculosis. Increasing spread of HIV has become a major contributor in increasing the incidence of tuberculosis. Both the problems should be simultaneously taken care to stop the future pandemic. Method: This is a retrospective study, 30 adult patients seropositive for HIV and having tuberculosis were included. Pleural fluid was collected for cell count, cell type and for analysis of sugar, proteins and chloride levels. Results: The prevalence of the disease was more in males compared to females. The tuberculin skin test was negative in most of the cases. The pleural effusion was unilateral in all except two patients and it was confined to right side in many. The lymphocytes were predominant cells in the fluid. The sugar and proteins were lower than the normal blood levels, and the chlorides were increased. Conclusion: Extrapulmonary tuberculosis is very common mostly in the form of plural effusion. Tuberculin skin testing and sputum acid-fast bacillus (AFB) do not contribute much to the diagnosis. Analysis of pleural fluid in all seropositive cases of HIV with clinical features of tuberculosis is absolutely necessary.

Keywords: HIV, tuberculosis, pleural effusion

uman immunodeficiency virus (HIV) is a fatal infection characterized by cellular immunodeficiency. It leaves the victim vulnerable to life-threatening opportunistic infections, neurological disorders or unusual malignancies.1 In the recent years, it has exponentially grown into a frightening worldwide epidemic. The disease is the first great pandemic of 20th century which has claimed thousands of lives throughout the world.2 Tuberculosis is the commonest opportunistic infection and the number one cause of death in HIV patients in developing countries. It accounts for about 40% of all manifestations seen in HIV patients.3 About 25-65% of patients with HIV have tuberculosis of any organ and tuberculosis accounts for about 13% of all HIV-related *Assistant Professor Dept. of Biochemistry, S Nijalingappa Medical College, Navanagar, Bagalkot, Karnataka **Associate Professor, Dept. of Medicine, S. Nijalingappa Medical College, Navanagar, Karnataka †Professor Dept. of Obstetrics and Gynecology, S. Nijalingappa Medical College, Nava Nagar Bagalkot, Karnataka ‡Associate Professor Dept. of Biochemistry, J N Medical College, Belgaum Address for correspondence Dr Sunita H Assistant Professor, Dept. of Biochemistry S. Nijalingappa Medical College, Nava Nagar, Bagalkot - 587 102, Karnataka E-mail: drsunitapujar@gmail.com

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deaths worldwide.4 The adverse interaction between HIV infection and tuberculosis poses difficult challenges to public health programs.5 HIV-infected individuals co-infected with tuberculosis have an annual risk of 5-15% of developing active tuberculosis.6 The SouthEast Asia region of the World Health Organization (WHO) accounts for nearly 40% of all tuberculosis cases globally and 18% of worlds HIV-infected also live in this region.7 India has one of the world’s highest burdens of both TB (1.96 million cases annually) and HIV infection (2.31 million prevalent cases).8.9 The prevalence of pulmonary tuberculosis in HIV patients is 25-60% in India.10 In India, there were an estimated 5.1 million people living with HIV at the end of the year 2002. Assuming that about 40% of these persons are co-infected with TB, the estimated TB-HIV co-infection figures will be around two million.11 In studies reported from India, extrapulmonary tuberculosis constituted 45-56% of all the cases of tuberculosis in persons with acquired immunodeficiency syndrome (AIDS).12 HIVassociated extrapulmonary tuberculosis has got many atypical presentations. They usually have significant weight loss and fever of long duration. Cough and hemoptyosis are less frequent, while pleural effusion is commonly reported in HIV-associated pulmonary tuberculosis.13 Bagalkot district is reported to have the highest number of HIV-infected population in

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Original Study Karnataka. The prevalence of HIV according to the recent survey is found to be 2.9%.14 Therefore, this study is conducted to analyze the pleural fluid contents in HIV-associated tuberculosis in adults in this area. Material and methods The present study was carried out jointly by the Dept. of Biochemistry and Medicine in S. Nijalingappa Medical College and HSK Hospital and Research Centre from June 2008 to July 2009. Institutional Ethical Committee approved the study and informed consent was taken from all the subjects. The study included 30 cases comprising 27 adult male and three female who were seropositive for HIV and having pulmonary tuberculosis, in the age group 20-40 years and from low socioeconomic status. Serological examination of HIV was done by tridot method and confirmed with western blot technique. They were evaluated by detailed medical history and thorough clinical examination. Clinical information with special reference to weight loss, duration of fever, hemoptyosis, chronic diarrhea, generalized lymphadenopathy and history of herpes zoster were noted. If three consecutive smears were negative, sputum was sent for acid-fast bacillus (AFB) culture. Tuberculin test was done in all cases. Chest X-ray and pleural fluid tapping were also done. Pleural effusion was noticed in nine patients.

Exclusion Criteria ÂÂ

ÂÂ

Patients with renal insufficiency/liver insufficiency/ on anti-TB drugs. Patients with diagnosis of lung malignancy, primary or secondary congestive cardiac failure, uremia with pulmonary manifestations, high eosinophil count suggestive of tropical eosinophilia and patients with multiple pathology of pleural effusion.

Pleural fluid was analyzed for cell count and cell type by microscopic method. The readings were taken on STATFAX 2000 reader. The levels of proteins,15 sugar16 and chloride17 were also analyzed. The pleural effusion of exudate nature with lymphocyte predominance was presumed to be of tubercular etiology.

and 43.3% between 31-40 years. The tuberculin skin test was positive in 26.6% patients. The sputum of 56.6% of patients was positive for AFB. The pleural effusion was bilateral in two patients; it was confined to right side in four and to left side in three patients. The levels of protein, sugar, chlorides, cell type and cell count in the pleural fluid of HIV-associated tuberculosis patients are shown in Table 2.

Results

Discussion

Table 1 shows the age distribution, sex distribution, tuberculin skin test status, sputum status and pleural effusion in HIV-associated tuberculosis patients. Among the patients, 56.7% were between 20-30 years

HIV epidemic has the potential to worsen the tuberculosis epidemic as has happened in certain African countries. This is mainly because HIV increases the risk of disease reactivation by progressively impairing cell-mediated immunity in people with latent tuberculosis and hence HIV-infected persons are more susceptible to new tuberculosis infection.18 Data from USA suggests that the annual risk of reactivation in tuberculin positive HIV-infected individual is 7.9%.19 Since, the beginning of epidemic in 1981, the prevalence has increased exponentially with a doubling time of 6-12 months.20

ÂÂ

Patients having pulmonary manifestations of rheumatoid arthritis.

Table 1. Age Distribution, Sex Distribution, Tuberculin Skin Test Status, Sputum Status and Pleural Effusion in HIV-associated Tuberculosis Patients Particulars

Number of patients Percentage (%)

Age distribution 21-30 years 31-40 years

17 13

56.70 43.30

Sex distribution Male Female

27 03

90.00 10.00

Tuberculin skin test Positive Negative

08 22

26.60 73.40

AFB Positive Negative

17 13

56.60 43.40

Pleural effusion Bilateral Right Left

02 04 03

22.20 44.40 33.30

Table 2. Pleural Effusion Analysis in HIV-associated Tuberculosis Patients Patient Sl No.

Cell type (%) P

394

Cell count

Protein (g/dl)

Sugar (mg/dl)

Chlorides (mmol/l)

Type

600

5.6

780

Exudate

1,560

2.6

101

680

Transudate

950

5.9

129

Hemorrhagic

300

3.5

240

Exudate

750

5.7

317

Exudate

100

5.0

100

Exudate

4.9

Exudate

Indian Journal of Clinical Practice, Vol. 23, No. 7, December 2012

In the present study, the prevalence of disease was more in the age group 20-30 years. This is in accordance with previous studies. This reflects that the sexually more active persons are at the increased risk for HIV infection and thereby for tuberculosis.21 The tuberculin skin test was positive in 26.6% of cases. Other studies have mentioned varying percentage of the positivity22 but our findings are nearly similar to the study by Houston et al.23 Although a positive tuberculin skin test increases the likelihood of tuberculosis, a negative test reflects the immunodeficiency status and does not rule out the presence of active tuberculosis.24 So, tuberculin test is not of much value in HIV-infected persons, particularly those with advanced disease.25 The sputum AFB was positive in 56.6% of cases. The profound impairment of the immunity seen in HIV infection may permit tubercle bacilli to multiply in such a large numbers as to become visible on smear examination.26 However, in Indian studies, AFB smear negativity has been reported as high as 82%.27 Pleural effusion occurs in 2-38% of all cases of pulmonary tuberculosis. It occurs on an immunological basis when a subpleural focus of Mycobacterium tuberculosis grows and ruptures into the pleural space.28 It results from direct hematogenous invasion of the pleural space by M. tuberculosis and is usually unilateral.29 In our study, pleural effusion was seen in nine cases, two patients had bilateral i.e. 22.2% which is a significant finding. It is an atypical finding as previous studies have reported bilateral pleural effusion in only 13.85% cases.22

Of all patients showing pleural effusion, analysis was done in seven patients. Of these seven samples, 5 showed increased lymphocytes ranging from 60 to 100% cell count (300-1,560 cells) and two patients showed very less count i.e. 30 and 65 cells. The polymorphs ranged from 4 to 40 cells. The differential cell count in pleural aspirates can aid in narrowing the differential diagnosis. The predominance of polymorphonuclear cells reflects an acute process.31 A lymphocytic pleural effusion is most often the result of tuberculosis.32 Pleural effusions are classified as transudates or exudates on the basis of the fluid protein level. Classically, a pleural fluid protein level >30g/l is an exudate and <30 g/l is a transudate, in the context of a normal serum protein level.33 Applying this criteria only one sample was transudate in our study. The result is similar to another study, where the pleural fluid protein 49.15 ± 12.2 mg/dl was reported.13 The pleural fluid glucose ranged from 29 to 101 mg/dl. This is much lower compared to the normal blood glucose (FBS: 80-120 mg/dl). This may be because the diffusion of glucose into the pleural space is impaired.27 This is in contrast to the study by Light et al, they reported pleural fluid glucose level below 60 mg/dl suggests malignancy.34 The chloride levels in the fluid ranged from 110 to 170 mmol/L, this is much higher than the reference range in serum of normal subjects (97-108 mmol/l). The findings are in accordance with previous workers, they suggest it could be due to impaired membrane permeability, there is diffusion of these electrolytes into the pleural space.35 Conclusion The evidence to date indicates that preventive therapy for tuberculosis in HIV-infected persons reduces the incidence of it by 50-60%. Analysis of pleural fluid can have an important contribution for investigation of tuberculous patients with pleural effusion. The study concludes that the analysis of pleural biopsy will be useful as an ultimate procedure in cases with diagnostic problems as it is a procedure which can give a definite tissue diagnosis. References 1. WHO Expert Committee on Venereal Diseases and Treponematoses. Sixth report. World Health Organ Tech Rep Ser 1986;736:1-141. 2. Kumari S, Rai A, Chattopadhya D, Khare S, Ichhpujani RL, Sehgal PN. Screening for seroprevalence of HTLV-III/ HIV infection in high risk groups in Delhi. J Commun Dis 1986;18(2):77-80.

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Original Study 3. Pape JW. Tuberculosis and HIV in the Caribbean: approaches to diagnosis, treatment, and prophylaxis. Top HIV Med 2004 Dec-2005 Jan;12(5):144-9. 4. Sharma SK, Kadhiravan T, Banga A, Goyal T, Bhatia I, Saha PK. Spectrum of clinical disease in a series of 135 hospitalised HIV-infected patients from north India. BMC Infect Dis 2004;4:52.

19. Selwyn PA, Hartel D, Lewis VA, Schoenbaum EE, Vermund SH, Klein RS, et al. A prospective study of the risk of tuberculosis among intravenous drug users with human immunodeficiency virus infection. N Engl J Med 1989;320(9):545-50. 20. WHO. Guidelines on AIDS in Europe. WHO, Copenhegan; 1986.

5. Havlir DV, Getahun H, Sanne I, Nunn P. Opportunities and challenges for HIV care in overlapping HIV and TB epidemics. JAMA 2008;300(4):423-30.

21. Barnes PF, Le HQ, Davidson PT. Tuberculosis in patients with HIV infection. Med Clin North Am 1993;77(6): 1369-90.

6. Rajasekaran S, Uma A, Kamakshi S, Jeyaganesh D, Senthamizhchelvan A, Savithri S, et al. Trend of HIV infection in patients with tuberculosis in rural south India. Indian J Tuber 2000;47:223-6.

22. Ahmad Z, Shameem M. Manifestations of tuberculosis in HIV infected patients. JIACM 2005;6(4):302-5.

7. Solomon S, Anuradha S, Rajasekaran S. Trend of HIV infection in patients with pulmonary tuberculosis in south India. Tuber Lung Dis 1995;76(1):17-9. 8. World Health Organisation. Global Tuberculosis control: Surveillance, planning, financing. WHO Report 2008, 393. Geneva, Switzerland. 9. National AIDS Control Organisation. HIV sentinel surveillance and HIV estimation in India 2007. A technical brief. New Delhi, India: Ministry of Health and Family Welfare, Government of India, 2008. 10. Sharma SK, Mohan A, Kadhiravan T. IV-TB co-infection: epidemiology, diagnosis & management. Indian J Med Res 2005;121(4):550-67. 11. National AIDS Control Organisation (NACO), 2003. Org/ guidelines/HIV-Tb guidelines.pdf. Available from: http:// www.nacoonline. 12. Sharma SK, Mohan A, Gupta R, Kumar A, Gupta AK, Singhal VK, et al. Clinical presentation of tuberculosis in patients with AIDS: an Indian experience. Indian J Chest Dis Allied Sci 1997;39(4):213-20. 13. Zay Soe, Wunna Hla Shwe, Soe Moe. A study on tuberculous pleural effusion. Int J Coll Res Int Med Pub Health 2010;2(3):32-48. 14. Becker ML, Ramesh BM, Washington RG, Halli S, Blanchard JF, Moses S. Prevalence and determinants of HIV infection in South India: a heterogeneous, rural epidemic. AIDS 2007;21(6):739-47. 15. Kaplan A, Lavemel LS. Proteins in body fluids. In: Clinical Chemistry: Interpretation and Techniques. 2nd edition, Lea and Febiger, Philadelphia 1983:p.147-71. 16. Trinder P. Determination of glucose in blood using glucose oxidase with an alternative oxygen acceptor. Ann Clin Biochem 1969;6:24-5. 17. Schoenfeld RG, Lewellen CJ. A colorimetric method for determination of serum chloride. Clin Chem 1964;10:533-9. 18. Sharma SK, Mohan A. Co-infection of Human immunodeficiency virus (HIV) and tuberculosis: Indian perspective. Indian J Tuberc 2004;51:5-16.

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23. Houston S, Ray S, Mahari M, Neill P, Legg W, Latif AS, et al. The association of tuberculosis and HIV infection in Harare, Zimbabwe. Tuber Lung Dis 1994;75(3): 220-6. 24. Prasad R, Verma SK, Kumar Y, Nag VL, Tripati AK. A clinico-radiological study of patients of tuberculosis with HIV co-infection. Curr Med Trends 2006;10:1971-7. 25. Swaminathan S, Sangeeta M, Arunkumar N. Clinical presentation and treatment of HIV-TB. Ind J Tub 2002;49:11-6. 26. Elliott AM, Luo N, Tembo G, Halwiindi B, Steenbergen G, Machiels L, et al. Impact of HIV on tuberculosis in Zambia: a cross sectional study. BMJ 1990;301(6749):412-5. 27. Verma SK, Mahajan V. HIV-tuberculosis co-infection. Int J Pulm Med .2008;10(1):1481-90. 28. Merino JM, Carpintero I, Alvarez T, Rodrigo J, Sánchez J, Coello JM. Tuberculous pleural effusion in children. Chest 1999;115(1):26-30. 29. Kim HJ, Lee HJ, Kwon SY, Yoon HI, Chung HS, Lee CT, et al. The prevalence of pulmonary parenchymal tuberculosis in patients with tuberculous pleuritis. Chest 2006;129(5):1253-8. 30. Light RW, Erozan YS, Ball WC Jr. Cells in pleural fluid. Their value in differential diagnosis. Arch Intern Med 1973;132(6):854-60. 31. Levine H, Metzger W, Lacera D, Kay L. Diagnosis of tuberculous pleurisy by culture of pleural biopsy specimen. Arch Intern Med 1970;126(2):269-71. 32. Light RW, Macgregor MI, Luchsinger PC, Ball WC Jr. Pleural effusions: the diagnostic separation of transudates and exudates. Ann Intern Med 1972;77(4):507-13. 33. Good JT Jr, Taryle DA, Maulitz RM, Kaplan RL, Sahn SA. The diagnostic value of pleural fluid pH. Chest 1980;78(1):55-9. 34. Light RW. Clinical practice. Pleural effusion. N Engl J Med 2002;346(25):1971-7. 35. Folaranmi OM, Adesiyan AA. Comparative study of plasma electrolytes (Na, K, Cl and HCO3) and urea levels in HIV/AIDS and pulmonary tuberculosis infected subjects. Biokemistri 2004;16(1):29-36.

Comparative Evaluation of Simultaneous Bone Marrow Aspiration and Trephine Biopsy Experience from Routine Hematology Practice S Tripathy*, Sharmila Dudani**

Abstract Background: A bone marrow evaluation encompasses bone marrow aspirate (BMA) and bone marrow biopsy (BMB) along with a review of peripheral smear examination. However, due to variations in practice, bone marrow core biopsy is not performed for all patients. Aim: To compare the diagnostic utility of simultaneous BMA and BMB and to study the concordance rate between the two. Material and methods: All BMA and BMB that were simultaneously done between January 2008 and December 2010 in a multispeciality hospital were reviewed and analyzed in detail. Results: Four hundred sixty-six aspiration and biopsy slides were reviewed. The commonest indication was anemia (40.3%) followed by pyrexia of unknown origin (36.2%); 15.2% aspirates and 6.4% biopsies were inadequate. The overall concordance rate between aspirates and biopsy was found to be 62.8%. Concordance was highest for acute and chronic leukemias, metastatic deposits, multiple myeloma and tuberculosis and least for lymphoproliferative disorders, myelofibrosis and marrow hypoplasia. Trephine biopsy was useful for patients’ with multiple myeloma, acute leukemias, lymphoproliferative disorders, myelofibrosis, marrow hypoplasia, osteitis fibrosacystica and metastasis. BMB and BMA could detect tuberculous granulomas in 85.17% and 57.14% cases, respectively. However, parasitic infections (kala-azar, malaria) could be diagnosed exclusively in BMA. Conclusions: BMA and BMB are important, useful complementary diagnostic tools giving a higher diagnostic yield when used in conjunction.

Keywords: Bone marrow aspiration, bone marrow biopsy, concordance

xamination of bone marrow has wide applications in clinical medicine. It is a useful investigative tool for the diagnosis of many hematological and nonhematological disorders. It also forms an important prerequisite for follow-up of patients’ undergoing chemotherapy, bone marrow transplantation and other modalities of medical treatment.1 In addition, it is also a formidable weapon in the clinician’s diagnostic armamentarium to hit an unsuspected diagnosis when other test results turn out to be noncontributory or inconclusive during the evaluation process. Ideally, a bone marrow examination encompasses examination of bone marrow histology, bone marrow aspirate (BMA) along with a review of peripheral smear. Though either procedure, alone may suffice to arrive at a diagnosis in a given clinical situation, when both methods are done simultaneously they complement each other *Professor **Associate Professor Dept. of Pathology, ACMS, Delhi Cantt, New Delhi Address for correspondence Dr S Tripathy ACMS, Delhi Cantt, New Delhi - 110 010 E-mail: sukantatripathy@rediffmail.com

and should be viewed in concert. The aspirates are used to mainly study the morphology and maturation of cells and they can also be useful for additional flow cytometric, immunophenotyping, cytogenetic and molecular studies. The trephine biopsies on the other hand provide information on details of marrow architecture, cellularity and distribution of cells and is especially useful in diagnosing focal lesions like granulomas, lymphoid or carcinoma infiltrates.2,3 Aim To evaluate the usefulness of simultaneous BMA and bone marrow biopsy (BMB) and study the concordance rate between the two. Material and Methods The study was conducted in the Dept. of Hematology of a multispeciality hospital. Between January 2008 to December 2010, a total of 495 patients’ underwent bone marrow evaluation for diagnostic purposes. Out of the above, 466 cases in which both BMB and BMA were carried out simultaneously were included in the study.

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Original Study For preparing the BMA, the standard technique of using Salah’s needle was applied for collection. About 0.25-0.5 ml of aspirate was obtained from the posterior superior iliac spine into a syringe and delivered onto a clean glass slide. After the smears were made the slides were air-dried and were stained subsequently with May-Grunwald Giemsa (MGG) stain. Trephine biopsies were performed using the Jamshidi needle with the length of biopsy ranging from 1 to 2 cm. The biopsies were fixed in Bouins fluid, decalcified for 48 hours and embedded in paraffin from which 4μ thin sections were made and stained with hematoxylin-eosin (H&E) stain. Other special stains like reticulin, periodic acid-Schiff (PAS) and Perls were done wherever indicated. BMA were labeled as unsatisfactory when marrow particles were absent or there was dilution of samples with peripheral blood. Trephine biopsies were considered inadequate when there were <3 intertrabecular spaces or when there was inadequate/total absence of hematopoietic elements.

n = 466

Anemia (187) PUO (168) Pancytopenia (17) Hepatosplenomegaly (06) Other (88)

Figure 1. Indications for bone marrow biopsy (n = 466).

Table 1. Distribution of Cases with a Positive Correlation between Aspirates and Biopsy (n = 293) Diagnosis

No. of cases

Acute leukemia

Chronic leukemia

Results

Metastatic deposits

A total of 466 cases were reviewed from January 2008 to December 2010. The age of the subjects ranged from three years to 83 years with a male predominance (2.4:1). Commonest indication for a bone marrow examination was anemia (40.3%) followed by pyrexia of unknown origin (36.2%) and pancytopenia (3.6%) (Fig. 1).

Multiple myeloma

About 15.2% aspirates were labeled as unsatisfactory and 6.4% biopsies were considered as inadequate. The overall concordance between BMA and BMB was found to be 62.8%. The results of comparative evaluation was further subdivided into: ÂÂ

ÂÂ

Reactive

Megaloblastic

Normal

Erythroid hyperplasia

Table 2. Diagnosis Made on Bone Marrow Biopsy Alone; Aspirates were Noncontributory (n = 25) Diagnosis

No. of cases

Tuberculous granuloma

Marrow hypoplasia

List of cases where diagnosis was possible on BMB alone and aspirates were not contributory (Table 2).

Lymphoproliferative disorders

Metastasis

Plasmacytoma

List of cases where diagnosis was possible on aspirates alone. BMB was not contributory (Table 3).

Myelofibrosis

CML

ALL

Osteitis fibrosacystica

Renal osteodystrophy

List of cases, which were concordant on both aspirates and biopsy (Table 1).

The highest positive concordance was seen in megaloblastic anemia and reactive marrow as 89 cases (30.37%) and 88 cases (30.03%), respectively. Other cases with a good positive correlation, even though the number of cases was small, include acute and chronic leukemias, metastatic deposits, multiple myeloma and tuberculous granuloma. Correlation was found to be least with lymphoproliferative disorders and negligible with myelofibrosis and marrow hypoplasia.

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Tuberculosis

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Discussion One of the objectives of our study was to examine the utility of simultaneous BMA and BMB in routine hematological practice. All the patients’ included in our study underwent simultaneous BMA and

Original Study Table 3. Diagnosis Made on Aspirates alone Biopsy was Noncontributory (n = 6) Diagnosis

No. of cases

CML

Kala-azar

Granuloma

Malaria

BMB evaluation as advocated by many.3,4 They were primarily newly presenting and undiagnosed cases. Generally, patients’ with hematological malignancies are not treated in our hospital and are referred to a specialized hematology tertiary care center. The failure rate of BMA and BMB in our study was 15.2% and 6.4%, respectively and was mainly due to a diluted marrow or a dry tap. Inadequate biopsies mainly comprised of subcortical bony tissue with no marrow elements. Many studies have been conducted to determine the rate of dry taps. Humphries et al reported a rate of 3.9% from 2,235 simultaneous bone marrow aspirations and biopsies.5 We feel the higher failure rate in our study could have been due to the lack of experience on the part of Junior Residents who performed these procedures. The overall percentage of cases, which were concordant on both aspirates and biopsy was 62.8%, which is in agreement with the study published by Ramji Rai et al6 who reported a positive concordance in 61.25% of the 160 patients’ studied. The highest correlation was seen with megaloblastic anemia and reactive marrow as 30.3% and 30.0%, respectively (Table 1). Most of our cases of megaloblastic anemia were diagnosed on BMA only with trephine biopsy being reported as hypercellular leading to the low concordance. Usually, BMA is performed alone in cases clinically suspected of having megaloblastic anemia and bone marrow trephine is not considered useful for its diagnosis.7 We had four cases of acute leukemia (3 AML, 1 ALL) all of which were detected on trephine biopsy. Aspirates were diagnostic in only 75% of cases (3 AML) as the BMA in the case of ALL was diluted with peripheral blood, hence no opinion could be given. Of the eight cases of chronic leukemias (3 CLL, 5 CML), all the chronic lymphocytic leukemias were concordant on aspirate and biopsy. The myeloid leukemias showed a 60% concordance. The aspirates were better able to classify the phases of CML (chronic phase n = 1, accelerated phase n = 2 and blastic phase n = 1) as compared to biopsy. One case of CML with myelofibrosis was inconclusive on aspirate. Though, it was possible to diagnose both

Figure 2 . Photomicrograph ( H&E stain 400 X). BMB showing compact masses of plasma cells.

Figure 3 . Photomicrograph (H&E stain 400 X). BMB showing granuloma with Langhans’ giant cell.

Figure 4 . Photomicrograph (H&E stain 400 X). BMB showing increased osteoclastic activity along bony trabeculae.

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Original Study

Original Study acute and chronic leukemias on peripheral smear examination, bone marrow evaluation was important as a baseline investigation to be compared with subsequent aspirations during treatment. There were seven cases of multiple myeloma, all of which could be diagnosed on trephine biopsy. Aspirates were diagnostic in only four cases (57.1%). In three cases, the aspirates were inconclusive since they showed a normal cellularity with scattered plasma cells. Studies done by Charles et al8 on 79 simultaneous BMA and trephine biopsies from multiple myeloma patients’ did not demonstrate any added benefit from routinely performed trephine biopsies after an adequate specimen was aspirated for the diagnosis of multiple myeloma. We however, tend to agree with the study by Sabharwal et al9 who found that in cases where BMA was inconclusive for multiple myeloma, BMB complemented BMA as it helped to identify compact masses of plasma cells with no stroma. This was seen in three of our 7 cases and it was a significant histological feature for differentiation between myelomatous and nonmyelomatous plasmacytosis and the role of BMB proved invaluable for this. All three cases of metastatic deposits (Adenocarcinoma) were detected on BMB. All the biopsies in these cases showed tumor associated desmoplastic reaction as was demonstrated by reticulin stain. BMA and BMB showed a 66.6% concordance in the diagnosis of metastatic tumors. This is in agreement with other authors who have found a lower sensitivity (30-50%) on aspirates in the diagnosis of metastatic tumors as compared to biopsy.10 The BMA and BMB is a useful tool in the diagnosis of unsuspected nonhematological malignancy. Though, the number of cases is small, it is in close agreement with the study by Ozkalemkas et al,11 who studied 19 cases of unsuspected nonhematological malignancies in aspirates and biopsy and found it to be a useful tool as it helped in cutting short the evaluation process leading to a definitive diagnosis where patients’ present with myriad clinical features. One case was diagnosed as osteitis fibrosacystica on BMB (Fig. 2). The patient had osteolytic lesions and was being investigated for suspected multiple myeloma. BMB showed increased osteoclastic activity affecting subperiosteal, osteonal and endosteal surfaces. When this diagnosis was offered, follow-up investigations revealed the patient to have hyperparathyroidism due to a parathyroid adenoma. Though osteitis fibrosacystica is uncommon, bone is a target tissue for parathyroid hormone (PTH) whose calcitropic effect is mediated largely via catabolic

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actions on it12 and can be useful in the diagnosis of metabolic bone disease. While the BMA done in a known case of chronic renal failure for anemia was inconclusive, BMB revealed features of high turnover renal osteodystrophy characterized by increased bone resorption predominating over bone formation.13 Bone marrow hypoplasia (n = 9) and myelofibrosis (n = 3) could only be diagnosed on biopsy. The aspirates in all the above cases could not offer any definitive opinion. Bone marrow histology in myelofibrosis was classified according to the criteria by Bartl et al.14 Reticulin was graded from 1+ to 4+ as per the grading system proposed by Bauertneister et al.15 All the cases were found to be in the intermediate stage of myelofibrosis i.e. Grade II characterized by hyperplastic areas of marrow mixed with fibrotic areas consisting of both reticulin and collagen fibers with reduction in erythrocytic and myelocytic elements. We found that 85.71% of granulomatous lesions in bone marrow were diagnosed by BMB alone (Fig. 3). Aspirates were diagnostic in only 57.14% cases. All these cases were tuberculous granulomas. Though AFB stain was positive in only one case, the clinical history, presentation, laboratory and radiological findings helped in reaching the diagnosis of tuberculous granuloma in the others. BMB had a higher yield in detecting granulomas as compared to BMA, which is consistent with other studies.16,17 In contrast, parasitic diseases like visceral leishmaniasis and malaria were diagnosed only on BMB. Leishmania is endemic in India and BMA could be a sensitive method for detecting the disease as compared to splenic aspirates.18 Our study, though encompassing 2-year data from a busy hospital, did have the limitation of not having a wide-spectrum of cases since these cases were directly referred to the tertiary hematology center situated in the same city. Thus, no follow-up studies or any additional ancillary tests could be carried out in many of these patients. Imprint smears from BMB were done in only a few cases and thus they did not form a part of our study. In our view, inclusion of imprint smears for all cases could help bring down the failure rates and increase our diagnostic yield.

smears being primarily used for a cytological diagnosis and trephine biopsies helpful for a histological diagnosis as cellularity, fibrosis and architectural patterns are better visualized. Metastatic deposits and focal lesions also have a better diagnostic yield on BMB. This view has been supported by other authors.19 Bone marrow examination was a very useful tool in the evaluation of unsuspected conditions such as metabolic bone disorders and metastasis as observed in our study. Despite the growing complexity and dependence on newer methodologies and ancillary assays including immunochemistry, cytogenetic analysis, flow cytometry and molecular assays, which may have augmented and refined the diagnostic criteria formerly obtained by light microscopy, the traditional role of examination of BMA and histopathological evaluation of BMB remains as important as it has been in the past. Suggested Reading 1. Riley RS, Hogan TF, Pavot DR, Forysthe R, Massey D, Smith E, et al. A pathologist’s perspective on bone marrow aspiration and biopsy: I. Performing a bone marrow examination. J Clin Lab Anal 2004;18(2):70-90. 2. Bain BJ. Bone marrow aspiration. J Clin Pathol 2001;54(9):657-63. 3. Bain BJ. Bone marrow trephine biopsy. J Clin Pathol 2001;54(10):737-42. 4. Lee SH, Erber WN, Porwit A, Tomonaga M, Peterson LC; International Council for Standardization In Hematology. ICSH guidelines for the standardization of bone marrow specimens and reports. Int J Lab Hematol 2008;30(5):349-64.

marrow pathology. 3rd edition, Blackwell Science, Italy 2001:p.372-3. 8. Charles KS, Winfield DA, Angel C, Goepel J. Audit of bone marrow aspirates and trephine biopsies in multiple myeloma - a single centre study. Clin Lab Haematol 2004;26(6):403-6. 9. Sabharwal BD, Malhotra V, Aruna S, Grewal R. Comparative evaluation of bone marrow aspirate particle smears, imprints and biopsy sections. J Postgrad Med 1990;36(4):194-8. 10. Grann V, Pool JL, Mayer K. Comparative study of bone marrow aspiration and biopsy in patients with neoplastic disease. Cancer 1966;19(12):1898-900. 11. Ozkalemkas F, Ali R, Ozkocaman V, Ozcelik T, Ozan U, Ozturk H, et al. The bone marrow aspirate and biopsy in the diagnosis of unsuspected nonhematologic malignancy: a clinical study of 19 cases. BMC Cancer 2005;5:144. 12. Malluche HH, Koszewski N, Monier-Faugere MC, Williams JP, Mawad H. Influence of the parathyroid glands on bone metabolism. Eur J Clin Invest 2006;36 Suppl 2:23-33. 13. Schwarz C, Sulzbacher I, Oberbauer R. Diagnosis of renal osteodystrophy. Eur J Clin Invest 2006;36 Suppl 2:13-22. 14. Gupta R, Setia N, Arora P, Singh S, Singh T. Hematological profile in pyrexia of unknown origin: role of bone marrow trephine biopsy vis-à-vis aspiration. Hematology 2008;13(5):307-12. 15. Basu D, Saravana R, Purushotham B, Ghotekar LH. Granulomas in bone marrow - a study of fourteen cases. Indian J Pathol Microbiol 2005;48(1):13-6. 16. Frisch B, Bartl R, Burkhardt R, Jäger K. Histologic criteria for classification and differential diagnosis of chronic myeloproliferative disorders. Haematologia (Budap) 1984;17(2):209-26.

5. Humphries JE. Dry tap bone marrow aspiration: clinical significance. Am J Hematol 1990;35(4):247-50.

17. Bauermeister DE. Quantitation of bone marrow reticulin a normal range. Am J Clin Pathol 1971;56(1):24-31.

6. Toi PCh, Varghese RG, Rai R. Comparative evaluation of simultaneous bone marrow aspiration and bone marrow biopsy: an institutional experience. Indian J Hematol Blood Transfus 2010;26(2):41-4.

18. da Silva MR, Stewart JM, Costa CH. Sensitivity of bone marrow aspirates in the diagnosis of visceral leishmaniasis. Am J Trop Med Hyg 2005;72(6):811-4.

7. Bain BJ, Clark DM, Lampert IA, Wilkins BS (Eds.). Bone

19. Westerman MP. Bone marrow needle biopsy: an evaluation and critique. Semin Hematol 1981;18(4):293-300.

Conclusion The utility and efficacy of BMB as compared to BMA have been discussed and debated. The answer, though complicated remains essentially the same. Both procedures complement each other with aspiration

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case report

A Rare Case of Superior Mesenteric Vein Aneurysm

use of iodinated intravenous contrast medium.5 Venous phase mesenteric angiography can be performed to confirm the diagnosis.6 The multiplaner capability of magnetic resonance imaging (MRI) along with the capacity to render angiogram-like images of vascular structures make MRI well-suited to the evaluation of such an aneurysm.

Anjana V Trivedi*, Maulik C Jethva**, Jatin G Bhatt†, Daxa L Chavda‡

Abstract Aneurysms of the superior mesenteric vein (SMV) are rare. Many aneurysms are asymptomatic and the diagnosis is established from radiologic findings. We present a case report of superior mesenteric vein aneurysm. The diagnosis of this anomaly was made after investigation of pain in abdomen. Computed tomography ( CT) scans demonstrated the mass. Case was treated by medical treatment.

Keywords: Venous aneurysm, superior mesenteric vein, CT scan

enous aneurysms are less common than arterial aneurysms in clinical practice, and the occurrence of isolated cases is a topic of publication. Aneurysms of superior mesenteric vein (SMV) are rare. The etiology of this aneurysm is unclear, as they are found in both asymptomatic individuals and in those with concurrent disease. Here, we present a case with no predisposing factor.

Case report A 55-year-old woman presented with pain in abdomen since last two months. This was not accompanied by any alteration in intestinal habits, increase in abdominal volume or weight loss. There was no history of abdominal trauma. Physical examination revealed good general health. Chest auscultation was normal. Clinically, the abdomen appeared normal except enlarged spleen. Vascular physical examination demonstrated normal arterial pulses and absence of edema. There was no evidence of collateral venous circulation in the abdomen. To find out the cause of pain in abdomen, sonography of abdomen was done, which showed splenomegaly

*Associate Professor **Radiologist Dept. of Radiology †Professor, Dept. of Surgery ‡Assistant Professor, Dept. of Radiology PDU Medical College and Sanya GIC Imaging Centre, Rajkot, Gujarat Address for correspondence Dr Anjana V Trivedi 3-Africa Colony,150-feet Ring Road, Near Water Tank, Rajkot - 360 007, Gujarat E-mail: dranjanatrivedi@yahoo.co.in

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and dilated portal vein with possibility of aneurismal dilatation of SMV. Liver and other structures were normal. For further evaluation, computed tomography (CT) was performed, which showed SMV dilated upto 3.5 cm, without internal thrombus (Fig. 1) near the level of the portal confluence. With contrast study, opacification of SMV up to (Fig. 2). Esophagoscopy was done To rule out esophageal varices, which showed esophageal varices. Case was treated by splenectomy and medical line of treatment. Discussion The portal vein is formed by the confluence of the SMV and splenic veins at the level of pancreatic head. It extends into the hepatoduodenal ligament and is divided into the right and left branches to supply both lobes of the liver.

SMV aneurysm

Figure 1. CT scan axial section shows a dilated (3.5 cm AP diameter) superior mesenteric vein without internal thrombosis.

Figure 2. CT scan (contrast) axial section shows a dilated (3.5 cm AP diameter) superior mesenteric vein with opacification.

The SMV is located anteriorly and to the right side of the superior mesenteric artery and posteromedial to the head of pancreas. Normally, the SMV measures 1.2 cm in diameter.1 Its size was reported as abnormal if it measured >1.6 cm in diameter. SMV aneurysm is a rare condition; the first case was reported by Barzilai and Kleckner in 1956.2 The origin of this aneurysm is unknown, but some theories have been put forward. Weakness of the vessel wall may give rise to venous dilatation, even under normal venous pressure.3 Another possibility involves an embryologic mechanism; i.e., the persistence of a remnant of the right vitelline vein during development of the portal system forms a diverticulum, which may persist and develop into an aneurysm.3 In clinical practice, venous aneurysms are not common; most patients with intra-abdominal venous aneurysm seek medical assistance because of vague abdominal pain. Some patients may have gastrointestinal bleeding, acute venous occlusion or pulmonary embolism.4 In most cases reported, sonography was the first imaging technique performed, because it is noninvasive. The aneurysm appeared as an anechnoic structure near the head of pancreas. Their vascular nature is confirmed with color Doppler. Sonography, which also reveals that these aneurysms fill completely with color flow unless they contain thrombosis. Duplex Doppler sonography demonstrates a monophasic wave form characteristic of the superior mesenteric vein. Flow within the superior mesenteric vein is directed toward the portal confluence. CT scan reveals the size and extent of the lesion, and confirms its vascular origin, but requires

However, due to invasiveness of angiographic procedure, sonography, CT and MRI are preferred in most instances. The number of cases of SMV aneurysm is small, so the natural history and clinical evolution of such aneurysms are not clear. First-line management has changed over time, with there being a shift from surgical to conservative management. Initially, it was thought that surgical intervention with either shunting or aneurysmorrhaphy procedure was the treatment of choice, particularly in cases with evidence of portal hypertension.7 However, instead of the surgical approach, it may now be appropriate to follow-up patients conservatively with serial imaging.6 Conclusion Because an SMV aneurysm is a rare anomaly and its long-term evolution is not known, patients should be clearly informed of possible complications, including rupture and thrombosis. References 1. Bolondi L, Gandolfi L, Arienti V, Caletti GC, Corcioni E, Gasbarrini G, et al. Ultrasonography in the diagnosis of portal hypertension: diminished response of portal vessels to respiration. Radiology 1982;142(1):167-72. 2. Barzilai R, Kleckner MS Jr. Hemocholecyst following ruptured aneurysm of portal vein; report of a case. AMA Arch Surg 1956;72(4):725-7. 3. Schild H, Schweden F, Braun B, Lang H. Aneurysm of the superior mesenteric vein. Radiology 1982;145(3):641-2. 4. Nishinari K, Wolosker N, Yazbek G, Nakagawa WT, Lopes A. Idiopathic aneurysm of inferior vena cava associated with retroperitoneal ganglioneuroma: case report. J Vasc Surg 2003;37(4):895-8. 5. Sedat J, Padovani B, Chanalet S. Aneurysm of the superior mesenteric vein. AJR Am J Roentgenol 1993;161(4):903-4. 6. Fulcher A, Turner M. Aneurysms of the portal vein and superior mesenteric vein. Abdom Imaging 1997;22(3):28792. 7. Perret WL, de Silva A, Elzarka A, Schelleman A. Portal circulation aneurysms: two case reviews. Australas Radiol 2007;51(1):87-90.

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practice guidElines

International Consensus Group Issues Recommendations for Management of Upper GI Bleeding

he clinical and economic burden of upper gastrointestinal (GI) bleeding is considerable, with the annual incidence ranging from 48 to 160 cases per 100,000 adults and mortality rates ranging from 10 to 14 percent. In response to new data that may lead to improved patient outcomes, the International Consensus Upper Gastrointestinal Bleeding Conference Group—a multidisciplinary group of 34 experts from 15 countries—developed international guidelines for managing nonvariceal upper GI bleeding. The guidelines include new recommendations, as well as updates to the 2002 guidelines from the British Society of Gastroenterology and the 2003 consensus guidelines from the Nonvariceal Upper GI Bleeding Consensus Conference Group. The evidence rating system implemented is defined as follows: 1A = strong recommendation, high-quality evidence; 1B = strong recommendation, moderate-quality evidence; 1C = strong recommendation, low- or very low-quality evidence; 2A = weak recommendation, highquality evidence; 2B = weak recommendation, moderatequality evidence; 2C = weak recommendation, low- or very low-quality evidence. Grade 1 recommendations should be interpreted as “do it” or “do not do it”; grade 2 recommendations should be interpreted as “probably do it” or “probably do not do it.”

Resuscitation, Risk Assessment, and Preendoscopy Management Revised recommendation: Prognostic scales are recommended for early stratification of patients into low- and highrisk categories for rebleeding and mortality. (Grade: 1C) Early identification of high-risk patients can facilitate appropriate intervention, which minimizes morbidity and mortality. Stratification should be based on clinical, laboratory, and endoscopic criteria. Predictors of increased risk of rebleeding include age older than 65 years; shock; poor overall health; comorbid illnesses; low initial hemoglobin (Hb) levels; melena; transfusion requirement; fresh red blood on rectal examination, in the emesis, or in the nasogastric aspirate; sepsis; and Source: Adapted from Am Fam Physician. 2010;81(12):1495-1497.

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elevated urea, creatinine, or serum transaminase levels. New recommendation: Blood transfusions should be administered in patients with an Hgb level of 7 g per dL (70 g per L) or less. (Grade: 1C) Patients should be considered for transfusion based on their underlying condition, hemodynamic status, and markers of tissue hypoxia in acute situations. Red blood cell transfusion is rarely needed in patients with an Hgb level greater than 10 g per dL (100 g per L) and is usually needed when the Hgb level is less than 6 g per dL (60 g per L). New recommendation: In patients receiving anticoagulants, correction of coagulopathy is recommended, but should not delay endoscopy. (Grade: 2C) Available data suggest that it may not be necessary to delay endoscopy in patients with mild to moderate coagulopathy. One study of patients undergoing endoscopy found no difference in rebleeding, surgery, mortality, or complication rates between patients receiving warfarin and those not receiving anticoagulants. New recommendation: Promotility agents should not be used routinely before endoscopy to increase the diagnostic yield. (Grade: 2B) Although promotility agents may be useful in selected patients with suspected blood in the stomach, they are not recommended for routine use in patients with upper GI bleeding. Revised recommendation: Selected patients with acute ulcer bleeding who are at low risk of rebleeding on the basis of clinical and endoscopic criteria may be discharged promptly after endoscopy. (Grade: 1A) One randomized controlled trial (RCT) assessing the role of early discharge in lowrisk patients found no difference in rates of recurrent bleeding. None of the patients who were discharged early experienced serious adverse events, underwent surgery, or died during the 30-day follow-up. Revised recommendation: Pre-endoscopic proton pump inhibitor (PPI) therapy may be considered to downstage the endoscopic lesion and decrease the need for endoscopic intervention, but should not delay endoscopy. (Grade: 1B) PPI therapy may be useful, especially in patients suspected to have high-risk stigmata. However, it has not been shown to affect rebleeding, surgery, or mortality. Endoscopic Management

Revised recommendation: Early endoscopy (within 24 hours of presentation) is recommended for most patients with acute upper GI bleeding. (Grade: 1B) Early endoscopy has been shown to be safe and effective in all risk groups, although it may need to be delayed or deferred in certain high-risk patients, such as those with active acute coronary syndrome or suspected perforation. Revised recommendation: The finding of a clot in an ulcer bed warrants targeted irrigation to attempt dislodgement, with appropriate treatment of the underlying lesion. (Grade: 2B) Revised recommendation: The role of endoscopic therapy for ulcers with adherent clots is controversial. Intensive PPI therapy alone may be sufficient. (Grade: 2B) Endoscopic therapy for adherent clots involves preinjecting with epinephrine before shaving, followed by applying combination treatment to the remaining stigmata of hemorrhage. A meta-analysis of five RCTs involving patients with adherent clots found no significant benefits for endoscopic therapy compared with no endoscopic therapy. Revised recommendation: Epinephrine injection alone provides suboptimal effectiveness and should be used in combination with another method. (Grade: 1B) Revised recommendation: Clips, thermocoagulation, or sclerosant injection should be used in patients with high-risk lesions, alone or in combination with epinephrine injection. (Grade: 1A) Meta-analyses showed that adding a second procedure (e.g., an injection of alcohol, thrombin, or fibrin glue; thermal contact; clips) to epinephrine injection is superior to epinephrine injection alone. Adding a second procedure for high-risk stigmata significantly reduced rebleeding, surgery, and mortality compared with epinephrine monotherapy. Revised recommendation: Routine second-look endoscopy is not recommended. (Grade: 2B) The most recent data do not show a benefit with second-look endoscopy (i.e., a preplanned systematic endoscopy performed 16 to 24 hours after initial endoscopy). When available, highdose intravenous PPI therapy is the current standard. Patients with high-risk presentations may benefit from second-look endoscopy, but more research is needed. Pharmacologic Management Revised recommendation: An intravenous bolus followed by continuous-infusion PPI therapy should be used to decrease rebleeding and mortality in patients with high-risk stigmata who have undergone successful endoscopic therapy. (Grade: 1A) Strong evidence supports the use of high-

dose intravenous PPI therapy following successful endoscopy. No conclusions may be made at this time regarding low-dose intravenous PPI therapy or highdose oral PPI therapy. New recommendation: Patients should be discharged with a prescription for a single daily dose oral PPI; the duration should be dictated by the underlying etiology. (Grade: 1C) Once-daily PPI therapy has been shown to be effective in patients with peptic ulcer disease. However, some studies demonstrate relatively low healing rates for complicated or severe esophagitis, and twice-daily doses may be needed. Nonendoscopic and Nonpharmacologic In-Hospital Management New recommendation: Most patients who have undergone endoscopic hemostasis for high-risk stigmata should remain hospitalized for at least 72 hours. (Grade: 1C) Studies show that after endoscopic therapy, it takes 72 hours for most high-risk lesions to become low-risk lesions. More research is needed to determine whether selected highrisk patients may be treated in the outpatient setting. New recommendation: Where available, percutaneous embolization can be considered as an alternative to surgery in patients for whom endoscopic therapy has been unsuccessful. (Grade: 2C) Percutaneous or transcatheter arterial embolization may be considered as an alternative to surgery, especially in patients who are high-risk candidates for surgery. Although uncommon, possible complications include bowel ischemia; secondary duodenal stenosis; and gastric, hepatic, and splenic infarction. Revised recommendation: Patients with bleeding peptic ulcers should be tested for Helicobacter pylori and receive eradication therapy if it is present, with confirmation of eradication. (Grade: 1A) New recommendation: Negative H. pylori diagnostic tests obtained in the acute setting should be repeated. (Grade: 1B) Diagnostic tests for H. pylori (e.g., serology, histology, urea breath test, rapid urease test, stool antigen, culture) may show increased false-negative rates in patients with acute bleeding; therefore, repeat testing after an initial negative result is needed. Postdischarge, Aspirin, and NSAIDs New recommendation: In patients with previous ulcer bleeding who require a nonsteroidal anti-inflammatory drug (NSAID), treatment with a traditional NSAID plus PPI or a cyclooxygenase-2 (COX-2) inhibitor alone is associated with a clinically important risk of recurrent bleeding. (Grade: 1B)

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photo quiz

practice Guidelines New recommendation: In patients with previous ulcer bleeding who require an NSAID, the combination of a PPI and a COX-2 inhibitor is recommended to reduce the risk of recurrent bleeding compared with COX-2 inhibitors alone. (Grade: 1B) Adding a PPI to traditional NSAID therapy is recommended to reduce the risk of upper GI complications, although the combination of a COX-2 inhibitor plus a PPI was associated with the greatest reduction in risk. Other studies found a decreased risk of endoscopic ulcers with a COX-2 inhibitor plus a PPI, compared with a COX-2 inhibitor alone. New recommendation: In patients who take low-dose aspirin and develop acute ulcer bleeding, aspirin therapy should be restarted as soon as the risk of cardiovascular complication is thought to outweigh the risk of bleeding. (Grade: 1B) Discontinuing aspirin therapy for an extended period

increases thrombotic risk in patients who require cardio-protective aspirin therapy. One meta-analysis showed that nonadherence or withdrawal of aspirin therapy is associated with a threefold risk of major adverse cardiac events. According to the American Heart Association, the decision to discontinue aspirin therapy in patients with acute ulcer bleeding should be made on an individual basis. New recommendation: In patients with previous ulcer bleeding who require cardiovascular prophylaxis, clopidogrel alone has a higher risk of rebleeding than aspirin combined with a PPI. (Grade: 1B) Two RCTs showed a significant reduction in rebleeding in patients taking aspirin plus a PPI compared with those receiving clopidogrel alone, although there was no significant effect on mortality.

Cyanosis in an Older Woman

n 82-year-old woman presented to the emergency department with right-sided leg pain and paresthesias that had lasted for five days. The patient had been bedridden for several years because of dementia. Examination revealed diffusely scattered cyanosis on the foot (see accompanying figure), ankle, and calf, but sparing the knee. Peripheral pulses, including popliteal, posterior tibial, and dorsal pedis, were absent on the affected side.

Question Based on the patientâ&#x20AC;&#x2122;s history and physical examination, which one of the following is the most likely diagnosis? A. Blue toe syndrome. B. Buerger disease. C. Diabetic gangrene.

D. Diffuse acute limb ischemia. E. Postthrombotic syndrome. Discussion SEE THE FOLLOWING PAGE FOR DISCUSSION.

Source: Adapted from Am Fam Physician. 2010;81(12):1491-1492.

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medilaw

photo quiz The answer is D: diffuse acute limb ischemia. Diffuse acute limb ischemia is caused by a sudden decrease in limb perfusion that threatens limb viability within two weeks of the acute event. The condition is called critical limb ischemia when symptoms last for more than two weeks.1 Skin examination typically shows a cool, pale extremity with delayed capillary refill. The level of occlusion is generally one joint above the line of demarcation between the normal and ischemic areas. The classic symptoms of large artery occlusion are described as the five Ps: pain, paleness, pallor, paresthesia, and paralysis. Irreversible damage occurs within six hours of ischemia. When arterial occlusion occurs in the setting of well-developed collateral circulation, the symptoms may be less remarkable (e.g., intolerance to ambulation, modest pain, paresthesia). Limb ischemia is more common in lower extremities than in upper extremities. Diagnosis can be made using arterial Doppler evaluation and angiography. Angiography is confirmatory and demonstrates the location and severity of the obstruction.2 Acute limb ischemia is usually caused by embolic events, and therefore warrants investigation for an embolic source. Most embolic events are of cardiac or large artery origin. Cardiac disorders that can cause embolism include atrial fibrillation, myocardial infarction, and ventricular aneurysm. Atherosclerosis, or aneurysm of the aorta and other large arteries, is another embolic source of embolism. Although less common, a venous thrombus may enter systemic circulation through a patent foramen ovale or other septal defect.2 Arterial thrombosis may occur in atheromatous, aneurysmal, or traumatized vessels. Treatment of embolism includes prompt initiation of heparin to prevent propagation of the clot,1 followed by intra-arterial thrombolytic therapy with urokinase or surgical intervention (embolectomy or a bypass procedure). Nonviable tissue requires debridement, and amputation if necessary.3 Delayed amputation increases the risk of infection, myoglobinuria, acute renal failure, and hyperkalemia. After successful limb salvage, continuous anticoagulation with heparin followed by oral warfarin is recommended to prevent recurrence.2 Blue toe syndrome is an acute embolic event at the digital artery that leads to sudden, painful cyanosis in the toe despite strong pedal pulse and a warm foot.4 This condition is analogous to transient ischemic attack in the central nervous system and leads to an impending ischemic event. Buerger disease is inflammation of distal arteries and

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Summary Table Condition

Characteristics

Blue toe syndrome

Acrocyanosis with strong pedal pulse and warm foot

Buerger disease

Small and medium vessel vasculitis causing ischemic pain and ulceration; more common in smokers and persons of Asian descent

Diabetic gangrene

Nonhealing ulcer, typically in persons with long-standing history of diabetes mellitus and multiple foot infections

Diffuse acute limb ischemia

Progressive pain, paleness, pallor, paresthesia, and paralysis

Postthrombotic syndrome

Pain, swelling, and heaviness; stasis ulcer may develop

veins causing ischemic pain and ulceration. Pathology shows inflammation of vessels; however, atherosclerosis is typically absent. Risk factors include Asian descent and cigarette smoking.2

What should a Private Hospital do when a Patient Needs an Intervention Cardiac Procedure but does not Pay for it? MC Gupta

Q. A patient comes to a private nursing home with acute MI. The relatives are not willing to pay the professional charges immediately and say they would pay later. There are two possible outcomes: a. We perform the procedure. The patient does not benefit. They refuse to pay on some ground or the other. b. We do not perform the procedure. The patient’s condition deteriorates. They initiate legal proceedings.

Ans. ÂÂ

ÂÂ

REFERENCES 1. Norgren L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, Fowkes FG; TASC II Working Group. Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). J Vasc Surg. 2007;45(suppl S): S5-67. 2. Creager MA, Dzau VJ. Vascular disease of the extremities. In: Fauci AS, Braunwald E, Kasper DL, et al., eds. Harrison’s Principles of Internal Medicine. 17 ed. New York, NY: McGraw-Hill; 2008. 3. Clagett GP, Sobel M, Jackson MR, Lip GY, Tangelder M, Verhaeghe R. Antithrombotic therapy in peripheral artery occlusive disease: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004;126(3 suppl):609S-626S. 4. Karmody AM, Powers SR, Monaco VJ, Leather RP. “Blue toe” syndrome. An indication for limb salvage surgery. Arch Surg. 1976;111(11):1263-1268. 5. Kahn SR. The post-thrombotic syndrome: progress and pitfalls. Br J Haematol. 2006;134(4):357-365.

At the same time, a request should be made to the state to reimburse the cost of treatment because the treatment was done and expenses incurred for the sake of public good and ensuring health, which is a fundamental right that operates against the state. It should be argued that the hospital provided services on behalf of the state because the state is supposed to help a citizen in emergency.

Details should be provided to the local IMA and heart specialists with a request that the patient may be black listed and not treated by other doctors. The IMA should be requested to take up the issue with the authorities concerned.

If all else fails, a writ petition should be filed, with the following as respondents: State; local government hospital; patient and guarantor.

The hospital should proceed as follows:

Diabetic gangrene manifests as a nonhealing ulcer, typically on the toe. It is caused by the combination of arterial atherosclerosis and peripheral nerve damage. Diabetic gangrene typically develops after long-standing diabetes mellitus with multiple foot infections. Postthrombotic syndrome is a common complication of deep venous thrombosis. Typical features include pain, swelling, and heaviness; a stasis ulcer may develop.5

What should the hospital do?

ÂÂ

If the procedure is not essential and there are reasonable grounds for adopting a conservative approach, the latter approach can be followed after getting a signed informed consent. If they give consent but refuse to sign, let three doctors/others give a signed statement that the relatives/patient consented for conservative approach but refused to sign consent. If the procedure is essential, the relatives should be advised to take the patient to a government hospital and informed consent/declaration should be taken about shifting the patient. A properly documented urgent request should be made to the local government hospital to transfer the patient itself. If the hospital refuses, the refusal should be documented. If the procedure is essential and the relatives ask for deferred payment, they should be asked to produce a guarantee/guarantor for paying the hospital bill. Such guarantor is liable in law to pay. If the procedure is essential and the relatives do not comply with any of the above requirements and do not shift the patient elsewhere, the essential/life saving treatment should be given and the following further actions should be taken if the patient leaves the hospital without paying: zz

A legal notice should be served upon the patient to pay up. If not paid, a civil suit for recovery should be initiated.

Advocate and Medicolegal Consultant, New Delhi

ÂÂ

If a WP is filed, the following may happen: zz

There is a slight possibility that if the point is argued forcefully and the court is so inclined, some amount may be granted.

If no amount is paid, at least the court might make directions/observations that a doctor or hospital is not bound to give costly treatment to all patients.

Such a WP would help in existing or future proceedings against the CEA.

The legal proceedings, including the WP, would send a message across the public doctors are not sitting ducks. It will also embolden the medical profession.

Indian Journal of Clinical Practice, Vol. 23, No. 7, December 2012

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Around the globe

News and Views Drug works for retinal vein occlusion

Probiotics may prevent C. difficile diarrhea

The newest anti-vascular endothelial growth factor (VEGF) drug in ophthalmology improved eyesight for patients with central retinal vein occlusion (CRVO), although efficacy diminished with a move to as-needed dosing, researchers said at the American Academy of Ophthalmology meeting. (Source: Medpage Today)

Patients at risk of Clostridium difficile-associated diarrhea had a 66% lower infection rate when they received prophylactic probiotics, results of a metaanalysis showed. (Source: Medpage Today)

Wider fibrate use urged in mild to moderate CKD A new meta-analysis shows that fibrate therapy improves lipid profiles and prevents cardiovascular events in people with chronic kidney disease (CKD), cutting CV deaths by 40%. The findings also show that despite increasing serum creatinine-a long-known side effect of fibrates-the drug class caused no harm to the kidneys in the long run and may even provide some renal benefits, say Dr Min Jun (George Institute for Global Health, Sydney, Australia) and colleagues in their paper published online October 17, 2012 in the Journal of the American College of Cardiology. (Source: Medscape) Dialysis patients live longer with CABG vs DES Researchers from the US Renal Data System (USRDS) have shown that Medicare patients on dialysis who need cardiac revascularization have better 1-year survival if they receive drug-eluting stents (DES), but their long-term survival was better if they received a coronary artery bypass graft (CABG). Charles Herzog, MD, director of the Cardiovascular Special Studies Center of the USRDS and professor of medicine at the University of Minnesota, Minneapolis, reported these findings here at Kidney Week 2012. (Source: Medscape) HF hits older women on breast cancer drugs Older women with breast cancer being treated with trastuzumab or trastuzumab plus anthracyclines are just as likely as younger women to get heart failure as a result of their cancer treatment, researchers found. (Source: Medpage Today)

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Tofacitinib succeeds in refractory disease When treatment with one or more anti-tumor necrosis factor (TNF) inhibitors fails to control rheumatoid arthritis symptoms, treatment with tofacitinib (Xeljanz) may produce clinical improvements as well as low disease activity, a pooled analysis of phase II and III trials showed. (Source: Medpage Today) FDA panel gives nod to bird flu vaccine An FDA advisory panel has voted in favor of a vaccine against the highly pathogenic H5N1 avian flu that would be stockpiled and used in case of pandemic. By twin votes of 14-0, the panel agreed that the immunogenicity and the safety of the vaccine, made in Quebec by GlaxoSmithKline, were enough to meet licensing standards under accelerated approval regulations. Those rules - set out in 2007 - allow rapid approval of a vaccine on the basis of markers that are likely to predict clinical benefit. In the case of this vaccine, dubbed Q-Pan H5N1, the surrogate marker was antibody response measured by a hemagglutinationinhibition (HI) assay. (Source: Medpage Today) Weight-loss surgery may not â&#x20AC;&#x2DC;cureâ&#x20AC;&#x2122; diabetes Although bariatric surgery is increasingly touted as a cure for type 2 diabetes, its remission was only temporary in about one-third of patients, researchers said. (Source: Medpage Today) Hospitals cut colorectal surgical-site infections by a third Seven academic medical centers reduced their rate of colorectal surgical site infections (SSIs) by 32% with interventions that included hand sanitizer, new sets of instruments for closure, and postoperative telephone calls to patients about wound care, leaders of the quality improvement campaign announced at a press conference. (Source: Medscape)

lighter reading

Information for Authors

God’s embroidery

Gut Buster

Then Mother would say to me, “My son, from underneath it did look messy and jumbled, but you did not realize that there was a pre-drawn plan on the top. It was a design. I was only following it. Now look at it from my side and you will see what I was doing.” Many times through the years I have looked up to my Heavenly Father and said, “Father, what are You doing?” He has answered, “I am embroidering your life.” I say, “But it looks like a mess to me. It seems so jumbled. The threads seem so dark. Why can’t they all be bright?” The Father seems to tell me, “’My child, you go about your business of doing My business, and one day I will bring you to Heaven and put you on My knee and you will see the plan from My side.”

A pharmacist comes back from his break and sees a man leaning against the wall, his face strained and nervous. He asks his assistant: “What’s wrong with that man over there?” “He came in looking for cough medicine,” she replies. “I couldn’t find any, so I gave him a whole bottle of laxatives.”

ILLUSION

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Dr. Good & Dr. Bad Situation: A patient with Mediclaim was advised MRI

It will not be covered

It will be covered

Quotes

—GM Singh

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Indian Journal of Clinical Practice, Vol. 23, No. 7, December 2012

Lesson: Post

hospitalization related medical expenses incurred during period up to 60 days after hospitalization of disease/illness/ injury sustained are covered as part of the claim. Dr KK Aggarwal

The covering letter should explain if there is any deviation from the standard IMRAD format (Introduction, Methods, Results and Discussion) and should outline the importance of the paper. Principal/Senior author must sign the covering letter indicating full responsibility for the paper submitted, preferably with signatures of all the authors. Articles must be accompanied by a declaration by all authors stating that the article has not been published in any other Journal/Book. Authors should mentioned complete designation and departments, etc. on the manuscript.

Manuscript – Three complete sets of the manuscript should be submitted and preferably with a CD; typed double spaced throughout (including references, tables and legends to figures).

post discharge.

—Ritu

“In Life, in every moment, something new happens; something that you never expected, something that you were waiting from a long while to happen and something you were expecting to happen.”

Manuscripts should be prepared in accordance with the ‘Uniform requirements for manuscripts submitted to biomedical journals’ compiled by the International Committee of Medical Journal Editors (Ann. Intern. Med. 1992;96: 766-767). Indian Journal of Clinical Practice strongly disapproves of the submission of the same articles simultaneously to different journals for consideration as well as duplicate publication and will decline to accept fresh manuscripts submitted by authors who have done so. The boxed checklist will help authors in preparing their manuscript according to our requirements. Improperly prepared manuscripts may be returned to the author without review. The checklist should accompany each manuscript. Authors may provide on the checklist, the names and addresses of experts from Asia and from other parts of the World who, in the authors’ opinion, are best qualified to review the paper. Covering letter

©IJCP Academy

When I was a little boy, my mother used to embroider a great deal. I would sit at her knee and look up from the floor and ask what she was doing. She informed me that she was embroidering. I told her that it looked like a mess from where I was. As from the underside I watched her work within the boundaries of the little round hoop that she held in her hand, I complained to her that it sure looked messy from where I sat. She would smile at me, look down and gently say, “My son, you go about your playing for awhile, and when I am finished with my embroidering, I will put you on my knee and let you see it from my side.” I would wonder why she was using some dark threads along with the bright ones and why they seemed so jumbled from my view. A few minutes would pass and then I would hear Mother’s voice say, “Son, come and sit on my knee.” This I did only to be surprised and thrilled to see a beautiful flower or a sunset. I could not believe it, because from underneath it looked so messy.

Laugh a While

An Inspirational Story

Lighter Side of Medicine

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The manuscript should be arranged as follow: Covering letter, Checklist, Title page, Abstract, Keywords (for indexing, if required), Introduction, Methods, Results, Discussion, References, Tables, Legends to Figures and Figures.

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All pages should be numbered consecutively beginning with the title page.

departments and institutions where the work was performed, name of the corresponding authors, acknowledgment of financial support and abbreviations used. – The title should be of no more than 80 characters and should represent the major theme of the manuscript. A subtitle can be added if necessary. – A short title of not more than 50 characters (including inter-word spaces) for use as a running head should be included. – The name, telephone and fax numbers, e-mail and postal addresses of the author to whom communications are to be sent should be typed in the lower right corner of the title page. – A list of abbreviations used in the paper should be included. In general, the use of abbreviations is discouraged unless they are essential for improving the readability of the text. Summary – The summary of not more than 200 words. It must convey the essential features of the paper. – It should not contain abbreviations, footnotes or references. Introduction – The introduction should state why the study was carried out and what were its specific aims/objectives. Methods – These should be described in sufficient detail to permit evaluation and duplication of the work by others. – Ethical guidelines followed by the investigations should be described. Statistics The following information should be given: – The statistical universe i.e., the population from which the sample for the study is selected. – Method of selecting the sample (cases, subjects, etc. from the statistical universe). – Method of allocating the subjects into different groups. – Statistical methods used for presentation and analysis of data i.e., in terms of mean and standard deviation values or percentages and statistical tests such as Student’s ‘t’ test, Chi-square test and analysis of variance or non-parametric tests and multivariate techniques.

Note: Please keep a copy of your manuscript as we are not responsible for its loss in the mail. Manuscripts will not be returned to authors.

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Title page Should contain the title, short title, names of all the authors (without degrees or diplomas), names and full location of the

– These should be concise and include only the tables and figures necessary to enhance the understanding of the text.

Confidence intervals for the measurements should be provided wherever appropriate.

Results

Indian Journal of Clinical Practice, Vol. 23, No. 7, December 2012

417

Discussion –

This should consist of a review of the literature and relate the major findings of the article to other publications on the subject. The particular relevance of the results to healthcare in India should be stressed, e.g., practicality and cost.

References These should conform to the Vancouver style. References should be numbered in the order in which they appear in the texts and these numbers should be inserted above the lines on each occasion the author is cited (Sinha12 confirmed other reports13,14...). References cited only in tables or in legends to figures should be numbered in the text of the particular table or illustration. Include among the references papers accepted but not yet published; designate the journal and add ‘in press’ (in parentheses). Information from manuscripts submitted but not yet accepted should be cited in the text as ‘unpublished observations’ (in parentheses). At the end of the article the full list of references should include the names of all authors if there are fewer than seven or if there are more, the first six followed by et al., the full title of the journal article or book chapters; the title of journals abbreviated according to the style of the Index Medicus and the first and final page numbers of the article or chapter. The authors should check that the references are accurate. If they are not this may result in the rejection of an otherwise adequate contribution. Examples of common forms of references are: Articles Paintal AS. Impulses in vagal afferent fibres from specific pulmonary deflation receptors. The response of those receptors to phenylguanide, potato S-hydroxytryptamine and their role in respiratory and cardiovascular reflexes. Q. J. Expt. Physiol. 1955;40:89-111.

Figures – Two complete sets of glossy prints of high quality should be submitted. The labelling must be clear and neat. – All photomicrographs should indicate the magnification of the print. – Special features should be indicated by arrows or letters which contrast with the background. – The back of each illustration should bear the first author’s last name, figure number and an arrow indicating the top. This should be written lightly in pencil only. Please do not use a hard pencil, ball point or felt pen. – Color illustrations will be accepted if they make a contribution to the understanding of the article. –

Do not use clips/staples on photographs and artwork.

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Illustrations must be drawn neatly by an artist and photographs must be sent on glossy paper. No captions should be written directly on the photographs or illustration. Legends to all photographs and illustrations should be typed on a separate sheet of paper. All illustrations and figures must be referred to in the text and abbreviated as “Fig.”.

Please complete the following checklist and attach to the manuscript: 1. Classification (e.g. original article, review, selected summary, etc.)_______________________________ 2. Total number of pages ________________________ 3. Number of tables ____________________________ 4. Number of figures ___________________________

Books

5. Special requests _____________________________

Stansfield AG. Lymph Node Biopsy Interpretation Churchill Livingstone, New York 1985.

6. Suggestions for reviewers (name and postal address)

Articles in Books

2.____________ 2.________________

Strong MS. Recurrent respiratory papillomatosis. In: Scott Brown’s Otolaryngology. Paediatric Otolaryngology Evans JNG (Ed.), Butterworths, London 1987;6:466-470.

3.____________ 3.________________

4.____________ 4.________________

Tables –

These should be typed double spaced on separate sheets with the table number (in Roman Arabic numerals) and title above the table and explanatory notes below the table.

Legends – These should be typed double spaces on a separate sheet and figure numbers (in Arabic numerals) corresponding with the order in which the figures are presented in the text. –

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The legend must include enough information to permit interpretation of the figure without reference to the text.

Indian Journal of Clinical Practice, Vol. 23, No. 7, December 2012

Indian 1.____________Foreign 1.________________

7. All authors’ signatures________________________ 8. Corresponding author’s name, current postal and e-mail address and telephone and fax numbers __________________________________________

Online Submission Also e- Issue @ www.ijcpgroup.com For Editorial Correspondence

Dr KK Aggarwal

Group Editor-in-Chief Indian Journal of Clinical Practice E-219, Greater Kailash, Part-1 New Delhi - 110 048. Tel: 40587513 E-mail: editorial@ijcp.com Website: www.ijcpgroup.com

R.N.I. No. 50798/90 Date of Publication 13th of Same Month Date of Posting 13-14 Same Month

DL (S)-01/3200/2012-2014 Posted in N.D. PSO New Delhi

Dr SM Rajendran