May 2017 by ejima

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JOURNAL OF THE INDIAN MEDICAL ASSOCIATION, VOL 115, NO 5,

MAY 2017

Dr K K Aggarwal

Dr R N Tandon

Dr Dilip Kumar Dutta

Dr Kakali Sen

National President IMA

Honorary Secretary General, IMA

Honorary Editor, JIMA

Honorary Secretary, JIMA

Volume 115 u Number 05 u Kolkata u May 2017

CONTENTS Editorial : u The future of biochemistry — Dilip Kumar Dutta, Santanu Banerjee.....................................5 Original Articles : u Passive smoking and pregnancy outcome — Vanita Suri, Neelam Aggarwal,

Rashmi Bagga, Dheeraj Gupta, Ashutosh N Aggarwal .........................................................8 u Morphometric study of lumbar pedicle obtained from 65 cadavers, in

Rewa region of central India — Amrish Tiwari, D C Naik, P G Khanwalkar, Meghana Mishra, Bhaskar Reddy ................................................................11 Observational Studies : u Primary closure of an abscess cavity : our observation

— Dnyanesh M Belekar, Ushma K Butala ............................................................................15 u Eye banking in India : current status and the way forward — Noopur Gupta,

Radhika Tandon, Sanjeev K Gupta, Praveen Vashist .............................................................19 u Fixation with pedicle screw for thoraco-lumbar spine fracture : our experience — Santosh Kumar, Indrajeet Kumar, Rajat Charan, Binay Pandey ......................................23 Case Report : u Broad ligament fibroid mimicking ovarian tumour based on ultrasonographic

study — Indranil Dutta, Sanchita Karmakar, Sourav Chowdhury, Nikhil Kumar..................26 Cinical Study : u Dosulepin as analgesic and antidepressant in chronic pain : a

clinical review — Venkateshwarlu Kolichana, Samir Adsule, Kartik Peethambaran ............28 Supplement : u Generic Drugs : IMA Perspective — K K Aggarwal, R N Tandon,

A Marthanda Pillai, Vinay Aggarwal, R V Asokan.................................................................33 Wcomments / Feedback 3

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JOURNAL OF THE INDIAN MEDICAL ASSOCIATION, VOL 115, NO 5,

MAY 2017

Editorial

JOURNAL OF THE INDIAN MEDICAL ASSOCIATION, VOL 115, NO 5,

MAY 2017

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JOURNAL OF THE INDIAN MEDICAL ASSOCIATION Founder Hony Editor Founder Hony Business Manager Ex-officio Members

: : :

Hony Editor Hony Secretary Hony Associate Editors

: : :

Assistant Secretary

Sir Nilratan Sircar Dr Aghore Nath Ghosh Dr Santosh Kumar Mandal Hony. Joint Secretary, IMA (Hqs), Kolkata Dr Santanu Sen Hony Jt Finance Secretary, IMA (Hqs), Kolkata Dr Dilip Kumar Dutta Dr Kakali Sen Dr Amitabha Bhattacharya Dr Dipanjan Bandyopadhyay Dr Gopal Das

Dr Dilip Kumar Dutta

Prof Santanu Banerjee

MD, PhD, FRCOG (Hon), FICOG, FIAMS, FICMCH, MAMS, DACOG (USA), DPS (Germany) Chairman, Indian College of Obstetrics & Gynecology (2015) Dean, Indian Academyt of Obstetrics & Gynecology (IAOG) 2017 Vice Chairman, ISAR Bengal 2015-2017 National Editor of 'Jogi Journal' Director, GICE, Kalyani, Nadia, WB Author of 36 books (Obstetrics and Gynaecology) Honorary Editor, Journal of the Indian Medical Association (JIMA)

MBBS, MD (Biochemistry) Principal, College of Medicine & JNM Hospital. Kalyani, West Bengal Guest Editor, JIMA

OFFICE BEARERS OF IMA (HQs)

The future of biochemistry National President Dr K K Aggarwal Honorary Secretary General Dr R N Tandon

IMA CGP (Chennai) Dean of Studies Dr V C Shanmuganandan (Karnataka) Honorary Secretary Dr R Gunasekaran (Tamil Nadu)

IMA AMS (Hyderabad) Chairman Dr Joseph Mani (Kerala) Honorary Secretary National President-Elect (2017-2018) Dr Ravi S Wankhedkar (Maharashtra) Dr Sadanand Rao Vulese (Telangana)

Immediate Past National President Dr S S Agarwal (Rajasthan)

National Vice-Presidents Dr Roy Abhram Kallivayalil (Kerala) Dr K Prakasam (Tamil Nadu) Dr Mahendra Choudhary (Gujarat) Dr Parmanand Prasad Pal (Bihar)

IMA AKN Sinha Institute (Patna) Director Dr Sarbari Dutta (Bengal) Honorary Executive Secretary Dr Raman Kumar Verma (Bihar)

Honorary Finance Secretary Dr V K Monga (Delhi)

JIMA (Calcutta) Honorary Editor Dr Dilip Kumar Dutta (Bengal) Honorary Secretary Dr Kakali Sen (Bengal)

Honorary Joint Secretaries Dr Vinod Khetarpal (Delhi) Dr Anil Goyal (Delhi) Dr Ashwini Kumar Dalmiya (Delhi) Dr Santosh Kumar Mandal (Bengal) Dr B B Gupta (Delhi) Honorary Assistant Secretaries Dr Dinesh Sahai (Delhi) Dr Amrit Pal Singh (Delhi) Honorary Joint Finance Secretaries Dr Manjul Mehta (Delhi) Dr Santanu Sen (Bengal)

Your Health (Calcutta) Honorary Editor Dr Ashok Kumar Chatterjee (Bengal) Honorary Secretary Dr Meenakshi Gangopadhyay (Bengal) IMA N.S.S.S. (Ahmedabad) Chairman Dr Kirti M Patel (Gujarat) Honorary Secretary Dr Yogendra S Modi (Gujarat)

IMA N.P.P.Scheme (Thiruvananthapuram) Chairman Dr Krishna M Parate (Maharashtra) Honorary Secretary Dr Jayakrishnan A V (Kerala) Apka Swasthya (Varanasi) Honorary Editor Dr Vivek Kumar (Uttar Pradesh) Honorary Secretary Dr Sanjay Kumar Rai (Uttar Pradesh) IMA Hospital Board of India Chairman Dr R V Asokan (Kerala) Honorary Secretary Dr Jayesh M Lele (Maharashtra) IMA National Health Scheme Chairman Dr Ashok SAdhao (Maharashtra) Honorary Secretary Dr Alex Franklin (Kerala) IMA National Pension Scheme Chairman Dr Sudipto Roy (Bengal) Honorary Secretary Dr K V Devadas (Kerala)

iochemistry is closely related to molecular biology, the study of the molecular mechanisms by which genetic information encoded in DNA is able to result in the processes of life. The contribution of molecular biochemistry for clinical diagnosis is through use of biomarkers for diagnosis and disease monitoring. Comprehensive molecular testing in this direction requires the service of genomics (microarray, epigenomics, and DNA methylation status of specific genes) and proteomics. For the past decade, the discovery of epigenetic biomarkers has been the major development in clinical translational science. Epigenomics is the study of the complete set of epigenetic modifications on the genetic material of a cell, known as the epigenome. The field is analogous to genomics and proteomics, which are the study of the genome and proteome of a cell. Epigenetic modifications are reversible modifications on a cellâ&#x20AC;&#x2122;s DNA or histones that affect gene expression without altering the DNA sequence. Recent research studies have demonstrated the ability of epigenetic biomarkers comprising DNA methylation, epigenetic histone modifications and changes in micro RNA expression using human biological samples or small tissue samples (laser micro dissection and use of formalin fixed specimens) as an improvement over current diagnostic tools. What is more exciting in epigenomic molecular diagnostics is the recent development of quantitative single step methylation analysis with native DNA template thus enabling feasibility of epigenomic biomarker as a high throughput analysis. Protein arrays are becoming valuable tools and use of biopsy specimens with small volumes offers a promising approach for the optimal evaluation of disease detection and progression. It is becoming clear that functional proteomics and nano LC-MS/MS based metabolomics is providing novel insights into molecular biochemistry of disease states. The next challenge is to validate these candidate biomarkers in clinical translational science. Once the candidate markers are identified, these markers can be developed as high throughput multiplex quantitative analysis.

Pharmacogenomics and Personalized Molecular Medicine of Biochemistry : The importance of genetic makeup an individual/s response to drug (pharmacogenetics) is being increasingly recognized and pharmacogenomic tests are being done to predict an individualâ&#x20AC;&#x2122;s response to drugs and determine the accurate dosage. In addition to pharmacogenomics, additional layers of molecular testing are pharmacoepigenomics and functional proteomics if one has to provide complete information of molecular tests for personalized molecular therapy. These laboratory services need establishment of epigenetic and proteome laboratory as a part of molecular testing laboratory.

Molecular Diagnostic Services of Biochemistry for Different Types of Laboratories : For small sized laboratories, initial efforts to provide tests such as gene polymorphism tests in relation to cancer risk, pharmacogenomics tests, and tests for single gene disorders and tests for microbial diagnostic services may be considered. This can easily be accomplished by setting a dedicated PCR laboratory in tertiary care hospitals affiliated to centre of Molecular biology. In addition to PCR laboratory, some of the large sized tertiary care hospitals with well established super specialities are capable of establishing mass spectrometry laboratory in clinical biochemistry. This will provide community based service for inherited disorders of metabolism, toxicology services and metabolomics as a part of translational research. Large sized referral laboratories in selective medical centers are in position to offer additional molecular testing services such as proteomics, transcriptomics and epigenomic tests.

Blood tests in biochemistry : Various biochemical parameters in blood now days are measured to diagnose as well as for prognosis of various systemic illness.

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JOURNAL OF THE INDIAN MEDICAL ASSOCIATION, VOL 115, NO 5,

Biochemistry and cancer : Biochemistry has unravelled the mystery of many diseases like cancer. Many research are going on in cancer now. May be in near future with the help of tools of biochemistry scientist may be able to untangle the drug of cancer. Among many of such marker few such important marker for cancer research are telomere, telomerase, p53 etc. Cancer cells require multiple mutations to become malignant. Each mutation probably uses 20–40 divisions before achieving a population size sufficient for another spontaneous mutation to occur, so premalignant cells usually come up against the barrier of replicative senescence before accumulating enough mutated pathways to become frank malignancies. There are various molecular biology markers are there, because of their mutation they leads to cancer. Few such important marker or gene is p53, telomeres and telomerase. One critical step in oncogenesis involves the up-regulation or reactivation of telomerase in order to overcome this limit, and approximately 85–90% of all tumor biopsies are telomerase positive.

Role of telomeres and telomerase in cancer : There is mounting evidence for the existence of an important relationship between telomeres and telomerase and cellular aging and cancer. Normal human cells progressively lose telomeres with each cell division until a few short telomeres become uncapped leading to a growth arrest known as replicative aging. In the absence of genomic alterations these cells do not die but remain quiescent producing a different constellation of proteins compared to young quiescent cells. Upon specific genetic and epigenetic alterations, normal human cells bypass replicative senescence and continue to proliferate until many telomere ends become uncapped leading to a phenomenon known as crisis. In crisis cells have critically shortened telomeres but continue to attempt to divide leading to significant cell death (apoptosis) and progressive genomic instability. Rarely, a human cell escapes crisis and these cells almost universally express the ribonucleoprotein, telomerase, and maintain stable but short telomeres. The activation of telomerase may be thought of as a mechanism to slow down the rate genomic instability due to dysfunctional telomeres. While telomerase does not drive the oncogenic process, it is permissive and required for the sustain growth of most advanced cancers. Since telomerase is not expressed in most normal human cells, this has led to the development of targeted telomerase cancer therapeutic approaches that are presently in advanced clinical trials.

Role of p53 in cancer: p53, also known as TP53 or tumor protein (EC: 2.7.1.37) is a gene that codes for a protein that regulates the cell cycle and hence functions as a tumor suppression. It is very important for

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cells in multicellular organisms to suppress cancer. P53 has been described as “the guardian of the genome”, referring to its role in conserving stability by preventing genome mutation (Strachan and Read, 1999). The name is due to its molecular mass: it is in the 53 kilodalton fraction of cell proteins. In health p53 is continually produced and degraded in the cell. The degradation of p53 is associated with MDM2 binding. In a negative feedback loop MDM2 is itself induced by p53. However mutant p53s often don’t induce MDM2, and are thus able to accumulate at very high concentrations. Worse, mutant p53 protein itself can inhibit normal p53 (Blagosklonny, 2002) and can lead to cancer.

Role of Cell free DNA: Cell free fetal DNA ( cffDNA) originates from the trophoblastic cells and enters in to the maternal circulation invading the feto-placental barrier. It was detected in maternal plasma in early eighties. Placental origin of cffDNA is identified, detectable as early as 5 weeks of gestation and constitute about 10% of cell free DNA, which is cleared rapidly from maternal circulation after delivery. It thus offers potential source of prenatal diagnosis for various genetic conditions like such as achondroplasia, autosomal recessive disorders, fetal thalassemia, aneuploidy, RHD genotyping. This gender-independent detection of cell free fetal DNA in maternal plasma using RASSF1A/beta-actin has curtained off a new dimension regarding its utility to predict the adverse pregnancy outcomes. Recent studies showed the utility of cffDNA using the methylation-dependent DSCR3 and RASSF1A markers along with total cell free DNA (cf-DNA) in maternal serum by HYP2 marker are useful in predicting preeclampsia, intrauterine growth restriction.The higher concentration of cffDNA in maternal serum is found in preeclampsia and particularly cffDNA and cf DNA ratio is twofold higher in severe preeclampsia group.

Future of Biochemistry : Liquid biopsies also present us with a unique opportunity to move forward with our understanding of metastatic disease development and they may help to identify signalling pathways involved in cell invasiveness and metastatic competence. Ultimately, at some point in the not too distant future, these tests will be used in the diagnosis of cancer. This will revolutionise cancer care, providing clinicians with rapid access to information on a molecular level at diagnosis, thereby optimising treatment choices.

Conclusion: Biochemistry will not only decide the future of internal medicine by its variety of diagnostic tests but also will help the clinician for better understanding of the process of malignancy, in predicting adverse pregnancy outcomes and many other disease process.

Disclaimer The information and opinions presented in the Journal reflect the views of the authors and not of the Journal or its Editorial Board or the Publisher. Publication does not constitute endorsement by the journal. JIMA assumes no responsibility for the authenticity or reliability of any product, equipment, gadget or any claim by medical establishments/institutions/manufacturers or any training programme in the form of advertisements appearing in JIMA and also does not endorse or give any guarantee to such products or training programme or promote any such thing or claims made so after. — Hony Editor

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MAY 2017

Original Article Passive smoking and pregnancy outcome 1

Vanita Suri , Neelam Aggarwal , Rashmi Bagga , Dheeraj Gupta , Ashutosh N Aggarwal

Passive smoking or exposure to environmental tobacco smoke during pregnancy can lead to adverse outcome. To study the effects of Environmental Tobacco smoke exposure on pregnancy outcome and birth weight of the newborn. One thousand women, who were non-smokers, were interviewed post delivery according to pre-designed structured questionnaire. Based on Environmental smoke exposure the population was divided into two groups: not exposed and exposed to Environmental Tobacco smoke. Pregnancy outcome was compared between the two groups. Out of 1000 women 312 patients (31.2%) had history of Environmental smoke exposure (Group I) and 688 patients (68.8%) were not exposed to tobacco smoke (Group II). There was no difference in incidence of Pregnancy Induced Hypertension, Gestational Diabetes Mellitus, Placenta previa and abruptio among both the groups. The incidence of Preterm labor was more in group exposed to Environmental smoke although was not statistically significant (24.7% versus 21.2%). The incidence of premature rupture of membranes was similar in both the groups. The mean birth weight of babies in group I was 2.398±0.626g and in group II was 2.530±0.649g. The difference was 132gms which is statistically significant (p<0.05). In group I, 163(52.2%) babies weighed less than 2.5Kg compared to 272(39.5%) babies in group II and this difference was statistically significant. Similarly more babies were less than 2Kg in group exposed to Environmental smoke than in unexposed group (24.4% versus 17.9%). This difference was also statistically significant. Environmental smoke exposure during pregnancy leads to significant reduction in birth weight and higher number of low birth weight babies. The incidence of PTL though is more but not statistically significant. [J Indian Med Assoc 2017; 115: 8-10 & 14]

Key words : Passive smoking, smoking, environmental smoke exposure, low birth weight.

moking can be active or passive ie, exposures to envi-ronmental tobacco smoke (ETS). Exposure to ETS is defined as the involuntary exposure to combined but diluted cigarette side stream smoke and the exhaled smoke from smokers. Nearly 85% of the smoke generated in a room results from side stream smoke which has higher pH, smaller particles, higher carbon monoxide concentrations and various cytotoxic substances such as polycyclic aromatic hydrocarbons, aromatic amines, ammonia, nitrosamines, heavy metals, poisonous gases, pesticides residues and radioactive elements in quantities much higher than those found from the cigarette mainstream smoke which is puffed by smokers . The effect of ETS exposure on reproductive outcome can be delayed conception, intrauterine growth restriction, congenital malformations and fetal loss including spontaneous abortions . Exposure to ETS during pregnancy is a strong risk factor for low birth 1

Department of Obstetrics & Gynaecology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012 1 MD, Professor 2 MD, Assistant Professor 3 MD, DM, Professor of Pulmonary Medicine 4 MD, DM, Additional Professor of Pulmonary Medicine

weight and preterm birth . This is a significant public health concern because low birth weight is the most important single determinant of neonatal and infant morbidity and mortality. Windham et al in a meta analysis calculated average birth weight decrements associated with ETS exposure in nonsmoking mothers. Based on studies that adjusted for confounders, the pooled birth weight difference was 28.5 gm. The effect of ETS exposure on reproductive outcome has been studied extensively in developing countries, but experience from India is limited. Therefore we planned a study to know the effects of ETS exposure on pregnancy outcome and birth weight of the newborn. 3-5

ETS exposure was defined as involuntary exposure of non-smoking pregnant women to tobacco smoke in their household from husbands and other family members or by other persons at their workplace any time during pregnancy. Cumulative ETS exposure was defined as the sum of ETS exposure at household and at workplace. Anemia in a pregnant woman was defined as hemoglobin concentration of less than 10.5 gm/dl as per WHO guidelines. Preterm delivery was defined when delivery occurred at less than 37 weeks of gestation. Low birth weight (LBW) was defined as birth weight less than 2500 gm. Pregnancy induced hypertension was defined as blood pressure >140/90 mm Hg on at least two consecutive occasions at least 6 hrs apart with or without proteinuria. Gestational diabetes mellitus (GDM) was defined as carbohydrate intolerance of variable severity with onset or first recognition during pregnancy. Placenta previa was defined as the lower edge of placenta <2 cm from internal os. Abruptio placentae was defined as premature separation of normally implanted placenta. Based on ETS exposure the population was divided into two groups; Group I not exposed to ETS and Group II exposed to ETS. Statistical analysis was done by using chi square test for categorical variables and unpaired‘t’ test for continuous variables. Univariate and multivariate regression analysis were performed to study the risk of adverse outcome in association with ETS exposure. Logistic regression was done for categorical outcome and linear regression for continuous variables. RESULTS

Out of 1000 women 312 patients (31.2%) had history of ETS exposure (group I) and 688 patients (68.8%) were not exposed to tobacco smoke (group II). Table 1 shows the maternal profile. The mean age in both the groups was

MATERIALS AND METHODS

Approval from institutional ethics committee was taken and the study was conducted in a tertiary institute of Northern India. The study group consisted of 1000 consecutive nonsmoking women delivering a singleton live baby. Each woman was interviewed post delivery according to a predesigned structured questionnaire. The questionnaire recorded details about ETS exposure. Demographic and medical details were noted down from the hospital records.

Table 1 — Maternal profile

Age (years) Parity(mean) Education* : Illiterate School only Graduate Occupation : Unemployed Employed Residence : Rural Urban Anemia* *p<0.05

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comparable. Mean parity, area of residence and employment status was comparable in both the groups. Education level was significantly different in both groups. More women were graduates in group II. Anemia was significantly more in group I. Other parameters like mean number of family members (5 ± 3 versus 5 ± 3), number of children (1 ± 1 versus 1 ± 1) and number of adults (4 ± 2 versus 5 ± 2) in both the groups were comparable. The difference in mean monthly income was statistically significant (Rs. 4547 ± 5145 versus Rs 6894 ± 6736). There was no difference in incidence of PIH, GDM, Placenta previa and abruption among both the groups. The incidence of Preterm labor was more in group exposed to ETS although was not statistically significant (24.7% versus 21.2%). The incidence of premature rupture of membranes was similar in both the groups (Table 2). The mean birth weight of babies in group I was 2.398 ± 0.626 g and in group II was 2.530 ± 0.649g. The difference was 132 gms which is statistically significant (p<0.05). In group I, 163 (52.2%) babies weighed less than 2.5Kg compared to 272 (39.5%) babies in group II and this difference was statistically significant. Similarly more babies were less than 2Kg in group exposed to ETS than in unexposed group (24.4% versus 17.9%). This difference was also statistically significant. The univariate and multivariate logistic regression analyses for outcome in relation to ETS exposure have been shown in Table 3. The crude and adjusted odds ratio (95% CI 1.278-2.191 and 1.222-2.264) was significant for low birth weight babies in the group exposed to ETS thus showing the adverse effect of ETS exposure. On analysing further it was seen that bidi smoke exposure had more effect than cigarette smoke (95% CI 1.449-2.629 and 1.228-2.421) (Table 3). DISCUSSION

ETS exposure was associated with low birth weight and more so with bidi smoke in the present study. The

Parameter

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ETS exposure (N=312)

No ETS exposure (N=688)

25 ± 4 1.85 ± 0.35

26 ± 4 1.75 ± 0.26

Parameter

50 (16%) 76 (24.4%) 186 (59.6%)

24 (3.5%) 90 (13.1%) 574 (83.4%)

291 (93.3%) 21 (6.7%)

615 (89.4%) 73 (10.6%)

154(49.4%) 158 (50.6%) 54 (17.3%)

330 (48%) 358 (52%) 42 (6.1%)

Pregnancy induced hypertension 90 (28.8%) Gestational diabetes mellitus 6 (1.9%) Placenta previa 14 (4.5%) Abruptio placentae 0 Premature rupture of membranes 3 (1%) Preterm labor 77 (24.7%) Baby weight* (mean ± SD) kg 2.398 ± 0.626 Low birth weight* (<2.5kg) 163 (52.2%) Low birth weight* (<2kg) 76 (24.4%)

Table 2 — Pregnancy outcome

*p < 0.05

ETS exposure (N=312)

No ETS exposure (N=688) 200 (29.1%) 15 (2.2%) 27 (3.9%) 1 (0.1%) 4 (0.6%) 146 (21.2%) 2.530 ± 0.649 272 (39.5%) 123 (17.9%)

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to be 1.664 (95% CI: 1.222-2.264). The increase in risk of LBW has also been reported Parameter Type of ETS Crude OR (95% CI) Adjusted* OR (95% CI) by Martin et al 11, the relative risk in their study was 2.17(95% CI: 0.90-2.56) after adjustment Pregnancy induced Total 0.989 (0.736-1.329) 1.070 (0.769-1.490) hypertension Cigarette 1.271 (0.763-2.118) 1.360 (0.795-2.325) for confounding factors. Ahluwalia et al (14) Bidi 0.911 (0.656-1.267) 0.978 (0.675-1.417) reported adjusted odds ratio for LBW of 2.42 Gestational diabetes Total 0.880 (0.338-2.289) 1.127 (0.381-3.337) (95% CI: 1.51-3.87) among the smokers 30 mellitus Cigarette 1.264 (0.283-5.639) 1.698 (0.343-8.407) Bidi 0.764 (0.251-2.324) 0.942 (0.269-3.305) years and older. Placenta previa Total 1.150 (0.595-2.225) 1.546 (0.713-3.354) The association of active maternal smoking Cigarette 0.340 (0.046-2.539) 0.488 (0.063-3.811) with pregnancy complications like abruption Bidi 1.408 (0.714-2.776) 1.921 (0.854-4.323) placentae, placenta previa, GDM and PIH is well Premature rupture Total 1.660 (0.369-7.463) 1.167 (0.229-5.948) known but data with regard to these antenatal of membranes Cigarette 4.817 (0.867-26.76) 5.833 (0.893-38.1) Bidi 0.718 (0.080-6.460) 0.392 (0.039-3.902) complications in relation to passive smoking is Preterm labor Total 1.216 (0.887-1.668) 1.301 (0.909-1.863) limited. We also did not observe any difference Cigarette 0.730 (0.383-1.392) 0.942 (0.481-1.844) in the incidence of above mentioned Bidi 1.387 (0.989-1.945) 1.424 (0.967-2.099) complications in both the groups. Low birth weight Total 1.673 (1.278-2.191) 1.664 (1.222-2.264) (<2.5kg) Cigarette 1.008 (0.616-1.650) 1.494 (0.881-2.533) The incidence of preterm delivery in the Bidi 1.952 (1.449-2.629) 1.724 (1.228-2.421) group exposed to ETS was more than the Low birth weight Total 1.479 (1.070-2.045) 1.454 (1.001-2.113) unexposed group but the difference was not (<2kg) Cigarette 0.815 (0.417-1.593) 1.716 (1.215-2.424) statistically significant (24.7% versus 21.2%). Bidi 1.142 (0.565-2.306) 1.548 (1.037-2.311) Ahluwalia et al have also shown increased risk *Adjusted for religion, residence, monthly income and number of family members of preterm delivery in ETS exposed group. and anemia In order to see the effect of type of tobacco product on perinatal outcome, further analysis was done. Bidi had more significant risk for causing low reduction in mean birth weight was 132 gms. Many studies birth weight babies (OR 1.952 95% CI: 1.449-2.629). In a have reported reduction in birth weight in regard to ETS study from Mumbai, by Pakhale et al , the levels of exposure during pregnancy. The reduction in mean weight nicotine and minor tobacco alkaloids in the mid stream in the present study is in accordance with earlier studies on and side stream smoke were analysed and were compared ETS exposure and birth weight. A meta-analysis of studies between bidi and cigarettes. They used gas conducted before mid-1995 reported an overall RR of 1.2 chromatography-flame ionization method and observed (95% CI, 1.1 to 1.3) for LBW at term or small-for- higher content of nicotine and minor tobacco alkaloids in gestational age among the infants born to mothers exposed tobacco from bidi (37.7 mg per gm) as compared to cigarettes (14-16 mg per gm). to ETS during pregnancy . In this study it was observed that Indian women did not Schwartz-Bickenbach et al reported that mean birth weight of babies born to ETS exposed mothers reduced by understand the concept of passive smoking and did not 205 gm. Haddow et al also reported a mean birth weight know the bad effects of smoke on the growing fetus. reduction of 108 gm. The reduction in mean birth weight Interestingly it was seen that there was a significant was 138 gm in an Indian study by Goel et al , where as difference in level of education in the women in ETS Mathai et al observed reduction of 63 gm after adjusting exposed and unexposed groups. More women were for the confounders. Similarly, the birth weights have been graduates in the unexposed group (83.4% versus 59.6%). There was no significant difference in other found to be lower in studies that have compared selfepidemiological factors. In summary, Environmental reported ETS exposure from all sources (home and work). smoke exposure during pregnancy leads to significant After adjustment for potential confounders, most of the reduction in birth weight and higher number of low birth studies showed small to moderate decrements in mean weight babies. birth weight (10 to 90g) associated with ETS exposure . Acknowledgement: Deepika, Leela Chauhan. The mean birth weight in the present study was not REFERENCES adjusted for gestational age and was calculated among all 1 Nelson E — The miseries of passive smoking. Hum Exp Toxicol 2001; 20: 61-83. the term and preterm babies. In a review by Misra et al it 2 AhluwalIa IB, Grummer-Strawn L, Scanlon KS — Exposure was observed that difference in birth weight was larger if to environmental tobacco smoke and birth outcome: birth weight was not adjusted for gestational age. Apart increased effects on pregnant women aged 30 years or from causing reduction in mean birth weight, exposure to older. Am J Epidemiol 1997; 146: 42-7. 3 Jaakkola JJ, Jaakkola N, Zahlsen K — Fetal ETS increases the risk of low birth weight (LBW). In the growth and length of gestation in relation present study the adjusted odds ratio for LBW was found Table 3 — Odds of ETS exposure for various pregnancy outcomes

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Original Article Morphometric study of lumbar pedicle obtained from 65 cadavers, in Rewa region of central India Amrish Tiwari1, D C Naik2, P G Khanwalkar3, Meghana Mishra4, Bhaskar Reddy5

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prenatal

exposure to environmental (Continued on page 14)

The aims of the study were to understand pedicle dimensions for the development of techniques and devices for spinal instrumentation because a misplaced or misdirected pedicle screw may cause injuries to the pedicle cortex, nerve root, facet joint and adjacent vital structures.The present study was conducted on 65 dry human lumbar vertebrae (20 atypical and 45 typical) obtained from 65 cadavers, in Department of Anatomy Shyam Shah Medical college Rewa, (Madhyapradesh).Pedicle vertical height (h), Pedicle width (w) and Interpedicular distance (IPD)were taken with the help of a sliding verniercaliper. Results indicated that in Rewa region of central India, Steffeepedicle screw of 4 mm and 15 mm size can be used safely for typical and atypical lumbarvertebrae respectively. [J Indian Med Assoc 2017; 115: 11-4]

Key words : Lumbar vertebrae, Pedicle dimensions, Spinal instrumentation, Screw size.

pedicle is the strongest part of a lumbar vertebra, which is made up of entirely cortical bone with a small core of cancellous bone . Strong and large pedicles of lumbar vertebra as compared with the thoracic and cervical ones make them ideal for screw instrumentation. Transpedicular screw fixation of spine has developed as a very successful method of spinal fixation. The fixation of lumbar spine is needed for various spinal problems like fracture in lumbar spine, resection of tumours in vertebral bodies, gross spondylolisthesis and lumbar instabilities. Majority of pedicle morphometric studies were based on white population in different parts of the world . Indian population forms the one-fifth of the total population of the world and the non-resident Indians are also distributed widely in many countries whereas only few studies are available on this population. Secondly there is a significant difference in size and shape of body parts in different places. The aim of this study is to report the results of a morphometric study of adult lumbar vertebrae’s pedicles, to provide morphometric inputs for the use of this vertebral component in implants fixation or as an access port to vertebral body through pedicle specially in Rewa region of central Indian population. 1

2,3,4,5

Department of Anatomy, Shyam Shah Medical College, Rewa 486001 1 MBBS, MS (Anatomy) Final year Postgraduate Student 2 MS (Anatomy), Professor and Head 3 MS (Anatomy), Professor 4 MS (Anatomy), Associate Professor 5 MSc (Anatomy), Assistant Professor

MATERIALS AND METHODS

We have randomly selected Sixty five dry Human lumbar vertebrae (20 atypical and 45 typical) obtained from 65 cadavers, in Department of Anatomy Shyam Shah Medical college, Rewa (Madhyapradesh), for pedicle morphometry. Geographically Rewa is bounded on the north by Uttar Pradesh, on the east and southeast by Sidhi, on the south by Shahdol, and on the west by Satna. It is part of Rewa Division and has an area of 6,240 km . Approximate population of the Rewa is about 235,422.All the vertebrae were fully ossified, we have excluded deformed and broken vertebrae from the study. Pedicle vertical height (h), pedicle width (w) and interpedicular distance (IPD) were measured using sliding vernier caliper. All measurements were done at three different sittings, and the mean of the values corrected to the nearest millimeter was recorded. We used following method for recording different measurements : Pedicle Vertical Height (h) — Two closest points on the upper and lower margins of the pedicles in the vertical plane on its lateral aspect, as shown in Fig 1. Pedicle Width (w) — Two closest points on the medial and lateral surfaces of the pedicle, at right angle to the long axis of pedicle, as shown in Fig 2. Interpedicular Distance (IPD) — Maximum distance between two closest points on medial surfaces of right and left pedicles of same vertebra as shown in Fig 3. 2

OBSERVATIONS AND RESULTS

Pedicle vertical height (h), Pedicle width (w), Interpedicular distance (IPD) of Atypical and Typical dry

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surgeons such as Boucher , Pennel et al , Louis and Maresca , Dick , Steffee et al , and others. Several different sizes and shapes of pedicle screws are available. These include cortical as well as cancellous Fig.1 — Pedicle vertical height Fig 2 — Pedicle width (w) Fig 3 — Interpedicular distance (IPD) screws of varying pitch and (h) measurement (lateral view) measurement (lateral view) measurement (superior view) screw patterns. Some are available in cannulated and uncannulated designs. Screw diameters human lumbar vertebrae were measured. Mean, Standard vary from 4.5 to 7.0 mm in outer and inner diameters. The deviation, Range, P value, Correlation coefficient for length of pedicle screws varies, most increasing from 30 height and width are depicted in Table 1 and Table 2. mm in 5-mm increments. The screws are designed to While measurements for interpedicular distance are connect with certain fixation devices, most commonly shown in Table 3. For both height and width,the difference either a plate or a rod. Porter et al (1989) suggested that increasing levels of in the measurements between the right and left side was physical activity were associated with increased strength statistically insignificant (p > 0.05). of vertebral column in individuals aged over 18 years. The Correlations between height and width of dry human variation in diameter of pedicles in different age groups lumbar vertebrae are shown in Graph 1, 2, 3, 4 indicating a may be due to the weight-bearing function. positive correlation between the two. Kothe et al also reported that difference of thickness DISCUSSION on vertebral pedicle’s corticals. According to these Pedicle screw fixation is rapidly becoming a widely authors, the pedicle’s lateral cortical thickness ranged used method of spinal instrumentation. Since King first from 0.4 to 0.6 mm, and the medial cortical from 0.9 to 1.7 placed short screws almost transversely across the lateral mm. Pedicle’s upper and lower corticals also showed articulations of the posterior column of lumbar different thickness at more cranial levels. In pedicle screw insertion, the screw is passed through vertebrae(transfacet screw placement), there has been an the posterior aspect of the pedicle into the body of the almost continuous development based on the work of 7

Table 1 — Pedicle height of lumbar vertebrae

Left

Atypical lumbar vertebrae

Mean(mm) SD Range(mm) P Value Correlation coefficient

14.565 1.862 11.5 – 18.4 1 0.863

14.565 1.576 11.7 – 17.5

Typical lumbar vertebrae

Mean(mm) SD Range(mm) P Value Correlation coefficient

13.442 1.539 10.7 – 16.1 0.251 0.803

13.068 1.531 10 – 15.8

Right

Left

Atypical lumbar vertebrae

Mean(mm) SD Range(mm) P Value Correlation coefficient

17.385 1.645 15 – 20.8 0.550 0.698

17.705 1.717 15 – 21.3

Typical lumbar vertebrae

Mean(mm) SD Range(mm) P Value Correlation coefficient

9.482 3.354 4 – 17.9 0.917 0.958

9.557 3.570 5 – 19.6

Table 3 — Interpedicular distance of lumbar vertebrae Interpedicular Distance

Graph 1 — Right side atypical

Graph 3 — Right side typical

Atypical lumbar SD vertebrae

Mean(mm) 1.989 Range(mm)

25.16 20.8 – 29.5

Typical lumbar vertebrae

Mean(mm) SD Range(mm)

22.075 2.673 15.4 – 30.5

Graph 2 — Left side atypical

Graph 4 — Left side atypical

CONCLUSION

In Rewa region of central India Steffee pedicle screw size that can be safely used: For typical lumbar vertebrae 4 mm and for atypical lumbar vertebrae 15 mm size is safe, with exceptions of congenitally malformed vertebrae and the vertebrae having anatomical variations.Since the diameter of the pedicle screw is governed by the mini-

vertebra anteriorly. Since the success of this technique depends upon the ability of the screw to obtain strength within the vertebral body, the choice of the screw to be used is determined by the minimum diameter of the pedicle. Therefore, morphometric data concerning Comparison of Present Study with Prior Works : pedicles is useful in preoperative planning and also in Vertebra Amonoo-kuofi Singel et al Arora et al designing pedicle screws and other implantable level Male Female Male Female Male Female devices. In our study in atypical lumbar vertebrae mean L1 Height 19.4 16.3 14.7 15.5 14.79 14.34 Width 10.3 8.7 8.2 8.5 7.51 7.49 pedicle vertical height was same on both right and left L2 Height 18.9 15.3 15 14.5 15.42 15.04 side (14.565 mm).While in typical lumbar vertebrae Width 10.7 9 8.5 8.75 7.95 7.91 mean height was 13.442 mm on right side and 13.068 L3 Height 19.3 15.9 14.7 14.8 16.42 15.6 Width 12.1 10.5 10.4 10.6 8.75 8.71 mm on left side. As compared to present study L4 Height 19.9 16.1 14 14 17.48 17.11 Width 13 11.1 13.5 13.8 13 12.97 Slightly higher values for vertical height were L5 Height 20.7 17.5 13.4 13.25 19.48 18.3 reported by Arora et al (2005) (16.42 mm in males Width 14.2 12.5 18.2 19.25 15.34 13.31 and 15.6 mm in females) and lower values by Singel *Height and width in millimeter et al (2004) (10.4 mm in males and 10.6 in females). 14

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Because screw diameter is decided by the minimum diameter of the pedicle, vertical height is of little significance. In our study in atypical lumbar vertebrae mean width of the pedicle was 17.385 mm on right side and 17.705 mm on left side, with minimum value of 15 mm on both sides. While in typical lumbar vertebrae mean width of the pedicle was 9.482 mm on right side and 9.557 mm on left side with minimum value of 4 mm on right side and 5 mm on left side. If we compare our study with prior works by other authors, some interesting facts comes out. In previous reports by Amonoo-Koufi and Singel et al , values for right and left pedicles of the lumbar vertebrae were nearly same. In our study also values for both sides were nearly same, as the p value was more than 0.05, so the difference is insignificant. Kunalchawla et al (2011) and prior studies says that vertical height is always greater than its width, contrast to our study results, which indicates that in typical vertebrae height is greater than width but in atypical vertebrae width is greater than height. Also our observations indicate that height and width are directly proportional, when we move towards atypical vertebrae from typical vertebrae. In our study Interpedicular distance (IPD) of typical vertebrae shows mean value of 20.075 mm while atypical vertebrae shows mean value of 25.16 mm.The anteroposterior shortening of the pedicle and the reduction in transverse interpedicular distance is one of the commonest causes of stenosis of the vertebral canal. 2

Table 2 — Pedicle width of lumbar vertebrae

Right

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Present study L1-L4 Mean height 13.25 Mean width 9.5 L5 Height 14.56 Width 17.54

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mum diameter of the pedicle, according to present study above size is safe in this region. It would be prudent to conduct further such type of studies in different parts of world given its wide usage and subsequent beneficial implications. REFRENCES 1 Roy-Camille R, Saillant G, Mazel C — Plating of thoracic, thoracolumbar and lumbar injuries with pedicle screw plates. Orthop Clin North Am 1986; 17: 147-59. 2 AmonooKuofi HS — Age-related variations in horizontal and vertical diameters of pedicles of lumbar spine. J Anatomy 1994; 186: 321-8. 3 Berry JL, Moran JM, Berg WS, Steffee AD — A morphometric study of human lumbar and selected thoracic vertebrae. Spine 1987; 12: 362-7. 4 Krag MH, Beynnon MS and Pope MH — An internal fixatar for posterior application to short segments of thoracic, lumbar or lumbosacral spine - Design and testing. Clinical Orthopaedics and Related Research 1986; 203: 75-98. 5 Zindrick MR, Wiltse LL and Widell EH — A biomechanical study of intrapedicular screw fixation in lumbosacral spine. Clinical Orthopedics and Related Research 1986; 203: 99112. 6 King D — Internal fixation for lumbosacral fusion. J Bone Joint Surg 1948; 30A: 560.

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7 Boucher HH — A method of spinal fusion. J Bone Joint Surg 1959; 41B: 248. 8 Pennal GF, McDonald GA, Dale GG — A method of spinal fusion using internal fixation. Clin Orthop 1964; 35-6. 9 Louis R — Fusion of the lumbar and sacral spine by internal fixation with screw plates. Clin Orthop 1986; 203: 18. 10 Dick W — Die Operative Behandlung der Thorakalen und LumbalenWirbebelfrakturenunterBesondererBeruecksichtig ung des Fixateur Interne. Doctoral dissertation, University of Basel, Switzerland, 1983. 11 Steffee AD, Sitkowski DJ, Topham LS — Total vertebral body and pedicle arthroplasty. Clin Orthop 1986; 203: 203. 12 Porter RW, Adams MA, Hutton WC — Physical activity and strength of lumbar spine. Spine 1989; 14: 201-3. 13 Kothe R, O’Holleran JD, Liu W, Panjabi MM — Internal architecture of the thoracic pedicle. An anatomic study. Spine 1996; 21: 264-70. 14 Arora L, Dada R, Singh V — Morphometric Study of Lumbar Pedicles in Delhi Region of Northern India. Indian J Practising Doctor 2005; 3. 15 Singel TC, Patel MM, Gohil DV — A study of width and height of lumbar pedicles in Saurashtra region. J AnatSoc India 2004; 53: 4-9. 16 Kunal Chawla, Mahesh Sharma, Avinash Abhaya, Suman Kochhar — Morphometry of the lumbar pedicle in North West India. Eur J Anat 2011; 15: 155-61.

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Primary closure of an abscess cavity : our observation Dnyanesh M Belekar1, Ushma K Butala2

Abscesses have been conventionally treated since ages by incision and drainage followed by packing of cavity and allowing secondary healing. Primary closure of abscesses has been practised in literature. Aim of study was to compare outcome of the alternative method over conventional method in terms of hospital stay, post operative pain and cost effectiveness. A prospective study of hundred patients with abscess was studied for a period of one year. Fifty patients were randomly subjected to primary closure(n=50) and fifty patients with abscess were treated with conventional open drainage (n=50). Data was evaluated and statistically analysed. Data was analysed and standard error of difference of proportion was calculated to assess difference in duration of healing, hospital stay, post operative pain and incidence of complication. There was significant difference in duration of hospital stay (SE =0.28, Z =7.8 )and expenditure of treatment (SE =30.09, Z=10.58). A significant difference was observed statistically in pain and use of analgesic. There was no difference in rate of complication in both the methods. Primary closure of acute superficial abscesses was associated with an improved outcome in terms of quality of healing, postoperative pain, length of hospitalization and, by implication, cost. This method may be considered as an alternative treatment that is superior to the open technique as analysed in our study. P

[J Indian Med Assoc 2017; 115: 15-8]

tobacco smoke assessed by hair nicotine concentration. Environ health Perspect 2001; 109: 557-61. Windham GC, Hopkins B, Fenster L — Prenatal active or passive tobacco smoke exposure and risk of preterm delivery or low birth weight. Epidemiology 2000; 11: 427-33. Rubin DH, Krasilinkoff PA, Leventhal JM — Effects of passive smoking on birth weight. Lancet 1986; 11: 415-7. Windham GC, Eaton A, Hopkins B — Evidence for an association between environmental tobacco smoke exposure and birth weight: a meta-analysis and new data. Paediatr Perinat Epidemiol 1999; 13: 35-57. Schwartz-Bickenbach D, Schulte-Hobein B, Abt S, Plum C, Nau H — Smoking and passive smoking during pregnancy and early infancy: Effect on birth weight, lactation period and cotinine concentration in mother’s milk and infant’s urine. Toxicology Letters 1987; 35: 73-81. Haddow JE, Knight GJ, Palomaki GE, McCarthy JE — Second trimester serum cotinine levels in nonsmokers in relation to birth weight. Am Obstet Gynecol 1988; 159: 4814. Goel P, Radotra A, Singh I, Aggarwal A, Dua D — Effects of passive smoking on outcome in pregnancy. J Postgrad Med 2004; 50: 12-6. Mathai M, Vijasari R, Babu S, Jayaseelam L — Passive

maternal smoking and birth weight in south Indian population. Br J Obstet Gynecol 1992; 99: 342-3. Martin TR, Bracken MB — Association of low birth weight with passive smoke exposure in pregnancy. Am J Epidemiol 1986; 124: 633-42. Lazzaroni F, Bonassi S, Manniello E, Morcaldi L, Repetto E, Ruocco A, et al — effect of passive smoking during pregnancy on selected perinatal parameters. Int J Epidemiol 1990; 19: 960-6. Misra DP, Nguyen RHN — Environmental tobacco smoke and low birth weight: A hazard in the workplace? Environ Health Perspect 1999; 107: 879-904. Ahluwalia IB, Grummer-strawn I, Scanlon KS — Exposure to environmental tobacco smoke and birth outcome: increase effects on pregnant women aged 30 years or older. Am J Epidemiol 1997; 146: 42-7. Mortensen JT, Thulstrup AM, Larsen H, Moller M and Sorensen HT — Smoking, sex of the offspring, and risk of placental abruption, placenta previa and pre-eclampsia: a population based cohort study. Acta Obstet Gynecol Scand 2001; 80: 894-8. Pakhale SS, Maru GB — Distribution of major and minor alkaloids in tobacco, mainstream and side-stream smoke of popular Indian smoking products. Food chem. Toxicol 1998; 36: 1131-8.

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Observational Study

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Key words : Abscess, primary closure, Incision and drainage.

bscesses are one of the most commonly encountered surgical problems. Since ages, management of an abscess has been incision and drainage and usually the wound is managed by secondary intention. In our study, we have evaluated the role of primary closure in management of various abscesses and its efficacy in various aspects and compared the results with conventional drainage, curettage and packing of abscess. MATERIALS AND METHODS

A prospective study was conducted at tertiary care Hospital And Research Centre, for a period of one year. Ethics approval was obtained from the ethics committee of the hospital. Study comprised of hundred patients diagnosed with superficial abscess. Of these patients, fifty cases underwent primary closure following drainage and fifty patients underwent conventional open drainage followed by packing. Criteria for eligibility : Inclusion criteria — • All age group Department of Surgery, K J Somaiya Medical College, Hospital & Research Centre, Mumbai 400022 1 MBBS, MS, FCPS, DNB, MNAMS, FAIS, FMAS, Associate Professor & Unit Head 2 MBBS, DNB, Assistant Professor

• Size of abscess > 1cm • Parent or patient consent Exclusion criteria — • Location of abscess on face • History of recurrent or chronic abscess • Immune compromised or unstable patient • Wound already burst open or drained • Patient not willing follow up • Large abscess (size >10 cm ) 100 patients with acute superficial abscess requiring drainage were randomly allocated to one of the 2 groups after obtaining informed consent. Patients with abscess size >4 cm were treated on day care basis. Appropriate theatre technique and discipline was followed. Antiseptic baths were given and optimal scrubbing was done. Both general and regional anaesthesia was used depending upon the site of abscess. For lower limb, gluteal, perineal and scrotal abscess regional anaesthesia was given. While in other cases, general anaesthesia in the form of laryngeal mask airway or total intravenous sedation was given. All patients were given intravenous broad spectrum antibiotics and then oral antibiotics were continued for 5 days in both the groups. Abscess was incised and a specimen of pus taken for both aerobic and anaerobic cultures. Wall of abscess was then removed by curettage by using Volkmann’s scoop

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till bleeding seen from remnant cavity wall. Wound was then washed with povidone iodine solution. In conventional open method, abscess cavity was packed with roller gauze and dressing done. If dressing was not soaked, pack was removed after 24 hrs and cavity irrigated and packed again. Frequent dressings were done till healing occur. In patients selected for primary closure, drain was kept in situ and skin was closed with monofilament mattress sutures (Fig 1). Wound was dressed. Wound was checked after 48 hrs or when dressing soaked. Drain was removed after 2 days and if wound was dry sutures removed after 7 days (Fig 2). In case of discharge and necrosis of skin, sutures were opened and wound was allowed to heal by secondary intention. Healing was considered to have occurred when the skin edges were closed and flat, pain and induration resolved with no discharge (Fig 3). Duration of pain and quality of pain in both the groups was assessed by visual analogue scale on day1 and on day3. Total cost of treatment was calculated by taking into consideration following criteria: • Number of dressings required after drainage which includes cost of dressing material (cost of each dressing

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Fig 3 — Scar of abdominal abscess after primary closure 4 weeks later

was calculated depending upon the amount of dressing material used) • Duration of hospital stay (per day hospital charges were taken into account) • Number of follow up visits of patient till complete wound healing achieved.(In case of open method till secondary healing accomplished. In closed method till suture removal done) All the data was tabulated and statistical analysis was done. RESULTS

Data was collected and analysed using SPSS 16.0. Duration of hospital stay, difference in pain and difference in expenditure in both the groups was compared. The level of significance was assessed by standard error of difference of mean (Table 1 & 2). Table 1 — Distribution of abscess site in both the groups Site of abscess Open method Closed method Fig 1 — Primary closure of scrotal abscess with drain

Head and neck Breast Axilla Abdominal wall Gluteal Thigh Lower limb Foot Back Scrotal and perineal

1 10 3 5 8 5 4 1 6 7

2 9 4 7 6 6 6 2 3 5

Table 2 — Distribution of abscess size in both the groups Size of abscess Open method Closed method Size <4 cm 18 23 Size > 4cm 32 27 Largest abscess drained by open method 8 cm (mean Fig 2 — Wound of scrotal abscess on day 7 after drain removal

size 5 cm). Largest size of the abscess by closed method 10 cm (mean size 4.5 cm). 18 patients in open method group and 23 patients in primary closure group had abscess size <4cm and were treated on day care basis (Table 3). Table 3 — Showing data of micro organisms cultured from abscess in both the groups Micro organism Open method Closed method detected Staphylococcus aureus 42 40 Proteus mirabilis 0 0 E coli 8 10 Pseudomonas 0 0 Others 0 0 Pus cultured in both the groups showed predominantly growth of gram positive (Staph. aureus) (Table 4). Table 4 — Showing mean hospital stay, mean dressings per patient, mean treatment cost and duration of wound healing in both the groups Parameter Open Closed method method Mean hospital stay(days) 4.5 2.28 Mean treatment cost(rupees) 441 114 Mean dressings per patient 5 2 Wound healing (weeks) 2.5 1 Duration of hospital, expenditure in both treatment methods and difference in pain was compared by calculating the mean and standard error of difference in mean. (Level of significance was set at p=0.05). A significant difference was observed between both the methods (Table 5). Table 5 — Showing mean pain score (VAS) in both groups on day 1 and day 3 Mean pain score (VAS) Open Closed method method Day 1 5.72 5.5 Day3 5.06 1.98 Mean pain score on day 1 and day3 in both the groups was calculated. Statistical analysis was done to assess significance in difference between both the methods by calculating standard error of difference between the means. (Z test was applied with p=.05). Significant difference was observed in both methods on day 3 (Table 6). Table 6 — Showing complications in both the groups Type of complication Open Closed method method Oedema 5 4 Wound gape 0 2 Wound infection 3 2 Wound infection in both the groups was persistent infection. These patients had significant erythema and oedema even after abscess drainage and developed skin necrosis at incision site. Cases in open method, underwent subsequent debridement under anaesthesia . Patients in closed method group, developed wound discharge and

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sutures had to be removed after 24 hours. These wounds healed by secondary intention. In both the groups, rate of complications was found to be same. DISCUSSION

An abscess is an abnormal collection of purulent material bordered by pyogenic membrane. Pus is generated by infectious process usually caused by bacteria or parasites. Organisms kill the local cells, resulting in the release of cytokines which trigger an inflammatory response. The final structure of an abscess is an abscess wall, which is formed by the adjacent healthy cell in attempt to keep the pus from infecting neighbouring structures. Such encapsulation tends to prevent immune cells from attacking bacteria in the pus, or from reaching the causative organisms. Since ages, a general surgical premise has been that highly infected wound should never be closed by primary intention because of risk of infection.. Hence the conventional treatment of superficial abscesses is incision, curettage, drainage and in some cases de-roofing prior to allowing open drainage . This is followed by secondary healing in which the open wound is allowed to heal by granulation tissue formation and reepithelization . Primary closure of abscess was first suggested and studied by Ellis, 1951 . Since then many studies have been mentioned in literature describing the successful use of incision and drainage followed by primary closure for a 2,3,4,5

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variety of abscesses including head, neck, breast, and extremities . In our study, 50 patients with superficial abscesses were treated with primary closure with a drain. In the open method 64% of patients had an abscess more than 4cm while 54% in the closed method had an abscess more than 4cm. These patients were admitted in hospital for 48 hrs and wound checked as per study protocol and then discharged. They were kept admitted as there was significant inflammation around large abscess and most of them needed prompt supervision.18 patients in open method group and 23 patients in closed method group had abscess <4 cm and were treated on day care basis. in our study , the most common organism that was cultured was gram positive bacteria (staphylococcus aureus) in about 84 patients which was similar to observations in previous studies . the organism showed highest sensitivity on culture to amoxicillin and ceftriaxone. In our study, we continued oral antibiotic for 5 day. However, there have been studies in past, which propose single dose antibiotic . Literature also mentions successful treatment of abscess by primary closure without use of antibiotics . Primary closure of abscess alleviates the need of daily packing of wounds. In our study, mean dressing required per person was more open method. It was observed that frequent packing and dressing of wounds led to missed days from work or school and utilization of health care resources. Also this procedure is painful and usually requires sedation especially in children. In our study, overall analgesic requirement was less in the patients treated by closed methods. There was no significant difference in pain between both the groups in immediate post operative period. However, statistically significant difference was observed after 48 hrs. Patients with abscess treated by primary closure had faster healing (1 week) as compared to the open method (2-3weeks). Excellent healing rates have been reported in the past after closure of breast, axilla and various other abscesses by primary closure . It was observed that patients treated by primary closure had a better quality scars at the end of 3 months as compared with the open method as seen in other studies in past . Duration of hospital stay was assessed in both the groups. There was statistically significant difference in length of hospital stay between both the groups as reported in other studies in literature . Patients treated with primary closure had to bear with cost of drain and monofilament suture. However, overall cost of treatment by primary closure was significantly less than the open group when analysed statistically. Expenditure was low in closed method due to decreased number of dressings, less need of analgesics and decreased duration of hospital stay. Various complications were observed following drainage of abscess like peri-wound oedema, wound 8

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discharge and gaping of primarily closed wound. However, there was no statistical difference in the rate of complications in both the groups. Patients with primary closure should be closely monitored for 48 to 72 hours to rule out any recurrence or wound discharge and additional opening of sutures. In our study, in closed method group, 2 patients developed wound infection and sutures had to be opened after 24 hours. While, 2 patients showed signs of healing, they later developed partial wound gape on removal of sutures. CONCLUSION

Primary closure of incised and drained abscess results in faster and better healing. There is lesser need of post operative analgesia along with lower treatment costs and lesser duration of hospital stay with no significant difference in complications and recurrence. REFERENCES 1 Mehta PH, Dunn KA, Bradfield JF, Austin PE — Contaminated wounds: infection rates with subcutaneous sutures. Ann Emerg Med 1996; 27: 43-8. 2 SM Barnes, P L Milsom — Abscesses: an open and shut case! Archives of Emergency Medicine 1988; 5: 200-5. 3 Korownyk C, Allan GM — Evidence-based approach to abscess management. Can Fam Physician 2007; 53: 16804. 4 Sabiston DC, Townsend CM — Soft tissue infections. In: Townsend CM, Beauchamp RD, Evers BM, Mattox K, editors. Sabiston textbook of surgery:the biological basis of modern surgical practice. 17th ed. Philadelphia: PA:Saunders; 2004. 263-8. 5 Derksen DJ — Incision and drainage of an abscess. In: Pfenninger JL, Fowler GC, editors. Pfenninger and Fowler’s procedures for primary care. 2nd ed. St Louis, MO: Mosby; 2003. 145-9. 6 Singer AJ, Thode HC Jr, Chale S, Taira BR, Lee C — Primary closure of cutaneous abscesses: a systematic review. Am J Emerg Med 2011; 29: 361-6. 7 Ellis M — The use of penicillin and sulphonamides in the treatment of suppuration. Lancet 1951; 7: 774-5. 8 Krishnarajah V — Treatment of abscesses by incision, curettage, and primary closure. Ceylon Med J 1984; 29: 1135. 9 Moran GJ, Krishnadasan A, Gorwitz RJ — Methicillinresistant S aureus infections among patients in the emergency department. N Engl J Med 2006; 355: 666-74. 10 PWH Blick, MW Flowers, AK Marsden, DH Wilson, ATM Ghoneim — Antibiotics in surgical treatment of acute abscesses. BMJ 1980; 111-2. 11 Rutherford WH, Calderwood JW, Hart D, Merrett ID — Antibiotics in surgical treatment of septic lesions. Lancet 1970; i: 1077-80. 12 Stewart MPM, Laing MR, Krukowski ZH — Treatment of acute abscesses by incision,curettage and primary suture without antibiotics:a controlled clinical trial. Br J Surg 1985; 72: 667. 13 Abraham N, Doudle M, Carson P — Open versus closed surgical treatment of abscesses: a controlled clinical trial. Aust N Z J Surg 1997; 67: 173-6. 14 Edino ST, Ihezue CH, Obekpa PO — Outcome of primary closure ofincised acute soft-tissue abscesses. Niger Postgrad Med J 2001; 8: 32-6. 15 Visvanathan R — Primary closure following drainage of a rectus sheath muscle abscess. Singapore Med J 1994; 35: 108-9.

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Observational Study Eye banking in India : current status and the way forward 1

Noopur Gupta , Radhika Tandon , Sanjeev K Gupta , Praveen Vashist

Corneal blindness is one of the priority diseases under the National Programme for Control of Blindness, India and an important cause of avoidable blindness in our country. A multi-pronged approach is needed to eliminate avoidable corneal blindness. Curable or treatable blindness requires a spectrum of care including medication, optical rehabilitation and corneal transplantation. Corneal transplantation for individuals with corneal blindness is dependent on availability of safe, donor eyes. There is a huge gap between demand and supply of donor corneal tissues in our country. In order to improve the eye banking system in the country, the Government of India supports eye banks through recurring and non-recurring grants for operational and infrastructure costs respectively. Strategic interventions by the government and non-government organizations include awareness by health promotion and education, community participation, sustainable source of donor cornea, adequate medical standards, accreditation and endeavors to strengthen eye banking systems and procedures through training and research. Model eye banking in India can be achieved only when the eye banking system is linked with the targeted infrastructure proposed under Vision 2020: Right to Sight-India. Considering these targets, we require 20 Eye bank training centres, 200 eye banks and 2000 Eye donation centres in the country. This would be a reality if Hospital Cornea Retrieval Program is strengthened in all private and government hospitals, medical standards are made uniform and mandatory for all eye banks and eye donation centres, and guidelines be devised for simplification of the registration and eye donation process to enhance community participation. [J Indian Med Assoc 2017; 115: 19-22]

Key words : Corneal blindness, eye banking, eye donation, keratoplasty.

lindness from corneal disease is a major ophthalmic public health problem in India. It is estimated that there are currently 1.14 million people with bilateral corneal blindness in the country . Moreover, it is estimated that there is an addition of approximately 25,000 to 30,000 corneal blind people every year . In a population-based study conducted in the state of Andhra Pradesh, India, the prevalence of corneal blindness was reported to be 0.10%, and prevalence of unilateral corneal blindness was 0.56% . Corneal transplantation is the only viable option for visual rehabilitation of people blind from corneal diseases. Based upon the availability of safe donor eyes and utilization rates, it is estimated that 2.7 lakh donor eyes are required for performing one lakh corneal transplants per year in India , an approximately six-fold increase from the donor eyes harvested currently. The wide disparity and paucity of donor human eyes in India poses a challenge to 1

Department of Community Ophthalmology, Dr Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi 110029 MS, DNB, Scientist Grade III (Ophthalmologist) MD, FRCO phth, Officer-In-Charge & Professor, National Eye Bank MD, Professor of Community Medicine MD, Additional Professor & Head 1

public health specialists and the health system, in general. Eye banking services in India : A three-tier community eye banking system has been proposed for India . The three tiers in the pyramid constitute Eye Donation Centres (EDC), Eye Banks (EB) and Eye Bank Training Centres (EBTC). The Eye Bank Training Centres are responsible for tissue harvesting, processing & distribution, creating public awareness as well as training and skill up-gradation of eye banking personnel. The middle tier comprises of eye banks (organizations which would comply with all the regulations stipulated by Eye Bank Association of India) . The Eye Donation Centres should provide public and professional awareness of eye donation, co-ordinate with donor families and hospitals to motivate eye donation, to harvest corneal tissue, and collect blood for serology and to ensure safe transportation of tissue to the parent eye bank. There are currently 249 functional eye banks in the country involved in collection and distribution of donated eyes as per the National Programme for Control of Blindness . This amounts to nearly one eye bank per 4-5 million population. However, a vast majority of these eye banks are concentrated in urban regions of the country. 5

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Many eye banks function more like collection centres rather than eye banks .There are very few eye banks, which maintain required quality and follow the prescribed medical standards as per Eye Bank Association of India (EBAI) . Cornea collection in the country as per NPCB in 201011 was 44926 as against a target of 60000;Tamil Nadu was responsible for more than one-fourth of donor eye collection . Cornea collection has shown a steady increase from 38646 donor cornea collected in 2007-08 . With the demand for corneas on the increase and the limited supply, it is imperative that the corneas received must be utilized to the maximum. Currently, the utilization rate ranges between 25% and 60% . The National Eye Bank, New Delhi collected 677 corneas during Jan-Dec 2010 from various sources. Out of these, 499 (77%) were utilized for both optical (39%) and non-optical purposes (34%) . In India, the eye banking infrastructure should be linked with the targeted infrastructure proposed under Vision 2020-Right to Sight for our country as shown in Fig 1. Considering these targets, each EDC should be available at the sub district level for every five lakh population, each eye bank should be available for every five million population, and all centres of excellence should be developed as Eye bank training centre. Hence we require 20 EBTC, 200 eye banks, 2000 EDC in the country. Eye donation awareness should be promoted at Vision Centre level. This will help in improved referral and linkage at all levels of health care delivery. Challenges ahead : Corneal transplantation offers the chance to restore sight in individuals who are visually impaired due to corneal disease. This, however, is dependent on the willingness of people to donate and pledge their eyes for eye donation. There are numerous barriers for collection of eyes. The level of awareness about eye donation and the willingness to donate eyes amongst the Indian population 7

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has been elucidated by different studies. In a study involving 507 subjects in South India, only half of the participants were aware of eye donation. Illiteracy and rural residence were more likely predictors for lack of awareness in this study. In rural Andhra Pradesh, 5572 subjects above 15 years of age were interviewed and awareness about eye donation was reported by 28% villagers . A similar study was conducted in 2522 urban subjects residing in Hyderabad. The awareness about eye donation in this population was 73.8%; however, only 1.9% had pledged their eyes . A hospital-based study conducted amongst relatives of 159 potential donors brought as postmortem cases (74.8% men and 25.2% women) to a tertiary care hospital in North India, revealed that none of the deceased had previously pledged their eyes . Willingness for eye donation was seen in 41.5% families. Major reasons for not donating eyes were refusal to discuss the issue and dissuasion by distant relatives, legal problems, and religious beliefs . Wellâ&#x20AC;&#x201C;informed nursing and medical students could be expected to influence eye donation rates, as they are the future health care providers. In a study involving 188 nursing students of Bangalore, majority (96.8%) of the students were aware that eyes can be donated after death; however only 38.2% knew that the ideal time of donation was within six hours of death Amongst medical students of Delhi, 99.4% knew that eyes can be donated after death; however only 41.1% knew about the ideal time of donation after death. Perceived reasons for not pledging eyes were lack of awareness (32.7%), objection by family members (27.7%), unsuitability to donate because of health problem (17.7%) and the unacceptable idea to separate the eye from the body (15.5%) . In a similar study, nearly one-third of the students were unaware that eyes should preferably be removed within six hours of death . There is a need to educate students in all fields, about eye donation so that the younger generation may act as motivators for enhancing eye donation rates in the community. Health professionals can counsel and motivate relatives and play an important link for the Hospital Cornea Retrieval Programme (HCRP). In a study involving 206 hospital staff members in Pune, 12.1% had excellent knowledge, 59.2% had good knowledge and 28.6% had poor knowledge about eye donation . Poor knowledge of the importance and procedure of eye donation among health professionals is of concern. Eye banking in India is in an evolving phase, ever since EBAI was established .The major challenges faced in this area include lack of organized eye banking system, improper regulation and non-supportive legislation. Quality issues like failure to adopt common medical standards for all eye banks, lack of properly trained eye banking personnel and lack of accreditation systems pose 12

16.

Fig 1 â&#x20AC;&#x201D; Proposed three-tier Eye Banking system linked to Vision 2020-Right to Sight India infrastructure targets. Each EDC (Eye Donation Centre) should be available for every 5 lac population, each Eye Bank (EB) for every five million population and each Eye Bank Training Centre (EBTC) for every five million population of the country

additional problems . Other areas of concern are inefficient public awareness programmes supplemented by need of consent from relatives, and no eventual benefit of pledging eyes before death. Surgical intervention for corneal blindness is rarely successful unless well-trained surgeons and nurses are available in conjunction with modern operating rooms, good equipment, reliable eye-bank facilities, and well established specialty clinical services for long-term follow up and treatment of graft rejections and other post keratoplasty complications. Factors that contribute to the upsurge of existing lacunae is the longer learning curve for keratoplasty surgery, decreased revenue generation for the private sector through this surgery, need of adequate infrastructure, human resource and networking needed to perform corneal transplantation and maintain an eye bank in order to produce good quality donor tissue. Due to nonequitable distribution of such specialized health care services in the country, timely management may not be available to people in the rural and underserved regions of the country, where the need of treatment and magnitude of corneal blindness may be the greatest . The poor outcome of penetrating keratoplasty, even if adequate donor quality tissue is available is an additional challenge. The outcome of penetrating keratoplasty in patients with bilateral corneal blindness was compared with unilaterally blind patients in a tertiary eye care hospital in North India . The outcome in patients with bilateral corneal blindness was poorer than those with unilateral corneal blindness, the most common cause of failure being graft infection (40%). The survival rates of corneal transplantation at one, two, and five years has been reported to be 79.6%, 68.7% and 46.5 % respectively in India . Way Forward : Most of the current awareness of eye donations has been achieved through publicity campaigns run by various non-governmental organizations and other voluntary organizations, supplemented by media campaigns by the government agencies. This is probably not effective in the illiterate population. Alternate strategies have to be developed to educate the illiterate and rural population, understanding their barriers and resolving their myths, giving due respect to their religious beliefs. For this, community participation and behaviour change at the local level is required. Moreover, it is estimated that there are insufficient corneal surgeons in rural areas to perform timely corneal transplant surgery even when good quality donor tissue may be available. This amounts to under utilization and wastage of donor corneas at this level. Although there is no dearth of knowledge, skills and resources to create a world class eye banking and corneal transplantation network in India , but a proactive national movement is definitely needed .The need of the hour is to strengthen existing strategies like widespread Hospital 21

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Cornea Retrieval Programme and grief counseling, favourable legislations, public awareness, medical standards, accreditation and continuous training programs for the personnel involved in eye banking . The regional variations and rural-urban gradient in the prevalence of various eye diseases like Vitamin A deficiency highlight the importance of health policy evaluation not only at the national and state levels but also at district and local community levels. This would help in fulfilling the goal of providing safe and high quality corneal tissue to everyone who needs corneal transplantation in the community in an equitable manner. Hospital Corneal Retrieval Programmes have been introduced to focus on active counseling of relatives in the hospitals after death. Trained eye donation counselors, commonly known as grief counselors, approach family members of the deceased in the hospital at an appropriate time, sharing their grief, and preparing them to take a positive step towards eye donation on behalf of their loved one . Although all this has helped in increasing eye donation rates, it has not reached the needed target. An improvement over this technique could be an introduction of a proforma with a request for eye donation filled up by the staff nurse on duty, especially at night, while giving the death certificate to the relatives in order to increase awareness and enhance eye donation rates in the hospital . It is suggested that a question on willingness of eye donation may be incorporated in the death certificate itself. The concept of pledging of eyes needs to be effectively translated into eye donation after death of an individual. Presumed consent should be followed in all such cases. Although HCRP form the backbone of most eye banks, home deaths, death places, cremation grounds through priests and faith leaders ; road traffic accidents & suicide deaths through casualty medical officers, emergency medical personnel and police officers should also be covered. A catalyst in those crucial hours after death can actually ensure that eyes are actually donated in most of the cases .The faith leaders can also inform the relatives of the deceased of the benefits of eye donation to the blind recipient and to the soul of the deceased. In this way, men and women of faith may positively influence potential donors and their next of kin. Local health volunteers and Accredited Social Health Activist identified under National Rural Health Mission can effectively participate in generation of community level awareness about eye donation . As they are recruited from the community itself, they are well known and acceptable to all the local inhabitants, and possess good communication skills with the local people. They can be instrumental in prevention and control of avoidable corneal blindness and visual impairment and act as mediator between the 3

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relatives and the nearest eye bank within early hours of death . A holistic approach involving comprehensive eye care with due emphasis on preventive, curative and rehabilitative aspects is the need of the hour. Prevention, health and nutrition education, timely presentation & referral in all cases of eye injuries and ulcers, establishing proper microbiology laboratories at primary care setting, awareness about knowledge of standard treatment protocols at the primary level will go a long way in improving the health status of the society. The focus in eye banking in the next millennium will have to be towards increase in corneal procurement, high quality and better utilization of all donor corneas received and lower costs of surgery. A sustained multi-pronged approach should be undertaken at all levels of health care, so that management and follow up of patients with corneal blindness is easily accessible and affordable to the rural poor. Community level workers, traditional healers and local practitioners need to be educated and their cooperation must be sought in order to direct patients to appropriate health care facilities and increase awareness about eye donation, so that corneal blindness may be avoided. 29

REFERENCES 1 Oliva MS, Schottman T, Gulati M — Turning the tide of corneal blindness. Indian J Ophthalmol 2012; 60: 423-7. 2 National Programme for Control of Blindness. http://pbhealth.gov.in/pdf/Blindness.pdf (accessed March 10, 2013). 3 Dandona R, Dandona L — Corneal blindness in a southern Indian population: need for health promotion strategies. Br J Ophthalmol 2003; 87: 133-41. 4 Saini JS — Realistic targets and strategies in eye banking. Indian J Ophthalmol 1997; 45: 141-2. 5 Standards of Eye Banking in India, 2009. http://npcb.nic.in/writereaddata/mainlinkfile/File176.pdf (accessed March 10, 2013): 109-117. 6 Functional Eye Banks-India-National Programme for C o n t r o l o f B l i n d n e s s . http://npcb.nic.in/writereaddata/mainlinkFile/File130.xls (accessed March 10, 2013) 7 Rahmathullah R, Srinivasan M, Rajkumar A, Selvam — Eye Banking For Developing Countries in the New Millennium. ttp://laico.org/v2020resource/files/eyebanking_ developingcountries.pdf (accessed March 10, 2013): 1-7. 8 Rao GN — What is eye banking? Indian J Ophthalmol 1996; 44: 1-2. 9 Cornea Collection during 11th Five Year Plan-National Programme for the Control of blindness. http://npcb.nic.in/writereaddata/mainlinkFile/File179.pdf (accessed on March 10, 2013).

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10 Raychaudhuri A, Raychaudhuri M, Banerjee AR — Availability of donor corneal tissue for transplantation. Trop Doct 2004; 34: 99-101. 11 N a t i o n a l E y e b a n k - R P c e n t r e , A I I M S . http://www.aiims.edu/aiims/departments/spcenter/RPC/eye bank/eyebank.htm. (accessed on March 10, 2013). 12 Priyadarshini B, Srinivasan M, Padmavathi A, Selvam S, Saradha R, Nirmalan PK — Awareness of eye donation in an adult population of southern India. A pilot study. Indian J Ophthalmol 2003; 51: 101-4. 13 Krishnaiah S, Kovai V, Nutheti R, Shamanna BR, Thomas R, Rao GN —Awareness of eye donation in the rural population of India. Indian J Ophthalmol 2004; 52: 73-8. 14 Dandona R, Dandona L, Naduvilath TJ, McCarty CA, Rao GN — Awareness of eye donation in an urban population in India. Aust N Z J Ophthalmol 1999; 27: 166-9. 15 Tandon R, Verma K, Vanathi M, Pandey RM, Vajpayee RB —Factors affecting eye donation from postmortem cases in a tertiary care hospital. Cornea 2004; 23: 597-601. 16 Gupta A, Jain S, Jain T, Gupta K — Awareness and perception regarding eye donation in students of a nursing college in Bangalore. Indian J Community Med 2009; 34: 122-5. 17 Singh MM, Rahi M, Pagare D, Ingle GK — Medical students’ perception on eye donation in Delhi. Indian J Ophthalmol 2007; 55: 49-52. 18 Dhaliwal U — Enhancing eye donation rates. Training students to be motivators. Indian J Ophthalmol 2002; 50: 209-12. 19 Gogate B, Gogate P, Khandekar R, Bhargava A, Kurpad S, Deshpande M — Knowledge and attitudes towards eye donation among health professionals in India. Asian J Ophthalmol 2008; 10: 171-3. 20 Kannan KA — Eye donation movement in India. J Indian Med Assoc 1999; 97: 318-9. 21 Rao GN — Eye banking—Are we really up to it in India? Indian J Ophthalmol 2004; 52: 183-4. 22 Foster A — Childhood blindness in India and Sri Lanka. Indian J Ophthalmol 1996; 44: 57-60. 23 Sinha R, Vanathi M, Sharma N, Titiyal JS, Vajpayee RB, Tandon R — Outcome of penetrating keratoplasty in patients with bilateral corneal blindness. Eye (Lond) 2005; 19: 451-4. 24 Dandona L, Naduvilath TJ, Janarthanan M, Ragu K, Rao GN — Survival analysis and visual outcome in a large series of corneal transplants in India. Br J Ophthalmol 1997; 81: 72631. 25 Rao GN, Gopinathan U — Eye banking: an introduction. Community Eye Health 2009; 22: 46-7. 26 Arya SK, Sood S, Sood R — Enhancing eye donation. Indian J Ophthalmol 2003; 51: 198. 27 Gogate B, Gogate P, Deshpande M — Eye donation programme through faith leaders. Br J Ophthalmol 2008; 92: 867-8. 28 Gogate B, Gogate P — Eye donation: Mere awareness and willingness not enough. Only a catalyst can improve corneal harvesting rates. Indian J Ophthalmol 2011; 59: 332-3. 29 Kalevar V — Eye banking in India. Indian J Ophthalmol 1989; 37: 110-1.

We request you to send Quality Article addressed to : Hony. Editor, Journal of IMA (JIMA), 53, Sir Nilratan Sircar Sarani (Creek Row), Kolkata 700014 Dr. Kakali Sen Hony. Secretary, JIMA

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Observational Study Fixation with pedicle screw for thoraco-lumbar spine fracture : our experience Santosh Kumar1, Indrajeet Kumar2, Rajat Charan3, Binay Pandey4 The thoracolumbar injuries are the commonest spinal cord injuries because dorsolumbar segment is an unstable zone between fixed dorsal and Mobile lumbar spine. The goal of the treatment of unstable thoracolumbar injuries is optimising neural decompression while providing stable internal fixation with interpedicular screw. This study was done on Thirty-two patients (M:F=3:1), 20-65 years (mean=38 years), with posttraumatic instability (duration <3weeks) of lower thoracic or upper lumbar spine were surgically managed. All the patients were mobilized on third or fourth days with thoracolumbar spinal brace (Rigid type), the spinal brace was worn for the three months postoperatively in all patients. The neurological status of the patients recorded using Frankel grading. All patients with incomplete neurological deficit had some amount of neurological recovery but no recovery was seen in 83.33% of patients with complete neurological injury. Complications like bed sore, superficial wound infections and peroperative dural tear were seen but all of which were treated successfully. Neurological deterioration after operation, screw pull out and implant failure were seen in none. This study indicates that short segment pedicular screw fixation is a safe and effective method for treatment of unstable spinal injury. [J Indian Med Assoc 2017; 115: 23-5]

Key words : Spinal Injury, Pedicular Screw, Neurological deficit.

he thoracolumbar injuries are the commonest spinal injuries because dorsolumbar segment is an unstable zone between fixed dorsal and Mobile lumbar spine . The treatment of unstable fractures and fracture dislocations of thoracolumbar spine remains controversial . The posterior approach with interpedicular screws and rods for segment stabilization was found appropriate method. The goal of the treatment of unstable thoracolumbar injuries is optimising neural decompression while providing stable internal fixation over the least number of spinal segments. Either anterior posterior or both approaches can be used to achieve fusion. However, posterior approach is less extensive. The pedicle screws are passed one level above and one level below the fractured vertebra via posterior approach. The aim of this study was to evaluate the use of pedicle screw fixation for preservation of remaining spinal cord function, restoration of spinal alignment, and achievement of pain-free fracture site, early mobilization and maximization of neurological recovery in Spinal Injury Patients. Pedicle screws allow the surgeon to instrument vertebrae with absent or Department of Orthopaedics, Indira Gandhi Institute of Medical Sciences, Patna 800014 MBBS, MS, Assistant Professor MBBS, MS, Senior Resident MBBS, MS, Consultant Orthopaedics BPT, Physiotherapist 2

fractured laminae directly. They provide three-column fixation in unstable injuries and limit the length of fusion in the lumbar spine.

2,3,4,5

Dr. Dilip Kumar Dutta Hony. Editor, JIMA

MAY 2017

MATERIAL AND METHODS

Thirty-two patients aged from 20-65 years (mean: 38 years), with posttraumatic instability (duration <3weeks) of lower thoracic or upper lumbar spine were surgically managed at the Department of Orthopaedics, IGIMS, Shekhpura, Patna. A detailed history and examination was carried out especially evaluating the mode of trauma, Frankel grading (Table 1), sensory level and any spinal deformity. Plain x-rays, in anteroposterior and lateral views were done and the instability of the spine was confirmed using Denis’ 3-column concept spinal (Table 2). MRI/CT scan was done to further evaluate the important relationships and instability of spine. Those patients with unstable spine were then explained pros and cons of the surgical treatment. All patients with dorsolumbar spinal injury were treated by pedicular screw fixation along with direct or indirect decompression. All patients underwent indirect reduction and internal fixation by posterior approach. Laminectomy to decompress spinal cord was carried out at the involved level and bone was saved to be used as bone graft as needed. Pedicles were localized using detailed anatomical landmarks and intraoperative image in-

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tensifier. Pedicle screws were inserted through pedicles into vertebral bodies, one level above and one level below fractured vertebra under fluoroscopy. The rod was coupled to Pedicle screws. Indirect reduction was achieved distracting the Pedicle screws. The cases in which bony fragment were protruded into spinal canal were reduced by punching the bony fragment with horse-shoe punch. The wound was then closed in layers. The patients were kept on injectable broad-spectrum antibiotics and analgesics for 7 days then oral antibiotics for another 7 days. Check x-rays were done on the fifth postoperative day. Thoracolumbar support was given to the patients for initial 3 months. Aggressive physiotherapy was started to mobilize patients. The neurological status of the patients and any other complications were noted up to one-and-a-half years.

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brace was worn for the three months postoperatively in all patients.

There were no patients with wound infection and implant failure. None patient developed DVT. One patient became severely depressed and required long term antidepressants. Two patient developed bedsores. No other complications of recumbency were found. All the paraplegics could mobilize with crutches independently by lattisimus dorsi rehabilitation. DISCUSSION

Preoperative MRI lateral section burst fracture L

Preoperative MRI cross section D – L

The management of fractures in the thoracolumbar region is a controversial subject. Disadvantages of conservative treatment include deterioration in neurological status in 17% of the patients, progressive kyphotic deformity in 20%, persistent backache, decubitus ulcer and deep venous thrombosis . Most of these complications can be avoided by early mobilization and decreased hospital stay by early surgery . The pedicle offers a strong point of attachment of the posterior elements to the vertebral body and pedicle screw instrumentation has revolutionized spine surgery. Pedicle screw fixation is considered biomechanically superior to other stabilization constructs or parapedicular screws and are exceptionally rigid . It has rapidly become one of the most popular strategies for achieving solid fusion. So instrumentation with pedicle screws is a commonly used procedure for correcting deformity and stabilizing the spine until bony fusion occurs. These instrumentation systems may be divided into those using rods and those using plates. Nowa-days, pedicle screw system using rods is more acceptable and it provides better stability than other implants . Operative stabilization consists of segmental distraction with pedicle screw fixation one level above and one level below the injured segment. By applying distraction, annulotaxis is exploited to aid in reduction of retro-pulsed bone and disc fragments. Similarly, pedicle screws have been shown to be superior to hooks and Hartshell fixation in spine .

Table 1 — ASIA impairment scale (modified Frankel’s)

Table 2 — Denis divided the spine into three columns - anterior, middle and posterior. If two or more of these columns are damaged then the spine is unstable • The anterior column comprises the anterior longitudinal ligament and the anterior half of the vertebral body. • The middle column comprises the posterior half of the vertebral body and the posterior longitudinal ligament. • The posterior column comprises the pedicles, the facet joints and the supraspinous ligaments.

Surgical technique : All patients were operated under general anesthesia in prone position, A mid line posterior approach was used. The injured site was defined; posterior decompression was performed whenever indicated to ensure that the disrupted soft tissue or bone fragments did not compress neural elements during final reduction . Decompression also included undercutting the disrupted lamina and evacuation of any Epidural hematoma, by using the fluoroscopy control to identify the proper site. The fracture was stabilized by bilateral pedicle screws with short segment fixation, distraction was used to reduce the posterior displacement of vertebral body toward the neural canal and maintain a good alignment of the spine and fracture site. Post operative care : All the patients were mobilized on third or fourth days with thoracolumbar spinal brace (Rigid type), the spinal 6

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The vertebral pedicle screw internal fixation was technologically applicable, which can efficiently reposition and stabilize the fractured vertebrae, indirectly decompress spinal canal, maintain spine stability, scatter stress of screw system, reduce the risk of loosening or breakage of screw and loss of vertebral height, and prevent the formation of posterior convex after operation. An early/immediate surgery in the form of pedicle screw fixation with decompression provides better relief in neurological recovery also. Pedicle screw devices allow immediate stable fixation as the screws traverse all the three columns

• A = Complete: No motor or sensory function is preserved in sacral S4S5 • B = Incomplete: Sensory but not motor function is preserved below the neurological level • C = Incomplete: Motor function is preserved below the neurological level(power<3) • D = Incomplete: Motor function is preserved below the neurological level(power>3) • E = Normal

MAY 2017

Postoperative X-Ray Lateral view

Postoperative X-Ray AP VEIW

OBSERVATION

There were 32 patients who were managed with pedicle screws for thoracolumbar injuries. There were 8 females and 24 males (1:3 ratio) . The age range was 20 to 65 years (mean age of 38 years) . Wedge compression was the commonest in 21 patients (65.62%) whereas Fracture subluxation was seen in 5 patients (15.62%). There were 4 burst fractures (12.5%), 2 translational injuries (6.25%) and no distraction injuries. No patient deteriorated after surgery. The neurological status of the patients (Frankel grading) and subsequent improvement is shown in Table 3. The Table 3 shows that the patients were progressively moving from worse grade to a better grade. All patients with incomplete neurodeficit had some amount of neurological recovery in terms of ASIA impairment scale but no neurological recovery was seen in 10 patients (83.33%) with complete neurological injury. Complications like bed sore, superficial wound infections and peroperative dural tear were seen but all of which were treated successfully. Neurological deterioration after operation, screw pull out and implant failure were seen in none. This study indicates that short segment pedicular screw fixation is a safe and effective method for treatment of unstable spinal injury. 7,8

Table 3 — Frankel Grading of the patients No of Patient

On admission At Follow-up

12 10

8 2

8 5

4 9

0 6

REFERENCES 1 knigntly JJ, sonntag VKH — Thoraco lumber fractures in : menezes A,sonntage V (eds) Principle of spinal surgery New York ; McGraw-Hill; 1996 : 919-49. Char DPK ,Ser SNK , Kaun KT : Non operative treatment in burst. 2 Fractures of lumber spine (LI - L5 ) with out neurological deficit. Spine 1993; 18: 971-6. 3 Sutherland CJ, Miller F, Wang CJ — Early post operative kyphosis following compression fractures. Clin Orthop 1983;

11,12

13,14

CONCLUSION

Short segment pedicular screw fixation is a safe and effective method for treatment of unstable spinal injury. Thoracolumbar injury is a common neurosurgical problem in road traffic accidents and fall from height. Surgical treatment is a better option for early ambulation and faster recovery. Pedicle screw fixation is a useful choice, which achieves reduction and stability in both anterior and posterior column injuries, does not require anterior decompression and does not affect extra motion segments.

173: 216-21. 4 Cantor JB, Lebwohl NH , Garvey T — Non operative Treatment in burst fractures with early ambulation and bracing. Spine 1993; 18: 971-6 . 5 Weinstein JN, Lollaltop, LehmanTR — Thoracic lumbler burst Fractures Treated1’conservatively. Along Term follow up. Spine 1988; 8: 3-13. 6 Benson DR — unstable thoraco lumber fractures with emphasis on the burst fracture. Clin Orthop Relate Res 1988, 230: 14-9. 7 Catty Hart — Paraplegia, Vol.32, 1994. 8 C Lan — Paraplegia, Vol 31, 1993. 9 Rechtineet al.(1999)[93] Spinal Disorders: Fundamentals of Diagnosis and Treatment. 10 Jacobs RR, Asher MA, Snider RK — Thoracolumbar spinal injuries: A comparative study of recumbent and operative treatment in 100 patients. Spine 1980; 5: 463-77. 11 Yue JJ, Sossan A, Selgrath C, Deutsch LS, Wilkens K, Testaiuti M, et al — The treatment of unstable thoracic spine fractures with transpedicular screw instrumentation: a 3year consecutive series. Spine 2002; 27: 2782-7. 12 Shafiq K, Iqbal M, Hameed A, Mian JM — Role of transpedicular fixation in thoracolumbar spinal injuries. Neurol Surg 1998; 1: 21-7. 13 Biomechanical evaluation of pedicle screws versus pedicle and laminar hooks in the thoracic spine. Spine J 2006; 6: 444-9. 14 Hitchon PW, Brenton MD, Black AG — In vitro biomechanical comparison of pedicle screws, sublaminar hooks, and sublaminar cables. J Neurosurg 2003; 99: 104-9.

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Case Report

Indranil Dutta , Sanchita Karmakar , Sourav Chowdhury , Nikhil Kumar

Broad ligament fibroids occur in rarity as such in females of reproductive age group. These fibroid usually undergo hyaline, cystic or red degeneration. In present case it had undergone cystic degeneration with septations present in between. Usually it is very difficult to differentiate true broad ligament fibroid from false one. Very rarely these fibroids degenerate and produce an mass along with fluid like interface hence overall appearing as an ovarian tumour (ref). clinically on per abdomen examination these masses are difficult to identify and typically wont present as an fibroid mass.(hard irregular/regular mass). Per abdominally sometimes they give us a mixed presentation giving us an doubt of ovarian origin mass. In present case the ultrasonographic findings suggested cystic mass with septations of size 18x16cm thus more so favoring diagnosis of ovarian tumour. Differential diagnosis was suspected as a giant fibroid with cystic degeneration which was confirmed on histopathology report. The patient underwent excision of broad ligament fibroid (sized 28x24cm) and we managed to save the uterus as she was in reproductive age group.

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vessels and cystic degeneration. No atypia/malignancy noted in the sections examined. Interpretation — Leiomyoma with cystic changes.

Broad ligament fibroid mimicking ovarian tumour based on ultrasonographic study 1

MAY 2017

DISCUSSION

Fig 1 — 28x24cm mass

Fig 2 — Mass seen arising separately from ovaries

[J Indian Med Assoc 2017; 115: 26-7]

Fibroids are known to attach itself to various structures such as omentum, Fig 3 — Post removal of mass, uterus noted broad ligament etc and obtain blood supply from them thus eventually separating it from uterine body. These grow up to form fibroid tumor later on. These broad ligament tumors, if they grow may result in compression of nearby structures such as bowel/bladder or uterus causing various associated problems. Hence may ultimately lead to its detection by ultrasongraphic/ct scan/MRI techniques. Leiomyoma usually have a whorled appearance with variable echogenicity. Main idea is to identify uterus and ovary separately as sometimes ovarian tumour mimic broad ligament fibroid hence has to be ruled out . Differential diagnosis include ovarian tumor/ broad ligament cyst. MRI can be an useful modality as it can help differentiate between ovarian and uterine masses. MRI can also help to differentiate from solid malignant tumors. Usually hyalinization is commonest type of degeneration ie 50%, cystic degeneration is very rare ie 2-3% of cases . Sometimes USG guided biopsy can be helpful. Commonest presentation of cystic lesion originate from ovary. Non ovarian origin maybe such as mucocoele of appendix, hydrosalphinx, peritoneal inclusion cysts, paraovarian cysts etc. only 2% of fibroids undergo cystic degeneration with edema, forming cystic and fluid filled spaces. 3

Key words : Broad ligament fibroid, ultrasonography. Fig 4&5 — Gross feature of specimen

ibroids are the commonest benign pelvic tumors which occur in reproductive age group. They are classified into subserosal, intramural, submucosal fibroids. Fibroids are common in age of reproductive age group. Extrauterine fibroids also occur but are very rare. Extrauterine fibroids appear where smooth muscles are present. Common symptoms of fibroids incude mennorhagia, dysmennorhea, pressure effects and secondary changes include degeneration, infection, hemorrhage, necrosis and sarcomatous changes . 1,2

CASE REPORT

A 26 years, P1L1, old female presented to Gynae OPD at IQ Medical College and NH Hospital, Durgapur, WB with complaints of vague abdominal pain from last 8 months. She also had mild degree of abdominal discomfort. Also complained of feeling of heaviness in abdomen. Her vitals including blood pressure (120/80mmgHg) and pulse rate(76/min) were apparently normal. She had no other associated co morbidities. Routine clinical examination suggested of a mass of approx 2426 weeks size varying in consistency. On Per vaginal examination mass appeared non mobile and was also non tender. There was no cervical motion tenderness. Investigations were done. USG revealed an ovarian cyst with solid cystic component and along with septations. Serum CA 125 report showed a value of 12IU/L. Other hematological findings Department of Obstetrics and Gynaecology, IQ City Medical College, Durgapur 713206 1 MBBS, MS (Gynae), FIAOG, FAGE, Assistant Professor 2 MBBS, MS (Obst & Gynae), Associate Professor 3 MBBS, DGO, Senior Resident 4 MBBS, MD (Pathol), Department of Pathology

were within normal range. On ultrasonography, a well defined, mixed echogenic lesion measuring 18x16cm was seen, ovary on right side could not be separately differentiated. There was moderate vascularity seen. Mild hydronephrosis was also seen right kidney probably due to pressure effect. Diagnosis of right ovarian complex cyst was made with solid cystic component seen. Thus with the provisional diagnosis of ovarian tumour, the patient was taken up for exploratory laparotomy. Intraoperatively, an abdominal pelvic mass was noted of size approximately 28x24cm (Fig 1) with variable consistency. Pedicle could be reached upto the right broad ligament area. Right sided fallopian tube, ovary and round ligament could be seen separately stretched over the mass. Right ovary appeared normal. Left ovary and tube also appeared normal (Fig 2). The mass was distorting the pelvic anatomy and since the patient wanted to preserve her fertility, we carefully dissected around the mass. Preventively we did an bilateral uterine artery ligation and also injected vasopressin into the fundus of uterus to differentiate mass from uterus. The broad ligament fibroid had obtained huge blood supply from the lateral wall of uterus hence those had to be ligated separately. The capsule had to be separated, the fluid drained, and the fibroid mass was carefully dissected out reaching upto the base of the capsule which was located in the right broad ligament area. The mass was separate from the uterus body. After dissection the loose peritoneum fold closed carefully. Hemostasis was secured (Fig 3). Post operative period was uneventful. The surgically resected specimen which included the mass of size 28x24cm was sent for histopathology. On gross examination, the cut section of the mass showed solid fleshy areas and cystic areas filled with hemorrhage (Figs 4&5). Sections from the mass

showed a benign tumor with interlacing bundles of smooth muscle cells, scattered thick walled blood vessels, and an evidence of cystic and myxoid degeneration (Figs 6,7,8,9). Final report was — On microscopic examination:- sections sow histological features of leiomyoma with prominent dilated blood

CONCLUSION

Fibroids of extrauterine origin may sometimes be misdiagnosed as ovarian tumors, as they may be mimicking the same hence it may be a diagnostic challenge to the radiologist. Symptomatically patient may have common symptoms hence may be difficult to differentiate. So if pelvic mass is present always differential diagnosis of broad ligament fibroid should be considered. REFERENCES

Fig 6 — leiomyoma with cystic changes and dilated blood vessels

Fig 8 — leiomyoma with myxoid changes

Fig 7 — Leiomyoma with dilated blood vessels

Fig 9 — leiomyoma with hemorrhagic areas

1 Berek JS — Novack’s Gynaecology. 15th ed. New Delhi: Lippincott Williams and Wilkins, Wolters Kluwer (India); 2007. Benign diseases of the female reproductive tract; 470. 2 Fasih N, Prasad Shanbhogue AK, Macdonald DB, FraserHill MA, Papadatos D, Kielar AZ, et al — Leiomyomas beyond the uterus: Unusual locations, rare manifestations. Radiographics 2008; 28: 1931-48. 3 Low SC, Chong CL — A case of cystic leiomyoma mimicking an ovarian malignancy. Ann Acad Med Singapore 2004; 33: 37. 4 Kaushik C, Prasad A, Singh Y, Baruah BP — Case series: Cystic degeneration in uterine leiomyomas. Indian J Radiol Imaging 2008; 18: 69-72.

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Clinical Study Dosulepin as analgesic and antidepressant in chronic pain: a clinical review 1

Venkateshwarlu Kolichana , Samir Adsule , Kartik Peethambaran

Evidences and literature search report a co-existence of pain and depression. Dysregulation of central monoaminergic neurotransmitters has a major role to play in depression. These neurotransmitters are involved in pain modulation systems such as pain descending inhibitory pathways. Hence, modulation of both the pathophysiological mechanisms with an antidepressant may result in better treatment outcomes in these conditions. Tricyclic antidepressants (TCA) were found to have a pivotal role in the management of the chronic pain. A TCA, ie, dosulepin or dothiepin hydrochloride, is structurally a thio-analogue of amitriptyline and is used due to its anxiolytic action. The favorable pharmacokinetic profile of dosulepin allows a convenient administration of a single dose which is very helpful for the depressive patients with insomnia symptoms. The efficacy and safety of dosulepin as anti-depressant and analgesic has been well demonstrated in many clinical studies. Further, in comparison with amitriptyline, the efficacy of dosulepin is found almost similar with lower incidence of sedative, cardiac and anticholinergic related adverse effects. Thus, the current review emphasized the bimodal analgesic and antidepressant action of dosulepin, which could influence the treatment outcomes in the management of chronic pain. [J Indian Med Assoc 2017; 115: 28-32]

Key words : Analgesic, antidepressant, chronic pain, dosulepin, dothiepin tri-cyclic antidepressant.

osulepin or dothiepin hydrochloride, a tricyclic antidepres-sant (TCA) drug with an associated

anxiolytic action1, is a thio-analogue of amitriptyline with molecular formula: C19H21NS (Fig 1); the International

dimethylpropan-1-amine; and molecular weight: 295.45 g/mol2. This drug molecule was synthesized by Rajsner and Provita in 1962 in the Research Institute for Pharmacy and Biochemistry, Prague . It was first introduced as an antidepressant in Czechoslovakia in 1964, while it entered India in 19874. So far, many clinical studies have confirmed dosulepin as an

Fig 1 â&#x20AC;&#x201D; Chemical Structures of Different Tricycle Antidepressants

effective and safe drug for the treatment of depression5. Furthermore, some studies have also reported an addition to its benefits in reducing the pain associated with depression. To understand the analgesic efficacy of dosulepin, the current review focuses on its mechanism of action in chronic pain, its

pharmaco dynamics and pharmacokinetics as well as its efficacy and safety in patients with chronic pain. Dosulepin : Mechanism of Action Analgesic action for chronic pain â&#x20AC;&#x201D; The analgesic action of dosulepin is generally contributed by central blockade of central nervous system (CNS) monoamine uptake, ie, by inhibiting serotonin, norepinephrine, or other neurotransmitters. In addition to monoaminergic effects, dosulepin may alter nociceptive processing by extending synaptic activity of monoamines, due to which descending inhibitory action in the spinal cord is enhanced. Besides, it also blocks various other

5,6

7,8

receptors associated in pain processing, which include H1histaminergic, a-adrenergic, and N-methyl- D-aspartate (NMDA) receptors. It also has a blocking action on sodium and calcium channel and is a weak stimulator of m-opioid receptors . Antidepressant action for depression â&#x20AC;&#x201D; The antidepressant activity of dosulepin is recognized by its ability to enable noradrenergic and probably serotoninergic neurotransmission which is interceded in part through inhibition of neuronal uptake of noradrenaline (norepinephrine) and serotonin (5hydroxytryptamine; 5-HT). However, the therapeutic effects of dosulepin were found to be delayed for two to four weeks which may be possibly due to secondary adaptive responses of the drug . A study by Badawy and Evans (1981) demonstrated that intraperitoneal injection of any antidepressant including dosulepin (10 mg/Kg) inhibits liver tryptophan pyrrolase which is involved in the degradation of tryptophan. The reduced rate of metabolism of tryptophan (a metabolic precursor of serotonin) thus increases the brain concentration of tryptophan. These changes may increase brain serotonin synthesis through the availability of circulating tryptophan . Dosulepin : Pharmacokinetics Immediately after oral administration, the swift absorption of dosulepin through gastro-intestinal tract helps in attaining its peak plasma concentration within two to four hours in healthy subjects. Either the drug is consumed three times daily or once daily, the steady state serum concentration is achieved in 12 days. Dothiepin-S-oxide, northiaden and northiaden-S-oxide are the metabolites of extensive hepatic metabolism, with an oral bioavailability of about 30% after firstpass hepatic metabolism. Dosulepin and its metabolites have mean terminal elimination halflives of 14 to 24 hours and 23 to 46 hours, respectively . Dosulepin : Pharmacodynamics In vitro study in human platelets have demonstrated dosulepin as a potent inhibitor of C-serotonin uptake as compared to its metabolite, which consequently enhances brain serotonin synthesis by inhibiting tryptophan-degrading enzyme, tryptophan pyrrolase. It also enables noradrenergic neurotransmission through its inhibitory action on neuronal uptake of noradrenaline. Dosulepin has demonstrated low affinity for a1- and a2-adrenoceptors and serotonin 5HT1- and 5HT2-receptors in neurotransmitter receptor binding studies. Compared to other antidepressants, it is relatively a potent antagonist of histamine H1-receptors . Dosulepin : Dosage and Duration Dosulepin treatment can be initiated at a dose of 75 mg/day orally once at bed time or can be divided, ie, three times a day. The therapeutic dose can be further increased to 150 mg/day depending on the severity of the condition, and can go to a maximum of 300 mg/day. However; in elderly patients, the treatment is recommended with a dose in the range 50 5

Union of Pure and Applied Chemistry (IUPAC) name : (3Z)-3( 6 H b e n z o [ c ] [ 1 ] b e n z o t h i e p i n - 11 - y l i d e n e ) - N , N -

Department of Neurology, Andhra Medical College, KGH, Visakhapatnam, Andhra Pradesh 530001 MBBS, MD, DM (Neurology), Emeritus Professor of Neurology MBBS, MD, Head, Medical Affairs, Abbott India Limited, Mumbai 400063 MBBS, MD, Senior Medical Advisor, Medical Sciences Division, Abbott India Limited, Mumbai 400063

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-75mg/day. It may be increased depending on the condition, but with caution . Higher doses, 225-300 mg/day are administered to inpatients under observation . A study conducted by Rees et al, (1976) in depressive patients suggested that a single daily dose of 75 mg of dosulepin is well tolerated and efficacious as compared to thrice daily regimen. Moreover, single dosing at night helps in relieving insomnia symptoms in depressed patients . Concomitant treatment of dosulepin is avoided in patients who are on monoamine oxidase inhibitors, sympathomimetic agents or adrenergic neurone blocking drugs . Concurrence of Chronic Pain and Depression According to Lepine et al, (2004) about 75% of patients with depression are associated with painful somatic symptoms such as neck pain, low back pain (LBP), headache, stomach pain, or nonspecific pain . In contrary, some studies also suggest that persistent pain is often associated with the depression and/or anxiety disorders . Von et al, 2005 has also established a relationship between chronic pain/pain and functional impairment . Interestingly, patients with chronic pain are often associated with co-morbid depression. This is evident among patients with fibromyalgia where prevalence of co-morbid depression was found to be in 20-40%. However, only 17.5% of patients with spinal pain had mood disorders . In a large longitudinal perspective survey, it has been found that back pain was the strongest predictor of depression and has shown that having a chronic painful medical condition increases the risk of major depression by more than twice . The studies emphasize that high concurrence of chronic pain and depression for long period of time may have negative impact on recognition and treatment response which may further lead to disability and may have an increased risk of suicidal behavior . Considering the biochemical nature of brain, it is a wellknown fact that dysregulation of central monoaminergic neurotransmitters has a major role in depression, including the decrease in serotonin and norepinephrine . These neurotransmitters are also associated in pain modulation systems like pain descending inhibitory pathways . Thus, antidepressants (such as dosulepin and amitriptyline), which increase the levels of serotonin and norepinephrine are proven to have beneficial effects on pain . Dosulepin : Clinical Studies Supporting Its Efficacy in Chronic Pain TCAs, specifically dosulepin, are well studied as antidepressant drugs, additionally its therapeutic effect appears to be independent of the antidepressant effect in pain release . Very few studies are available to recommend or confirm the use of dosulepin as a treatment option for chronic pain. Studies conducted by Feinmann et al (1984) and Caruso et al (1987) and Puttini et al (1988) have reported dosulepin as a significantly 9

2,5

12-15

11,15,16

17,18

19-21

23,24

27-29

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efficacious and safe treatment molecule for treating patients with 27,30,31

chronic pain in comparison with placebo . The clinical summary of dosulepin in the management of chronic pain in various disease condition is elucidated in Table 1. Dosulepin : Safety Overview Compared to other TCA’s, the safety profile of dosulepin is more or less similar. Though the frequency of these side effects vary, they are quite tolerable and do not interfere with the efficacy outcomes. Literature review and pooled analysis of comparative and non-comparative clinical trials was conducted by Lancaster et al (1989) to evaluate the tolerability of dosulepin. The analysis was conducted in a total of 5755 patients under treatment for 4-6 weeks. Largely dry mouth (24%) was observed as the most common side effect followed by drowsiness which indicates sedative or anxiolytic properties of the drug. However, in comparable doses, the incidence of sedative, cardiac and anticholinergic side effects were reported lower than other

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Dosulepin and Amitriptyline Clinical studies on TCA’s such as dosulepin and amitriptyline reporting similar significant effect as antidepressant had probed researcher or clinicians to evaluate the safety of these drugs especially with respect to cardiotoxicity. In 1975, Rotrekl and his colleagues compared the cardiotoxic effects of dosulepin, amitriptyline and imipramine and revealed that the cardiotoxic effect was lesser with dosulepin as compared to amitriptyline29,32. A study by Lambourn and Rees (1974) comparing the efficacy and safety of dosulepin and amitriptyline has found the incidence and severity of side effects were significantly less in dosulepin compared to amitriptyline33. Later study conducted by Khan (1975) reported that dosulepin (2 patients) was well-tolerated as compared to amitriptyline (3 patients) with minor changes in electro cardiograph recording (ECG) which were not associated with clinically significant changes in cardiovascular state, pulse and blood pressure readings34. Similar safety outcomes specifically with respect to anticholinergic, central nervous system and cardiovascular

amitriptyline5.

Table 1 — Clinical summary of dosulepin in chronic pain Author et al Type of Pain (year and ref.no)

Study design

Therapeutic dose

Efficacy outcome

Safety outcome

Feinmann et al, (1984; 27)

• N=93 • 9-week, randomized, placebocontrolled double-blind study

150mg (25mg single night dose every 3 days upto 150mg at night)

• Pain relief: 71% dosulepin vs 47% placebo • Of 84 patients followed for 12 months only 81% had pain relief. • Dosulepin is efficacious than Placebo

At month 12 adverse life events such as bereavement or family ill health

• The number of tender points and subjective pain severity were significantly reduced (P<0.01) compared to baseline • Dosulepin is significantly more effective than placebo

18 in dosulepin vs 6 in placebo experienced mild side effects that are transient, indicating dosulepin appears to have good tolerability in addition to reduction in pain

• Dosulepin showed significant reduction in day time pain compared with placebo

Side effects were mild and transient and did not interfere with the treatment outcomes • The Hamilton rating scale was significantly improved in depressed patients

Caruso et al, (1987; 30)

Puttini et al, (1988; 31)

Ash et al, (1999; 29)

Temporomandibular pain

Primary Fibromyalgia • N=60 with musculoskeletal • 8-week, aching, stiffness, fatigue, doubleblind, multiple tender points placebocontrolled and disturbed sleep study

Rheumatoid arthritis with pain and associated depression

Rheumatoid arthritis and depression

• N=60 • 4-week, doubleblind placebocontrolled study with/without depression

• N=48 females • 10-week, doubleblind placebocontrolled study with depression and/or anxiety

75mg/day single dose

75mg single dose at night and 600mg ibuprofen thrice daily

First 2 weeks 75md/day single dose and 150mg/day twice in divided dose for next 8 weeks

• Significant reduction in pain, disability and reduction in morning stiffness, also associated with improvement in anxiety and depression

Not assessed

effects were reported by Stratas (1984) . However, a study by Sharma (1981) has revealed that though the two drugs showed similar side effect profile where the tolerability in patients treated with amitriptyline was less compared to dosulepin36. Guideline Recommendations TCAs have been strongly recommended as the first-line therapy by the EFNS (European Federation of Neurological Societies), Canadian Pain Society (CPS), and NeuPSIG (Neuropathic Pain Special Interest Group of IASP) for the management of chronic neuropath pain37-39. Moreover, their high efficacy in treating peripheral neuropathic pain along with their low cost has made TCAs a preferable choice of treatment in pain and depression40. Conclusion : In view of the available literature support on the extensive use of dosulepin as antidepressant, the current review focused on the therapeutic effect of dosulepin in chronic pain indicating that it is not only equally efficacious as an analgesic in patients with chronic pain, but is well-tolerated as well. As there exists a cooccurrence of depression and chronic pain, dosulepin would be a tolerable alternative in these cases. Further, in comparison with other TCAs including amitriptyline, the frequency of side effects associated with dosulepin were low. Since there are very few preliminary studies that support the use of dosulepin in chronic pain, the current review suggests to conduct more systematic and controlled studies in future to establish dosulepin as a first line of therapeutic intervention for chronic pain. Author Contributions All authors contributed to study design, data interpretation, and development of this manuscript and approved the final manuscript for submission. All authors met the ICMJE criteria for authorship and all those who met those criteria are listed as authors. Conflict of Interest All authors have indicated that they have no conflict of interest regarding the content of this article. REFERENCES 1 Wing YK — Recent advances in the management of depression psychopharmacology. Hong Kong Med J 2000; 6: 85-92. 2 Zusky P, Manschreck TC, Blanchard C, Rosenbaum J, Elliot C, Lou P — Dothiepin hydrochloride: treatment efficacy and safety. J Clin Psychiatry 1986; 47: 504-7. 3 Rajsner M, Protiva M — Synthetic ataractics VII-(3dimethylaminotropylidene) VI, IIdihydrodibenzo (b,e)thiepin. Cesk Farm 1962; 11: 404-9. 4 Ramakrishnan K, Kulkarni VN, Paul AD, Bakshi JS — Clinical experience with dothiepin in an Indian population. J Drug Dev 1991; 4: l5l-9.

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5 Lancaster SG, Gonzalez JP — Dothiepin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in depressive illness. Drugs 1989; 38: 123-47. 6 Dharmshaktu P, Tayal V, Kalra BS — Efficacy of antidepressants as analgesics: a review. J Clin Pharmacol 2012; 52: 6-17. 7 Badawy AA, Evans M — Inhibition of rat liver tryptophan pyrrolase activity and elevation of brain tryptophan concentration by administration of antidepressants. Biochem Pharmacol 1981; 30: 1211-6. 8 Badawy AA, Evans M — Inhibition of rat liver tryptophan pyrrolase activity and elevation of brain tryptophan concentration by acute administration of small doses of antidepressants. Br J Pharmacol 1982; 77: 59-67. 9 Khan AU — A comparison of the therapeutic and cardiovascular effects of a single nightly dose of Prothiaden (dothiepin, dosulepin) and Lentizol (sustained-release amitriptyline) in depressed elderly patients. J Int Med Res 1981; 9: 108-12. 10 Rees JA, Risdall PC — An evaluation of a once daily dosage régime of dothiepin hydrochloride (prothiaden). J Int Med Res 1976; 4: 319-25. 11 Lépine JP, Briley M — The epidemiology of pain in depression. Hum Psychopharmacol 2004; 19: S3-7. 12 Currie SR, Wang J — Chronic back pain and major depression in the general Canadian population. Pain 2004; 107: 54-60. 13 Cocksedge K, Shankar R, Simon C — Depression and pain: the need for a new screening tool. Prog Neurol Psychiatry 2016; 20: 26-32. 14 Mc Williams LA, Goodwin RD, Cox BJ — Depression and anxiety associated with three pain conditions: results from a nationally representative sample. Pain 2004; 111: 77-83. 15 Hudson JL, Hudson MS, Pliner LF, Goldenberg DL, Pope HG Jr — Fibromyalgia and major affective disorder: a controlled phenomenology and family history study. Am J Psychiatry 1985; 142: 441-6. 16 Von Korff M, Crane P, Lane M, Miglioretti DL, Simon G, Saunders K, et al — Chronic spinal pain and physical-mental comorbidity in the United States: results from the national comorbidity survey replication. Pain 2005; 113: 331-9. 17 Patten SB — Long-term medical conditions and major depression in a Canadian population study at waves 1 and 2. J Affect Disord 2001; 63: 35-41. 18 Magni G, Moreschi C, Rigatti-Luchini S, Merskey H — Prospective study on the relationship between depressive symptoms and chronic musculoskeletal pain. Pain 1994; 56: 289-97. 19 Dersh J, Gatchel RJ, Polatin P, Mayer T — Prevalence of psychiatric disorders in patients with chronic work-related musculoskeletal pain disability. J Occup Environ Med 2002; 44: 459-68. 20 Garbi MD, Hortense P, Gomez RR, Silva TD, Castanho AC, Sousa FA — Pain intensity, disability and depression in individuals with chronic back pain. Rev Lat Am Enfermagem 2014; 22: 569-75.

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21 Lin EH, Katon W, Von KM, Tang L, Williams JW Jr, Kroenke K, et al — Effect of improving depression care on pain and functional outcomes among older adults with arthritis: a randomized controlled trial. JAMA 2003; 290: 2428-9. 22 Verrocchio MC, Carrozzino D, Marchetti D, Andreasson K, Fulcheri M, Bech P — Mental Pain and Suicide: A Systematic Review of the Literature. Front Psychiatry 2016; 7: 108. 23 Hasler G — Pathophysiology of depression: Do we have any solid evidence of interest to clinicians? World Psychiatry 2010; 9: 155-61. 24 Berney A, Nishikawa M, Benkelfat C, Debonnel G, Gobbi G, Diksic M — An index of 5-HT synthesis changes during early anti-depressant treatment: alpha-[11C]methyl-L-tryptophan PET study. Neurochem Int 2008; 52: 701-8. 25 Bair MJ, Robinson RL, Katon W, Kroenke K — Depression and pain comorbidity: a literature review. Arch Intern Med 2003; 163: 2433-45. 26 Lynch ME — Antidepressants as analgesics: a review of randomized controlled trials. J Psychiatry Neurosci 2001; 26: 30-36. 27 Feinmann C, Harris M — Psychogenic facial pain. Part 2: management and prognosis. Br Dent J 1984; 156: 205-12. 28 Sharav Y, Singer E, Schmidt E, Dionne RA, Dubner R — The analgesic effect of amitriptyline on chronic facial pain. Pain 1987; 31: 199-209. 29 Ash G, Dickens CM, Creed FH, Jayson MI, Tomenson B — The effects of dothiepin on subjects with rheumatoid arthritis and depression. Rheumatology (Oxford). 1999; 38: 959-67. 30 Caruso I, Puttini PCS, Boccassini L, Santandrea S, Locati M, Volpato R, et al — Double-blind study of dothiepin versus placebo in the treatment of primary fibromyalgia syndrome. J Int Med Res 1987; 15: 1549. 31 Puttini PS, Cazzola M, Boccassini L, Ciniselli G, Santandrea S, Caruso I, et al — A comparison of

dothiepin versus placebo in the treatment of pain in rheumatoid arthritis and the association of pain with depression. J Int Med Res 1988 Sep; 16: 331-7. Rotrekl J, Náhunek K, Homola D, Svestka J, Srnová V, Rysánek K — Proceedings: The comparison of the cardiotoxic effect of prothiaden, imipramine and amitriptyline. Act Nerv Super (Praha) 1975; 17: 232-3. Lambourn J, Rees JA — A general practitioner study of dothiepin and amitryptiline. J Int Med Res 1974; 2: 210. Khan AU — A study of dothiepin hydrochloride in elderly patients with special reference to cardiovascular system. Modern Geriatrics 1975; 5: 26. Stratas NS — A double blind study of the efficacy and safety of Dothiepin hydrochloride in the treatment of major depressive disorder. J Clin Psychiatry 1984; 45: 466-9 Sharma SD — A double-blind comparison of dothiepin and amitriptyline in the treatment of depression with anxiety. J Assoc Physicians India 1981; 29: 725-9. Attal N, Cruccu G, Baron R, Haanpää M, Hansson P, Jensen TS, et al — EFNS guidelines on the pharmacological treatment of neuropathic pain: 2010 revision. Eur J Neurol 2010; 17: 1113-23. Moulin DE, Boulanger A, Clark AJ, Clark H, Dao T, Finley G, et al — Pharmacological management of chronic neuropathic pain - consensus statement and guidelines from the Canadian Pain Society. Pain Res Manag 2007; 12: 13-21. Dworkin RH, O’Conner AB, Audette J, Baron R, Gourlay GK, Haanpää ML, et al — Recommendations for pharmacological management of neuropathic pain: an overview and literature update. Mayo Clin Proc 2010; 85: S3-14. Sindrup SH, Otto M, Finnerup NB, Jensen TS — Antidepressants in the treatment of neuropathic pain. Basic & clinical pharmacology & toxicology 2005; 96: 399-409.

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Supplement Generic Drugs : IMA Perspective K K Aggarwal , R N Tandon , A Marthanda Pillai , Vinay Aggarwal , R V Asokan 1

Preface Hon’ble Prime Minister, Sh. Narendra Modi Ji has said that the Government is contemplating a legislation that will make it mandatoryfor the registered medical practitioners to prescribe generic only drugs (generic- generic drugs or writing a generic drug without a brand name). IMA, in principle, welcomes usage of generic-generic drugs yet has very serious concerns regarding quality assurance and other complex issues involved. To understand the whole issue, we first need to understand various terms used in the law In India, a generic drug can be marketed with following business model :1. Generic-Generic or Generic only drug (without brand name) and usually is supplied in institutional supplies. “Generic name of the drug” is not same as generic drug and means the chemical name of the drug only. Generic-Generic is made and marketed by local companies in theunorganized sector as the preparation with questionable quality. 2. Trade Generic (Generic marketed under a brand name) and usually is marketed and promoted through the trade chemists in theunorganized sector without any Medical Sales Representative and other Marketing Staff, no R&D set up, Lack of current Good Manufacturing Practices (cGMP) assurance in manufacturing plants with high margins to the chemists etc. 3. Branded Generic (Generic marketed under a brand name) and is usually marketed and promoted through the doctors using organized set up of well-trained medical sales representatives, marketing, medical staff, R&D set up, cGMP assurance in manufacturing set up called organized sector etc. A single company may pursue one, two or all the three business models. If manufactured by the same company in the organized sector and/or if procured from other manufacturers in the unorganized sector, the quality may not be the same but the price may vary with very high trade margin in trade generic as compared to branded generic. WHO and Generic drugs : WHO and Schedule M of Drugs and Cosmetics Act, 1947 provides a comprehensive set of guidelines including recommendations on cGMP, inspection, product assess

National President, IMA Hony Secretary, General, IMA Past National President, IMA 4 Chairman, IMA Hospital Board of India 2

ment, licensing, quality assurance, manufacturing, good laboratory practices, quality control, testing and release etc. The most important characteristics of any drug is its Bioequivalence (BE) to the innovator product to prove its safety, clinical efficacy equivalence and cGMP compliance on continuous basis for sustainable supply. The BE of any drug depends on its formulation process, choice of excipients, dissolution profile, stability under different conditions to prove its claimed shelf life, in process manufacturing and quality controls, packaging, storage conditions, transportation, validation studies, annual stability data review, analytical testing validated procedures, continuous engineering maintenance of every equipment in the plant, continuous training and development of people, reviewing regularly manufacturing/plant/site data, taking action on deviations eg. Out Of Specifications, Out Of Limit, batch specific deviations, change control, presence of impurities and mode of release of the drug etc. to name a few. While the manufacturing practices of a company in the organized sector making all three versions may be the same but those making the ‘generic only’ and Trade Generic version in the unorganized sector may not and usually does not comply with the cGMP of WHO and schedule M, especially if the company is a local company catering to the State/Region and not national market through the state licensing system. A 2014 study has shown that 10.9% of the products tested were of poor-quality with presence of none or less than the required dosage of active pharmaceutical ingredients. Of this 10.9 percent, 7 percent contained less than the required dosage of active ingredients, while 3.9 percent were drugs without any of the necessary active ingredients. It is worthwhile to mention here that testing some samples of a batch does not provide assurance of the product quality and safety. Batch to batch reproducibility, stability of the product is possible only through a comprehensively designed Quality Management System in a company complying to cGMP standards. India and Generic drugs :As discussed above ‘trade generics’ are sold at significantly higher prices in India with very high margin to chemist. It is also true that given the widespread poverty, making available reasonably priced quality medicines in the market would benefit everyone. This led to the origin of “Pradhan Mantri Bhartiya Janaushadhi Pariyojana” in 2008 under the concept “Quality Medicines at affordable prices

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for all”. It was envisaged that the scheme would run on a selfsustaining business model. It was to be run on the principle of “No Profit, No Loss”. BPPI (Bureau of Pharma PSUs of India), under the administrative control of the Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Government of India is the Implementing quality assurance agency of PMBJP. In April 2010, BPPI got registered as an independent society under the Societies Registration Act, 1860 as a separate legal entity. The vision of the project is to bring down the healthcare budget of every citizen of India through providing quality generic- generic medicines at affordable prices. Unfortunately, this initiative failed to benefit the public. It has not addressed the purpose for which it was launched since there were few takers due to lack of faith in quality. IMA and Jan Aushadhi : India Medical Association (IMA) is for affordable, accessible and quality healthcare. IMA policy is to prescribe quality drugs at affordable cost. IMA promotes usage of drugs from NLEM (National List of Essential Medicines). To promote Pradhan Mantri Bhartiya Jan Aushadhi Pariyojana, IMA has opened a Pradhan Mantri Bhartiya Jan Aushadhi Kendra (PMBJK) in its head quarter premises and recommends such Kendras should be opened in all the IMA buildings in India. Medical Council and Generic drugs: The clause 1.5 of the Indian Medical Council (Professional Conduct, Etiquette and Ethics) Regulations, 2002 has been amended in 2016 and notified in the Gazette of India on 21.09.2016, which reads as under: “1.5 - Use of Generic names of drugs: Every physician SHOULD prescribe drugs with generic names legibly and preferably in capital letters and he/ she SHALL ensure that there is a rational prescription and use of drugs.” MCI by a circular dated 21.04.2017 has reinstated that all the Registered Medical Practitioners under the IMC Act to comply with the aforesaid provisions of the Regulations in its letter and spirit and has warned that any violation will attract disciplinary action by the concerned SMC/MCI. In an RTI reply MCI has admitted that it does not have even the definition of generic drug. MCI circular neither make it mandatory to write the generic name of the drug nor does it mentions not to write the name of the brand. IMA does not feel that the current circular of MCI is for mandating not writing the brand name. If that was so, then the ‘Jan Aushidhi’ drugs would not have been marketed in the country as it is also a brand for the purpose of marketing. Even if we interpret MCI circular as mandating writing generic name of the drug without a brand name then the MCI circular is out of touch with realities on the ground and is bound to cause havoc in patient care and patient safety.

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In India where substantial population of manufacturer operate in the unorganized sector, quality of the final product may not be assured and the law enforcement on quality of drugs needs substantial improvement, mere ordering the doctors to write generic drugs without a brand name is not in the interest of the society. The objective of MCI is to regulate and prescribe minimum standards in medical education and the yardstick of ethics cannot be applied on this matter of usage of generic drugs with or without a brand name. Doctors and Generic drugs: If the Government’s intention is to have doctors write only the generic name without the brand name for making drugs affordable, just shifting the onus on to the doctors alone will not help the purpose. The root cause of the problem has to be analysed and solved by a multi-pronged approach. It is well known that from the same company the genericgeneric and trade- generic versions of a drug may be less expensive than the branded- generic ones but with very high distribution and retail margins sometimes more than 1,000% of the manufacturer’s price. Distributors Retailers have a strong financial incentive to push generic- generic or trade – generic drugs, even if doctors prescribe branded drugs. Such high discounts and price variations must be stopped. Therefore the rout cause of the challenge is when there is a differential pricing of generic- generic, trade- generic, and branded generic from the same company. If there is one price of the same drug from one company doctors can be sure about the affordability part and can then choose the brand offering consistent quality assurance. The quality assurance mechanism in our country is very weak. India has more than 67,000 drug formulations, the quality assurance mechanism in our country can ascertain the quality control of only 15753 drugs annually (Combined testing capacity of all the Central Drugs Testing Laboratories). Time and again, major adverse events including death occur due to poor quality of drugs or contaminated drugs. e.g. one of the major reasons for number of deaths that had occurred in the sterilization camp held in Chhattisgarh was due to generic drugs used. The verdict of the Chhattisgarh High Court in this issue has gone in favor of the doctor. He has been exonerated and the deaths had been found due to substandard generic drugs used during the operative course. It is not Government Laboratory testing the product that will assure quality of the product but strong overview, oversight by the regulator with strong teeth to act on the pharmaceutical manufacturers should they not comply to cGMP norms. When generic name only prescriptions are insisted, anyone can buy any medicine from chemist stores even without prescription (Over The Counter sale of drugs). Even if doctors prescribe in generic name, it will be the

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sales person (may not be qualified pharmacist) in the chemist shop who has no knowledge about drugs will decide which brand or form of drug is to be given. By shifting the responsibility of choosing the brand to the salesperson in the chemist shop, the objective of reducing the cost of drug is not going to be achieved and other risks of safety and lack of efficacy due to poor quality will additionally emerge. Eventually what is appearing to be economical or affordable potentially may not a quality product and its pharmacoeconomic cost will be far higher. The Government is serious about making drugs affordable, hence should insist with policy to ensure manufacturers market drugs underone drug- one price- one

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company policy. The Government should ban irrational combinations. Even our day to day commodities carry ISI mark before they come into the market. But no batch of drugs available in the market carries the seal of quality. Government should strengthen the licensing, inspection, cGMP compliance, quality assurance mechanism in drug manufacturing and ensure that each batch of drug available in the market is quality assured on sustainable basis. IMA FOMA Delhi Resolutions (Federation of Medical Associations): 1. The judgement to choose a rational drug and its formatvests only with the Registered Medical Practitioners. This right of the medical profession is sacrosanct. 2. IMA- FOMA also wants the Government to

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strengthen Quality Assurance mechanisms to ensure adherence to cGMP standards whether generic - generic or branded generic for patient safety. 3. For a rational prescription, doctors should choose drugsgeneric - generic or branded generic based on quality, efficacy, safety and affordability and write legibly and preferably in capital letters. 4. IMA-FOMA recommends that Government should ban differential pricing of a drug under different brand names (generic generic, trade generic or branded generic) by one company i.e. allow only one chemical drug, one company, one price) 5. IMA FOMA will be meeting the President of MCI, Union Health Minister and Prime Minister of India about the views of the medical fraternity on this issue. All the constituent members of IMA-FOMA shall communicate these IMA-FOMA Delhi Resolutions to its members. IMA demands: 1) Generic drugs (whether generic-generic or branded generic) should comply with: a. Efficient and effective quality assurance mechanism where every batch of the drug is of assured quality on sustainable basis. b. Uniform process of manufacturing, quality control and release with strong regulatory oversight. c. Ensured pharmaceutical equivalent and bioequivalence to innovator product. d. Ensured adequate storage conditions and shelf life duly supported by adequate stability studies. e. Uniform price of generic drugs irrespective of their formats f. Has the same clinical indications Seven steps for Government of India 1. Raise the Government expenditure on Health to 2.5 % of GDP from the current abysmal 1.1%. 2. Strong overview and oversight by DCGI and State Drug Controllers on compliance to cGMP practices in drug industry. 3. Strengthen the quality assurance infrastructure to the required level so that the quality of every batch of drugs is assured. 4. Deploy adequate regulatory manpower to enforce the laws regarding drugs.

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5. Stop the Over the Counter (OTC) sale of prescription drugs without prescription and do not allow a company to market same drug in different prices under different brands. 6. Prevent quacks and alternative system from using modern medicine drugs. 7. Initiate awareness movement amongst doctors and patients to buy quality affordable drugs. Conclusion: Doctors are committed to the welfare and safety of patients. Economy of drugs is only one dimension of the issue. The multiple concerns as enlisted above have to be addressed first. IMA shall remain the voice of voiceless and continue its service in nation building diligently.

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Activity Report

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Activity Report

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