CMJ Journal Medical Ethics issue 2018

Caribbean Medical Journal

Official Journal of the Trinidad & Tobago Medical Association

EDITORIAL COMMITTEE Editor - Dr. Solaiman Juman FRCS FRCS (Otol)

University of the West Indies, Trinidad

Assistant Editor - Ms Mary Hospedales

Loyola University, New Orleans, USA

Deputy- Editor - Dr. Ian Ramnarine FRCS FRCS (CTh)

Eric Williams Medical Sciences Complex, Trinidad

Dr. Shamir Cawich DM FACS

University of the West Indies, Trinidad

Dr. Rasheed Adam FRCSC

T&T Ambulance Authority

Dr. Trevor Seepaul FRCS

University of the West Indies, Trinidad

Dr. Rohan Maharaj BSc. MHSc DM FCCFP

University of the West Indies, Trinidad

Professor Hariharan Seetharaman FCCM

University of the West Indies, Trinidad

Dr. Darren Dookeram DM FRSPH

Sangre Grande District Hospital, Trinidad

Dr. Saeeda Mohammed DM

Port-of-Spain General Hospital, Trinidad

Mrs Leela Phekoo

Medical Librarian

ASSOCIATE EDITORS Professor Dilip Dan FACS

University of the West Indies, Trinidad

Dr. Victor Wheeler FRCOG

Scarborough General Hospital, Tobago

Dr. Sonia Roache FCCFP

Family Practitioner, Trinidad

Dr. Donald Simeon BSc MSc PhD

Caribbean Health Research Council

Dr. David Bratt MD MPH

Independent Paediatrician, Trinidad

Dr. Lester Goetz FRCS

San Fernando Teaching Hospital, Trinidad

ADVISORY BOARD Professor Zulaika Ali FRCPCH

University of the West Indies, Trinidad

Dr. Avery Hinds MBBS MPhil

Caribbean Public Health Agency

Professor Gerard Hutchinson DM MS MPh

University of the West Indies, Trinidad

Professor Vijay Naraynsingh FRCS

University of the West Indies, Trinidad

Professor Lexley Pinto-Perreira MD

University of the West Indies, Trinidad

Professor Samuel Ramsewak - FRCOG FACOG MD

University of the West Indies, Trinidad

Professor Howard Francis MD

John Hopkins Medicine, Baltimore, USA

Professor Grannum Sant MD

Tufts University, Boston, USA

Dr. Ian Sammy FRCEM FRCP FRCS (Ed)

University of Sheffield, UK

Professor Surujpal Teelucksingh FRCP PhD

University of the West Indies, Trinidad

Dr Kanter Ramcharan FAAN FRCP

San Fernando Teaching Hospital, Trinidad

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Caribbean Medical Journal

Editorial Since 2010 I have had the pleasure and privilege of being the Editor of the Caribbean Medical Journal.

The journey has been an exciting one, assisted by dedicated, committed individuals who have put in sterling service.

The look and the format of the CMJ have been revised and updated. It is a fully peer-reviewed journal and is indexed on the EBSCO database.

Our Editorial Committee, Associate Editors and Advisory Board represent the highest standard of academia locally, regionally and internationally. The back issues of the CMJ – going back to its origin in 1938- are being digitized in a joint project with the University of the West indies. As the official publication of the Trinidad & Tobago Medical Association, the journal is an important means of recording the activities of the T&TMA and other medical news in Trinidad & Tobago.

But we have to aspire to be even better. Inclusion in more databases, setting up a dedicated website and having a dedicated secretariat – are some of the issues being discussed. An injection of new energy is required to continue the progress of the CMJ. It is with some sadness that I announce my retirement as the Editor of the CMJ, but it is with great joy that I introduce to you, Professor Hariharan Seetharaman, as the new editor of this great journal. He brings a wealth of experience in academia and has published extensively.

I wish Professor Seetharaman and the T&TMA all the best and look forward to a bright and exciting future for the Caribbean Medical Journal Solaiman Juman FRCS Editor

Caribbean Medical Journal

Contents Original Scientific Article The Use of Magnetic Resonance Spectroscopy in the Preoperative grading of Astrocytomas

1-3

N. Ramnarine, P. Knight & D. Ramnarine An Audit of Medical Records in the Orthopedic Department at a Tertiary Institution

4-6

Calderon, A. Nicholas & E. Budhoo Case Report When the thyroid function test results do not fit? Some uncommon causes of abnormal thyroid function test results

7-9

L Gonzales, M Omar, A Bridgelal-Gonzales, R Abdul, S Teelucksingh Rituximab use in a case of successfully treated anti–NMDA receptor encephalitis in Trinidad

10-11

A. Panday & C. A. Beers Ethics Challenges of Conflicts of Interest in the Caribbean: An Ethical Concern

12-16

D. E. Aarons The Right to Die – Who Decides?

17-19

L. Bernstein, DMD, MPH CME A case of Giant Cell Arteritis

20-21

L. Gonzales, L. M Pinto Pereira, S. Teelucksingh Commentary The Development of Children: Points to Ponder

22-24

Jane Holmes Bernstein Review Paraneoplastic Syndromes Affecting the Locomotor System - A Review P. J Rooney & J. Rooney

ISSN 0374-7042 C O D E N

25-27

Caribbean Medical Journal

Original Scientific Article The Use of Magnetic Resonance Spectroscopy in the Preoperative grading of Astrocytomas N. Ramnarine (MRCS), P. Knight (MRCS) & D. Ramnarine FRCSEd (Neuro Surg) Department of Neurological Surgery, Eric Williams Medical Sciences Complex, Trinidad and Tobago

Abstract Astrocytomas represent the most common intraaxial brain tumour, approximately 12000 cases per year in the US. Their grading remains controversial and represents a challenge both preoperatively and post operatively to both surgeon and pathologist. In difficult lesions such as Astrocytomas, MRS may provide assistance in diffentiating high grade from low grade lesions, which could dictate change in management.

Lesions such as primary neoplasms (high- and low-grade), secondary (metastatic) neoplasms, lymphoma, tumefactive demyelinating lesions, abscesses, and encephalitis, may be diffentiated with the assistance of MRS. We present a case of a 64year old right handed male with a 1 year history of progressive left sided hemiparesis. MRI scan demonstrated a diffusely infiltrating abnormality in deep white matter tracts, in the Corona radiata and in the hand area of the motor strip, which was highly suspicious of neoplastic process.

A scan was repeated six months later with special request for MRS . Using multi vauxhall spectroscopy the area with highest choline peak, which was most likely to represent malignant transformation in a low grade tumour, a frameless stereotactic biopsy was performed. Histology of the tumour was reported as a grade 2 astrocytoma however small areas of peripheral necrosis was suspicious of malignant transformation.

characteristics, and the chemical makeup of certain compounds of masses.

The role of MR spectroscopy in the diagnosis and classification of intraaxial brain tumors in adults is invaluable. In difficult lesions such as Astrocytomas, MRS may provide assistance in diffentiating high grade from low grade lesions, which could dictate change in management. Lesions such as primary neoplasms (highand low-grade), secondary (metastatic) neoplasms, lymphoma, tumefactive demyelinating lesions, abscesses, and encephalitis, may be diffentiated with the assistance of MRS. Clinical Presentation A 64 year old right handed male, past medical history of Hypertension, Ischaemic Heart Disease and coronary bypass, presented with a 1yearr history of progressive left sided hemiparesis. Examination revealed MRC grade 3/5 power in the left upper extremity and 4/5 power in theleft lower extremity with brisk reflexes with mild facial weakness MRI scan demonstrated a diffusely infiltrating abnormality in deep white matter tracts, in the Corona radiata and in the hand area of motor strip (fig.1). The lesion was highly suspicious of neoplastic process.

This case reiterated that MRS although a relatively new imaging technique it has proven to be quite useful in the diagnosis and grading of clinically difficult intracranial tumours.

Key Words: Magnetic Resonance Spectroscopy, Grading of Astrocytomas Introduction Astrocytomas represent the most common intraaxial brain tumour, approximately 12000 cases per year in the US. Their grading remains controversial and represents a challenge both preoperatively and post operatively to both surgeon and pathologist. Special concerns of specimen sampling error as tumours may have different grades in different areas, as well as dedifferentiation since low grade astrocytomas may progress in malignancy over months to years, necessitate the use of all available investigations in the diagnosis of these tumours.

Astrocytomas presents a dilemma, as both their diagnosis and surgical management may be controversial, especially that of High grade( Gd III and Gd IV ) astrocytomas.

The role of imaging is no longer limited to merely providing anatomic details. Sophisticated magnetic resonance (MR) imaging techniques allow insight into such processes as the freedom of water molecule movement, the microvascular integrity and hemodynamic

Fig. 1 T1 weighted MRI scan demonstrating a diffusely infiltrating abnormality in deep white matter tracts, in the Corona radiata and in the hand area of motor strip A scan was repeated six months later with special request for MRS. This scan demonstrated enhancement with gadolinium suggestive of tumour. Using multi vauxhall spectroscopy the area with highest choline peak, which was most likely to represent high grade transformation in a low grade tumour, was selected (figure2).

A.

B.

1

Caribbean Medical Journal The Use of Magnetic Resonance Spectroscopy in the Preoperative grading of Astrocytomas

Figure 2. A. multi vauxhall spectroscopy at area suspicious of tumour, showing a high choline peak with decresed NAA peak. B. Comparative spectroscopy to normal opposite side revealing decresed Choline peak with high NAA peak The volumetric scan data was loaded and an image guided biopsy performed using brainlab neuronavigation system.

The patient had an uneventful postoperative course.

Figure 3. MRS The volumetric scan data Histology of the tumour was reported as a grade 2 astrocytoma however small areas of periperal necrosis was suspicious of malignant transformation Discussion Localized brain proton MR spectroscopy (1 H-MRS), has attempted to provide semiquantitative measures of metabolite levels to characterize brain tumors with a view to answering a number of important research and clinical questions. Combining advanced MRI techniques such as MR spectroscopy can help in solving difficult cases and increase confidence in diagnosis. However, there is still need for caution in the final interpretation. These advanced MR imaging techniques are useful in both the clinical and research settings, however, they should be considered supplementary tools to the patients’ clinical history, examination and conventional MRI findings when making a neuro-diagnosis.

The basic metabolite changes common to brain tumors include elevation in Choline (Cho), Lactate (Lac), Lipids (L), decrease in N-Acetyl Aspartate (NAA) and decrease in Creatine (Cr). As clinical spectroscopy becomes more sophisticated, metabolites identified with short echo time (TE) MRS are also becoming important in increasing the specificity of MRS in brain tumor diagnosis.

The increase in Cho in simple terms is attributed to cell membrane turnover and proliferation [1,2].In proton spectroscopy, an elevation in Cho may be due to either cell membrane synthesis, destruction or both. Measurable levels of Cho vary considerably, depending on the cellular density, tumor grade and presence or absence of necrosis [4,5,6]. Cho resonance is most prominent in regions with high neoplastic cellular density and is progressively lower in moderate and low-grade tumors [3,4,6,7] . Paradoxically, some highly malignant tumors and some GBMs may show low Cho because of extensive necrosis [8,9]. Histologic markers of proliferative activity in gliomas, Ki-67 labeling and MIB-1 labeling indices have a strong linear correlation with Cho levels. Under normal circumstances, lactate is present only in minute amounts in the brain and is not 2

resolved with clinical spectroscopy. However, conditions in which aerobic oxidation fails and anaerobic glycolysis takes over, such as hypoxia, metabolic disorders and macrophage accumulation (areas of inflammation), lactate levels increase significantly. Lactate also accumulates in tissues that have poor washout, like cysts and necrotic foci, hence lipids and lactate are found in necrotic and cystic tumors. The exact role of NAA is presently not known. NAA is a marker of neuronal density and viability.

It is generally felt to be neuron specific, NAA can also be found in immature oligodendrocytes and astrocyte progenitor cells [10]. NAA is also found in axons, as it is transported along the axons from the site of synthesis in the neuronal mitochondria [3].The decrease in NAA represents the replacement of normal functioning neurons and axons with neoplastic tissue [3,1,2]. The levels of Cr and phosphocreatine (PCr) in brain tumors is variable [1,12]. In simplistic terms, Cr is a marker of ‘‘energy metabolism’’ and is reduced in tumors due to the increased metabolic activity of tumors consuming energy.

These metabolite alterations have prompted some investigators to use ratios or statistical indices based on metabolites in an attempt to optimize the differences in metabolite concentration in brain tumors. For example the elevation in Cho and decrease in NAA would suggest that a Cho/NAA ratio or a statistical Cho to NAA index (CNI) would be very sensitive to detecting tumoral activity [13,14] . In the clinical setting, Cr is assumed to remain stable and is used as a reference for calculating metabolite ratios, (Cho/Cr and NAA/Cr ratios) providing a method for self-correction for hardware and localization method differences, gain instabilities and partial volume effects with CSF containing structures. However, regional and individual variability in Cr concentrations is known and, particularly in the research setting, absolute metabolite quantification may increase the sensitivity and specificity of MRS [15].

The spectroscopic findings in a number of intracranial masses is sometimes non-specific. There is overlap in the spectroscopic appearance of many ring-enhancing lesions such as gliomas, metastases, inflammatory lesions, demyelinating lesions and some AIDS related lesions. In fact the spectrum from a normal neonatal brain will have the same spectrum as that of a high grade glioma [15].

However, the combination of clinical findings, conventional MRI and MRS, can increase our diagnostic accuracy and confidence. Furthermore, a number of techniques can be employed in the clinical setting to improve our specificity. First, comparing metabolite values from the lesion to contralateral normal appearing brain and obtaining Cho/Cho(n) and Cho/Cr(n) ratios rather than the conventional Cho/Cr or Cho/NAA ratios provides a more specific internal standard for semiquantifi- cation of metabolites [17,18]. Second, obtaining MRSI data from not only the tumoral but also the peritumoral region can help differentiate between infiltrating edema around a primary glioma versus pure vasogenic edema around metastases and other noninfiltrating lesions [19]. Third, there are some pathologies where finding resonances such as leucine, isoleucine,

Caribbean Medical Journal The Use of Magnetic Resonance Spectroscopy in the Preoperative grading of Astrocytomas

valine, alanine, acetate, succinate and glycine helps with the diagnosis of a bacterial abscess [20]. The use of MRS is not only limited to defining different intracranial masses, but also in in defining different grades of tumours.

both the equipment and familiarity in its assessment.

It should be used when spectral data will provide clinical information that is not obtained by other imaging techniques.

The grading of gliomas has significant clinical importance, since high-grade gliomas are usually treated with adjuvant radio- or chemotherapy after resection whereas low-grade gliomas are not. Histopathological assessment, the current gold standard for tumor grading, has limitations such as inherent sampling error associated with the limited number of biopsy samples. Even with cytoreductive surgery, histology can only be performed on excised tumor and residual tumor tissue cannot be examined.

Importantly it is well known that residual low grade tumor has the propensity for malignant transformation.

The histopathologic classification of gliomas itself is a controversial subject, under constant discussion and revision [21]. High grade gliomas generally have higher Cho levels than low grade gliomas[22]. Recently, the percent change in Cho/NAA has been shown to be useful in predicting tumor progression in children with brain tumors [23]. A review of the literature, taking into account differences in spectroscopic technique such as the choice of echo time (TE) and method for determination of metabolite ratios, demonstrates maximal values obtained for Cho/Cr, Cho/NAA and minimum values for NAA/Cr to be of utility in differentiating between LGGs and HGGs [7,23]. There are differences in Cho levels between LGGs and HGGs, with LGGs generally demonstrating lower Cho than HGGs. This difference is appreciated even using different methods for quantifying Cho [7]. McKnight et al demonstrated 90% sensitivity and 86% specificity by using a Cho/NAA statistical index (CNI) of 2.5 in distinguishing tumoral tissue from non-tumoral tissue [13]. The median CNI values for grade II/IV, grade III/IV and grade IV/IV gliomas are 6.9, 7.1 and 9.37 respectively, with a large variation in the maximum CNIs in the grade IV/IV group [12].

Conflict of interest: None declared Corresponding author: D. Ramnarine devindra.ramnarine@gmail.com

The clinical utility of tumoral proton MR spectra in glioma grading is still being investigated. At this point, it is important to understand that MRS is very sensitive to abnormal metabolic changes but the specificity is relatively low [24]. Clinically it is not uncommon to find some LGGs with very high Cho/Cr and Cho/NAA ratios and conversely HGGs with lower Cho/Cr and Cho/NAA ratios due primarily to extensive necrosis , which increases false positive rate and false negative rates respectively.

There is some overlap in CNI between tumors of different grades [12] . It may also be related to the variability in using metabolite ratios rather than absolute quantification to compare glioma grades [15,25]. Lipid and lactate elevation correlate with necrosis in HGGs and has also been shown to be useful in differentiating HGG from LGGs [5,14,26].

Conclusion MRS is a relatively new imaging technique that could be quite useful in the diagnosis and grading of clinically difficult intracranial tumours. This however is not without its challenges, as MRS is a specialised technique requiring

References 1. Castillo M. Proton MR Spectroscopy in Neoplastic and NonNeoplastic Brain Disorders. MRI Clinics of North America.

1998;6:1–19.

2. Danielson ER, Ross BD. Magnetic Resonance Spectroscopy of Neurological Diseases. New York: Marcel Dekker Inc, 1998.

3. Fulham MJ, Bizzi A, Dietz MJ, et al. Mapping of brain tumor metabolites with proton MR spectroscopic imaging: clinical relevance.

Radiology. 1992;185:675–686.

4. Gupta RK, Cloughesy TF, Sinha U, et al. Relationships between choline magnetic resonance spectroscopy, apparent diffusion coefficient and quantitative histopathology in human glioma. J Neurooncol. 2000;50: 215–226.

5. Lehnhardt FG, Rohn G, Ernestus RI, et al. 1H and (31) P-MR Spectroscopy of primary and recurrent human brain tumors in vitro: malignancy- characteristic profiles of water soluble and lipophilic spectral components. NMR Biomed. 2001;14:307–317.

6. Meyerand ME, Pipas JM, Mamourian A, et al. Classification of biopsyconfirmed brain tumors using single-voxel MR spectroscopy.

AJNR Am J Neuroradiol. 1999;20:117–123 7. Shimizu H, Kumabe T, Tominaga T, et al. Noninvasive evaluation of malignancy of brain tumors with proton MR spectroscopy. AJNR Am J Neuroradiol. 1996;17:737–747.

8. Castillo M, Kwock L. Proton MR spectroscopy of common brain tumors. Neuroimaging Clin N Am. 1998;8:733–752.

9. Kwock L. Localized MR Spectroscopy. Neuroimaging Clin N Am. 1998;8:713–732.

10. Urenjak J, Williams SR, Gadian DG, et al. Specific expression of Nacetylaspartate in neurons, oligodendrocyte- type-2 astrocyte progenitors, and immature oligodendrocytes in vitro. J Neurochem.

1992;59:55–61.

11. Negendank WG, Sauter R, Brown TR, et al. Proton magnetic resonance spectroscopy in patients with glial tumors: a multicenter study. J Neurosurg. 1996;84:449–458.

12. Nelson SJ, McKnight TR, Henry RG. Characterization of untreated gliomas by magnetic resonance spectroscopic imaging. Neuroimaging Clin N Am. 2002;12:599–613.

13. McKnight TR, von dem Bussche MH, Vigneron DB, et al.

Histopathological validation of a three-dimensional magnetic resonance spectroscopy index as a predictor of tumor presence. J Neurosurg. 2002;97:794– 802.

14. Li X, Lu Y, Pirzkall A, et al. Analysis of the spatial characteristics of metabolic abnormalities in newly diagnosed glioma patients. J Magn Reson Imaging. 2002;16:229–237.

15. Li BS, Wang H, Gonen O. Metabolite ratios to assumed stable creatine level may confound the quantification of proton brain MR spectroscopy. Magn Reson Imaging. 2003;21:923–928.

16. Holshouser BA, Ashwal S, Luh GY, et al. Proton MR spectroscopy after acute central nervous system injury: outcome prediction in neonates, infants, and children. Radiology. 1997;202:487–496.

17. Isobe T, Matsumura A, Anno I, et al. Quantification of cerebral metabolites in glioma patients with proton MR spectroscopy using T2 relaxation time correction. Magn Reson Imaging. 2002;20:343– 349.

18. Rabinov JD, Lee PL, Barker FG, et al. in vivo 3-T MR Spectroscopy in the Distinction of Recurrent Glioma versus Radiation Effects: Initial Experience. Radiology. 2002;225:871–879.

19. Law M, Cha S, Knopp EA, et al. High-Grade Gliomas and Solitary Metastases: Differentiation by Using Perfusion and Proton Spectroscopic MR Imaging. Radiology. 2002;222:715–721.

20. Dev R, Gupta RK, Poptani H, et al. Role of in vivo Proton Magnetic Resonance Spectroscopy in the Diagnosis and Management of Brain Abscesses. Neurosurgery. 1998;42:37–43.

21. Daumas-Duport C, Scheithauer B, OFallon J, et al. Grading of astrocytomas: a simple and reproducible method. Cancer.

1988;62:2152–2165.

22. Law M, Yang S, Wang H, et al. Glioma grading: sensitivity, specificity, and predictive values of perfusion MR imaging and proton MR spectroscopic imaging compared with conventional MR imaging.

AJNR Am J Neuroradiol. 2003;24:1989–1998.

23. Yang D, Korogi Y, Sugahara T, et al. Cerebral gliomas: prospective comparison of multivoxel 2D chemical- shift imaging proton MR spectroscopy, echoplanar perfusion and diffusion-weighted MRI. Neuroradiology. 2002;44:656–666.

24. Kwock L, Smith JK, Castillo M, et al. Clinical applications of proton MR spectroscopy in oncology. Technol Cancer Res Treat. 2002;1:17–28.

25. Lin A, Bluml S, Mamelak AN. Efficacy of proton magnetic resonance spectroscopy in clinical decision making for patients with suspected malignant brain tumors. J Neurooncol. 1999;45:69–81.

26. Howe FA, Barton SJ, Cudlip SA, et al. Metabolic profiles of human brain tumors using quantitative in vivo 1H magnetic resonance spectroscopy. Magn Reson Med. 2003;49:223–232.

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Caribbean Medical Journal

Original Scientific Article An Audit of Medical Records in the Orthopedic Department at a Tertiary Institution C. Calderon –M.B.B.S (Hons), A. Nicholas - MBBS & E. Budhoo DM (Orthopaedics) Eric Williams Medical Sciences Complex, Mt. Hope, Trinidad Abstract Record keeping is a fundamental aspect of the physician’s life and at times may become mundane. However, adequate and appropriate record keeping is vital to patient care. We sought to identify any areas of insufficiency in our medical data keeping.

A clinical audit was conducted using the Crabel score to assess medical records of five orthopedic firms in the Eric Williams Medical Sciences Complex. Data showed a summative average of eighty four percent (84%) for the five firms, with the most superior marks being noted in the consent and discharge letters.

Poorer results were noted in the subcategory of subsequent entries into the patient files, especially with omission of patient name and number, and proper closing off of an entry with signature, name, and post.

Keywords: audit, Crabel score, Trinidad Introduction Record keeping is an essential aspect of every physician’s everyday work life. It is linked positively to the methodical outlining of the progress of patient care and management and can be utilized in research to achieve greater comprehension of disease and formatting of new surgical techniques. When there is error in this process, seen and unseen, this may be detrimental not only to the patient, but to the physician as well. Audits play a fundamental role in ensuring that the standard of practice is near optimal.

Method This was a clinical audit assessing medical note keeping at a tertiary institution. Medical notes were selected randomly; two from each of the five Orthopedic firms at the Eric Williams Medical Sciences Complex (EWMSC).

The auditing tool utilized was the CRABEL score, developed by Crawford, Beresford and Lafferty(2001), which assesses the initial clerk, subsequent entries, consent and the discharge letter from each medical file (see figure 3, 4). A total of fifty marks are awarded to each of the two files per orthopedic firm, giving a summated value of hundred per firm, and hence a percentage. [2] Results

Figure 1: Distribution of marking proforma of five orthopedic firms Using the criteria of the Crabel study, an average score from the five firms was calculated to be approximately 84% - with the highest and lowest scores being 87% and 79% respectively. Most firms received full points in the categories of “consent” and “discharge letter” assessment areas.

On further analysis, an area of major deduction was noted in “subsequent entries”. This included the assessments of patient name and number, date and time, heading, results, legibility and signature/name/post/bleep number. Of note, given that bleep numbers are not part of our system; this was not assessed or taken into consideration. From these, most affected was signature/name/post. For the most part, entries never indicated all three on closing off an insertion into the notes, with the majority of physicians opting to sign their names only, with the exception of a few who wrote and signed their names.

Documentation of patient name and number varied- with the omission of one or both, and the recording of results requested were insufficient in some areas. The best subcategories noted were “heading” for each entry and “legibility” of handwriting. The latter being assessed by two independent observers.

Higher scores, as noted with consent taking for surgical operation and the discharge letter on being dismissed from care, coincided with the availability of specific forms that highlighted the sub categories being assessed by the Crabel score. As such, the converse was noted, in areas where pre- headed forms were unavailable.

Discussion Data auditing should be an essential part of any department especially in the medical field. Medical records provide important information not only about the progress of the patient, but are critical to research collection, and of course, the ever rising medico-legal concerns.[1,6] It is important to note that record keeping extends beyond what is documented in patient’s file – but also pertains to and is integral to other aspects such as, prescription writing. [5] The pivotal nature of appropriate record keeping cannot be more stressed in this 21st century – as it must be etched on our forebrains that, if it is not written / documented – it might as well have not been done. Proper record keeping is demanded by insurance companies in terms

4

Caribbean Medical Journal An Audit of Medical Records in the Orthopedic Department at a Tertiary Institution

of financial claims and by law institutions when claims of negligence are being investigated. Although many individuals are pertinent to the process of up keeping a comprehensive medical file – the chief personnel likely to be held accountable is the medical physician.

In first world countries, the number of medical litigations has been trending upward steadily, with millions of dollars being spent each year. [4] In our region, the number and rate of medico legal issues are evolving, and we must remain conscientious to what is trending worldwide. We must remain mindful that “Poor records mean poor defense, no records mean no defense”. [1] In the surgical field, where incidents may occur within the blink of an eye, it is essential that documentation be made prospectively in detailing circumstances involving injury/disease, consequences, management, expected course and possible complications.

Conclusion The audit tool utilized was the Crabel score, which has shown to be a reliable, easy to use and applicable to our setting. From the use of this auditing contrivance, deficiencies were noted in certain areas of note keeping, however overall results were satisfactory. Consent and discharge letter forms are up to date and acceptable, but the need to stress on documenting of date and time at the beginning of each entry and the signing and writing of name and post must be highlighted. All the knowledge and insight obtained will be shared in the department – to keep the standard of note keeping optimal and even aiming for better.

Tables and Legends:

Initial Clerking Subsequent Entries Consent Discharge Letter Total

A 14

B 15

C 15

D 18

E 16

50 8

48 10

45 9

50 9

54 8

10 82

10 83

10 79

10 87

9 87

Table 1: Distribution of marking guidelines using Crabel score of five orthopedic firms (corresponds to Figure 1 ) Subsequent entries Patient name and number Date and time Heading Results Legibility Signature/ name/post

A

B

C

D

E Total

2 2 0 1 0

3 1 1 2 0

3 0 6 2 0

2 2 0 0 0

1 1 0 1 0

11 6 7 6 0

5

5

4

6

3

23

Table 2: Distribution of deducted scores for the category of subsequent entry from marking proforma of Crabel score (corresponds to Figure 2)

Figure 2: Graph showing distribution of deducted scores for the category of subsequent entry from marking proforma of Crabel score Appendix: THE CRABEL SCORE Firm: MARKING PROFORMA { } { }patient initials INITIAL CLERKING {10} patient name patient hospital number referral source consultant date/time diagnosis management plan investigation results clinician signature clinician name/ post/ bleep no.

SUBSEQUENT ENTRIES {30} patient name and number date and time heading results legibility signature/ name/ post/ bleep no.

CONSENT patient name hospital number operation in full risks/ complications signatures

{5}

DISCHARGE LETTER { 5 } patient details admission/ discharge dates diagnosis/ management drugs follow-up TOTAL DEDUCTIONS

{ }

+

CRABEL SCORE (100 – DEDUCTIONS) =

{ } = % 5

Caribbean Medical Journal An Audit of Medical Records in the Orthopedic Department at a Tertiary Institution

Figure 3 : Marking sheet used to assess Crabel score Appendix: Table 1 CRABEL score.

One point is deducted for each omission of any of the following details Initial clerking (10 points) • Patient’s name (at top of history sheet) • Patient’s hospital number (at top of history sheet) • Referral source (general practitioner, dentist, A&E department) • Admitting consultant • Date/time of clerking • Working diagnosis or differential diagnosis • Management plan • Results of investigations • Signature of clinician at end of clerking • Name, post and bleep number of clinician (all details required) Subsequent entries (up to 6 entries, 30 points) • Patient’s name and number at the top of each history sheet • Date and time of each entry • Heading (ward round and consultant’s name) • Results (to be documented in notes) • Notes should be legible • Signature, name, post and bleep number clearly printed at the end of each entry Consent (5 points) • Patient’s name at top of sheet • Hospital number at top of sheet • Operation in full without abbreviations • Risk or complications appropriate to the procedure documented • Signatures of clinician and patient or guardian Discharge letter (5 points) • Patient’s details (name and address) • Admission and discharge dates • Diagnosis and management • Medication on discharge • Follow-up plans Figure 4 : Detailed outline of Crabel score marking proforma

6

Conflict of interest: None declared Corresponding author: C. Calderon - ccalderon88@gmail.com References: 1. Joseph Thomas. Medical records and issues in negligence. Indian J Urol. 2009 25(3) 2. Crawford JR, Beresford TP, Lafferty KL. The CRABEL score--a method for auditing medical records. Annals of The Royal College of Surgeons of England2001; 83(1):65-68.

3. Arotiba JT, Akinmoladun VI, Okoje VN. An audit of medical recordkeeping in maxillofacial surgery at the University College Hospital, Ibadan using the CRABEL Scoring system. Afr J Med Med Sci. 2006 4. Harold Ellis. Medico-legal litigation and its links with surgical anatomy.

Surgery Journal 2002 vol 20 issue 8 5. Amit Bali, Deepika Bali, Nageshwar Iyer, Meenakshi Iyer.

Management of Medical Records: Facts and Figures for Surgeons. J Maxillofac Oral Surg. 2011; 10(3) 6. Wedad Abdelrahman, Abdelrahman Abdelmageed. Medical record keeping: clarity, accuracy, and timeliness are essential. BMJ 2014 7. Ho MY, Anderson AR, Nijjar A, Thomas C, Goenka A, Hossain J, Curley PJ.Use of the CRABEL Score for improving surgical casenote quality. Ann R Coll Surg Engl. 2005 Nov;87(6)

Caribbean Medical Journal

Case Report When the thyroid function test results do not fit? Some uncommon causes of abnormal thyroid function test results L Gonzales MBBS1, M Omar MBBS1, A Bridgelal-Gonzales MBBS2, R Abdul MBBS1, S Teelucksingh FRCP1 1 2

Medical Associates Hospital, St Joseph. Trinidad and Tobago District Medical Office, Eastern Regional Health Authority

Introduction Thyroid disorders are common and combining a careful history, thorough physical examination and modern biochemical panels usually establishes a firm diagnosis of the state of thyroid dysfunction. Thus, the usual biochemical pattern is that of an inverse relationship between thyrotropin (TSH) and free levothyroxine (Free T4) in circulation. This relationship helps maintain homeostasis within the hypothalamic-pituitary-thyroid axis (HPT). Sometimes, thyroid function test results do not follow the typical patterns expected and this can be due to lab errors, assay interferences by other blood constituents such as biotin, intercurrent illness, concomitant use of oral contraceptives and drugs such as amiodarone, as well as pregnancy. Occasionally however, rare causes of thyroid disease may show up and the clinician should not be taken by surprise. [1] The following case vignettes outline the clinical presentation, investigations, and management of three patients with uncommon thyroid diseases presenting to a specialty endocrinology clinic in Trinidad.

Case 1: A 24-year-old female was referred by her general practitioner with a history of repeatedly low TSH values on biochemical testing over the past year. The patient’s main complaints included palpitations and intermittent attacks of dyspnoea on mild exertion for approximately one year. Fatigue, malaise, feelings of sadness and tearfulness were other prominent symptoms. She denied fever, excessive sweating, anorexia, weight loss, diarrhoea or constipation. Her menses were regular and there were no features of menorrhagia. She denied a history of past illnesses, hospitalizations or surgeries. Six months prior to her presentation, her general practitioner started her on 2.5mg of carbimazole, which did not improve her symptoms. She was then switched to propylthiouracil one tablet daily, the only medication that she was taking at the time of referral.

There was no family history of thyroid disease. She is a full-time university student (studying social sciences) and reports difficulty coping with increasingly tougher exams and assignments over the last year, as she is nearing the end of her program.

Physical examination was unremarkable. There was no goitre, thyroid bruit nor features of thyroid eye disease.

There was no tremor nor psychomotor agitation. Her pulse was 80 beats per minute, regular and non-collapsing.

Her skin was normal neither dry nor sweaty. Deep tendon

reflexes were normal throughout. Auscultation of her heart and lungs revealed no abnormalities..

Investigations Thyroid function tests revealed a TSH of 0.1 mU/L [NR: 0.3 – 3.0) and a free T4 of 1.5 ng/dl [NR: 0.8 – 2.0].

Thyrotropin Receptor Antibodies were negative, and her complete blood count was normal. Thyroid ultrasonography was normal, and her thyroid scintigram revealed a normal uptake of 2.5% [NR: 1 – 4%].

Discussion: Non-thyroidal illness syndrome.

A normal thyroid scintigram excludes hyperthyroidism.

The absence of a goitre, no eye signs, and negative thyroid receptor antibodies excludes Graves’ disease. This patient’s disturbed hypothalamic pituitary thyroid axis is secondary to her mood disturbance. Non-thyroidal illness syndrome (also called Euthyroid Sick Syndrome) is the occurrence of altered thyroid function test during times of critical illness, in patients without a previous history of thyroid disease [2]. It represents an adaptive or physiological response to illness by mechanisms that are not fully understood. Some authors believe it is a protective response to help reduce the catabolism that occurs during critical illness. Some patients may be clinically euthyroid, in which case there is usually an elevated level of reverse T3 in circulation; while others may have central hypothyroidism because of their illness (making nonthyroidal illness syndrome a more appropriate description than sick euthyroid syndrome) [3].

In both instances, there is no consistent evidence demonstrating any clear benefit or harm from thyroid hormone replacement. Patients’ thyroid function tests are expected to return to normal after recovery from their illness.

Our patient’s propylthiouracil was discontinued and she was reassured that there was no indication for treatment with anti-thyroid medications. Routine follow up with repeat thyroid function test was recommended. Contact information was given to alert the medical team if any new concerns or changes before her scheduled appointment. She declined psychiatry referral.

Case 2: A 49-year-old female patient was referred for evaluation of an abnormal thyroid function test discovered during pre-operative work up for metabolic surgery. She had a history of type 2 diabetes, hypertension and obesity. There were no symptoms suggestive of hyperthyroidism such 7

Caribbean Medical Journal When the thyroid function test results do not fit? Some uncommon causes of abnormal thyroid function test results

as palpitations, fatigue, excessive sweating, heat intolerance, diarrhoea or weight loss. Her weight was in fact steady over many years and she has been unable to lose weight despite many attempts with lifestyle changes such as diet and exercise. Her menses were regular and she denied mood or sleep disturbance. She has had no previous surgeries or admissions to hospital. Her medications include: metformin, lisinopril, and atenolol.

She denied use of the oral contraceptive pill, herbal therapy or supplements of any kind. There was a family history of obesity and a thyroid disorder affecting her mother, but no other diseases ran in her immediate family. She denied tobacco and ethanol use.

On examination, her weight was 110 Kg, height 1.55m, BMI was 44 Kg/m2 and waist circumference 121 cm. Her blood pressure was 126/84 mm/Hg and pulse 85 beats per minute, regular and non-collapsing. There was no goitre and no postural tremor.

Examination of her heart, lungs and abdomen was normal.

There no evidence of proximal myopathy and her skin was normal (not dry or moist and no evidence of purpura or purple striae).

Investigations: HbA1c 6.6%, total cholesterol 125 mg/dl, HDL 24mg/dl, LDL 45mg/dl and triglycerides 228 mg/dl. Complete blood count, renal and liver function test were normal.

Her chest radiograph was normal and her echocardiogram showed mild left ventricular hypertrophy with a preserved ejection fraction.

Date May

TSH (NR 0.3 – 3.0 mIU/L) 0.9

Free T4 (NR 0.7-1.9 ng/dl) 2.5

June

0.4

2.7

nervousness [6]. This patient was reassured that no intervention was required, and routine follow up for any changes in her clinical condition was recommended.

Case 3: A 39-year-old female was referred to our clinic with a one-month history of fatigue, muscle pains, and cold intolerance. The patient had a history of well controlled asthma and allergic rhinitis on inhaled beta agonist and oral antihistamines as needed. She also had a recent diagnosis of hyperthyroidism two months prior to presentation. Her complaints two months ago were odynophagia, neck pain, malaise, palpitations, weight loss of approximately five pounds and excessive sweating.

Thyroid function testing at that time (see table below) was consistent with thyrotoxicosis and her GP initiated anti-thyroid medications carbimazole 10mg twice daily and propranolol 10mg twice daily. On examination at our clinic, her blood pressure was 102/70 mmHg, pulse was 94 beats per minute and her thyroid was just palpable but non-tender. Cardiovascular and respiratory examination was normal. Her skin was dry and ankle reflexes were slow relaxing suggestive of hypothyroidism.

Repeat thyroid function tests and anti-thyroid peroxidase antibodies were requested and she was advised to discontinue any further anti-thyroid medications. Her repeat thyroid function tests returned consistent with hypothyroidism and her anti-TPO antibodies were negative. Her overall clinical picture was consistent with a viral thyroiditis in the hypothyroid phase. The patient was counselled about her diagnosis and reassured that no treatment was required. On review six weeks later off all medications, she was clinically and biochemically euthyroid.

Table 2. Laboratory results.

Date

Table 1. Thyroid Function Test Results.

Discussion: The syndrome of impaired sensitivity to thyroid hormones.

This patient is clinically euthyroid, lacking any symptoms and signs suggestive of hyperthyroidism. She has no goitre nor eye signs to suggest Graves’ disease, the most common cause of hyperthyroidism. This combination of an elevated free T4 and a non-suppressed TSH, in a clinically euthyroid patient, is consistent with the syndrome of thyroid hormone resistance (now called impaired sensitivity to thyroid hormones). This is a rare condition that occurs in 1 in 40, 000 live births. The diagnosis can be confirmed by genetic testing to identify germline mutations in the thyroid hormone beta receptor gene, the most common known aetiology to date [4,5].

The importance of recognising this syndrome is to avoid inappropriate treatment with anti-thyroid medications, which would likely produce symptoms of hypothyroidism in this patient and further complicate the clinical picture.

Some patients, however, may require symptomatic treatment such as beta blockers for palpitations or

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TSH

Total T4 Free T4 Anti-TPO antibodies 0.3–3 4.5 -12 0.8–2.0 mIU/L mg/dl ng/dl

ESR

March 0.016

19.0

-

-

-

May

94.2

-

0.5

Negative

35mm/hr

July

3.1

-

0.8

-

-

Discussion: Subacute (De Quervain’s) Thyroiditis.

Subacute thyroiditis following a non-specific viral illness is the most likely explanation for this patient’s symptoms and thyroid dysfunction. She became markedly hypothyroid because of the natural history of her thyroiditis coupled with the inappropriate use of high dose anti-thyroid medications. Hashimoto's disease can present with an initial thyrotoxic phase, but negative antithyroid peroxidase (TPO) antibodies makes Hashimoto’s less likely in this case. De Quervain's thyroiditis can be diagnosed clinically by the presence of a painful and tender thyroid gland with systemic symptoms such as

Caribbean Medical Journal When the thyroid function test results do not fit? Some uncommon causes of abnormal thyroid function test results

fever, malaise, and fatigue [7,8]. The pain may radiate to the jaw or ears and sometimes patients may have odynophagia. Symptoms of thyrotoxicosis may also be present such as palpitations, excessive sweating, anxiousness, and weight loss. When the diagnosis is in doubt the presence of an elevated ESR, and reduced radioactive iodine uptake on a thyroid scintigram are consistent with the diagnosis of a thyroiditis [8]. Treatment is symptomatic: nonsteroidal anti-inflammatory drugs, or a short course of corticosteroids are effective for the management of associated pain [9].

Conflict of Interests: None Declared Corresponding Author: Lorenzo Gonzales ackoms.razor@gmail.com References 1. Koulouri O, Moran C, Halsall D, Chatterjee K, Gurnell M. Pitfalls in the measurement and interpretation of thyroid function tests. Best Pract Res Clin Endocrinol Metab. 2013;27(6):745-762.

2. Lee S, Farwell AP. Euthyroid Sick Syndrome. Compr Physiol. 2016; 6(2):1071-80.

3. Chopra IJ. Clinical review 86: Euthyroid sick syndrome: is it a misnomer? J Clin Endocrinol Metab. 1997;82(2):3 4. Dumitrescu AM, Refetoff S. The syndromes of reduced sensitivity to thyroid hormone. Biochim Biophys Acta. 2013; 1830(7):3987-4003 5. Rivas AM, Lado-Abeal J. Thyroid hormone resistance and its management. Proc Bayl Univ Med Cent 2016; 29:209–11.

6. Weiss RE, Refetoff S. Treatment of resistance to thyroid hormoneprimum non nocere. J Clin Endocrinol Metab. 1999; 84(2):401–404 7. Engkakul P1, Mahachoklertwattana P, Poomthavorn P. Eponym: de Quervain thyroiditis. Eur J Pediatr. 2011;170(4):427-31.

8. Fatourechi V1, Aniszewski JP, Fatourechi GZ, Atkinson EJ, Jacobsen SJ. Clinical features and outcome of subacute thyroiditis in an Incidence Cohort: Olmsted County, Minnesota, Study. J Clin Endocrinol Metab.

2003; 88(5):2100-5.

9. Kubota S, Nishihara E, Kudo T, Ito M, Amino N, Miyauchi A. Initial treatment with 15 mg of prednisolone daily is sufficient for most patients with subacute thyroiditis in Japan. Thyroid.

2013; 23(3):269-72

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Caribbean Medical Journal

Case Report Rituximab use in a case of successfully treated anti–NMDA receptor encephalitis in Trinidad A. Panday MRCP 1 & C. A. Beers Phd 2 1 2

Department of Medicine, Eric Williams Medical Sciences Complex.

Cumming School of Medicine, University of Calgary.

Abstract Anti-NMDA receptor encephalitis is a newly recognized syndrome that often presents with a constellation of seeming unrelated findings: encephalopathic symptoms, ovarian teratomas, and CSF immunological abnormalities. Caused by autoantibodies to a ubiquitous neurotransmitter receptor, antiNMDA receptor encephalitis is also very responsive to treatment with many patients returning to baseline function with prompt and appropriate treatment. We present herein a case of antiNMDA receptor encephalitis with an atypical presentation of acute onset seizures and dystonic facial movements which commenced while aboard an international flight, who failed to respond to first-line therapy but was successfully treated with rituximab and who we believe, represents the first successfully treated case treated in Trinidad with Rituximab therapy.

Keywords: Anti–NMDA receptor encephalitis, rituximab, Trinidad Introduction Encephalitis is a notoriously difficult presentation to diagnose and treat, often leading to poor outcomes.

Autoimmune encephalitis, where the body mounts an immune response against CNS proteins, may present with a wide variety of neurological symptoms as any part of the nervous system may be attacked. Here we present the case of a patient with a newly recognized autoimmune encephalitis, anti-NMDA receptor encephalitis. This case exhibited a challenging presentation and our treatment ultimately led to a positive outcome.

Case Report We present the case of a previously healthy 33-year-old, female who presented with abnormal, involuntary orofacial and upper limb dyskinetic movements associated with an altered level of consciousness. The patient’s initial presentation occurred while aboard an international flight.

Prior to takeoff she had taken prochlorperazine and dimenhydrate. She had history of motion sickness and had previously taken these medications with no ill effects.

On board, she was observed to have a generalized tonicclonic convulsion followed by 5 minutes of post-ictal drowsiness. Afterwards her level of consciousness was markedly decreased, and the patient became aggressive and exhibited abnormal facial grimacing and repetitive slow eye-closure movements.

At hospital she was found to be hemodynamically stable with no focal neurological signs. She displayed multiple orofacial-brachial dyskinetic movements as well as oculogyric crisis. She did not respond appropriately to verbal or tactile stimulation. A non-enhanced CT Brain

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and MRI Brain were normal, and a lumbar puncture revealed an opening pressure of 18mmH2O with CSF protein of 10 and a lymphocytic pleocytosis of 91 lymphocytes and 1 neutrophil. The gram stain as well as India ink were negative. The CSF HSV 1 IgM was negative, but the IgG was mildly positive at 2.02 (normal <2.0). A technically difficult electro-encephalogram revealed diffuse slowing of the background but no epileptiform activity was noted.

Due to clinical suspicion, a CT Abdomen/Pelvis/Chest was done which revealed a right adnexal mass which was further confirmed by transvaginal ultrasound and titres were sent for serum anti-NMDA (which were subsequently positive). Laparoscopy revealed the right adnexal mass to be a fibroid in nature but the left ovary was noted to be enlarged leading to a left oophorectomy confirming the presence of a mature benign dermoid cyst.

The patient had no significant past medical history, however her sister had undergone an oophorectomy for a benign mature dermoid cyst in the past.

Initially the patient was given 3 doses of benztropine and a 7 day course of acyclovir with no improvement in symptoms. Phenytoin was also loaded and commenced.

After removal of the teratoma, she underwent a 5-day course of intravenous immunoglobulins (IVIG 2g/kg) then pulsed intravenous methylprednisolone (1g/day for 3 days). At first there was modest improvement in her continuous involuntary movements but relief was temporary and her cognitive function progressed to catatonia. A repeat lumbar puncture revealed a lymphocytic predominant pleocytosis with negative gram stain, negative India ink and negative bacterial culture.

She was then treated with rituximab (1000mg on Days 1 and 15). Immediate improvement was noted on day 16.

Her abnormal dyskinetic movements ceased and her cognitive function dramatically improved. The patient was subsequently discharged with continued cognitive improvement. This was sustained after discharge and at two-year follow-up, she is seizure free and back to work at her previous job and position.

Discussion Anti–NMDA receptor encephalitis was first described as a syndrome in 2005 in a small series of young women presenting with acute psychiatric symptoms, decreased level of consciousness, seizures, memory deficits, central hypoventilation, ovarian teratomas, and CSF inflammatory abnormalities [1]. Unlike other types of autoimmune encephalitis, this group of patients responded well to

Caribbean Medical Journal Rituximab use in a case of successfully treated antiâ&#x20AC;&#x201C;NMDA receptor encephalitis in Trinidad

treatment via removal of the teratoma and subsequent immunosuppression or chemotherapy. In addition, immunolabeling of hippocampal neurons from the patients identified an unknown antigen being targeted that was suspected to be a major causative factor of this syndrome.

Since 2008, more than 200 manuscripts have been published on the disease (Medline search, July 2016).

In the prodromal period of the disease, non-specific symptoms including fever, rhinitis, vomiting, headache, and diarrhea have been found followed by psychiatric manifestations in the following two weeks: anxiety, psychosis, insomnia, stereotypic behavior, and visual or auditory hallucinations. Behavioural changes are common including mania, increased aggressiveness, social withdrawal, agitation, and hypersexuality. The neurologic manifestations of anti-NMDA encephalitis include both generalized and focal seizures, movement disorders such as dyskinesias are common, and cognitive decline involving the language and memory domains can be seen in most patients. Autonomic dysfunction characterized by dysregulation of heartrate, blood pressure, respiratory rate, and temperature are typical features, with hyperthermia often leading clinicians to pursue an infectious diagnosis.

Physical exam findings are often non-specific in antiNMDA receptor encephalitis with patients showing signs of diffuse encephalopathy and varying levels of consciousness [2]. In terms of investigations, both structural (CT, MRI) and functional (SPECT, PET, EEG) neuroimaging have yet to provide a consistent means of diagnosing this disease. The presence of ovarian teratoma appears to be a common finding in women with antiNMDA receptor encephalitis: in a sample of 100 patients (91 of whom were female), 56 patients had tumours, 49 of which were ovarian teratomas [3]. Additionally, in the aforementioned 557 subject observational study, 94% of all tumours found were ovarian teratomas [3]. Indeed, the finding of an ovarian teratoma in the patient presented here was vital in the path leading to our diagnosis. The screening for ovarian abnormalities in female patients presenting with encephalopathic symptoms of unknown etiology should be a priority.

Treatment of anti-NMDA receptor encephalitis is typically approached as illustrated in Figure 1 (adapted from UpToDate [4]). In a large multi-centre observational study, 557 patients with the disease were examined and their symptoms, treatments, and outcomes reported [3]. Of the 472 patients treated, 221 (49%) did not respond to firstline therapy, considered to be tumour removal with or without immunosuppression. Of the non-responders who were then treated with second-line therapy (rituximab, cyclophosphamide), 125 (57%) had a better outcome than those who did not. Indeed, other smaller studies have also shown rituximab to be effective after failure of first-

line therapies, particularly in those patients without identifiable tumours [2]. In the patient, we presented herein, rituximab provided nearly immediate improvement of the patientâ&#x20AC;&#x2122;s dyskinetic and cognitive symptoms after first-line therapy failed to provide relief.

In conclusion, anti-NMDA receptor encephalitis is a serious neurological condition that has a high potential for positive outcome if recognized and treated promptly and appropriately. Though rituximab is considered a secondline therapy in treating this disease, care should be exercised to initiate treatment promptly should first-line therapy (tumour removal, corticosteroids, IVIG, plasma exchange) fail.

Clinical suspicion of anti-NMDA encephalitis

Antibodies to NMDA receptors in CSF/serum

No

Yes

Consider alternative Dx

Tumor removal corticosteroids, IVIG, plasma exchange Response to treatment

No

Yes

Rituximab, cyclophosphamide

Tumor surveillance, chronic immunosuppression

Figure 1. Typical treatment algorithm for anti-NMDA receptor encephalitis. Adapted from UpToDate entry Paraneoplastic and autoimmune encephalitis (http://www.uptodate.com/contents/paraneoplasticand-autoimmune-encephalitis).

Conflict of interests: None declared Corresponding author: Avidesh Panday MBBS, MRCP avidesh.panday@gmail.com REFERENCES 1. Vitaliani, R., et al., Paraneoplastic encephalitis, psychiatric symptoms, and hypoventilation in ovarian teratoma. Ann Neurol, 2005. 58(4): p.

594-604.

2.

Jones, K.C., S.M. Benseler, and M. Moharir, Anti-NMDA Receptor Encephalitis. Neuroimaging Clin N Am, 2013. 23(2): p. 309-20.

3. Titulaer, M.J., et al., Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurol, 2013. 12(2): p. 157-65.

4. Dalmau, J. and M. Rosenfeld, Paraneoplastic and autoimmune encephalitis. UpToDate, Post TW (Ed).

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Caribbean Medical Journal

Ethics Challenges of Conflicts of Interest in the Caribbean: An Ethical Concern D. E. Aarons MB.BS., M.Sc.(Bioethics), PhD Caribbean Public Health Agency Abstract A conflict of interest occurs when a person, institution, organization, or government allows a secondary interest to interfere with a primary interest. The issue does not necessarily refer to character or integrity, as even the most highly placed persons may have several competing interests. However, governments should adhere to prescribed policies for procurement and awarding of contracts. Public health personnel and organizations should not align themselves with corporate entities and industries whose products are high in sugar, salt, and fat, all of which contribute to chronic and non-communicable diseases.

Health care personnel whose primary obligation concerns the best interests of their patients may be conflicted when they accept gifts from pharmaceutical companies seeking to have doctors prescribe their particular products. Specialists who receive honoraria from drug companies to address medical meetings are likewise conflicted when the disease condition about which they speak is amenable to a product produced by the particular company. Clinical researchers who enrolled their patients in research are also conflicted regarding the best interests of their patients and the possible outcome of the research that could bring fame, fortune, or promotion. Doctors who give expert testimonies in court hearings may also be conflicted.

Institutions, organizations, and members of governments may also be conflicted as local companies, international corporations and other private sector entities seek to influence them on specific matters. Where possible, conflicts of interest should be avoided, and when not possible, they should be managed as described in this article.

Keywords: Conflict of interest, ethics, public trust, accountability, public disclosure Background The term ‘conflict of interest’ is often used in civil society and political arenas in many countries. In a biomedical setting, a conflict of interest occurs when a clinician, researcher, public health official, research ethics committee/IRB member, university official, medical author, medical reviewer, journal editor, or a public health institution/organization, civil society organization, or government interacting with the private sector, allows a secondary interest (e.g. financial gain, career advancement, outside employment, publication opportunity, personal considerations, personal relationships, personal investments, or gifts) to interfere with a primary interest (e.g. patient welfare, research validity, the publication of research, or an obligation to act in the best interest of another person, group of persons, or an entity) [1].

The term does not speak to the ‘character’ or integrity of the person concerned, as anyone, even those most highly placed or with an impeccable character, may find

12

themselves in a conflict of competing interests. According to the World Health Organization (WHO) in its Declaration of Interests: A conflict of interest occurs when “the expert or his or her partner (a spouse or a person with a close personal relationship), or the administrative unit with which the expert has an employment relationship – has a financial or other interest that could unduly influence the expert’s opinion with respect to the subject matter under consideration.” [2] An ‘apparent conflict of interest’ exists when the existence of another interest could result in the person’s objectivity being questioned by others [2]. This questioning is a real if not foreseeable possibility, especially in situations where transparency and impartiality are desirable. Consequently, situations of possible conflicts in the public arena would best be avoided. This article outlines some examples of conflicts of interest and recommends procedures for their effective management.

Examples of interest Interests may be ‘tangible’ and ‘intangible.’ A tangible interest is quantifiable or measurable (e.g. financial), while intangible interests are not easily measured, such as scholarly, academic, professional or social concerns (e.g. an interest in one’s reputation). Conflicting financial interests include: conflicting salary, fees (e.g. speakers’ fees), or other forms of income (e.g. corporate advisory committee memberships, providing expert testimony in legal cases), invention rights (intellectual property rights) and royalties, and investment interests [2].

We may also have conflicting duties or other interests, such as: employment interests (e.g. professional position, title), working on a project that can directly benefit a friend or relative, a professional relationship with any entity involved in tobacco production, distribution, or sale, interests that compromise the well-being of participants in clinical research, favouritism (e.g. involving someone who paid you a salary, a fee, honorarium, or similar, or involving an individual with whom you have a close personal or professional relationship), or gifts offered as inducements (e.g. gratuity, favour, discount, entertainment, hospitality, loans, travel costs, or other items having monetary value) [1].

Added to these are the various non-financial sources of bias, such as political bias (political beliefs or opinions influencing decisions), ideological bias (decisions influenced by ideological considerations), professional bias (e.g. professional jealousy), and religious bias (religious beliefs, concerns, or considerations possibly influencing decisions).

Caribbean Medical Journal Challenges of Conflicts of Interest in the Caribbean: An Ethical Concern

The anatomy of a conflict of interest The process that may result in a conflict of interest involves three stages: Stage 1 – The Antecedent Acts: These are factors that condition a person’s mind towards ‘partiality’, thereby compromising the person and their duty to foster the public’s interest over their own private or personal interest [1]. Example: government employees accepting gifts, paid dinners, and similar.

Stage 2 – The State of Mind: This represents the affected sentiments, dispositions, proclivities, or affinities that are conditioned by the antecedent acts. So, a politician who accepts a substantial campaign contribution from an individual may be more inclined to favour that individual’s special business needs in legislative decisions, or in the awarding of contracts, etc., than if no contribution were given [1].

Stage 3 – The ‘Outcome’ behaviour or Behaviour of Partiality: Those actions taken by the conflicted individual (decisional behaviour) arising from the state of mind affected by the antecedent acts [1]. The outcome behaviour could result in self-aggrandizement, or in rewarding friends or associates at the expense of the general public and their best interests.

Examples of conflicts of interest Conflicts of interest invariably raise ethical concerns of potential bias, perceived deception, and loss of trust.

Some countries have policies and legislation that govern contracts and procurement, and these customarily underscore the principles of accountability and transparency [3]. In public procurement, there are direct as well as indirect ways that personal relationships can create problems, and these customarily involve close and extended family members, suppliers, bidders, consultants, contractors, friends, and employees.

Conflicts of interest are also deeply embedded in many areas of public health. For example, commercial entities whose products are high in fat, salt, and sugar may contribute to obesity and non-communicable diseases, therefore, persons who work in the public health arena and are thus entrusted with safeguarding the public’s best interests should not be perceived to be accepting gifts, lunches, or ‘drinks’ from persons or companies whose primary interests do not lie in the same public domain [4].

Ministries of Health and other public health organizations should also adopt a similar approach. In the past, corporate funding and partnerships have been associated with biased outcomes in scientific studies and the adoption of less effective measures in public health partnerships for NCD prevention [4]. So while ministries and public health organizations may wish to partner with members of the private sector to ameliorate specific problems, the choice of the private sector partner should be made carefully against the background of public perception, as the aims of the two entities may be different. The primary aim of the private sector company may be financial gain,

while that for the public health organization is to prevent and mitigate disease states in the general population.

In the health care sector, medical practitioners treat patients with chronic diseases, and numerous medications exist on the market for these diseases. Pharmaceutical representatives frequently visit private doctors’ offices with the aim of influencing increased prescriptions for their pharmaceutical products. Some doctors may receive small mementos as reminders, while others may receive substantial gifts including airfares to attend overseas conferences.

Specialists may receive honoraria to speak at medical meetings or conferences about a specific chronic disease which may be amenable to the medical product that the particular company manufactures. These specialists, whose primary duty is to promote and prescribe the best medication for patients, may be conflicted since the drug company will expect them to promote and prescribe their marketed products.

A conflict of interest may also exist for the clinical researcher, a medical doctor who does research. In medicine and health care, the medical doctor has a primary duty to always seek to benefit the individual patient under their care [6-11]. In research, the aim is to acquire new knowledge to benefit the wider society [12]. The focus is not the individual patient who may be enrolled in the research. A positive outcome to the research may bring fame, fortune, and promotion to the individual researcher [13]. The researcher is therefore conflicted in regards to the interests of the enrolled participants and their specific interest in the outcome of the research [14]. Consequently, researchers may be tempted to understate or not disclose all the possible risks of the research when seeking to enrol their patients, as they seek to achieve the required number of research participants.

In seeking to protect their reputation and trust in the validity of published research, most medical journals now require researchers to make a declaration of any conflicts of interest before their manuscripts are accepted for publication [5]. This is important, since professional judgement concerning a primary interest – the integrity of research, may be adversely influenced by a secondary interest – financial gain, particularly where the researcher may have a financial relationship with a pharmaceutical company.

Thus, a company might finance a researcher with the understanding that he or she will publish only the data that is favourable to the company’s financial interest [5].

If this happens, the published study might constitute only a fraction of the work that was undertaken. Readers, even experts in that field, might not be able to properly assess the primary data on which the conclusions of the study were based, yet in research, it is crucial that persons be able to assess the trustworthiness of their source [15].

Consequently, such disclosure is necessary to alert regarding possible bias in the study design and conclusions.

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Caribbean Medical Journal Challenges of Conflicts of Interest in the Caribbean: An Ethical Concern

Doctors and other scientists, based on their perceived expertise, may also be called to provide expert testimony in a court proceeding [5]. Their opinions are likely to be accepted as authoritative, as the judge and members of the jury are unlikely to have the requisite knowledge to critically assess what the doctor said. If the doctor is testifying about an injury to their patient, the doctor could be further conflicted. The court should therefore be informed of any relationships, financial or otherwise, that may compromise the judgement and pronouncements of the doctor or scientist, and expert witnesses should be cross-examined with regard to possible conflicts of interest.

This can help the jury assess the witness’s reliability as an expert on the issues under discussion [5].

‘Ethics’ versus ‘law’ The USA has federal conflict of interest laws that are designed to protect the government process from ‘actual or apparent conflicts of interest’ (e.g. the 1972 Federal Advisory Committee Act [FACA]) (1). However, Caribbean countries do not have such legislation and so must depend on a respect for ‘ethics’ and ethical considerations. Unfortunately, however, a disregard for ‘ethics’ carries no legislative penalty.

We should also note that ‘law’ is minimalistic in its approach, specifying what we ought not to do – at the risk of some penalty, but law doesn’t tell us what we ought to do. The latter falls to the domain of ‘ethics.’

‘Ethics’ functions within the parameter or perimeter that is set by the law, and has 2 aims: 1) It tells what ‘ought’ to be done, and 2) It provides strong reasons for doing so (ethical justification or rationale). Both of these stipulations are crucial for every society, and persons or groups that break society’s ethics ‘dictates’ are customarily publicly shamed in the media or elsewhere, and may be socially ostracized in the process. However, the penalty may not be as devastating as those imposed by law.

Managing conflicts of interest It is difficult, if not impossible, to determine to what extent a person’s secondary interest (personal, financial, etc.) is likely to interfere with or influence the judgement that they are required to make regarding the primary interest under consideration. This matter assumes even greater importance when the public’s interest is one of, if not the main issue of concern [16]. Regardless of its source, the bias that is associated with conflict of interest situations may permanently damage both the public’s trust, as well as a person’s reputation. Hence, whenever possible, conflicts of interest situations should be avoided.

The ‘reasonable person’ standard: A person should re-consider their level of involvement in a project, if a ‘reasonable person’ who knew the circumstances, could: a) legitimately question the degree of fairness in the issue, or b) imply bias or favouritism.

Despite the foregoing, in the smaller islands of the Caribbean or within small communities, conflicts of interests are very likely to occur.

14

If conflicts of interest cannot be avoided, then effective steps should be undertaken to ‘manage’ the conflicts.

Three essential steps are required. There must be: 1. A public disclosure of the conflict of interest 2. A limitation of the conflicted person’s involvement in the particular decision or work; or 3. An exclusion of the conflicted person from the work altogether!

In such disclosure, both the nature of the conflict as well as its magnitude are very important considerations [5].

Nevertheless, we should note that simple disclosure does not eliminate bias. Complicating this approach is the perception of ‘possible bias’ by the person in the eyes of the public. One can never ‘prove’ the absence of bias in the decision-making process, and so the option of ‘simple disclosure’ of a conflict of interest may not be fully satisfactory in matters that are related to the public’s interest. Therefore, limiting the person’s involvement in decisions in which they have an interest, or totally excluding them from particular positions where their decision-making may be questioned, are options that should be taken, depending on the particulars of each case.

In addition to conflicts of interest occurring at the ‘micro’ or individual level, conflicts may also occur at the ‘meso’ level (the level of institutions or organizations) and at the ‘macro’ level (national or governmental level). For example, at the organizational level, the UK Royal College of Paediatrics and Child Health was recently strongly criticized when it voted in October 2016 to continue accepting funding from manufacturers of breast milk substitutes [17]. At the national level, transnational corporations often interfere in the policy-formulation process of governments, and seek to avoid any existing regulations that would inhibit market concentration and wealth accumulation [18]. The potential for major private sector donors or partners to distort the priorities of governments and international agencies has been a major concern [19].

Due to conflicts of interest arising at that level, in 2015 the WHO developed principles and policies of engagement with non-State actors that distinguished between actors in the public and in the commercial interest, and the avoidance, prevention, and management of conflicts of interest [18]. Private commercial actors can benefit greatly when they are able to influence the formulation of WHO policies. Likewise, transnational corporations lobby countries in order to gain influence in matters related to their own financial interests. Unfortunately, political power is sensitive to and highly influenced by economic considerations and pressures.

Yet global health partnerships have contributed to both the manner in which global health is governed as well as to improved global health outcomes [20]. However, the need to accelerate the development, production, and distribution of beneficial products to meet the health needs of the poor and vulnerable must be balanced and supported by good governance and the avoidance or

Caribbean Medical Journal Challenges of Conflicts of Interest in the Caribbean: An Ethical Concern

adequate management of conflicts of interest. Strong strategic planning, transparency and accountability, well defined roles and responsibilities of partners in the process, policies and funding allocations that are based solely on the strategic priorities, identification of cost-effective remedies for anticipated problems, and adequate attention to promoting equitable access are all crucial to the process [20].

Conflict of interest policies In light of all the foregoing, written policies should exist to manage conflicts of interest, and be implemented to reduce or eliminate perceived bias [21]. Such policies should include a definition of terms, a policy statement of the institution or organization, examples of relevant interests, and the step-wise process for managing conflicts of interests as outlined above.

Where institutions or organizations wish to engage or enter into partnerships with commercial entities, there must be a priori deep deliberation regarding whether: 1) The partnership is desirable or necessary (risk/benefit assessment); 2) It allows independence, and the maintenance of integrity and credibility; 3) It may positively advance public health, beneficial public agendas, or the common good; 4) Ethical assessment and due diligence will be done before engaging the commercial entity; 5) On-going reviews of the engagement or partnership will be done to assess the degree to which it is meeting the initial objectives; and 6) Whether criteria for disengagement will be developed. In order to proceed, the answers to all the above-mentioned questions and related concerns should be positive [21].

These policies should also be made public to foster public trust. Individuals or organizations that promote transparency will be better able to recognize when conflicts of interest might or will occur. Objectivity is fundamental for identifying situations of conflicts of interest. At the institutional, organizational and national levels, the analysis should not only include, for instance, the contents of any products manufactured by the commercial interests,

but also their policies and practices, mission, goals, aims, principles, and vision [18]. The specific interests of a company can reveal possible sources of conflicts of interest for entities that may wish to engage with them. Publicprivate partnerships with large corporations offer potential benefits to the health sector, but adequate and appropriate safeguards should exist [19].

Conclusion Written policies and procedures that can help identify and eliminate conflicts of interests should exist within all centres, institutions and organizations. Within any conflict of interest management plan, there should be a public disclosure of the conflict and a modification of the plan of work, as necessary. There should also be a monitoring of the work by independent persons to ensure that the conflicted person eliminates their conflicting interest. If not, then the person should be removed and replaced by someone who is not conflicted in the matter.

Institutions and organizations should follow the procedures outlined in this article to manage conflicts of interest. The criteria outlined for possible engaging in partnerships should also be followed.

Acknowledgement The author was requested to prepare this topic for a presentation at the Healthy Caribbean Coalition (HCC) Conference on Advocacy, Accountability, and Conflict of Interest.

Conflict of interest: I do not have any financial interests or dual commitments that would represent a conflict of interest in this regard.

However, I was sponsored by the Health Caribbean Coalition (HCC) to present this topic to its Meeting of civil society organizations (CSOs) on NCDs: Advocacy, Accountability, and Conflict of Interest.

Corresponding author: Dr. D.E. Aarons aaronsderrick27@gmail.com

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Caribbean Medical Journal Challenges of Conflicts of Interest in the Caribbean: An Ethical Concern

REFERENCES 1. Lemmens T., Waring D.F. Law and Ethics in Biomedical Research: Regulation, Conflict of Interest, and Liability. Toronto: University of Toronto Press; 2006, pp. 63-71.

2. World Health Organization. Declaration of Interests for WHO Experts.

WHO: Geneva, Switzerland. http://www.who.int/ occupational_health/declaration_of_interest.pdf 3. Sutherland, A. ‘Parson musn’t crisen him pickney at all.’ Jamaica Observer. 2017 Jan. 23: p.10.

4. UK Health Prevention First Forum. Meeting Report: Improving health through better governance – Strengthening the governance of diet and nutrition partnerships for the prevention of chronic diseases.

Rockefeller Foundation Bellagio Center, October 27-29, 2015.

5. Jansen LA, Sulmasy DP. Bioethics, Conflicts of Interest, and the Limits of Transparency. Hastings Center Report 2003; 33(4); 40-43.

6. Aarons DE. Medical Ethics: A Sensitization to some important Issues.

West Indian Med J 1996; 45(3): 74-77.

7. Aarons DE. The Health Care Ethics Consultant and Beneficence in Medicine [Editorial]. West Indian Med J 1997; 46(1): 1-2.

8. Aarons DE. Ethics, Medicine, and Society: Imperatives for the Future. West Indian Med J 1999; 48(4): 179-182.

9. Aarons DE. Medicine and Its Alternatives: Health Care Priorities in the Caribbean.

Hastings Center Report 1999; 29(4); 23-27.

10. Aarons DE. Issues in Bioethics: Teaching Medical Ethics to Health Professionals. West Indian Medical Journal 2002; 51(2): 59 – 63.

11. Aarons DE. Issues in Bioethics: Ethics and Professional Responsibilities. West Indies Med J 2003; 52(1); 4-9.

12. Aarons DE. Research Ethics. West Indian Med J 1995; 44(4): 1158.

13. Aarons DE. Research: An ethical answer in addressing our people’s

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health problems and inequities. West Indian Med J 2015; 64(Suppl 2): 97-100.

14. Aarons DE. Issues in Bioethics: Teaching Research Ethics. West Indian Med J 2003; 52(2); 145-50.

15. Aarons DE. Ethical issues surrounding Body Integrity and Research.

West Indian Med J 2014: 63(5); 399-401.

16. Aarons DE. Family health, public health, and vulnerability in research: A Caribbean perspective. Redbioetica UNESCO J Jul - Dec 2016; 14; 17. Costello A, Branca F, Rollins N, Stahlhofer M, Grummer-Strawn L. Health professional associations and industry funding. The Lancet 2017; 389(10069): 597-598.

18. Gomes F.S. Conflicts of interest in food and nutrition. Cad. Saúde Pública 2015; 31(10): 1-8.

19. Galea G, McKee M. Public-private partnerships with large corporations: Setting the ground rules for better health. Health Policy 2014; 115: 138-140.

20. Buse K, Tanaka S. Global public-private health partnerships: Lessons learnt from ten years of experience and evaluation. International Dental J 2011; 61(Suppl.2): 2-10.

21. Aarons DE. Conflict of Interest Policy & Guide – Draft. A presentation to the Conference on ‘Advocacy, Accountability, and Conflict of Interest’ of the Health Caribbean Coalition (HCC). St. Johns, Antigua: Feb. 18, 2017.

Caribbean Medical Journal

Ethics The Right to Die – Who Decides?

L. Bernstein, DMD, MPH Introduction Over the past 10 years the number of articles on the concept of dying with legal help, the right to die, dying with dignity, or other related terminology has increased each year. The various articles have brought to the forefront the many complexities surrounding these difficult issues and the dilemmas they produce. Why the increasing interest in these subjects?

There are several reasons for this, most of them based on demographics and economics. A good part of this results from the increasing numbers of people in a rapidly aging demographic group and the ever-increasing amount of money being expended on this group in attempts to sustain life.

The cohort of people born before the post- World War II baby boom was relatively small compared to the total number of the so-called baby boomers. A post-WWII expanding economy gave the baby boomers in the United States and other countries enough money to meet the initial costs of their parents’ old age needs. However, a rapidly extending average life span due to better public health measures and advances in medicine and pharmaceuticals started to change the balance. Along with a longer life came the diseases of not just the old, but the old-old.

Also, and especially prior to WWII, the nuclear family of multi-generations still existed, under which the old raised the young and the young looked after the old. The postwar era changed the equation; single-family homes in the exploding suburbs and small family apartment dwellings became the norm with single families of a mother, father and two children. Not only was this cohort required to provide for their old, often disabled, parents and support their own families, they now had to contend with the increasingly complicated and expensive costs of care of the old, old.

Those same baby-boomers are themselves now much older, are retiring in greater numbers and are often incurring large care costs themselves. Meanwhile their parents were getting older, sicker and were being afflicted with expensive cost-caring diseases, namely heart disease, cancer and dementia. Further, many of their parents are no longer able to live on their own and many are widowed or divorced. Along with the sick, they too often require an expensive full-time care facility. For these now aging children, along with incurring the medical costs, the total can be financially bankrupting. At the extreme, it can strain education funding for their own children, compromise their own retirement savings plans, and, at the least, cause a downgrading of their own life-style.

Cost of Dying Some statistics are worth looking at: For the United States,

the total health-care expenditures are now US$3,250,000,000,000.00 per year, that’s 3 and ? trillion, not billion, dollars per year. Of all those dollars, including the 20-25% that goes as profits and expenses to the health insurance industry (one of the reasons the increasing call for a single-payer system), 50% is spent in the last two years of a person’s life and 50% of that is spent on just those three diseases, heart disease, cancer and dementia.

In an article in Forbes magazine on the United States, “according to one study (Banarto, McClellan, Kagy and Garber, 2004), 30% of all Medicare expenditures are attributed to the 5% of beneficiaries that die each year, with 1/3 of that cost occurring in the last month of life”.

The author points out that other studies say slightly different things but the bottom line is that an incredible amount of money is spent on that last year of life. The author asks if it is worth it and answers by saying it seems to be no. This is an incredible admission that the cost of dying has entered the debate.

However, that debate is tied into the general debate on dying and will be part of the resolution on the debate on the right to die and dying with dignity. So the question is not only on the right to die but dying with dignity. Also entering the equation is the question as to what is more important: life itself or the quality of that life?

Quantity of Life vs Quality of life The May 25, 2017 edition of the New York Times included the story “At His Own Wake, Celebrating Life and the Gift of Death” by columnist Catherine Porter which told of the dignified self-imposed death of Canadian citizen John Shields. Here, instead of a suicide, a very charged word, being described, let it be described as a dignicide, a self- chosen death of a human being dying with dignity.

The story and subsequent Letters to the Editor did not cover all aspects of this controversial issue. As well as the financial ones noted above, there are several others.

A major and continuing issue in easing the path for those wishing the right to die and to die with dignity is, has been, and continues to be, the centrality of the physician.

As a result of historical precedent, the physician has been given the responsibility. Not only to be the provider but he/she then has to be willing to provide the necessary medications. This need not be the case.

There is a long history as to why this responsibility devolved to the physician centering on the development of medicine since ancient; going from the shaman to the barber surgeon to the physician. The responsibility seems to have devolved more by default than design as society and medicine evolved in complexity. It does not have to be so.

Likewise, there is a long history on the development of the concept of dying with dignity as exemplified by Seneca, who lived from 4 BCE to 65 CE. Seneca wrote, 17

Caribbean Medical Journal The Right to Die – Who Decides?

“I will not escape by death from disease so long as it may be healed and leaves my mind unimpaired; I will not raise my hand against myself….but if I know I must suffer without hope or relief, I will depart.” Here it is 2000 years later and the issues are still the same.

Not only are the prescribing and willingness to prescribe issues of concern but as Ms. Porter points out, the issue concerning those incapable of taking the medications themselves. Not only an issue in Canada but also in jurisdictions in the United States where it is legal. Some western European countries not only allow for the providing of the necessary medications but also allow for assistance in taking them. In Canada and in US jurisdictions, it is, however, currently illegal for anyone to assist anyone in the taking of the medications.

“Cruel and Unusual punishment” Addressing the issue of assistance, there is much justification for allowing for assistance. An argument can be made that not allowing assistance is “cruel and unusual punishment” for someone suffering from what is commonly known as Lou Gehrig’s Disease (Amyotrophic Lateral Sclerosis or ALS). For example, such a person may be able to take the medication on one day but, then unable to do so the next day. The question can be asked why he/she should be denied the ability to be assisted to take it the next day and to have to horribly die by what is essentially a slow asphyxiation. A similar situation exists for those judged mentally incompetent. The question can pointedly be asked as “mentally incompetent” when, if they were mentally competent, could have this right. Is this not also “cruel and unusual punishment”?

This concern especially extends to children, for whom there are also no provisions in any of the laws.

Unfortunately, children do not vote and are judged incompetent to make such decisions even though there are recorded instances of children expressing the desire to leave. Currently, this means that a parent, loved one or guardian is forced to sit and watch a child dying in agony or so consumed by narcotics as to be essentially brain dead. Is this not also “cruel and unusual punishment”?

A more recent New York Times contribution to this debate is an article in the August 8, 2017 New York Times entitled, “Should I Help My Patients Die?” by California physician Jessica Nutik Zitter. In this article Dr. Zitter starts by commenting on what transpired after she was confronted with her “first request for assistance to shorten the life of a patient”. She makes references as to how uncomfortable many physicians are in being assigned this role.

Hippocratic Oath One reference Dr. Zitter makes is to what many physicians see as a conflict with the Hippocratic oath admonition not to administer “poison”. However, there is a great difference in a physician being asked to prescribe a medication allowed by law to terminate a life and an arbitrary decision by a physician to administer a poison.

Dr. Zitter’s next reservation is not that she disapproved of providing the medications but that “we didn’t want to 18

automatically become the go-to people on this very complex issue”. Later, she admits to wanting this option for herself and her family as she has seen much suffering around death. But then, she admits that she is not sure she is comfortable with helping to intentionally hasten the death of anyone for any reason.

Later in her article she observes that “As our population continues to grow older and sicker and more people learn that this law exists, we will need a highly trained work force to steward patients through this process.”.

Here, she has raised an important concept; that being the need for a “highly trained work force”. Along with this raises another question: Has the complexity and over-mechanization of dying in America “created a public health crisis”? Lastly, she calls for identifying a cadre of the best qualified clinicians and then training them appropriately to do this work. Her calls and concerns coincide with my arguments in Bernstein, L., Changing the Physician Mindset, Caribbean Medical Journal, Jan. 2017.

Right to die and Dying with dignity In this article, I present two theses. The first is that the right to die and dying with dignity is a societal issue and not per se a medical issue and as such, it is primarily a public health issue. The second thesis is that, as a public health issue, in lieu of the physician having the responsibility thrust upon them by society, the providing of these medications should be the responsibility of specially trained public health people, who indeed may or may not be physicians. The physician should be relieved of the burden of responsibility for providing the medications. The responsibility should be given back to society in the form of trained public health providers.

Ethical Issues There are other arguments made against the providing of medications to end life; which is the issue of whether it is ethical. One opinion is by an “ethicist”, expressed in a letter to the editor to the New York Times Porter article, who described the providing of such medications by physicians as constituting assisting in suicide. I find the circumlocutions of “ethicists” (What constitutes an ethicist?) of interest. Ethical questions appear to be essentially dilemmas. I look at ethical dilemmas by lining up all the pro arguments on one side of a page and the con arguments on the other, then think about them, and come to my conclusion. However, my conclusion would not necessarily be that of someone else. Or what about differing decisions by a committee of ethicists? Does the majority rule in such a case? Is the majority decision “fair” to all? I keep in mind the adage about the essence of democracy being the protection of the minority against the tyranny of the majority. Nothing is ever simple or black or white and the decision/opinion of an ethicist does not make it so. It seems to have become the norm now that their pronouncements to be taken as the final word with no questioning? The pronouncements of an ethicist are not ipso facto the final and only word. Their opinions should be questioned and not granted the validity of being tantamount to law.

Caribbean Medical Journal The Right to Die – Who Decides?

The most recent addition to the debate appeared in the August 7, 2017 edition New York Times in an article by Dan Bilefsky entitled For Parents of Children Like Charlie Gard, Learning to ‘Redefine Hope’.

The Bilefsky article presents the issues entered in the debate by the sad tragedy of the above mentioned incurably ill British baby, Charlie Gard, who was born blind, deaf and unable to move on his own. This greatly discussed baby presented new and compelling issues into the debate. In this case, Charlie’s parents “engaged in a painful and protracted legal battle to try to keep him alive” while the hospital, with the agreement of the courts, wanted to disconnect his life support systems. Ultimately, Charlie’s parents came to accept the fact of his death but, due to logistical problems, were denied by the hospital to be transported home to die rather than in the hospital.

An entirely different set of circumstances and dilemmas was posed by the then 12-year-old Daisy Nimmo who was partly blind and could speak only a few words, although was an active, albeit wheelchair-bound girl.

During her relatively short life she had undergone 50 surgical procedures and, at age 11, the death by bowel cancer of her father. Subsequently, Daisy’s condition worsened and she went into septic shock and cardiac arrest. She was put on life support and, at this point, her mother “decided it was time to let her go”. Her mother is quoted as saying, “As a parent, the decision to take your child off of life support is the most selfless thing you can do because you want your child to live, ---- But you have to ask, ‘Who am I doing this for?’” Mrs. Nimmo came to the realization that “her greatest achievement would be to give the girl a “good death.”

Another aspect on these dilemmas is that presented by 16 year old David Langton-Gilks who died as the result of a brain tumor, a medulloblastoma. His mother had been determined to find a cure and in the interim before his death he had undergone “two relapses, 11 brain operations, years of chemotherapy, a stem-cell transplant, and experimental treatment that had burned through David’s esophagus”. At that point, she decided to give her child “a happy end of life and send-off”. She was initially of the opinion that it was her right to decide on any treatment for her child. She said, “How dare they tell me what to do!” The ultimate reality for her was her final decision, a new understanding and a final coming to terms. Ms. Langton-Gilks concluded her dilemma by realizing that, “You have to accept that your child will die to give him or her a good death, to stop the suffering and strive for quality of life over life at all costs.”

The opinion of Ms. Langton-Gilks that it was her right to decide on any treatment for her child raises the issue of who has the right to decide when there are conflicting opinions among the parent, the doctor, the hospital, and the state. In her article Dr. Zitter refers to comments by Dr. Dominic Wilkinson, a neonatologist and professor of medical ethics at Oxford University. He says that parental wishes sometimes need to be overridden by the doctors

and hospitals. He opines that, “Parents shouldn’t be allowed to make decisions that carry a significant risk of serious harm to a child”, “especially in refusing treatment or demanding treatments without obvious benefit”. His argument relates to the issue of when the state decides to invoke its right to protect children from parents in the case of Jehovah’s Witnesses and Christian Scientists. At what point is the autonomy of the individual, the parent, to be over-ridden by society, the state? The issue of autonomy is also at the crux of whether an individual has the right to decide to end life using state-granted access to medications.

Hostility Adding to the complexity of the many issues already noted is that there is much hostility towards the right to die and dying with dignity from other segments of society.

Much of this hostility is generated from religious beliefs held by adherents who are adamant that their religious beliefs should supersede any other considerations and are opposed to self or assisted termination of life under any circumstances. This hostility has been further compounded by the publication of US Vice-President Pence’s book on the subject. There is also the known hostility of recently appointed US Supreme Court judge Neil Gorsuch. The well-known hostility of the Catholic Church, but, interestingly, not the majority of Catholics, is also noted.

For all those opposed, the ultimate question is who has the right to decide? The issue of when is one’s autonomy, the existentialist concept of being responsible for one’s own life, to be superseded? This is probably the central core of all public debate on these highly complex lifedeciding issues.

Irrespective of all the forces opposed, the percentage of the US population moving in favor of the right to die, dying with dignity, keeps increasing. Such is the value of debate on the issue and the value of articles, books and lectures. The goal is to expose the arguments on the right to die and dying with dignity for people to think about them and to form their own opinions.

Conclusion I look forward to the continuing evolution of the acceptance of granting those in end of life situations the autonomy of being able to choose for themselves, and to be able to make choices for those unable to do so themselves, the right to die and to do so with dignity. To use a term, everyone should be granted the right to a dignicide, a self-imposed dignified way of committing what is a true sui (self) cide (death) in a dignified manner. After all, in the final analysis, no one gets out of all this alive and in any event, a painful lingering death should not be part of the process. Let us make available this ending for all those in intolerable circumstances, for those in intolerable pain and agony, a dignicide.

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Caribbean Medical Journal

CME A case of Giant Cell Arteritis L. Gonzales MBBS(Hons) , L. M Pinto Pereira, MBBS,MD & S. Teelucksingh FRCP(Edin) Internal Medicine Department, Medical Associates Hospital, St Joseph. Trinidad. W.I.

Case History A 57-year-old-female patient was referred to our outpatient clinic with a three week history of severe headache and neck pain. The headache was localized to the left side of her head and was associated with neck stiffness and tenderness. The pain was constant and increasing in severity as the weeks past. She was unable to sleep through the night due to severe pain and at the time of presentation she was wearing a neck collar as the pain was exacerbated with neck movement. Analgesics and muscle relaxants provided only minimal and short relief from the pain.

There was no jaw claudication or visual disturbance. She did experience stiffness in the shoulders on mornings, that improved as the day progressed. There was anorexia, weight loss of a few pounds but no altered bowel habit.

Her past medical history included type 2 diabetes of 16 years duration without any known complications. She underwent total abdominal hysterectomy 20 years ago.

She was taking a combination preparation of metformin 1000mg and vildagliptin 50mg once daily. There was no history of tobacco, ethanol or illicit drug use. She was selfemployed and unable to work for the past three weeks.

On examination, the patient appeared unwell with temporalis muscle wasting. There was marked tenderness on palpation of the left temporal and frontal areas of the head. The temporal artery and left strap muscles of the neck were also tender. Her blood pressure= 147/74 mm/Hg, pulse = 99 beats per minute and capillary glucose was 204 mg/dl. There was no focal neurological deficit.

Her hearts sounds were normal and her lungs were clear on auscultation. Abdominal examination was also unremarkable.

Questions: 1. What are your differential diagnoses?

2. What investigations would you order for this patient?

Answers 1. Differential Diagnoses: a. Giant Cell Arteritis (Temporal arteritis) b. Polymyalgia Rheumatica 2. Investigations: a. CBC b. ESR c. CRP d. LFT e. RFT f. HbA1c g. Lipid profile h. TSH & free T4

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Test ESR TSH Free T4 HbA1c WBC PLT

Result 100 mm/hr 34 mIU/L 0.9 ng/dl 12.1% 11.2 x109/L 568 x103/mcL

Normal Range < 20mm/hr 0.3 â&#x20AC;&#x201C; 3.0 0.8 â&#x20AC;&#x201C; 2.2 < 7% 4 - 11 150 - 400

Table 1. Results of initial investigations.

Questions 1. What are the main issues at this point?

2. What other investigation(s) will you like to consider?

3. How would you manage this patient?

Answers The main issues are: 1. Giant Cell Arteritis This is a systemic inflammatory vasculitis, rare before age 50 years, with a median age of onset of 75 years.

It is the most common vasculitis of elderly patients with an incidence of about 20 per 100, 000 people over 50 years. The female to male ratio is approximately 4:1; with female smokers being at a much higher risk.

[1-3] 2. Poorly controlled type 2 diabetes (HbA1c 12.1 %) 3. Subclinical Hypothyroidism 4. Anaemia and a reactive thrombocytosis secondary to inflammatory disease Other investigations: 1. Temporal artery biopsy demonstrating the histopathological finding of granulomatous inflammation is considered the gold standard for the diagnosis of giant cell arteritis. This should be performed within one week of starting treatment.

Temporal artery biopsy however, is not always performed in suspected cases of giant cell arteritis when the clinical and laboratory findings are highly suggestive.

2. Positron Emission Topography (PET), Magnetic Resonance Imaging (MRI) and Colour Duplex Ultrasound scanning are proving to be useful noninvasive means of confirming the diagnosis of temporal arteritis. [4]

Caribbean Medical Journal A case of Giant Cell Arteritis

Treatment: 1. Optimize glycaemic control 2. Corticosteroid therapy +/- Temporal artery biopsy a. Bone protection (calcium and vitamin D +/bisphosphonate) b. Consider PPI during steroid therapy 3. Plan for screening and management of any diabetes related complications such as retinopathy, neuropathy and nephropathy once settled.

4. Plan for routine age appropriate cancer screenings a. Mammogram b. Colonoscopy c. Pap smear (not indicated post total hysterectomy) 5. Age appropriate vaccinations (will be on corticosteroids long term & T2 diabetes) a. Pneumococcal b. Yearly influenza c. Ensure up to date with tetanus toxoid The patient was started on a therapeutic trial of prednisolone 15mg /day and her metformin and vildagliptin dose was doubled. She was counselled about the possible worsening of glycaemic control while on steroid therapy as well as other side-effects. One week later the patient was happier, able to sleep and reported significant improvement overall with only mild headache intermittently. There was no temporal artery, neck or shoulder tenderness; the neck collar was gone and her ESR was now 72 mm/hr.

Serial follow up over the next few weeks showed a progressive improvement in her ESR dropping to 38mm/hour after three months of treatment. Her HbA1c was now down to 10 % and her fasting blood sugar readings range from 60-70 mg/dl. Her post prandial readings however were very high, sometimes over 300 mg/dl despite triple oral therapy (metformin, vildagliptin and glimepiride).

Answers: 1. Glucocorticosteroid induced hyperglycaemia is usually transient and related to the dose and duration of treatment. It is characteristically associated with an exaggerated postprandial hyperglycaemia caused by defective postprandial insulin secretion, increase in hepatic gluconeogenesis and inhibition of insulin induced peripheral glucose uptake. Corticosteroids increase appetite by increasing leptin expression and decreasing adiponectin expression thereby promoting weight gain which leads to increased insulin resistance.

There is usually a minimal effect on fasting glucose levels. [5] 2. Using corticosteroids at the lowest dose and shortest duration possible to achieve the desired benefit is important to help limit side effects. Treatment of the hyperglycaemia, if not controlled with oral hypoglycemic agents, may require a basal insulin along with preprandial boluses of short-acting insulins to mitigate the marked post prandial hyperglycaemia that can occur.

Conflict of interests: None declared Corresponding author : Lexley M Pinto Pereira lexleyp@gmail.com References 1. Salvarani C; Gabriel SE; O'Fallon WM; Hunder GG. The incidence of giant cell arteritis in Olmsted County, Minnesota: apparent fluctuations in a cyclic pattern. Ann Intern Med. 1995; 123(3):1924 (ISSN: 0003-4819) 2. Smeeth L; Cook C; Hall AJ. Incidence of diagnosed polymyalgia rheumatica and temporal arteritis in the United Kingdom, 19902001. Ann Rheum Dis. 2006; 65(8):1093-8 (ISSN: 0003-4967) 3. Seetharaman, M. "Giant Cell Arteritis (Temporal Arteritis)." Practice Essentials, Pathophysiology, Etiology. Medscape, 25 May 2017.

Retrieved on 03 July 2017 from http://emedicine.medscape.com/article/332483-overview#a5.

4. Bowling K1, Rait J1, Atkinson J1, Srinivas G1. Temporal artery biopsy in the diagnosis of giant cell arteritis: Does the end justify the means?

Ann Med Surg (Lond). 2017 Jun 15;20:1-5.

5. Tamez-Pérez HE, Quintanilla-Flores DL, Rodríguez-Gutiérrez R, González-González JG, Tamez-Peña AL. Steroid hyperglycemia: Prevalence, early detection and therapeutic recommendations: A narrative review. World Journal of Diabetes. 2015;6(8):1073-1081.

Questions: 1. What is the likely cause of her hyperglycaemia?

2. How would you manage her hyperglycaemia?

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Caribbean Medical Journal

Commentary The Development of Children: Points to Ponder Jane Holmes Bernstein Ph.D. Neuropsychology Program, Department of Psychiatry Center for Neuropsychology, Boston Children’s Hospital Associate Professor, Harvard Medical School Introduction In the last few years several themes have become salient in the public discourse concerning medicine and health.

One, modern disease cannot be understood in purely biological terms. Traditional characterizations of disease in biological terms have yielded to a more complex formulation framed as an interaction of biological, psychological and social variables. Two, many diseases that appear in adulthood are increasingly being recognized as long-term outcomes of developmental variables, with roots in events and experiences that date back not only to early childhood, but also to intrauterine life. Three, the role of genes in shaping behavior at both the species and the individual levels is not all powerful; outcomes can be determined by behavioral as well as biological influences via the workings of epigenetic forces. These themes in the public discourse have great resonance in the behavioral disciplines and significant implications for how we view the well-being and progress not only of our youngest citizens but also of the society of which they will become a part. I would like to draw attention to several “points to ponder”.

Brain-Context-Development I start by noting that my perspective is that of a developmental neuropsychologist whose primary focus is on behavior in children and the ways in which it develops. I do my work and thinking in a BRAINCONTEXT-DEVELOPMENT matrix: BRAIN is the necessary substrate for behavior; brains do not/ cannot work (develop, function, maintain capacities) in a vacuum, but depend throughout life on the CONTEXT of action; DEVELOPMENT is not linear and additive, but a dynamic, re-organizing process of change. I work with children and families to understand the impact of disease on the development of behavioural skills and use relevant brain knowledge and developmental principles to promote optimal outcomes for children as they move through childhood and adolescence. My “neurodevelopmental story” thus centers on two major themes: How the brain works; How children develop. The approach is clearly one that fits into the “bio-psycho-social” framework.

Point to Ponder #1 The first Point to Ponder is taken from the work of Terrie Moffitt and her colleagues [1]. The study examines the relationships between early childhood measures of selfcontrol and later adult outcomes involving health, wealth and public safety in a cohort of individuals living in Dunedin, New Zealand. The research is remarkable for the length of time over which the data were collected and the low rate of attrition from the earliest to the latest points of measurement – reflecting the relatively non-mobile 22

characteristic of the New Zealand population. Measures of self-control in children had been obtained at 3, 5, 7, 9 and 11 years of age and were analyzed against publically available records documenting a range of variables pertaining to health, wealth and public safety in the same individuals at 32 years. The better a child's acquisition of age expected self-control in the early years the better the outcomes with respect to their adjustment in society as adults. Thus, at 32 years of age, a health index derived from cardiovascular, respiratory, dental and sexual health measures plus a rating of substance use was positively related to self-control in childhood independent of social class of origin and IQ. With respect to wealth, poorer selfcontrol added incremental validity to social class of origin and IQ in predicting adult outcomes (likelihood of single parenting, fewer future financial supports, less stable income). Examination of court records indicated that poorer self-control was associated with higher rates of criminal offending, again independent of social class and IQ. Additionally, data collected from adolescents as 13, 15, 18 and 21 years indicated those with a history of less self-control as children were more prone to make “adolescent mistakes” that raised the risk of engaging in risky lifestyles. And, in a related study, the authors found that self-control measures predicted different outcomes even in siblings raised together: better self-control, better outcomes. The impact of childhood behaviour in later years makes it clear that how we support our children’s early development pays off!

But what is self-control in this context? Self-control, or self-regulation, depends on a suite of teachable skills for managing emotions, thoughts, and behaviors. These turn out to be essential for children to learn, to make friends, to achieve goals. They are taught, shaped and honed in the context of relationships with (initially) parents, and then peers and other adults over the course of childhood and adolescence. A broad literature now documents the importance of self-regulation and provides the foundation for intervention and programming for parents and educators to promote relevant skills in children of different ages.

Point to Ponder #2 I turn to a remarkable study that was undertaken by Betty Hart and Todd R. Risley [2] in the United States in the 1980s, the results of which have been carefully detailed in their book Meaningful Differences in the Everyday Experience of Young American Children, published by Paul Brookes Publishing in 1995. Points to Ponder 2, 3 and 4 are all taken from this body of work.

The first point is that of the marked disparities in the cumulative vocabulary of children from low SES

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(approximately 370 words), middle SES (approximately 580 words) and high SES families (around 1100 words) that were revealed in the study. (http://centerforeducation.rice.edu/images/slc_image s/LongitudinalStudies/30ChildrensVocabulary.jpg) Vocabulary growth can be used as an index of early language development: it reflects the rate at which the child is learning words. Hart and Risley demonstrated that the size of a child’s vocabulary is directly related to the number of words spoken to the child. (The range of utterances documented was from 178 per hour to 487 per hour.) The implication is clear: children need more words.

Not, however, not just more words, but richer utterances that involve labeling of objects and features of objects; descriptions of objects, actions and intentions; discussions of how one thing causes another; talk about past and future; using of abstractions; labeling of feelings. Which means… that you have to talk with children. Not talk to… Not talk at… But……TALK WITH !!!

Point to Ponder #3 It turned out that it was not just the number of words used that shaped the child’s development: the KIND of words spoken made a difference. Hart and Risley documented the number of utterances that could be considered encouraging and those that could be seen as discouragements. There are, of course, necessary ‘discouraging’ words, the words of basic instructions, directions; the words that are needed in caring for and socializing young children. You have to tell a child “No!”.

They have to learn safety and social expectations. It turns out, however, that you have to be very careful with those “No!”s.

The balance between encouragements and discouragements is important. In Hart and Risley's work the ratio of encouragements and discouragements in families with different social resources was quite discrepant. [adapted from Hart & Risley 1995] Encouraging language includes affirmations (Yeah!! Great job!! Show granny what you can do!!), questions (What’s that? what color is it? what does it do? how do you think it works?) and more complex sentences (Wow! That’s a very complicated picture with all those lines and colors, isn’t it? Can you find the big red one that is lying on the ground?). Discouraging language includes prohibitions (No! You can’t do that! Stop what you’re doing!) and discouragements (Uh-uh! You need to do that again! Your dad won’t like it! That’s stupid! I told you!!).

Encouraging words/utterances and discouraging word/utterances are not just differently represented in the language interactions of families with different social resources. They can have very different effects on children's experience. The Hart and Risley data revealed that not only was the children’s vocabulary acquisition correlated

with later IQ scores (the range of scores ran from 79 to 117), but also that the kinds of words used were related to IQ scores. More encouragements were associated with a positive effect on IQ scores; more discouragements were associated with a negative effect on IQ scores.

Overall, the key findings of the Hart and Risley study can be summarized as follows [1]. The variation in children’s IQs and language abilities is relative to the amount parents speak to their children [2]. Children’s academic successes at ages nine and ten are attributable to the amount of talk they hear from birth to age three [3]. Parents of advanced children talk significantly more to their children than parents of children who are not as advanced Point to Ponder #4 What is language anyway? It is not just for communicating.

Language functions as a cognitive or thinking tool.

Language helps you understand how you feel. Language helps you pay attention. Language tells you how the world works. Language helps you solve problems.

Language helps you regulate (control) yourself. Language helps you learn. All of these functions of language are critical to the development of the child’s behaviour and adjustment.

Point to Ponder #5 If language is so important for the development of children's social, emotional, regulatory and thinking capacities, then clearly the fostering of language development in the young child is critical. “Talking-with” is important here. The fostering of language behavior – as is true for all behaviour – depends on relationships, the reciprocal exchange of care and conversation. (Talkingwith, not talking-to!) In promoting the development of young children, there are two critical requirements: adult responding needs to be consistent across time and contingent at each time on what is happening right then.

A country like Trinidad and Tobago, with its British colonial history, still, apparently, has to contend with an old attitude attributed to Queen Victoria, namely, that "children shall be seen and not heard". Later research has demonstrated rather conclusively, however, that children do indeed need to be heard; all individuals need a voice – and finding one’s voice takes place from the earliest periods in one's existence. With support and encouragement from those who nurture us we learn to interact with our world, to interact with people, to find out who we are. These are the important precursors of successful progress through life.

Point to Ponder #6.

The provocative study here is one led by Mike Assel [3], a member of the research team of Susan Landry of the University of Texas. Among other variables he examined the role of early parenting factors on academic outcomes.

Specifically, he contrasted the type of language offered to a child at 12 months of age with that offered to a child of 24 months of age and used as his target outcome at 8 years of age not a language capacity, but grade-referenced performance in mathematics. He found that the parenting

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behaviours that led to good outcomes in terms of the later maths performance were not the same for one year olds as for two year olds. Children whose mothers used a lot of “That is __!” expressions at age one did well in mathematics classes later. However, children of mothers who were still using “That is __!” expressions at two years of age did not do better later. The children who did do better later were the ones whose mothers had shifted to a “what is__?” form of interaction. Supporting the child’s engagement with the world through language is critical.

There are three messages here. One, language experience is important - and depends on language interactions which also depend on relationships. Two, adults’ language behaviour cannot be in a fixed form, but must change as the child builds more skills, responding to the child’s increasing competencies in exploring the world. Three, the foundations of later abilities are not precursor abilities of the same type. In particular, academic skills at 3 years of age do not predict academic skills at 7, 10 or 13 years.

What does predict successful academic skills are the foundation skills of social engagement, interest in learning, problem-solving in the real world and managing oneself.

Early childhood is a critical developmental epoch.

Something important is going on. It’s going on early. It has long-term ramifications. It has to do with language and regulation.

Point to Ponder #7 - The Role of Play No discussion of early childhood development can end without the introduction of a “four-letter word” (which in some circles does indeed seem to be a “dirty word”!).

The focus of Point to Ponder #7 is PLAY! Opportunities for young children to play are not just important: they are essential to successful development of social, emotion, thinking (cognitive) and self-management skills. Why is play important? It is important because children learn through play. They learn through looking, through listening, through touching, through tasting, through smelling. To do all these they need to move through their world and match their bodily motions to the information they retrieve from their senses. Locomotion is important too! Children learn by exploring their environment (trying things out, seeing what happens), by observing others (adults, children of different ages); they learn through the media (books, television, movies, video games) and from talking and making conversation; they learn through feedback (praise, prohibition, limits, rewards), and trial and error (practice and experience), and through explanations from others.

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In the early preschool and primary years, the findings are clear. Children who learn mainly through playful activities fare much better at both their work and social responsibilities than those in an academic instructionoriented class. But note, the goal of “learning through play” in the classroom is NOT a recipe for unstructured, unsupervised, chaotic mayhem!! What preschool and primary children need is a balance – of child-initiated PLAY in presence of engaged teachers.

Play – at home or at school, alone or in groups – promotes language development; it promotes self-regulation (self control). Mastery of language and self-regulation promote learning – and then thinking – and success. These earlyacquired foundational skills pay dividends in optimal adult outcomes.

Conclusion So? What are the implications of this for physicians?

Parents – indeed all adults - need education, information and tools to promote the development of the next generation. For the medical profession this cannot be just a contribution of the pediatricians monitoring the child’s well-being, nor of the obstetricians/gynecologists supporting fetal life, but must be a responsibility of all physicians (general practitioners, internists, specialists) who provide care to parents, future parents – and grandparents. Promoting the health of a society depends on laying the proper foundations for both biology and behaviour in early life and then building on them throughout growth and development. All adults have a responsibility to do this. Members of the medical profession, as major contributors to the health of the nation, must play a central role.

Conflict of Interest: None declared Corresponding Author: Jane Bernstein Jane.Bernstein@childrens.harvard.edu References [1] Moffitt TE, Arseneault L., Belsky D. et al. A gradient of childhood self-control predicts health, wealth, and public safety. PNAS, 108 (7), 2693–2698. 2011. www.pnas.org/cgi/doi/10.1073/pnas.1010076108 [2] Hart B, Risley TR. Meaningful Differences in the Everyday Experience of Young American Children. Paul Brookes Publishing. 1995 [3] Assel M., Landry S., Swank P. et al. Precursors to mathematical skills: examining the roles of visual–spatial skills, executive processes, and parenting factors. Applied Developmental Science, 7, 1, 27-38.

2003.

[4] Miller E., Almon J. Crisis in the Kindergarten. Why Children Need to Play in School. A Report of the Alliance For Childhood, 2009.

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Review Paraneoplastic Syndromes Affecting the Locomotor System - A Review P. J Rooney & J. Rooney St. Georgeâ&#x20AC;&#x2122;s University, Grenada Abstract Background and Aims: Paraneoplastic syndromes present diagnostic difficulties in every specialty of medicine. The authors have prepared a short review of those affecting the locomotor system, as these are not uncommon presentations to their specialties of rheumatology, internal medicine and family medicine.

Methods and Results: The authors searched Medline and PubMed using the search terms paraneoplastic syndromes, finger clubbing, hypertrophic pulmonary osteoarthropathy, polymyositis and dermatomyositis.

In order to keep this review brief, the authors have attempted to focus on articles which provide key insights and clinical features of these problems.

Conclusions: This short review will provide a concise guide to clinicians encountering these syndromes and their current management.

Key words: Carcinoma arthritis, pulmonary osteoarthropathy, polymyositis, dermatomyositis.

Introduction Cancer occurs when genes involved in cell proliferation and/or differentiation are sufficiently dysfunctional that uncontrolled growth of the specific cells occurs and interferes with normal cell function and metabolism.

Primitive genes and gene function may become active again, or abnormal genes may interfere with normal cell regulation and metabolism. The proteins and polypeptides resulting may have significant effects on distant systems or cells through enzymatic [1], hormonal [2] or immunological [3, 4] mechanisms.

The development of malignant neoplasms is frequently recognized by the occurrence of paraneoplastic disorders which result from these effects on systems separate from that of the primary tumour. These effects may be musculoskeletal [5], endocrine [6], neurological [7], hematological [8] or mucocutaneous [9].

Any presenting clinical problem, to be classified as a paraneoplastic disorder, must occur in synchrony with the tumour, must not be a direct effect of the tumour, either by direct pressure or invasion, and effective treatment of the tumour should result in amelioration or cure of the disorder [5, 10].

A large number of paraneoplastic disorders affect the locomotor apparatus in the form of arthritis, inflammatory disorders of bone, muscle and/or joint and as neurological disorders. This review will focus on paraneoplastic

syndromes affecting the musculoskeletal system.

When such musculoskeletal problems present, it is essential that clinicians be aware of them and make every effort to identify and treat the underlying malignancy [11, 12].

Hypertrophic Osteoarthropathy The most frequently recognized paraneoplastic syndrome affecting the peripheral limbs is clubbing of the fingers (and toes). Digital clubbing was first described by Hippocrates [13] but not as a paraneoplastic condition, rather as an accompanying feature of empyema thoracis, one of many disorders associated with finger clubbing [14, 15]. There is a close association between clubbing and hypertrophic osteoarthropathy (HOA). Small cell lung cancer is the most common cause of both conditions and thus clubbing is most often encountered as a paraneoplastic disorder [16, 17, 18]. HOA may be seen also as an inherited autosomal dominant condition - Primary HOA or pachydermoperiostosis. The secondary paraneoplastic variety is much more common. HOA, usually presents as painful periosteal new bone formation at the end of the distal limb long bones. Both primary and secondary HOA may be limited to this bony feature [19], but an inflammatory polyarthritis is considered an additional feature and patients often present with joint pain and swelling [20, 21]. NSAIDs, steroids or biphosphonates are often effective symptomatic remedies for HOA [22, 23], but the disorder responds best to effective treatment of the underlying tumour [5]. Unfortunately, curative treatment of this type of lung cancer remains rare [24].

Other cancers with a more benign course may also lead to HOA [25, 26, 27]. Recognizing the problem and establishing the underlying neoplastic cause is essential.

Physical examination usually reveals a triad of features â&#x20AC;&#x201C; finger clubbing, arthritis, and periostitis [28]. There may be clinically detectable joint effusions but the cell count is usually low, and Martinez-Lavin et al [29] consider these effusions to be sympathetic to the periosteal inflammation [1]. The knees and ankles are most often affected but any joint can be involved [30, 31]. Often there is soft tissue swelling with pitting oedema over the distal long bones especially the tibia and fibula and they are often exquisitely tender. Plain radiographs will show the characteristic subperiosteal new bone formation typical of HOA [32].

Carcinomatous Inflammatory Polyarthritis A true inflammatory polyarthritis, closely resembling classical rheumatoid arthritis may be also a paraneoplastic manifestation [33]. Seropositivity for rheumatoid factor and erosion of cartilage and bone are sometimes seen [33, 34]. A migratory polyarthritis [10] in a middle aged person, is often the warning sign of one of a variety of solid

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tumours. It can precede the detection of the neoplasm sometimes by years [35, 36, 37, 38]. The arthritis is frequently asymmetrical [39]. Zupancic et al (2008) [10] review the range of different carcinomatous tissues that have been associated with this type of arthritis. Sheon et al (1977) [40] consider carcinoma of the breast as the commonest cause of asymmetrical arthritis in women. As noted, it is often migratory, and it has a predilection for the joints of the lower limbs [39]. However, Zupancic and her colleagues [10] warn that there is no typical presentation, and distinguishing carcinomatous arthritis from rheumatoid arthritis can be very difficult.

Occasionally HOA and carcinomatous arthritis can present in the same patient [35, 41].

NSAIDs are often not very helpful in the treatment of carcinomatous arthritis [10, 36]. Although by no means universal, symptomatic improvement is most often achieved if the underlying neoplasm can be successfully treated. Many other anti-rheumatic medications have been tried with varying success [35]. Indeed, failure of standard anti-rheumatic medications should further alert the physician to the possibility that the arthritis is a paraneoplastic feature.

Polymyositis/Dermatomyositis Polymyositis and dermatomyositis have been recognized as paraneoplastic syndromes for more than 100 years [42, 43]. A wide variety of tumours have been considered the primary cause, but lung, ovary and haematological malignancies appear to be the most common [44, 45]. The association with cancer is, as one might expect, highest when the muscle disorder is first diagnosed and falls in frequency with time. Chow et al. [45] found that the risk of an accompanying malignancy was six times the normal population risk in the first year after diagnosis. The incidence of malignancy in inflammatory myopathies has varied in different reported series from about 16% [46] to as high as 40% [44, 47)] and the incidence is, generally, much higher in patients who demonstrate also the inflammatory skin involvement of dermatomyositis [44].

In most series of inflammatory myopathies there is a preponderance of women [46, 48, 49]. This is even more pronounced in polymyositis [45] but when either disease is paraneoplastic the sex distribution in both is much closer to equal [50].

In general, the management of the inflammatory muscle disorder is the same whether there is an accompanying neoplasm or not. The response of the paraneoplastic muscle inflammation to corticosteroid and other immunosuppressive agents is the same [44, 47, 48, 50]. As would be anticipated, the mortality is greater in those patients with an associated malignancy due to the prognosis of the tumour, but successful treatment of the tumour does not always result in resolution of the muscle disease [51].

Conclusion The musculoskeletal system is just as vulnerable as others to paraneoplastic disorders. Disorders that are recognized to be often paraneoplastic may occur in association with 26

more benign conditions. The most common paraneoplastic phenomenon, finger clubbing, can be associated with many distal infectious and inflammatory diseases.

However, it is essential to recognize this type of problem and to search diligently for an underlying malignancy as the identification of such a neoplasm at an early stage may lead to major improvements in the prognosis and mortality.

Acknowledgements: The authors have not received any financial support in the preparation of this review.

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The Editor, St. George’s University Scottish Medical Journal PO Box 7 smjsubmit@yahoo.com St. George’s, Grenada,

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Instructions to Authors CMJ, The Caribbean Medical Journal is a peer-reviewed journal with an international scope. The Mission of this journal is to promote publication of medical research as well as other information relevant to medicine within the region, which are not only important locally, but also regionally and internationally, while enhancing the collaboration between academic medicine and the general practitioner.

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Authors are encouraged to contact the editorial office (Telephone: 868 671 7378; Tel/fax: 868 671 5160; e-mail: medassoc@tntmedical.com) with any questions regarding topic selection or manuscript development.

Manuscript submission guidelines Manuscript submission guidelines The guidelines are in accordance with the “Uniform Requirements for Manuscripts Submitted to Biomedical Journals” published by the International Committee of Medical Journal Editors (www.icmje.org).

Criteria for authorship Authorship credit should be based only on 1) substantial contributions to conception and design, or acquisition of data, or analysis and interpretation of data; 2) drafting the article or revising it critically for important intellectual content; and 3) final approval of the version to be published. Conditions 1, 2, and 3 must all be met. Acquisition of funding, the collection of data, or general supervision of the research group, by themselves, do not justify authorship.

Previous publication or duplicate/salami papers Manuscripts are considered for publication in CMJ, with the understanding that they have not been either submitted for review elsewhere or published previously. Research papers presented at a meeting (and published as an ‘abstract’ or ‘conference proceedings’) will be considered for publication. However, this should be notified while submission.

Human and Animal Research Appropriate Institutional Review Board (IRB) or Ethics Committee approval must have been obtained for all research involving humans and animals. A statement must be included in the manuscript that “Approval was obtained for the research” quoting the Authority that approved the study. In case of registered trials the number may be quoted. Case Reports/Series should accompany an informed consent from the patient or legal guardian where applicable (please see below).

When reporting experiments on human subjects, indicate whether the procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation and with the Helsinki Declaration of 1975, as revised in 1983. Do not use patients’ names, initials, or hospital numbers, or identifiers especially in illustrative material.

When reporting experiments on animals, indicate whether the institutional/national guidelines for, or any national law on, the care and use of laboratory animals was followed.

Conflicts of interest / Sources of Funding CMJ requires that all authors disclose any conflicts of interest the research may introduce between authors and/or other personnel. Also the authors’ individual primary financial relationships (including, but not limited to, equities or paid consultancies) with companies whose products or whose competitors’ products are discussed in the manuscript and the sources of funding for the research if any must be explicitly stated on the title page of the manuscript.

Copyright Authors of accepted manuscripts agree to transfer copyright to CMJ. Copyright transfer forms need to be submitted with page proofs of accepted manuscripts.

Manuscript preparation Manuscripts should be submitted electronically to Editor, CMJ via medassoc@tntmedical.com . Hard copy submission will not be accepted.

Cover letter

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Caribbean Medical Journal

Instructions to Authors Submissions must include a cover letter stating 1) the intent of submitting the work for publication in CMJ, 2) that the article is original and has not been previously published or is currently being considered for publication elsewhere, 3) All authors have read and approved the manuscript and 4) There are no conflicts of interest nor ethical issues pertaining to the manuscript.

This letter should be addressed to the Editor-in-Chief of CMJ, signed by the submitting author, and be scanned and emailed or faxed to the following address: Dr Solaiman Juman Editor-in-Chief, Caribbean Medical Journal The Medical House 1 Sixth Avenue, Orchard Gardens Chaguanas Trinidad W.I E-mail: medassoc@tntmedical.com Title page The titles must be brief and specific. The title page should include the full names (first name and surname), academic degrees, titles, and affiliations of all authors. The corresponding author should also include current mailing address, telephone and fax numbers, and e-mail address. The title page should also include a brief statement on financial support and conflicts of interest if any.

Abstracts and key words All original research articles and review articles should include 3 to 5 key words. Abstracts should be structured and 250 words in length and present an overview of the manuscript. Abstracts should not contain references and abbreviations.

Complicated statistical values and specific numeric results should be avoided when possible.

The sub-headings of the abstract for original articles should be Objectives, Study Design, Subjects and Methods, Results and Conclusion. For review articles, it should be Background & Objectives, Review Methods, Results and Conclusion.

Text Manuscripts should be typed, double-spaced, with at least 1-inch margins. Please adhere to British English style throughout the manuscript. Manuscripts should be written as concisely as possible and must be paged consecutively. Use 12 point font in Times New Roman style.

Statistics Describe statistical methods with enough detail to enable a knowledgeable reader with access to the original data to verify the reported results. Avoid relying solely on statistical testing, such as the use of P values, which may fail to convey important quantitative information. Specify any computer software programmes used. Restrict tables and figures to those needed to explain the argument of the paper and to provide support. Use graphs as an alternative to tables with many entries; do not duplicate data in graphs and tables.

Manuscript categories Original Research Articles Original research articles are the primary preferred manuscripts for the Journal, and should be usually between 2500 – 4000 words in length. All articles must include a title page, structured abstract, text comprising of the following components: “Introduction”, “Methods”, “Results”, and “Discussion”. The “Discussion” section should include limitations, recommendations and the conclusions of the study.

Review Articles Both narrative and systematic reviews can be submitted and should be usually 4000-5000 words in length with a maximum of 100 references. All articles must include a title page, structured abstract, text comprising of the following components: “Introduction”, “Review Strategies and Methods”, “Results”, and “Discussion”. The “Discussion” section should include limitations, recommendations and the conclusions of the review.

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