Vol. 3.

Issue 1 | January 2014

Formerly The Family Practitioner of India

Emeritus Editor Prof. Dr. S. Arulrhaj, India Editorial Board Dr. T.N. Ravisankar, Chennai Dr. J.A. Jayalal, Chennai Dr. Raman Kumar, Delhi Advisors National Dr. Adrija Rahman Chattopadya, Bangaluru Dr. Bahulesh Metha Mumbai Dr. Satish Chug, Hariyana Dr. Abbas Ali, UP. Dr. Akilesh Varma, Bilalpur Dr. Hari Dass, Kerala Dr. Panigrahi, Mumbai Dr. Bahulesh Metha, Mumbai Dr. Ravi Wankehedkar, Mumbai Dr. Anilkumar Singh, Bihar International Prof. Dr. Riaz Qureshi Saudi Arabia Prof. Dr. Pratap Prasad Kathmandu Dr. Preethi Wijayaguna Wardane Srilanka Dr. Antonetto Perera Srilanka Dr. ALP Seneverethne Srilanka Dr. Azizkhan Tank Pakistan Dr. Noor Akthar Pakistan Dr. Kanu Bala Bangladesh Dr. Falahuzzaman Khan Bangladesh Dr. Katherine Currow Australia Dr. Sivashunmuganathan Malaysia Dr. J.P. Tabon Malta Dr. Ohneba Owusu Danso Ghana Dr. Garth Manning CEO, WONCA

Editor Dr. K.M. Abul Hassan, India

Contents
First Feature
Minimizing CVD risk in diabetic patients by maintaining ABC: A1c, Blood pressure, and Cholesterol .......................................... 4

Dr. Punitha Rebacca, Chennai Dr. K.Surya Rao, AP

Guideline Updates
Management of dyslipidemia and prevention of atherosclerosis...................................9

Evidence
Are antihistamine-analgesicdecongestant combinations effective in reducing the duration and alleviating the symptoms of the common cold in adults and children? ........13

Journal Scans ...................... 15 Case in Question

A sporadic case of meningoencephalomylitis with malaria and Goldenhar syndrome .........................................19

Executive-Editorial Vishvanatha M Shoukath Ali Kareem Design & Layout Ganesh KB Gurumahesh MR

Earth Siege: Diseases that impact our WORLD

Diabetes mellitus and Tuberculosis: Convergence of two epidemics ............................22
`100 Per Copy

IMA College of General Practitioners

Indian Medical Association College of General Practitioners (IMACGP) is the academic wing of Indian Medical Association catering to the academic needs of Family Physicians of India and Asia. Started in the year 1963 by Dr. P C Bhatla, IMA CGP was aimed at providing knowledge to General Practitioners awarding Fellowship of the College of General Practitioners with definite syllabus and curriculum approved by the College of General Practitioners. Changing times and the need for International exposure and recognition has made IMA CGP collaborate with other Universities. MRCGP (International) from Royal College of GPs London Post Graduate Diploma in Emergency Medicine from George Washington University, USA Diploma in Family Medicine & Diploma in Emergency Medicine from Vinayaka Missions University, Salem Diploma and M.D (Family Medicine) from Colombo Various diploma courses through St. Peters University, Chennai.

IMA CGP conducts an annual Conference - International Congress of Family Physicians, at State, Regional and National levels with the best international faculty gracing the event. IMA CGP organises an All India Young Doctor Convention every year with the objective to advocate young doctors to pursue family medicine practice as their choice and not by chance. An International Study tour every year refreshes the members as well as provides them with first-hand information of the Family Doctor concept in other countries. Reincarnation of THE FAMILY DOCTOR - the motto of IMA CGP is pursued with all vigour by the College.

IMA College of General Practitioners - HQRS, Chennai, India. IMA TN State Hqrs Building, Doctors Colony, Via Bharathi Nagar First Main Road, Off. Mudichur Road, Tambaram, Chennai 600 045. Tel: 044 29000325 | Email: cgpima@gmail.com | Web: www.imacgpindia.com National President, IMA Dr. K. Vijayakumar Chief Patron, IMACGP Prof. Dr. S. Arulrhaj Governing Council Members: Dr. Akhilesh Verma Dr. Avdhesh Kumar Gupta Dr. Neeraj Kumar Gupta Dr. P. Radha Krishna Murthy Dr. Amrit Pal Singh Secretary, General IMA Dr. Narendra Saini Dean,IMACGP Dr. Pulla Rao Secretary, IMACGP Dr. K.M. Abul Hassan IMA Past Secretary Dr. T.N. Ravisankar Joint Secretaries Dr. A. Rajarajeswar Dr. R. Anburajan Dean Elect Dr. Anil Panchnekear

Dr. Amutha Karunanidhi Dr. Kiranshankar Wasudeo Deoras Dr. Piyush Kanti Roy Dr. Satish Chandra Pandey

Academic Director Dr. J.A. Jayalal

The Family Doctor, The official Journal of IMA College of General Practitioners, is published by Medeka Health Pvt Ltd. #2, Jyothi Tower 1st floor, 1st Cross, Kumaracot Layout, Highgrounds, Bangalore 560 001. Although great care has been taken in compiling and checking the information given in this publication, the author/s, purchaser/s, sponsor/s, advertiser/s shall not be responsible or in any way liable for the present and or continued accuracy of the information or for any errors, omissions or inaccuracies in this publication whether arising from negligence or otherwise howsoever, or for any consequences arising there from. Opinions expressed do not necessarily reflect the views of the publisher, editor or the editorial board.

Editorial

Dear Colleagues,
Warm Golden Jubilee Greeting from IMA College of General Practitioners, India.
IMACGP was established in the year 1963. 2013 is the Golden Jubilee year. To commemorate this historic landmark, the official publication of IMACGP, The Family Practioner of India has been rechristined as The Family Doctor with professional touch in the exterior and interior. The pilot copy of the first issue The Family Doctor was launched on 19th Saturday, October 2013 at Hyderabad during the Golden Jubilee Conference, GPCON and ICON 2013. The ancestorial Family Doctor is the custodian of health of the citizen through his effective and compassionate primary care and emergency primary care. In course of time with civilization, Family Doctor system is forgotten and tertiary care system has come to the frontline. Though hitech health care has flourished well in India, Accessible, Affordable and Equitable Health Care has become a nightmare for Indian and citizen of many developing nations. Governments and people have started evaluating the health care system in countries and finally landed at primary care can only offer Affordable, Accessible and Equitable Health Care to all the citizen. The fulcrum of Universal Health Collage (UHC) lies in primary care. The key objective of IMACGP is to strengthen primary care in India by strengthening the knowledge and skills of general practitioners through print, electronic, academic materials, courses and certification, so that they can offer efficient curative and preventive health care to Indians. In this direction The Family Doctor will be a milestone to strengthen primary care in our vast nation. I am thankful to the Editorial Board, National and International Advisors for synergizing their mind and pens to make the journal highly purposeful and satisfying to the GPs. Medeka Health Pvt Ltd. Bengaluru, our co-publisher needs appreciations for their efforts to fit into this Mission. Waiting to receive your directions on the further issues of The Family Doctor moving towards its target. Accessible, Affordable and Equitable Health Care can only be through Primary care Physician.

Jai hind

Best Wishes

Prof. Dr. S. Arulrhaj Chief Patron, Emeritus Editor, IMACGP www.drarulrhaj.com | www. healthy-india.net

Minimizing CVD risk in diabetic patients

Minimizing CVD risk in diabetic patients by maintaining ABC: A1c, Blood pressure, and Cholesterol
UKPDS risk engine: To estimate the risk of coronary heart disease and stroke for 10 years using the following risk factors age, gender, race, current smoking status, glycosylated hemoglobin (HbA1c), systolic blood pressure, total cholesterol, HDL-C, and presence or absence of atrial fibrillation. Prof. Dr. S. Arulrhaj, MD, FRCP (Glasg)
Chairman & Head Acute Medicine, Sundaram Arulrhaj Hospitals 145/5B, Jeyaraj Road, Tuticorin - 628 002 Tamil Nadu, India

Diabetes mellitus A potential risk factor for CVD

Diabetes mellitus is characterized by insulin resistance and is usually accompanied with metabolic syndrome, which comprises of central obesity, high levels of free fatty acids, high triglyceride levels, high low-density lipoprotein cholesterol (LDL-C) levels, low high-density lipoprotein cholesterol (HDL-C) levels, and hypertension.1 The clustering of these factors signicantly increases the risk for cardiovascular disease (CVD). CVD is the most common cause of death in patients with type 2 diabetes mellitus.2 Nearly 65% of people with type 2 diabetes (2 out 3 people with diabetes) die from CVD.1 The prevalence of CVD is 24 times higher in diabetic patients compared to non-diabetic patients.3 Type 2 diabetes mellitus decreases life expectancy.1 Additionally, it is projected that 85% of the health care costs owing to complications of type 2 diabetes are linked to CVD.4 Identifying, assessing, and correcting the CV risk factors associated with type 2 diabetes is essential for the prevention of CV morbidity and mortality.5

FIRST EATURE F

Minimizing CVD risk in diabetic patients

CVD risk assessment

The risk of CVD increases with the onset of type 2 diabetes.5 The United Kingdom Prospective Diabetes Study (UKPDS) has identied various factors associated with increased risk of CVD in patients with type 2 diabetes. The factors are:6 m Hyperglycemia m Dyslipidemia m Hypertension m Central obesity m Cigarette smoking Seon et al. suggested the following methods to estimate CVD risk in type 2 diabetic patients5: UKPDS risk engine: To estimate the risk of coronary heart disease and stroke for 10 years using the following risk factors age, gender, race, current smoking status, glycosylated hemoglobin (HbA1c), systolic blood pressure, total cholesterol, HDL-C, and presence or absence of atrial brillation. Biochemical tests: To estimate blood pressure, blood glucose, and blood cholesterol levels. Vascular examinations: m Carotid intima-media thickness (CIMT) for early detection of atherosclerosis. m Pulse wave velocity (PWV) and augmentation index (AI) to assess arterial stiffness. m Flow-mediated dilation (FMD) to assess early endothelial cell dysfunction.

The United Kingdom Prospective Diabetes Study (UKPDS) has identified various factors associated with increased risk of CVD in patients with type 2 diabetes.

Treatment goals: The ABC of diabetes care

Regulatory authorities like the American Diabetes Association (ADA), the Joint National Committee (JNC) on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure, and the National Cholesterol Education Program (NCEP) have suggested that vascular complications in people with diabetes can be reduced through control of glycemia, blood pressure, and blood lipid levels, as well as through smoking cessation.7,8,9 Further, the National Diabetes Education Program (NDEP) has promoted the concept of ABCs of diabetes care.1

A represents HbA1c
Signies the importance of blood glucose control in preventing the complications of diabetes.10

Each 1% decrease in HbA1c reduces the frequency of microvascular complications by 3540%.10 The suggested target goal for glycosylated hemoglobin (HbA1c) level: <7%.1,7

B represents blood pressure

Signies the importance of blood pressure control in preventing both microvascular and macrovascular complications.10

Signies the importance of urine microalbumin level as an indicator of diabetic nephropathy and CVD.10 The suggested target level for blood pressure control: <130/80 mmHg.1,7,8 Reducing/eliminating microalbuminuria is a goal of antihypertensive therapy.10

C represents cholesterol
Signies the important role of lipid management and aspirin prophylaxis in the prevention of CVD and stroke.10 The suggested target level for LDL-C: 100 mg/dL.7 The suggested target level for HDL-C: >40 mg/dL in men, >50 mg/dL in women.7 The suggested target level for triglycerides: <150 mg/dL.1,7 The suggested target level for total cholesterol: <200 mg/dL.9

Minimizing CVD risk in diabetic patients

Inadequate control of CVD risk factors: A major challenge

According to a National Health and Nutrition Examination Survey (NHANES), less than 10% of people with type 2 diabetes have the three major CVD risk factors under control (Figure 1).11

Figure 1. Less than 10% of diabetic patients have the three major risk factors under control 60 50 Adults (%) 40 30 20 10
NHANES III (n=1204) NHANES 1999-2000 (n=370)

Action plan: Interventions and recommendations to reduce CVD risk

Lifestyle modication is the cornerstone of treatment for reducing CV complications in people with diabetes. Optimal control of blood glucose levels, lipid levels, and blood pressure usually requires regular physical activity and a diet designed to reduce sodium intake, alter lipid patterns, lower blood glucose levels, and induce weight loss. If the patient displays inadequate response to dietary modications and exercise, drug therapy (Figure 2) may be able to achieve target HbA1c, blood pressure, and cholesterol levels.1 Treatment of hyperglycemia with medications like sulfonylureas, metformin, glitazones, acarbose, voglibose, and insulin has signicant effects.1 Lipid-lowering therapy (statins, brates) should be considered in patients with diabetes and dyslipidemia, specically in those with coronary artery disease.1 Thiazide diuretics provide effective management of hypertension. Diabetesassociated CVD can also be prevented or delayed by angiotensin converting enzyme (ACE) inhibitors.1 Smoking cessation and aspiring therapy are also important factors in the reduction of risk of CVDs.1 In addition, patient adherence and acceptance are often challenging in patients with type 2 diabetes mellitus and are important aspects in the management of the diease.2

HbA1c level <7%

BP <130/80 mmHg

Total cholesterol level <200 mg/dL (5.18 mmol/L)

Good control

Vascular disease risk factors

NHANES: National Health and Nutrition Examination Survey; HbA1c: Glycosylated hemoglobin.

Figure 2. Interventions to reduce cardiovascular events in diabetic patients

Hyperglycemia

Diet, exercise, oral hypoglycemic agents, insulin

Hypertension

Diet, exercise, thiazide diuretics, ACE inhibitors, other antihypertensive agents as needed to achive target BP levels

Hyperlipidemia

Diet, exercise, cholesterol lowering medications (statins, fibrates)

Tobacco use/ smoking

Physician counseling, smoking cessation programmes, medications

Vascular events

Diet, exercise, daily aspirin therapy, maintaince of blood gluose and blood choesterol levels, -blockers for MI

Obesity

Diet, exercise, medications, bariatric surgery (weight-loss surgery)

ACE: Angiotensin converting enzyme; BP: Blood pressure; MI: Myocardial infarction.

ABC care reduces the risk of CVD: Evidence from landmark trials
A The UKPDS trial has demonstrated that with each 1% reduction in mean HBA1c level in diabetic patients was associated with a risk reduction of: 21% for any diabetes-related endpoint (p<0.0001) 37% for microvascular endpoints (p<0.0001) 14% for myocardial infarction (p<0.0001).12

B Tight blood pressure control has signicant and superior effects on clinical outcomes of CVDs associated with diabetes (Figure 3).13-16

Minimizing CVD risk in diabetic patients C Studies have shown that rigorous lipid reduction therapy can reduce the risk for CVD in people with diabetes. In addition, it can cause signicant reduction in the incidence of stroke, myocardial infarction, coronary artery disease, and CV mortality (Figure 4).17-22
Figure 3. Reduced CVD risk by lowering BP in people with diabetes

0 10 Decrease in CV events (%) 20

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Take home message

Diabetes is associated with signicant CV morbidity and mortality. In order to prevent CVD in type 2 diabetes patients, the control of risk factors is important. The CVD risk can be effectively minimized with ABC care: A1c, blood pressure, and cholesterol. Daily aspirin intake and lifestyle modications are also important for CVD risk reduction.

21 UKPDS 30 40 50 60 32 UKPDS 44 UKPDS

51 HOT

33 CAPPP

37 HOPE

CV: Cardiovascular; CVD: Cardiovascular disease; UKPDS: United Kingdom Prospective Diabetes Study; HOT: Hypertension Optimal Treatment; CAPPP: Captopril Prevention Project; HOPE: Heart Outcomes Prevention Evaluation.

7.

Figure 4. Lipid treatment in diabetes yields CV risk reduction

8.

American Diabetes Association. Standards of medical care for patients with diabetes mellitus. Diabetes Care. 2003;26(1):S33S50. Chobanian AV, Bakris GL, Black HR, et al. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 report. JAMA. 2003;289(19):256072. National Cholesterol Education Program Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults. Executive summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001;285:248697. Abbate SL. Expanded ABCs of diabetes. Clinical Diabetes. 2003;21(3):128133. Saydah SH, Fradkin J, Cowie CC. Poor control of risk factors for vascular disease among adults with previously diagnosed diabetes. JAMA. 2004;291(3):33542. Stratton IM, Adler AI, Neil HA, et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): Prospective observational study. BMJ. 2000;321(7258):40512. UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ. 1998;317(7160):70313. Hansson L, Zanchetti A, Carruthers SG, et al. Effects of intensive bloodpressure lowering and low-dose aspirin in patients with hypertension: Principal results of the Hypertension Optimal Treatment (HOT) randomised trial. HOT Study Group. Lancet. 1998;351(9118):175562. Niskanen L, Hedner T, Hansson L, et al. Reduced cardiovascular morbidity and mortality in hypertensive diabetic patients on first-line therapy with an ACE inhibitor compared with a diuretic/beta-blocker-based treatment regimen: A subanalysis of the Captopril Prevention Project. Diabetes Care. 2001;24(12):20916. Gerstein HC. Diabetes and the HOPE study: Implications for macrovascular and microvascular disease. Int J Clin Pract Suppl. 2001;(117):812. Colhoun HM, Betteridge DJ, Durrington PN, et al. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): Multicentre randomised placebo-controlled trial. Lancet. 2004;364:68596. Collins R, Armitage J, Parish S, et al. MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: A randomised placebo-controlled trial. Lancet. 2003 Jun 14;361(9374):200516. Sacks FM, Pfeffer MA, Moye LA, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. N Engl J Med. 1996;335(14):10019. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. N Engl J Med. 1998;339(19):134957. Rubins HB, Robins SJ, Collins D, et al. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. N Engl J Med. 1999;341(6):4108. Akauola H, Alford F, Barter P, et al. Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): Randomised controlled trial. Lancet. 2005;366:184961.

0 5 10 Reduction in CV risk (%) 15 20 25 30 35 40

l n tin ozi atin atin tati sta fibr ) ast ast vas rva v v m o a a m e g t r r i A mg) S mg) P mg) P mg) G 0 m 0 (10 (40 (40 (12 (40

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10. 11.

11 FIELD

12.

13.

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19 LIPID 25 CARE 24 VAHIT

14.

15.

37 CARDS

16. 17.

CV: Cardiovascular; CARDS: Collaborative Atorvastatin Diabetes Study; HPS: Heart Protection Study; CARE: Cholesterol and Recurrent Events; LIPID: Long-term Intervention with Pravastatin in Ischemic Disease; VAHIT: Veterans Affairs High-Density Lipoprotein Intervention Trial; FIELD: Fenofibrate Intervention and Event Lowering in Diabetes.

18.

References
1. 2. 3. 4. 5. 6. Gavin JR 3rd, Peterson K, Warren-Boulton E. Reducing cardiovascular disease risk in patients with type 2 diabetes: A message from the National Diabetes Education Program. Am Fam Physician. 2003;68(8):156974. Baldwin MD. Assessing cardiovascular risk factors and selecting agents to successfully treat patients with type 2 diabetes mellitus. J Am Osteopath Assoc. 2011;111(7 Suppl 5):S212. American Diabetes Association. Treatment of hypertension in adults with diabetes. Diabetes Care. 2002;25(1):S713. Gomes MB, Giannella-Neto D, Faria M, et al. Estimating cardiovascular risk in patients with type 2 diabetes: A national multicenter study in Brazil. Diabetol Metab Syndr. 2009;1(1):22. Seon CS, Min KW, Lee SY, et al. Cardiovascular risk assessment with vascular function, carotid atherosclerosis and the UKPDS risk engine in Korean patients with newly diagnosed type 2 diabetes. Diabetes Metab J. 2011;35(6):61927. Turner RC, Millns H, Neil HA, et al. Risk factors for coronary artery disease in non-insulin dependent diabetes mellitus: United Kingdom Prospective Diabetes Study (UKPDS: 23) BMJ. 1998;316(7134):8238.

19.

20.

21.

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AACE Guidelines yslipidemia is a major risk factor for coronary artery disease (CAD) and ischemic stroke. Evidence suggests that insulin resistance is an important risk factor for peripheral vascular disease, stroke, and CAD (Evidence level 3). It is well known that an increased serum level of low density lipoprotein (LDL) is a major cause of atherosclerosis and coronary heart disease (CHD). Other serum lipoproteins such as triglyceride (TG)-rich lipoproteins, very lowdensity lipoproteins (VLDL), chylomicrons, and high density lipoproteins (HDL) also play a vital role in the pathophysiology of atherosclerosis.1 LDL, VLDL remnants, chylomicron remnants, small dense LDL (sdLDL), lipoprotein-A [Lp(a)], and oxidized LDL are pro-atherogenic lipoproteins, whereas HDL is an anti-atherogenic lipoprotein.2 The American Association of Clinical Endocrinologists (AACE) Medical Guidelines for Clinical Practice provide a practical guide for the diagnosis and treatment of dyslipidemia and prevention of atherosclerosis.3

AACE Guidelines: Management of dyslipidemia and prevention of atherosclerosis

Dr. A. Muruganathan, MD, FRCP (GLASG), FACP (USA), FPCP (Philippines), FICP
Adjunct Professor The Tamilnadu Dr MGR Medical University Chairman, AG Hospital, 34 KPN Colony, 3rd Street, Tirupur - 641 601, Tamil Nadu, India.

Treatment recommendations in patients with dyslipidemia and CAD risk

Treatment goals by AACE

Lipid goals for all patients should be personalized by levels of the risk. The AACE recommended treatment goals for major lipid parameters in patients at risk for CAD are given below.3 TC <200 mg/dL LDL-C <100 mg/dL; <70 mg/dL (very high risk patients) HDL-C As high as possible, but at least >40 mg/dL in both men and women NonHDL-C 30 mg/dL above LDL-C goal

id li

10

AACE Guidelines Patients at high-risk, healthy, and functional older (Grade A; BEL 1).3

TG <150 mg/dL Apo B <90 mg/dL (patients at risk of CAD, including those with diabetes). <80 mg/dL (patients with CAD or diabetes plus 1 additional risk factor)

Combination therapy is recommended when

The cholesterol level is markedly increased and monotherapy does not achieve the therapeutic goal (Grade A; BEL 1). Mixed dyslipidemia is present (Grade C; BEL 3). Niacin or brates in combination with statins may be appropriate options for many patients with hypertriglyceridemia and associated low HDL-C (Grade B; BEL 2) The risk of dosage-related adverse effects has to be reduced (Grade D; BEL 4).3

Pharmacological therapy
Drug therapy is essential to lower LDL-C to less than 100 mg/dL and has been shown to reduce vascular mortality in patients at high risk (Grade A; Best evidence level [BEL] 1), decrease coronary death, myocardial infarction (MI), or any cardiovascular events (Grade A; BEL 1). The rst-line approach to primary prevention in patients with lipid disorders involves the implementation of lifestyle changes, including physical activity and medical nutrition therapy. Treatment may also involve pharmacotherapy (Table 1) and patient education programs (such as smoking cessation and weight loss) to reduce further risk. 3
Table 1. Pharmacotherapy for dyslipidemia Drug class Statins Lovastatin Pravastatin Simvastatin Fluvastatin Atorvastatin Rosuvastatin Pitavastatin Fibrates Fenofibrate Gemfibrozil Fenofibric acid Niacin Immediate-release Extended-release Bile acid sequestrants Cholestyramine Colestipol Colesevelam Cholesterol absorption inhibitors Ezetimibe Combination therapies (single-pill) Ezetimibe/simvastatin Extended-release niacin/simvastatin
aSimvastatin

Recommended starting daily dosage 20 mg 40 mg 2040 mg 40 mg 1020 mg 10 mg 2 mg 48145 mg 1200 mg 45135 mg 250 mg 500 mg 816 g 2g 3.8 g 10 mg 10/20 mg 500/20 mg

Dosage range

1080 mg 1080 mg 580 mga 2080 mg 1080 mg 540 mg 24 mg 48145 mg 1200 mg 45135 mg 2503000 mg 50 mg, 02000 mg 424 g 216 g 3.84.5 g 10 mg 10/10 to 10/80 mg 500/20 to 1000/20 mg

The AACE recommends combination therapy with cholesterol absorption inhibitors and statins to improve the benecial effects of statins on TGs and HDL-C.3

Diabetic dyslipidemia
Type 2 diabetes is also associated with atherogenic dyslipidemias (an interrelated group of lipoprotein abnormalities that lead to the development of CHD), and hence patients with type 2 diabetes have a signicantly increased risk of developing cardiovascular disease. Once clinical cardiovascular disease develops, these patients have a poorer prognosis than normoglycemic patients. The combination of increased TG levels and decreased HDL-C levels, which constitutes the most common dyslipidemic pattern in type 2 diabetes, is known as diabetic dyslipidemia. Individuals with diabetic dyslipidemia tend to have atherogenic sdLDL cholesterol particles, whether or not LDL-C levels are

(80 mg)-not approved for therapy unless patient has been on treatment for more than 1 year without

myopathy.

Patients for whom AACE recommends aggressive therapy

Patients undergoing coronary artery bypass grafting (Grade A; BEL 1). Patients with acute coronary syndrome (Grade A; BEL 1).

AACE Guidelines elevated.4 Among LDL particles, sdLDL are more susceptible to oxidation, and have longer residence time and higher afnity to the extracellular matrix. Delayed clearance of TG-rich lipoproteins results in the formation of sdLDL, which is associated with insulin resistance and postprandial hyperlipidemia.2

11

Treatment goals by AACE

The AACE recommended treatment LDL goals for diabetic patients are3 Diabetes alone <100 mg/dL Diabetes and one or more additional risk factors <70 mg/dL

Management of diabetic dyslipidemia

The AACE recommends a comprehensive strategy to control lipid levels and to address associated metabolic abnormalities and modiable risk factors such as hypertension, diabetes, obesity, and cigarette smoking, (Table 2).3
Table 2. Treatment of dyslipidemia (monotherapy) in patients with diabetes mellitus Drug class Statins Metabolic effect Primarily LDL-C reduction (2155%) (Grade A: BEL 1) Does not increase HDL-C effectively (210%) Primarily TG reduction (2035%) (Grade A: BEL 1) Less effect on increasing HDL-C (6-18%) May decrease LDL-C (2035%) and TC Reduces LDL-C (1025%), TG (2030%) and HDL-C (1035%) (Grade B: BEL 2) Primarily LDL-C reduction (1525%) (Grade B: BEL 1) Reduces apo B Increases HDL-C, TG Primarily LDL-C reduction (1018%) (Grade A: BEL 1) Reduces apo B Monitored parameters Myopathy/rhabdomyolysis in rare cases, liver function test

Fibrates

GI symptoms, possible cholelithiasis

Niacin

Skin flushing, pruritus, abdominal discomfort, hepatoxicity (rare but may be severe), nausea, peptic ulcer Frequent nonlife-threatening GI events, has many potential drug interactions, may reduce absorption of folic acid and fatsoluble vitamins Myopathy/rhabdomyolysis

Bile acid sequestrants

Cholesterol absorption inhibitors

apo: Apolipoprotein; GI: Gastrointestinal; HDL-C: High-density lipoprotein cholesterol; LDL-C: Low-density lipoprotein cholesterol; TG: Triglycerides; VLDL-C: Very low-density lipoprotein cholesterol; TC: Total cholesterol.

References
1. 2. 3. Grundy SM. Pathogenesis of Atherogenic Dyslipidemia. Information available at http://www. medscape.com/viewarticle/412684_2. Accessed on 16.9.2013. Koba S, Hirano T. Dyslipidemia and atherosclerosis. Nihon Rinsho. 2011;69(1):13843. Jellinger PS, Smith DA, Mehta AE, et al. American Association of Clinical Endocrinologists Guidelines for management of dyslipidemia and prevention of atherosclerosis. AACE Task Force for management of dyslipidemia and prevention of atherosclerosis. Endocr Pract. 2012;18 Suppl 1:178. Garber AJ. Attenuating cardiovascular risk factors in patients with type 2 diabetes. Am Fam Physician. 2000;62(12):26332642.

4.

Antihistamine-analgesicdecongestants for cold

13

Dr. B. Sundara Rajan, MS DLO

Senior ENT Consultant Beent Hospital 19, Devadoss Street Vedachala Nagar Chengalpattu - 603 001 Tamil Nadu, India

EVIDENCE
EBM for clinicians
Are antihistamine-analgesicdecongestant combinations effective in reducing the duration and alleviating the symptoms of the common cold in adults and children?
Several over-the-counter (OTC) preparations comprising of antihistamines, decongestants, and/or analgesics are being widely used in the treatment of the common cold. However, the efcacy of these preparations has been questioned by conicting clinical evidence. These unclear and conicting results urged a group of Belgian researchers to evaluate the efcacy of these combinations in reducing the duration and alleviating the symptoms of the common cold in adults and children. In this study, data was procured from the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2011, Issue 4), which contains the Cochrane Acute Respiratory Infections Groups Specialized Register, OLD MEDLINE (1953 to 1965), MEDLINE (1966 to November Week 3, 2011), and EMBASE (1990 to December 2011). Only those randomized controlled trials which had evaluated the efcacy of antihistamine-decongestant-analgesic combinations in comparison to placebo and other active treatments (excluding antibiotics) were included. The trials were categorized according to the active ingredients studied. Two review authors independently extracted and summarized

Evidence for ancient medicinal remedies found in 5,100-year-old Egyptian wine jars
A selection of wine jars from Scorpion Is tomb at Abydos, laid out on the desert sand. (Photograph courtesy of German Institute of Archaeology, Cairo.)
For further details, visit http://www.pennmuseum.org/pressreleases/658-5100-year-old-chemical-evidence-for-ancientmedicinal-remedies-discovered-in-ancient-egyptian-wine-jars.html

14

Antihistamine-analgesicdecongestants for cold data on general recovery, nasal obstruction, rhinorrhea, sneezing, cough, and side effects. A total of 27 trials (n=5117) were considered. Of these, 14 trials evaluated antihistamine-decongestant combinations, 2 studied antihistamineanalgesic combinations, 6 studied analgesic-decongestant combinations, and 5 studied antihistamine-analgesic-decongestant combinations. Active ingredients were used in 6 trials, whereas placebo was used in 21 trials. In most of the trials, there were large differences in design, participants, interventions, and outcomes, and moreover, pooling was possible only for a limited number of studies and outcomes. Based on the clinical results obtained for various combinations (Table 1), the authors of the study concluded that antihistamine-analgesic-decongestant combinations have some general benets in adults and older children (but not in young children). However, these benets must be weighed against the risk of adverse effects.
Table 1. Results of various clinical trials Formulation (No. of trials) Observation Clinical findings About 66% of the participants in the active treatment group showed favorable response compared to 41% in the placebo group. Adverse effects Antihistamine-decongestant had more adverse effects compared to placebo; however, this was insignificant. About 19% and 13% of the patients treated with antihistaminedecongestant and placebo experienced 1 or more adverse effects, respectively. About 12% and 10% of the patients treated with antihistamine-analgesic and placebo experienced 1 or more adverse effects, respectively.

AntihistamineEight trials reported on global decongestant (12) effectiveness, of which only 6 could be pooled (Active treatment: n=309; Placebo: n=312). OR of treatment failure was 0.27. NNTB was 4.

Antihistamineanalgesic (3)

Two trials reported on global effectiveness, data from 1 study was presented (n=290 on active treatment, n=292 ascorbic acid). OR of treatment failure was 0.33. NNTB was 6.67.

After 6 days of treatment, 43% were cured in the control group and 70% in the active treatment group. The second study also showed an effect in favor of active treatment. Analgesic-decongestant was beneficial in 73% of the patients, whereas paracetamol was beneficial only in 52% of the patients.

Analgesicdecongestant (6)

One trial reported on global effectiveness

Analgesic-decongestant combinations had significantly more adverse effects than control. NNTH was 14. None of the other 2 combinations caused significantly more adverse effects.

Antihistamineanalgesicdecongestant (5)

Four trials reported on global effectiveness, of which, 2 trials could be pooled Global effectiveness was 52% and 34% with active treatment and placebo, respectively OR of treatment failure was 0.47 NNTB was 5.6

The 2 trials did not report any benefits, and another 2 studies did not show any effects. Two studies with antihistamine-decongestant (113 children) could not be pooled.

In 1 study, incidence of adverse effects was more with active treatment compared to placebo (2% vs. 4%).

Two other trials reported no differences between treatment groups but numbers were not Active treatment did not show reported. any significant effect.

NNTB: Number needed to treat for an additional beneficial outcome; OR: Odds ratio; NNTH: Number needed to treat for an additional harmful outcome.

Reference
De Sutter AI, van Driel ML, Kumar AA, et al. Oral antihistamine-decongestant-analgesic combinations for the common cold. Cochrane Database Syst Rev. 2012;2:CD004976.

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15

Impact of a fixed-dose combination strategy on adherence and risk factors in patients with or at high risk of CVD
Fixed-dose combinations (FDCs) of drugs for the treatment of blood pressure (BP), cholesterol, and platelet control signicantly improve long-term adherence in patients with or at high risk of cardiovascular disease (CVD) when compared to usual care, suggests the investigators of the UMPIRE trial. Majority of the patients with CVD fail to adhere to long-term therapy. Previously published studies have evaluated the short-term effects of FDCs in comparison to placebo or no treatment. Thus, the objective of the UMPIRE trial was to assess whether treatment with FDC comprising of aspirin, statin, and two antihypertensive drugs improves longterm adherence (dened as self-reported use of antiplatelets, statins, and 2 antihypertensives) and changes in systolic blood pressure (SBP) and low-density lipoprotein cholesterol (LDL-C) from baseline. In this randomized, open-label, blinded-end-point trial, participants with established CVD or at risk of CVD (n=2004) were randomly treated with either of the following FDC-based strategies (1:1): 75 mg aspirin, 40 mg simvastatin, 10 mg lisinopril, and 50 mg atenolol (n=1002) (or) 75 mg aspirin, 40 mg simvastatin, 10 mg lisinopril, and 12.5 mg hydrochlorothiazide Usual care (n=1002) Antiplatelets, statins, and 2 antihypertensives were used in 1233 participants. At baseline, the mean BP was 137/78 mmHg and LDL-C was 91.5 mg/dL. After a median follow-up of 15 months, medication adherence was signicantly high with FDC when compared to usual care (86% vs. 65%; p<0.001). In addition, signicant reduction was observed in SBP (2.6 mmHg; p<0.001) and LDL-C (6.6 to 1.9 mg/dL; p<0.001) at the end of the study. In predened subgroups (n=727), evidence existed of larger benets in patients with lower adherence at baseline. At the end of the study, medication adherence was 77% (p<0.001) and SBP and LDL-C reduced by 4.9 mmHg (p=0.01) and 6.7 mg/dL (p=0.11) respectively. There were no signicant differences in serious adverse events or cardiovascular events in patients treated with FDC or usual care.
Thom S, Poulter N, Field J, et al. UMPIRE Collaborative Group. Effects of a fixed-dose combination strategy on adherence and risk factors in patients with or at high risk of CVD: The UMPIRE Randomized Clinical Trial. JAMA. 2013;310(9):918929.

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J O U R N A L

SCANS

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High glucose level increases risk of dementia in individuals with or without diabetes
Diabetes is a risk factor for dementia. However, it is not known whether patients without diabetes are also at high risk for the development of dementia. A team of US researchers examined the association between glucose levels and the risk of dementia in subjects without dementia (n=2067). Out of 2067 subjects, 232 participants had diabetes. During the study period, 35,264 clinical measurements for glucose levels and 10,208 measurements for glycated hemoglobin levels were performed to assess the relationship between glucose levels and the risk of dementia. The Cox regression model stratied patients according to diabetes status and adjusted for age, sex, study cohort, educational level, level of exercise, blood pressure, status with respect to coronary and cerebrovascular diseases, atrial brillation, smoking, and treatment for hypertension. Based on the below clinical ndings, the study researchers opined that higher glucose levels increase the risk of dementia irrespective of the presence or absence of diabetes mellitus. Clinical ndings After a median follow-up period of 6.8 years, dementia was observed in 74 subjects with diabetes and 450 subjects without diabetes. The risk of dementia signicantly (p=0.01) increased with increase in average glucose levels in the preceding 5 years in subjects without diabetes. The risk of dementia signicantly (p=0.02) increased with increase in average glucose levels among participants with diabetes.

Impact of esomeprazole on sleep disturbances in patients with GERD

Sleep disturbance is usually seen in patients with gastrooesophageal reux disease (GERD); however, there is no much data to support the same in patients already receiving drug therapy for GERD. A cluster-randomized, open-label study assessed the sleep problem through a questionnaire-based test (PASS test) and evaluated the efcacy of esomeprazole in improving sleep disturbances in patients with GERD. In this primary carebased study, subjects were divided into two groups: Intervention group and control group. Patients who failed in the PASS test continued with the control group (current treatment) or switched to the intervention group (esomeprazole 20 or 40 mg/day for 4 weeks). At the end of the treatment, study outcomes were assessed based on sleep questions, which were extracted from the Quality of Life in Reux and Dyspepsia (QOLRAD) questionnaire. The PASS questionnaire was used to evaluate the presence or absence of sleep disturbances. Overall 1388 patients with evaluable data were included in the 4-week analysis. About 825 patients experienced GERD-related sleep disturbance at baseline. A greater number of patients in the control group reported continued sleep disturbances when compared to the intervention group (Figure 1). Furthermore, patients in the intervention group showed improvement in QOLRAD scores associated with sleep when compared to patients in the control group. Researchers concluded that a PASS strategy aids in recognising sleep disturbance in patients with GERD in primary care and may be helpful in modifying acid-suppressive therapy.
Figure 1. Continued sleep disturbance is high in the control group when compared to the intervention group 60 Continued sleep disturbance (%) 50 40 30 20 10 0 Control group Intervention group 22.5 55

Moayyedi P, Hunt R, Armstrong D, et al. The impact of intensifying acid suppression on sleep disturbance related to gastro-oesophageal reflux disease in primary care. Aliment Pharmacol Ther. 2013;37(7):7307.

Avian H7N9 is a communicable virus

An epidemiological investigation study assessed the transmissibility of novel avian inuenza H7N9 virus. The study also aimed to determine its efciency of transmission. The study included 2 patients (father and his daughter), their close

Crane PK, Walker R, Hubbard RA, et al. Glucose levels and risk of dementia. N Engl J Med. 2013;369(6):5408.

Journal scans contacts, and relevant environments. During this research study, clinical data and the history of exposure before the onset of illness were obtained from the patients. Real time reverse transcriptase-polymerase chain reaction (rRT-PCR), viral culture, and hemagglutination inhibition assay methods were used to identify the pathogens. It was observed that the index patient (i.e. father) developed symptoms 5 to 6 days after his last exposure to poultry. Subsequently, his daughter (aged 32 years), who had no known exposure to poultry and provided unprotected bedside care, also developed symptoms 6 days after her last contact with her father. According to the results from laboratory investigations (i.e. genome sequence and phylogenetic trees analysis), the blood samples of both the patients were positive for the same novel avian inuenza H7N9 virus. Further, 43 close contacts of both patients were identied. One had mild illness but had negative results for avian H7N9 by rRT-PCR. All 43 close contacts tested negative for hemagglutination inhibition antibodies specic for avian H7N9. The study researchers concluded that avian H7N9 is a communicable virus and that transmissibility is limited and non-sustainable.
Qi X, Qian YH, Bao CJ, et al. Probable person to person transmission of novel avian influenza A (H7N9) virus in Eastern China, 2013: Epidemiological investigation. BMJ. 2013;347:f4752.

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In patients initially under observation, it is recommended to initiate an antimicrobial treatment.

Wald ER, Applegate KE, Bordley C, et al. Clinical practice guideline for the diagnosis and management of acute bacterial sinusitis in children aged 1 to 18 years. Pediatrics. 2013;132(1):e26280.

High plasma levels of vitamin C and E may increase risk of knee osteoarthritis
A nested case-control study of incident of whole knee radiographic osteoarthritis (WKROA) was performed in cohort of about 3026 men and women aged 50 to 79 years, with a high risk of knee osteoarthritis (OA). Incident cases were those subjects who had knees that were not affected tibiofemoral (TF) or patellofemoral (PF) OA at baseline but developed the condition by the 30-month follow-up visit. Those subjects who did not develop either of the specied OA were included in the control (2 knees per case) group. Assays were conducted at baseline to determine the serum and plasma levels of vitamin C and E. The association of genderspecic tertiles of both these vitamins with incident WKROA was also examined. It was observed that the subjects who were WKROA-free at baseline, but had the highest tertiles of vitamin C had higher incidences of WKROA (adjusted OR=2.20 [95% CI: 1.12 4.33]; p=0.021), when compared with those subjects who had the lowest tertiles of vitamin C. Similar results were obtained for those subjects who were WKROA-free at baseline, but had the highest tertiles of vitamin E (adjusted OR=1.89 [95% CI: 1.023.50]; p=0.042). Therefore, higher levels of serum or plasma vitamin C and E were not associated in providing protection from knee OA, instead can increase the risk for the development of incident knee OA.
Chaganti RK, Tolstykh I, Javaid MK, et al. High Plasma Levels of Vitamin C and E Are Associated with Incident Radiographic Knee Osteoarthritis. Osteoarthritis Cartilage. 2013 Nov 28. pii: S1063 4584(13)01013-3.

Revised guidelines for the diagnosis and management of acute bacterial sinusitis in children
The American Academy of Pediatrics panel analyzed the medical literature published since 2001 and made the following recommendations: In patients with suspected acute bacterial sinusitis, a physician can either initiate the treatment immediately or observe the patient with persistent symptoms for 3 days. The physician should initiate an antimicrobial therapy in patients with severe onset or worsening course of symptoms or continuing illness for 3 days or more. Imaging studies are not recommended to distinguish between uncomplicated acute bacterial sinusitis from viral upper respiratory infections as these do not aid in the diagnosis. Amoxicillin, with or without clavulanic acid, is the recommended rst-line agent in acute bacterial sinusitis. Reassessment of initial therapy should be carried out if further worsening of condition or failure to contain the symptoms is reported within 3 days of starting the initial therapy.

Case in Question

19

A sporadic case of meningoencephalomylitis with malaria and Goldenhar syndrome

Dr. Amol Supe, DNB Medicine Dr. S. Arulrhaj, MD, FRCP, (Glasg)
Chairman & Head Acute Medicine, Sundaram Arulrhaj Hospitals 145/5B, Jeyaraj Road, Tuticorin - 628 002 Tamil Nadu, India

CASE

in

Question

27-year-old male was hospitalized in an unconscious state after he was referred from another private hospital. The patient had convulsions the previous day, abdominal distension and decreased urine output since 2 days, and high grade intermittent fever and headache since 10 days.

Examination
Parameters Pulse Blood pressure Temperature Respiratory rate Cyanosis Clubbing Icterus Lymphadenopathy Pallor and edema Eye Findings 110 beats/min 140/80 mmHg 103oF 38 breaths/min None None None None None Right eye: Dermoid cyst, corneal ulcer, and haziness, F=not able to see (Figure 1) , Left eye: Dermoid cyst F=Normal (Figure 2), EOM=Fixed, Pupil=Normal size not reacting to light Preauricular skin tags on both sides (Figure 3) + + Bilateral crept 80% Distention + S1, S2 sounds were normal. No murmur

Ear DTR Planter Neck rigidity Respiratory system SpO2 Pelvic abdomen Cardiovascular system

Central nervous system Patient was unconscious disoriented

EOM: Extra ocular movement; DTR: Deep tendon reflex; SpO2: Saturation of peripheral oxygen.

20

Case in Question

Figure 1. Right eye with dermoid cyst and corneal ulcer

Figure 2. Left eye with dermoid cyst

Figure 3. Preauricular skin tags

What would be your provisional diagnosis?

a) Meningoencephalitis b) Congenital abnormality

Further investigations
Investigations Hemoglobin Total count Differential count Platelets Blood sugar Blood urea Serum creatinine Serum bilirubin Serum protein Serum alkaline phosphate SGOT SGPT Electrolyte Serum calcium Widal/MP/Dengue/ Chikungunya Blood / Urine culture HIV/ VDRL Chest X-ray ECG USG abdomen ADA MP for Plasmodium falciparum (ICT method) EEG CSF analysis CSF malaria CSF C&S CSF cytology CT brain MRI brain Findings 12 g/dL 8300 Neutrophils 60%, Lymphocytes 35%, Eosinophils 5% 2.8 Lakhs/L 142 mg/dL 36 mg/dL 1.1 mg/dL Direct bilirubin: 0.9 mg/dL, Indirect bilirubin: 0.5 mg/dL, Total bilirubin: 0.4 mg/dL Protein total: 7.3 g/dL, Albumin: 4 g/dL, Globulin: 3.2 g/dL 120 IU/L 28 U/L 11 IU/L Sodium: 136 mEq/L, Potassium: 4.6 mEq/L, Chloride: 95 mEq/L, 8.5 mg/dL Negative Negative Negative Prominent bronchial marking Normal Borderline hepatomegaly 1.4 (Positive) Positive Normal Cell Count: 36 (p-20% L= 80%), Sugar: 79 mg/dL, Protein: 78 mg/dL, Globulin: Positive, Chloride: 120 mEq/L Negative Negative No immature cell Cerebral edema (Figure 4) Mild prominence left ventricle, mild enhancement of leptomeningis seen in temporoparietal region, suggestive of meningitis (Figure 5)

ESR: Erythrocyte sedimentation rate; SGOT: Serum glutamic oxaloacetic transaminase; SGPT: Serum glutamic pyruvate transaminase; MP: Malarial parasite; HIV: Human immunodeficiency virus; VDRL: Venereal Disease Research Laboratory; CSF: Cerebrospinal fluid; MRI: Magnetic resonance imaging; ICT: Immunochromatographic test; ADA: Adenosine deaminase test; EEG: Electroencephalography; CT: Computed tomography

Case in Question Centers for Disease Control Tuberculous meningitis should What do the findings be considered in the differential suggest that tuberculous of CT and MRI of brain meningitis should be treated and CSF test suggest? diagnosis of individuals a) Tuberculous meningoencephalitis

21

presenting with subacute onset of headache and fever. If tuberculous meningitis is suspected, antituberculosis b) Plasmodium falciparum (anti-TB) therapy should be malaria initiated immediately.2 In c) Goldenhar syndrome this case, the patient had headache, fever, and meningeal d) All of the above symptoms such Treatment Final Diagnosis: as neck rigidity (Nuchal rigidity, a The patient Tuberculous pathognomonic was immediately sign of meningeal Meningitis provided irritation) and ventilation, altered mental With Malaria intubated with status suggestive an endotracheal And Goldenhar of tuberculous tube, and treated meningitis. In Syndrome with the following addition, Kernigs drugs: and Brudzinskis signs are also classic signs of meningeal Meropenem irritation. The diagnosis of Antitubercular drugs tuberculous meningitis was further evidenced by ndings Steroids from the MRI scan which Antiepileptics showed mild prominence of Antimalarials the left ventricle with mild enhancement of leptomeninges Other supportive care in temporoparietal region (Figure 5). The American Prognosis Thoracic Society and the The patient showed good prognosis as he became conscious and afebrile without any complaints of seizures or other complications.

with antituberculosis (anti-TB) drugs for at least 1 year. However, the duration of therapy may be extended to another 6 months if the cultures remain positive, if signs/ symptoms do not improve, or if the patient is infected with HIV. Generally, the anti-TB regimen should comprise of at least 3 drugs isoniazid, pyrazinamide, and rifampin. Patients with tuberculous meningitis should also be treated with corticosteroids, especially if they present with any neurologic signs or if they are comatose (Stages II and III).3 In this case, the patient was immunocompetent (ie, HIV test was negative) and was treated with anti-TB drugs and corticosteroids (as the patient was unconscious). Besides tuberculous meningitis, the patient was also diagnosed to have Goldenhar syndrome due to the presence of preauricular skin tags, dermoid cyst, and diminished Continued on page 24

Discussion
Tuberculous meningitis is an infection of the membranes covering the brain and spinal cord (meninges). It is a major global health problem and is the most severe form of extrapulmonary tuberculosis, with a high rate of mortality.1

Figure 4. CT brain showing cerebral edema

Figure 5. Mild prominence of left ventricle with mild enhancement of leptomeninges in temporoparietal region

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Diabetes D Di ab bet etes es a and d Tub Tuberculosis Tu uberc ercul rc culos os sis

Earth

Siege

Diseases that impact our WORLD

well known.3 Numerous studies have reported that the prevalence of diabetes is high among patients with TB when compared to the general population.4 Diabetes not only increases the risk of TB but also increases the risk of treatment failure, death and relapses of TB, suggests Baker and colleagues.1 The Tuberculosis-Diabetes Study Group from India suggests that early screening for diabetes in patients with TB provides opportunities for better management of the comorbidity.5

DIABETES FACTS
About 350 million people are affected by diabetes. India is the diabetes capital of the world with 41 million Indians having diabetes; every fth diabetic in the world is an Indian. It is predicted that the global diabetes prevalence will increase by 50% by the year 2030. The prevalence of diabetes is similar in both high- and lowincome countries. Over 80% of diabetes deaths occur in low and middle income countries.6,7

Dr. A. Rajasekaran, MD, DTCD

Chest Physician Deputy Director of Medical Services (TB) Erode Tamil Nadu, India

Introduction
Globally, tuberculosis (TB) represents a major source of morbidity and mortality.1 Diabetes is another disease that is increasing in prevalence worldwide and is certain to be one of the most challenging health problems in the 21st century, especially in developing countries.2 The association between TB and diabetes mellitus and their synergistic role in causing human disease is

TB FACTS
More than 9 million people are affected by TB every year. Over 1.5 million die from TB every year; the majority of the deaths occur in the developing world. One in three people in the world are infected with latent TB. People infected with latent TB have a lifelong risk of developing and falling sick with active TB.6

Links between TB and diabetes: An interesting fact

The risk of developing active TB is a 2-step process: initial exposure to Mycobacterium tuberculosis and disease progression. 3

Diabetes and Tuberculosis

About 10% of global TB cases are linked to diabetes. The risk of developing TB is 23 times higher in diabetic patients when compared to people without diabetes. The risk of progression of latent to active TB is high in diabetic patients.6,8

23

Diagnosis
Having said that diabetes is an important risk factor for TB, most clinicians do not routinely screen for diabetes due to negligence. The majority of people with diabetes as well as TB are not diagnosed, or are diagnosed too late.6 A team of Indian

WHO recommendations for diagnosis of diabetes in patients with TB All TB patients should be screened for diabetes Screening should be considered, especially in settings with high TB prevalence

Tuberculosis should be suspected in diabetes patients who do not achieve good glycaemic control and have an increasing insulin requirement. Proper screening to rule out TB is mandatory. Diabetes patients on oral hypoglycaemic agents should be switched over to insulin, as it is essential for strict control of hyperglycaemia.

Double burden of TB and diabetes

The combination of TB and diabetes mellitus represents a major global health problem.3 TB might induce glucose intolerance and worsen glycemic control in diabetics. 3 Diabetes worsens the course of TB.4

Diabetes mellitus and

Tuberculosis:
Convergence of two epidemics
researchers evaluated the feasibility of screening for diabetes in patients with TB (n=8269) in more than 60 peripheral health institutions across India. The researchers reported that it is important and feasible to screen for diabetes mellitus in TB patients. Further, the early screening for diabetes provides opportunities for better management of comorbidities.5 Another recent study published in the British Medical Journal reported that the presence of diabetes mellitus alone does not justify screening for and treatment of latent TB infection. However, when combined with other risk factors for TB, the presence of diabetes mellitus may be sufcient to justify screening and treatment of latent TB infection.8

Key points
The risk of developing TB is 23 times higher in individuals with diabetes. All TB patients should be screened for diabetes. Diabetes not only increases the risk of TB but also increases the risk of treatment failure, death and relapses of TB. WHO recommends rigorous therapy in individuals having both diabetes and TB.

Diabetes leads to TB: Understanding the pathophysiology

It is well established that diabetes mellitus is a common chronic disease that is associated with impaired immune function.8 Thus, uncontrolled diabetes not only increases the risk of vascular disease and neuropathic complications but also increases the susceptibility to infections, especially those caused by Mycobacterium tuberculosis. Several mechanisms have been known to play an important role in the pathophysiology of diabetes leading to TB. The mechanisms include those directly affecting hyperglycemia and cellular insulinopenia and those which indirectly affect macrophage and lymphocyte function.3

Treatment and prognosis

Th presence of TB complicates the management of diabetes and hence it is important that proper care for diabetes is provided to those that are suffering from either of these 2 diseases. Diabetes is reported to be associated with poor TB treatment outcomes in TB patients.1 It has also been reported that the risk of death is high during TB treatment and TB relapse after treatment. In view of these complications, the WHO recommends that therapy should be rigorously implemented in individuals having both diabetes and TB.6

References
1. Baker MA, Harries AD, Jeon CY, et al. The impact of diabetes on tuberculosis treatment outcomes: A systematic review. BMC Medicine. 2011;9:81. 2. Singh J. Economic burden of diabetes. Chapter 45. Available at: http://www. apiindia.org/medicine_update_2013/chap45. pdf. Accessed on: 13.9.2013. 3. Dooley KE, Chaisson RE. Tuberculosis and diabetes mellitus: Convergence of two epidemics. Lancet Infect Dis. 2009;9(12):73746. 4. Muruganathan A, Viswanathan V. The double burden of tuberculosis and diabetes in India. Chapter 32. Available at: http://www.apiindia.org/medicine_update_2013/ chap32.pdf Accessed on: 13.9.2013. 5. India Tuberculosis-Diabetes Study Group. Screening of patients with tuberculosis for diabetes mellitus in India. Trop Med Int Health. 2013;18(5):636 45. 6. Tuberculosis & Diabetes. Collaborative framework for care and control of tuberculosis and diabetes Available at: http://www.who. int/tb/publications/diabetes_tb.pdf. Accessed on: 13.9.2013. 7. Joshi SR, Parikh RM. Indiadiabetes capital of the world: Now heading towards hypertension. J Assoc Physicians India. 2007;55:3234. 8. Dobler CC, Flack JR, Marks GB. Risk of tuberculosis among people with diabetes mellitus: An Australian nationwide cohort study. BMJ Open. 2012;2(1):e000666.

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Case in Question
Continued from page 21

eye vision. Goldenhar syndrome was rst reported by Goldenhar in the year 1952.4 This syndrome is characterized by the maldevelopment of the rst and second branchial arches, ocular dermoids, and vertebral anomalies. All three signs have a variable presentation and are considered part of a spectrum of auriculo-vertebral anomalies. Thus, Goldenhar syndrome is also known as oculoauriculovertebral syndrome. The exact cause for Goldenhar syndrome is unknown. Its occurrence is sporadic in nature but many familial cases have also been identied.5 Ocular manifestations, ear anomalies, and vertebral defects are the major clinical features of

Goldenhar syndrome. Ocular and ear manifestations include reduced visual acuity and preauricular tags and/or pits. In the present case, preauricular skin tags and dermoid cysts were observed. Surgical interventions such as the removal of epibulbar dermoids, repair of cleft lip/palate, combined surgical-orthodontic approach for dental occlusion, and distraction osteogenesis are methods that are employed in the management of Goldenhar syndrome.6 The immunochromatographic (ICT) test for Plasmodium falciparum was positive, and hence the patient was diagnosed to have malaria

also and was treated with antimalarial drugs accordingly. At the time of discharge, the patient was stable without any complications.

References
1. Mucaj S, Dreshaj S, Kabashi S, et al. Tuberculous meningoencephalitis. Med Arh. 2010;64(3):18990. Nozaki H, Koto A, Amano T, et al. Clinical features of 10 cases of tuberculous meningitis--with special reference to patients delay and doctors delay. Kekkaku. 1996;71(3):23944. Byrd T, Zinser P. Tuberculosis meningitis. Curr Treat Options Neurol. 2001;3(5):427 432. Maan MA, Saeed G, Akhtar SJ, et al. Goldenhar syndrome: Case reports with review of literature. Journal of Pakistan Association of Dermatologists. 2008;18: 5355. Anderson PJ, David DJ. Spinal anomalies in Goldenhar syndrome. Cleft Palate Craniofac J. 2005;42(5):47780. Chen H. Goldenhar syndrome. In: Atlas of Genetic Counseling and Diagnosis. 2nd ed. USA: Springer; 2012.

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Highlights
A meta-analysis shows that depression is associated with low concentrations of zinc in peripheral blood. Biol Psychiatry. 2013;74:872-878. Slow Eating Might Help Curb Calories. Study found some people consume more when meals are rushed. J Acad Nutri Diet Jan, 2, 2014, Statin medication use in postmenopausal women is associated with an increased risk for diabetes mellitus. Arch Intern Med. 2012 Jan 23;172(2):144-52.