Fixed dose combination of aspirin and pantoprazole: Results of a multicenter, comparative, randomized, double-blind, double dummy, phase III study in Indian patients.

OBJECTIVE: To compare the efficacy and safety of a fixed-dose combination of aspirin and pantoprazole with that of aspirin alone for the prevention of gastro duodenal mucosal damage in patients taking aspirin for secondary prevention of cardiovascular disease or cerebrovascular disease. METHODS: This was a comparative, double-blind, double-dummy, randomized, multicenter, phase III study conducted in patients taking aspirin ≤150 mg daily for ≥3 to ≤6 months and expected to require daily aspirin therapy for at least 6 months for the secondary prevention of cardiovascular disease or cerebrovascular disease. RESULTS: A total of 240 patients were randomized to receive either a fixed-dose combination of aspirin 150 mg and pantoprazole 20 mg or aspirin 150 mg alone in a 2:1 ratio. The proportion of non-responders (patients experiencing gastroduodenal events) was 9.7 % in the test group (fixed-dose combination of aspirin 150 mg and pantoprazole 20 mg) compared to 19.7 % in the comparator group (aspirin 150 mg) at week 12, while the proportions were 11.0 % in the test group and 22.4 % in the comparator group at the end of 24 weeks of treatment (p-value was <0.05 at week 12 and 24). GI injuries were significantly less in test group as compared to comparator group. Both drugs were well tolerated by all patients. CONCLUSION: The fixed-dose combination of aspirin 150 mg and pantoprazole 20 mg was found to be more efficacious and safer compared to aspirin 150 mg alone for the prevention of gastroduodenal mucosal damage in patients receiving aspirin.

Efficacy and Safety of Orally Administered Acotiamide Extended-Release Tablets Among Functional Dyspepsia-Postprandial Distress Syndrome Patients: A Randomized, Double-Blind, Multicenter Study.

BACKGROUND: Acotiamide, is the world's first-in-class, prokinetic drug and world's first approved treatment for postprandial distress syndrome (PDS) symptoms of functional dyspepsia (FD). An extended-release (ER) formulation of this drug product, developed first-time in the world has been evaluated in phase 3, a comparative trial to explore the efficacy and safety in patients with FD-PDS. METHODS: In this study, 219 patients with FD-PDS aged 18-65 years were randomized (1:1) to receive either acotiamide ER 300 mg once daily or acotiamide 100 mg three times daily for four weeks. The primary efficacy endpoint was responder rates for the overall treatment effect (OTE) at end of week 4. Secondary efficacy endpoints included OTE at each week, elimination rate of postprandial fullness, upper abdominal bloating and early satiation, improvement of individual symptom scores, and quality of life (QoL). The safety endpoints included assessments of treatment-emergent adverse events (TEAEs). RESULTS: The responder rate for OTE at the end of the four week period, in acotiamide ER 300 mg OD versus acotiamide 100 mg TID group was 92.66% and 94.39% (97.5% CI -8.3,4.8), respectively, in per-protocol (PP) population and 92.66% and 92.73% (97.5% CI -7.0,6.8), respectively, in intent to treat (ITT) population. All other secondary efficacy endpoints, including QoL, were significantly improved with acotiamide ER 300 mg. Both the formulations of acotiamide significantly improved symptom severity and eliminated meal-related symptoms in patients with FD. Adverse events were reported by 7.9% of patients in acotiamide ER 300 mg and 9.2% in acotiamide 100 mg patients; the most common adverse event reported was a headache. CONCLUSIONS: The efficacy and safety of acotiamide ER 300 mg once daily were observed to be comparable to acotiamide immediate release 100 mg thrice daily. A significant improvement in QoL over a four-week treatment period in FD-PDS patients was observed.

Glycemic Status at the Time of Presentation in Acute Organophosphorous Poisoning and its Correlation with Severity and Clinical Outcome.

BACKGROUND: Organophosphorus insecticides (OPI) are one of the most extensively used classes of insecticides. Huge scientific body of evidence suggests that OPI exposure is a major toxicological threat that may affect human and animal health because of their various toxicities such as neurotoxicity, endocrine toxicity, immunotoxicity, reproductive toxicity, genotoxicity and ability to induce organ damage, alterations in cellular oxidative balance and disrupt glucose homeostasis. Mortality among organophosphorous (OP) poisoning patients despite advancements in its management is of concern.Of the various contributing factors,extremes and fluctuation in the glycemic status is a well documented parameter affecting the outcomes in critical illness although studies with respect to OP poisoning are deficient. All varieties of glycemic changes from hypoglycemia to hyperglycemia and ketoacidosis in OP poisoning along with other toxicological effects are reported,studies corroborating these findings are only few. The present endeavor was undertaken to study various glycemic changes in acute OP poisoning and it's bearing on clinical severity and clinical outcome. AIMS AND OBJECTIVES: 1. To assess the glycemic status by estimating random blood glucose level at the time of admission in cases of acute organophosphorous poisoning 2. To assess severity of the poisoning with various poisoning scales(PSS and POP) and level of serum pseudocholinesterase. 3. To correlate the documented blood glucose level with the severity and clinical outcome. METHOD: A prospective analytical study of 100 patients with diagnosed acute poisoning, above the age of 18 years, non diabetic, with no history of mixed poisoning or condition affecting blood glucose levels and fulfilling the inclusion and exclusion criterias was done over a period of one year. The glycemic status at the time of presentation was documented and the patients were grouped into hypoglycemics, euglycemics and hyperglycemics and the same was correlated with the severity and clinical outcome using descriptive statistics, association and test of significance using MedCalc. RESULTS: A prospective analytical study of 100 patients of acute organophosphate poisoning was done and on the basis of blood glucose levels at the time of presentation were further categorised into hypoglycemics (37%), euglycemics (52%) hyperglycaemic (11%). The outcome in terms of mortality was 59.45%,9.6% and 63.63% in the respective groups. The ventilator requirements among the three groups were 94.59%,53.84% and 100% respectively. Chisquare test to study the association between the presentation Random Blood Glucose (RBG) and the established Peradeniya Organophosphorous Poisoning Scale (POP) (Table 1) and Poisoning Severity Scale (PSS) (Table 2) revealed the study to be statistically significant (p value= 0.001)indicating both the extremes of glycemic status are associated with higher clinical severity and poorer outcomes. CONCLUSION: We conclude that the glycemic status at the time of presentation in acute organophosphate poisoning patients is a simple, cheap, reliable marker in guiding the clinical severity and outcome when considered with clinical severity scores and S.ChE in a resource limited country like India.

Challenges in the successful management of a case of acute intermittent porphyria in India.

Acute intermittent porphyria (AIP) is a rare metabolic disease involving a defect in haem biosynthesis resulting in the accumulation and excessive secretion of porphyrins and its precursors. Acute attacks present with episodes of severe abdominal pain, nausea, confusion and severe life-threatening seizures. A high index of suspicion is required for the initial diagnosis of AIP.

Cirrhosis: an unusual presentation of sickle cell disease.

Hepatobiliary complications of sickle cell disease are relatively rare but well recognised in literature. Clinical syndromes range from mild intrahepatic cholestasis and gallstones to life threatening sequestration crisis. Most patients, homozygous for sickle cell anaemia, present before adolescence. We report a case of an adult man with no prior symptoms who presented for the first time with decompensated cirrhosis, which was found to be due to underlying previously unrecognised sickle cell anaemia.

Acute multiple cranial neuropathy: An oculopharyngeal variant of Guillain-Barré Syndrome.

We report the case of a 20-year-old male who presented to us with acute bilateral multiple cranial neuropathy in the form of bilateral total ophthalmoplegia and bulbar dysfunction. The patient had normal haematological and biochemical investigations, however, cerebrospinal fluid (CSF) analysis showed raised protein (96mg/dl) in the second week of illness. Peripheral nerve conduction studies and an MRI of the brain were normal. The patient showed gradual improvement after three weeks of supportive treatment. Considering the course of illness and the clinical and investigational profile, a diagnosis of an oculopharyngeal variant of Guillain-Barré syndrome (GBS) was made.

Atypical neuroimaging in Wilson's disease.

Wilson's disease is a rare metabolic disease involving copper metabolism. Neuroimaging plays an important part in evaluation of patients with a neuropsychiatric presentation. We present a case of a 14-year-old girl with atypical confluent white matter disease and cystic degeneration on MRI, with a rapidly progressive course, who succumbed to complications despite treatment with trientine. Wilson's disease should be considered as a differential for leucoencephalopathy in young patients with progressive neurological disease for its early recognition and optimum outcome.

Serotonin syndrome versus neuroleptic malignant syndrome: a challenging clinical quandary.

Serotonin syndrome and neuroleptic malignant syndrome are two drug toxidromes that have often overlapping and confusing clinical pictures. We report a case of a young man who presented with alteration of mental status, autonomic instability and neuromuscular hyperexcitability following ingestion of multiple psychiatric and antiepileptic medications. The patient satisfied criteria for serotonin syndrome and neuroleptic malignant syndrome, and based on the characteristic clinical features, laboratory findings and clinical course it was concluded that the patient had both toxidromes. The patient was managed with cyproheptadine and supportive measures, and recovered over the course of 3 weeks. A brief review of literature highlighting the diagnostic clues as well as the importance of recognising and distinguishing the often missed and confounding diagnoses follows.

Cardiovascular disease and menopause.

AIM: The aim of the study was to study the abnormalities in the cardiovascular profile in postmenopausal Indian women and to compare the same with the cardiovascular profile of pre menopausal Indian women belonging to the same age group; taken as controls. The goal was to throw some light on the cardiovascular risk in postmenopausal women of the Indian population as this population is thought to be at higher risk than their western counterparts and significant studies of the same kind in this population have been few. MATERIALS AND METHODS: A cross-sectional comparative study on 100 women who were either postmenopausal or premenopausal and were between the age group of 40 to 55 years was carried out over a period of ten months at our hospital. The variations in the cardiovascular profile between both groups were studied. All the women were subjected to a detailed history, thorough examination, investigations and imaging studies. RESULTS: The evaluation revealed that Coronary Artery Disease (CAD), hypertension, abnormal Body Mass Index (BMI) and abnormal Waist Hip Ratio (WHR) were significantly higher in the postmenopausal group as compared to the premenopausal group. The post menopausal women had significantly higher prevalence of abnormal lipid profiles as compared to their premenopausal counterparts. The postmenopausal women with a normal lipid profile also had increased prevalence of CAD and SAHT, which emphasizes the non-lipid cardiovascular benefits of estrogen. CONCLUSION: Thus, we can conclude that cardiovascular disease was more common in postmenopausal women of age group 40-55 years as compared to those not yet achieved menopause in a population of western Indian women. And this risk was significantly associated with central obesity, an abnormal lipid profile and the postmenopausal state in itself.

Non-Alcoholic Fatty Liver Disease (NAFLD) in Obesity.

BACKGROUND AND OBJECTIVES: Limited studies have been undertaken to characterize Non-Alcoholic Fatty Liver Disease (NAFLD) in the Indian population. The main objective of our study was to document the prevalence of NAFLD amongst a cohort of obese Indian patients and demonstrate its relationship with other components of the metabolic syndrome. METHODS: A total of 60 adult obese patients were subjected to a detailed history, clinical exam, anthropometric study and laboratory workup. Focus was on liver function and components of the metabolic syndrome like blood pressure, glycemic status and lipid profile. Subjects enrolled were divided into two groups Group A (n=48), with NAFLD and Group B (n=12) without NAFLD. The two groups were then compared amongst themselves as well as with data from previous similar studies. RESULTS: A comparison of the anthropometric measurements revealed a statistically significant difference between the Body mass index (BMI) and Waist Hip Ratio of the two groups and in the mean triglyceride values between the two groups. Although the mean bilirubin levels measured in the serum were not statistically different the mean levels of SGOT and SGPT in the two groups was found to be statistically significant. On the contrary no significant difference in the values of alkaline phosphatase and synthetic liver functions could be discerned. A statistically highly significant difference in the mean liver span is seen. INTERPRETATION AND CONCLUSIONS: NAFLD is common in Indian obese populations and is associated with significant differences in anthropometric, clinical, laboratory and ultrasonographic aspects as compared with obese individuals not affected with liver disease.

Widespread bullous fixed drug eruption.

A 53-year-old man developed a widespread erythematous eruption which rapidly evolved into fluid-filled bulla mostly involving the distal areas of all four limbs and erosions on the oral as well as anogenital mucosa. Based on clinical presentation, chronology of drug exposure, past events and histopathology as diagnosis of widespread bullous fixed drug eruption was made over Steven Johnson-toxic epidermal necrolysis syndrome. Steroids were deferred and the lesions healed with minimal pigmentation within a week. Differentiating between the two entities has been historically difficult, and yet can have significant therapeutic and prognostic implications.

Pseudohypoparathyroidism, rare cause of hypocalcaemia!

Pseudohypoparathyroidism is a rare disorder which is characterized by end organ parathormone resistance, which causes hypocalcaemia, hyperphosphataemia and high parathormone levels. We are reporting here case of a young male who had symptoms of chronic hypocalcaemia, with a positive Trousseau's and Chvostek's sign on examination, without any features of Albright's hereditary osteodystrophy. Lab investigations revealed low calcium, high phosphate and high PTH levels. The patient was diagnosed as having Pseudohypoparathyroidism and he was treated successfully with Calcium and Vitamin D supplements.

Bardet biedel syndrome: a very rare entity in India.

Bardet Biedel Syndrome (BBS) is a rare autosomal recessive disease which is characterized by obesity, retinitis pigmentosa, polydactyly, neuro-developmental retardation and renal defects amongst others. It is a genetically heterogeneous ciliopathic disorder with inter and intra familial variations. Very few cases have been reported from India. We are reporting here a case of an adolescent girl who was diagnosed at the age of 16, with additional features of insulin resistance and non-alcoholic fatty liver disease. A review of recent literature and a short discussion on the care and management of this uncommon condition follow.

Diabetic ketoacidosis: an unusual presentation of acromegaly.

Secondary diabetes mellitus is known to occur in acromegaly due to insulin resistance caused by growth hormone excess. However, diabetes in acromegaly usually does not lead to ketosis. We describe an unusual case of a patient that presented with diabetic ketoacidosis in the emergency room with thirst, polyuria and dyspnoea. The patient was subsequently diagnosed with a growth hormone-secreting pitutary macroadenoma as the underlying pathology; after initial stabilisation with insulin and fluids, the patient was successfully treated with trans-sphenoidal surgery.

A study on prevalence of thyroid auto-immunity in type 1 diabetes mellitus.

Type 1 diabetes mellitus is an auto-immune disease. It is associated with other auto-immune endocrine disorders and auto-immune impairment of non-endocrine tissue. Auto-immune thyroid disease is one of the most frequent auto-immune diseases associated with it. Hypothyroidism can decrease insulin requirement in such patients and hyperthyroidism may cause glucose intolerance. This study attempts to review this concept and detect overt and subclinical forms of auto-immune thyroid disease in type 1 diabetics and to find its correlation with age, sex and duration of diabetes. Fifty type 1 diabetes mellitus patients were selected from SSG Hospital, Vadodara between April 2007 and September 2008. After detailed history and examination, haemogram, urine analysis, fasting and 2-hour postprandial blood glucose level, serum free T4, TSH and antithyroid peroxidase antibody level were performed. The prevalence of auto-immune thyroid disease in type 1 diabetics was 60% with 40% having thyroid disorders (24% overt hypothyroidism, 8% subclinical hypothyroidism and 8% hyperthyroidism). Patients who were females (70% versus 53% in males), older (53.3% in 15-20 years age group versus 71% in 25-30 years age group), had a longer duration of diabetes (25% in those with the disease for <2 years and 100% in those >6 years) were more likely to have auto-immune thyroid disease than their counterparts. Thyroid auto-immunity is frequently associated with type 1 diabetes mellitus and patients should undergo antibody screening to detect the same and to find out assosiated undiagnosed thyroid dysfunction.

A rare case of plasma cell leukemia in a 35 year old.

Plasma cell leukemia is a rare, aggressive form of multiple myeloma. A 35-year-old male presented with backache, generalized weakness, and facial puffiness. His complete blood count showed anemia and a high WBC count with atypical cells on peripheral smear. Bone marrow examination showed more than 90% of atypical plasma cells, confirming a diagnosis of plasma cell leukemia. Patient also had azotemia, hypercalcemia, and hyperuricemia. The patient was started on chemotherapy along with supportive care. Patient improved dramatically and he was discharged on regular follow-up.