An Expert Review and Recommendations on the Rational Use of Proton Pump Inhibitors: Indian Perspective.

BACKGROUND: Proton pump inhibitors (PPIs) are the mainstay of treatment for acid peptic diseases (APDs), but are often irrationally prescribed in clinical practice. Appropriate prescription of PPIs is needed to optimize outcomes, and minimize risks and cost burden on the healthcare system. OBJECTIVE: To review available literature on efficacy and safety of proton pump inhibitors (PPIs) and give recommendations for rational use of PPIs from an Indian perspective. METHODS: Twelve healthcare professionals (9 gastroenterologists, 1 cardiologist, 1 orthopedist, 1 clinical pharmacologist) comprised the expert group; members disclosed conflicts of interest. The creation of the expert review was through a process that included meetings (in-person, online, telephone) where each professional contributed their experiences with regards to efficacy and safety of PPIs. Articles published between the years 2000 and 2017 were reviewed for evaluation of safety and efficacy of PPIs in treatment of various APDs. CONCLUSION: This expert review provides key recommendations for decision making in order to minimize the irrational use of PPIs. Some significant recommendations include: patients with GERD and acid-related complications should take a PPI for minimum 12 weeks for healing of esophagitis, and for maximum up to 48 weeks for symptom control. Patients with Barrett's esophagus should take long-term PPI. Patients at high risk for ulcer-related bleeding from NSAIDs including aspirin should take a PPI if they continue to take NSAIDs. Best practice recommendations are meant to merely assist with decision making in conjunction with patients' clinical history, and are not intended to dictate mandatory rules.

Brain heparan sulphate proteoglycans are altered in developing foetus when exposed to in-utero hyperglycaemia.

In-utero exposure of foetus to hyperglycaemic condition affects the growth and development of the organism. The brain is one of the first organs that start to develop during embryonic period and glycosaminoglycans (GAGs) and proteoglycans (PGs) are one of the key molecules involved in its development. But studies on the effect of hyperglycaemic conditions on brain GAGs/PGs are few and far between. We, therefore, looked into the changes in brain GAGs and PGs at various developmental stages of pre- and post-natal rats from non-diabetic and diabetic mothers as well as in adult rats induced with diabetes using a diabetogenic agent, Streptozotocin. Increased expression of GAGs especially that of heparan sulphate class in various developmental stages were observed in the brain as a result of in-utero hyperglycaemic condition but not in that of adult rats. Changes in disaccharides of heparan sulphate (HS) were observed in various developmental stages. Furthermore, various HSPGs namely, syndecans-1 and -3 and glypican-1 were overexpressed in offspring from diabetic mother. However, in adult diabetic rats, only glypican-1 was overexpressed. The offsprings from diabetic mothers became hyperphagic at the end of 8 weeks after birth which can have implications in the long run. Our results highlight the likely impact of the in-utero exposure of foetus to hyperglycaemic condition on brain GAGs/PGs compared to diabetic adult rats.

Effect of pathological conditions on peritoneal macrophage glycosaminoglycans: Impact on cytoadherence.

Glycosaminoglycans (GAGs) have a plethora of functions to play. They are widely present in extracellular matrix, cell surface and inside the cell. During pathological conditions remodeling of GAGs leads to modifications in their structure and functions. In the present work, peritoneal macrophages were isolated from normal, diabetic, and diet-induced hypercholesterolemic rats and evaluated in terms of GAGs and cytoadherence to various extracellular matrix (ECM) components. Peritoneal macrophages are known to play important roles in the control of infection and inflammation. Isolated GAGs were characterized as belonging to heparan sulfate/heparin class. There were quantitative changes in sulfated GAGs in diabetic and hypercholesterolemic groups when compared to normal rats. Dose-dependent changes in cytoadherence were observed only with respect to fibronectin in LPS-activated macrophages from diabetic animals but not with laminin and type IV collagen when compared to macrophages from normal rats. Cytoadherence was significantly decreased on treatment with heparinase indicating that cytoadherence was at least partly mediated by heparan sulfate/heparin class of GAGs. Global disaccharide composition analysis showed that GAGs from macrophages of diabetic animals had higher sulfation ratio when compared to that of control and hypercholesterolemic animals.

Single-center experience with drug-induced liver injury from India: causes, outcome, prognosis, and predictors of mortality.

OBJECTIVES: Although drug-induced liver injury (DILI) is rare, it may result in significant morbidity or death. The causes and outcome vary according to regions, with acetaminophen and complementary medicines common in the West and the Far East, respectively. This study evaluates the causes, outcomes, predictors, and models for 90-day mortality from DILI from India. METHODS: Consecutive patients with DILI from 1997 to 2008 based on International Consensus Criteria from a medical college hospital setting were studied. RESULTS: Of the 313 patients, 58% were males. Leading causes were a combination of four anti-tuberculous drugs (ATDs) (58%), anti-epileptics (11%), olanzapine (5.4%), and dapsone (5.4%). The overall 90-day mortality of 17.3% was significantly higher for ATD hepatitis (21.5%) vs. those without (11.4%) (P=0.02). The highest mortality was for leflunomide (75%). Seventy-eight percent of patients received more than one drug. Fulminant hepatic failure developed more commonly in females than in males (23% vs. 17%). Of the 66% of cases with jaundice and/or icterus, mortality was 26%. Multivariable models for mortality using a combination of encephalopathy, ascites, and bilirubin, or a combination of albumin, prothrombin time, and white blood cell count yielded a C-statistic of at least 0.86 by recursive partitioning and 0.92 by logistic regression. Model for end stage liver disease (MELD) scores of 38 and 46 yield probabilities of death of 0.90 (confidence interval (CI): 0.71-0.97) and 0.99 (CI: 0.90-1.00), respectively. CONCLUSIONS: DILI results in significant overall mortality (17.3%). ATDs, anti-convulsants, sulphonamides, and olanzapine are the leading causes of DILI. Although common in males, more females developed fulminant hepatic failure. High-MELD score or a combination of ascites, encephalopathy, high bilirubin, prothrombin time, and leukocyte count are predictive of mortality.

Hypercoagulable state in idiopathic ulcerative colitis: role of hyperhomocysteinemia and hyperfibrinogenemia.

BACKGROUND: Previous reports on hypercoagulable factors in inflammatory bowel diseases involve heterogeneous populations and patients on various medications. AIMS: To determine the frequency of thrombotic complications in ulcerative colitis (UC); to evaluate for hyperhomocysteinemia and its relationship to vitamin B12 and folate levels and methylene tetrahydrofolate reductase (MTHFR) mutation; and to evaluate for hyperfibrinogenemia and factor V Leiden mutation. METHODS: Eighty-six adult patients with UC were seen during the study period; 28 of them underwent blood tests and constituted the study population. Patients who received medications that affect these factors were among the 58 excluded. Tests were obtained at baseline and after 2 months during remission. Patients received folic acid in addition to treatment for UC. RESULTS: Vascular thrombotic events were noted in 4 patients during follow up. Hyperhomocysteinemia was detected in 11 (39.3%) patients (controls 15/100, p=0.007). Heterozygous state for MTHFR C677T mutation was found in 5 (17.9%) patients (controls: 0.2% homozygous, 13.6% heterozygous, p>0.05). Plasma homocysteine did not correlate with extent, severity or duration of disease, or with MTHFR C677T heterozygous state, but correlated with serum folic acid level (p=0.003) and BMI (p=0.03). With folate supplementation, homocysteine decreased significantly in patients who had hyperhomocysteinemia at baseline. Hyperfibrinogenemia was detected in 3 patients (none in 100 controls). Plasma fibrinogen was not affected by duration, extent or severity of UC and did not decrease with remission of disease. Only one patient had heterozygous factor V Leiden mutation. CONCLUSION: Vascular thrombosis occurred in less than a fifth of the UC population studied. Hyperhomocysteinemia reversible by folate supplementation and hyperfibrinogenemia were observed, but their contribution and that of factor V Leiden mutation appear to be insignificant.