The presence of two reduced function variants in CYP2C9 influences the acute response to glipizide.

AIMS: To examine whether the presence of two common missense variants in the CYP2C9 gene (rs1799853, encoding Arg144Cys and denoted as *2, and rs1057910, encoding Ile359Leu and denoted as *3) influences the acute physiological response to a single glipizide dose in individuals naïve to diabetes medications. METHODS: In the Study to Understand the Genetics of the Acute Response to Metformin and Glipizide in Humans (SUGAR-MGH), 786 individuals genotyped for rs1799853/rs41291560 (*2) and rs1057910/rs9332214 (*3) were treated with 5 mg glipizide in the fasting state. Glucose and insulin levels were measured at baseline, 30, 60, 90, 120, 180 and 240 min for calculation of phenotypic endpoints of glipizide response. The challenge was aborted as a result of hypoglycaemia, defined as glucose <2.8 mmol/l or hypoglycaemia-related symptoms. RESULTS: Carriers with two reduced function alleles had a 50% larger insulin area under the curve than carriers with zero or one copy (P=0.037), although this finding was primarily driven by an individual with a robust insulin response. In adjusted analyses, the risk of aborting the glipizide challenge was doubled in two-copy carriers (P=0.034). No significant findings were observed in glucose-based endpoints. CONCLUSIONS: Carriers of two reduced function alleles in CYP2C9 may experience an increased insulin response to glipizide and be predisposed to a higher risk of hypoglycaemia, although no effect of genotype was seen in glucose-based measurements. Further studies are needed to clarify the utility of CYP2C9 genotyping to guide sulfonylurea treatment.

Composite endpoints in trials of type-2 diabetes.

Composite endpoints (CEPs) are being used more frequently as outcomes for trials of drugs in type-2 diabetes. We reviewed the literature to determine how CEPs have been used to date in trials of drugs for type-2 diabetes. A systematic search was undertaken on Medline, Embase and Cochrane databases and Clinicaltrials.gov for randomized controlled trials of currently marketed agents including SGLT-2 inhibitors (dapagliflozin), GLP-1 agonists (exenatide, liraglutide) and DPP-4 inhibitors (linagliptin, saxagliptin, sitagliptin and vildagliptin). CEPs used were identified as well as numbers and percentages of patients achieving each. Thirty-six studies were identified that reported results on ≥1 CEP; 15 different CEPs were reported (7 with 2 components, 8 with 3 components). All CEPs addressed goals recommended by the American Diabetes Association (ADA). All included HbA1c<7%; other endpoints measured weight, blood pressure and hypoglycaemic events. Results were obtained for CEPs from 6 months to 2 years. Rates of achieving CEPs decreased with increasing numbers of components and outcomes assessed. CEPs are becoming used as indicators of clinical outcomes in type-2 diabetes trials, but are still not common. More research is required to identify optimal CEPs. Standardization of outcomes and their reporting is needed.

Profile of blood donors and reasons for deferral in coastal South India.

BACKGROUND: A blood transfusion is a life-saving procedure in many instances. An adequate supply of safe blood is ensured by exercising donor deferral criteria and screening for Transfusion Transmitted Infections (TTI). The aim of this paper is to study the profile of blood donors and reasons for donor deferral in coastal South India. METHOD: The study was conducted at a tertiary care hospital in Mangalore. All those who donated between 1 January 2008 and 31 December 2008 were included in the study. Data was collected using a pre-tested semi-structured proforma and analysed using SPSS version 11.5. RESULTS: Most of the donors were under the age of 25 (42.92%). Donors were predominantly male (95.20%). In terms of occupation, most subjects were students (28.01%) followed by businessmen (18.61%). Slightly more than three-quarters of the donors (77.20%) were replacement donors. The main reasons for deferral were consumption of medication in the past 72 hours (15.15%), hypertension (13.18%), a low haemoglobin level (12.34%) and alcohol intake in the past 72 hours (12.20%). Among the TTIs identified, most samples were positive for Hepatitis B surface Antigen - HBsAg (0.87%) or tested positive for Anti-Hepatitis C (HCV antibodies (0.36%). CONCLUSION: From the study it was concluded that the majority of the donor population was young and educated. The reason for donation was mainly replacement rather than voluntary. This issue needs to be addressed by exercising proactive measures to increase the number of voluntary, nonremunerated, low-risk donors.

Outpatient parenteral antibiotic therapy in Singapore.

Outpatient parenteral antibiotic therapy (OPAT) remains in its infancy in Singapore, with the first patients enrolled 4 years ago. Singapore's three largest hospitals, with over 3000 inpatient beds, now have designated and approved OPAT services. This study reviews the demographic, clinical and cost data of all patients enrolled in 2005 to facilitate benchmarking between services in Singapore and abroad and also to identify common needs for further development. In 2005, 225 OPAT enrollments in 208 different patients resulted in 4050 days of OPAT care. Orthopaedic diagnoses constituted 40% of admissions. Vancomycin was the most frequently used antibiotic (34%). The re-admission rate was 8.9%, but complications of OPAT care were only occasionally implicated. An estimated $207,200 was saved by patients despite there being significant financial disincentives to subsidised patients. OPAT is a safe, cost-efficient system that is becoming increasingly accepted in Singapore by patients, clinicians and management. Our three services have evolved independently into very similar practices. There is potential for further innovation, including outreach and carer-delivered dosing. However, major financial disincentives require review.

Incorporation of brewery waste in supplementary feed and its impact on growth in some carps.

Brewery waste (brewer's grains) was used at four different levels (10%, 20%, 30% and 40% w/w) replacing rice bran in fish diet under a semi-intensive culture system and its impact on the growth of catla, Catla catla; rohu, Labeo rohita and mrigal, Cirrhina mrigala, was studied. Growth in terms of body weight gain was maximum in C. catla and L. rohita fed on a diet containing 30% brewery waste in the feed, whereas C. mrigala, fed on a diet containing brewery waste at the above mentioned levels showed poorer growth than the control. A better growth performance was attributed to better absorption and utilization ability.

Puerperal psychosis--analysis of 35 cases.

Thirty-five patients admitted with psychosis either immediately or within six months of delivery were analysed for various risk factors. Primiparity, previous psychiatric history, antenatal complications, caesarean section, perinatal death and female baby were all associated with an increased risk of psychiatric admission, suggesting that psychological stresses do contribute to high psychiatric morbidity in puerperium. Women with history of affective disorder had a much higher risk of psychiatric admissions in the puerperium than those with history of schizophrenia or depressive neurosis.

Exploring the scope for advocacy by paediatricians.

AIMS: To ascertain the type and extent of problems requiring advocacy in paediatrics. To develop an approach for analysing problems according to their root causes and the level of society at which advocacy is needed. METHODS: Nine paediatricians kept detailed clinical diaries for two weeks to identify problems. Classifications were developed to categorise problems by cause and the level of society at which they needed to be addressed. The press was surveyed for one week for childhood issues attracting media attention. RESULTS: 60 problems requiring advocacy were identified. Root causes included failures within agencies, between agencies, and inadequate provision. In addition to advocacy required individually, "political" action was needed at the community level (16 issues), city level (16 issues), and nationally (15 issues). 103 articles were found in the press, these did not relate closely to issues identified by clinicians. CONCLUSIONS: Many opportunities for advocacy arise in the course of daily work. A systematic way of analysing them has been developed for use in planning action. To optimise the health and health care of children, there is a need to train and support paediatricians in advocacy work for local as well as national issues. Ten issues were identified that might be prioritised by paediatricians working on an agenda for action.

A search for the evidence supporting community paediatric practice.

AIM: Controversy exists regarding the evidence base of medicine. Estimates range from 20% to 80% in various specialties, but there have been no studies in paediatrics. The aim of this study was to ascertain the evidence base for community paediatrics. METHODS: Twelve community paediatricians working in clinics and schools in Yorkshire, Manchester, Teesside, and Cheshire carried out a prospective review of consecutive clinical contacts. Evidence for diagnostic processes, prescribing, referrals, counselling/advice, and child health promotion was found by searching electronic databases. This information was critically appraised and a consensus was obtained regarding quality and whether it supported actions taken. RESULTS: Two hundred and forty-seven consultations and 1149 clinical actions were performed. Good evidence was found from a randomised controlled trial or other appropriate study for 39.9% of the 629 actions studied; convincing non-experimental evidence for 7%; inconclusive evidence for 25.4%; evidence of ineffectiveness for 0.2%; and no evidence for 27.5%. Prescribing and child health promotion activities had the highest levels of quality evidence, and counselling/advice had the lowest. CONCLUSIONS: An encouraging amount of evidence was found to support much of community paediatric practice. This study improved on previous research in other specialties because actions other than medications and surgery were included.

Prevalence of tuberculosis in Kishtwar Tehsil of Jammu region in Jammu and Kashmir State.

A study of prevalence of tuberculosis in Kishtwar tehsil of Jammu region was conducted from June 1991 to May 1992. A total of one thousand two hundred ninety-eight rural as well as urban population suffering from various types of lung diseases was studied for prevalence of tuberculosis and a sizeable number (98) of patients were found to be positive of various types of tuberculosis, viz, pulmonary tuberculosis, tuberculous pleural effusion and miliary tuberculosis. Of the population studied 7.55% were found to be positive for tuberculosis and among them 88.76% patients were anaemic and the commonest type of anaemia was normocytic normochromic and normocytic hypochromic. The ESR was raised in almost of all the patients. Of the population, 80.61% were seen to be positive on skiagram chest and 58.16% were found to be positive on other diagnostic tests like Mantoux's tests, sputum for acid-fast bacilli, etc. Mantoux's test was positive in 27.55% cases and sputum was positive in 30.61% cases. All the cases studied were subjected to special investigations. The changes in parameters are consistent with the diagnosis of tuberculosis. Large family size, poverty, excessive smoking, illiteracy, etc, are the major contributing factors.

Sexual and treatment behaviour of STD patients.

PIP: Many individuals infected with STDs have their infections/diseases misdiagnosed and mistreated by people who are not qualified to practice medicine. This paper looks at HIV infection and treatment behavior in India. All STD patients attending the private clinic of a senior dermatologist and venereologist in Varanasi during a 6-month period were interviewed. There were 54 men and 6 women of mean age 27.5 years in the range of 18-52. 40 of the men were younger than age 30 years, while most patients had contracted infection from prostitutes. A fair number of more casual contacts were also reported. Infections among males came from known prostitutes in 22 cases, girlfriends in 13, relatives in 10, and a neighbor in 9. 69% of the men were married, with 40.6% of these men living with their wives at the time of exposure. Viral STDs such as herpes genitalis were common. 20 of the men consulted a qualified venereologist after the first exposure to infection. Indigenous "gupt rog" specialists in sexual medicine attracted the second largest number of patients after first exposure. On subsequent visit, however, none of the men returned to a gupt rog specialist. Good compliance as in the case of primary syphilis, gonorrhea, and non-gonococcal urethritis was probably due to good symptomatic response. Poor compliance in the case of herpes genitalis was probably the result of recurrence and inconvenient treatment regimens.^ieng