Safety and efficacy of liraglutide in patients with type 2 diabetes with elevated liver enzymes: individual patient data meta-analysis of the LEAD programme

BackgroundFatty liver disease has reached epidemic proportions in type 2 diabetes. Glucagon-like peptide-1 (GLP-1) analogues are licensed for treatment of type 2 diabetes, yet little data exist on efficacy and safety in liver injury. We aimed to assess the safety and efficacy of 26 weeks' liraglutide on liver function compared with an active placebo.MethodsIndividual patient data meta-analysis was done with patient level data combined from six 26-week, phase 3, double-blind randomised controlled trials on type 2 diabetes, which comprise the Liraglutide Effect and Action in Diabetes (LEAD) programme. In addition, the LEAD-2 sub-study was analysed to assess the effect on CT-measured hepatic steatosis.FindingsOf 4442 patients analysed, 2241 (50·8%) had an abnormal alanine aminotransferase (ALT) at baseline (mean 33·8 IU/L [SD 14·9] in female participants; 47·3 [18·3] in male participants). Liraglutide 1·8 mg reduced ALT in these patients compared with placebo (?8·20 vs ?5·01 IU/L, p=0·003), and was dose dependent (no significant differences vs placebo with liraglutide 0·6 or 1·2 mg). This effect was lost after adjustment for liraglutide's effect on reduction of weight (corrected mean ALT difference vs placebo ?1·41 IU/L, p=0·21) and HbA1c (corrected mean ALT difference vs placebo 0·57 IU/L, p=0·63). Adverse effects with 1·8 mg liraglutide were similar between patients with and without baseline abnormal ALT. In the LEAD-2 sub-study, liraglutide 1·8 mg (26 weeks) improved hepatic steatosis (CT-measured liver:spleen attenuation ratio) from baseline (0·10, p=0·001) and showed a trend towards improvement compared with placebo (0.10 vs 0·00, p=0·07).Interpretation26 weeks of liraglutide (1·8 mg) is safe, well tolerated, and improves liver enzymes compared with placebo in patients with type 2 diabetes.FundingWellcome Trust.     

猪嵴病毒福建株全基因克隆及序列分析

目的为研究猪嵴病毒（porcinekobuvirus,PKV）福建株的基因组结构特征。材料与方法根据猪嵴病毒基因组特征设计特异性朝物,运用RT—PCR方法,对猪嵴病毒福建株进行全基因克隆,并运用RACE方法对猪嵴病毒福建株的5,和3’末端进行扩增。结果与结论所获得的猪嵴病毒福建株基因组全长为8210bp,其5’末端长度为576bp·3’末端长度为167bp,编码一个大的多聚蛋白,长度为7467bp,编码2488个氨基酸。其多聚蛋白核苷酸同源性和我国猪嵴病毒分离株cH／HNxx-4／2012（GenBank登录号JX401523）同源性最高,均为89．2％,和匈牙利猪嵴病毒分离株swine／S—1-HUN／2007／Hungary（GenBank登录号（GenBank登录号EU787450）同源性最低,达87．6％。     

Vaginal trichomoniasis among HIV patients attending primary health care centers of Jos,Nigeria

ObjectiveTo determine the prevalence of trichomonal infection in HIV/AIDS and non-HIV control group of patients in a population of women with abnormal vaginal discharge.MethodsWe conducted a simple cross-sectional study. Primary health care centers in Jos metropolis and Jos University Teaching Hospital, during December 2006 to December 2007. Seven hundred high vaginal swabs were collected; 350 from HIV positive and another 350 from HIV-negative control group of patients with abnormal vaginal discharge attending primary health care centers in Jos metropolis and analysed for microscopy and culture in Jos University Teaching Hospital. Data on epidemiologic indices from the patients, using structured interviewer-administered questionnaires were collected.ResultsThe rate of trichomoniasis among all participants in the study was 17% (n=120/700). The prevalence rate of trichomoniasis among persons with HIV was 24% while it was found to be 10.3% among HIV negative controls. The difference was statistically significant (χ² =23.172; df=1; P<0.05). The rate of co-infection of Trichomonas vaginalis (T. vaginalis) in bacterial vaginosis was 42% (n=50/120), while it was 24% (n=29/120) in candidiasis. The singles had a 35% high rate of trichomonal infection. The infected women had a median age of 26 years, and a median number of 3 intra-vaginal sex partners per week.ConclusionsThere was a significant statistical difference in prevalence of T. vaginalis between HIV/AIDS group and non-HIV(control) group of patients in the study (P<0.05). Local HIV prevention strategies should target such women with trichomonal infection for intervention efforts, especially in HIV endemic area of sub-continent of Africa to further reduce the burden of HIV in the population.     

Maturation of the lower oesophageal sphincter in the preterm baby.

There are few reported studies of the lower oesophageal sphincter in preterm infants and none has investigated babies of less than 34 weeks gestation. Using a modified manometric technique suitable for use on very low birth weight infants we have measured sphincter pressures on 68 occasions in 25 infants of postconceptional age between 27 and 41 weeks. In even the most preterm infants the lower oesophageal sphincter could be defined. The mean effective sphincter pressure rose from 3.8 mmHg in infants of less than 29 weeks gestation to 18.1 mmHg in the term infant. This rise in effective sphincter pressure correlated well with increasing postconceptional age (r = 0.81). This pattern of maturation in our patients was unaffected by intrauterine growth retardation, postnatal illness, or concurrent xanthine administration.     

Neonatal gut function, measured by the one hour blood D (+) xylose test: influence of gestational age and size.

D(+) Xylose absorption, assessed by one hour blood xylose levels, has been measured after intraduodenal infusion of the sugar in 35 infants of differing gestational age and size. The test was performed between the 2nd and 6th days of life. Full-term appropriately grown infants had higher blood xylose levels (1.41+/-0.07 mmol/l) at one hour than pre-term appropriately grown infants (1.17+/-0.07 mmol/l; P less than 0.05), or 'light for dates' infants, both full-term (0.73+/-0.06 mmol/l; P less than 0.001) and pre-term (0.96+/-0.17 mmol/l; P less than 0.05). Serial studies of 11 infants were made two to five times between the 3rd and 20th day of life. The levels for one hour xylose rose in all groups, but the 'light for dates' infants showed the least rise. There was no sign of catch-up in this group, and some results appeared to fall further behind those of appropriately grown infants. These results suggest that the primal small intestine is maturing in the perinatal period, and that intrauterine growth retardation may impair intestinal absorption. The nutritional significance is not known.     

Monitoring transfusionist practices: a strategy for improving transfusion safety

BACKGROUND: Data from New York State indicate that about 1 of every 33,000 red cell units transfused is ABO-incompatible with the recipient. National application of these data suggests that as many as 360 ABO-incompatible whole blood and red cell transfusions might occur annually in the United States. Phlebotomy and blood bank laboratory errors cause some of these ABO-incompatible transfusions, but the greatest number result either partially or solely from the failure of transfusionists to identify properly either a patient or the blood component a patient receives. STUDY DESIGN AND METHODS: A quality assessment/quality improvement (QA/QI), process is described that allowed for the direct oversight (monitoring) of transfusionists' practices and for the assessment of institutional policies for blood administration. RESULTS: At the beginning of the QA/QI process, monitoring of blood administration practices revealed that a variance from institutional blood administration policy occurred during 50 percent of blood and component transfusions. As a result of the QA/QI process, the percentage of transfusions with an associated variance from institutional policy dropped to nearly zero. CONCLUSION: The QA/QI process described in this report, or one similar to it, could improve transfusion safety and serve as a model for increased involvement by transfusion service medical directors in the oversight of transfusionists' practices.     

Postnatal development of disaccharidase activities in jejunal fluid of preterm neonates.

Because human fetuses of 26-30 weeks gestation are known to have low levels of intestinal mucosal lactase activity, it has been assumed that live born preterm neonates of comparable gestational age are also lactase deficient. We have previously shown that disaccharidase activities in jejunal fluid in infants are highly significantly correlated with enzyme activities in the adjacent mucosa. We have now measured disaccharidase activities cross-sectionally and longitudinally in the jejunal fluid of a group of very preterm neonates of 26-29 weeks gestation who were fed with pasteurised human milk. Lactase activity was within the normal range for older infants and children within the first week of life. Sucrase: lactase ratios fell significantly in the second and third weeks of life, strongly suggesting a further increase in lactase activity. This increase was independent of postconceptional age. Preterm neonates are not as lactase deficient as previously believed, and this has implications in the search for optimal feeding regimes.     

Polymorphonuclear leucocyte transfusion in neonatal septicaemia

In one neonatal intensive care unit during a 15 month period 6 infants developed septicaemia which was resistant to antibiotic treatment. The infants' mean gestational age and birthweight were 32.7 weeks and 1519 g respectively. Intravenous infusions of polymorphonuclear leucocytes were given. Three infants died and the remainder survived without complications. No side effects of the treatment were identified.