Bleeding events and associated factors in a cohort of adult patients taking warfarin in Sarawak,Malaysia

Evidence is emerging that rates of adverse events in patients taking warfarin may vary with ethnicity. This study investigated the rates of bleeds and thromboembolic events, the international normalised ratio (INR) status and the relationship between INR and bleeding events in Malaysia. Patients attending INR clinic at the Heart Centre, Sarawak General Hospital were enrolled on an ad hoc basis from May 2010 and followed up for 1 year. At each routine visit, INR was recorded and screening for bleeding or thromboembolism occurred. Variables relating to INR control were used as predictors of bleeds in logistic regression models. 125 patients contributed to 140 person-years of follow-up. The rates of major bleed, thromboembolic event and minor bleed per 100 person-years of follow-up were 1.4, 0.75 and 34.3. The median time at target range calculated using the Rosendaal method was 61.6 % (IQR 44.6–74.1 %). Of the out-of-range readings, 30.0 % were below range and 15.4 % were above. INR variability, (standard deviation of individuals’ mean INR), was the best predictor of bleeding events, with an odds ratio of 3.21 (95 % CI 1.10–9.38). Low rates of both major bleeds and thromboembolic events were recorded, in addition to a substantial number of INR readings under the recommended target range. This may suggest that the recommended INR ranges may not represent the optimal warfarin intensity for this population and that a lower intensity of therapy, as observed in this cohort, could be beneficial in preventing adverse events.     

Molecular basis of non-alcoholic fatty liver disease and metabolic syndrome in a subset of South Asians

International Journal of Diabetes in Developing Countries - Metabolic syndrome (MetS) and non-alcoholic fatty liver disease (NAFLD) are emerging threats in Pakistan. The prevalence of MetS is...     

Prolonged maternal separation decreases granule cell number in the dentate gyrus of 3-week-old male rats

Maternal separation (MS) early in life affects many aspects of development and we have previously observed significant decreases in NMDA and AMPA receptor and elevated glutamate transporter expression in the hippocampus of MS360 animals relative to MS15. We hypothesized that this disruption of the glutamatergic system in adult animals was a sign of a reduction in hippocampal neuronal number in 3-week-old animals. Male Wistar rat pups were separated litter-wise for 15 min (MS15) or 360 min (MS360) from postnatal day 1 to 21. Conventional laboratory reared animals were also included. At postnatal day 22, brains were dissected and sliced on a cryostat. Immunohistochemistry labeled neurons (NeuN) and astrocytes (GFAP) and the number of neurons was quantified using the disector method and Cavalieri principle for stereology for the CA1, CA2, CA3 and dentate gyrus regions of the hippocampus. The volume of 4 regions did not differ across the 3 experimental groups. Numerical density of neurons, however, was significantly different in CA3 (one-way ANOVA; p = 0.044) and the dentate gyrus (one-way ANOVA; p < 0.0001) with post hoc differences MS360 vs. MS15. Finally, the total number of neurons was calculated and MS360 animals had significantly fewer neurons than MS15 animals in the dentate gyrus. Therefore, the maternal separation procedure affected development of the hippocampus directly at 3 weeks of age. The differences observed consequently place young MS360 animals in a vulnerable state for challenges later in life.     

The Prokinetic,Laxative, and Antidiarrheal Effects of Morus nigra: Possible Muscarinic,Ca2+ Channel Blocking,and Antimuscarinic Mechanisms

Morus nigra Linn. (black mulberry) is used in gastrointestinal ailments. This study demonstrates gut modulatory properties of M. nigra. The prokinetic, laxative, and antidiarrheal activities of M. nigra were assessed in mice, while isolated rabbit jejunum and guinea‐pig ileum were used to explore insight into mechanism(s). At 30 and 70 mg/kg, the crude extract of M. nigra (Mn.Cr) exhibited atropine‐sensitive prokinetic and laxative effects, similar to carbachol (CCh). While at higher doses (100, 300, and 500 mg/kg), Mn.Cr offered protection against castor oil‐induced diarrhea. In rabbit jejunum, Mn.Cr and its chloroform fraction inhibited CCh‐induced contractions more potently compared with high K⁺ (80 mm ). Conversely, petroleum fraction was more potent against high‐K⁺‐induced contractions. At 0.01 mg/mL, Mn.Cr caused a parallel shift in acetylcholine concentration–response curves (CRCs) followed by a non‐parallel shift at 0.03 mg/mL, similar to dicyclomine. At further tested concentrations, Mn.Cr (0.1 and 0.3 mg/mL) and petroleum fraction suppressed Ca²⁺ CRCs, similar to verapamil. In guinea‐pig ileum, Mn.Cr, its aqueous and ethyl acetate fractions exhibited atropine‐sensitive gut stimulant activity along with additional uncharacterized excitatory response in the aqueous fraction only. These results suggest that black mulberry possesses prokinetic, laxative, and antidiarrheal effects, putatively mediated through cholinomimetic, antimuscarinic, and Ca²⁺ antagonist mechanisms, respectively. Copyright © 2016 John Wiley & Sons, Ltd.     

Understanding Factors Associated with Postpartum Visit Attendance and Contraception Choices: Listening to Low-Income Postpartum Women and Health Care Providers

Background While there is considerable variability with respect to attendance at the postpartum visit, not much is known about women’s preferences with respect to postpartum care. Likewise, there is also limited information on providers’ practices regarding the postpartum visit and care including the delivery of contraception. To understand and address deficits in the delivery and utilization of postpartum care, we examined the perceptions of low-income postpartum women with respect to barriers to and preferences for the timing and location of the postpartum visit and receipt of contraception. We also examined providers’ current prenatal and postnatal care practices for promoting the use of postpartum care and their attitudes toward alternative approaches for delivering contraceptive services in the postpartum period. Methods Qualitative face-to-face interviews were completed with 20 postpartum women and in-depth qualitative phone interviews were completed with 12 health care providers who had regular contact with postpartum women. Interviews were coded using Atlas.ti software and themes were identified. Results Women believed that receiving care during the postpartum period was an important resource for monitoring physical and mental health and also strongly supported the provision of contraception earlier than the 6-week postpartum visit. Providers reported barriers to women’s use of postpartum care on the patient, provider, and system levels. However, providers were receptive to exploring new clinical practices that may widen the reach of postpartum care and increase access to postpartum contraception. Conclusion Approaches that increase the flexibility and convenience of postpartum care and the delivery of postpartum contraception may increase the likelihood that women will take advantage of essential postpartum services.     

Analysis of common PTPN1 gene variants in type 2 diabetes, obesity and associated phenotypes in the French population

Background  

The protein tyrosine phosphatase-1B, a negative regulator for insulin and leptin signalling, potentially modulates glucose and energy homeostasis. PTP1B is encoded by the PTPN1 gene located on chromosome 20q13 showing linkage with type 2 diabetes (T2D) in several populations. PTPN1 gene variants have been inconsistently associated with T2D, and the aim of our study was to investigate the effect of PTPN1 genetic variations on the risk of T2D, obesity and on the variability of metabolic phenotypes in the French population.     

A systematic review and meta-analysis of biological treatments targeting tumour necrosis factor α for sciatica

Purpose

Systematic review comparing biological agents, targeting tumour necrosis factor α, for sciatica with placebo and alternative interventions.

Methods

We searched 21 electronic databases and bibliographies of included studies. We included randomised controlled trials (RCTs), non-RCTs and controlled observational studies of adults who had sciatica treated by biological agents compared with placebo or alternative interventions.

Results

We pooled the results of six studies (five RCTs and one non-RCT) in meta-analyses. Compared with placebo biological agents had: better global effects in the short-term odds ratio (OR) 2.0 (95 % CI 0.7–6.0), medium-term OR 2.7 (95 % CI 1.0–7.1) and long-term OR 2.3 [95 % CI 0.5 to 9.7); improved leg pain intensity in the short-term weighted mean difference (WMD) −13.6 (95 % CI −26.8 to −0.4), medium-term WMD −7.0 (95 % CI −15.4 to 1.5), but not long-term WMD 0.2 (95 % CI −20.3 to 20.8); improved Oswestry Disability Index (ODI) in the short-term WMD −5.2 (95 % CI −14.1 to 3.7), medium-term WMD −8.2 (95 % CI −14.4 to −2.0), and long-term WMD −5.0 (95 % CI −11.8 to 1.8). There was heterogeneity in the leg pain intensity and ODI results and improvements were no longer statistically significant when studies were restricted to RCTs. There was a reduction in the need for discectomy, which was not statistically significant, and no difference in the number of adverse effects.

Conclusions

There was insufficient evidence to recommend these agents when treating sciatica, but sufficient evidence to suggest that larger RCTs are needed.

Electronic supplementary material

The online version of this article (doi:10.1007/s00586-013-2739-z) contains supplementary material, which is available to authorized users.