Re-analysis of safety data supporting doxylamine use for nausea and vomiting of pregnancy.

Antihistamines are commonly used to treat nausea and vomiting of pregnancy (NVP). We re-analyzed the 24 primary studies cited in a 1997 meta-analysis that concluded antihistamine use for NVP was safe as they had been studied in more than 200,000 participating women and the pooled odds ratio for congenital malformations was 0.76 (95% confidence interval [CI]: 0.60-0.94). Our analysis of this meta-analysis showed that 139,414 women were included in 22 original studies involving antihistamines, 129,108 of which were in studies involving doxylamine. In these studies, 23,485 women were exposed to antihistamines, 14,624 of which were exposed to doxylamine. The summary relative risk (cohort studies) and odds ratio (case-control studies) for congenital malformations from antihistamine exposure were 1.09 (95% CI: 1.01-1.18) and 1.04 (95% CI: 0.91-1.19), and for doxylamine exposure, the summary relative risk and odds ratio were 0.94 (95% CI: 0.80-1.10) and 1.07 (95% CI: 0.93-1.23), respectively. Although not a new systematic review, our re-analysis demonstrates that the safety data for antihistamines, and doxylamine in particular, are based on many fewer than 200,000 participating women and exposures, and that doxylamine use is not associated with a decreased risk of malformations as previously reported.

Non traumatic lower extremity amputations in younger patients: an 11-year retrospective study.

The purpose of this study was to assess morbidity and mortality in patients undergoing non traumatic lower extremity amputations ≤65 years to identify the specific needs of these younger patients. A retrospective study was conducted to determine the demographics, comorbidity and mortality with below-knee amputations and above-knee amputations from 1998 to 2008. A total of 203 amputations were performed on 176 patients who were ≤65 years. Major comorbidities and associated physical findings were peripheral vascular disease, diabetes, pain, gangrene, hypertension, ulcer, local wound infection and hypercholesterolemia. Compared to patients who were not deceased post-amputation, those deceased had a higher prevalence of diabetes, renal failure, coronary artery disease (CAD) and sepsis. Significant predictors of mortality were renal failure (hazard ratio [HR] = 4·19; 95% CI 1·96-8·93), CAD (HR = 3·33; 95% CI 1·42-7·81) and amputation site (above-knee) (HR = 3·26; 95% CI 1·51-7·04). This study showed that younger patients may benefit from an interdisciplinary approach in treating local foot ulcers aggressively and optimising their cardiovascular, renal and diabetic risk factors.

Molecular events surrounding collagen fibril assembly in the early healing rabbit medial collateral ligament--failure to recapitulate normal ligament development.

??Although injuries to the medial collateral ligament (MCL) can heal functionally without surgical intervention, the collagen fibers in the healing tissue remain compromised. The molecular basis for this poor healing potential was investigated by examining extracellular matrix-modifying molecules such as bone morphogenetic protein 1 (BMP-1), procollagen C proteinase enhancer (PCOLCE), lysyl oxidase (LOX), and transforming growth factor beta 1 (TGF-ß1) involved in collagen fibrillogenesis during normal early postnatal ligament maturation and at comparable intervals after MCL injury. Samples of midsections of rabbit MCLs were collected from 3-, 6-, 14-, and 52-week-old normal animals and at 3, 6, and 14 weeks postinjury. Harvested midsubstance tissues were analyzed for collagen fibril diameter by transmission electron microscopy (TEM), and mRNA levels were assessed by reverse transcription-polymerase chain reaction (RT-PCR). Results showed different patterns of expression between normal MCL maturation and during scar maturation. BMP-1 and PCOLCE mRNA levels were upregulated in the 3?14-week period during maturation of normal ligaments but decreased at skeletal maturity. The scar tissue exhibited a 3.5-fold increase in PCOLCE mRNA levels during the early healing phase, but these decreased with time. After injury, BMP-1 mRNA levels in scars were low and did not change during healing. Both LOX and TGF-ß1 mRNA levels were low during normal MCL development compared with levels at maturity and exhibited elevated mRNA levels during early healing that decreased with time postinjury. These results suggest that gene expression in scars during MCL healing does not recapitulate expression in normal ligament fibroblasts during maturation.