Correction to: Role of complement and potential of complement inhibitors in myasthenia gravis and neuromyelitis optica spectrum disorders: a brief review

Journal of Neurology - The original version of this article unfortunately contained a mistake. Fifth sentence of the fourth paragraph in the section “Non-nAChR autoantibody targets in...     

Performance of BNP and NT-proBNP for diagnosis of heart failure in primary care patients: a systematic review

National and international guidelines have been published recommending the use of natriuretic peptides as an aid to the diagnosis of heart failure (HF) in acute settings; however, few specific recommendations exist for governing the use of these peptides in primary care populations. To summarize the available data relevant to the diagnosis of HF in primary care patient population, we systematically reviewed the literature to identify original articles that investigated the diagnostic accuracy of B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) in primary care settings. The search yielded 25,864 articles in total: 12 investigating BNP and 20 investigating NT-proBNP were relevant to our objective and included in the review. QUADAS-2 and GRADE were used to assess the quality of the included articles. Diagnostic data were pooled based on three cutpoints: lowest and optimal, as chosen by study authors, and manufacturers’ suggested. The effect of various determinants (e.g., age, gender, BMI, and renal function) on diagnostic performance was also investigated. Pooled sensitivity and specificity of BNP and NT-proBNP using the lowest [0.85 (sensitivity) and 0.54 (specificity)], optimal (0.80 and 0.61), and manufacturers’ (0.74 and 0.67) cutpoints showed good performance for diagnosing HF. Similar performance was seen for NT-proBNP: lowest (0.90 and 0.50), optimal (0.86 and 0.58), and manufacturers’ (0.82 and 0.58) cutpoints. Overall, we rated the strength of evidence as high because further studies will be unlikely to change the estimates diagnostic performance.     

Incremental value of natriuretic peptide measurement in acute decompensated heart failure (ADHF): a systematic review

The aim of this systematic review was to determine whether B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) independently add incremental value for predicting mortality and morbidity in patients with acute decompensated heart failure (ADHF). Medline^®, Embase?, AMED, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and CINAHL were searched from 1989 to June 2012. We also searched reference lists of included articles, systematic reviews, and the gray literature. Studies were screened for eligibility criteria and assessed for risk of bias. Data were extracted on study design, population demographics, assay cutpoints, prognostic risk prediction model covariates, statistical methods, outcomes, and results. From 183 citations, only seven studies (5 BNP and 2 NT-proBNP) considered incremental value in ADHF subjects admitted to acute care centers. Admission assay levels and length of follow-up varied for BNP studies (31 days to 12 months) and for NT-proBNP studies (25–82 months). All studies presented at least one estimate of incremental value of BNP/NT-proBNP relative to the base prognostic model. Using discrimination or likelihood statistics, these studies consistently showed that BNP or NT-proBNP increased model performance. Three studies used reclassification and model validation computations to establish incremental value; these studies showed less consistency with respect to added value. In conclusion, the literature assessing incremental value of BNP/NT-proBNP in ADHF populations is limited to seven studies evaluating only mortality outcomes and at moderate risk of bias. Although there were differences in the base risk prediction models, assay cutpoints, and lengths of follow-up, there was consistency in BNP/NT-proBNP adding incremental value in prediction models in ADHF patients.     

Metformin in pregnancy to avert gestational diabetes in women at high risk: Meta‐analysis of randomized controlled trials

Previous randomized and observational studies on the efficacy of metformin in pregnancy to reduce incident gestational diabetes mellitus (GDM) in women at high risk (obesity, polycystic ovary syndrome [PCOS], or pregestational insulin resistance) have been conflicting and several groups are planning further randomized controlled trials (RCTs) to answer this question conclusively. This work assesses the efficacy of metformin in pregnancy to avert one outcome—incident GDM in women at high risk. We included RCTs comparing metformin with usual care or placebo controls in terms of incident GDM and recruiting women at high risk during early pregnancy. Eleven eligible trials enrolled 2370 adult women whose intervention arm consisted of metformin started at conception or before 20 weeks of gestation. Risk of GDM was similar in intervention compared with controls (risk ratio [RR] 1.03; 95% confidence interval [CI], 0.85‐1.24). The data were of sufficient quality meeting the criteria for consistency and directness. We conclude that metformin does not contribute to averting the GDM outcome in women at high risk when initiated in pregnancy. The evidence provided by this synthesis affirms that further broad clinical trials investigating this question are no longer needed.     

Telomere fusions in early human breast carcinoma

Several lines of evidence suggest that defects in telomere maintenance play a significant role in the initiation of genomic instability during carcinogenesis. Although the general concept of defective telomere maintenance initiating genomic instability has been acknowledged, there remains a critical gap in the direct evidence of telomere dysfunction in human solid tumors. To address this topic, we devised a multiplex PCR-based assay, termed TAR (telomere-associated repeat) fusion PCR, to detect and analyze chromosome end-to-end associations (telomere fusions) within human breast tumor tissue. Using TAR fusion PCR, we found that human breast lesions, but not normal breast tissues from healthy volunteers, contained telomere fusions. Telomere fusions were detected at similar frequencies during early ductal carcinoma in situ and in the later invasive ductal carcinoma stage. Our results provide direct evidence that telomere fusions are present in human breast tumor tissue and suggest that telomere dysfunction may be an important component of the genomic instability observed in this cancer. Development of this robust method that allows identification of these genetic aberrations (telomere fusions) is anticipated to be a valuable tool for dissecting mechanisms of telomere dysfunction.     

Upregulation of GAD65 mRNA in the medulla of the rat model of metabolic syndrome

Although alterations in the function of the neurotransmitter system have been implicated in the pathology of Alzheimer's disease (AD), the mechanisms that underlie this pathological change are not well understood. Beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) is a key protease in the generation of beta-amyloid, an important trigger protein in the pathogenesis of AD. The expression and activity of BACE1 are increased in the brains of sporadic AD patients, and a role for BACE1 in neurotransmission has been suggested recently. This study examines whether BACE1 plays a role in regulated exocytosis in PC12 cells. Treatment of PC12 cells with a beta-secretase inhibitor reduced stimulus-dependent secretion of neurotransmitters, suggesting a potential role of BACE1 in regulated exocytosis. Using transfected human growth hormone as a reporter for a regulated secretory pathway in PC12 cells, we found that the transient overexpression of BACE1 increased basal secretion in the absence of a stimulus and reduced stimulus-dependent secretion in intact PC12 cells. In digitonin-permeabilized PC12 cells, an overexpression of BACE1 enhanced the Ca2+-independent and ATP-independent component of the secretory pathway. Furthermore, expression of the glycosylation-deficient mutant of BACE1, BACE1N354Q, led to an elevation of basal secretions over that by BACE1 wild-type, suggesting a role of BACE1 glycosylation in basal secretion. These results demonstrate an unknown role for BACE1 in secretion, and suggest that elevated levels of BACE1 in AD brains may contribute to the altered neurotransmitter pathology of AD through stimulation of spontaneous basal secretion under resting conditions.     

Men’s perspectives on women’s empowerment and intimate partner violence in rural Bangladesh

Intimate partner violence (IPV) may increase as women in patriarchal societies become empowered, implicitly or explicitly challenging prevailing gender norms. Prior evidence suggests an inverse U-shaped relationship between women’s empowerment and IPV, in which violence against women first increases and then decreases as more egalitarian gender norms gradually gain acceptance. By means of focus-group discussions and in-depth interviews with men in 10 Bangladeshi villages, this study explored men’s evolving views of women, gender norms and the legitimacy of men’s perpetration of IPV in the context of a gender transition. It examines men’s often-contradictory narratives about women’s empowerment and concomitant changes in norms of masculinity, and identifies aspects of women’s empowerment that are most likely to provoke a male backlash. Findings suggest that men’s growing acceptance of egalitarian gender norms and their self-reported decreased engagement in IPV are driven largely by pragmatic self-interest: their desire to improve their economic status and fear of negative consequences of IPV.     

Euthanasia and physician-assisted suicide in the Dutch homecare sector: the role of the district nurse

AIM: This paper is a report of the findings of a study into the role of district nurses in euthanasia and physician-assisted suicide in homecare organizations, conducted as part of a study into the role of nurses in medical end-of-life decisions. BACKGROUND: Issues concerning legislation and regulation with respect to the role of nurses in euthanasia and physician-assisted suicide gave the Minister for Health reason to commission a study into the role of nurses in medical end-of-life decisions in hospitals, nursing homes and homecare organizations. This is the first quantitative study from the perspective of nurses. Previous quantitative studies were conducted under physicians and information on the role of nurses was obtained indirectly. METHOD: A questionnaire was sent in 2003 to 500 district nurses employed in 55 homecare organizations. The absolute response rate was 86.0% and 81.6% (408) could be used for analysis. RESULTS: In 22.3% of 278 cases, the district nurse was the first with whom patients discussed their request for euthanasia or physician-assisted suicide. In about half (49.8%) of 267 cases nurses were not involved in the general practitioner's decision-making process, and in only 13.3% of 264 cases, did they attend the administration of the lethal drugs. District nurses had provided some degree of aftercare to the surviving relatives in 80.3% of 264 cases. CONCLUSION: Collaboration between general practitioners and district nurses needs improvement, particularly in relation to decision-making. Our Dutch data could help nurses in other countries to define their (future) role in euthanasia and physician-assisted suicide.