N-acetylcysteine for non-paracetamol drug-induced liver injury: a systematic review protocol

BACKGROUND: Drug-induced liver injury (DILI) refers to acute or chronic liver injury that may occur as a consequence of using drugs and herbal or dietary supplements. Specific therapies for DILI are limited. There is considerable evidence for efficacy and safety of N-acetylcysteine (NAC) in management of paracetamol-induced liver injury. More recently, research has explored the use of NAC in non-paracetamol drug-induced liver injury. It is important to summarise the evidence of NAC for non-paracetamol DILI to determine if NAC may be considered a therapeutic option in this condition.METHODS/DESIGN:We will conduct a systematic review of the benefit and harm of NAC in non-paracetamol drug-induced liver injury. Primary and secondary outcomes of interest are pre-specified. Primary outcomes include all-cause mortality, mortality due to DILI, time to normalisation of liver biochemistry (e.g. return of alanine transaminase to <100 U/l and/or international normalized ratio (INR) <1.5) and adverse events. Secondary outcomes include transplantation rate, time to transplantation, transplant-free survival and duration of hospitalisation. We will include randomized controlled trials (RCTs) and prospective cohort studies. RCTs will contribute to the evaluation of safety and efficacy of NAC, whereas, the cohort studies will contribute exclusively to the evaluation of safety. We will search several bibliographic databases (including PubMed, Scopus, CINAHL, CENTRAL), grey literature sources, conference proceedings and ongoing trials. Following data extraction and assessment of the risk of bias, we will conduct a meta-analysis if feasible, as well as subgroup analyses. We will assess and explore clinical and statistical heterogeneity.DISCUSSION:The aim of this review is to provide evidence on the effectiveness and safety of NAC in non-paracetamol DILI. We anticipate that the results could aid health care practitioners, researchers and policymakers in the decision-making regarding the use of NAC in patients with non-paracetamol DILI.SYSTEMATIC REVIEW REGISTRATION:PROSPERO CRD4201400877

Carbon Speciation and Solubility in Silicate Melts

To improve our understanding of the Earth's global carbon cycle, it is critical to characterize the distribution and storage mechanisms of carbon in silicate melts. Presently, the carbon budget of the deep Earth is not well constrained and is highly model-dependent. In silicate melts of the uppermost mantle, carbon exists predominantly as molecular carbon dioxide and carbonate, whereas at greater depths, carbon forms complex polymerized species. The concentration and speciation of carbon in silicate melts is intimately linked to the melt's composition and affects its physical and dynamic properties. Here we review the results of experiments and calculations on the solubility and speciation of carbon in silicate melts as a function of pressure, temperature, composition, polymerization, water concentration, and oxygen fugacity

Associations between neighbourhood characteristics and depression: a twin study.

BACKGROUND: Depression is an important contributor to the global burden of disease. Besides several known individual-level factors that contribute to depression, there is a growing recognition that neighbourhood environment can also profoundly affect mental health. This study assessed associations between three neighbourhood constructs-socioeconomic deprivation, residential instability and income inequality-and depression among adult twin pairs. The twin design is used to examine the association between neighbourhood constructs and depression, controlling for selection factors (ie, genetic and shared environmental factors) that have confounded purported associations. METHODS: We used multilevel random-intercept Poisson regression among 3738 same-sex twin pairs from a community-based twin registry to examine the association between neighbourhood constructs and depression. The within-pair association controls for confounding by genetic and environmental factors shared between twins within a pair, and is the main parameter of interest. Models were adjusted for individual-level income, education and marital status, and further by neighbourhood-level population density. RESULTS: When twins were analysed as individuals (phenotypic model), all neighbourhood constructs were significantly associated with depression. However, only neighbourhood socioeconomic deprivation showed a significant within-pair association with depression. A 10-unit within-pair difference in neighbourhood socioeconomic deprivation was associated with 6% greater depressive symptoms (1.06, 95% CI 1.01 to 1.11); the association did not substantially change in adjusted models. CONCLUSION: This study provides new evidence linking neighbourhood socioeconomic deprivation with greater depression. Future studies should employ longitudinal designs to better test social causation versus social selection

The effect of a domestic violence interclerkship on the knowledge, attitudes, and skills of third-year medical students

PURPOSE: To determine whether participation in an intensive domestic violence interclerkship (DVI) improved the knowledge, attitudes, and skills of two successive cohorts of students at the University of Massachusetts Medical School. METHOD: The authors measured the knowledge, attitudes, and skills pertaining to domestic violence of third-year students in the classes of 1997 and 1998 using a validated written examination administered before, immediately after, and six months after participation in a 3.5-day or two-day DVI, respectively; they compared the scores using paired t-tests. Nine months after the DVI, the students\u27 domestic violence screening skills were measured by a performance-based assessment (OSCE); using unpaired t-tests, the authors compared the OSCE scores with those of a previous third-year class that had not participated in a DVI. Immediately after the OSCE, the students reported their levels of confidence in domestic violence screening and their satisfaction with the domestic violence curriculum; using chi-square analysis, those self-reports were compared with those of the class with no DVI. RESULTS: The students who participated in the DVIs immediately and significantly improved their knowledge, attitudes, and skills (p \u3c .001), and fully or partially sustained those improvements six months later (p \u3c .001). Nine months after the DVI, the students performed domestic violence screening more effectively (p \u3c .001), expressed greater comfort with domestic violence screening (p \u3c .001), and felt better-prepared by the curriculum to address domestic violence issues (p \u3c .001) than did the students with no DVI. CONCLUSION: Participation in a short, focused DVI curriculum produced sustainable improvements in knowledge, attitudes, and skills that were successfully applied by third-year medical students to effective domestic violence screening. Interclerkships are an effective way to fit into the clinical curriculum those subjects that transcend the traditional biomedical domain and intersect all areas of medical practice

Glycolytic and Gluconeogenic Growth of \u3cem\u3eEscherichia coli\u3c/em\u3e O157:H7 (EDL933) and \u3cem\u3eE. coli\u3c/em\u3e K-12 (MG1655) in the Mouse Intestine

Escherichia coli EDL933, an O157:H7 strain, is known to colonize the streptomycin-treated CD-1 mouse intestine by growing in intestinal mucus (E. A. Wadolkowski, J. A. Burris, and A. D. O\u27Brien, Infect. Immun. 58:2438-2445, 1990), but what nutrients and metabolic pathways are employed during colonization has not been determined. In this study, when the wild-type EDL933 strain was fed to mice along with an EDL933 ΔppsA ΔpckA mutant, which is unable to utilize tricarboxylic acid cycle intermediates and gluconeogenic substrates for growth, both strains colonized the mouse intestine equally well. Therefore, EDL933 utilizes a glycolytic substrate(s) for both initial growth and maintenance when it is the only E. coli strain fed to the mice. However, in the presence of large numbers of MG1655, a K-12 strain, it is shown that EDL933 utilizes a glycolytic substrate(s) for initial growth in the mouse intestine but appears to utilize both glycolytic and gluconeogenic substrates in an attempt to maintain colonization. It is further shown that MG1655 predominantly utilizes glycolytic substrates for growth in the mouse intestine whether growing in the presence or absence of large numbers of EDL933. Data are presented showing that although small numbers of EDL933 grow to large numbers in the intestine in the presence of large numbers of MG1655 when both strains are fed to mice simultaneously, precolonization with MG1655 affords protection against subsequent colonization by EDL933. Moreover, in mice that are precolonized with EDL933, small numbers of MG1655 are able to grow rapidly in the intestine and EDL933 is eliminated. In situ hybridization experiments using E. coli-specific rRNA probes showed that while MG1655 is found only in mucus, EDL933 is found both in mucus and closely associated with intestinal epithelial cells. The data are discussed with respect to competition for nutrients and to the protection that some intestinal commensal E. coli strains might afford against infection by O157:H7 strains

Carbon nutrition of \u3cem\u3eEscherichia coli\u3c/em\u3e in the mouse intestine

Whole-genome expression profiling revealed Escherichia coli MG1655 genes induced by growth on mucus, conditions designed to mimic nutrient availability in the mammalian intestine. Most were nutritional genes corresponding to catabolic pathways for nutrients found in mucus. We knocked out several pathways and tested the relative fitness of the mutants for colonization of the mouse intestine in competition with their wild-type parent. We found that only mutations in sugar pathways affected colonization, not phospholipid and amino acid catabolism, not gluconeogenesis, not the tricarboxylic acid cycle, and not the pentose phosphate pathway. Gluconate appeared to be a major carbon source used by E. coli MG1655 to colonize, having an impact on both the initiation and maintenance stages. N-acetylglucosamine and N-acetylneuraminic acid appeared to be involved in initiation, but not maintenance. Glucuronate, mannose, fucose, and ribose appeared to be involved in maintenance, but not initiation. The in vitro order of preference for these seven sugars paralleled the relative impact of the corresponding metabolic lesions on colonization: gluconate \u3e N-acetylglucosamine \u3e N-acetylneuraminic acid = glucuronate \u3e mannose \u3e fucose \u3e ribose. The results of this systematic analysis of nutrients used by E. coli MG1655 to colonize the mouse intestine are intriguing in light of the nutrient-niche hypothesis, which states that the ecological niches within the intestine are defined by nutrient availability. Because humans are presumably colonized with different commensal strains, differences in nutrient availability may provide an open niche for infecting E. coli pathogens in some individuals and a barrier to infection in others

Baker Center Journal of Applied Public Policy - Vol. IV, No.II

This special edition includes articles from speakers at a 2010 conference - Howard H. Baker, Jr: A Life in Public Service and a special addendum including photographs and cartoons from Sen. Baker\u27s career

Associations between lifestyle factors and quality of life among older long-term breast, prostate, and colorectal cancer survivors

BACKGROUND: Older cancer survivors are at increased risk for secondary cancers, cardiovascular disease, obesity, and functional decline and, thus, may benefit from health-related interventions. However, to the authors' knowledge, little is known regarding the health behaviors of older cancer survivors and the associations of those behaviors with quality-of-life outcomes, especially during the long-term post-treatment period. METHODS: In total, 753 older (aged ≥65 years) long-term survivors (≥5 years postdiagnosis) of breast, prostate, and colorectal cancer completed 2 baseline telephone interviews to assess their eligibility for a diet and exercise intervention trial. The interviews assessed exercise, diet, weight status, and quality of life. RESULTS: Older cancer survivors reported a median of 10 minutes of moderate-to-vigorous exercise per week, and only 7% had Healthy Eating Index scores >80 (indicative of healthful eating habits relative to national guidelines). Despite their suboptimal health behaviors, survivors reported mental and physical quality of life that exceeded age-related norms. Greater exercise and better diet quality were associated with better physical quality-of-life outcomes (eg, better vitality and physical functioning; P < .05), whereas greater body mass index was associated with reduced physical quality of life (P < .001). CONCLUSIONS: The current results indicated a high prevalence of suboptimal health behaviors among older, long-term survivors of breast, prostate, and colorectal cancer who were interested in lifestyle modification. In addition, the findings pointed to the potential negative impact of obesity and the positive impact of physical activity and a healthy diet on physical quality of life in this population. Cancer 2009

‘What are you going to do, confiscate their passports?’ Professional perspectives on cross-border reproductive travel

Objective: This article reports findings from a UK-based study which explored the phenomenon of overseas travel for fertility treatment. The first phase of this project aimed to explore how infertility clinicians and others professionally involved in fertility treatment understand the nature and consequences of cross-border reproductive travel. Background: There are indications that, for a variety of reasons, people from the UK are increasingly travelling across national borders to access assisted reproductive technologies. While research with patients is growing, little is known about how ‘fertility tourism’ is perceived by health professionals and others with a close association with infertility patients. Methods: Using an interpretivist approach, this exploratory research included focussed discussions with 20 people professionally knowledgeable about patients who had either been abroad or were considering having treatment outside the UK. Semi-structured interviews were recorded, transcribed verbatim and subjected to a thematic analysis. Results: Three conceptual categories are developed from the data: ‘the autonomous patient’; ‘cross-border travel as risk’, and ‘professional responsibilities in harm minimisation’. Professionals construct nuanced, complex and sometimes contradictory narratives of the ‘fertility traveller’, as vulnerable and knowledgeable; as engaged in risky behaviour and in its active minimisation. Conclusions: There is little support for the suggestion that states should seek to prevent cross-border treatment. Rather, an argument is made for less direct strategies to safeguard patient interests. Further research is required to assess the impact of professional views and actions on patient choices and patient experiences of treatment, before, during and after travelling abroad

Effects of Antiretroviral Therapy and Depressive Symptoms on All-Cause Mortality Among HIV-Infected Women

Abstract Depression affects up to 30% of human immunodeficiency virus (HIV)-infected individuals. We estimated joint effects of antiretroviral therapy (ART) initiation and depressive symptoms on time to death using a joint marginal structural model and data from a cohort of HIV-infected women from the Women's Interagency HIV Study (conducted in the United States) from 1998–2011. Among 848 women contributing 6,721 years of follow-up, 194 participants died during follow-up, resulting in a crude mortality rate of 2.9 per 100 women-years. Cumulative mortality curves indicated greatest mortality for women who reported depressive symptoms and had not initiated ART. The hazard ratio for depressive symptoms was 3.38 (95% confidence interval (CI): 2.15, 5.33) and for ART was 0.47 (95% CI: 0.31, 0.70). Using a reference category of women without depressive symptoms who had initiated ART, the hazard ratio for women with depressive symptoms who had initiated ART was 3.60 (95% CI: 2.02, 6.43). For women without depressive symptoms who had not started ART, the hazard ratio was 2.36 (95% CI: 1.16, 4.81). Among women reporting depressive symptoms who had not started ART, the hazard ratio was 7.47 (95% CI: 3.91, 14.3). We found a protective effect of ART initiation on mortality, as well as a harmful effect of depressive symptoms, in a cohort of HIV-infected women