Towards Optimizing Hospitalized Older adults' MEdications (TO HOME): Multi-centre study of medication use and outcomes in routine care.

AIMS: Comprehensively investigate prescribing in usual care of hospitalized older people with respect to polypharmacy; potentially inappropriate medications (PIMs) according to Beers criteria; and cumulative anticholinergic and sedative medication exposure calculated with Drug Burden Index (DBI). Specifically, to quantify exposure to these measures on admission, changes between admission and discharge, associations with adverse outcomes and medication costs. METHODS: Established new retrospective inpatient cohort of 2000 adults aged ≥75 years, consecutively admitted to 6 hospitals in Sydney, Australia, with detailed information on medications, clinical characteristics and outcomes. Conducted cross-sectional analyses of index admission data from cohort. RESULTS: Cohort had mean (standard deviation) age 86.0 (5.8) years, 59% female, 21% from residential aged care. On admission, prevalence of polypharmacy was 77%, PIMs 34% and DBI > 0 in 53%. From admission to discharge, mean difference (95% confidence interval) in total number of medications increased 1.05 (0.92, 1.18); while prevalence of exposure to PIMs (-3.8% [-5.4, -2.1]) and mean DBI score (-0.02 [-0.04, -0.01]) decreased. PIMs and DBI score were associated with increased risks (adjusted odds ratio [95% confidence interval]) of falls (PIMs 1.63 [1.28, 2.08]; DBI score 1.21[1.00, 1.46]) and delirium (PIMs 1.76 [1.38, 1.46]; DBI score 1.42 [1.19, 1.71]). Each measure was associated with increased risk of adverse drug reactions (polypharmacy 1.42 [1.19, 1.71]; PIMs 1.87 [1.40, 2.49]; DBI score 1.90 [1.55, 2.15]). Cost (AU$/patient/hospital day) of medications contributing to PIMs and DBI was low ($0.29 and $0.88). CONCLUSION: In this large cohort of older inpatients, usual hospital care results in an increase in number of medications and small reductions in PIMs and DBI, with variable associations with adverse outcomes

Effectiveness of Mechanisms and Models of Coordination between Organizations, Agencies and Bodies Providing or Financing Health Services in Humanitarian Crises: A Systematic Review.

BACKGROUND: Effective coordination between organizations, agencies and bodies providing or financing health services in humanitarian crises is required to ensure efficiency of services, avoid duplication, and improve equity. The objective of this review was to assess how, during and after humanitarian crises, different mechanisms and models of coordination between organizations, agencies and bodies providing or financing health services compare in terms of access to health services and health outcomes. METHODS: We registered a protocol for this review in PROSPERO International prospective register of systematic reviews under number PROSPERO2014:CRD42014009267. Eligible studies included randomized and nonrandomized designs, process evaluations and qualitative methods. We electronically searched Medline, PubMed, EMBASE, Cochrane Central Register of Controlled Trials, CINAHL, PsycINFO, and the WHO Global Health Library and websites of relevant organizations. We followed standard systematic review methodology for the selection, data abstraction, and risk of bias assessment. We assessed the quality of evidence using the GRADE approach. RESULTS: Of 14,309 identified citations from databases and organizations' websites, we identified four eligible studies. Two studies used mixed-methods, one used quantitative methods, and one used qualitative methods. The available evidence suggests that information coordination between bodies providing health services in humanitarian crises settings may be effective in improving health systems inputs. There is additional evidence suggesting that management/directive coordination such as the cluster model may improve health system inputs in addition to access to health services. None of the included studies assessed coordination through common representation and framework coordination. The evidence was judged to be of very low quality. CONCLUSION: This systematic review provides evidence of possible effectiveness of information coordination and management/directive coordination between organizations, agencies and bodies providing or financing health services in humanitarian crises. Our findings can inform the research agenda and highlight the need for improving conduct and reporting of research in this field

Population‐based cohort study of outcomes following cholecystectomy for benign gallbladder diseases

Background The aim was to describe the management of benign gallbladder disease and identify characteristics associated with all‐cause 30‐day readmissions and complications in a prospective population‐based cohort. Methods Data were collected on consecutive patients undergoing cholecystectomy in acute UK and Irish hospitals between 1 March and 1 May 2014. Potential explanatory variables influencing all‐cause 30‐day readmissions and complications were analysed by means of multilevel, multivariable logistic regression modelling using a two‐level hierarchical structure with patients (level 1) nested within hospitals (level 2). Results Data were collected on 8909 patients undergoing cholecystectomy from 167 hospitals. Some 1451 cholecystectomies (16·3 per cent) were performed as an emergency, 4165 (46·8 per cent) as elective operations, and 3293 patients (37·0 per cent) had had at least one previous emergency admission, but had surgery on a delayed basis. The readmission and complication rates at 30 days were 7·1 per cent (633 of 8909) and 10·8 per cent (962 of 8909) respectively. Both readmissions and complications were independently associated with increasing ASA fitness grade, duration of surgery, and increasing numbers of emergency admissions with gallbladder disease before cholecystectomy. No identifiable hospital characteristics were linked to readmissions and complications. Conclusion Readmissions and complications following cholecystectomy are common and associated with patient and disease characteristics

A Single E627K Mutation in the PB2 Protein of H9N2 Avian Influenza Virus Increases Virulence by Inducing Higher Glucocorticoids (GCs) Level

While repeated infection of humans and enhanced replication and transmission in mice has attracted more attention to it, the pathogenesis of H9N2 virus was less known in mice. PB2 residue 627 as the virulent determinant of H5N1 virus is associated with systemic infection and impaired TCR activation, but the impact of this position in H9N2 virus on the host immune response has not been evaluated. In this study, we quantified the cellular immune response to infection in the mouse lung and demonstrate that VK627 and rTsE627K infection caused a significant reduction in the numbers of T cells and inflammatory cells (Macrophage, Neutrophils, Dendritic cells) compared to mice infected with rVK627E and TsE627. Further, we discovered (i) a high level of thymocyte apoptosis resulted in impaired T cell development, which led to the reduced amount of mature T cells into lung, and (ii) the reduced inflammatory cells entering into lung was attributed to the diminished levels in pro-inflammatory cytokines and chemokines. Thereafter, we recognized that higher GCs level in plasma induced by VK627 and rTsE627K infection was associated with the increased apoptosis in thymus and the reduced pro-inflammatory cytokines and chemokines levels in lung. These data demonstrated that VK627 and rTsE627K infection contributing to higher GCs level would decrease the magnitude of antiviral response in lung, which may be offered as a novel mechanism of enhanced pathogenicity for H9N2 AIV

Thalassemias in South Asia:clinical lessons learnt from Bangladesh

Abstract Thalassemias are emerging as a global public health concern. Due to remarkable success in the reduction of childhood mortality by controlling infectious diseases in developing countries, thalassemias are likely to be a major public health concern in the coming decades in South Asia. Despite the fact that Bangladesh lies in the world’s thalassemia belt, the information on different aspects (epidemiology, clinical course, mortality, complications and treatment outcomes) of thalassemias is lacking. In this comprehensive review, the aim is to to depict the epidemiological aspects of thalassemias, mutation profile and current treatment and management practices in the country by sharing the experience of dealing with 1178 cases over 2009–2014 time periods in a specialized thalassemia treatment centre. We have also discussed the preventative strategies of thalassemias from the context of Bangladesh which could be effective for other developing countries

FTO gene polymorphisms and obesity risk: a meta-analysis

<p>Abstract</p> <p>Background</p> <p>The pathogenesis of obesity is reportedly related to variations in the fat mass and an obesity-associated gene (<it>FTO</it>); however, as the number of reports increases, particularly with respect to varying ethnicities, there is a need to determine more precisely the effect sizes in each ethnic group. In addition, some reports have claimed ethnic-specific associations with alternative SNPs, and to that end there has been a degree of confusion.</p> <p>Methods</p> <p>We searched PubMed, MEDLINE, Web of Science, EMBASE, and BIOSIS Preview to identify studies investigating the associations between the five polymorphisms and obesity risk. Individual study odds ratios (OR) and their 95% confidence intervals (CI) were estimated using per-allele comparison. Summary ORs were estimated using a random effects model.</p> <p>Results</p> <p>We identified 59 eligible case-control studies in 27 articles, investigating 41,734 obesity cases and 69,837 healthy controls. Significant associations were detected between obesity risk and the five polymorphisms: rs9939609 (OR: 1.31, 95% CI: 1.26 to 1.36), rs1421085 (OR: 1.43, 95% CI: 1.33 to 1.53), rs8050136 (OR: 1.25, 95% CI: 1.13 to 1.38), rs17817449 (OR: 1.54, 95% CI: 1.41 to 1.68), and rs1121980 (OR: 1.34, 95% CI: 1.10 to 1.62). Begg's and Egger's tests provided no evidence of publication bias for the polymorphisms except rs1121980. There is evidence of higher heterogeneity, with <it>I</it>²test values ranging from 38.1% to 84.5%.</p> <p>Conclusions</p> <p>This meta-analysis suggests that <it>FTO </it>may represent a low-penetrance susceptible gene for obesity risk. Individual studies with large sample size are needed to further evaluate the associations between the polymorphisms and obesity risk in various ethnic populations.</p

Peripheral Blood Signatures of Lead Exposure

BACKGROUND: Current evidence indicates that even low-level lead (Pb) exposure can have detrimental effects, especially in children. We tested the hypothesis that Pb exposure alters gene expression patterns in peripheral blood cells and that these changes reflect dose-specific alterations in the activity of particular pathways. METHODOLOGY/PRINCIPAL FINDING: Using Affymetrix Mouse Genome 430 2.0 arrays, we examined gene expression changes in the peripheral blood of female Balb/c mice following exposure to per os lead acetate trihydrate or plain drinking water for two weeks and after a two-week recovery period. Data sets were RMA-normalized and dose-specific signatures were generated using established methods of supervised classification and binary regression. Pathway activity was analyzed using the ScoreSignatures module from GenePattern. CONCLUSIONS/SIGNIFICANCE: The low-level Pb signature was 93% sensitive and 100% specific in classifying samples a leave-one-out crossvalidation. The high-level Pb signature demonstrated 100% sensitivity and specificity in the leave-one-out crossvalidation. These two signatures exhibited dose-specificity in their ability to predict Pb exposure and had little overlap in terms of constituent genes. The signatures also seemed to reflect current levels of Pb exposure rather than past exposure. Finally, the two doses showed differential activation of cellular pathways. Low-level Pb exposure increased activity of the interferon-gamma pathway, whereas high-level Pb exposure increased activity of the E2F1 pathway