Chimeric Claudins: A New Tool to Study Tight Junction Structure and Function.

The tight junction (TJ) is a structure composed of multiple proteins, both cytosolic and membranal, responsible for cell-cell adhesion in polarized endothelium and epithelium. The TJ is intimately connected to the cytoskeleton and plays a role in development and homeostasis. Among the TJ's membrane proteins, claudins (CLDNs) are key to establishing blood-tissue barriers that protect organismal physiology. Recently, several crystal structures have been reported for detergent extracted recombinant CLDNs. These structural advances lack direct evidence to support quaternary structure of CLDNs. In this article, we have employed protein-engineering principles to create detergent-independent chimeric CLDNs, a combination of a 4-helix bundle soluble monomeric protein (PDB ID: 2jua) and the apical-50% of human CLDN1, the extracellular domain that is responsible for cell-cell adhesion. Maltose-binding protein-fused chimeric CLDNs (MBP-CCs) used in this study are soluble proteins that retain structural and functional aspects of native CLDNs. Here, we report the biophysical characterization of the structure and function of MBP-CCs. MBP-fused epithelial cadherin (MBP-eCAD) is used as a control and point of comparison of a well-characterized cell-adhesion molecule. Our synthetic strategy may benefit other families of 4-α-helix membrane proteins, including tetraspanins, connexins, pannexins, innexins, and more.

Cost-Effectiveness of Different Formats for Delivery of Cognitive Behavioral Therapy for Depression: A Systematic Review Based Economic Model.

OBJECTIVES: Cognitive behavioral therapy (CBT) is an effective treatment for depression. Different CBT delivery formats (face-to-face [F2F], multimedia, and hybrid) and intensities have been used to expand access to the treatment. The aim of this study is to estimate the long-term cost-effectiveness of different CBT delivery modes. METHODS: A decision-analytic model was developed to evaluate the cost-effectiveness of different CBT delivery modes and variations in intensity in comparison with treatment as usual (TAU). The model covered an average treatment period of 4 months with a 5-year follow-up period. The model was populated using a systematic review of randomized controlled trials and various sources from the literature. RESULTS: Incremental cost-effectiveness ratios of treatments compared with the next best option after excluding all the dominated and extended dominated options are: £209/quality-adjusted life year (QALY) for 6 (sessions) × 30 (minutes) F2F-CBT versus TAU; £4 453/QALY for 8 × 30 F2F versus 6 × 30 F2F; £12 216/QALY for 8 × 60 F2F versus 8 × 30 F2F; and £43 072/QALY for 16 × 60 F2F versus 8 × 60 F2F. The treatment with the highest net monetary benefit for thresholds of £20 000 to £30 000/QALY was 8 × 30 F2F-CBT. Probabilistic sensitivity analysis illustrated 6 × 30 F2F-CBT had the highest probability (32.8%) of being cost-effective at £20 000/QALY; 16 × 60 F2F-CBT had the highest probability (31.0%) at £30 000/QALY. CONCLUSIONS: All CBT delivery modes on top of TAU were found to be more cost-effective than TAU alone. Four F2F-CBT options (6 × 30, 8 × 30, 8 × 60, 16 × 60) are on the cost-effectiveness frontier. F2F-CBT with intensities of 6 × 30 and 16 × 60 had the highest probabilities of being cost-effective. The results, however, should be interpreted with caution owing to the high level of uncertainty.

An expert consensus on the most effective components of cognitive behavioural therapy for adults with depression: a modified Delphi study.

Designing new approaches to delivering cognitive behavioural therapy (CBT) requires an understanding of the key components. This study aimed to establish an expert consensus on the effective components of CBT for depressed adults. An international panel of 120 CBT experts was invited to participate in a modified Delphi study. Thirty-two experts participated in round 1; 21 also provided data in round 2. In round 1, experts rated the effectiveness of 35 content and process components. A priori rules identified components carried forward to round 2, in which experts re-rated items and final consensus items were identified. Consensus was achieved for nine content components (ensuring understanding; developing and maintaining a good therapeutic alliance; explaining the rationale for CBT; eliciting feedback; identifying and challenging avoidant behaviour; activity monitoring; undertaking an initial assessment; relapse prevention methods; homework assignments); and three process components (ensuring therapist competence; scheduling sessions flexibly; scheduling sessions for 45-60 mins). Five of the twelve components identified were generic therapeutic competences rather than specific CBT items. There was less agreement about the effectiveness of cognitive components of CBT. This is an important first step in the development of novel approaches to delivering CBT that may increase access to treatment for patients.

The process and delivery of CBT for depression in adults: a systematic review and network meta-analysis.

Cognitive-behavioural therapy (CBT) is an effective treatment for depressed adults. CBT interventions are complex, as they include multiple content components and can be delivered in different ways. We compared the effectiveness of different types of therapy, different components and combinations of components and aspects of delivery used in CBT interventions for adult depression. We conducted a systematic review of randomised controlled trials in adults with a primary diagnosis of depression, which included a CBT intervention. Outcomes were pooled using a component-level network meta-analysis. Our primary analysis classified interventions according to the type of therapy and delivery mode. We also fitted more advanced models to examine the effectiveness of each content component or combination of components. We included 91 studies and found strong evidence that CBT interventions yielded a larger short-term decrease in depression scores compared to treatment-as-usual, with a standardised difference in mean change of -1.11 (95% credible interval -1.62 to -0.60) for face-to-face CBT, -1.06 (-2.05 to -0.08) for hybrid CBT, and -0.59 (-1.20 to 0.02) for multimedia CBT, whereas wait list control showed a detrimental effect of 0.72 (0.09 to 1.35). We found no evidence of specific effects of any content components or combinations of components. Technology is increasingly used in the context of CBT interventions for depression. Multimedia and hybrid CBT might be as effective as face-to-face CBT, although results need to be interpreted cautiously. The effectiveness of specific combinations of content components and delivery formats remain unclear. Wait list controls should be avoided if possible.

Effect of a mindfulness exercise on stress in veterinary students performing surgery.

OBJECTIVE: To determine students' stress while performing surgery and evaluate the ability of a mindfulness intervention to reduce this stress. STUDY DESIGN: Quasi-experimental design. SAMPLE POPULATION: Eighteen fourth-year DVM program students (n = 9 student/group). METHODS: Utilizing a quasi-experimental design, students were randomly assigned to a control or treatment group. The treatment group performed a 5-minute breathing (mindfulness) exercise immediately prior to performing surgery. Each student provided 3 samples of saliva, at time 0, at 10 minutes before surgery, and at 10 minutes after surgery. Students' salivary cortisol and α-amylase levels were compared between groups. Students' self-reported mood measures were also correlated to levels of salivary biomarkers. RESULTS: Cortisol and α-amylase levels of students in both groups greatly exceeded normative reference groups (>90th percentile) prior to surgery and diminished to average levels (50th-60th percentile) after surgery but did not differ between groups at any time point. Immediately prior to surgery when stress values were likely to peak, salivary α-amylase levels decreased approximately 30 U/L units for students in the treatment group compared with an increase of approximately 10 U/L units for students in the control group. Students in the treatment group reported being more calm (mean [M] 2.67, SD 1.03, d = 0.75) and relaxed (M 2.33, SD 1.51, d = 0.90) than students in the control group (M 3.44, SD 1.01 and M 3.44, SD 0.88, respectively). CONCLUSION: This study provides some evidence that the mindfulness intervention temporarily decreased stress levels and improved students' sense of calmness and relaxation immediately before operating on a live animal. CLINICAL IMPACT: Students who are experiencing less stress may be less likely to commit a medical error and negatively impact animal health. This study, the first of its kind in veterinary surgery, may serve as a model for related future studies.

Using Cultured Mammalian Neurons to Study Cellular Processes and Neurodegeneration: A Suite of Undergraduate Lab Exercises.

Cell culture is a powerful tool for exploring cellular function. Culturing primary neurons has revealed how neurons communicate in learning and memory (Kandel, 2006) and provided insights into the mechanisms of neurodegenerative diseases such as Parkinson's and Alzheimer's disease (Alberio et al., 2012; Trinchese, et al., 2004). Here we describe a series of four modular laboratory exercises to integrate this neuroscience technique in undergraduate teaching laboratories. First, we describe the modular approach. Then we provide educators with simple techniques for culturing rat primary neurons, performing immunohistochemistry to label cellular components, and illustrating neurodegeneration caused by reactive oxygen species. We describe teaching exercises that culminate in student-generated research projects. Finally, we describe potential barriers students may face when integrating modern cell culture experiments into teaching laboratories.

The effect of surface on knee landing mechanics and muscle activity during a single-leg landing task in recreationally active females.

OBJECTIVE: Investigate the effect of surface on frontal plane knee angle, knee moment and muscle activity. DESIGN: Randomised cross over. SETTING: University Laboratory. METHODS: Twenty females performed single-leg hop-landings onto sand, grass and firm surfaces. Kinematic, kinetic and muscle activity data were obtained. Compatibility curves were used to visualise parameter estimates alongside P- values, and S-value transforms. RESULTS: Knee angle for firm-sand (mean difference (d)‾ = -2.2°; 95% compatibility interval (CI): -4.6 to 0.28, p = 0.083, s = 3.6) and firm-grass (d‾ = -1.9; 95% CI: -4.3 to 0.5, p = 0.125, S = 3) yielded <4 bits of reputational information against the null hypothesis (H). 5 bits (p = 0.025) of information against H were observed for knee moment between firm-sand (d‾ = 0.17 N m/kg-1. m-1; 95% CI: 0.02 to 0.31) with similar effects for firm-grass (d‾ = 0.14 N m/kg-1. m-1; 95% CI: -0.02 to 0.29, p = 0.055, S = 4). Muscle activity across surfaces ranged from almost no (S = 1) reputational evidence against H (Quadriceps and Hamstrings) to 10-13 'bits' against H for lateral gastrocnemius (lower on sand). CONCLUSIONS: Our study provides valuable information for practitioners of the observed effect sizes for lower-limb landing mechanics across surfaces in asymptomatic females.

Retrospective study of Oestrus ovis larvae infestation in small ruminants in Grenada, West Indies.

Oestrosis is a nasal cavity myiasis caused by Oestrus ovis larvae from Oetrus ovis diptera flies in small ruminants. The presence of the larvae in the nasal cavity is known to cause rhinitis and sinusitis which can negatively impact the productivity of small ruminants. The aim of the present study was to estimate the prevalence of Oestrus ovis larvae infestation in sheep and goats presented for necropsy. We reviewed necropsy records of sheep and goats submitted to the Veterinary Pathology diagnostic laboratory at St. George's University from 2001 to 2017. Out of 104 goat necropsy cases, Oestrus ovis larvae were observed in 8 goats giving a prevalence of 7.7% (95% confidence interval (CI):3.38% to 14.6%). Similarly, from the 47 sheep necropsies, Oestus ovis larvae were observed in 4 sheep (8.5%) (95% CI: 2.83% to 20.46%). There was no significant difference in Oestrus ovis larvae infestation rates between sheep and goats (p = 1.000, Fisher's exact test). Oestrosis was an incidental finding in all the small ruminants examined at necropsy. This is the first report on Oestrus ovis larvae infestation in small ruminants in Grenada.

Closer to Home: A Quality Improvement Initiative to Optimize Satellite Site Bed Capacity.

BACKGROUND: The coronavirus disease 2019 pandemic resulted in the underutilization of inpatient beds at our satellite location. A lack of clarity and standardized admission criteria for the satellite led to frequent transfers to the main campus, resulting in patients traveling larger distances to receive inpatient care. We sought to optimize inpatient resource use at the satellite campus and keep patients "closer to home" by admitting eligible patients to that inpatient unit (LA4). Our aim was to increase bed capacity use at the satellite from 45% to 70% within 10 months. Our process measure was to increase the proportion of patients needing hospitalization who presented to the satellite emergency department (ED) and were then admitted to LA4 from 76% to 85%. METHODS: A multidisciplinary team used quality improvement methods to optimize bed capacity use. Interventions included (1) the revision and dissemination of satellite admission guidelines, (2) steps to create shared understanding of appropriate satellite admissions between ED and inpatient providers, (3) directed provider feedback on preventable main campus admissions, and (4) consistent patient and family messaging about the potential for transfer. Data were collected via chart review. Annotated run charts were used to assess the impact of interventions over time. RESULTS: Average LA4 bed capacity use increased from 45% to 69%, which was sustained for 1 year. The average percentage of patients admitted from the satellite ED to LA4 increased from 76% to 84%. CONCLUSIONS: We improved bed capacity use at our satellite campus through transparent admission criteria and shared mental models of patient care needs between ED and inpatient providers.

Autonomic dysregulation, cognition and fatigue in people with depression and in active and healthy controls: observational cohort study.

BACKGROUND: Autonomic nervous system (ANS) dysregulation might be relevant to the pathophysiology of fatigue and cognitive impairment in depression and perhaps should be considered when making prescribing decisions. AIMS: To determine the relationship of self-reported ANS symptoms with fatigue, cognition and prescribed medication in people with a diagnosis of depression, in comparators without depression but with other mental health, neurodevelopmental or neurodegenerative disorders (active controls) and in healthy controls. METHOD: Cross-sectional analysis of an opportunistic sample from England. Self-reported data were collected on demographics, diagnosis, medication, ANS symptoms (Composite Autonomic Symptom Scale-31, COMPASS-31) and fatigue (Visual Analogue Scale for Fatigue, VAS-F). A subsample completed cognitive tests (THINC-it), including the subjective Perceived Deficits Questionnaire five-item version (PDQ-5). Spearman's correlation and mediation models were used to explore the relationship between COMPASS-31, VAS-F and PDQ-5 scores. RESULTS: Data were obtained for 3345 participants, 22% with depression. The depression group had significantly (P < 0.01) more severe autonomic dysregulation as measured by COMPASS-31 scores (median 30) than active (median 23) and healthy controls (median 10). The depression group had significantly higher symptom severity (P < 0.01) than both control groups on the VAS-F and PDQ-5. Overall, there was a significantly positive correlation (P < 0.01) between COMPASS-31, VAS-F scores (Spearman's rho rs = 0.44) and PDQ-5 scores (rs = 0.56). COMPASS-31 scores mediated greater symptom severity on the VAS-F and PDQ-5 for those with depression. COMPASS-31 scores remained significantly different between the depression group and both control groups independently of medication. CONCLUSIONS: People with a diagnosis of depression report worse fatigue and cognition than active and healthy comparators; this appears to be mediated by ANS dysregulation.

Characterization of a new mouse model of empyema and the mechanisms of pleural invasion by Streptococcus pneumoniae.

Although empyema affects more than 65,000 people each year in the United States and in the United Kingdom, there are limited data on the pathogenesis of pleural infection. We investigated the pathogenesis of empyema using animal and cell culture models of Streptococcus pneumoniae infection. The pathological processes during the development of empyema associated with murine pneumonia due to S. pneumoniae (strain D39) were investigated. Lungs were examined using histology, and pleural fluid and blood bacterial colony-forming units, cytokine levels, and cellular infiltrate were determined over time. Bacterial migration across mesothelial monolayers was investigated using cell culture techniques, flow cytometry, and confocal microscopy. After intranasal inoculation with 10(7) S. pneumoniae D39 strain, mice developed pneumonia associated with rapid bacterial invasion of the pleural space; raised intrapleural IL-8, VEGF, MCP-1, and TNF-α levels; and caused significant intrapleural neutrophilia followed by the development of fibrinous pleural adhesions. Bacterial clearance from the pleural space was poor, and in vitro assays demonstrated that S. pneumoniae crossed mesothelial layers by translocation through cells rather than by a paracellular route. This study describes key events during the development of S. pneumoniae empyema using a novel murine model of pneumonia-associated empyema that closely mimics human disease. The model allows for future assessment of molecular mechanisms involved in the development of empyema and evaluation of potential new therapies. The data suggest that transmigration of bacteria through mesothelial cells could be important in empyema development. Furthermore, upon entry the pleural cavity offers a protected compartment for the bacteria.

The role of extracellular vesicles in acquisition of resistance to therapy in glioblastomas.

Glioblastoma (GBM) is the most aggressive primary brain tumor with a median survival of 15 months despite standard care therapy consisting of maximal surgical debulking, followed by radiation therapy with concurrent and adjuvant temozolomide treatment. The natural history of GBM is characterized by inevitable recurrence with patients dying from increasingly resistant tumor regrowth after therapy. Several mechanisms including inter- and intratumoral heterogeneity, the evolution of therapy-resistant clonal subpopulations, reacquisition of stemness in glioblastoma stem cells, multiple drug efflux mechanisms, the tumor-promoting microenvironment, metabolic adaptations, and enhanced repair of drug-induced DNA damage have been implicated in therapy failure. Extracellular vesicles (EVs) have emerged as crucial mediators in the maintenance and establishment of GBM. Multiple seminal studies have uncovered the multi-dynamic role of EVs in the acquisition of drug resistance. Mechanisms include EV-mediated cargo transfer and EVs functioning as drug efflux channels and decoys for antibody-based therapies. In this review, we discuss the various mechanisms of therapy resistance in GBM, highlighting the emerging role of EV-orchestrated drug resistance. Understanding the landscape of GBM resistance is critical in devising novel therapeutic approaches to fight this deadly disease.

Acute Ischemic Stroke as a Result of Paradoxical Embolus in a Patient with Renal Cell Carcinoma, Intravenous Tumor Thrombus Extension, and Patent Foramen Ovale.

INTRODUCTION: Patent foramen ovale is a common congenital cardiac abnormality. An association with acute ischemic stroke is well described. Extension of renal cell carcinoma (RCC) into the adjacent veins is common. Surgical resection is felt to be an effective approach to treatment, even in the setting of extensive venous involvement. CASE REPORT: A 55-year-old woman with recently diagnosed right renal mass and cavoatrial tumor thrombus was transferred to our facility for surgical resection. She subsequently underwent open radical right nephrectomy, regional lymph node dissection, inferior vena cava and right atrial tumor thrombectomy, and resection of the infrahepatic vena cava. An intraoperative transesophageal echocardiogram confirmed the absence of tumor thrombus from the inferior vena cava and right atrium and also identified a patent foramen ovale (PFO). Upon weaning sedation, she was noted to be agitated and have left hemiplegia. Her National Institutes of Health Stroke Scale (NIHSS) was 30 and Glasgow Coma Scale (GCS) 6. The computerized tomography scan of head revealed extensive hypoattenuation right in the middle and left posterior cerebral artery territories. There was associated cerebral edema and 5-mm midline shift. In the setting of devastating neurological injury, her family elected to transition to comfort care and the patient died on the postoperative day 7. CONCLUSIONS: This is the first reported case of intraoperative paradoxical embolism in the setting of RCC with cavoatrial extension and PFO. The presence of PFO may be a risk factor for severe cerebrovascular complications in the surgical management of RCC with venous involvement.

Treatment interventions to maintain abstinence from alcohol in primary care: systematic review and network meta-analysis.

OBJECTIVE: To determine the most effective interventions in recently detoxified, alcohol dependent patients for implementation in primary care. DESIGN: Systematic review and network meta-analysis. DATA SOURCES: Medline, Embase, PsycINFO, Cochrane CENTRAL, ClinicalTrials.gov, and the World Health Organization's International Clinical Trials Registry Platform. STUDY SELECTION: Randomised controlled trials comparing two or more interventions that could be used in primary care. The population was patients with alcohol dependency diagnosed by standardised clinical tools and who became detoxified within four weeks. DATA EXTRACTION: Outcomes of interest were continuous abstinence from alcohol (effectiveness) and all cause dropouts (as a proxy for acceptability) at least 12 weeks after start of intervention. RESULTS: 64 trials (43 interventions) were included. The median probability of abstinence across placebo arms was 25%. Compared with placebo, the only intervention associated with increased probability of abstinence and moderate certainty evidence was acamprosate (odds ratio 1.86, 95% confidence interval 1.49 to 2.33, corresponding to an absolute probability of 38%). Of the 62 included trials that reported all cause dropouts, interventions associated with a reduced number of dropouts compared with placebo (probability 50%) and moderate certainty of evidence were acamprosate (0.73, 0.62 to 0.86; 42%), naltrexone (0.70, 0.50 to 0.98; 41%), and acamprosate-naltrexone (0.30, 0.13 to 0.67; 17%). Acamprosate was the only intervention associated with moderate confidence in the evidence of effectiveness and acceptability up to 12 months. It is uncertain whether other interventions can help maintain abstinence and reduce dropouts because of low confidence in the evidence. CONCLUSIONS: Evidence is lacking for benefit from interventions that could be implemented in primary care settings for alcohol abstinence, other than for acamprosate. More evidence from high quality randomised controlled trials is needed, as are strategies using combined interventions (combinations of drug interventions or drug and psychosocial interventions) to improve treatment of alcohol dependency in primary care. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016049779.

Optimized commercial desktop cutter technique for rapid-prototyping of microfluidic devices and application to Taylor dispersion.

Microfluidics provides a platform for efficient and transportable microanalysis, catalyzing advancements in fields such as biochemistry, materials science, and microbial ecology. While the analysis is cost-effective, standard device fabrication techniques are disproportionately expensive and specialized. A commercially available desktop cutting plotter provides an accessible method for rapidly fabricating microfluidic devices at extremely low costs. The optimized technique described in the present work enables fabrication of microchannels with dimensions as small as ∼100 µm. Straightness of channel walls is comparable to other common fabrication techniques but achieved here at a fraction of the cost and fabrication time. Solute dispersion experiments are performed using the rapidly prototyped channels to measure the effective dispersion coefficient in laminar flow through rectangular channels. The results of these experiments compare favorably to predictions from classical Taylor-Aris dispersion theory. This note provides all necessary tools for researchers and educators to seamlessly apply the desktop cutter fabrication technique. Materials list, fabrication instructions, and detailed channel characterization results are available in the supplementary material.

Management of treatment-resistant depression in primary care: a mixed-methods study.

BACKGROUND: Non-response to antidepressant medication is common in primary care. Little is known about how GPs manage patients with depression that does not respond to medication. AIM: To describe usual care for primary care patients with treatment-resistant depression (TRD). DESIGN AND SETTING: Mixed-methods study using data from a UK primary care multicentre randomised controlled trial. METHOD: In total, 235 patients with TRD randomised to continue with usual GP care were followed up at 3-month intervals for a year. Self-report data were collected on antidepressant medication, number of GP visits, and other treatments received. In addition, 14 semi-structured face-to-face interviews were conducted with a purposive sample after the 6-month follow-up and analysed thematically. RESULTS: Most patients continued on the same dose of a single antidepressant between baseline and 3 months (n = 147/186 at 3 months, 79% (95% confidence interval [CI] = 73 to 85%)). Figures were similar for later follow-ups (for example, 9-12 months: 72% (95% CI = 63 to 79%). Medication changes (increasing dose; switching to a different antidepressant; adding a second antidepressant) were uncommon. Participants described usual care mainly as taking antidepressants, with consultations focused on other (physical) health concerns. Few accessed other treatments or were referred to secondary care. CONCLUSION: Usual care in patients with TRD mainly entailed taking antidepressants, and medication changes were uncommon. The high prevalence of physical and psychological comorbidity means that, when these patients consult, their depression may not be discussed. Strategies are needed to ensure the active management of this large group of patients whose depression does not respond to antidepressant medication.

Systematic review of interventions to improve patient uptake and completion of pulmonary rehabilitation in COPD.

Pulmonary rehabilitation is considered a key management strategy for chronic obstructive pulmonary disease (COPD), but its effectiveness is undermined by poor patient uptake and completion. The aim of this review was to identify, select and synthesise the available evidence on interventions for improving uptake and completion of pulmonary rehabilitation in COPD. Electronic databases and trial registers were searched for randomised trials evaluating the effect of an intervention compared with a concurrent control group on patient uptake and completion. The primary outcomes were the number of participants who attended a baseline assessment and at least one session of pulmonary rehabilitation (uptake), and the number of participants who received a discharge assessment (completion). Only one quasi-randomised study (n=115) (of 2468 records identified) met the review inclusion criteria and was assessed as having a high risk of bias. The point estimate of effect did, however, indicate greater programme completion and attendance rates in participants allocated to pulmonary rehabilitation plus a tablet computer (enabled with support for exercise training) compared with controls (pulmonary rehabilitation only). There is insufficient evidence to guide clinical practice on interventions for improving patient uptake and completion of pulmonary rehabilitation in COPD. Despite increasing awareness of patient barriers to pulmonary rehabilitation, our review highlights the existing under-appreciation of interventional trials in this area. This knowledge gap should be viewed as an area of research priority due to its likely impact in undermining wider implementation of pulmonary rehabilitation and restricting patient access to a treatment considered the cornerstone of COPD.

Therapeutic interventions for alcohol dependence in non-inpatient settings: a systematic review and network meta-analysis (protocol).

BACKGROUND: Alcohol dependence is common and serious cause of social and physical harm. However, the optimal management of those with moderate and severe alcohol dependence in primary and community care after detoxification remains unclear. The aim of this review is to evaluate the effectiveness of interventions for maintaining abstinence in people with alcohol dependence following detoxification. METHODS: We will systematically search electronic databases and clinical trial registries for randomized controlled trials (RCTs) examining the effectiveness of pharmacological and/or psychosocial interventions for maintaining abstinence in recently detoxified, alcohol-dependent adults. The searches will be complemented by checking references and citations from included studies and other relevant systematic reviews. No limitation on language, year, or publication status will be applied. RCTs will be selected using prespecified criteria. Descriptive information, study characteristics, and results of eligible RCTs will be extracted. A revised version of the Cochrane Risk of Bias tool (RoB 2.0) will be used to assess the risk of bias in eligible RCTs. Results will be synthesized and analyzed using network meta-analysis (NMA). Overall strength of the evidence and publication bias will be evaluated. Subgroup and sensitivity analysis will also be performed. DISCUSSION: This network meta-analysis aims to appraise and summarize the total evidence of therapeutic interventions for alcohol-dependent patients that require support for detoxification and can be treated in the community. The evidence will determine which combination of interventions are most promising for current practice and further investigation. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016049779.

Unemployment and prostate cancer mortality in the OECD, 1990-2009.

The global economic downturn has been associated with increased unemployment in many countries. Insights into the impact of unemployment on specific health conditions remain limited. We determined the association between unemployment and prostate cancer mortality in members of the Organisation for Economic Co-operation and Development (OECD). We used multivariate regression analysis to assess the association between changes in unemployment and prostate cancer mortality in OECD member states between 1990 and 2009. Country-specific differences in healthcare infrastructure, population structure, and population size were controlled for and lag analyses conducted. Several robustness checks were also performed. Time trend analyses were used to predict the number of excess deaths from prostate cancer following the 2008 global recession. Between 1990 and 2009, a 1% rise in unemployment was associated with an increase in prostate cancer mortality. Lag analysis showed a continued increase in mortality years after unemployment rises. The association between unemployment and prostate cancer mortality remained significant in robustness checks with 46 controls. Eight of the 21 OECD countries for which a time trend analysis was conducted, exhibited an estimated excess of prostate cancer deaths in at least one of 2008, 2009, or 2010, based on 2000-2007 trends. Rises in unemployment are associated with significant increases in prostate cancer mortality. Initiatives that bolster employment may help to minimise prostate cancer mortality during times of economic hardship.

Scales for the identification of adults with attention deficit hyperactivity disorder (ADHD): a systematic review.

Attention deficit hyperactivity disorder (ADHD) is prevalent in the adult population. The associated co-morbidities and impairments can be relieved with treatment. Therefore, several rating scales have been developed to identify adults with ADHD who may benefit from treatment. No systematic review has yet sought to evaluate these scales in more detail. The present systematic review was undertaken to describe the properties, including psychometric statistics, of the currently available adult ADHD rating scales and their scoring methods, along with the procedure for development. Descriptive synthesis of the data is presented and study quality has been assessed by an objective quality assessment tool. The properties of each scale are discussed to make judgements about their validity and usefulness. The literature search retrieved 35 validation studies of adult ADHD rating scales and 14 separate scales were identified. The majority of studies were of poor quality and reported insufficient detail. Of the 14 scales, the Conners' Adult ADHD Rating scale and the Wender Utah Rating Scale (short version) had more robust psychometric statistics and content validity. More research into these scales, with good quality studies, is needed to confirm the findings of this review. Future studies of ADHD rating scales should be reported in more detail so that further reviews have more support for their findings.