Commercial Immunoglobulin Products Contain Neutralizing Antibodies Against Severe Acute Respiratory Syndrome Coronavirus 2 Spike Protein.

BACKGROUND: Patients with antibody deficiency respond poorly to coronavirus disease 2019 (COVID-19) vaccination and are at risk of severe or prolonged infection. They are given long-term immunoglobulin replacement therapy (IRT) prepared from healthy donor plasma to confer passive immunity against infection. Following widespread COVID-19 vaccination alongside natural exposure, we hypothesized that immunoglobulin preparations will now contain neutralizing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike antibodies, which confer protection against COVID-19 disease and may help to treat chronic infection. METHODS: We evaluated anti-SARS-CoV-2 spike antibody in a cohort of patients before and after immunoglobulin infusion. Neutralizing capacity of patient samples and immunoglobulin products was assessed using in vitro pseudovirus and live-virus neutralization assays, the latter investigating multiple batches against current circulating Omicron variants. We describe the clinical course of 9 patients started on IRT during treatment of COVID-19. RESULTS: In 35 individuals with antibody deficiency established on IRT, median anti-spike antibody titer increased from 2123 to 10 600 U/mL postinfusion, with corresponding increase in pseudovirus neutralization titers to levels comparable to healthy donors. Testing immunoglobulin products directly in the live-virus assay confirmed neutralization, including of BQ1.1 and XBB variants, but with variation between immunoglobulin products and batches.Initiation of IRT alongside remdesivir in patients with antibody deficiency and prolonged COVID-19 infection (median 189 days, maximum >900 days with an ancestral viral strain) resulted in clearance of SARS-CoV-2 at a median of 20 days. CONCLUSIONS: Immunoglobulin preparations now contain neutralizing anti-SARS-CoV-2 antibodies that are transmitted to patients and help to treat COVID-19 in individuals with failure of humoral immunity.

Interventions for female drug-using offenders.

BACKGROUND: This review represents one in a family of three reviews focusing on the effectiveness of interventions in reducing drug use and criminal activity for offenders. OBJECTIVES: To assess the effectiveness of interventions for female drug-using offenders in reducing criminal activity, or drug use, or both. SEARCH METHODS: We searched 12 electronic bibliographic databases up to February 2019. SELECTION CRITERIA: We included randomised controlled trials (RCTs). DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included 13 trials with 2560 participants. Interventions were delivered in prison (7/13 studies, 53%) and community (6/13 studies, 47%) settings. The rating of bias was affected by the lack of clear reporting by authors, and we rated many items as 'unclear'. In two studies (190 participants) collaborative case management in comparison to treatment as usual did not reduce drug use (risk ratio (RR) 0.65, 95% confidence interval (CI) 0.20 to 2.12; 1 study, 77 participants; low-certainty evidence), reincarceration at nine months (RR 0.71, 95% CI 0.32 to 1.57; 1 study, 77 participants; low-certainty evidence), and number of subsequent arrests at 12 months (RR 1.11, 95% CI 0.83 to 1.49; 1 study, 113 participants; low-certainty evidence). One study (36 participants) comparing buprenorphine to placebo showed no significant reduction in self-reported drug use at end of treatment (RR 0.57, 95% CI 0.27 to 1.20) and three months (RR 0.58, 95% CI 0.25 to 1.35); very low-certainty evidence. No adverse events were reported. One study (38 participants) comparing interpersonal psychotherapy to a psychoeducational intervention did not find reduction in drug use at three months (RR 0.67, 95% CI 0.30 to 1.50; low-certainty evidence). One study (31 participants) comparing acceptance and commitment therapy (ACT) to a waiting list showed no significant reduction in self-reported drug use using the Addiction Severity Index (mean difference (MD) -0.04, 95% CI -0.37 to 0.29) and abstinence from drug use at six months (RR 2.89, 95% CI 0.73 to 11.43); low-certainty evidence. One study (314 participants) comparing cognitive behavioural skills to a therapeutic community programme and aftercare showed no significant reduction in self-reported drug use (RR 0.86, 95% CI 0.58 to 1.27), re-arrest for any type of crime (RR 0.73, 95% CI 0.52 to 1.03); criminal activity (RR 0.80, 95% CI 0.63 to 1.03), or drug-related crime (RR 0.95, 95% CI 0.68 to 1.32). A significant reduction for arrested (not for parole) violations at six months follow-up was significantly in favour of cognitive behavioural skills (RR 0.43, 95% CI 0.25 to 0.77; very low-certainty evidence). A second study with 115 participants comparing cognitive behavioural skills to an alternative substance abuse treatment showed no significant reduction in reincarceration at 12 months (RR 0.70, 95% CI 0.43 to 1.12; low certainty-evidence. One study (44 participants) comparing cognitive behavioural skills and standard therapy versus treatment as usual showed no significant reduction in Addiction Severity Index (ASI) drug score at three months (MD 0.02, 95% CI -0.05 to 0.09) and six months (MD -0.02, 95% CI -0.09 to 0.05), and incarceration at three months (RR 0.46, 95% CI 0.04 to 4.68) and six months (RR 0.51, 95% CI 0.20 to 1.27); very low-certainty evidence. One study (171 participants) comparing a single computerised intervention versus case management showed no significant reduction in the number of days not using drugs at three months (MD -0.89, 95% CI -4.83 to 3.05; low certainty-evidence). One study (116 participants) comparing dialectic behavioural therapy and case management (DBT-CM) versus a health promotion intervention showed no significant reduction at six months follow-up in positive drug testing (RR 0.67, 95% CI 0.43 to 1.03), number of people not using marijuana (RR 1.23, 95% CI 0.95 to 1.59), crack (RR 1.00, 95% CI 0.87 to 1.14), cocaine (RR 1.02, 95% CI 0.93 to 1.12), heroin (RR 1.05, 95% CI 0.98 to 1.13), methamphetamine (RR 1.02, 95% CI 0.87 to 1.20), and self-reported drug use for any drug (RR 1.20, 95% CI 0.92 to 1.56); very low-certainty evidence. One study (211 participants) comparing a therapeutic community programme versus work release showed no significant reduction in marijuana use at six months (RR 1.03, 95% CI 0.19 to 5.65), nor 18 months (RR 1.00, 95% CI 0.07 to 14.45), heroin use at six months (RR 1.59, 95% CI 0.49 to 5.14), nor 18 months (RR 1.92, 95% CI 0.24 to 15.37), crack use at six months (RR 2.07, 95% CI 0.41 to 10.41), nor 18 months (RR 1.64, 95% CI 0.19 to 14.06), cocaine use at six months (RR 1.09, 95% CI 0.79 to 1.50), nor 18 months (RR 0.93, 95% CI 0.64 to 1.35). It also showed no significant reduction in incarceration for drug offences at 18 months (RR 1.45, 95% CI 0.87 to 2.42); with overall very low- to low-certainty evidence. One study (511 participants) comparing intensive discharge planning and case management versus prison only showed no significant reduction in use of marijuana (RR 0.79, 95% CI 0.53 to 1.16), hard drugs (RR 1.12, 95% CI 0.88 to 1.43), crack cocaine (RR 1.08, 95% CI 0.75 to 1.54), nor positive hair testing for marijuana (RR 0.75, 95% CI 0.55 to 1.03); it found a significant reduction in arrests (RR 0.19, 95% CI 0.04 to 0.87), but no significant reduction in drug charges (RR 1.07, 95% CI 0.75 to 1.53) nor incarceration (RR 1.09, 95% CI 0.86 to 1.39); moderate-certainty evidence. One narrative study summary (211 participants) comparing buprenorphine pre- and post-release from prison showed no significant reduction in drug use at 12 months post-release; low certainty-evidence. No adverse effects were reported. AUTHORS' CONCLUSIONS: The studies showed a high degree of heterogeneity for types of comparisons, outcome measures and small samples. Descriptions of treatment modalities are required. On one outcome of arrest (no parole violations), we identified a significant reduction when cognitive behavioural therapy (CBT) was compared to a therapeutic community programme. But for all other outcomes, none of the interventions were effective. Larger trials are required to increase the precision of confidence about the certainty of evidence.

Interventions for drug-using offenders with co-occurring mental health problems.

BACKGROUND: This review represents one from a family of three reviews focusing on interventions for drug-using offenders. Many people under the care of the criminal justice system have co-occurring mental health problems and drug misuse problems; it is important to identify the most effective treatments for this vulnerable population. OBJECTIVES: To assess the effectiveness of interventions for drug-using offenders with co-occurring mental health problems in reducing criminal activity or drug use, or both.This review addresses the following questions.• Does any treatment for drug-using offenders with co-occurring mental health problems reduce drug use?• Does any treatment for drug-using offenders with co-occurring mental health problems reduce criminal activity?• Does the treatment setting (court, community, prison/secure establishment) affect intervention outcome(s)?• Does the type of treatment affect treatment outcome(s)? SEARCH METHODS: We searched 12 databases up to February 2019 and checked the reference lists of included studies. We contacted experts in the field for further information. SELECTION CRITERIA: We included randomised controlled trials designed to prevent relapse of drug use and/or criminal activity among drug-using offenders with co-occurring mental health problems. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as expected by Cochrane . MAIN RESULTS: We included 13 studies with a total of 2606 participants. Interventions were delivered in prison (eight studies; 61%), in court (two studies; 15%), in the community (two studies; 15%), or at a medium secure hospital (one study; 8%). Main sources of bias were unclear risk of selection bias and high risk of detection bias.Four studies compared a therapeutic community intervention versus (1) treatment as usual (two studies; 266 participants), providing moderate-certainty evidence that participants who received the intervention were less likely to be involved in subsequent criminal activity (risk ratio (RR) 0.67, 95% confidence interval (CI) 0.53 to 0.84) or returned to prison (RR 0.40, 95% CI 0.24 to 0.67); (2) a cognitive-behavioural therapy (one study; 314 participants), reporting no significant reduction in self-reported drug use (RR 0.78, 95% CI 0.46 to 1.32), re-arrest for any type of crime (RR 0.69, 95% CI 0.44 to 1.09), criminal activity (RR 0.74, 95% CI 0.52 to 1.05), or drug-related crime (RR 0.87, 95% CI 0.56 to 1.36), yielding low-certainty evidence; and (3) a waiting list control (one study; 478 participants), showing a significant reduction in return to prison for those people engaging in the therapeutic community (RR 0.60, 95% CI 0.46 to 0.79), providing moderate-certainty evidence.One study (235 participants) compared a mental health treatment court with an assertive case management model versus treatment as usual, showing no significant reduction at 12 months' follow-up on an Addictive Severity Index (ASI) self-report of drug use (mean difference (MD) 0.00, 95% CI -0.03 to 0.03), conviction for a new crime (RR 1.05, 95% CI 0.90 to 1.22), or re-incarceration to jail (RR 0.79, 95% CI 0.62 to 1.01), providing low-certainty evidence.Four studies compared motivational interviewing/mindfulness and cognitive skills with relaxation therapy (one study), a waiting list control (one study), or treatment as usual (two studies). In comparison to relaxation training, one study reported narrative information on marijuana use at three-month follow-up assessment. Researchers reported a main effect < .007 with participants in the motivational interviewing group, showing fewer problems than participants in the relaxation training group, with moderate-certainty evidence. In comparison to a waiting list control, one study reported no significant reduction in self-reported drug use based on the ASI (MD -0.04, 95% CI -0.37 to 0.29) and on abstinence from drug use (RR 2.89, 95% CI 0.73 to 11.43), presenting low-certainty evidence at six months (31 participants). In comparison to treatment as usual, two studies (with 40 participants) found no significant reduction in frequency of marijuana use at three months post release (MD -1.05, 95% CI -2.39 to 0.29) nor time to first arrest (MD 0.87, 95% CI -0.12 to 1.86), along with a small reduction in frequency of re-arrest (MD -0.66, 95% CI -1.31 to -0.01) up to 36 months, yielding low-certainty evidence; the other study with 80 participants found no significant reduction in positive drug screens at 12 months (MD -0.7, 95% CI -3.5 to 2.1), providing very low-certainty evidence.Two studies reported on the use of multi-systemic therapy involving juveniles and families versus treatment as usual and adolescent substance abuse therapy. In comparing treatment as usual, researchers found no significant reduction up to seven months in drug dependence on the Drug Use Disorders Identification Test (DUDIT) score (MD -0.22, 95% CI -2.51 to 2.07) nor in arrests (RR 0.97, 95% CI 0.70 to 1.36), providing low-certainty evidence (156 participants). In comparison to an adolescent substance abuse therapy, one study (112 participants) found significant reduction in re-arrests up to 24 months (MD 0.24, 95% CI 0.76 to 0.28), based on low-certainty evidence.One study (38 participants) reported on the use of interpersonal psychotherapy in comparison to a psychoeducational intervention. Investigators found no significant reduction in self-reported drug use at three months (RR 0.67, 95% CI 0.30 to 1.50), providing very low-certainty evidence. The final study (29 participants) compared legal defence service and wrap-around social work services versus legal defence service only and found no significant reductions in the number of new offences committed at 12 months (RR 0.64, 95% CI 0.07 to 6.01), yielding very low-certainty evidence. AUTHORS' CONCLUSIONS: Therapeutic community interventions and mental health treatment courts may help people to reduce subsequent drug use and/or criminal activity. For other interventions such as interpersonal psychotherapy, multi-systemic therapy, legal defence wrap-around services, and motivational interviewing, the evidence is more uncertain. Studies showed a high degree of variation, warranting a degree of caution in interpreting the magnitude of effect and the direction of benefit for treatment outcomes.

A cross-sectional audit showed that most Cochrane intervention reviews searched trial registers.

OBJECTIVE: The objective of this study was to assess current Cochrane Review practice in identifying and incorporating information from clinical trial registers. STUDY DESIGN AND SETTING: A cross-sectional study was conducted to assess a sample of new or updated intervention reviews from all Cochrane Review Groups up to February 1, 2017. Two assessors independently extracted data from each review using a pretested audit questionnaire. Data were analyzed relating to the frequency of reporting (1) the register source and search strategy; (2) the results of trial register searches; and (3) the use of trial register information in the review. RESULTS: Over 90% (236/260) of Cochrane Reviews reported searching a trial register (e.g., ClinicalTrials.gov or the WHO International Clinical Trials Registry Platform). In reviews that reported trial register searches, 39% (92/236) indicated the number of trial records retrieved and 56.8% (134/236) used information from the trial register records in the review. Trial record information was incorporated into the results (39.6%; 53/134), risk of bias assessments (53.7%; 72/134), and discussion (24.6%, 33/134) and conclusion sections (25.4%, 34/134). CONCLUSION: Most audited reviews used trial register information. Guidance may be needed to better incorporate information from these valuable resources in Cochrane Reviews to assist future research decisions made by funders and prospective study investigators.

Allogeneic hematopoietic stem cell transplantation for severe, refractory juvenile idiopathic arthritis.

Patients with juvenile idiopathic arthritis (JIA) can experience a severe disease course, with progressive destructive polyarthritis refractory to conventional therapy with disease-modifying antirheumatic drugs including biologics, as well as life-threatening complications including macrophage activation syndrome (MAS). Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative immunomodulatory strategy for patients with such refractory disease. We treated 16 patients in 5 transplant centers between 2007 and 2016: 11 children with systemic JIA and 5 with rheumatoid factor-negative polyarticular JIA; all were either refractory to standard therapy, had developed secondary hemophagocytic lymphohistiocytosis/MAS poorly responsive to treatment, or had failed autologous HSCT. All children received reduced toxicity fludarabine-based conditioning regimens and serotherapy with alemtuzumab. Fourteen of 16 patients are alive with a median follow-up of 29 months (range, 2.8-96 months). All patients had hematological recovery. Three patients had grade II-IV acute graft-versus-host disease. The incidence of viral infections after HSCT was high, likely due to the use of alemtuzumab in already heavily immunosuppressed patients. All patients had significant improvement of arthritis, resolution of MAS, and improved quality of life early following allo-HSCT; most importantly, 11 children achieved complete drug-free remission at the last follow-up. Allo-HSCT using alemtuzumab and reduced toxicity conditioning is a promising therapeutic option for patients with JIA refractory to conventional therapy and/or complicated by MAS. Long-term follow-up is required to ascertain whether disease control following HSCT continues indefinitely.

Authors' response to comments from Nachman KE et al.

Authors' response to comments letter to the editor from Nachman KE et al.

PERFORMANCE OF OVID MEDLINE SEARCH FILTERS TO IDENTIFY HEALTH STATE UTILITY STUDIES.

OBJECTIVES: This study was designed to assess the sensitivity of three Ovid MEDLINE search filters developed to identify studies reporting health state utility values (HSUVs), to improve the performance of the best performing filter, and to validate resulting search filters. METHODS: Three quasi-gold standard sets (QGS1, QGS2, QGS3) of relevant studies were harvested from reviews of studies reporting HSUVs. The performance of three initial filters was assessed by measuring their relative recall of studies in QGS1. The best performing filter was then developed further using QGS2. This resulted in three final search filters (FSF1, FSF2, and FSF3), which were validated using QGS3. RESULTS: FSF1 (sensitivity maximizing) retrieved 132/139 records (sensitivity: 95 percent) in the QGS3 validation set. FSF1 had a number needed to read (NNR) of 842. FSF2 (balancing sensitivity and precision) retrieved 128/139 records (sensitivity: 92 percent) with a NNR of 502. FSF3 (precision maximizing) retrieved 123/139 records (sensitivity: 88 percent) with a NNR of 383. CONCLUSIONS: We have developed and validated a search filter (FSF1) to identify studies reporting HSUVs with high sensitivity (95 percent) and two other search filters (FSF2 and FSF3) with reasonably high sensitivity (92 percent and 88 percent) but greater precision, resulting in a lower NNR. These seem to be the first validated filters available for HSUVs. The availability of filters with a range of sensitivity and precision options enables researchers to choose the filter which is most appropriate to the resources available for their specific research.

Comparative assessment of the efficacy of onabotulinumtoxinA and oral therapies (anticholinergics and mirabegron) for overactive bladder: a systematic review and network meta-analysis.

OBJECTIVES: To compare the efficacy of onabotulinumtoxinA, mirabegron, and anticholinergics in adults with idiopathic overactive bladder (OAB) using network meta-analysis (NMA). PATIENTS AND METHODS: Information sources were searched for blinded randomised controlled trials (RCTs), of ≥2 weeks duration, comparing any dose of onabotulinumtoxinA, eligible oral/transdermal anticholinergics, or mirabegron, with each other or placebo, in adults with OAB. Bayesian random-effects models were used to synthesise the results at week 12: NMA for responder analyses and network meta-regression (NMR) for change from baseline analyses. The NMR was used to adjust for differences in baseline severity between studies. Sensitivity analysis, excluding studies considered to be at a high risk of methodological bias, was conducted. RESULTS: In all, 56 RCTs were included in the networks. For each outcome, results are reported for all licensed treatment doses. For each NMR, results are based on patients with an average number of episodes of the outcome at baseline. After 12 weeks, all treatments were more efficacious than placebo. Patients who received onabotulinumtoxinA (100 U) had, on average, the greatest reductions in urinary incontinence episodes (UIE), urgency episodes, and micturition frequency, and the highest odds of achieving decreases of 100% and ≥50% from baseline in UIE/day. When comparing onabotulinumtoxinA with other pharmacotherapies, mean differences favoured onabotulinumtoxinA 100 U over all comparators for UIE and urgency episodes (credible intervals excluded zero) and all but two of the comparators for micturition frequency. OnabotulinumtoxinA 100 U was also associated with higher odds of achieving a 100% and ≥50% decrease in UIE/day than most other licensed treatments in the network. The exclusion of studies with a high risk of bias had little impact on the conclusions. CONCLUSION: The results indicate that, after 12 weeks, onabotulinumtoxinA 100 U provides greater relief of OAB symptoms compared with most other licensed doses of other pharmacotherapies in the network.

Updated systematic review: associations between proximity to animal feeding operations and health of individuals in nearby communities.

OBJECTIVE: The objective of this review was to update a systematic review of associations between living near an animal feeding operation (AFO) and human health. METHODS: The MEDLINE® and MEDLINE® In-Process, Centre for Agricultural Biosciences Abstracts, and Science Citation Index databases were searched. Reference lists of included articles were hand-searched. Eligible studies reported exposure to an AFO and an individual-level human health outcome. Two reviewers performed study selection and data extraction. RESULTS: The search returned 3702 citations. Sixteen articles consisting of 10 study populations were included in the analysis. The health outcomes were lower and upper respiratory tracts, MRSA, other infectious disease, neurological, psychological, dermatological, otologic, ocular, gastrointestinal, stress and mood, and other non-infectious health outcomes. Most studies were observational and used prevalence measures of outcome. An association between Q fever risk and proximity to goat production was reported. Other associations were unclear. Risk of bias was serious or critical for most exposure-outcome associations. Multiplicity (i.e., a large number of potentially correlated outcomes and exposures assessed on the same study subjects) was common in the evidence base. CONCLUSIONS: Few studies reported an association between surrogate clinical outcomes and AFO proximity for respiratory tract-related outcomes. There were no consistent dose-response relationships between surrogate clinical outcome and AFO proximity. A new finding was that Q fever in goats is likely associated with an increased Q fever risk in community members. The review results for the non-respiratory health outcomes were inconclusive because only a small number of studies were available or the between-study results were inconsistent. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42014010521.

SYSTEMATIC REVIEWS OF ECONOMIC EVALUATIONS: HOW EXTENSIVE ARE THEIR SEARCHES?

OBJECTIVES: Economic evaluation (EE) is an accepted element of decision making and priority setting in healthcare. As the number of published EEs grows, so does the number of systematic reviews (SRs) of EEs. Although search methodology makes an important contribution to SR quality, search methods in reviews of EEs have not been evaluated in detail. We investigated the resources used to identify studies in recent, published SRs of EEs, and assessed whether the resources reflected recommendations. METHODS: We searched MEDLINE for SRs of EEs published since January 2013 and extracted the following from eligible reviews: databases searched, health technology assessment (HTA) sources searched, supplementary search techniques used. Results were compared against the minimum search resources recommended by National Institute for Health and Care Excellence (NICE) (MEDLINE, Embase, NHS EED, EconLit) for economic evidence for single technology appraisals, and resource types suggested in the summary of current best evidence from SuRe Info (economic databases, general databases, HTA databases, HTA agency Web pages, gray literature). RESULTS: Sixty-five SRs met the inclusion criteria; data were extracted from forty-two. Five reviews (12 percent) met or exceeded the NICE recommended resources. Nine reviews (21 percent) searched at least four of the five types of resource recommended by SuRe Info. Five reviews (12 percent) searched all five. Twenty-three reviews (55 percent) did not meet the NICE recommendations or four of five of the SuRe Info recommended resource types. Search reporting was frequently unclear or incorrect. CONCLUSIONS: Searches conducted for the majority of recently published SRs of EEs do not meet two published approaches.

Systematic review of the magnitude of change in prevalence and quantity of Salmonella after administration of pathogen reduction treatments on pork carcasses.

OBJECTIVE: In this systematic review, we summarized change in Salmonella prevalence and/or quantity associated with pathogen reduction treatments (washes, sprays, steam) on pork carcasses or skin-on carcass parts in comparative designs (natural or artificial contamination). METHODS: In January 2015, CAB Abstracts (1910-2015), SCI and CPCI-Science (1900-2015), Medline® and Medline® In-Process (1946-2015) (OVIDSP), Science.gov, and Safe Pork (1996-2012) were searched with no language or publication type restrictions. Reference lists of 24 review articles were checked. Two independent reviewers screened 4001 titles/abstracts and assessed 122 full-text articles for eligibility. Only English-language records were extracted. RESULTS: Fourteen studies (5 in commercial abattoirs) were extracted and risk of bias was assessed by two reviewers independently. Risk of bias due to systematic error was moderate; a major source of bias was the potential differential recovery of Salmonella from treated carcasses due to knowledge of the intervention. The most consistently observed association was a positive effect of acid washes on categorical measures of Salmonella; however, this was based on individual results, not a summary effect measure. CONCLUSION: There was no strong evidence that any one intervention protocol (acid temperature, acid concentration, water temperature) was clearly superior to others for Salmonella control.

The scale of the evidence base on the health effects of conventional yogurt consumption: findings of a scoping review.

BACKGROUND: The health effects of conventional yogurt have been investigated for over a century; however, few systematic reviews have been conducted to assess the extent of the health benefits of yogurt. OBJECTIVE: The aim of this scoping review was to assess the volume of available evidence on the health effects of conventional yogurt. METHODS: The review was guided by a protocol agreed a priori and informed by an extensive literature search conducted in November 2013. Randomized controlled trials were selected and categorized according to the eligibility criteria established in the protocol. RESULTS: 213 studies were identified as relevant to the scoping question. The number of eligible studies identified for each outcome were: bone health (14 studies), weight management and nutrition related health outcomes (81 studies), metabolic health (6 studies); cardiovascular health (57 studies); gastrointestinal health (24 studies); cancer (39 studies); diabetes (13 studies), Parkinson's disease risk (3 studies), all-cause mortality (3 studies), skin complaints (3 studies), respiratory complaints (3 studies), joint pain/function (2 studies); the remaining 8 studies reported a variety of other outcomes. For studies of a similar design and which assessed the same outcomes in similar population groups, we report the potential for the combining of data across studies in systematic reviews. CONCLUSIONS: This scoping review has revealed the extensive evidence base for many outcomes which could be the focus of systematic reviews exploring the health effects of conventional yogurt consumption.

Interventions for drug-using offenders with co-occurring mental illness.

BACKGROUND: This is an updated version of an original Cochrane review published in Issue 3 2006 (Perry 2006). The review represents one from a family of four reviews focusing on interventions for drug-using offenders. This specific review considers interventions aimed at reducing drug use or criminal activity, or both for drug-using offenders with co-occurring mental illness. OBJECTIVES: To assess the effectiveness of interventions for drug-using offenders with co-occurring mental illness in reducing criminal activity or drug use, or both. SEARCH METHODS: We searched 14 electronic bibliographic databases up to May 2014 and 5 Internet resources (searched between 2004 and 11 November 2009). We contacted experts in the field for further information. SELECTION CRITERIA: We included randomised controlled trials designed to reduce, eliminate, or prevent relapse of drug use and criminal activity, or both in drug-using offenders with co-occurring mental illness. We also reported data on the cost and cost-effectiveness of interventions. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by The Cochrane Collaboration. MAIN RESULTS: Eight trials with 2058 participants met the inclusion criteria. The methodological quality of the trials was generally difficult to rate due to a lack of clear reporting. On most 'Risk of bias' items, we rated the majority of studies as unclear. Overall, we could not statistically combine the results due to the heterogenous nature of the different study interventions and comparison groups. A narrative summary of the findings identified that the interventions reported limited success with reducing self report drug use, but did have some impact on re-incarceration rates, but not re-arrest. In the single comparisons, we found moderate-quality evidence that therapeutic communities determine a reduction in re-incarceration but reported less success for outcomes of re-arrest, moderate quality of evidence and self report drug use. Three single studies evaluating case management via a mental health drug court (very low quality of evidence), motivational interviewing and cognitive skills (low and very low quality of evidence) and interpersonal psychotherapy (very low quality of evidence) did not report significant reductions in criminal activity and self report drug use respectively. Quality of evidence for these three types of interventions was low to very low. The trials reported some cost information, but it was not sufficient to be able to evaluate the cost-effectiveness of the interventions. AUTHORS' CONCLUSIONS: Two of the five trials showed some promising results for the use of therapeutic communities and aftercare, but only in relation to reducing subsequent re-incarceration. Overall, the studies showed a high degree of variation, warranting a degree of caution in the interpretation of the magnitude of effect and direction of benefit for treatment outcomes. More evaluations are required to assess the effectiveness of interventions for drug-using offenders with co-occurring mental health problems.

Pharmacological interventions for drug-using offenders.

BACKGROUND: The review represents one in a family of four reviews focusing on a range of different interventions for drug-using offenders. This specific review considers pharmacological interventions aimed at reducing drug use or criminal activity, or both, for illicit drug-using offenders. OBJECTIVES: To assess the effectiveness of pharmacological interventions for drug-using offenders in reducing criminal activity or drug use, or both. SEARCH METHODS: We searched Fourteen electronic bibliographic databases up to May 2014 and five additional Web resources (between 2004 and November 2011). We contacted experts in the field for further information. SELECTION CRITERIA: We included randomised controlled trials assessing the efficacy of any pharmacological intervention a component of which is designed to reduce, eliminate or prevent relapse of drug use or criminal activity, or both, in drug-using offenders. We also report data on the cost and cost-effectiveness of interventions. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as expected by Cochrane. MAIN RESULTS: Fourteen trials with 2647 participants met the inclusion criteria. The interventions included in this review report on agonistic pharmacological interventions (buprenorphine, methadone and naltrexone) compared to no intervention, other non-pharmacological treatments (e.g. counselling) and other pharmacological drugs. The methodological trial quality was poorly described, and most studies were rated as 'unclear' by the reviewers. The biggest threats to risk of bias were generated through blinding (performance and detection bias) and incomplete outcome data (attrition bias). Studies could not be combined all together because the comparisons were too different. Only subgroup analysis for type of pharmacological treatment were done. When compared to non-pharmacological, we found low quality evidence that agonist treatments are not effective in reducing drug use or criminal activity, objective results (biological) (two studies, 237 participants (RR 0.72 (95% CI 0.51 to 1.00); subjective (self-report), (three studies, 317 participants (RR 0.61 95% CI 0.31 to 1.18); self-report drug use (three studies, 510 participants (SMD: -0.62 (95% CI -0.85 to -0.39). We found low quality of evidence that antagonist treatment was not effective in reducing drug use (one study, 63 participants (RR 0.69, 95% CI 0.28 to 1.70) but we found moderate quality of evidence that they significantly reduced criminal activity (two studies, 114 participants, (RR 0.40, 95% CI 0.21 to 0.74).Findings on the effects of individual pharmacological interventions on drug use and criminal activity showed mixed results. In the comparison of methadone to buprenorphine, diamorphine and naltrexone, no significant differences were displayed for either treatment for self report dichotomous drug use (two studies, 370 participants (RR 1.04, 95% CI 0.69 to 1.55), continuous measures of drug use (one study, 81 participants, (mean difference (MD) 0.70, 95% CI -5.33 to 6.73); or criminal activity (one study, 116 participants, (RR 1.25, 95% CI 0.83 to 1.88) between methadone and buprenorphine. Similar results were found for comparisons with diamorphine with no significant differences between the drugs for self report dichotomous drug use for arrest (one study, 825 participants, (RR 1.25, 95% CI 1.03 to 1.51) or naltrexone for dichotomous measures of reincarceration (one study, 44 participants, (RR 1.10, 95% CI 0.37 to 3.26), and continuous outcome measure of crime, (MD -0.50, 95% CI -8.04 to 7.04) or self report drug use (MD 4.60, 95% CI -3.54 to 12.74). AUTHORS' CONCLUSIONS: When compared to non-pharmacological treatment, agonist treatments did not seem effective in reducing drug use or criminal activity. Antagonist treatments were not effective in reducing drug use but significantly reduced criminal activity. When comparing the drugs to one another we found no significant differences between the drug comparisons (methadone versus buprenorphine, diamorphine and naltrexone) on any of the outcome measures. Caution should be taken when interpreting these findings, as the conclusions are based on a small number of trials, and generalisation of these study findings should be limited mainly to male adult offenders. Additionally, many studies were rated at high risk of bias.

Interventions for female drug-using offenders.

BACKGROUND: This is an updated version of a Cochrane review first published in Issue 3, 2006 (Perry 2006). The review represents one in a family of four reviews focusing on the effectiveness of interventions in reducing drug use and criminal activity for offenders. This specific review considers interventions for female drug-using offenders. OBJECTIVES: To assess the effectiveness of interventions for female drug-using offenders in reducing criminal activity, or drug use, or both. SEARCH METHODS: We searched 14 electronic bibliographic databases up to May 2014 and five additional Website resources (between 2004 and November 2011). We contacted experts in the field for further information. SELECTION CRITERIA: We included randomised controlled trials (RCTs) designed to reduce, eliminate or prevent relapse of drug use or criminal activity in female drug-using offenders. We also reported data on the cost and cost-effectiveness of interventions. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by The Cochrane Collaboration. MAIN RESULTS: Nine trials with 1792 participants met the inclusion criteria. Trial quality and risks of bias varied across each study. We rated the majority of studies as being at 'unclear' risk of bias due to a lack of descriptive information. We divided the studies into different categories for the purpose of meta-analyses: for any psychosocial treatments in comparison to treatment as usual we found low quality evidence that there were no significant differences in arrest rates, (two studies; 489 participants; risk ratio (RR) 0.82, 95% confidence interval (CI) 0.45 to 1.52) or drug use (one study; 77 participants; RR 0.65, 95% CI 0.20 to 2.12), but we found moderate quality evidence that there was a significant reduction in reincarceration, (three studies; 630 participants; RR 0.46, 95% CI 0.34 to 0.64). Pharmacological intervention using buprenorphine in comparison to a placebo did not significantly reduce self reported drug use (one study; 36 participants; RR 0.58, 95% CI 0.25 to 1.35). No cost or cost-effectiveness evidence was reported in the studies. AUTHORS' CONCLUSIONS: Three of the nine trials show a positive trend towards the use of any psychosocial treatment in comparison to treatment as usual showing an overall significant reduction in subsequent reincarceration, but not arrest rates or drug use. Pharmacological interventions in comparison to a placebo did not significantly reduce drug use and did not measure criminal activity. Four different treatment comparisons showed varying results and were not combined due to differences in the intervention and comparison groups. The studies overall showed a high degree of heterogeneity for types of comparisons and outcome measures assessed, which limited the possibility to pool the data. Descriptions of treatment modalities are required to identify the important elements for treatment success in drug-using female offenders. More trials are required to increase the precision of confidence with which we can draw conclusions about the effectiveness of treatments for female drug-using offenders.

The association between proximity to animal-feeding operations and community health: a protocol for updating a systematic review.

BACKGROUND: Livestock and poultry operations that feed large numbers of animals are common. Facility capacity varies, but it is not uncommon for facilities to house 1,000 swine with multiple barns at a single site, feedlots to house 50,000 cattle, and poultry houses to house 250,000 hens. There is primary research that suggests livestock facilities that confine animals indoors for feeding can represent a health hazard for surrounding communities. In this protocol, we describe a review about the association between proximity to animal-feeding operations (AFOs) and the health of individuals in nearby communities. A systematic review of the topic was published by some members of our group in 2010. The purpose of this review is to update that review. METHODS/DESIGN: The populations of interest are people living in communities near livestock production facilities. Outcomes of interest are any health outcome measured in humans such as respiratory disease, gastrointestinal disease, and mental health. Measures of antibiotic resistance in people from the communities compared to measures of resistance found in animals and the environment on animal-feeding operations will also be summarized. The exposure of interest will be exposure to livestock production using a variety of metrics such as distance from facilities, endotoxin levels, and measures of odor. Electronic searches will be conducted using MEDLINE and MEDLINE In-Process (via OvidSP), CAB Abstracts (via Web of Knowledge), and Science Citation Index (via Web of Knowledge). No language or date restriction will be applied. We will access the risk of bias using a pilot version of a tool developed by the Methods Groups of the Cochrane Collaboration for non-randomized interventions.We propose to conduct a meta-analysis for each health metric (e.g., combining all respiratory disease outcomes, combining all gastrointestinal outcomes). A planned subgroup analysis will be based on the domains of the risk of bias. DISCUSSION: This systematic review will provide synthesis of current evidence reporting the association between living near an animal-feeding operation and human health. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42014010521.

Searching ClinicalTrials.gov and the International Clinical Trials Registry Platform to inform systematic reviews: what are the optimal search approaches?

BACKGROUND: Since 2005, International Committee of Medical Journal Editors (ICMJE) member journals have required that clinical trials be registered in publicly available trials registers before they are considered for publication. OBJECTIVES: The research explores whether it is adequate, when searching to inform systematic reviews, to search for relevant clinical trials using only public trials registers and to identify the optimal search approaches in trials registers. METHODS: A search was conducted in ClinicalTrials.gov and the International Clinical Trials Registry Platform (ICTRP) for research studies that had been included in eight systematic reviews. Four search approaches (highly sensitive, sensitive, precise, and highly precise) were performed using the basic and advanced interfaces in both resources. RESULTS: On average, 84% of studies were not listed in either resource. The largest number of included studies was retrieved in ClinicalTrials.gov and ICTRP when a sensitive search approach was used in the basic interface. The use of the advanced interface maintained or improved sensitivity in 16 of 19 strategies for Clinicaltrials.gov and 8 of 18 for ICTRP. No single search approach was sensitive enough to identify all studies included in the 6 reviews. CONCLUSIONS: Trials registers cannot yet be relied upon as the sole means to locate trials for systematic reviews. Trials registers lag behind the major bibliographic databases in terms of their search interfaces. IMPLICATIONS: For systematic reviews, trials registers and major bibliographic databases should be searched. Trials registers should be searched using sensitive approaches, and both the registers consulted in this study should be searched.

Interventions for drug-using offenders with co-occurring mental illness.

BACKGROUND: This is an updated version of an original Cochrane review published in Issue 3 2006 (Perry 2006). The review represents one from a family of four reviews focusing on interventions for drug-using offenders. This specific review considers interventions aimed at reducing drug use or criminal activity, or both for drug-using offenders with co-occurring mental illness. OBJECTIVES: To assess the effectiveness of interventions for drug-using offenders with co-occurring mental illness in reducing criminal activity or drug use, or both. SEARCH METHODS: We searched 14 electronic bibliographic databases (searched between 2004 and 21 March 2013) and five internet resources (searched between 2004 and 11 November 2009). We contacted experts in the field for further information. SELECTION CRITERIA: We included randomised controlled trials designed to reduce, eliminate or prevent relapse in drug-using offenders with co-occurring mental illness. We also reported data on the cost and cost effectiveness of interventions. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by The Cochrane Collaboration. MAIN RESULTS: We identified 76 trials across the four reviews. Following a process of pre-screening, we judged eight trials to meet the inclusion criteria for this specific review (three of the five trials are awaiting classification). The five included 1502 participants. The interventions reported on case management via a mental health drugs court, a therapeutic community, and an evaluation of a motivational interviewing technique and cognitive skills in comparison to relaxation training. The methodological quality of the trials was generally difficult to rate due to a lack of clear reporting. On most risk of bias items, we rated the majority of studies as unclear. Overall, the combined interventions did not show a statistically significant reduction in self reported drug use (2 studies, 715 participants; risk ratio (RR) 0.82, 95% confidence interval (CI) 0.44 to 1.55). A statistically significantly reduction was shown for re-incarceration (4 studies, 627 participants; RR 0.40, 95% CI 0.24 to 0.67 and mean difference (MD) 28.72, 95% CI 5.89 to 51.54) but not re-arrest (2 studies, 518 participants; RR 1.00, 95% CI 0.90 to 1.12). A specific subgroup analysis combining studies using therapeutic community interventions showed a statistically significant reduction in re-incarceration (2 studies, 266 participants; RR 0.29, 95% CI 0.16 to 0.54) but not re-arrest (1 study, 428 participants; RR 0.90, 95% CI 0.61 to 1.33). Case management via a mental health court and motivational interviewing with cognitive skills did not show a statistically significant reduction in criminal activity (1 study, 235 participants; RR 1.05, 95% CI 0.90 to 1.22) or self reported drug misuse (1 study, 162 participants; MD -7.42, 95% CI -20.12 to 5.28). Due to the small number of studies, we were unable to analyse the impact of setting on outcome. Some cost information was provided in the trials but not sufficient to be able to evaluate the cost effectiveness of the interventions. AUTHORS' CONCLUSIONS: This review highlights the paucity of evidence for drug misusing offenders with co-occurring mental health problems. Two of the five trials showed some promising results for the use of therapeutic communities and aftercare, but only in relation to reducing subsequent re-incarceration. The studies overall, showed a high degree of statistical variation demonstrating a degree of caution in the interpretation of the magnitude of effect and direction of benefit for treatment outcomes. More evaluations are required to assess the effectiveness of interventions for drug-using offenders with co-occurring mental health problems.

Interventions for female drug-using offenders.

BACKGROUND: This is an updated version of a Cochrane review first published in Issue 3, 2006 (Perry 2006). The review represents one in a family of four reviews focusing on the effectiveness of interventions in reducing drug use and criminal activity for offenders. This specific review considers interventions for female drug-using offenders. OBJECTIVES: To assess the effectiveness of interventions for female drug-using offenders in reducing criminal activity or drug use, or both. SEARCH METHODS: We searched 14 electronic bibliographic databases (between 2004 and 21st March 2013) and five additional web resources (between 2004 and November 2011). We contacted experts in the field for further information. SELECTION CRITERIA: We include randomised controlled trials designed to reduce, eliminate or prevent relapse in female drug-using offenders. We also report data on the cost and cost effectiveness of interventions. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by the Cochrane Collaboration. MAIN RESULTS: We identified 76 trials across the four reviews. Following a process of prescreening, we judged that 11 trials met the inclusion criteria of the specified review; four of the 11 trials are awaiting classification in the review. The remaining seven trials cover 1236 participants. The interventions included in this review report on therapeutic communities (TCs), gender-responsive treatment (GRT), use of case management and cognitive skills, and a pharmacological intervention using buprenorphine. Trial quality and risks of bias varied across each study. The majority of studies were rated as being at 'unclear' risk of bias due to a lack of descriptive information. Overall the interventions showed statistically significant reductions in self-reported drug use, (four studies, 734 participants, risk ratio (RR) 0.68; 95% confidence interval (CI) 0.58 to 0.80) and re-incarceration, (four studies, 745 participants, RR 0.55; 95% CI 0.41 to 0.72). We found a statistically non-significant result for re-arrest (three studies, 803 participants, RR 0.80; 95% CI 0.53 to 1.19). Individual treatment results found that TCs and a GRT programme showed a statistically significant reduction in re-incarceration (one study, 509 participants, RR 0.42; 95% CI 0.29 to 0.60) but not for re-arrest, (one study, 314 participants, RR 0.73; 95% CI 0.52 to 1.03) and self-reported drug use (two studies, 825 participants, RR 0.47; 95% CI 0.14 to 1.53). Case management and cognitive skills programmes did not significantly reduce re-arrests, (one study, 183 participants RR 1.12; 95% CI 0.89 to 1.41) or self-reported drug use, (one study, 77 participants, RR 0.65; 95% CI 0.20 to 2.12), but did show a statistically significant reduction in re-incarceration, (three studies, 236 participants, RR 0.63; 95% CI 0.49 to 0.81). Buprenorphine did not significantly reduce self-reported drug use (RR 0.58; 95% CI 0.25 to 1.35), but this result came from a single study with only 36 participants. Due to the small number of studies we were unable to analyse the impact of treatment setting on outcome. No cost and cost effectiveness evidence was reported in the studies. AUTHORS' CONCLUSIONS: The seven trials show some positive results for the use of treatments to reduce self-reported drug use and subsequent re-incarceration. However, the studies overall showed a high degree of statistical variation, requiring a degree of caution in the interpretation of the magnitude of effect and direction of benefit for treatment outcomes. Descriptions of treatment modalities are required to identify the important elements for treatment success in drug-using female offenders. More trials are required to increase the confidence with which we can draw conclusions about the effectiveness of treatments for female drug-using offenders.