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.

[The PRISMA 2020 statement: an updated guideline for reporting systematic reviewsDeclaración PRISMA 2020: una guía actualizada para la publicación de revisiones sistemáticas]. / A declaração PRISMA 2020: diretriz atualizada para relatar revisões sistemáticas.

The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, published in 2009, was designed to help systematic reviewers transparently report why the review was done, what the authors did, and what they found. Over the past decade, advances in systematic review methodology and terminology have necessitated an update to the guideline. The PRISMA 2020 statement replaces the 2009 statement and includes new reporting guidance that reflects advances in methods to identify, select, appraise, and synthesise studies. The structure and presentation of the items have been modified to facilitate implementation. In this article, we present the PRISMA 2020 27-item checklist, an expanded checklist that details reporting recommendations for each item, the PRISMA 2020 abstract checklist, and the revised flow diagrams for original and updated reviews.

La declaración PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses), publicada en 2009, se diseñó para ayudar a los autores de revisiones sistemáticas a documentar de manera transparente el porqué de la revisión, qué hicieron los autores y qué encontraron. Durante la última década, ha habido muchos avances en la metodología y terminología de las revisiones sistemáticas, lo que ha requerido una actualización de esta guía. La declaración PRISMA 2020 sustituye a la declaración de 2009 e incluye una nueva guía de presentación de las publicaciones que refleja los avances en los métodos para identificar, seleccionar, evaluar y sintetizar estudios. La estructura y la presentación de los ítems ha sido modificada para facilitar su implementación. En este artículo, presentamos la lista de verificación PRISMA 2020 con 27 ítems, y una lista de verificación ampliada que detalla las recomendaciones en la publicación de cada ítem, la lista de verificación del resumen estructurado PRISMA 2020 y el diagrama de flujo revisado para revisiones sistemáticas.

The PRISMA 2020 statement: An updated guideline for reporting systematic reviews.

Matthew Page and co-authors describe PRISMA 2020, an updated reporting guideline for systematic reviews and meta-analyses.

Evidence-based searching for health technology assessment: keeping up to date with SuRe Info.

BACKGROUND: Evidence syntheses of all types have their foundation in literature searches. Literature searching is developing in line with the growing use of evidence synthesis and is also informed, as a field of work, by the spirit of being evidence-based. Increasing numbers of research papers about information retrieval are being published, and keeping up to date with the latest developments in this ever more wide-ranging field is demanding. METHODS: Summarized Research in Information Retrieval for HTA (SuRe Info) is a Web site (http://www.sure-info.org) that summarizes research-based information on effective and efficient evidence identification for the different aspects of health technology assessment (HTA) and evidence synthesis. This paper describes the rationale, processes, and challenges of producing SuRe Info and insights into the pace of development in the field of evidence-based information retrieval. The paper also provides scenarios suggesting how SuRe Info can help searchers in their daily work and with specific questions. RESULTS: SuRe Info currently comprises seventeen chapters, falling into two categories: (i) chapters about general search methods relating to all types of research and (ii) chapters summarizing the methods to use when searching for specific aspects of HTA (as defined in the HTA Core Model® by the European Network for Health Technology Assessment (EUnetHTA)). CONCLUSIONS: SuRe Info is not a substitute for methods handbooks, but by providing an overview of current research evidence for major issues in information retrieval in HTA, it helps searchers in this field to keep abreast of the latest research.

Which are the most sensitive search filters to identify randomized controlled trials in MEDLINE?

OBJECTIVE: The Cochrane Handbook of Systematic Reviews contains search filters to find randomized controlled trials (RCTs) in Ovid MEDLINE: one maximizing sensitivity and another balancing sensitivity and precision. These filters were originally published in 1994 and were adapted and updated in 2008. To determine the performance of these filters, the authors tested them and thirty-six other MEDLINE filters against a large new gold standard set of relevant records. METHODS: We identified a gold standard set of RCT reports published in 2016 from the Cochrane CENTRAL database of controlled clinical trials. We retrieved the records in Ovid MEDLINE and combined these with each RCT filter. We calculated their sensitivity, relative precision, and f-scores. RESULTS: The gold standard comprised 27,617 records. MEDLINE searches were run on July 16, 2019. The most sensitive RCT filter was Duggan et al. (sensitivity=0.99). The Cochrane sensitivity-maximizing RCT filter had a sensitivity of 0.96 but was more precise than Duggan et al. (0.14 compared to 0.04 for Duggan). The most precise RCT filters had 0.97 relative precision and 0.83 sensitivity. CONCLUSIONS: The Cochrane Ovid MEDLINE sensitivity-maximizing RCT filter can continue to be used by Cochrane reviewers and to populate CENTRAL, as it has very high sensitivity and a slightly better precision relative to more sensitive filters. The results of this study, which used a very large gold standard to compare the performance of all known RCT filters, allows searchers to make better informed decisions about which filters to use for their work.

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.

Development of a search filter to identify reports of controlled clinical trials within CINAHL Plus.

BACKGROUND: Evidence synthesis reviews in health care rely on the efficient identification of research evidence, particularly evidence from randomised controlled trials (RCTs). There are no recently validated filters to identify RCTs in the Cumulative Index to Nursing and Allied Health Literature (CINAHL Plus). OBJECTIVES: To develop, test and validate a search filter to identify reports of RCTs from CINAHL Plus. METHODS: Nine sets of relevant and irrelevant records were identified to develop and test search filters iteratively. Two sets were used to validate the sensitivity and precision of the filters. The performance of two previously published filters and the filter built into EBSCOhost was evaluated. RESULTS: We present a validated filter which offers sensitivity of 0.88 (95% CI: 0.77-0.95) and precision of 0.36 (95% CI: 0.31-0.41). This is comparable to the sensitivity of published filters, but has much better precision. CONCLUSIONS: A sensitive and precise filter, developed using records selected based on title and abstract information, is available for identifying reports of RCTs in the CINAHL Plus database via EBSCOhost. Using this filter is likely to reduce the number of results needing to be screened to a quarter of those retrieved by other published filters.

Translating the Cochrane EMBASE RCT filter from the Ovid interface to Embase.com: a case study.

BACKGROUND: Information specialists frequently translate search filters from one interface to another. Publications advise that translation can be complex and should be undertaken carefully. OBJECTIVES: To investigate the issues arising when translating the Cochrane Embase RCT search filter from one interface (Ovid) to another (Embase.com). METHODS: We drafted a translation of the Cochrane Ovid RCT filter to run in Embase.com. We compared the line-by-line results of the Ovid filter with the results of the translation. We revised the filter. We identified differences between database versions including records with different publication years and subject headings. Some records were in Embase in one interface but not in the other. We encountered expected interface differences relating to proximity operators. We also encountered unexpected interface issues around truncation and the use of the original title or original abstract field. DISCUSSION: Filter conversion is challenging and time consuming revealing unexpected differences in interfaces and databases. Careful planning can pre-empt some issues, but others may only emerge during testing. We identified interface anomalies that have led database publishers to review aspects of the way their interfaces work. CONCLUSIONS: Translators should be vigilant for known and unknown differences in both interfaces and database versions.

Systematic Review and Network Meta-Analysis of Treatments for Chemotherapy-Naive Patients with Asymptomatic/Mildly Symptomatic Metastatic Castration-Resistant Prostate Cancer.

OBJECTIVES: To estimate the relative effectiveness of enzalutamide in chemotherapy-naive metastatic castration-resistant prostate cancer by conducting a systematic literature review and a network meta-analysis (NMA). METHODS: A systematic literature review identified randomized controlled trials comparing enzalutamide, abiraterone/prednisone, radium-223, sipuleucel-T, or docetaxel with each other or placebo in chemotherapy-naive or mixed populations (with and without prior chemotherapy) with asymptomatic/mildly symptomatic metastatic castration-resistant prostate cancer. Feasibility assessment evaluated the trials' suitability for NMA inclusion. The main outcomes were hazard ratios (HRs) for overall survival (OS) and radiographic progression-free survival (rPFS). RESULTS: Searches of relevant bibliographic databases, trial registers, Web sites, and conference abstracts conducted in October 2014 identified 25,712 records. Ten randomized controlled trials were eligible for the NMA. Enzalutamide was superior to placebo for OS and rPFS (fixed-effects model). NMA results (fixed-effects model) showed no evidence of a difference between enzalutamide and abiraterone/prednisone (HR 0.95 [95% CrI 0.77-1.16]), sipuleucel-T (HR 1.07 [95% CrI 0.84-1.37]), or radium-223 (HR 1.10 [95% CrI 0.87-1.37]) for OS. HRs were similar for the random-effects model. Nevertheless, results (fixed-effects model) suggested that enzalutamide was superior to abiraterone/prednisone (HR 0.59 [95% CrI 0.48-0.72]) and sipuleucel-T (HR 0.32 [95% CrI 0.25-0.42]) for rPFS. Results also suggested superiority of enzalutamide versus placebo, abiraterone/prednisone, or sipuleucel-T for time to chemotherapy. CONCLUSIONS: For rPFS, the NMA suggests that enzalutamide is superior to abiraterone/prednisone and sipuleucel-T. There is no evidence of a statistically significant difference in OS between enzalutamide and abiraterone/prednisone, sipuleucel-T, or radium-223. Given the limitations in network construction and underlying assumptions made to complete these analyses, results should be interpreted with caution.

WHICH DATABASES SHOULD BE USED TO IDENTIFY STUDIES FOR SYSTEMATIC REVIEWS OF ECONOMIC EVALUATIONS?

OBJECTIVES: This study investigated which databases and which combinations of databases should be used to identify economic evaluations (EEs) to inform systematic reviews. It also investigated the characteristics of studies not identified in database searches and evaluated the success of MEDLINE search strategies used within typical reviews in retrieving EEs in MEDLINE. METHODS: A quasi-gold standard (QGS) set of EEs was collected from reviews of EEs. The number of QGS records found in nine databases was calculated and the most efficient combination of databases was determined. The number and characteristics of QGS records not retrieved from the databases were collected. Reproducible MEDLINE strategies from the reviews were rerun to calculate the sensitivity and precision for each strategy in finding QGS records. RESULTS: The QGS comprised 351 records. Across all databases, 337/351 (96 percent) QGS records were identified. Embase yielded the most records (314; 89 percent). Four databases were needed to retrieve all 337 references: Embase + Health Technology Assessment database + (MEDLINE or PubMed) + Scopus. Four percent (14/351) of records could not be found in any database. Twenty-nine of forty-one (71 percent) reviews reported a reproducible MEDLINE strategy. Ten of twenty-nine (34.5 percent) of the strategies missed at least one QGS record in MEDLINE. Across all twenty-nine MEDLINE searches, 25/143 records were missed (17.5 percent). Mean sensitivity was 89 percent and mean precision was 1.6 percent. CONCLUSIONS: Searching beyond key databases for published EEs may be inefficient, providing the search strategies in those key databases are adequately sensitive. Additional search approaches should be used to identify unpublished evidence (grey literature).

A systematic review of known interventions for the treatment of chronic nonhypovolaemic hypotonic hyponatraemia and a meta-analysis of the vaptans.

International and national guidelines on the treatment of chronic nonhypovolaemic hypotonic hyponatraemia differ; therefore, we have undertaken this systematic review and meta-analysis to investigate the efficacy and safety of interventions for the treatment of chronic nonhypovolaemic hypotonic hyponatraemia. Following registration of the review protocol with PROSPERO, systematic literature searches were conducted to identify randomized and quasi-randomized controlled trials assessing any degree of fluid restriction or any drug treatment with the aim of increasing serum sodium concentration in patients with chronic nonhypovolaemic hypotonic hyponatraemia. Where appropriate, outcome data were synthesized in a meta-analysis. A total of 45 716 bibliographic records were identified from the searches and 18 trials (assessing conivaptan, lixivaptan, tolvaptan and satavaptan) met the eligibility criteria. Results suggest that all four vasopressin receptor agonists ("vaptans") significantly improve serum sodium concentration. Lixivaptan, satavaptan and tolvaptan were associated with greater rates of response versus placebo. There was no evidence of a difference between each of the vaptans compared with placebo for mortality, discontinuation and rates of hypernatraemia. No RCT evidence of treatments other than the vaptans for hyponatraemia such as oral urea, salt tablets, mannitol, loop diuretics demeclocycline or lithium was identified. Vaptans demonstrated superiority over placebo for outcomes relating to serum sodium correction. Few trials documented the potential benefit of vaptans on change in health-related quality of life as a result of treatment. There was also a lack of high-quality RCT evidence on the comparative efficacy of the vaptans and other treatment strategies for the treatment of chronic nonhypovolaemic hypotonic hyponatraemia.

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.

Systematic review and network meta-analysis of tedizolid for the treatment of acute bacterial skin and skin structure infections caused by MRSA.

BACKGROUND: Tedizolid, the active moiety of tedizolid phosphate, is approved in the United States, the European Union, Canada and a number of other countries for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by certain susceptible bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). This network meta-analysis (NMA) evaluates the comparative effectiveness of tedizolid and other antibacterials indicated for the treatment of ABSSSI caused by MRSA. METHODS: Systematic review of 10 databases was undertaken to inform an NMA to estimate the relative effectiveness of tedizolid and established monotherapy comparators (ceftaroline, daptomycin, linezolid, teicoplanin, tigecycline, vancomycin) for treating MRSA-associated ABSSSI. Randomized controlled trials enrolling adults with ABSSSI or complicated skin and skin structure infections caused by suspected/documented MRSA were eligible for inclusion. Networks were developed based on similarity of study design, patient characteristics, outcome measures and available data. Outcomes of interest included clinical response at end of therapy (EOT), post-therapy evaluation (PTE) or test-of-cure assessment and treatment discontinuations resulting from adverse events (AEs). Bayesian NMA was conducted for each outcome using fixed-effects and random effects models. RESULTS: Literature searches identified 3,618 records; 15 trials met the inclusion criteria and were considered suitable for NMA comparison. In fixed-effects models, tedizolid had higher odds of clinical response at EOT (odds ratio [OR], 1.7; credible interval, 1.0, 3.0) and PTE than vancomycin (OR, 1.6; credible interval, 1.1, 2.5). No differences in odds of clinical response at EOT or PTE were observed between tedizolid and other comparators. There was no evidence of a difference among treatments for discontinuation due to AEs. Results from random effects and fixed-effects models were generally consistent. CONCLUSIONS: Tedizolid was superior to vancomycin for clinical response at EOT and PTE. There was no evidence of a difference between tedizolid and other comparators and no evidence of a difference between tedizolid and all comparators when evaluating discontinuation due to AEs. These findings suggest that tedizolid provides an alternative option for the management of serious skin infections caused by suspected or documented MRSA. This study is subject to the limitations inherent in all NMAs, and the results should be interpreted accordingly.

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.

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.

Understanding factors affecting patient and public engagement and recruitment to digital health interventions: a systematic review of qualitative studies.

BACKGROUND: Numerous types of digital health interventions (DHIs) are available to patients and the public but many factors affect their ability to engage and enrol in them. This systematic review aims to identify and synthesise the qualitative literature on barriers and facilitators to engagement and recruitment to DHIs to inform future implementation efforts. METHODS: PubMed, MEDLINE, CINAHL, Embase, Scopus and the ACM Digital Library were searched for English language qualitative studies from 2000 - 2015 that discussed factors affecting engagement and enrolment in a range of DHIs (e.g. 'telemedicine', 'mobile applications', 'personal health record', 'social networking'). Text mining and additional search strategies were used to identify 1,448 records. Two reviewers independently carried out paper screening, quality assessment, data extraction and analysis. Data was analysed using framework synthesis, informed by Normalization Process Theory, and Burden of Treatment Theory helped conceptualise the interpretation of results. RESULTS: Nineteen publications were included in the review. Four overarching themes that affect patient and public engagement and enrolment in DHIs emerged; 1) personal agency and motivation; 2) personal life and values; 3) the engagement and recruitment approach; and 4) the quality of the DHI. The review also summarises engagement and recruitment strategies used. A preliminary DIgital Health EnGagement MOdel (DIEGO) was developed to highlight the key processes involved. Existing knowledge gaps are identified and a number of recommendations made for future research. Study limitations include English language publications and exclusion of grey literature. CONCLUSION: This review summarises and highlights the complexity of digital health engagement and recruitment processes and outlines issues that need to be addressed before patients and the public commit to digital health and it can be implemented effectively. More work is needed to create successful engagement strategies and better quality digital solutions that are personalised where possible and to gain clinical accreditation and endorsement when appropriate. More investment is also needed to improve computer literacy and ensure technologies are accessible and affordable for those who wish to sign up to them. SYSTEMATIC REVIEW REGISTRATION: International Prospective Register of Systematic Reviews CRD42015029846.

A review of the systematic review process and its applicability for use in evaluating evidence for health claims on probiotic foods in the European Union.

This paper addresses the use of systematic review and meta-analysis to evaluate the strength of evidence for health benefits of probiotic foods, especially relating to health claim substantiation in the European Union. A systematic review is a protocol-driven, transparent and replicable approach, widely accepted in a number of scientific fields, and used by many policy-setting organizations to evaluate the strength of evidence to answer a focused research question. Many systematic reviews have been published on the broad category of probiotics for many different outcomes. Some of these reviews have been criticized for including poor quality studies, pooling heterogeneous study results, and not considering publication bias. Well-designed and -conducted systematic reviews should address such issues. Systematic reviews of probiotics have an additional challenge - rarely addressed in published reviews - in that there must be a scientifically sound basis for combining evidence on different strains, species or genera. The European Food Safety Authority (EFSA) is increasingly adopting the systematic review methodology. It remains to be seen how health claims supported by systematic reviews are evaluated within the EFSA approval process. The EFSA Panel on Dietetic Products, Nutrition and Allergies deems randomized trials to be the best approach to generating evidence about the effects of foods on health outcomes. They also acknowledge that systematic reviews (with or without meta-analyses) are the best approach to assess the totality of the evidence. It is reasonable to use these well-established methods to assess objectively the strength of evidence for a probiotic health claim. Use of the methods to combine results on more than a single strain or defined blend of strains will require a rationale that the different probiotics are substantively similar, either in identity or in their mode of action.

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.