Context: Editorial peer review is widely used to select submissions to journals for publication and is presumed to improve their usefulness. Sufficient research on peer review has been published to consider a synthesis of its effects. Methods To examine the evidence of the effects of editorial peer-review processes in biomedical journals, we conducted electronic and full-text searches of private and public databases to June 2000 and corresponded with the World Association of Medical Editors, European Association of Science Editors, Council of Science Editors, and researchers in the field to locate comparative studies assessing the effects of any stage of the peer-review process that made some attempt to control for confounding. Nineteen of 135 identified studies fulfilled our criteria. Because of the diversity of study questions, methods, and outcomes, we did not pool results. Results: Nine studies considered the effects of concealing reviewer/author identity. Four studies suggested that concealing reviewer or author identity affected review quality (mostly positively); however, methodological limitations make their findings ambiguous, and other studies' results were either negative or inconclusive. One study suggested that a statistical checklist can improve report quality, but another failed to find an effect of publishing another checklist. One study found no evidence that training referees improves performance and another showed increased interrater reliability; both used open designs, making interpretation difficult. Two studies of how journals communicate with reviewers did not demonstrate any effect on review quality. One study failed to show reviewer bias, but the findings may not be generalizable . One nonrandomized study compared the quality of articles published in peer-reviewed vs other journals. Two studies showed that editorial processes make articles more readable and improve the quality of reporting, but the findings may have limited generalizability to other journals. Conclusions: Editorial peer review, although widely used, is largely untested and its effects are uncertain.
\n \n\n \n \nObjective: To review systematically the evidence of effectiveness of physical interventions to interrupt or reduce the spread of respiratory viruses. Data sources: Cochrane Library, Medline, OldMedline, Embase, and CINAHL, without restrictions on language or publication. Data selection: Studies of any intervention to prevent the transmission of respiratory viruses (isolation, quarantine, social distancing, barriers, personal protection, and hygiene). A search of study designs included randomised trials, cohort, case-control, crossover, before and after, and time series studies. After scanning of the titles, abstracts and full text articles as a first filter, a standardised form was used to assess the eligibility of the remainder. Risk of bias of randomised studies was assessed for generation of the allocation sequence, allocation concealment, blinding, and follow-up. Non-randomised studies were assessed for the presence of potential confounders and classified as being at low, medium, or high risk of bias. Data synthesis: 58 papers of 59 studies were included. The quality of the studies was poor for all four randomised controlled trials and most cluster randomised controlled trials; the observational studies were of mixed quality. Meta-analysis of six case-control studies suggested that physical measures are highly effective in preventing the spread of severe acute respiratory syndrome: handwashing more than 10 times daily (odds ratio 0.45, 95% confidence interval 0.36 to 0.57; number needed to treat=4, 95% confidence interval 3.65 to 5.52), wearing masks (0.32, 0.25 to 0.40; NNT=6, 4.54 to 8.03), wearing N95 masks (0.09, 0.03 to 0.30; NNT=3, 2.37 to 4.06), wearing gloves (0.43, 0.29 to 0.65; NNT=5, 4.15 to 15.41), wearing gowns (0.23, 0.14 to 0.37; NNT=5, 3.37 to 7.12), and handwashing, masks, gloves, and gowns combined (0.09, 0.02 to 0.35; NNT=3, 2.66 to 4.97). The combination was also effective in interrupting the spread of influenza within households. The highest quality cluster randomised trials suggested that spread of respiratory viruses can be prevented by hygienic measures in younger children and within households. Evidence that the more uncomfortable and expensive N95 masks were superior to simple surgical masks was limited, but they caused skin irritation. The incremental effect of adding virucidals or antiseptics to normal handwashing to reduce respiratory disease remains uncertain. Global measures, such as screening at entry ports, were not properly evaluated. Evidence was limited for social distancing being effective, especially if related to risk of exposure - that is, the higher the risk the longer the distancing period. Conclusion: Routine long term implementation of some of the measures to interrupt or reduce the spread of respiratory viruses might be difficult. However, many simple and low cost interventions reduce the transmission of epidemic respiratory viruses. More resources should be invested into studying which physical interventions are the most effective, flexible, and cost effective means of minimising the impact of acute respiratory tract infections.
\n \n\n \n \nBackground: A systematic review found that 3% of working adults who had received influenza vaccine and 5% of those who were unvaccinated had laboratory-proven influenza per season; in healthcare workers (HCWs) these percentages were 5% and 8% respectively. Healthcare workers may transmit influenza to patients. Objectives: To identify all randomised controlled trials (RCTs) and non-RCTs assessing the effects of vaccinating healthcare workers on the incidence of laboratory-proven influenza, pneumonia, death from pneumonia and admission to hospital for respiratory illness in those aged 60 years or older resident in long-term care institutions (LTCIs). Search methods: We searched CENTRAL (2015, Issue 9), MEDLINE (1966 to October week 3, 2015), EMBASE (1974 to October 2015) and Web of Science (2006 to October 2015), but Biological Abstracts only from 1969 to March 2013 and Science Citation Index-Expanded from 1974 to March 2013 due to lack of institutional access in 2015. Selection criteria: Randomised controlled trials (RCTs) and non-RCTs of influenza vaccination of healthcare workers caring for individuals aged 60 years or older in LTCIs and the incidence of laboratory-proven influenza and its complications (lower respiratory tract infection, or hospitalisation or death due to lower respiratory tract infection) in individuals aged 60 years or older in LTCIs. Data collection and analysis: Two authors independently extracted data and assessed risk of bias. Effects on dichotomous outcomes were measured as risk differences (RDs) with 95% confidence intervals (CIs). We assessed the quality of evidence with GRADE. Main results: We identified four cluster-RCTs and one cohort study (n = 12,742) of influenza vaccination for HCWs caring for individuals \u2265 60 years in LTCIs. Four cluster RCTs (5896 residents) provided outcome data that addressed the objectives of our review. The studies were comparable in their study populations, intervention and outcome measures. The studies did not report adverse events. The principal sources of bias in the studies related to attrition, lack of blinding, contamination in the control groups and low rates of vaccination coverage in the intervention arms, leading us to downgrade the quality of evidence for all outcomes due to serious risk of bias. Offering influenza vaccination to HCWs based in long term care homes may have little or no effect on the number of residents who develop laboratory-proven influenza compared with those living in care homes where no vaccination is offered (RD 0 (95% CI -0.03 to 0.03), two studies with samples taken from 752 participants; low quality evidence). HCW vaccination probably leads to a reduction in lower respiratory tract infection in residents from 6% to 4% (RD -0.02 (95% CI -0.04 to 0.01), one study of 3400 people; moderate quality evidence). HCW vaccination programmes may have little or no effect on the number of residents admitted to hospital for respiratory illness (RD 0 (95% CI -0.02 to 0.02, one study of 1059 people; low quality evidence). We decided not to combine data on deaths from lower respiratory tract infection (two studies of 4459 people) or all cause deaths (four studies of 8468 people). The direction and size of difference in risk varied between the studies. We are uncertain as to the effect of vaccination on these outcomes due to the very low quality of evidence. Adjusted analyses, which took into account the cluster design, did not differ substantively from the pooled analysis with unadjusted data. Authors' conclusions: Our review findings have not identified conclusive evidence of benefit of HCW vaccination programmes on specific outcomes of laboratory-proven influenza, its complications (lower respiratory tract infection, hospitalisation or death due to lower respiratory tract illness), or all cause mortality in people over the age of 60 who live in care institutions. This review did not find information on co-interventions with healthcare worker vaccination: hand-washing, face masks, early detection of laboratory-proven influenza, quarantine, avoiding admissions, antivirals and asking healthcare workers with influenza or influenza-like illness (ILI) not to work. This review does not provide reasonable evidence to support the vaccination of healthcare workers to prevent influenza in those aged 60 years or older resident in LTCIs. High quality RCTs are required to avoid the risks of bias in methodology and conduct identified by this review and to test further these interventions in combination.
\n \n\n \n \n\u00a9 Purpose Trustworthy reporting of quadrivalent human papillomavirus (HPV) vaccine trials is the foundation for assessing the vaccine's risks and benefits. However, several pivotal trial publications incompletely reported important methodological details and inaccurately described the formulation that the control arms received. Under the Restoring Invisible and Abandoned Trials initiative (RIAT), we aim to restore the public record regarding the content and rationale of the controls used in the trials. Methods We assembled a cohort (five randomised controlled trials) described as placebo-controlled using clinical study reports (CSRs) obtained from the European Medicines Agency. We extracted the content and rationale for the choice of control used in each trial across six data sources: trial publications, register records, CSR synopses, CSR main bodies, protocols and informed consent forms. Results Across data sources, the control was inconsistently reported as \u00e2 \u20ac placebo'-containing aluminium adjuvant (sometimes with dose information). Amorphous aluminium hydroxyphosphate sulfate (AAHS) was not mentioned in any trial registry entry, but was mentioned in all publications and CSRs. In three of five trials, consent forms described the control as an \u00e2 \u20ac inactive' substance. No rationale for the selection of the control was reported in any trial publication, register, consent form, CSR synopsis or protocol. Three trials reported the rationale for choice of control in CSRs: to preserve blinding and assess the safety of HPV virus-like particles as the \u00e2 \u20ac safety profile of (AAHS) is well characterised'. Conclusions The stated rationale of using AAHS control-to characterise the safety of the HPV virus-like particles-lacks clinical relevance. A non-placebo control may have obscured an accurate assessment of safety and the participant consent process of some trials raises ethical concerns. Trial registration numbers NCT00092482, NCT00092521, NCT00092534, NCT00090220, NCT00090285.
\n \n\n \n \nIntroduction: There is growing interest in the use of both proton beam therapy (PBT) and carbon ion radiation therapy (CIRT), which are types of hadrontherapy. Although neither are new technologies they have been subject to assessment by several Health Technology Assessment (HTA) agencies over the past years. The main claimed benefit of PBT and CIRT is a reduction in toxicity compared to conventional radiation therapy, resulting in fewer harms and a lower risk of induced secondary malignancies. Such an advantage would be particularly relevant to children and young adults. Sizeable hadrontherapy centres expansion is underway worldwide, while evidence supporting claims of superiority over conventional radiation therapy is thought to be currently insufficient. Objectives: The report is aimed at presenting the state of the art of clinical research in both PBT and CIRT, by summarising the evidence findings from most recent and uptodate HTA reports and by providing a description of all currently ongoing clinical studies. Methods: The search for HTA reports was carried out on 3 databases to identify reports published between January 2011 and June 2019. The quality of the identified reports was assessed using the AMSTAR instrument. The search for ongoing studies was carried out on four public registers in July 2019. All identified ongoing studies were included. Results: The overview of available evidence for PBT is drawn from five HTA reports on a total of 16 oncology indications, including 295 primary studies of any study design. One HTA report also included eight guidelines. All included HTA reports concluded that the quality of research is low and that there is insufficient evidence to support the claimed benefits of PBT. Seventytwo non-comparative ongoing studies and 25 comparative ongoing studies were identified. Seventeen were randomized controlled studies comparing Proton Beam Therapy with current practice. The search for HTA reports assessing the use of CIRT in oncology identified five reports, two of which were up to date and of good quality reporting data from primary studies. The largest report identified 56 studies on 13 indications, but only 27 studies (including only one randomised trial) could be included in a qualitative synthesis, providing no evidence of differences in efficacy and safety of CIRT compared to photontherapy. The other report focused on the effects of CIRT on chordomas and chondrosarcomas, highlighting the heterogeneity and inconsistency of available data mostly coming from low-quality studies. Thirtyseven ongoing studies were identified, 5 of which were RCT versus conventional treatment and 32 were single-arm studies. Table A summarises the findings, by clinical indication, from the included HTA reports and from the overview of ongoing clinical research. The Table reports the current level of certainty on superiority of PBT or CIRT compared to photon radiation therapy and the likelihood that future research results would resolve current uncertainty. Conclusions. Despite the growing number of studies being published and the growing number of PBT and/or CIRT centres opening or at a planning stage, there is persistent uncertainty on the added clinical benefit of hadrontherapy treatments over conventional radiation therapy. Clinical research currently underway may not contribute to solve this uncertainty. There is a lack of agreement on the appropriate study design to assess the effects of hadrontherapies and lack of coordination between centres in the production of joint research protocols to generate the necessary evidence. This has led to the production of numerous small, poorly designed and reported studies. These shortcomings might confine the use of PBT and CIRT to experimental treatments and require that patients willing to undergo PBT or CIRT be fully informed of the risks and uncertainties of the outcomes.
\n \n\n \n \nIn this chapter several application examples derived from the literature and from the real world show how new elementary mathematics like: Topological Weighted Centroid (TWC); Self Topological Weighted Centroid (STWC); Proximity Scalar Field; Gradient of the Scalar Field Relative Topological Weighted Centroid (TWCi); Paths from Arithmetic Centroid to entities; Paths between entities; Scalar Field of the trajectories, may help decision makers in situations characterized by limited amount of information, and how mathematics of complex system can improve the level of accuracy obtained with classical statistics. In particular the TWC proposes itself as a powerful method to identify the source of epidemic spread. The impressive results obtained in the example of Russian influenza spreading in Sweden in 1889 and in the colera spreading in London in 1854 are consistent with the idea that the spread of infectious disease is not random but follows a progression which is based on inherent but as yet undiscovered mathematical laws based on probabilistic density function. These methods, which require further for field evaluation and validation, could provide an additional powerful tool for the investigation of the early stages of an epidemic, and constitute the basis of new simulation methods to understand the process through which a disease is spread. \u00a9 2009 Bentham Science Publishers Ltd.
\n \n\n \n \nThis study evaluated the feasibility of using published data from more than one register to define the performance of different hip implants. In order to obtain estimates of performance for specific types of hip system from different register, we analysed data from the annual reports of five national and one Italian regional register. We extracted the number of implants and rates of implant survival at different periods of follow-up. Our aim was to assess whether estimates of cumulative survival rate were comparable with data from registers from different countries, and our conclusion was that such a comparison could only be performed incompletely. \u00a92009 British Editorial Society of Bone and Joint Surgery.
\n \n\n \n \nThis is the protocol for a review and there is no abstract. The objectives are as follows: To systematically review the evidence of effectiveness of interventions to interrupt or reduce the spread of respiratory viruses causing influenza-like illnesses (excluding vaccines and antivirals, which have already been covered by Cochrane Reviews) (Demicheli 2004; Jefferson 1999; Jefferson 2006b; Matheson 2003; Smith 2006; Swingler 2003). Copyright \u00a9 2006 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
\n \n\n \n \nBackground. In an attempt to reduce the burden of influenza-like illness (ILI) on health resources, the Italian Ministry of Health released clinical practice guidelines (CPGs) on ILI management that include specific indications for the admission of children to the hospital. The aim of this study was to evaluate whether application of these CPGs reduced the rate of inappropriate hospital admissions. Methods. In the first phase, 2 independent observers recorded the number and clinical condition of children presenting with ILI to the emergency department (ED) of a large urban pediatric hospital and the main reasons for hospital admission. The latter were compared with the CPG indications for hospital admission to evaluate appropriateness. One year later (phase 2), we recorded the number of children with ILI admitted to the hospital by pediatricians trained in a 3-hour course on CPGs and by \"untrained\" control pediatricians. Results. In phase 1 of the study, 854 children accessed the ED; 318 (37.2%) had ILI. Of the latter, 26.2% were admitted to the hospital, and 33.7% of admissions were inappropriate according to CPG criteria. In phase 2, 16% of the children with ILI were admitted by CPG-trained pediatricians and 25.8% by control pediatricians. The number of inappropriate hospital admissions was higher among control than among CPG-trained pediatricians. Conclusions. ILI in children is associated with a high rate of inappropriate hospital admissions. Training of ED pediatricians in the application of a specific CPG may result in a substantial decrease of the admission rate and of inappropriate admissions. Copyright \u00a9 2005 by the American Academy of Pediatrics.
\n \n\n \n \n