Luis Eduardo Santos Fontes

Objectives To assess the efficacy and safety of pharmacological interventions for preventing upper gastrointestinal (GI) bleeding in people admitted to intensive care units (ICUs). Design and setting Systematic review and frequentist network meta-analysis using standard methodological procedures as recommended by Cochrane for screening of records, data extraction and analysis. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the certainty of evidence. Participants Randomised controlled trials involving patients admitted to ICUs for longer than 24 hours were included. Search methods The Cochrane Gut Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and Latin American and Caribbean Health Science Information database (LILACS) databases were searched from August 2017 to March 2022. The search in MEDLINE was updated in April 2023. We also searched ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP). Main outcome measures The primary outcome was the prevention of clinically important upper GI bleeding. Results We included 123 studies with 46 996 participants. Cimetidine (relative risk (RR) 0.56, 95% CI 0.40 to 0.77, moderate certainty), ranitidine (RR 0.54, 95% CI 0.38 to 0.76, moderate certainty), antacids (RR 0.48, 95% CI 0.33 to 0.68, moderate certainty), sucralfate (RR 0.54, 95% CI 0.39 to 0.75, moderate certainty) and a combination of ranitidine and antacids (RR 0.13, 95% CI 0.03 to 0.62, moderate certainty) are likely effective in preventing upper GI bleeding. The effect of any intervention on the prevention of nosocomial pneumonia, all-cause mortality in the ICU or the hospital, duration of the stay in the ICU, duration of intubation and (serious) adverse events remains unclear. Conclusions Several interventions seem effective in preventing clinically important upper GI bleeding while there is limited evidence for other outcomes. Patient-relevant benefits and harms need to be assessed under consideration of the patients’ underlying conditions.

INTRODUCTION: Different biologically active products have been applied for management of pain and mandibular functional disability in intra-articular TMD but without the ability to effectively control degenerative joint disease. Platelet concentrates aim to enhance tissue healing and facilitate its regeneration. Intra-articular injections of liquid Platelet-Rich Fibrin (PRF) in patients with TMD have demonstrated effectiveness in the management of pain and dysfunction, also having a stimulatory effect on cartilage and bone tissues. OBJECTIVE: The objective of this review is to examine how research has been conducted regarding use of PRF as a treatment tool for temporomandibular joint disorders (TMD). INCLUSION CRITERIA: This review will focus on studies that address adults with TMD without restrictions on gender or ethnicity. TMD will be classified according to the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) physical axis (Axis I). Also, we will include publications in any language or date of publication. METHODS: This protocol will follow the JBI guidance for Scoping Reviews. We shall conduct a literature search to identify published research, with no limits on year of publication/conception, format, or language. Two independent reviews will screen and select publications, based on inclusion criteria. Review decision process will be provided in a flowchart based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations for Scoping Reviews. Finally, we shall present extracted data from each study in piloted forms in conceptual categories such as intervention type, population and sample size, duration of intervention, aims, methodology adopted, key findings and gaps in the research.

Background Obstructive sleep apnoea syndrome (OSAS) is associated with several chronic diseases, including erectile dysfunction (ED). The association of OSAS and ED is far more common than might be found by chance; the treatment of OSAS with non‐invasive positive airway pressure therapy is associated with improvement of respiratory symptoms, and may contribute to the improvement of associated conditions, such as ED. Objectives To assess the effectiveness and acceptability of non‐invasive positive airway pressure therapy for improving erectile dysfunction in OSAS. Search methods We identified studies from the Cochrane Airways Trials Register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, AMED EBSCO, and LILACS, the US National Institutes of Health ongoing trials register ClinicalTrials.gov, and the World Health Organisation international clinical trials registry platform to 14 June 2021, with no restriction on date, language, or status of publication. We checked the reference lists of all primary studies, and review articles for additional references, and relevant manufacturers' websites for study information. We also searched specific conference proceedings for the British Association of Urological Surgeons; the European Association of Urology; and the American Urological Association to 14 June 2021. Selection criteria We considered randomised controlled trials (RCTs) with a parallel or cross‐over design, or cluster‐RCTs, which included men aged 18 years or older, with OSAS and ED. We considered RCTs comparing any non‐invasive positive airway pressure therapy (such as continuous positive airways pressure (CPAP), bilevel positive airway pressure (BiPAP), variable positive airway pressure (VPAP), or similar devices) versus sham, no treatment, waiting list, or pharmacological treatment for ED. The primary outcomes were remission of ED and serious adverse events; secondary outcome were sex‐related quality of life, health‐related quality of life, and minor adverse events. Data collection and analysis Two review authors independently conducted study selection, data extraction, and risk of bias assessment. A third review author solved any disagreement. We used the Cochrane RoB 1 tool to assess the risk of bias of the included RCTs. We used the GRADE approach to assess the certainty of the body of evidence. To measure the treatment effect on dichotomous outcomes, we used the risk ratio (RR); for continuous outcomes, we used the mean difference (MD). We calculated 95% confidence intervals (CI) for these measures. When possible (data availability and homogeneous studies), we used a random‐effect model to pool data with a meta‐analysis. Main results We included six RCTs (all assessing CPAP as the non‐invasive positive airway pressure therapy device), with a total of 315 men with OSAS and ED. All RCTs presented some important risk of bias related to selection, performance, assessment, or reporting bias. None of included RCTs assessed the ED remission rate, and we used the provided ED mean scores as a proxy. CPAP versus no CPAP There is uncertainty about the effect of CPAP on mean ED scores after 4 weeks, using the International index of erectile function (IIEF‐5, higher = better; MD 7.50, 95% CI 4.05 to 10.95; 1 RCT; 27 participants; very low‐certainty evidence), and after 12 weeks (IIEF‐ED, ED domain; MD 2.50, 95% CI ‐1.10 to 6.10; 1 RCT; 57 participants; very low‐certainty evidence, downgraded due to methodological limitations and imprecision). There is uncertainty about the effect of CPAP on sex‐related quality of life after 12 weeks, using the Self‐esteem and relationship test (SEAR, higher = better; MD 1.00, 95% CI ‐8.09 to 10.09; 1 RCT; 57 participants; very low‐certainty evidence, downgraded due to methodological limitations and imprecision); no serious adverse events were reported after 4 weeks (1 RCT; 27 participants; very low‐certainty evidence, downgraded due to methodological limitations and imprecision). CPAP versus sham CPAP One RCT assessed this comparison (61 participants), but we were unable to extract outcomes for this comparison due to the factorial design and reporting of this trial. CPAP versus sildenafil (phosphodiesterase type 5 inhibitors) Sildenafil may slightly improve erectile function at 12 weeks when compared to CPAP, measured with the IIEF‐ED (MD ‐4.78, 95% CI ‐6.98 to ‐2.58; 3 RCTs; 152 participants; I² = 59%; low‐certainty evidence, downgraded due to methodological limitations). There is uncertainty about the effect of CPAP on sex‐related quality of life after 12 weeks, measured with the Erectile Dysfunction Inventory of Treatment Satisfaction questionnaire (EDITS, higher = better; MD ‐1.24, 95% CI ‐1.80 to ‐0.67; 2 RCTs; 122 participants; I² = 0%; very low‐certainty evidence, downgraded due to methodological limitations). No serious adverse events were reported for either group (2 RCTs; 70 participants; very low‐certainty evidence, downgraded due to methodological limitations and imprecision). There is uncertainty about the effects of CPAP when compared to sildenafil for the incidence of minor adverse events (RR 1.33, 95% CI 0.34 to 5.21; 1 RCT; 40 participants; very low‐certainty evidence, downgraded due to methodological limitations and imprecision). The confidence interval was wide and neither a significant increase nor reduction in the risk of minor adverse events can be ruled out with the use of CPAP (4/20 men complained of nasal dryness in the CPAP group, and 3/20 men complained of transient flushing and mild headache in the sildenafil group). Authors' conclusions When compared with no CPAP, we are uncertain about the effectiveness and acceptability of CPAP for improving erectile dysfunction in men with obstructive sleep apnoea. When compared with sildenafil,...

Cochrane devolves most editorial governance of the Cochrane Database of Systematic Reviews (CDSR), including title prioritization, protocol registration, peer‐review, editorial oversight and subsequent review deposition, to specific Cochrane Review Group (CRG) editorial boards. Current Cochrane policy stipulates authors of reviews who are also members of the supporting CRG declare this non‐financial conflict of interest and confirm no involvement in the review editorial process. The aim of this cross‐sectional analysis was to assess adherence to Cochrane's editorial conflict of interest policy. All 260 published Cochrane reviews (CR) in issues 1 to 6 from 2019 of the CDSR were reviewed. A total of 133 (51.2%, 133/260) of CRs had at least one author that was also listed as an editor in the CRG. Of these, only five (3.8%, 5/133) appropriately declared the conflict according to Cochrane policy. In 6.5% (17/133) CRs, the contact author had a leading editorial position within the CRG and in only four of 17 was this declared according to Cochrane policy. No CR with the contact author who also had a leading editorial position described methods to prevent any potential issues related to this scenario during the editorial process in accordance with Cochrane policy. We propose a specific form to improve the transparency and reliability of editorial conflict of interest reporting in CRs. The suggested form can be adapted to other contexts.

Brain dysfunction is associated with poor outcome in critically ill patients. In a post hoc analysis of the Intensive Care over Nations (ICON) database, we investigated the effect of brain dysfunction on hospital mortality in critically ill patients. Brain failure was defined as a neurological sequential organ failure assessment (nSOFA) score of 3–4, based on the assumed Glasgow Coma Scale (GCS) score. Multivariable analyses were performed to assess the independent roles of nSOFA and change in nSOFA from admission to day 3 (ΔnSOFA) for predicting hospital mortality. Data from 7192 (2096 septic and 5096 non-septic) patients were analyzed. Septic patients were more likely than non-septic patients to have brain failure on admission (434/2095 (21%) vs. 617/4665 (13%), p < 0.001) and during the ICU stay (625/2063 (30%) vs. 736/4665 (16%), p < 0.001). The presence of sepsis (RR 1.66 (1.31–2.09)), brain failure (RR 4.85 (3.33–7.07)), and both together (RR 5.61 (3.93–8.00)) were associated with an increased risk of in-hospital death, but nSOFA was not. In the 3280 (46%) patients in whom ΔnSOFA was available, sepsis (RR 2.42 (1.62–3.60)), brain function deterioration (RR 6.97 (3.71–13.08)), and the two together (RR 10.24 (5.93–17.67)) were associated with an increased risk of in-hospital death, whereas improvement in brain function was not.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the effects and safety of pneumococcal conjugate vaccines for preventing invasive pneumococcal disease and pneumonia in children aged up to five years.

Sackett, in a remarkable paper published in 1979, ‘Bias in Analytic Research’, was the first to propose a catalogue that would include a list of biases that ‘may distort the design, execution, analysis and interpretation of research’.1 2 Sacket’s pioneering work identified, labelled and discussed 35 biases. In the conclusion of this paper, Sackett highlighted, among others, two priorities for future researches: the continued development of the proposed catalogue and the empirical evaluation of the proposed biases.2

Background Helicobacter pylori (H pylori) is one of the most common pathogens to establish and cause infection in human beings, affecting about 50% of the world's population. Prevalence may be as high as 83% in Latin American countries and as low as 17% in North America. Approximately 20% of infected people will manifest disease; people at high risk include those who live in low‐ and middle‐income countries with poor sanitary conditions, since the mechanism of transmission seems to be oral‐oral or faecal‐oral (mostly during infancy). There are several antibiotic regimens to treat the infection, but antibiotic resistance is growing around the world. New adjuvant drugs — such as probiotics, statins, curcumin, and N‐acetylcysteine (NAC) — are being tested to enhance eradication rates. N‐acetylcysteine can destabilise the biofilm structure; it also has synergic action with antibiotics, and bactericidal effects. In addition, NAC has antioxidant properties, and has a primary mucolytic effect by reducing the thickness of the gastric mucus layer, both of which may exert beneficial adjuvant effects on H pylori eradication. Objectives To assess the efficacy and safety of N‐acetylcysteine as an adjuvant therapy to antibiotics for Helicobacter pylori eradication. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1966 to April 2018), Embase (1988 to April 2018), CINAHL (1982 to April 2018), LILACS (1982 to April 2018), grey literature databases and trials registries. We handsearched the reference lists of relevant studies. We screened 726 articles and assessed 18 for eligibility. Selection criteria We included randomised controlled trials (RCTs) of any antibiotic regimen plus NAC, in adults infected with H pylori. To be included, trials had to use a control consisting of the same antibiotic regimen with or without placebo. Outcomes of interest were eradication rates, and gastrointestinal, toxic, and allergic adverse events. Reporting of the primary outcomes listed here was not an inclusion criterion for the review. Data collection and analysis Two review authors independently reviewed and extracted data and completed the 'Risk of bias' assessments. A third review author independently confirmed the 'Risk of bias' assessments. We used Review Manager 5 software for data analysis. We contacted study authors if there was missing information. Main results We included eight RCTs (with a total of 559 participants) in this review. The studies recruited outpatients aged between 17 and 76 years who were referred to endoscopy centres in several different countries. The certainty of evidence was reduced for most outcomes due to the poor methodological quality of included studies; issues mainly related to the generation of allocation sequence, allocation concealment, and blinding (this last domain related specifically to adverse outcomes). We are uncertain whether the addition of NAC to antibiotics improves H pylori eradication rates, compared with the addition of placebo or no NAC (38.8% versus 49.1%, risk ratio (RR) 0.74, 95% confidence interval (CI) 0.51 to 1.08; participants = 559; studies = eight; very low‐certainty evidence). A post‐hoc sensitivity analysis, in which we removed studies that tested antibiotic regimens no longer recommended in clinical practice, showed that the addition of NAC may improve eradication rates compared to control (27.2% versus 37.6%, RR 0.71, 95% CI 0.53 to 0.94; participants = 397; published studies = five). We are uncertain whether NAC is associated with a higher risk of gastrointestinal adverse events compared to control (23.9% versus 18.9%, RR 1.25, 95% CI 0.85 to 1.85; participants = 336; studies = five; very low‐certaintyevidence), or allergic adverse events (2% versus 0%, RR 2.98, 95% CI 0.32 to 27.74; participants = 336; studies = five; very low‐certainty evidence). There were no reports of toxic adverse events amongst included studies. Authors' conclusions We are uncertain whether the addition of NAC to antibiotics improves H pylori eradication rates compared with the addition of placebo or no NAC. Due to the clinical, statistical and methodological heterogeneity found in included studies, and the uncertainty observed when analysing therapy subgroups, any possible beneficial effect of NAC should be regarded cautiously. We are uncertain whether NAC is associated with a higher risk of gastrointestinal or allergic adverse events compared with placebo or no NAC. There were no reports of toxic adverse events amongst the included studies. Further large, well‐designed, randomised clinical studies should be conducted, with good reporting standards and appropriate collection of efficacy and safety outcomes, especially for current recommended antibiotic regimens.

Composite outcomes – the devil is in the details