Non-invasive positive airway pressure therapy for improving erectile dysfunction in men with obstructive sleep apnoea.

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, there is some evidence that sildenafil may slightly improve erectile function at 12 weeks.

N-acetylcysteine as an adjuvant therapy for Helicobacter pylori eradication.

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.

Interventions for preventing upper gastrointestinal bleeding in people admitted to intensive care units.

BACKGROUND: Upper gastrointestinal (GI) bleeding due to stress ulcers contributes to increased morbidity and mortality in people admitted to intensive care units (ICUs). Stress ulceration refers to GI mucosal injury related to the stress of being critically ill. ICU patients with major bleeding as a result of stress ulceration might have mortality rates approaching 48.5% to 65%. However, the incidence of stress-induced GI bleeding in ICUs has decreased, and not all critically ill patients need prophylaxis. Stress ulcer prophylaxis can result in adverse events such as ventilator-associated pneumonia; therefore, it is necessary to evaluate strategies that safely decrease the incidence of GI bleeding. OBJECTIVES: To assess the effect and risk-benefit profile of interventions for preventing upper GI bleeding in people admitted to ICUs. SEARCH METHODS: We searched the following databases up to 23 August 2017, using relevant search terms: MEDLINE; Embase; the Cochrane Central Register of Controlled Trials; Latin American Caribbean Health Sciences Literature; and the Cochrane Upper Gastrointestinal and Pancreatic Disease Group Specialised Register, as published in the Cochrane Library (2017, Issue 8). We searched the reference lists of all included studies and those from relevant systematic reviews and meta-analyses to identify additional studies. We also searched the World Health Organization International Clinical Trials Registry Platform search portal and contacted individual researchers working in this field, as well as organisations and pharmaceutical companies, to identify unpublished and ongoing studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs with participants of any age and gender admitted to ICUs for longer than 48 hours. We excluded studies in which participants were admitted to ICUs primarily for the management of GI bleeding and studies that compared different doses, routes, and regimens of one drug in the same class because we were not interested in intraclass effects of drugs. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as recommended by Cochrane. MAIN RESULTS: We identified 2292 unique records.We included 129 records reporting on 121 studies, including 12 ongoing studies and two studies awaiting classification.We judged the overall risk of bias of two studies as low. Selection bias was the most relevant risk of bias domain across the included studies, with 78 studies not clearly reporting the method used for random sequence generation. Reporting bias was the domain with least risk of bias, with 12 studies not reporting all outcomes that researchers intended to investigate.Any intervention versus placebo or no prophylaxisIn comparison with placebo, any intervention seems to have a beneficial effect on the occurrence of upper GI bleeding (risk ratio (RR) 0.47, 95% confidence interval (CI) 0.39 to 0.57; moderate certainty of evidence). The use of any intervention reduced the risk of upper GI bleeding by 10% (95% CI -12.0% to -7%). The effect estimate of any intervention versus placebo or no prophylaxis with respect to the occurrence of nosocomial pneumonia, all-cause mortality in the ICU, duration of ICU stay, duration of intubation (all with low certainty of evidence), the number of participants requiring blood transfusions (moderate certainty of evidence), and the units of blood transfused was consistent with benefits and harms. None of the included studies explicitly reported on serious adverse events.Individual interventions versus placebo or no prophylaxisIn comparison with placebo or no prophylaxis, antacids, H2 receptor antagonists, and sucralfate were effective in preventing upper GI bleeding in ICU patients. Researchers found that with H2 receptor antagonists compared with placebo or no prophylaxis, 11% less developed upper GI bleeding (95% CI -0.16 to -0.06; RR 0.50, 95% CI 0.36 to 0.70; 24 studies; 2149 participants; moderate certainty of evidence). Of ICU patients taking antacids versus placebo or no prophylaxis, 9% less developed upper GI bleeding (95% CI -0.17 to -0.00; RR 0.49, 95% CI 0.25 to 0.99; eight studies; 774 participants; low certainty of evidence). Among ICU patients taking sucralfate versus placebo or no prophylaxis, 5% less had upper GI bleeding (95% CI -0.10 to -0.01; RR 0.53, 95% CI 0.32 to 0.88; seven studies; 598 participants; moderate certainty of evidence). The remaining interventions including proton pump inhibitors did not show a significant effect in preventing upper GI bleeding in ICU patients when compared with placebo or no prophylaxis.Regarding the occurrence of nosocomial pneumonia, the effects of H2 receptor antagonists (RR 1.12, 95% CI 0.85 to 1.48; eight studies; 945 participants; low certainty of evidence) and of sucralfate (RR 1.33, 95% CI 0.86 to 2.04; four studies; 450 participants; low certainty of evidence) were consistent with benefits and harms when compared with placebo or no prophylaxis. None of the studies comparing antacids versus placebo or no prophylaxis provided data regarding nosocomial pneumonia.H2 receptor antagonists versus proton pump inhibitorsH2 receptor antagonists and proton pump inhibitors are most commonly used in practice to prevent upper GI bleeding in ICU patients. Proton pump inhibitors significantly more often prevented upper GI bleeding in ICU patients compared with H2 receptor antagonists (RR 2.90, 95% CI 1.83 to 4.58; 18 studies; 1636 participants; low certainty of evidence). When taking H2 receptor antagonists, 4.8% more patients might experience upper GI bleeding (95% CI 2.1% to 9%). Nosocomial pneumonia occurred in similar proportions of participants taking H2 receptor antagonists and participants taking proton pump inhibitors (RR 1.02, 95% CI 0.77 to 1.35; 10 studies; 1256 participants; low certainty of evidence). AUTHORS' CONCLUSIONS: This review shows that antacids, sucralfate, and H2 receptor antagonists might be more effective in preventing upper GI bleeding in ICU patients compared with placebo or no prophylaxis. The effect estimates of any treatment versus no prophylaxis on nosocomial pneumonia were consistent with benefits and harms. Evidence of low certainty suggests that proton pump inhibitors might be more effective than H2 receptor antagonists. Therefore, patient-relevant benefits and especially harms of H2 receptor antagonists compared with proton pump inhibitors need to be assessed by larger, high-quality RCTs to confirm the results of previously conducted, smaller, and older studies.