Pharmacological interventions for preventing upper gastrointestinal bleeding in people admitted to intensive care units: a network meta-analysis.

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.

High certainty evidence is stable and trustworthy, whereas evidence of moderate or lower certainty may be equally prone to being unstable.

OBJECTIVES: To assess to what extent the overall quality of evidence indicates changes to observe intervention effect estimates when new data become available. METHODS: We conducted a meta-epidemiological study. We obtained evidence from meta-analyses of randomized trials of Cochrane reviews addressing the same health-care question that was updated with inclusion of additional data between January 2016 and May 2021. We extracted the reported effect estimates with 95% confidence intervals (CIs) from meta-analyses and corresponding GRADE (Grading of Recommendations Assessment, Development, and Evaluation) assessments of any intervention comparison for the primary outcome in the first and the last updated review version. We considered the reported overall quality (certainty) of evidence (CoE) and specific evidence limitations (no, serious or very serious for risk of bias, imprecision, inconsistency, and/or indirectness). We assessed the change in pooled effect estimates between the original and updated evidence using the ratio of odds ratio (ROR), absolute ratio of odds ratio (aROR), ratio of standard errors (RoSE), direction of effects, and level of statistical significance. RESULTS: High CoE without limitations characterized 19.3% (n = 29) out of 150 included original Cochrane reviews. The update with additional data did not systematically change the effect estimates (mean ROR 1.00; 95% CI 0.99-1.02), which deviated 1.06-fold from the older estimates (median aROR; interquartile range [IQR]: 1.01-1.15), gained precision (median RoSE 0.87; IQR 0.76-1.00), and maintained the same direction with the same level of statistical significance in 93% (27 of 29) of cases. Lower CoE with limitations characterized 121 original reviews and graded as moderate CoE in 30.0% (45 of 150), low CoE in 32.0% (48 of 150), and very low CoE in 18.7% (28 of 150) reviews. Their update had larger absolute deviations (median aROR 1.12 to 1.33) and larger gains in precision (median RoSE 0.78-0.86) without clear and consistent differences between these categories of CoE. Changes in effect direction or statistical significance were also more common in the lower quality evidence, again with a similar extent across categories (without change in 75.6%, 64.6%, and 75.0% for moderate, low, very low CoE). As limitations increased, effect estimates deviated more (aROR 1.05 with zero, 1.11 with one, 1.25 with two, 1.24 with three limitations) and changes in direction or significance became more frequent (93.2% stable with no limitations, 74.5% with one, 68.2% with two, and 61.5% with three limitations). CONCLUSION: High-quality evidence without methodological deficiencies is trustworthy and stable, providing reliable intervention effect estimates when updated with new data. Evidence of moderate and lower quality may be equally prone to being unstable and cannot indicate if available effect estimates are true, exaggerated, or underestimated.

Excited-State Proton Transfer in Luminescent Dyes: From Theoretical Insight to Experimental Evidence.

The effective utilization of luminescent dyes often relies on a comprehensive understanding of their excitation and relaxation pathways. One such pathway, Excited-State Proton Transfer (ESPT), involves the tautomerization of the dye in its excited state, resulting in a new structure that exhibits distinct emission properties, such as a very large Stokes' shift or dual-emission. Although the ESPT phenomenon is well-explained theoretically, its experimental demonstration can be challenging due to the presence of numerous other phenomena that can yield similar experimental observations. In this review, we propose that an all-encompassing methodology, integrating experimental findings, computational analyses, and a thorough evaluation of diverse mechanisms, is essential for verifying the occurrence of ESPT in luminescent dyes. Investigations have offered significant understanding of the elements impacting the ESPT process and the array of approaches that can be used to validate the existence of ESPT. These discoveries hold crucial ramifications for the advancement of molecular probes, sensors, and other applications that depend on ESPT as a detection mechanism.

Influence of the Intramolecular Hydrogen Bond on the Fluorescence of 2-ortho-Aminophenyl Pyridines.

The dynamic nature of excited-state intramolecular proton transfer (ESIPT) and its effect on emission spectra is an attractive strategy to create multi-emissive dyes. Here we describe the behavior of a series of hydrogen-bonded triphenylpyridines with a set of donor-acceptor combinations that allowed us to perceive the influence of each substitution on the photophysical properties of the dyes. The susceptibility of these ESIPT moieties to pH variations was also studied, elucidating that the level of protonation had a significant effect on the emission color. The assignment of each emission band was made by using DFT and td-DFT calculations that were in agreement with the experimental results. This study emphasizes the versatility of triphenylpyridines that can be synthesized effortlessly with a logical and independent C-2, C-4 and C-6 substitution in order to have the desired ESIPT modulation and subsequent multi-emission response.

High quality (certainty) evidence changes less often than low-quality evidence, but the magnitude of effect size does not systematically differ between studies with low versus high-quality evidence.

RATIONALE, AIMS, AND OBJECTIVES: It is generally believed that evidence from low quality of evidence generate inaccurate estimates about treatment effects more often than evidence from high (certainty) quality evidence (CoE). As a result, we would expect that (a) estimates of effects of health interventions initially based on high CoE change less frequently than the effects estimated by lower CoE (b) the estimates of magnitude of effect size differ between high and low CoE. Empirical assessment of these foundational principles of evidence-based medicine has been lacking. METHODS: We reviewed the Cochrane Database of Systematic Reviews from January 2016 through May 2021 for pairs of original and updated reviews for change in CoE assessments based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) method. We assessed the difference in effect sizes between the original versus updated reviews as a function of change in CoE, which we report as a ratio of odds ratio (ROR). We compared ROR generated in the studies in which CoE changed from very low/low (VL/L) to moderate/high (M/H) versus M/H to VL/L. Heterogeneity and inconsistency were assessed using the tau and I2 statistic. We also assessed the change in precision of effect estimates (by calculating the ratio of standard errors) (seR), and the absolute deviation in estimates of treatment effects (aROR). RESULTS: Four hundred and nineteen pairs of reviews were included of which 414 (207 × 2) informed the CoE appraisal and 384 (192 × 2) the assessment of effect size. We found that CoE originally appraised as VL/L had 2.1 [95% confidence interval (CI): 1.19-4.12; p = 0.0091] times higher odds to be changed in the future studies than M/H CoE. However, the effect size was not different (p = 1) when CoE changed from VL/L → M/H [ROR = 1.02 (95% CI: 0.74-1.39)] compared with M/H → VL/L (ROR = 1.02 [95% CI: 0.44-2.37]). Similar overlap in aROR between the VL/L → M/H versus M/H → VL/L subgroups was observed [median (IQR): 1.12 (1.07-1.57) vs. 1.21 (1.12-2.43)]. We observed large inconsistency across ROR estimates (I2 = 99%). There was larger imprecision in treatment effects when CoE changed from VL/L → M/H (seR = 1.46) than when it changed from M/H → VL/L (seR = 0.72). CONCLUSIONS: We found that low-quality evidence changes more often than high CoE. However, the effect size did not systematically differ between the studies with low versus high CoE. The finding that the effect size did not differ between low and high CoE indicate urgent need to refine current EBM critical appraisal methods.

Adherence to conflicts of interest policy in Cochrane reviews where authors are also editorial board members: A cross-sectional analysis.

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.

Archaeological and Chemical Investigation on Mortars and Bricks from a Necropolis in Braga, Northwest of Portugal.

This investigation intends to study and characterize the mortars and bricks from walls and floors used in the funerary nucleus of the archaeological site of Dr. Gonçalo Sampaio Street (Braga, Portugal), associated with the Via XVII necropolis of the Bracara Augusta Roman city. The diversity of the funeral structures and their exceptional state of conservation make this sector of the necropolis an unprecedented case and a reference site in the archaeology of Braga, a determinant for its conservation and musealization. Nineteen mortars samples were analysed by X-ray Fluorescence. The results showed clear chemical composition differences among coating and floor mortars (CFM), masonry mortars (MM) and bricks (B) groups of samples. The chemical affinity between CFM from the V to IV centuries, CFM from the IV to V centuries, MM from brick walls (IV-V centuries), MM from stone walls (V-VII centuries) and B from the IV to V centuries samples were confirmed by statistical analyses. Their composition was distinctly related to the use of different raw materials, according to their chronological context; in mortars, according to their function in the structures; and in some samples, from contamination.

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.

General anaesthesia versus other types of anaesthesia in patients undergoing surgery for treatment of cutaneous melanoma: a systematic review and meta-analysis.

General and local anaesthetics alter tumour behaviour in experimental models. Objectives: To investigate the relationship between general anaesthesia and recurrence or survival in patients who received surgery for malignant melanoma. A meta-analysis was performed based on a comprehensive literature search. Controlled and observational studies of patients undergoing surgery for melanoma under general anaesthesia, compared with other types of anaesthesia, were included. The primary outcomes were overall survival and disease-free survival. The secondary outcomes included cancer-specific survival, cost analysis, and adverse events. Risk of bias was assessed. Individual study information was summarized. The meta-analysis was performed using a random-effects model. The GRADE approach was used to summarise the certainty of evidence. Eight studies were included (n = 5,832). The use of general anaesthesia was not associated with any statistical difference in overall survival (p = 0.087; 1 NRS; n= 104; very low certainty of evidence) or disease-free survival (HR: 1.266; 95% CI: 0.904-1.773; p = 0.169; 1 NRS; n = 281; very low certainty of evidence). However, general anaesthesia was associated with worse melanoma-specific survival (HR: 1.46; 95% CI: 1.22-1.68: p < 0.00001; 3 NRS; n = 4654; low certainty of evidence). Three studies reported increased intraoperative costs associated with the use of general anaesthesia (3 NRT; n = 513; very low certainty of evidence). No study adequately reported other primary or secondary outcomes. General anaesthesia may reduce melanoma-specific survival in patients undergoing surgery for treatment of cutaneous melanoma. We are uncertain whether general anaesthesia impacts the other reported outcomes.

Repetitive transcranial magnetic stimulation on the modulation of cortical and spinal cord excitability in individuals with spinal cord injury.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) has been applied for modulating cortical excitability and treating spasticity in neurological lesions. However, it is unclear which rTMS frequency is most effective in modulating cortical and spinal excitability in incomplete spinal cord injury (SCI). OBJECTIVE: To evaluate electrophysiological and clinical repercussions of rTMS compared to sham stimulation when applied to the primary motor cortex (M1) in individuals with incomplete SCI. METHODS: A total of 11 subjects (35±12 years) underwent three experimental sessions of rTMS (10 Hz, 1 Hz and sham stimulation) in a randomized order at 90%intensity of the resting motor threshold and interspersed by a seven-day interval between sessions. The following outcome measures were evaluated: M1 and spinal cord excitability and spasticity in the moments before (baseline), immediately after (T0), 30 (T30) and 60 (T60) minutes after rTMS. M1 excitability was obtained through the motor evoked potential (MEP); spinal cord excitability by the Hoffman reflex (H-reflex) and homosynaptic depression (HD); and spasticity by the modified Ashworth scale (MAS). RESULTS: A significant increase in cortical excitability was observed in subjects submitted to 10 Hz rTMS at the T0 moment when compared to sham stimulation (p = 0.008); this increase was also significant at T0 (p = 0.009), T30 (p = 0.005) and T60 (p = 0.005) moments when compared to the baseline condition. No significant differences were observed after the 10 Hz rTMS on spinal excitability or on spasticity. No inter-group differences were detected, or in the time after application of 1 Hz rTMS, or after sham stimulation for any of the assessed outcomes. CONCLUSIONS: High-frequency rTMS applied to M1 was able to promote increased cortical excitability in individuals with incomplete SCI for at least 60 minutes; however, it did not modify spinal excitability or spasticity.

The Prognostic Value of Brain Dysfunction in Critically Ill Patients with and without Sepsis: A Post Hoc Analysis of the ICON Audit.

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.

Temporal changes in the epidemiology, management, and outcome from acute respiratory distress syndrome in European intensive care units: a comparison of two large cohorts.

BACKGROUND: Mortality rates for patients with ARDS remain high. We assessed temporal changes in the epidemiology and management of ARDS patients requiring invasive mechanical ventilation in European ICUs. We also investigated the association between ventilatory settings and outcome in these patients. METHODS: This was a post hoc analysis of two cohorts of adult ICU patients admitted between May 1-15, 2002 (SOAP study, n = 3147), and May 8-18, 2012 (ICON audit, n = 4601 admitted to ICUs in the same 24 countries as the SOAP study). ARDS was defined retrospectively using the Berlin definitions. Values of tidal volume, PEEP, plateau pressure, and FiO2 corresponding to the most abnormal value of arterial PO2 were recorded prospectively every 24 h. In both studies, patients were followed for outcome until death, hospital discharge or for 60 days. RESULTS: The frequency of ARDS requiring mechanical ventilation during the ICU stay was similar in SOAP and ICON (327[10.4%] vs. 494[10.7%], p = 0.793). The diagnosis of ARDS was established at a median of 3 (IQ: 1-7) days after admission in SOAP and 2 (1-6) days in ICON. Within 24 h of diagnosis, ARDS was mild in 244 (29.7%), moderate in 388 (47.3%), and severe in 189 (23.0%) patients. In patients with ARDS, tidal volumes were lower in the later (ICON) than in the earlier (SOAP) cohort. Plateau and driving pressures were also lower in ICON than in SOAP. ICU (134[41.1%] vs 179[36.9%]) and hospital (151[46.2%] vs 212[44.4%]) mortality rates in patients with ARDS were similar in SOAP and ICON. High plateau pressure (> 29 cmH2O) and driving pressure (> 14 cmH2O) on the first day of mechanical ventilation but not tidal volume (> 8 ml/kg predicted body weight [PBW]) were independently associated with a higher risk of in-hospital death. CONCLUSION: The frequency of and outcome from ARDS remained relatively stable between 2002 and 2012. Plateau pressure > 29 cmH2O and driving pressure > 14 cmH2O on the first day of mechanical ventilation but not tidal volume > 8 ml/kg PBW were independently associated with a higher risk of death. These data highlight the continued burden of ARDS and provide hypothesis-generating data for the design of future studies.

The clinical relevance of oliguria in the critically ill patient: analysis of a large observational database.

BACKGROUND: Urine output is widely used as one of the criteria for the diagnosis and staging of acute renal failure, but few studies have specifically assessed the role of oliguria as a marker of acute renal failure or outcomes in general intensive care unit (ICU) patients. Using a large multinational database, we therefore evaluated the occurrence of oliguria (defined as a urine output < 0.5 ml/kg/h) in acutely ill patients and its association with the need for renal replacement therapy (RRT) and outcome. METHODS: International observational study. All adult (> 16 years) patients in the ICON audit who had a urine output measurement on the day of admission were included. To investigate the association between oliguria and mortality, we used a multilevel analysis. RESULTS: Of the 8292 patients included, 2050 (24.7%) were oliguric during the first 24 h of admission. Patients with oliguria on admission who had at least one additional 24-h urine output recorded during their ICU stay (n = 1349) were divided into three groups: transient-oliguria resolved within 48 h after the admission day (n = 390 [28.9%]), prolonged-oliguria resolved > 48 h after the admission day (n = 141 [10.5%]), and permanent-oliguria persisting for the whole ICU stay or again present at the end of the ICU stay (n = 818 [60.6%]). ICU and hospital mortality rates were higher in patients with oliguria than in those without, except for patients with transient oliguria who had significantly lower mortality rates than non-oliguric patients. In multilevel analysis, the need for RRT was associated with a significantly higher risk of death (OR = 1.51 [95% CI 1.19-1.91], p = 0.001), but the presence of oliguria on admission was not (OR = 1.14 [95% CI 0.97-1.34], p = 0.103). CONCLUSIONS: Oliguria is common in ICU patients and may have a relatively benign nature if only transient. The duration of oliguria and need for RRT are associated with worse outcome.

Impact of general anaesthesia in overall and disease-free survival compared to other types of anaesthesia in patients undergoing surgery for cutaneous melanoma: a systematic review and meta-analysis protocol.

INTRODUCTION: Cutaneous melanoma is an aggressive type of skin cancer. Anaesthetic agents may have an impact on the immune response, postoperative neurohumoral response and tumour progression. This systematic review aims to evaluate the impact of general anaesthesia on overall and disease-free survival compared with other types anaesthesia in patients undergoing surgery for cutaneous melanoma. METHODS AND ANALYSIS: The review will analyse data from controlled and observational studies of patients undergoing surgery for melanoma under general anaesthesia compared with other types of anaesthesia. The primary outcomes are overall survival and disease-free survival. The secondary outcomes are health-related quality of life, time to tumour progression, distant disease-free survival, time to treatment failure, cancer-specific survival, biochemical recurrence, return of intended oncological therapy, days alive and out of the hospital at 90 days, cost analysis and adverse events. A comprehensive literature search will be performed using the MEDLINE, EMBASE, Cochrane CENTRAL, Web of Science, LILACS and IBECS databases. Grey literature will also be searched. Risk of methodological bias will be assessed using The Cochrane Collaboration's revised tool for assessing risk of bias in randomised trials (RoB 2.0) and the Newcastle-Ottawa scale. Two reviewers will independently assess the eligibility of studies and risk of bias; a third author will solve discrepancies. One author will perform data extraction and the other will check the process and data. Qualitative analysis will be carried out using all included studies. A meta-analysis using a random-effects model for pooled risk estimates will be carried out for the two main outcomes and for selected secondary outcomes if they conform to previously stated criteria. The GRADE approach will be used to summarise the quality of evidence. ETHICS AND DISSEMINATION: Ethics approval is not required as we analyse data from previously reported studies. PROSPERO REGISTRATION NUMBER: CRD42018114918.

A worldwide perspective of sepsis epidemiology and survival according to age: Observational data from the ICON audit.

PURPOSE: To investigate age-related differences in outcomes of critically ill patients with sepsis around the world. METHODS: We performed a secondary analysis of data from the prospective ICON audit, in which all adult (>16 years) patients admitted to participating ICUs between May 8 and 18, 2012, were included, except admissions for routine postoperative observation. For this sub-analysis, the 10,012 patients with completed age data were included. They were divided into five age groups - ≤50, 51-60, 61-70, 71-80, >80 years. Sepsis was defined as infection plus at least one organ failure. RESULTS: A total of 2963 patients had sepsis, with similar proportions across the age groups (≤50 = 25.2%; 51-60 = 30.3%; 61-70 = 32.8%; 71-80 = 30.7%; >80 = 30.9%). Hospital mortality increased with age and in patients >80 years was almost twice that of patients ≤50 years (49.3% vs 25.2%, p < .05). The maximum rate of increase in mortality was about 0.75% per year, occurring between the ages of 71 and 77 years. In multilevel analysis, age > 70 years was independently associated with increased risk of dying. CONCLUSIONS: The odds for death in ICU patients with sepsis increased with age with the maximal rate of increase occurring between the ages of 71 and 77 years.

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.