Transitional discharge interventions for people with schizophrenia.

BACKGROUND: Schizophrenia is a chronic mental illness characterized by delusions, hallucinations, and important functional and social disability. Interventions labeled as 'transitional' add to care plans made during the hospital stay in preparation for discharge. They also include interventions developed after discharge to support people with serious mental illness as they make the transition from the hospital to the community. Transitional discharge interventions may anticipate the future needs of the patient after discharge by co-ordinating the different levels of the health system that can effectively guarantee continuity of care in the community. This occurs through the provision of therapeutic relationships which give a safety net throughout the discharge and community reintegration processes to improve the general condition of users, level of functioning, use of health resources, and satisfaction with care. OBJECTIVES: To assess the effects of transitional discharge interventions for people with schizophrenia. SEARCH METHODS: On 7 December 2022, we searched the Cochrane Schizophrenia Group's Study-Based Register of Trials, which is based on CENTRAL, MEDLINE, Embase, PubMed, CINAHL, ClinicalTrials.gov, ISRCTN, PsycINFO, and WHO ICTRP. SELECTION CRITERIA: Randomized controlled trials (RCTs) evaluating the effects of transitional discharge interventions in people with schizophrenia and schizophrenia-related disorders. Eligible interventions included three key elements: predischarge planning, co-ordination of care and follow-up, and postdischarge support. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Outcomes of this review included global state (relapse), service use (hospitalization), general functioning, satisfaction with care, adverse effects/events, quality of life, and direct costs. For binary outcomes, we calculated risk ratios (RRs) and their 95% confidence intervals (CIs). For continuous outcomes, we calculated the mean difference (MD) or standardized mean difference (SMD) and their 95% CIs. We used GRADE to assess certainty of evidence. MAIN RESULTS: We found 12 studies with 1748 participants comparing transitional discharge interventions to usual care. All were parallel-group RCTs. No studies assessed global state (relapse) or reported data about adverse events/effects. All studies had a high risk of bias, mainly due to serious concerns about allocation concealment, deviations from intended interventions, measurement of the outcomes, and missing outcome data. Transitional discharge interventions may make little to no difference in service use (hospitalization) at short- and long-term follow-ups, but the evidence is very uncertain (RR 1.18, 95% CI 0.55 to 2.50; I2 = 54%; 4 studies, 462 participants; very low-certainty evidence). Transitional discharge intervention may increase the levels of functioning after discharge (clinically important change in general functioning) (SMD 0.95, 95% CI -0.06 to 1.97; I² = 95%; 4 studies, 437 participants; very low-certainty evidence) and may increase the proportion of participants who are satisfied with the intervention (clinically important change in satisfaction) (RR 1.96, 95% CI 1.37 to 2.80; 1 study, 76 participants; very low-certainty evidence), but for both outcomes the evidence is very uncertain. Transitional discharge intervention may make little to no difference in quality of life compared to treatment as usual (SMD 0.24, 95% CI -0.30 to 0.78; I² = 90%; 4 studies, 748 participants; very low-certainty evidence), but we are very uncertain. For direct costs, one study with 124 participants did not report full details and thus the results were inconclusive. AUTHORS' CONCLUSIONS: There is currently no clear evidence for or against implementing transitional discharge interventions for people with schizophrenia. Transitional discharge interventions may improve patient satisfaction and functionality, but this evidence is also very uncertain. For future research, it is important to improve the quality of the conduct and reporting of these trials, including using validated tools for measuring their outcomes.

Cardiovascular health metrics in low and middle-income countries: A scoping review.

BACKGROUND: In 2010 the American Heart Association defined the concept of ideal cardiovascular health to renew the focus on primordial prevention for cardiovascular disease. Evidence primarily from high-income countries suggests ideal CVH prevalence is low and decreases with age, with vulnerable populations differentially affected. We aimed to identify and characterize the evidence relevant to CVH metrics in low- and middle-income countries (LMICs). METHODS: We followed the Joanna Briggs Institute guideline for the conduct of this scoping review. We searched MEDLINE, Embase, LILACS and study registers from inception to 14 March 2022. We included cross-sectional and cohort studies in populations representing a geographically-defined unit (urban or rural) in LMICs, and with data on CVH metrics i.e. all health or clinical factors (cholesterol, blood pressure, glycemia and body mass index) and at least one health behavior (smoking, diet or physical activity). We report findings following the PRISMA-Scr extension for scoping reviews. RESULTS: We included 251 studies; 85% were cross-sectional. Most studies (70.9%) came from just ten countries. Only 6.8% included children younger than 12 years old. Only 34.7% reported seven metrics; 25.1%, six. Health behaviors were mostly self-reported; 45.0% of studies assessed diet, 58.6% physical activity, and 90.0% smoking status. CONCLUSIONS: We identified a substantial and heterogeneous body of research presenting CVH metrics in LMICs. Few studies assessed all components of CVH, especially in children and in low-income settings. This review will facilitate the design of future studies to bridge the evidence gap. This scoping review protocol was previously registered on OSF: https://osf.io/sajnh.

Search strategies (filters) to identify systematic reviews in MEDLINE and Embase.

BACKGROUND: Bibliographic databases provide access to an international body of scientific literature in health and medical sciences. Systematic reviews are an important source of evidence for clinicians, researchers, consumers, and policymakers as they address a specific health-related question and use explicit methods to identify, appraise and synthesize evidence from which conclusions can be drawn and decisions made. Methodological search filters help database end-users search the literature effectively with different levels of sensitivity and specificity. These filters have been developed for various study designs and have been found to be particularly useful for intervention studies. Other filters have been developed for finding systematic reviews. Considering the variety and number of available search filters for systematic reviews, there is a need for a review of them in order to provide evidence about their retrieval properties at the time they were developed. OBJECTIVES: To review systematically empirical studies that report the development, evaluation, or comparison of search filters to retrieve reports of systematic reviews in MEDLINE and Embase. SEARCH METHODS: We searched the following databases from inception to January 2023: MEDLINE, Embase, PsycINFO; Library, Information Science & Technology Abstracts (LISTA) and Science Citation Index (Web of Science). SELECTION CRITERIA: We included studies if one of their primary objectives is the development, evaluation, or comparison of a search filter that could be used to retrieve systematic reviews on MEDLINE, Embase, or both. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data using a pre-specified and piloted data extraction form using InterTASC Information Specialist Subgroup (ISSG) Search Filter Evaluation Checklist. MAIN RESULTS: We identified eight studies that developed filters for MEDLINE and three studies that developed filters for Embase. Most studies are very old and some were limited to systematic reviews in specific clinical areas. Six included studies reported the sensitivity of their developed filter. Seven studies reported precision and six studies reported specificity. Only one study reported the number needed to read and positive predictive value. None of the filters were designed to differentiate systematic reviews on the basis of their methodological quality. For MEDLINE, all filters showed similar sensitivity and precision, and one filter showed higher levels of specificity. For Embase, filters showed variable sensitivity and precision, with limited study reports that may affect accuracy assessments. The report of these studies had some limitations, and the assessments of their accuracy may suffer from indirectness, considering that they were mostly developed before the release of the PRISMA 2009 statement or due to their limited scope in the selection of systematic review topics. Search filters for MEDLINE Three studies produced filters with sensitivity > 90% with variable degrees of precision, and only one of them was developed and validated in a gold-standard database, which allowed the calculation of specificity. The other two search filters had lower levels of sensitivity. One of these produced a filter with higher levels of specificity (> 90%). All filters showed similar sensitivity and precision in the external validation, except for one which was not externally validated and another one which was conceptually derived and only externally validated. Search filters for Embase We identified three studies that developed filters for this database. One of these studies developed filters with variable sensitivity and precision, including highly sensitive strategies (> 90%); however, it was not externally validated. The other study produced a filter with a lower sensitivity (72.7%) but high specificity (99.1%) with a similar performance in the external validation. AUTHORS' CONCLUSIONS: Studies reporting the development, evaluation, or comparison of search filters to retrieve reports of systematic reviews in MEDLINE showed similar sensitivity and precision, with one filter showing higher levels of specificity. For Embase, filters showed variable sensitivity and precision, with limited information about how the filter was produced, which leaves us uncertain about their performance assessments. Newer filters had limitations in their methods or scope, including very focused subject topics for their gold standards, limiting their applicability across other topics. Our findings highlight that consensus guidance on the conduct of search filters and standardized reporting of search filters are needed, as we found highly heterogeneous development methods, accuracy assessments and outcome selection. New strategies adaptable across interfaces could enhance their usability. Moreover, the performance of existing filters needs to be evaluated in light of the impact of reporting guidelines, including the PRISMA 2009, on how systematic reviews are reported. Finally, future filter developments should also consider comparing the filters against a common reference set to establish comparative performance and assess the quality of systematic reviews retrieved by strategies.

Minimally invasive treatments for benign prostatic hyperplasia: a Cochrane network meta-analysis.

OBJECTIVE: To assess the comparative effectiveness and ranking of minimally invasive treatments (MITs) for lower urinary tract symptoms (LUTS) in men with benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: We searched multiple databases up to 24 February 2021. We included randomized controlled trials assessing the following treatments: convective radiofrequency water vapour thermal therapy (WVTT; or Rezum); prostatic arterial embolization (PAE); prostatic urethral lift (PUL; or Urolift); temporary implantable nitinol device (TIND); and transurethral microwave thermotherapy (TUMT) compared to transurethral resection of the prostate (TURP) or sham surgery. We performed a frequentist network meta-analysis. RESULTS: We included 27 trials involving 3017 men. The overall certainty of the evidence of most outcomes according to GRADE was low to very low. Compared to TURP, we found that PUL and PAE may result in little to no difference in urological symptoms, while WVTT, TUMT and TIND may result in worse urological symptoms. MITs may result in little to no difference in quality of life, compared to TURP. MITs may result in a large reduction in major adverse events compared to TURP. We were uncertain about the effects of PAE and PUL on retreatment compared to TURP, however, TUMT may result in higher retreatment rates. We were very uncertain of the effects of MITs on erectile function and ejaculatory function. Among MITs, PUL and PAE had the highest likelihood of being the most efficacious for urinary symptoms and quality of life, TUMT for major adverse events, WVTT and TIND for erectile function and PUL for ejaculatory function. Excluding WVTT and TIND, for which there were only studies with short-term (3-month) follow-up, PUL had the highest likelihood of being the most efficacious for retreatment. CONCLUSIONS: Minimally invasive treatments may result in similar or worse effects concerning urinary symptoms and quality of life compared to TURP at short-term follow-up.

Antioxidants to prevent respiratory decline in people with Duchenne muscular dystrophy and progressive respiratory decline.

BACKGROUND: Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder characterised by progressive muscle weakness beginning in early childhood. Respiratory failure and weak cough develop in all patients as a consequence of muscle weakness leading to a risk of atelectasis, pneumonia, or the need for ventilatory support. There is no curative treatment for DMD. Corticosteroids are the only pharmacological intervention proven to delay the onset and progression of muscle weakness and thus respiratory decline in DMD. Antioxidant treatment has been proposed to try to reduce muscle weakness in general, and respiratory decline in particular.  OBJECTIVES: To assess the effects of antioxidant agents on preventing respiratory decline in people with Duchenne muscular dystrophy during the respiratory decline phase of the condition.  SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and two trials registers to 23 March 2021, together with reference checking, citation searching, and contact with study authors to identify additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs that met our inclusion criteria. We included male patients with a diagnosis of DMD who had respiratory decline evidenced by a forced vital capacity (FVC%) less than 80% but greater than 30% of predicted values, receiving any antioxidant agent compared with other therapies for the management of DMD or placebo.  DATA COLLECTION AND ANALYSIS: Two review authors screened studies for eligibility, assessed risk of bias of studies, and extracted data. We used standard methods expected by Cochrane. We assessed the certainty of the evidence using the GRADE approach. The primary outcomes were FVC and hospitalisation due to respiratory infections. Secondary outcomes were quality of life, adverse events, change in muscle function, forced expiratory volume in the first second (FEV1), and peak expiratory flow (PEF).  MAIN RESULTS: We included one study with 66 participants who were not co-treated with corticosteroids, which was the only study to contribute data to our main analysis. We also included a study that enrolled 255 participants treated with corticosteroids, which was only available as a press release without numerical results. The studies were parallel-group RCTs that assessed the effect of idebenone on respiratory function compared to placebo. The trial that contributed numerical data included patients with a mean (standard deviation) age of 14.3 (2.7) years at the time of inclusion, with a documented diagnosis of DMD or severe dystrophinopathy with clinical features consistent with typical DMD. The overall risk of bias across most outcomes was similar and judged as 'low'.  Idebenone may result in a slightly less of a decline in FVC from baseline to one year compared to placebo (mean difference (MD) 3.28%, 95% confidence interval (CI) -0.41 to 6.97; 64 participants; low-certainty evidence), and probably has little or no effect on change in quality of life (MD -3.80, 95% CI -10.09 to 2.49; 63 participants; moderate-certainty evidence) (Pediatric Quality of Life Inventory (PedsQL), range 0 to 100, 0 = worst, 100 = best quality of life). As a related but secondary outcome, idebenone may result in less of a decline from baseline in FEV1 (MD 8.28%, 95% CI 0.89 to 15.67; 53 participants) and PEF (MD 6.27%, 95% CI 0.61 to 11.93; 1 trial, 64 participants) compared to placebo. Idebenone was associated with fewer serious adverse events (RR 0.42, 95% CI 0.09 to 2.04; 66 participants; low-certainty evidence) and little to no difference in non-serious adverse events (RR 1.00, 95% CI 0.88 to 1.13; 66 participants; low-certainty evidence) compared to placebo. Idebenone may result in little to no difference in change in arm muscle function (MD -2.45 N, 95% CI -8.60 to 3.70 for elbow flexors and MD -1.06 N, 95% CI -6.77 to 4.65 for elbow extensors; both 52 participants) compared to placebo. We found no studies evaluating the outcome hospitalisation due to respiratory infection.  The second trial, involving 255 participants, for which data were available only as a press release without numerical data, was prematurely discontinued due to futility after an interim efficacy analysis based on FVC. There were no safety concerns. The certainty of the evidence was low for most outcomes due to imprecision and publication bias (the lack of a full report of the larger trial, which was prematurely terminated). AUTHORS' CONCLUSIONS: Idebenone is the only antioxidant agent tested in RCTs for preventing respiratory decline in people with DMD for which evidence was available for assessment. Idebenone may result in slightly less of a decline in FVC and less of a decline in FEV1 and PEF, but probably has little to no measurable effect on change in quality of life. Idebenone is associated with fewer serious adverse events than placebo. Idebenone may result in little to no difference in change in muscle function. Discontinuation due to the futility of the SIDEROS trial and its expanded access programmes may indicate that idebenone research in this condition is no longer needed, but we await the trial data. Further research is needed to establish the effect of different antioxidant agents on preventing respiratory decline in people with DMD during the respiratory decline phase of the condition.

Palivizumab for preventing severe respiratory syncytial virus (RSV) infection in children.

BACKGROUND: Respiratory viruses are the leading cause of lower respiratory tract infection (LRTI) and hospitalisation in infants and young children. Respiratory syncytial virus (RSV) is the main infectious agent in this population. Palivizumab is administered intramuscularly every month during five months in the first RSV season to prevent serious RSV LRTI in children. Given its high cost, it is essential to know if palivizumab continues to be effective in preventing severe RSV disease in children. OBJECTIVES: To assess the effects of palivizumab for preventing severe RSV infection in children. SEARCH METHODS: We searched CENTRAL, MEDLINE, three other databases and two trials registers to 14 October 2021, together with reference checking, citation searching and contact with study authors to identify additional studies. We searched Embase to October 2020, as we did not have access to this database for 2021. SELECTION CRITERIA: We included randomised controlled trials (RCTs), including cluster-RCTs, comparing palivizumab given at a dose of 15 mg/kg once a month (maximum five doses) with placebo, no intervention or standard care in children 0 to 24 months of age from both genders, regardless of RSV infection history.  DATA COLLECTION AND ANALYSIS: We used Cochrane's Screen4Me workflow to help assess the search results. Two review authors screened studies for selection, assessed risk of bias and extracted data. We used standard Cochrane methods. We used GRADE to assess the certainty of the evidence. The primary outcomes were hospitalisation due to RSV infection, all-cause mortality and adverse events. Secondary outcomes were hospitalisation due to respiratory-related illness, length of hospital stay, RSV infection, number of wheezing days, days of supplemental oxygen, intensive care unit length of stay and mechanical ventilation days. MAIN RESULTS: We included five studies with  a total of 3343 participants. All studies were parallel RCTs, assessing the effects of 15 mg/kg of palivizumab every month up to five months compared to placebo or no intervention in an outpatient setting, although one study also included hospitalised infants. Most of the included studies were conducted in children with a high risk of RSV infection due to comorbidities like bronchopulmonary dysplasia and congenital heart disease. The risk of bias of outcomes across all studies was similar and predominately low.  Palivizumab reduces hospitalisation due to RSV infection at two years' follow-up (risk ratio (RR) 0.44, 95% confidence interval (CI) 0.30 to 0.64; 5 studies, 3343 participants; high certainty evidence). Based on 98 hospitalisations per 1000 participants in the placebo group, this corresponds to 43 (29 to 62) per 1000 participants in the palivizumab group. Palivizumab probably results in little to no difference in mortality at two years' follow-up (RR 0.69, 95% CI 0.42 to 1.15; 5 studies, 3343 participants; moderate certainty evidence). Based on 23 deaths per 1000 participants in the placebo group, this corresponds to 16 (10 to 27) per 1000 participants in the palivizumab group. Palivizumab probably results in little to no difference in adverse events at 150 days' follow-up (RR 1.09, 95% CI 0.85 to 1.39; 3 studies, 2831 participants; moderate certainty evidence). Based on 84 cases per 1000 participants in the placebo group, this corresponds to 91 (71 to 117) per 1000 participants in the palivizumab group. Palivizumab probably results in a slight reduction in hospitalisation due to respiratory-related illness at two years' follow-up (RR 0.78, 95% CI 0.62 to 0.97; 5 studies, 3343 participants; moderate certainty evidence). Palivizumab may result in a large reduction in RSV infection at two years' follow-up (RR 0.33, 95% CI 0.20 to 0.55; 3 studies, 554 participants; low certainty evidence). Based on 195 cases of RSV infection per 1000 participants in the placebo group, this corresponds to 64 (39 to 107) per 1000 participants in the palivizumab group. Palivizumab also reduces the number of wheezing days at one year's follow-up (RR 0.39, 95% CI 0.35 to 0.44; 1 study, 429 participants; high certainty evidence). AUTHORS' CONCLUSIONS: The available evidence suggests that prophylaxis with palivizumab reduces hospitalisation due to RSV infection and results in little to no difference in mortality or adverse events. Moreover, palivizumab results in a slight reduction in hospitalisation due to respiratory-related illness and may result in a large reduction in RSV infections. Palivizumab also reduces the number of wheezing days. These results may be applicable to children with a high risk of RSV infection due to comorbidities. Further research is needed to establish the effect of palivizumab on children with other comorbidities known as risk factors for severe RSV disease (e.g. immune deficiencies) and other social determinants of the disease, including children living in low- and middle-income countries, tropical regions, children lacking breastfeeding, living in poverty, or members of families in overcrowded situations.

Transurethral microwave thermotherapy for the treatment of lower urinary tract symptoms in men with benign prostatic hyperplasia.

BACKGROUND: Transurethral resection of the prostate (TURP) has been the gold-standard treatment for alleviating urinary symptoms and improving urinary flow in men with symptomatic benign prostatic hyperplasia (BPH). However, the morbidity of TURP approaches 20%, and less invasive techniques have been developed for treating BPH. Transurethral microwave thermotherapy (TUMT) is an alternative, minimally-invasive treatment that delivers microwave energy to produce coagulation necrosis in prostatic tissue. This is an update of a review last published in 2012. OBJECTIVES: To assess the effects of transurethral microwave thermotherapy for the treatment of lower urinary tract symptoms in men with benign prostatic hyperplasia. SEARCH METHODS: We performed a comprehensive search using multiple databases (the Cochrane Library, MEDLINE, Embase, Scopus, Web of Science, and LILACS), trials registries, other sources of grey literature, and conference proceedings published up to 31 May 2021, with no restrictions by language or publication status. SELECTION CRITERIA: We included parallel-group randomized controlled trials (RCTs) and cluster-RCTs of participants with BPH who underwent TUMT. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion at each stage and undertook data extraction and risk of bias and GRADE assessments of the certainty of the evidence (CoE). We considered review outcomes measured up to 12 months after randomization as short-term and beyond 12 months as long-term. Our main outcomes included: urologic symptoms scores, quality of life, major adverse events, retreatment, and ejaculatory and erectile function. MAIN RESULTS: In this update, we identified no new RCTs, but we included data from studies excluded in the previous version of this review. We included 16 trials with 1919 participants, with a median age of 69 and moderate lower urinary tract symptoms. The certainty of the evidence for most comparisons was moderate-to-low, due to an overall high risk of bias across studies and imprecision (few participants and events). TUMT versus TURP Based on data from four studies with 306 participants, when compared to TURP, TUMT probably results in little to no difference in urologic symptom scores measured by the International Prostatic Symptom Score (IPSS) on a scale from 0 to 35, with higher scores indicating worse symptoms at short-term follow-up (mean difference (MD) 1.00, 95% confidence interval (CI) -0.03 to 2.03; moderate certainty). There is likely to be little to no difference in the quality of life (MD -0.10, 95% CI -0.67 to 0.47; 1 study, 136 participants, moderate certainty). TUMT likely results in fewer major adverse events (RR 0.20, 95% CI 0.09 to 0.43; 6 studies, 525 participants, moderate certainty); based on 168 cases per 1000 men in the TURP group, this corresponds to 135 fewer (153 to 96 fewer) per 1000 men in the TUMT group. TUMT, however, probably results in a large increase in the need for retreatment (risk ratio (RR) 7.07, 95% CI 1.94 to 25.82; 5 studies, 337 participants, moderate certainty) (usually by repeated TUMT or TURP); based on zero cases per 1000 men in the TURP group, this corresponds to 90 more (40 to 150 more) per 1000 men in the TUMT group. There may be little to no difference in erectile function between these interventions (RR 0.63, 95% CI 0.24 to 1.63; 5 studies, 337 participants; low certainty). However, TUMT may result in fewer cases of ejaculatory dysfunction compared to TURP (RR 0.36, 95% CI 0.24 to 0.53; 4 studies, 241 participants; low certainty). TUMT versus sham Based on data from four studies with 483 participants we found that, when compared to sham, TUMT probably reduces urologic symptom scores using the IPSS at short-term follow-up (MD -5.40, 95% CI -6.97 to -3.84; moderate certainty). TUMT may cause little to no difference in the quality of life (MD -0.95, 95% CI -1.14 to -0.77; 2 studies, 347 participants; low certainty) as measured by the IPSS quality-of-life question on a scale from 0 to 6, with higher scores indicating a worse quality of life. We are very uncertain about the effects on major adverse events, since most studies reported no events or isolated lesions of the urinary tract. TUMT may also reduce the need for retreatment compared to sham (RR 0.27, 95% CI 0.08 to 0.88; 2 studies, 82 participants, low certainty); based on 194 retreatments per 1000 men in the sham group, this corresponds to 141 fewer (178 to 23 fewer) per 1000 men in the TUMT group. We are very uncertain of the effects on erectile and ejaculatory function (very low certainty), since we found isolated reports of impotence and ejaculatory disorders (anejaculation and hematospermia). There were no data available for the comparisons of TUMT versus convective radiofrequency water vapor therapy, prostatic urethral lift, prostatic arterial embolization or temporary implantable nitinol device. AUTHORS' CONCLUSIONS: TUMT provides a similar reduction in urinary symptoms compared to the standard treatment (TURP), with fewer major adverse events and fewer cases of ejaculatory dysfunction at short-term follow-up. However, TUMT probably results in a large increase in retreatment rates. Study limitations and imprecision reduced the confidence we can place in these results. Furthermore, most studies were performed over 20 years ago. Given the emergence of newer minimally-invasive treatments, high-quality head-to-head trials with longer follow-up are needed to clarify their relative effectiveness. Patients' values and preferences, their comorbidities and the effects of other available minimally-invasive procedures, among other factors, can guide clinicians when choosing the optimal treatment for this condition.

Antioxidants to prevent respiratory decline in people with Duchenne muscular dystrophy and progressive respiratory decline.

BACKGROUND: Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder characterised by progressive muscle weakness beginning in early childhood. Respiratory failure and weak cough develop in all patients as a consequence of muscle weakness leading to a risk of atelectasis, pneumonia, or the need for ventilatory support. There is no curative treatment for DMD. Corticosteroids are the only pharmacological intervention proven to delay the onset and progression of muscle weakness and thus respiratory decline in DMD. Antioxidant treatment has been proposed to try to reduce muscle weakness in general, and respiratory decline in particular.  OBJECTIVES: To assess the effects of antioxidant agents on preventing respiratory decline in people with Duchenne muscular dystrophy during the respiratory decline phase of the condition.  SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and two trials registers to 23 March 2021, together with reference checking, citation searching, and contact with study authors to identify additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs that met our inclusion criteria. We included male patients with a diagnosis of DMD who had respiratory decline evidenced by a forced vital capacity (FVC%) less than 80% but greater than 30% of predicted values, receiving any antioxidant agent compared with other therapies for the management of DMD or placebo.  DATA COLLECTION AND ANALYSIS: Two review authors screened studies for eligibility, assessed risk of bias of studies, and extracted data. We used standard methods expected by Cochrane. We assessed the certainty of the evidence using the GRADE approach. The primary outcomes were FVC and hospitalisation due to respiratory infections. Secondary outcomes were quality of life, adverse events, change in muscle function, forced expiratory volume in the first second (FEV1), and peak expiratory flow (PEF).  MAIN RESULTS: We included one study with 66 participants who were not co-treated with corticosteroids, which was the only study to contribute data to our main analysis. We also included a study that enrolled 255 participants treated with corticosteroids, which was only available as a press release without numerical results. The studies were parallel-group RCTs that assessed the effect of idebenone on respiratory function compared to placebo. The trial that contributed numerical data included patients with a mean (standard deviation) age of 14.3 (2.7) years at the time of inclusion, with a documented diagnosis of DMD or severe dystrophinopathy with clinical features consistent with typical DMD. The overall risk of bias across most outcomes was similar and judged as 'low'.  Idebenone may result in a slightly less of a decline in FVC from baseline to one year compared to placebo (mean difference (MD) 3.28%, 95% confidence interval (CI) -0.41 to 6.97; 64 participants; low-certainty evidence), and probably has little or no effect on change in quality of life (MD -3.80, 95% CI -10.09 to 2.49; 63 participants; moderate-certainty evidence) (Pediatric Quality of Life Inventory (PedsQL), range 0 to 100, 0 = worst, 100 = best quality of life). As a related but secondary outcome, idebenone may result in less of a decline from baseline in FEV1 (MD 8.28%, 95% CI 0.89 to 15.67; 53 participants) and PEF (MD 6.27%, 95% CI 0.61 to 11.93; 1 trial, 64 participants) compared to placebo. Idebenone was associated with fewer serious adverse events (RR 0.42, 95% CI 0.09 to 2.04; 66 participants; low-certainty evidence) and little to no difference in non-serious adverse events (RR 1.00, 95% CI 0.88 to 1.13; 66 participants; low-certainty evidence) compared to placebo. Idebenone may result in little to no difference in change in arm muscle function (MD -2.45 N, 95% CI -8.60 to 3.70 for elbow flexors and MD -1.06 N, 95% CI -6.77 to 4.65 for elbow extensors; both 52 participants) compared to placebo. We found no studies evaluating the outcome hospitalisation due to respiratory infection.  The second trial, involving 255 participants, for which data were available only as a press release without numerical data, was prematurely discontinued due to futility after an interim efficacy analysis based on FVC. There were no safety concerns. The certainty of the evidence was low for most outcomes due to imprecision and publication bias (the lack of a full report of the larger trial, which was prematurely terminated). AUTHORS' CONCLUSIONS: Idebenone is the only antioxidant agent tested in RCTs for preventing respiratory decline in people with DMD for which evidence was available for assessment. Idebenone may result in slightly less of a decline in FVC and less of a decline in FEV1 and PEF, but probably has little to no measurable effect on change in quality of life. Idebenone is associated with fewer serious adverse events than placebo. Idebenone may result in little to no difference in change in muscle function. Discontinuation due to the futility of the SIDEROS trial and its expanded access programmes may indicate that idebenone research in this condition is no longer needed, but we await the trial data. Further research is needed to establish the effect of different antioxidant agents on preventing respiratory decline in people with DMD during the respiratory decline phase of the condition.

Minimally invasive treatments for lower urinary tract symptoms in men with benign prostatic hyperplasia: a network meta-analysis.

BACKGROUND: A variety of minimally invasive treatments are available as an alternative to transurethral resection of the prostate (TURP) for management of lower urinary tract symptoms (LUTS) in men with benign prostatic hyperplasia (BPH). However, it is unclear which treatments provide better results. OBJECTIVES: Our primary objective was to assess the comparative effectiveness of minimally invasive treatments for lower urinary tract symptoms in men with BPH through a network meta-analysis. Our secondary objective was to obtain an estimate of relative ranking of these minimally invasive treatments, according to their effects. SEARCH METHODS: We performed a comprehensive search of multiple databases (CENTRAL, MEDLINE, Embase, Scopus, Web of Science and LILACS), trials registries, other sources of grey literature, and conference proceedings, up to 24 February 2021. We had no restrictions on language of publication or publication status. SELECTION CRITERIA: We included parallel-group randomized controlled trials assessing the effects of the following minimally invasive treatments, compared to TURP or sham treatment, on men with moderate to severe LUTS due to BPH: convective radiofrequency water vapor therapy (CRFWVT); prostatic arterial embolization (PAE); prostatic urethral lift (PUL); temporary implantable nitinol device (TIND); and transurethral microwave thermotherapy (TUMT). DATA COLLECTION AND ANALYSIS: Two review authors independently screened the literature, extracted data, and assessed risk of bias. We performed statistical analyses using a random-effects model for pair-wise comparisons and a frequentist network meta-analysis for combined estimates. We interpreted them according to Cochrane methods. We planned subgroup analyses by age, prostate volume, and severity of baseline symptoms. We used risk ratios (RRs) with 95% confidence intervals (CIs) to express dichotomous data and mean differences (MDs) with 95% CIs to express continuous data. We used the GRADE approach to rate the certainty of evidence. MAIN RESULTS: We included 27 trials involving 3017 men, mostly over age 50, with severe LUTS due to BPH. The overall certainty of evidence was low to very low due to concerns regarding bias, imprecision, inconsistency (heterogeneity), and incoherence. Based on the network meta-analysis, results for our main outcomes were as follows. Urologic symptoms (19 studies, 1847 participants): PUL and PAE may result in little to no difference in urologic symptoms scores (MD of International Prostate Symptoms Score [IPSS]) compared to TURP (3 to 12 months; MD range 0 to 35; higher scores indicate worse symptoms; PUL: 1.47, 95% CI -4.00 to 6.93; PAE: 1.55, 95% CI -1.23 to 4.33; low-certainty evidence). CRFWVT, TUMT, and TIND may result in worse urologic symptoms scores compared to TURP at short-term follow-up, but the CIs include little to no difference (CRFWVT: 3.6, 95% CI -4.25 to 11.46; TUMT: 3.98, 95% CI 0.85 to 7.10; TIND: 7.5, 95% CI -0.68 to 15.69; low-certainty evidence). Quality of life (QoL) (13 studies, 1459 participants): All interventions may result in little to no difference in the QoL scores, compared to TURP (3 to 12 months; MD of IPSS-QoL score; MD range 0 to 6; higher scores indicate worse symptoms; PUL: 0.06, 95% CI -1.17 to 1.30; PAE: 0.09, 95% CI -0.57 to 0.75; CRFWVT: 0.37, 95% CI -1.45 to 2.20; TUMT: 0.65, 95% CI -0.48 to 1.78; TIND: 0.87, 95% CI -1.04 to 2.79; low-certainty evidence). Major adverse events (15 studies, 1573 participants): TUMT probably results in a large reduction of major adverse events compared to TURP (RR 0.20, 95% CI 0.09 to 0.43; moderate-certainty evidence). PUL, CRFWVT, TIND and PAE may also result in a large reduction in major adverse events, but CIs include substantial benefits and harms at three months to 36 months; PUL: RR 0.30, 95% CI 0.04 to 2.22; CRFWVT: RR 0.37, 95% CI 0.01 to 18.62; TIND: RR 0.52, 95% CI 0.01 to 24.46; PAE: RR 0.65, 95% CI 0.25 to 1.68; low-certainty evidence). Retreatment (10 studies, 799 participants): We are uncertain about the effects of PAE and PUL on retreatment compared to TURP (12 to 60 months; PUL: RR 2.39, 95% CI 0.51 to 11.1; PAE: RR 4.39, 95% CI 1.25 to 15.44; very low-certainty evidence). TUMT may result in higher retreatment rates (RR 9.71, 95% CI 2.35 to 40.13; low-certainty evidence). Erectile function (six studies, 640 participants): We are very uncertain of the effects of minimally invasive treatments on erectile function (MD of International Index of Erectile Function [IIEF-5]; range 5 to 25; higher scores indicates better function; CRFWVT: 6.49, 95% CI -8.13 to 21.12; TIND: 5.19, 95% CI -9.36 to 19.74; PUL: 3.00, 95% CI -5.45 to 11.44; PAE: -0.03, 95% CI -6.38, 6.32; very low-certainty evidence). Ejaculatory dysfunction (eight studies, 461 participants): We are uncertain of the effects of PUL, PAE and TUMT on ejaculatory dysfunction compared to TURP (3 to 12 months; PUL: RR 0.05, 95 % CI 0.00 to 1.06; PAE: RR 0.35, 95% CI 0.13 to 0.92; TUMT: RR 0.34, 95% CI 0.17 to 0.68; low-certainty evidence). TURP is the reference treatment with the highest likelihood of being the most efficacious for urinary symptoms, QoL and retreatment, but the least favorable in terms of major adverse events, erectile function and ejaculatory function. Among minimally invasive procedures, PUL and PAE have the highest likelihood of being the most efficacious for urinary symptoms and QoL, TUMT for major adverse events, PUL for retreatment, CRFWVT and TIND for erectile function and PUL for ejaculatory function. AUTHORS' CONCLUSIONS: Minimally invasive treatments may result in similar or worse effects concerning urinary symptoms and QoL compared to TURP at short-term follow-up. They may result in fewer major adverse events, especially in the case of PUL and PAE; resulting in better rankings for symptoms scores. PUL may result in fewer retreatments compared to other interventions, especially TUMT, which had the highest retreatment rates at long-term follow-up. We are very uncertain about the effects of these interventions on erectile function. There was limited long-term data, especially for CRFWVT and TIND. Future high-quality studies with more extended follow-up, comparing different, active treatment modalities, and adequately reporting critical outcomes relevant to patients, including those related to sexual function, could provide more information on the relative effectiveness of these interventions.

Ventriculo-peritoneal shunting devices for hydrocephalus.

BACKGROUND: Hydrocephalus is a common neurological disorder, caused by a progressive accumulation of cerebrospinal fluid (CSF) within the intracranial space that can lead to increased intracranial pressure, enlargement of the ventricles (ventriculomegaly) and, consequently, to brain damage. Ventriculo-peritoneal shunt systems are the mainstay therapy for this condition, however there are different types of shunt systems. OBJECTIVES: To compare the effectiveness and adverse effects of conventional and complex shunt devices for CSF diversion in people with hydrocephalus. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (2020 Issue 2); Ovid MEDLINE (1946 to February 2020); Embase (Elsevier) (1974 to February 2020); Latin American and Caribbean Health Science Information Database (LILACS) (1980 to February 2020); ClinicalTrials.gov; and World Health Organization International Clinical Trials Registry Platform. SELECTION CRITERIA: We selected randomised controlled trials or quasi-randomised trials of different types of ventriculo-peritoneal shunting devices for people with hydrocephalus. Primary outcomes included: treatment failure, adverse events and mortality. DATA COLLECTION AND ANALYSIS: Two review authors screened studies for selection, assessed risk of bias and extracted data. Due to the scarcity of data, we performed a Synthesis Without Meta-analysis (SWiM) incorporating GRADE for the quality of the evidence. MAIN RESULTS: We included six studies with 962 participants assessing the effects of standard valves compared to anti-syphon valves, other types of standard valves, self-adjusting CSF flow-regulating valves and external differential programmable pressure valves. All included studies started in a hospital setting and offered ambulatory follow-up. Most studies were conducted in infants or children with hydrocephalus from diverse causes. The certainty of the evidence for most comparisons was low to very low. 1. Standard valve versus anti-syphon valve Three studies with 296 randomised participants were included under this comparison. We are uncertain about the incidence of treatment failure in participants with standard valve and anti-syphon valves (very low certainty of the evidence). The incidence of adverse events may be similar in those with standard valves (range 0 to 1.9%) and anti-syphon valves (range 0 to 2.9%) (low certainty of the evidence). Mortality may be similar in those with standard valves (0%) and anti-syphon valves (0.9%) (RD 0.01%, 95% CI -0.02% to 0.03%, low certainty of the evidence). Ventricular size and head circumference may be similar in those with standard valves and anti-syphon valves (low certainty of the evidence). None of the included studies reported the quality of life of participants. 2. Comparison between different types of standard valves Two studies with 174 randomised participants were included under this comparison. We are uncertain about the incidence of treatment failure in participants with different types of standard valves (early postoperative period: RR 0.41, 95% CI 0.13 to 1.27; at 12 months follow-up: RR 1.17, 95% CI 0.72 to 1.92, very low certainty of the evidence). None of the included studies reported adverse events beyond those included under "treatment failure". We are uncertain about the effects of different types of standard valves on mortality (range 2% to 17%, very low certainty of the evidence). The included studies did not report the effects of these interventions on quality of life, ventricular size reduction or head circumference. 3. Standard valve versus self-adjusting CSF flow-regulating valve One study with 229 randomised participants addressed this comparison. The incidence of treatment failure may be similar in those with standard valves (42.98%) and self-adjusting CSF flow-regulating valves (39.13%) (low certainty of the evidence). The incidence of adverse events may be similar in those with standard valves (range 0 to 1.9%) and those with self-adjusting CSF flow-regulating valves (range 0 to 7.2%) (low certainty of the evidence). The included study reported no deaths in either group in the postoperative period. Beyond the early postoperative period, the authors stated that nine patients died (no disaggregated data by each type of intervention was available, low certainty of the evidence). The included studies did not report the effects of these interventions on quality of life, ventricular size reduction or head circumference. 4. External differential programmable pressure valve versus non-programmable valve One study with 377 randomised participants addressed this comparison. The incidence of treatment failure may be similar in those with programmable valves (52%) and non-programmable valves (52%)  (RR 1.02, 95% CI 0.84 to 1.24, low certainty of the evidence). The incidence of adverse events may be similar in those with programmable valves (6.19%) and non-programmable valves (6.01%) (RR 0.97, 95% CI 0.44 to 2.15, low certainty of the evidence). The included study did not report the effect of these interventions on mortality, quality of life or head circumference. Ventricular size reduction may be similar in those with programmable valves and non-programmable valves (low certainty of the evidence). AUTHORS' CONCLUSIONS: Standard shunt valves for hydrocephalus compared to anti-syphon or self-adjusting CSF flow-regulating valves may cause little to no difference on the main outcomes of this review, however we are very uncertain due to the low to very low certainty of evidence. Similarly, different types of standard valves and external differential programmable pressure valves versus non-programmable valves may be associated with similar outcomes. Nevertheless, this review did not include valves with the latest technology, for which we need high-quality randomised controlled trials focusing on patient-important outcomes including costs.

High-flow nasal cannula during pulmonary rehabilitation for people with chronic obstructive pulmonary disease: A systematic review and meta-analysis.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is an increasingly concerning global public health issue due to its high burden of morbidity and mortality. Pulmonary rehabilitation (PR) is a comprehensive intervention to improve patients' physical and psychological conditions, commonly involving oxygen supplementation. The potential benefits of high-flow nasal cannula (HFNC) have recently sparked interest as oxygen therapy. In this context, this study aims to assess the effects of HFNC during the exercise training component of a PR program in people with COPD. METHODS: Systematic review (CRD42022330929). We included randomised controlled trials (RCTs), including crossover RCTs with adults with stable COPD. We included trials using oxygen therapy with HFNC during the exercise training component of a PR programme. PRIMARY OUTCOMES: disease-specific health-related quality of life (HRQoL), exercise capacity (EC) and adverse events. SECONDARY OUTCOMES: treatment adherence, breathlessness and future exacerbations. RESULTS: We included five studies with 300 participants with moderate to severe COPD. The certainty of the evidence was primarily low or very low for all outcomes of interest due to risk of bias, inconsistency or imprecision. HFNC has little to no difference in HRQoL (4 studies, 129 participants, MD 0.17, 95% CI -1.20 to 1.54; I2 50%). HFNC may result in little to no difference in EC (3 studies, 212 participants, mean difference 18.73, 95% CI -20.49 to 28.94; I2 56%), and we are uncertain about the effect of HFNC on breathlessness (4 studies; 244 participants, MD of -0.07, 95% CI -0.4 to 0.26; I2 63%). Only one study with 44 participants reported a participant's withdrawal because of progressive dyspnoea during lower limb exercise. CONCLUSIONS: We are uncertain about the effect of HFNC during the exercise component of a PR programme in HRQoL, EC or dyspnoea compared to usual care or conventional supplementary oxygen. Non-domiciliary oxygen patients showed improvements in HRQoL, EC and dyspnoea.

Post-covid-19 conditions in adults: systematic review and meta-analysis of health outcomes in controlled studies.

Objective: To assess the impact of post-covid-19 conditions among adults. Design: Systematic review and meta-analysis of health outcomes in controlled studies. Data sources: Two sources were searched from database inception to 20 October 2022: Cochrane covid-19 study register (comprising Cochrane Central Register of Controlled Trials, Medline, Embase, clinicalTrials.gov, World Health Organization's International Clinical Trials Registry Platform, medRxiv) and WHO's covid-19 research database. Eligibility criteria: Cohort studies recruiting more than 100 participants with a control group and a follow-up of at least 12 weeks were included. Adults who were documented to have SARS-CoV-2 infection based on clinical, imaging, or laboratory criteria were included. Data extraction and synthesis: Two independent reviewers extracted data. The main outcomes included quality of life, functionality in daily activities, use of resources, recovery rates (cluster of symptoms), and the incidence of new medical diagnoses. Data were pooled using a random effects model. The risk of bias was assessed with the Joanna Briggs Institute critical appraisal tool for cohort studies. Results: We included 63 controlled cohort studies, encompassing more than 96 million participants. Based on five studies, we found a reduction in overall quality of life between individuals with confirmed SARS-CoV-2 infection versus controls at six to 24 months follow-up, although heterogeneity was very high (mean difference in EQ-5D scale -5.28 (95% confidence interval -7.88 to 2.68; I2=93.81%). Evidence from ten studies, which could not be pooled in a meta-analysis, indicated that an increased rate of functional impairment associated with SARS-CoV-2 infection. Use of care increased compared with controls at six to 24 months follow-up at intensive care units (risk ratio 2.00 (95% confidence interval 0.69 to 5.80), five studies, I2=91.96%) and in outpatient care (1.12 (1.01 to 1.24), seven studies, I2=99.51%). Regarding persistent symptoms, individuals with documented SARS-CoV-2 infection had an increased risk of having two or more persistent symptoms at follow-up, especially those related to neurological clusters (ie, risk ratio 1.51 (95% confidence interval 1.17 to 1.93), I2=98.91%). Evidence also showed an increased incidence of a wide variety of metabolic, cardiovascular, neurological, respiratory, haematological and other incident diagnoses. Conclusion: Evidence suggests functional impairment after SARS-CoV-2 infection, in addition to a higher use of resources and a higher incidence of widely varying medical diagnoses. These results should be interpreted with caution, considering the high heterogeneity across studies and study limitations related to outcome measurement and attrition of participants. Systematic review registration: Open Science Framework, osf.io/drm39.

Transurethral Microwave Thermotherapy for Benign Prostatic Hyperplasia: An Updated Cochrane Review.

PURPOSE: To assess the effects of transurethral microwave thermotherapy (TUMT) for the treatment of lower urinary tract symptoms in men with benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: We performed a comprehensive search using multiple databases up to May 2021, with no language or publication status restrictions. We included parallel-group randomized controlled trials of participants with BPH who underwent TUMT. We used standard Cochrane methods, including a GRADE assessment of the certainty of the evidence (CoE). RESULTS: In this update of a previous Cochrane review, we included 16 trials with 1,919 participants. TUMT probably results in little to no difference in urologic symptom scores at short-term follow-up compared to transurethral resection of the prostate (TURP). There is likely to be little to no difference in the quality of life. TUMT likely results in fewer major adverse events. TUMT, however, probably results in a large increase in the need for retreatment. There may be little to no difference in erectile function between these interventions. However, TUMT may result in fewer cases of ejaculatory dysfunction compared to TURP. The overall CoE was moderate to low. CONCLUSIONS: TUMT provides a similar reduction in urinary symptoms compared to TURP, with fewer major adverse events and fewer cases of ejaculatory dysfunction at short-term follow-up. However, TUMT probably results in a large increase in retreatment rates. Study limitations and imprecision reduced the confidence we can place in these results.

Patients' participation in government-sponsored guidelines in Latin America: a cross-sectional study.

BACKGROUND: It is recommended that patients actively participate in clinical practice guideline (CPG) development, which allows consideration of their values and preferences and improves adherence to recommendations. The development of CPGs throughout Latin America is variable and diverse, and the inclusion of patients' participation is unknown. OBJECTIVES: To evaluate the methods of patients' participation in government-sponsored CPGs in Latin America, the type of CPG development and the use of Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methods. DESIGN: Cross-sectional study. We included CPGs developed over the last 10 years through a comprehensive hand search in official national government websites and biomedical databases. MAIN OUTCOME MEASURE: The type of patients' participation was coded according to five predefined categories. We also report the proportion of application of GRADE methods. RESULTS: We included 408 CPGs from 10 countries: 74% (n=303) were de novo development, 13%(n=55) used an adaptation method and 10%(n=41) used both adaptation and de novo methods. Only 45% (n=185) applied the GRADE approach, ranging from 14% (n=12) of CPGs in Brazil to 89% (n=56) of CPGs in Colombia. Only 23% (n=95) of CPGs included at least one method of patients' participation. Mexico was one of the largest CPG producers (100 CPGs), but none included methods of patients' participation; in turn, in countries with lower production of government-sponsored CPGs, patients' participation was found in almost 88%. Guidelines using the GRADE approach were more likely to use methods of patients' participation. These methods were highly variable: 46% (n=44) incorporated patients in the panel, 81% (n=77) searched for evidence about patients' values and preferences, 43% (n=39) used an external review of the draft recommendations by patients, 38% (n=36) used public comments, and 2% included other methods for stakeholders' participation. CONCLUSION: Only one quarter of government-sponsored CPGs in the Latin American region incorporated a method for patients' participation, which varied considerably across the selected countries. These findings highlight the need to improve CPG development methods to systematically incorporate patients' values and preferences when drafting recommendations.

Short and Long-Term Wellbeing of Children following SARS-CoV-2 Infection: A Systematic Review.

Post-COVID conditions in children and adolescents were mostly investigated as the incidence of individual or clusters of symptoms. We aimed to describe the findings of studies assessing key outcomes related to global wellbeing and recovery in children and adolescents from a public health perspective. We searched the Cochrane COVID-19 Study Register and WHO COVID-19 Global literature on coronavirus disease database on 5 November 2021 and tracked ongoing studies published after this date. We included observational studies on children and adolescents with a follow-up greater than 12 weeks and focused on the outcomes of quality of life, recovery/duration of symptoms, school attendance and resource use/rehabilitation. We assessed their methodological quality, and we prepared a narrative synthesis of the results. We included 21 longitudinal and 4 cross-sectional studies (6 with a control group) with over 68 thousand unvaccinated children and adolescents with mostly asymptomatic or mild disease. Study limitations included convenience sampling, a poor description of their study population and heterogeneous definitions of outcomes. Quality of life was not largely affected in adolescents following COVID-19, but there might be greater impairment in young children and in those with more severe forms of the disease (4 studies). There might also be an impairment in daily activities and increased school absenteeism following COVID-19, but the findings were heterogeneous (5 studies). A total of 22 studies provided highly variable estimates based on heterogeneous definitions of overall persistence of symptoms (recovery), ranging from 0 to 67% at 8-12 weeks and 8 to 51% at 6-12 months. We found limited data on resource use and the need for rehabilitation. One controlled study indicated that the quality of life of infected children and adolescents might not substantially differ from controls. All controlled studies found a higher burden of persistent symptoms in COVID-19 cases compared with test-negative controls or cases of influenza. There is limited evidence on the short and long-term well-being of children following SARS-CoV-2 infection. High-quality longitudinal studies with control groups are needed to describe the outcomes in this population, especially in vaccinated children and those affected by new variants of the virus.

Long-Term Health Symptoms and Sequelae Following SARS-CoV-2 Infection: An Evidence Map.

Post-COVID-19 conditions, also known as 'Long-COVID-19', describe a longer and more complex course of illness than acute COVID-19 with no widely accepted uniform case definition. We aimed to map the available evidence on persistent symptoms and sequelae following SARS-CoV-2 in children and adults. We searched the Cochrane COVID-19 Study Register and the WHO COVID-19 Global literature on coronavirus disease database on 5 November 2021. We included longitudinal and cross-sectional studies and we extracted their characteristics, including the type of core outcomes for post-COVID-19 conditions. We included 565 studies (657 records). Most studies were uncontrolled cohort studies. The median follow-up time was 13 weeks (IQR 9 to 24). Only 72% of studies were conducted in high-income countries, 93% included unvaccinated adults with mild-to-critical disease, only 10% included children and adolescents, and less than 5% included children under the age of five. While most studies focused on health symptoms, including respiratory symptoms (71%), neurological symptoms (57%), fatigue (54%), pain (50%), mental functioning (43%), cardiovascular functioning (40%), and post-exertion symptoms (28%), cognitive function (26%), fewer studies assessed other symptoms such as overall recovery (24%), the need for rehabilitation (18%), health-related quality of life (16%), changes in work/occupation and study (10%), or survival related to long-COVID-19 (4%). There is a need for controlled cohort studies with long-term follow-up and a focus on overall recovery, health-related quality of life, and the ability to perform daily tasks. Studies need to be extended to later phases of the pandemic and countries with low resources.

Diaphragmatic dysfunction associated with invasive mechanical ventilation in critically ill adult patients / [Disfunción diafragmática asociada a la ventilación mecánica invasiva en pacientes adultos críticamente enfermos]

Invasive mechanical ventilation (VMI) is a life support therapy that is not free of complications, such as ventilator induced diaphragmatic dysfunction, which is characterized by atrophy and weakness of the muscle. Interest in this pathology seems to be based on the association found with negative clinical results. The prevalence ranges between 29 and 80%, probably due to the variability between the different diagnostic methods and the time of evaluation. The gold standard continues to be the transdiaphragmatic negative pressure generated by the bilateral stimulation of the phrenic nerves, although due to the lack of practicality, diaphragmatic ultrasound began to be used. Although it has several modalities, not all of them have correlation analysis with the gold standard. Another problem arises when analyzing the independent association between pathology and VMI, since confusing factors are not easy to isolate.

La ventilación mecánica invasiva (VMI) es una terapia de soporte vital que no está exenta de complicaciones, como la disfunción diafragmática inducida por la ventilación mecánica, que se caracteriza por atrofia y debilidad de dicho musculo. El interés en esta patología parece estar basado en la asociación encontrada con resultados clínicos negativos. La prevalencia oscila entre 29 y 80%, probablemente debido a la variabilidad entre los diferentes métodos diagnósticos y el momento de la evaluación. El patrón de oro continúa siendo la presión negativa transdiafragmática generada por la estimulación bilateral de los nervios frénicos, aunque por la falta de practicidad, se comenzó a utilizar la ecografía diafragmática. Si bien cuenta con varias modalidades, no todas tienen análisis de correlación con el patrón de oro. Otra problemática surge al momento de analizar la asociación independiente entre la patología y la VMI, ya que los factores confusores no son sencillos de aislar.

The GRADE approach, Part 1: how to assess the certainty of the evidence. / Metodología GRADE, parte 1: cómo evaluar la certeza de la evidencia.

The certainty of the evidence for interventions is the certainty or confidence that the true effect is within a particular range or relative to a threshold. In the new pyramid of evidence, systematic reviews represent the magnifying glass through which this certainty is evaluated. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach arises in response to the existence of multiple evidence classification systems, and it offers a transparent and structured process to develop and present summaries of evidence considering its certainty and, in a second step, the strength of the recommendations that they inform. The GRADE process begins with an explicit question that includes all important and critical outcomes explicitly. The main domains used to assess the certainty of the evidence are risk of bias, inconsistency, indirectness of evidence, imprecision, and publication bias. The factors that can increase the certainty of the evidence are dose-response gradient, large magnitude of an effect, and effect of plausible residual confounding. Finally, the Summary of Findings tables summarize the process in a simplified way and with controlled language. This narrative reviews purpose is to address the GRADE approachs theoretical and practical underlying concepts in a simplified way and with practical examples.

La certeza de la evidencia para las intervenciones es la seguridad o confianza de que el verdadero efecto se encuentra dentro de un rango particular o en relación con un umbral. En la nueva pirámide de la evidencia, las revisiones sistemáticas representan la lupa a través de la cual se evalúa dicha certeza. La metodología GRADE (Grading of Recommendations Assessment, Development and Evaluation) surge como respuesta a la existencia de múltiples sistemas de clasificación de la evidencia y ofrece un proceso transparente y estructurado para desarrollar y presentar resúmenes de evidencia considerando la certeza de esta y, en un segundo paso, la fuerza de las recomendaciones que informan. El proceso GRADE comienza con una pregunta explícita, que incluye las especificaciones de todos los desenlaces importantes y críticos. Los principales dominios que se utilizan para valorar la certeza de la evidencia son: 1. El riesgo de sesgo, 2. La inconsistencia, 3. Evidencia indirecta, 4. Imprecisión, y 5. El sesgo de publicación. Los factores que pueden aumentar la certeza de la evidencia son: 1. Gradiente dosis respuesta, 2. Gran magnitud del efecto, 3. Efecto de los potenciales factores de confusión residual. Finalmente, las tablas de resumen de hallazgos (Summary of Findings) sintetizan el proceso de manera simplificada y con un lenguaje controlado. El objetivo general de esta revisión narrativa es abordar los principales conceptos básicos teóricos y prácticos de la metodología GRADE de manera simplificada y con ejemplos prácticos.

The GRADE approach, Part 2: Evidence to decision frameworksoutlining decision-making in health. / Metodología GRADE, parte 2: de la evidencia a la decisión—esquematizando la toma de decisiones en salud.

The GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology provides a framework for assessing the certainty of the evidence and making recommendations. The Evidence to Decision Framework (EtD) is a transparent and structured system for formulating health recommendations. Once the problem is identified and the certainty of the evidence is assessed, EtD provides several criteria for formulating a recommendation. These criteria include the trade-off between benefits and harms, patients values and preferences, acceptability, feasibility, resource use, and impact on equity. The resulting recommendations may differ in strength (strong or weak) and direction (for or against). The process is transparent, allowing other users to adjust the framework of recommendations by modifying the criteria to fit the desired context through an adaptation-adoption process. Given the extensive information available on EtD and the GRADE methodology in general, this narrative review seeks to explain the main concepts involved in decision-making in health by using simplified and friendly descriptions, accompanied by practical examples, thus facilitating its understanding by inexperienced readers.

La metodología GRADE (Grading of Recommendations Assessment, Development and Evaluation) provee un método para valorar la certeza de la evidencia y para la formulación de recomendaciones que ayuden en la toma de decisiones en salud. Una vez identificado el problema y valorada la certeza de la evidencia, los marcos de la evidencia a la decisión (Evidence to decision frameworks o EtD) utilizan un sistema transparente y estructurado para formular recomendaciones, en que se consideran criterios como el balance entre beneficios y daños, valores y preferencias de los pacientes, aceptabilidad, factibilidad, equidad y uso de recursos para establecer una recomendación en salud. Esta podrá tener distinta fuerza (fuertes o débiles) y dirección (a favor o en contra). La transparencia de este proceso permite que otros usuarios puedan adaptar un marco de recomendaciones según el contexto deseado, mediante un proceso de adaptación-adopción. Ante la extensa información disponible sobre marcos de la evidencia a la decisión y la metodología GRADE en general, esta revisión narrativa busca entregar una explicación acerca de los principales conceptos involucrados en la toma de decisiones en salud, a través de descripciones simplificadas, amigables y con ejemplos prácticos, con el fin de facilitar su entendimiento por lectores inexpertos.

Introduction to network meta-analysis for evidence synthesis. / Introducción a los metanálisis en red para la síntesis de evidencia.

This article belongs to a collaborative methodological series of narrative reviews about biostatistics and clinical epidemiology. The goal is to present basics concepts concerning the systematics reviews of multiple treatments comparisons with network meta-analysis. For clinical ques-tions with several therapeutic alternatives to be compared, the central question is how to classify or rank their effectiveness (benefit and harm) to choose the best option. The network meta-analysis aims to answer questions related to the effectiveness and safety of comparing multiple treatments by the simultaneous analysis of results raised from direct and indirect comparisons. The network geometry is the general graphical representation of the network meta-analysis and allows to understand and assess the strength of comparisons. The network meta-analysis should check several assumptions to be valid, especially the transitivity assumption, which allows assuming that there are no systematic differences among the included comparisons, except their compared interventions. Thus, it is possible to know the relative therapeutic effectiveness of each pair of interventions included in the network meta-analysis and their ranking in terms of categorization. It has been proposed to use a modified Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) approach considering the distinctive features of network meta-analysis to assess the certainty of the evidence for each comparison and the ranking of interventions.

Este artículo forma parte de una serie metodológica colaborativa de revisiones narrativas sobre bioestadística y epidemiología clínica. El objetivo de este trabajo es presentar conceptos básicos respecto de las revisiones sistemáticas de intervenciones múltiples con metanálisis en red. Para las preguntas clínicas en las que hay muchas alternativas terapéuticas que compiten (o se comparan) entre sí. La pregunta central es cómo clasificar u ordenar jerárquicamente su efecto (beneficio y/o daño) para escoger la mejor opción. Los metanálisis en red buscan responder a preguntas relacionadas con la efectividad o seguridad de múltiples tratamientos comparados entre sí, mediante el análisis simultáneo de resultados surgidos tanto de comparaciones directas como de comparaciones indirectas. La geometría de la red (network geometry) es la representación gráfica general de los metanálisis en red y permite comprender e incluso evaluar la fuerza de las comparaciones. Para que un metanálisis de comparaciones múltiples sea válido debe cumplir una serie de supuestos, destacándose el supuesto de transitividad que permite asumir que no hay diferencias sistemáticas entre las comparaciones disponibles, a excepción de las intervenciones comparadas. Así, es posible conocer la efectividad terapéutica relativa entre cualquier par de intervenciones del metanálisis en red y el orden de las intervenciones en términos de su categorización. Se ha propuesto utilizar el modelo Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) modificado en cuanto a las particularidades de los metanálisis en red para valorar la certeza de la evidencia, tanto para cada comparación como para la jerarquización de intervenciones.