Pharmacological treatment for central sleep apnoea in adults.

BACKGROUND: The term central sleep apnoea (CSA) encompasses diverse clinical situations where a dysfunctional drive to breathe leads to recurrent respiratory events, namely apnoea (complete absence of ventilation) and hypopnoea sleep (insufficient ventilation) during sleep. Studies have demonstrated that CSA responds to some extent to pharmacological agents with distinct mechanisms, such as sleep stabilisation and respiratory stimulation. Some therapies for CSA are associated with improved quality of life, although the evidence on this association is uncertain. Moreover, treatment of CSA with non-invasive positive pressure ventilation is not always effective or safe and may result in a residual apnoea-hypopnoea index. OBJECTIVES: To evaluate the benefits and harms of pharmacological treatment compared with active or inactive controls for central sleep apnoea in adults. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 30 August 2022. SELECTION CRITERIA: We included parallel and cross-over randomised controlled trials (RCTs) that evaluated any type of pharmacological agent compared with active controls (e.g. other medications) or passive controls (e.g. placebo, no treatment or usual care) in adults with CSA as defined by the International Classification of Sleep Disorders 3rd Edition. We did not exclude studies based on the duration of intervention or follow-up. We excluded studies focusing on CSA due to periodic breathing at high altitudes. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were central apnoea-hypopnoea index (cAHI), cardiovascular mortality and serious adverse events. Our secondary outcomes were quality of sleep, quality of life, daytime sleepiness, AHI, all-cause mortality, time to life-saving cardiovascular intervention, and non-serious adverse events. We used GRADE to assess certainty of evidence for each outcome. MAIN RESULTS: We included four cross-over RCTs and one parallel RCT, involving a total of 68 participants. Mean age ranged from 66 to 71.3 years and most participants were men. Four trials recruited people with CSA associated with heart failure, and one study included people with primary CSA. Types of pharmacological agents were acetazolamide (carbonic anhydrase inhibitor), buspirone (anxiolytic), theophylline (methylxanthine derivative) and triazolam (hypnotic), which were given for between three days and one week. Only the study on buspirone reported a formal evaluation of adverse events. These events were rare and mild. No studies reported serious adverse events, quality of sleep, quality of life, all-cause mortality, or time to life-saving cardiovascular intervention. Carbonic anhydrase inhibitors versus inactive control Results were from two studies of acetazolamide versus placebo (n = 12) and acetazolamide versus no acetazolamide (n = 18) for CSA associated with heart failure. One study reported short-term outcomes and the other reported intermediate-term outcomes. We are uncertain whether carbonic anhydrase inhibitors compared to inactive control reduce cAHI in the short term (mean difference (MD) -26.00 events per hour, 95% CI -43.84 to -8.16; 1 study, 12 participants; very low certainty). Similarly, we are uncertain whether carbonic anhydrase inhibitors compared to inactive control reduce AHI in the short term (MD -23.00 events per hour, 95% CI -37.70 to 8.30; 1 study, 12 participants; very low certainty) or in the intermediate term (MD -6.98 events per hour, 95% CI -10.66 to -3.30; 1 study, 18 participants; very low certainty). The effect of carbonic anhydrase inhibitors on cardiovascular mortality in the intermediate term was also uncertain (odds ratio (OR) 0.21, 95% CI 0.02 to 2.48; 1 study, 18 participants; very low certainty). Anxiolytics versus inactive control Results were based on one study of buspirone versus placebo for CSA associated with heart failure (n = 16). The median difference between groups for cAHI was -5.00 events per hour (IQR -8.00 to -0.50), the median difference for AHI was -6.00 events per hour (IQR -8.80 to -1.80), and the median difference on the Epworth Sleepiness Scale for daytime sleepiness was 0 points (IQR -1.0 to 0.00). Methylxanthine derivatives versus inactive control Results were based on one study of theophylline versus placebo for CSA associated with heart failure (n = 15). We are uncertain whether methylxanthine derivatives compared to inactive control reduce cAHI (MD -20.00 events per hour, 95% CI -32.15 to -7.85; 15 participants; very low certainty) or AHI (MD -19.00 events per hour, 95% CI -30.27 to -7.73; 15 participants; very low certainty). Hypnotics versus inactive control Results were based on one trial of triazolam versus placebo for primary CSA (n = 5). Due to very serious methodological limitations and insufficient reporting of outcome measures, we were unable to draw any conclusions regarding the effects of this intervention. AUTHORS' CONCLUSIONS: There is insufficient evidence to support the use of pharmacological therapy in the treatment of CSA. Although small studies have reported positive effects of certain agents for CSA associated with heart failure in reducing the number of respiratory events during sleep, we were unable to assess whether this reduction may impact the quality of life of people with CSA, owing to scarce reporting of important clinical outcomes such as sleep quality or subjective impression of daytime sleepiness. Furthermore, the trials mostly had short-term follow-up. There is a need for high-quality trials that evaluate longer-term effects of pharmacological interventions.

Adapting shift work schedules for sleep quality, sleep duration, and sleepiness in shift workers.

BACKGROUND: Shift work is associated with insufficient sleep, which can compromise worker alertness with ultimate effects on occupational health and safety. Adapting shift work schedules may reduce adverse occupational outcomes. OBJECTIVES: To assess the effects of shift schedule adaptation on sleep quality, sleep duration, and sleepiness among shift workers. SEARCH METHODS: We searched CENTRAL, PubMed, Embase, and eight other databases on 13 December 2020, and again on 20 April 2022, applying no language restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and non-RCTs, including controlled before-after (CBA) trials, interrupted time series, and cross-over trials. Eligible trials evaluated any of the following shift schedule components. • Permanency of shifts • Regularity of shift changes • Direction of shift rotation • Speed of rotation • Shift duration • Timing of start of shifts • Distribution of shift schedule • Time off between shifts • Split shifts • Protected sleep • Worker participation We included studies that assessed sleep quality off-shift, sleep duration off-shift, or sleepiness during shifts. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the titles and abstracts of the records recovered by the search, read through the full-text articles of potentially eligible studies, and extracted data. We assessed the risk of bias of included studies using the Cochrane risk of bias tool, with specific additional domains for non-randomised and cluster-randomised studies. For all stages, we resolved any disagreements by consulting a third review author. We presented the results by study design and combined clinically homogeneous studies in meta-analyses using random-effects models. We assessed the certainty of the evidence with GRADE. MAIN RESULTS: We included 11 studies with a total of 2125 participants. One study was conducted in a laboratory setting and was not considered for drawing conclusions on intervention effects. The included studies investigated different and often multiple changes to shift schedule, and were heterogeneous with respect to outcome measurement. Forward versus backward rotation Three CBA trials (561 participants) investigated the effects of forward rotation versus backward rotation. Only one CBA trial provided sufficient data for the quantitative analysis; it provided very low-certainty evidence that forward rotation compared with backward rotation did not affect sleep quality measured with the Basic Nordic Sleep Questionnaire (BNSQ; mean difference (MD) -0.20 points, 95% confidence interval (CI) -2.28 to 1.89; 62 participants) or sleep duration off-shift (MD -0.21 hours, 95% CI -3.29 to 2.88; 62 participants). However, there was also very low-certainty evidence that forward rotation reduced sleepiness during shifts measured with the BNSQ (MD -1.24 points, 95% CI -2.24 to -0.24; 62 participants). Faster versus slower rotation Two CBA trials and one non-randomised cross-over trial (341 participants) evaluated faster versus slower shift rotation. We were able to meta-analyse data from two studies. There was low-certainty evidence of no difference in sleep quality off-shift (standardised mean difference (SMD) -0.01, 95% CI -0.26 to 0.23) and very low-certainty evidence that faster shift rotation reduced sleep duration off-shift (SMD -0.26, 95% CI -0.51 to -0.01; 2 studies, 282 participants). The SMD for sleep duration translated to an MD of 0.38 hours' less sleep per day (95% CI -0.74 to -0.01). One study provided very low-certainty evidence that faster rotations decreased sleepiness during shifts measured with the BNSQ (MD -1.24 points, 95% CI -2.24 to -0.24; 62 participants). Limited shift duration (16 hours) versus unlimited shift duration Two RCTs (760 participants) evaluated 80-hour workweeks with maximum daily shift duration of 16 hours versus workweeks without any daily shift duration limits. There was low-certainty evidence that the 16-hour limit increased sleep duration off-shift (SMD 0.50, 95% CI 0.21 to 0.78; which translated to an MD of 0.73 hours' more sleep per day, 95% CI 0.30 to 1.13; 2 RCTs, 760 participants) and moderate-certainty evidence that the 16-hour limit reduced sleepiness during shifts, measured with the Karolinska Sleepiness Scale (SMD -0.29, 95% CI -0.44 to -0.14; which translated to an MD of 0.37 fewer points, 95% CI -0.55 to -0.17; 2 RCTs, 716 participants). Shorter versus longer shifts One RCT, one CBA trial, and one non-randomised cross-over trial (692 participants) evaluated shorter shift duration (eight to 10 hours) versus longer shift duration (two to three hours longer). There was very low-certainty evidence of no difference in sleep quality (SMD -0.23, 95% CI -0.61 to 0.15; which translated to an MD of 0.13 points lower on a scale of 1 to 5; 2 studies, 111 participants) or sleep duration off-shift (SMD 0.18, 95% CI -0.17 to 0.54; which translated to an MD of 0.26 hours' less sleep per day; 2 studies, 121 participants). The RCT and the non-randomised cross-over study found that shorter shifts reduced sleepiness during shifts, while the CBA study found no effect on sleepiness. More compressed versus more spread out shift schedules One RCT and one CBA trial (346 participants) evaluated more compressed versus more spread out shift schedules. The CBA trial provided very low-certainty evidence of no difference between the groups in sleep quality off-shift (MD 0.31 points, 95% CI -0.53 to 1.15) and sleep duration off-shift (MD 0.52 hours, 95% CI -0.52 to 1.56). AUTHORS' CONCLUSIONS: Forward and faster rotation may reduce sleepiness during shifts, and may make no difference to sleep quality, but the evidence is very uncertain. Very low-certainty evidence indicated that sleep duration off-shift decreases with faster rotation. Low-certainty evidence indicated that on-duty workweeks with shift duration limited to 16 hours increases sleep duration, with moderate-certainty evidence for minimal reductions in sleepiness. Changes in shift duration and compression of workweeks had no effect on sleep or sleepiness, but the evidence was of very low-certainty. No evidence is available for other shift schedule changes. There is a need for more high-quality studies (preferably RCTs) for all shift schedule interventions to draw conclusions on the effects of shift schedule adaptations on sleep and sleepiness in shift workers.

Non-invasive positive pressure ventilation for central sleep apnoea in adults.

BACKGROUND: Central sleep apnoea (CSA) is characterised by abnormal patterns of ventilation during sleep due to a dysfunctional drive to breathe. Consequently, people with CSA may present poor sleep quality, sleep fragmentation, inattention, fatigue, daytime sleepiness, and reduced quality of life. OBJECTIVES: To assess the effectiveness and safety of non-invasive positive pressure ventilation (NIPV) for the treatment of adults with CSA. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and Scopus on 6 September 2021. We applied no restrictions on language of publication. We also searched clinical trials registries for ongoing and unpublished studies, and scanned the reference lists of included studies to identify additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) reported in full text, those published as abstract only, and unpublished data. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion, extracted data, and assessed risk of bias of the included studies using the Cochrane risk of bias tool version 1.0, and the certainty of the evidence using the GRADE approach. In the case of disagreement, a third review author was consulted. MAIN RESULTS: We included 15 RCTs with a total of 1936 participants, ranging from 10 to 1325 participants. All studies had important methodological limitations. We assessed most studies (11 studies) as at high risk of bias for at least one domain, and all studies as at unclear risk of bias for at least two domains. The trials included participants aged > 18 years old, of which 70% to 100% were men, who were followed from one week to 60 months. The included studies assessed the effects of different modes of NIPV and CSA. Most participants had CSA associated with chronic heart failure. Because CSA encompasses a variety of causes and underlying clinical conditions, data were carefully analysed, and different conditions and populations were not pooled. The findings for the primary outcomes for the seven evaluated comparisons are presented below.  Continuous positive airway pressure (CPAP) plus best supportive care versus best supportive care in CSA associated with chronic heart failure In the short term, CPAP plus best supportive care may reduce central apnoea hypopnoea index (AHI) (mean difference (MD) -14.60, 95% confidence interval (CI) -20.11 to -9.09; 1 study; 205 participants). However, CPAP plus best supportive care may result in little to no difference in cardiovascular mortality compared to best supportive care alone. The evidence for the effect of CPAP plus best supportive care on all-cause mortality is very uncertain. No adverse effects were observed with CPAP, and the results for adverse events in the best supportive care group were not reported. Adaptive servo ventilation (ASV) versus CPAP in CSA associated with chronic heart failure The evidence is very uncertain about the effect of ASV versus CPAP on quality of life evaluated in both the short and medium term. Data on adverse events were not reported, and it is not clear whether data were sought but not found. ASV versus bilevel ventilation in CSA associated with chronic heart failure In the short term, ASV may result in little to no difference in central AHI. No adverse events were detected with ASV, and the results for adverse events in the bilevel ventilation group were not reported. ASV plus best supportive care versus best supportive care in CSA associated with chronic heart failure In the medium term, ASV plus best supportive care may reduce AHI compared to best supportive care alone (MD -20.30, 95% CI -28.75 to -11.85; 1 study; 30 participants). In the long term, ASV plus best supportive care likely increases cardiovascular mortality compared to best supportive care (risk ratio (RR) 1.25, 95% CI 1.04, 1.49; 1 study; 1325 participants). The evidence suggests that ASV plus best supportive care may result in little to no difference in quality of life in the short, medium, and long term, and in all-cause mortality in the medium and long term. Data on adverse events were evaluated but not reported. ASV plus best supportive care versus best supportive care in CSA with acute heart failure with preserved ejection fraction Only adverse events were reported for this comparison, and no adverse events were recorded in either group. ASV versus CPAP maintenance in CPAP-induced CSA In the short term, ASV may slightly reduce central AHI (MD -4.10, 95% CI -6.67 to -1.53; 1 study; 60 participants), but may result in little to no difference in quality of life. Data on adverse events were not reported, and it is not clear whether data were sought but not found. ASV versus bilevel ventilation in CPAP-induced CSA In the short term, ASV may slightly reduce central AHI (MD -8.70, 95% CI -11.42 to -5.98; 1 study; 30 participants) compared to bilevel ventilation. Data on adverse events were not reported, and it is not clear whether data were sought but not found. AUTHORS' CONCLUSIONS: CPAP plus best supportive care may reduce central AHI in people with CSA associated with chronic heart failure compared to best supportive care alone. Although ASV plus best supportive care may reduce AHI in people with CSA associated with chronic heart failure, it likely increases cardiovascular mortality in these individuals. In people with CPAP-induced CSA, ASV may slightly reduce central AHI compared to bilevel ventilation and to CPAP. In the absence of data showing a favourable impact on meaningful patient-centred outcomes and defining clinically important differences in outcomes in CSA patients, these findings need to be interpreted with caution. Considering the level of certainty of the available evidence and the heterogeneity of participants with CSA, we could draw no definitive conclusions, and further high-quality trials focusing on patient-centred outcomes, such as quality of life, quality of sleep, and longer-term survival, are needed to determine whether one mode of NIPV is better than another or than best supportive care for any particular CSA patient group.

Economic evaluation of CPAP therapy for obstructive sleep apnea: a scoping review and evidence map.

PURPOSE: To synthesize findings of economic evaluations investigating cost-effectiveness of continuous positive airway pressure (CPAP) for obstructive sleep apnea (OSA) and of strategies of organization of care related to CPAP therapy. METHODS: Scoping review with searches conducted in MEDLINE, CRD, LILACS, and Embase in August 2020. Eligible studies were economic evaluations comparing CPAP to other alternative or assessing strategies of care for CPAP therapy. Results were presented narratively, and incremental cost-effectiveness ratios (ICER) were presented in evidence maps. RESULTS: Of 34 studies, 3 concluded that CPAP is less costly and more effective when compared to usual care. Most studies indicated that CPAP is associated with better health outcomes, but at higher prices. ICER ranged from USD 316 to 98,793 per quality-adjusted life years (QALY) gained (median 16,499; IQR 8267 to 33,119). One study concluded that CPAP is more costly and less effective, when treatment is applied to all patients, regardless of disease severity. Variability of ICER was mainly due to definition of population and applied time horizons. When CPAP was compared to mandibular advancement device, ICER ranged from USD 21,153 to 361,028 (median 89,671; IQR 26,829 to 295,983), which represents the investment in CPAP therapy required to obtain one extra QALY. Three studies assessed the effects of organizing CPAP therapy in primary care, which was cost-effective or cost-saving. CONCLUSIONS: Compared to usual care, CPAP is cost-effective after the second year of treatment, when indicated for moderate-to-severe OSA. CPAP therapy may be even more cost-effective by using different strategies of organization of care. These findings may inform decision making related to CPAP reimbursement in health systems. CLINICAL TRIAL REGISTRATION NUMBER: Not applicable.

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.

Telehealth to support referral management in a universal health system: a before-and-after study.

BACKGROUND: Management of patient flow within a healthcare network, allowing equitable and qualified access to healthcare, is a major challenge for universal health systems. Implementation of telehealth strategies to support referral management has been shown to increase primary care resolution and to promote coordination of care. The objective of this study was to assess the impact of telehealth strategies on waiting lists and waiting times for specialized care in Brazil. METHODS: Before-and-after study with measures obtained between January 2019 and February 2020. Baseline measurements of waiting lists were obtained immediately before the implementation of a remotely operated referral management system. Post-interventional measurements were obtained monthly, up to six months after the beginning of operation. Data was extracted from the database of the project. General linear models were applied to assess interaction of locality and time over number of cases on waiting lists and waiting times. RESULTS: At baseline, the median number of cases on waiting lists ranged from 2961 to 12,305 cases. Reductions of the number of cases on waiting lists after six months of operation were observed in all localities. The magnitude of the reduction ranged from 54.67 to 88.97 %. Interaction of time measurements was statistically significant from the second month onward. Median waiting times ranged from 159 to 241 days at baseline. After six months, there was a decrease of 100 and 114 waiting days in two localities, respectively, with reduction of waiting times only for high-risk cases in the third locality. CONCLUSIONS: Adoption of telehealth strategies resulted in the reduction of number of cases on waiting lists. Results were consistent across localities, suggesting that telehealth interventions are viable in diverse settings.

Palliative care interventions for people with multiple sclerosis.

BACKGROUND: People with multiple sclerosis (MS) have complex symptoms and different types of needs. These demands include how to manage the burden of physical disability as well as how to organise daily life, restructure social roles in the family and at work, preserve personal identity and community roles, keep self-sufficiency in personal care, and how to be part of an integrated care network. Palliative care teams are trained to keep open full and competent lines of communication about symptoms and disease progression, advanced care planning, and end-of-life issues and wishes. Teams create a treatment plan for the total management of symptoms, supporting people and families on decision-making. Despite advances in research and the existence of many interventions to reduce disease activity or to slow the progression of MS, this condition remains a life-limiting disease with symptoms that impact negatively the lives of people with it and their families. OBJECTIVES: To assess the effects (benefits and harms) of palliative care interventions compared to usual care for people with any form of multiple sclerosis: relapsing-remitting MS (RRMS), secondary-progressive MS (SPMS), primary-progressive MS (PPMS), and progressive-relapsing MS (PRMS) We also aimed to compare the effects of different palliative care interventions. SEARCH METHODS: On 31 October 2018, we conducted a literature search in the specialised register of the Cochrane MS and Rare Diseases of the Central Nervous System Review Group, which contains trials from CENTRAL, MEDLINE, Embase, CINAHL, LILACS, Clinical trials.gov and the World Health Organization International Clinical Trials Registry Platform. We also searched PsycINFO, PEDro and Opengrey. We also handsearched relevant journals and screened the reference lists of published reviews. We contacted researchers in palliative care and multiple sclerosis. SELECTION CRITERIA: Randomised controlled trials (RCTs) and cluster randomised trials were eligible for inclusion, as well as the first phase of cross-over trials. We included studies that compared palliative care interventions versus usual care. We also included studies that compared palliative care interventions versus another type of palliative interventions. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. We summarised key results and certainty of evidence in a 'Summary of Finding' table that reported outcomes at six or more months of post-intervention. MAIN RESULTS: Three studies (146 participants) met our selection criteria. Two studies compared multidisciplinary, fast-track palliative care versus multidisciplinary standard care while on a waiting-list control, and one study compared a multidisciplinary palliative approach versus multidisciplinary standard care at different time points (12, 16, and 24 weeks). Two were RCTs with parallel design (total 94 participants) and one was a cross-over design (52 participants). The three studies assessed palliative care as a home-based intervention. One of the three studies included participants with 'neurodegenerative diseases', with MS people being a subset of the randomised population. We assessed the risk of bias of included studies using Cochrane's 'Risk of Bias' tool.We found no evidence of differences between intervention and control groups in long-time follow-up (> six months post-intervention) for the following outcomes: mean change in health-related quality of life (SEIQoL - higher scores mean better quality of life; MD 4.80, 95% CI -12.32 to 21.92; participants = 62; studies = 1; very low-certainty evidence), serious adverse events (RR 0.97, 95% CI 0.44 to 2.12; participants = 76; studies = 1, 22 events, low-certainty evidence) and hospital admission (RR 0.78, 95% CI 0.24 to 2.52; participants = 76; studies = 1, 10 events, low-certainty evidence).The three included studies did not assess the following outcomes at long term follow-up (> six months post intervention): fatigue, anxiety, depression, disability, cognitive function, relapse-free survival, and sustained progression-free survival.We did not find any trial that compared different types of palliative care with each other. AUTHORS' CONCLUSIONS: Based on the findings of the RCTs included in this review, we are uncertain whether palliative care interventions are beneficial for people with MS. There is low- or very low-certainty evidence regarding the difference between palliative care interventions versus usual care for long-term health-related quality of life, adverse events, and hospital admission in patients with MS. For intermediate-term follow-up, we are also uncertain about the effects of palliative care for the outcomes: health-related quality of life (measured by different assessments: SEIQoL or MSIS), disability, anxiety, and depression.

Workplace lighting for improving alertness and mood in daytime workers.

BACKGROUND: Exposure to light plays a crucial role in biological processes, influencing mood and alertness. Daytime workers may be exposed to insufficient or inappropriate light during daytime, leading to mood disturbances and decreases in levels of alertness. OBJECTIVES: To assess the effectiveness and safety of lighting interventions to improve alertness and mood in daytime workers. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, seven other databases; ClinicalTrials.gov and the World Health Organization trials portal up to January 2018. SELECTION CRITERIA: We included randomised controlled trials (RCTs), and non-randomised controlled before-after trials (CBAs) that employed a cross-over or parallel-group design, focusing on any type of lighting interventions applied for daytime workers. DATA COLLECTION AND ANALYSIS: Two review authors independently screened references in two stages, extracted outcome data and assessed risk of bias. We used standardised mean differences (SMDs) and 95% confidence intervals (CI) to pool data from different questionnaires and scales assessing the same outcome across different studies. We combined clinically homogeneous studies in a meta-analysis. We used the GRADE system to rate quality of evidence. MAIN RESULTS: The search yielded 2844 references. After screening titles and abstracts, we considered 34 full text articles for inclusion. We scrutinised reports against the eligibility criteria, resulting in the inclusion of five studies (three RCTs and two CBAs) with 282 participants altogether. These studies evaluated four types of comparisons: cool-white light, technically known as high correlated colour temperature (CCT) light versus standard illumination; different proportions of indirect and direct light; individually applied blue-enriched light versus no treatment; and individually applied morning bright light versus afternoon bright light for subsyndromal seasonal affective disorder.We found no studies comparing one level of illuminance versus another.We found two CBA studies (163 participants) comparing high CCT light with standard illumination. By pooling their results via meta-analysis we found that high CCT light may improve alertness (SMD -0.69, 95% CI -1.28 to -0.10; Columbia Jet Lag Scale and the Karolinska Sleepiness Scale) when compared to standard illumination. In one of the two CBA studies with 94 participants there was no difference in positive mood (mean difference (MD) 2.08, 95% CI -0.1 to 4.26) or negative mood (MD -0.45, 95% CI -1.84 to 0.94) assessed using the Positive and Negative Affect Schedule (PANAS) scale. High CCT light may have fewer adverse events than standard lighting (one CBA; 94 participants). Both studies were sponsored by the industry. We graded the quality of evidence as very low.We found no studies comparing light of a particular illuminance and light spectrum or CCT versus another combination of illuminance and light spectrum or CCT.We found no studies comparing daylight versus artificial light.We found one RCT (64 participants) comparing the effects of different proportions of direct and indirect light: 100% direct lighting, 70% direct lighting plus 30% indirect lighting, 30% direct lighting plus 70% indirect lighting and 100% indirect lighting. There was no substantial difference in mood, as assessed by the Beck Depression Inventory, or in adverse events, such as ocular, reading or concentration problems, in the short or medium term. We graded the quality of evidence as low.We found two RCTs comparing individually administered light versus no treatment. According to one RCT with 25 participants, blue-enriched light individually applied for 30 minutes a day may enhance alertness (MD -3.30, 95% CI -6.28 to -0.32; Epworth Sleepiness Scale) and may improve mood (MD -4.8, 95% CI -9.46 to -0.14; Beck Depression Inventory). We graded the quality of evidence as very low. One RCT with 30 participants compared individually applied morning bright light versus afternoon bright light for subsyndromal seasonal affective disorder. There was no substantial difference in alertness levels (MD 7.00, 95% CI -10.18 to 24.18), seasonal affective disorder symptoms (RR 1.60, 95% CI 0.81, 3.20; number of participants presenting with a decrease of at least 50% in SIGH-SAD scores) or frequency of adverse events (RR 0.53, 95% CI 0.26 to 1.07). Among all participants, 57% had a reduction of at least 50% in their SIGH-SAD score. We graded the quality of evidence as low.Publication bias could not be assessed for any of these comparisons. AUTHORS' CONCLUSIONS: There is very low-quality evidence based on two CBA studies that high CCT light may improve alertness, but not mood, in daytime workers. There is very low-quality evidence based on one CBA study that high CCT light may also cause less irritability, eye discomfort and headache than standard illumination. There is low-quality evidence based on one RCT that different proportions of direct and indirect light in the workplace do not affect alertness or mood. There is very low-quality evidence based on one RCT that individually applied blue-enriched light improves both alertness and mood. There is low-quality evidence based on one RCT that individually administered bright light during the afternoon is as effective as morning exposure for improving alertness and mood in subsyndromal seasonal affective disorder.

Clinical interventions for Takayasu arteritis: A systematic review.

INTRODUCTION: Takayasu arteritis (TA) is a rare systemic vasculitis that affects large vessels often resistant to treatment and associated with high morbidity and mortality. Treatment is defied by the relapsing nature of the disease and frequent adverse effects of corticosteroids and immunosuppressors, rendering failure of treatment in a significant portion of patients. Considering the low quantity and quality of published studies focusing on treatment of TA, synthesis and critical assessment of the available evidence is fundamental to establish recommendations for clinical practice. OBJECTIVE: To evaluate the effectiveness and safety of clinical interventions for TA. METHODS: Systematic review conducted in accordance to recommendations stated in the Cochrane Handbook, with inclusion of all comparative studies focusing on any type of clinical intervention for TA. RESULTS: Five comparative studies were included (one randomised clinical trial, two non-randomised clinical trials, and two historical cohorts) totalling 342 patients, aiming at the assessment of effectiveness of corticosteroids, immunosuppressors, biologics and other types of pharmacological treatment for distinct clinical presentations of TA. The quality of studies, assessed by the use of instruments developed specifically for each study design, was considered low. Data scarcity and clinical heterogeneity prevented quantitative synthesis (meta-analysis). CONCLUSION: Despite an extensive literature search, few comparative studies with small sample sizes were retrieved. The quality of these studies was considered low, preventing recommendations on effectiveness and safety of the studied interventions for clinical practice. Until new comparative studies with more robust sample sizes are conducted, treatment of TA should be guided individually taking into account the severity of disease and the availability of treatment options.

Cost-Utility Analysis of Continuous Positive Airway Pressure Therapy Compared With Usual Care for Obstructive Sleep Apnea in the Public Health System in Brazil.

OBJECTIVES: This study aimed to conduct a cost-utility analysis of continuous positive airway pressure (CPAP) therapy compared with usual care as treatment of moderate to severe cases of obstructive sleep apnea (OSA) in Brazil, where decentralized policies of CPAP provision are in place. METHODS: Markov cohort model comparing CPAP therapy with usual care, that is, no specific treatment for OSA, for moderate to severe cases was used. The payer perspective from the Unified Health System, Brazil, was adopted. Effectiveness parameters and costs related to health states were informed by literature review. Resource use related to CPAP therapy was defined by specialists and costs informed by recent purchase and leasing contracts. Incremental cost-effectiveness ratios were generated for purchase and leasing contracts to reflect current practices. A conservative willingness-to-pay threshold was set at 1 gross domestic product per capita per quality-adjusted life-year (QALY) (Brazilian reais [BRL] 40 712/QALY). Uncertainties were explored in deterministic and probabilistic sensitivity analyses. RESULTS: Incremental cost-effectiveness ratio for the purchase modality was 8303 BRL/QALY and for leasing 45 192 BRL/QALY. Considering the adopted willingness-to-pay threshold, provision of CPAP by the purchase modality was considered cost-effective but not the leasing modality. The parameter related to the greatest uncertainty was the reduction in the risk of having a stroke attributable to CPAP. Probabilistic analysis confirmed the robustness of results. CONCLUSIONS: CPAP therapy is a cost-effective alternative compared with usual care for moderate to severe OSA for the purchase modality. These results should help underpinning the decision making related to a uniform policy of CPAP provision across the country.

Legal action for access to resources inefficiently made available in health care systems in Brazil: a case study on obstructive sleep apnea.

OBJECTIVE: Obstructive sleep apnea (OSA) is a highly prevalent chronic disease, associated with morbidity and mortality. Although effective treatment for OSA is commercially available, their provision is not guaranteed by lines of care throughout Brazil, making legal action necessary. This study aimed at presenting data related to the volume of legal proceedings regarding the access to diagnosis and treatment of OSA in Brazil. METHODS: This was a descriptive study of national scope, evaluating the period between January of 2016 and December of 2020. The number of lawsuits was analyzed according to the object of the demand (diagnosis or treatment). Projections of total expenses were carried out according to the number of lawsuits. RESULTS: We identified 1,462 legal proceedings (17.6% and 82.4% related to diagnosis and treatment, respectively). The projection of expenditure for OSA diagnosis in the public and private spheres were R$575,227 and R$188,002, respectively. The projection of expenditure for OSA treatment in the public and private spheres were R$2,656,696 and R$253,050, respectively. There was a reduction in the number of lawsuits between 2017 and 2019. CONCLUSIONS: Legal action as a strategy for accessing diagnostic and therapeutic resources related to OSA is a recurrent practice, resulting in inefficiency and inequity. The reduction in the number of lawsuits between 2017 and 2019 might be explained by the expansion of local health care policies or by barriers in the journey of patients with OSA, such as difficulties in being referred to specialized health care and low availability of diagnostic resources.

Telehealth Strategies to Support Referral Management to Secondary Care in Brazil: A Cost-Effectiveness Analysis.

OBJECTIVES: This study aimed to assess the cost-effectiveness of a remotely operated referral management system (RORMS) compared with a conventional referral management system (CRMS) in Brazil. METHODS: This is a model-based cost-effectiveness analysis under the perspective of the Unified Healthcare System (Sistema Único de Saúde [SUS]) in Brazil. A Markov microsimulation model was developed to compare costs and referral outcomes of the RORMS and the CRMS. Model consisted of 4 states representative of sequential stepwise assessments of referral suitability, 3 states representative of referral outcomes, and 1 exit model state. Target population represented cases being referred from primary healthcare units to specialized care in SUS. Model inputs related to costs and effectiveness in the RORMS arm were obtained from the data set of a RORMS between July and December 2019. Model inputs for the CRMS model arm were obtained from administrative data sets of 2 Brazilian localities for the year 2019. Relative effect size of RORMS in comparison with CRMS in SUS was obtained from published studies. Effectiveness outcome was unnecessary referrals averted. The incremental cost-effectiveness ratio was calculated for the base case. Probabilistic sensitivity analysis was conducted. RESULTS: In the base-case analyses, RORMS dominated CRMS, with expected cost-savings from $50.42 to $80.62 per unnecessary referral averted. RORMS was the dominant strategy in 83.7% of 100 000 simulations in the probabilistic sensitivity analysis. In 16.2% of simulations, incremental cost-effectiveness ratio was between $0 and $222 per unnecessary referral averted. CONCLUSIONS: Model-based simulations indicate that the RORMS is likely to be cost saving in comparison with the CRMS.

COVID-19 pandemic is associated with increased sleep disturbances and mental health symptoms but not help-seeking: a cross-sectional nation-wide study.

Objective: This study aimed firstly to describe sleep-related and mental health symptoms before and during the COVID-19 pandemic in a national-wide sample and, secondly, to verify attitudes towards help-seeking to treat these symptoms. Material and Methods: Data were collected through an online questionnaire sent through the Brazilian Sleep Association's social media. The questionnaire included sociodemographic and sleep aspects questions currently and before the pandemic period. In addition, the survey addressed current and previous anxiety, depression, and burnout symptoms. The outcome help-seeking was addressed in the questionnaire as well by a single question asked when the participant reported mental or sleep problems. Results: The study covered 6,360 participants, mean age 43.5 years (SD=14.3), 76.7% female and 63.7% with undergraduate or higher degree filled out the survey. Seventy percent of participants reported sleep disturbances and 80% reported symptoms of anxiety during the pandemic. Help-seeking behavior was found only in one third of them. Hours of sleep reduced from 7.12 to 6.2h, which can be related with the increase in 28.2% of dissatisfaction with sleep duration during the pandemic. The highest frequency of complaints related to sleep was difficulty to fall asleep three or more times a week (going from 27.6% before the pandemic to 58.9% during the pandemic; p<0.001). Moreover, it was observed that help-seeking was more prevalent in men than women, and more in younger participants than in older ones. Conclusion: There was an increase of sleep and mental self-reported problems during the pandemic, which was not followed by help-seeking.

Insomnia episodes, new-onset pharmacological treatments, and other sleep disturbances during the COVID-19 pandemic: a nationwide cross-sectional study in Brazilian health care professionals.

STUDY OBJECTIVES: To evaluate the impact of the coronavirus disease 2019 (COVID-19) pandemic on insomnia and other sleep disturbances in health care professionals. METHODS: A survey was distributed using social media and organizational emails to Brazilian active health care professionals during the COVID-19 outbreak. We explored potential associated factors including age, sex, occupation, workplace, work hours, income, previous infection with COVID-19, recent/current contact with COVID-19 patients, regional number of incident deaths, anxiety, and burnout. We evaluated new-onset/previous insomnia worsening episodes (primary outcome), new pharmacological treatments, sleep quality, duration, nightmares, and snoring (secondary outcomes). RESULTS: A total of 4,384 health professionals from all regions of the country were included in the analysis (44 ± 12 years, 76% females, 53.8% physicians). Overall, 55.7% were assisting patients with COVID-19, and 9.2% had a previous COVID-19 infection. The primary outcome occurred in 32.9% of respondents in parallel to 13% new pharmacological treatments for insomnia. The sleep quality worsened for 61.4%, while 43.5% and 22.8% reported ≥ 1-hour sleep duration reduction and worsening or new-onset nightmares, respectively. Multivariate analyses showed that age (odds ratio [OR]: 1.008; 95% confidence interval [CI] 1.001-1.015), females (OR: 1.590; 95% CI 1.335-1.900), weight change (decrease: OR: 1.772; 95% CI 1.453-2.161; increase: OR: 1.468; 95% CI 1.249-1.728), prevalent anxiety (OR: 3.414; 95% CI 2.954-3.948), new-onset burnout (OR: 1.761; 95% CI 1.489-2.083), family income reduction > 30% (OR: 1.288; 95% CI 1.069-1.553), and assisting patients with COVID-19 (OR: 1.275; 95% CI 1.081-1.506) were independently associated with new-onset or worsening of previous insomnia episodes. CONCLUSIONS: We observed a huge burden of insomnia episodes and other sleep disturbances in health care professionals during the COVID-19 pandemic. CITATION: Drager LF, Pachito DV, Moreno CRC, et al. Insomnia episodes, new-onset pharmacological treatments, and other sleep disturbances during the COVID-19 pandemic: a nationwide cross-sectional study in Brazilian health care professionals. J Clin Sleep Med. 2022;18(2):373-382.

The effect of exposure to long working hours on alcohol consumption, risky drinking and alcohol use disorder: A systematic review and meta-analysis from the WHO/ILO Joint Estimates of the Work-related Burden of Disease and Injury.

BACKGROUND: The World Health Organization (WHO) and the International Labour Organization (ILO) are developing Joint Estimates of the work-related burden of disease and injury (WHO/ILO Joint Estimates), with contributions from a large network of experts. Evidence from mechanistic data suggests that exposure to long working hours may increase alcohol consumption and cause alcohol use disorder. In this paper, we present a systematic review and meta-analysis of parameters for estimating the number of deaths and disability-adjusted life years from alcohol consumption and alcohol use disorder that are attributable to exposure to long working hours, for the development of the WHO/ILO Joint Estimates. OBJECTIVES: We aimed to systematically review and meta-analyse estimates of the effect of exposure to long working hours (three categories: 41-48, 49-54 and ≥55 h/week), compared with exposure to standard working hours (35-40 h/week), on alcohol consumption, risky drinking (three outcomes: prevalence, incidence and mortality) and alcohol use disorder (three outcomes: prevalence, incidence and mortality). DATA SOURCES: We developed and published a protocol, applying the Navigation Guide as an organizing systematic review framework where feasible. We searched electronic bibliographic databases for potentially relevant records from published and unpublished studies, including the WHO International Clinical Trials Register, Ovid MEDLINE, PubMed, Embase, and CISDOC on 30 June 2018. Searches on PubMed were updated on 18 April 2020. We also searched electronic grey literature databases, Internet search engines and organizational websites; hand-searched reference list of previous systematic reviews and included study records; and consulted additional experts. STUDY ELIGIBILITY AND CRITERIA: We included working-age (≥15 years) workers in the formal and informal economy in any WHO and/or ILO Member State but excluded children (<15 years) and unpaid domestic workers. We considered for inclusion randomized controlled trials, cohort studies, case-control studies and other non-randomized intervention studies with an estimate of the effect of exposure to long working hours (41-48, 49-54 and ≥55 h/week), compared with exposure to standard working hours (35-40 h/week), on alcohol consumption (in g/week), risky drinking, and alcohol use disorder (prevalence, incidence or mortality). STUDY APPRAISAL AND SYNTHESIS METHODS: At least two review authors independently screened titles and abstracts against the eligibility criteria at a first stage and full texts of potentially eligible records at a second stage, followed by extraction of data from publications related to qualifying studies. Two or more review authors assessed the risk of bias, quality of evidence and strength of evidence, using Navigation Guide and GRADE tools and approaches adapted to this project. RESULTS: Fourteen cohort studies met the inclusion criteria, comprising a total of 104,599 participants (52,107 females) in six countries of three WHO regions (Americas, South-East Asia, and Europe). The exposure and outcome were assessed with self-reported measures in most studies. Across included studies, risk of bias was generally probably high, with risk judged high or probably high for detection bias and missing data for alcohol consumption and risky drinking. Compared to working 35-40 h/week, exposure to working 41-48 h/week increased alcohol consumption by 10.4 g/week (95% confidence interval (CI) 5.59-15.20; seven studies; 25,904 participants, I2 71%, low quality evidence). Exposure to working 49-54 h/week increased alcohol consumption by 17.69 g/week (95% confidence interval (CI) 9.16-26.22; seven studies, 19,158 participants, I2 82%, low quality evidence). Exposure to working ≥55 h/week increased alcohol consumption by 16.29 g/week (95% confidence interval (CI) 7.93-24.65; seven studies; 19,692 participants; I2 82%, low quality evidence). We are uncertain about the effect of exposure to working 41-48 h/week, compared with working 35-40 h/week on developing risky drinking (relative risk 1.08; 95% CI 0.86-1.36; 12 studies; I2 52%, low certainty evidence). Working 49-54 h/week did not increase the risk of developing risky drinking (relative risk 1.12; 95% CI 0.90-1.39; 12 studies; 3832 participants; I2 24%, moderate certainty evidence), nor working ≥55 h/week (relative risk 1.11; 95% CI 0.95-1.30; 12 studies; 4525 participants; I2 0%, moderate certainty evidence). Subgroup analyses indicated that age may influence the association between long working hours and both alcohol consumption and risky drinking. We did not identify studies for which we had access to results on alcohol use disorder. CONCLUSIONS: Overall, for alcohol consumption in g/week and for risky drinking, we judged this body of evidence to be of low certainty. Exposure to long working hours may have increased alcohol consumption, but we are uncertain about the effect on risky drinking. We found no eligible studies on the effect on alcohol use disorder. Producing estimates for the burden of alcohol use disorder attributable to exposure to long working hours appears to not be evidence-based at this time. PROTOCOL IDENTIFIER: https://doi.org/10.1016/j.envint.2018.07.025. PROSPERO REGISTRATION NUMBER: CRD42018084077.

The effect of exposure to long working hours on depression: A systematic review and meta-analysis from the WHO/ILO Joint Estimates of the Work-related Burden of Disease and Injury.

BACKGROUND: The World Health Organization (WHO) and the International Labour Organization (ILO) are developing the WHO/ILO Joint Estimates of the Work-related Burden of Disease and Injury (WHO/ILO Joint Estimates), supported by a large number of individual experts. Evidence from previous reviews suggests that exposure to long working hours may cause depression. In this article, we present a systematic review and meta-analysis of parameters for estimating (if feasible) the number of deaths and disability-adjusted life years from depression that are attributable to exposure to long working hours, for the development of the WHO/ILO Joint Estimates. OBJECTIVES: We aimed to systematically review and meta-analyse estimates of the effect of exposure to long working hours (three categories: 41-48, 49-54 and ≥55 h/week), compared with exposure to standard working hours (35-40 h/week), on depression (three outcomes: prevalence, incidence and mortality). DATA SOURCES: We developed and published a protocol, applying the Navigation Guide as an organizing systematic review framework where feasible. We searched electronic academic databases for potentially relevant records from published and unpublished studies, including the WHO International Clinical Trial Registers Platform, Medline, PubMed, EMBASE, Web of Science, CISDOC and PsycInfo. We also searched grey literature databases, Internet search engines and organizational websites; hand-searched reference lists of previous systematic reviews; and consulted additional experts. STUDY ELIGIBILITY AND CRITERIA: We included working-age (≥15 years) workers in the formal and informal economy in any WHO and/or ILO Member State but excluded children (aged <15 years) and unpaid domestic workers. We included randomized controlled trials, cohort studies, case-control studies and other non-randomized intervention studies with an estimate of the effect of exposure to long working hours (41-48, 49-54 and ≥55 h/week), compared with exposure to standard working hours (35-40 h/week), on depression (prevalence, incidence and/or mortality). STUDY APPRAISAL AND SYNTHESIS METHODS: At least two review authors independently screened titles and abstracts against the eligibility criteria at a first stage and full texts of potentially eligible records at a second stage, followed by extraction of data from qualifying studies. Missing data were requested from principal study authors. We combined odds ratios using random-effects meta-analysis. Two or more review authors assessed the risk of bias, quality of evidence and strength of evidence, using Navigation Guide and GRADE tools and approaches adapted to this project. RESULTS: Twenty-two studies (all cohort studies) met the inclusion criteria, comprising a total of 109,906 participants (51,324 females) in 32 countries (as one study included multiple countries) in three WHO regions (Americas, Europe and Western Pacific). The exposure was measured using self-reports in all studies, and the outcome was assessed with a clinical diagnostic interview (four studies), interview questions about diagnosis and treatment of depression (three studies) or a validated self-administered rating scale (15 studies). The outcome was defined as incident depression in all 22 studies, with first time incident depression in 21 studies and recurrence of depression in one study. We did not identify any study on prevalence of depression or on mortality from depression. For the body of evidence for the outcome incident depression, we had serious concerns for risk of bias due to selection because of incomplete outcome data (most studies assessed depression only twice, at baseline and at a later follow-up measurement, and likely have missed cases of depression that occurred after baseline but were in remission at the time of the follow-up measurement) and due to missing information on life-time prevalence of depression before baseline measurement. Compared with working 35-40 h/week, we are uncertain about the effect on acquiring (or incidence of) depression of working 41-48 h/week (pooled odds ratio (OR) 1.05, 95% confidence interval (CI) 0.86 to 1.29, 8 studies, 49,392 participants, I2 46%, low quality of evidence); 49-54 h/week (OR 1.06, 95% CI 0.93 to 1.21, 8 studies, 49,392 participants, I2 40%, low quality of evidence); and ≥ 55 h/week (OR 1.08, 95% CI 0.94 to 1.24, 17 studies, 91,142 participants, I2 46%, low quality of evidence). Subgroup analyses found no evidence for statistically significant (P < 0.05) differences by WHO region, sex, age group and socioeconomic status. Sensitivity analyses found no statistically significant differences by outcome measurement (clinical diagnostic interview [gold standard] versus other measures) and risk of bias ("high"/"probably high" ratings in any domain versus "low"/"probably low" in all domains). CONCLUSIONS: We judged the existing bodies of evidence from human data as "inadequate evidence for harmfulness" for all three exposure categories, 41-48, 48-54 and ≥55 h/week, for depression prevalence, incidence and mortality; the available evidence is insufficient to assess effects of the exposure. Producing estimates of the burden of depression attributable to exposure to long working appears not evidence-based at this point. Instead, studies examining the association between long working hours and risk of depression are needed that address the limitations of the current evidence.

The effect of exposure to long working hours on ischaemic heart disease: A systematic review and meta-analysis from the WHO/ILO Joint Estimates of the Work-related Burden of Disease and Injury.

BACKGROUND: The World Health Organization (WHO) and the International Labour Organization (ILO) are developing Joint Estimates of the work-related burden of disease and injury (WHO/ILO Joint Estimates), with contributions from a large network of experts. Evidence from mechanistic data suggests that exposure to long working hours may cause ischaemic heart disease (IHD). In this paper, we present a systematic review and meta-analysis of parameters for estimating the number of deaths and disability-adjusted life years from IHD that are attributable to exposure to long working hours, for the development of the WHO/ILO Joint Estimates. OBJECTIVES: We aimed to systematically review and meta-analyse estimates of the effect of exposure to long working hours (three categories: 41-48, 49-54 and ≥55 h/week), compared with exposure to standard working hours (35-40 h/week), on IHD (three outcomes: prevalence, incidence and mortality). DATA SOURCES: We developed and published a protocol, applying the Navigation Guide as an organizing systematic review framework where feasible. We searched electronic databases for potentially relevant records from published and unpublished studies, including MEDLINE, Scopus, Web of Science, CISDOC, PsycINFO, and WHO ICTRP. We also searched grey literature databases, Internet search engines and organizational websites; hand-searched reference lists of previous systematic reviews; and consulted additional experts. STUDY ELIGIBILITY AND CRITERIA: We included working-age (≥15 years) workers in the formal and informal economy in any WHO and/or ILO Member State but excluded children (aged < 15 years) and unpaid domestic workers. We included randomized controlled trials, cohort studies, case-control studies and other non-randomized intervention studies which contained an estimate of the effect of exposure to long working hours (41-48, 49-54 and ≥55 h/week), compared with exposure to standard working hours (35-40 h/week), on IHD (prevalence, incidence or mortality). STUDY APPRAISAL AND SYNTHESIS METHODS: At least two review authors independently screened titles and abstracts against the eligibility criteria at a first stage and full texts of potentially eligible records at a second stage, followed by extraction of data from qualifying studies. Missing data were requested from principal study authors. We combined relative risks using random-effect meta-analysis. Two or more review authors assessed the risk of bias, quality of evidence and strength of evidence, using Navigation Guide and GRADE tools and approaches adapted to this project. RESULTS: Thirty-seven studies (26 prospective cohort studies and 11 case-control studies) met the inclusion criteria, comprising a total of 768,751 participants (310,954 females) in 13 countries in three WHO regions (Americas, Europe and Western Pacific). The exposure was measured using self-reports in all studies, and the outcome was assessed with administrative health records (30 studies) or self-reported physician diagnosis (7 studies). The outcome was defined as incident non-fatal IHD event in 19 studies (8 cohort studies, 11 case-control studies), incident fatal IHD event in two studies (both cohort studies), and incident non-fatal or fatal ("mixed") event in 16 studies (all cohort studies). Because we judged cohort studies to have a relatively lower risk of bias, we prioritized evidence from these studies and treated evidence from case-control studies as supporting evidence. For the bodies of evidence for both outcomes with any eligible studies (i.e. IHD incidence and mortality), we did not have serious concerns for risk of bias (at least for the cohort studies). No eligible study was found on the effect of long working hours on IHD prevalence. Compared with working 35-40 h/week, we are uncertain about the effect on acquiring (or incidence of) IHD of working 41-48 h/week (relative risk (RR) 0.98, 95% confidence interval (CI) 0.91 to 1.07, 20 studies, 312,209 participants, I2 0%, low quality of evidence) and 49-54 h/week (RR 1.05, 95% CI 0.94 to 1.17, 18 studies, 308,405 participants, I2 0%, low quality of evidence). Compared with working 35-40 h/week, working ≥55 h/week may have led to a moderately, clinically meaningful increase in the risk of acquiring IHD, when followed up between one year and 20 years (RR 1.13, 95% CI 1.02 to 1.26, 22 studies, 339,680 participants, I2 5%, moderate quality of evidence). Compared with working 35-40 h/week, we are very uncertain about the effect on dying (mortality) from IHD of working 41-48 h/week (RR 0.99, 95% CI 0.88 to 1.12, 13 studies, 288,278 participants, I2 8%, low quality of evidence) and 49-54 h/week (RR 1.01, 95% CI 0.82 to 1.25, 11 studies, 284,474 participants, I2 13%, low quality of evidence). Compared with working 35-40 h/week, working ≥55 h/week may have led to a moderate, clinically meaningful increase in the risk of dying from IHD when followed up between eight and 30 years (RR 1.17, 95% CI 1.05 to 1.31, 16 studies, 726,803 participants, I2 0%, moderate quality of evidence). Subgroup analyses found no evidence for differences by WHO region and sex, but RRs were higher among persons with lower SES. Sensitivity analyses found no differences by outcome definition (exclusively non-fatal or fatal versus "mixed"), outcome measurement (health records versus self-reports) and risk of bias ("high"/"probably high" ratings in any domain versus "low"/"probably low" in all domains). CONCLUSIONS: We judged the existing bodies of evidence for human evidence as "inadequate evidence for harmfulness" for the exposure categories 41-48 and 49-54 h/week for IHD prevalence, incidence and mortality, and for the exposure category ≥55 h/week for IHD prevalence. Evidence on exposure to working ≥55 h/week was judged as "sufficient evidence of harmfulness" for IHD incidence and mortality. Producing estimates for the burden of IHD attributable to exposure to working ≥55 h/week appears evidence-based, and the pooled effect estimates presented in this systematic review could be used as input data for the WHO/ILO Joint Estimates.

Legal action for access to resources inefficiently made available in health care systems in Brazil: a case study on obstructive sleep apnea / Judicialização para acesso a recursos disponibilizados de forma ineficiente nos sistemas de saúde do Brasil: estudo de caso sobre apneia obstrutiva do sono

ABSTRACT Objective: Obstructive sleep apnea (OSA) is a highly prevalent chronic disease, associated with morbidity and mortality. Although effective treatment for OSA is commercially available, their provision is not guaranteed by lines of care throughout Brazil, making legal action necessary. This study aimed at presenting data related to the volume of legal proceedings regarding the access to diagnosis and treatment of OSA in Brazil. Methods: This was a descriptive study of national scope, evaluating the period between January of 2016 and December of 2020. The number of lawsuits was analyzed according to the object of the demand (diagnosis or treatment). Projections of total expenses were carried out according to the number of lawsuits. Results: We identified 1,462 legal proceedings (17.6% and 82.4% related to diagnosis and treatment, respectively). The projection of expenditure for OSA diagnosis in the public and private spheres were R$575,227 and R$188,002, respectively. The projection of expenditure for OSA treatment in the public and private spheres were R$2,656,696 and R$253,050, respectively. There was a reduction in the number of lawsuits between 2017 and 2019. Conclusions: Legal action as a strategy for accessing diagnostic and therapeutic resources related to OSA is a recurrent practice, resulting in inefficiency and inequity. The reduction in the number of lawsuits between 2017 and 2019 might be explained by the expansion of local health care policies or by barriers in the journey of patients with OSA, such as difficulties in being referred to specialized health care and low availability of diagnostic resources.

RESUMO Objetivo: A apneia obstrutiva do sono (AOS) é uma doença crônica altamente prevalente, associada a morbidade e mortalidade. Embora tratamentos efetivos para a AOS estejam disponíveis comercialmente, seu fornecimento não é garantido pelos fluxos de atendimento em todo o Brasil, tornando necessária a judicialização. Este estudo teve como objetivo apresentar dados referentes ao volume de processos judiciais relacionados ao acesso ao diagnóstico e tratamento da AOS no Brasil. Métodos: Estudo descritivo de abrangência nacional, avaliando o período entre janeiro de 2016 e dezembro de 2020. O número de demandas judiciais foi analisado de acordo com o objeto da demanda (diagnóstico ou tratamento). As projeções das despesas totais foram realizadas de acordo com o número de demandas judiciais. Resultados: Foram identificados 1.462 processos judiciais (17,6% e 82,4% referentes a diagnóstico e tratamento, respectivamente). A projeção dos gastos com o diagnóstico da AOS nas esferas pública e privada foi de R$ 575.227 e R$ 188.002, respectivamente. A projeção dos gastos com o tratamento da AOS nas esferas pública e privada foi de R$ 2.656.696 e R$ 253.050, respectivamente. Houve redução do número de demandas judiciais entre 2017 e 2019. Conclusões: A judicialização como estratégia de acesso a recursos diagnósticos e terapêuticos relacionados à AOS é uma prática recorrente, resultando em ineficiência e iniquidade. A redução do número de demandas judiciais entre 2017 e 2019 pode ser explicada pela expansão das políticas locais de saúde ou por barreiras na jornada dos pacientes com AOS, como dificuldades de encaminhamento para atendimento especializado e a baixa disponibilidade de recursos diagnósticos.

WHO/ILO work-related burden of disease and injury: Protocol for systematic reviews of exposure to long working hours and of the effect of exposure to long working hours on alcohol consumption and alcohol use disorders.

BACKGROUND: The World Health Organization (WHO) and the International Labour Organization (ILO) are developing a joint methodology for estimating the national and global work-related burden of disease and injury (WHO/ILO joint methodology), with contributions from a large network of experts. In this paper, we present the protocol for two systematic reviews of parameters for estimating the number of deaths and disability-adjusted life years from alcohol consumption and alcohol use disorder attributable to exposure to long working hours, to inform the development of the WHO/ILO joint methodology. OBJECTIVES: We aim to systematically review studies on exposure to long working hours (Systematic Review 1) and systematically review and meta-analyse estimates of the effect of exposure to long working hours on alcohol consumption and alcohol use disorder (Systematic Review 2), applying the Navigation Guide systematic review methodology as an organizing framework. DATA SOURCES: Separately for Systematic Reviews 1 and 2, we will search electronic academic databases for potentially relevant records from published and unpublished studies, including MEDLINE, Embase, Web of Science, CISDOC and PsychINFO. We will also search electronic grey literature databases, Internet search engines and organizational websites; hand-search reference list of previous systematic reviews and included study records; and consult additional experts. STUDY ELIGIBILITY AND CRITERIA: We will include working-age (≥15 years) workers in the formal and informal economy in any WHO and/or ILO Member State but exclude children (<15 years) and unpaid domestic workers. For Systematic Review 1, we will include quantitative prevalence studies of relevant levels of exposure to long working hours (i.e., 35-40, 41-48, 49-54 and ≥55 h/week) stratified by country, sex, age and industrial sector or occupation. For Systematic Review 2, we will include randomized controlled trials, cohort studies, case-control studies and other non-randomized intervention studies with an estimate of the relative effect of a relevant level of exposure to long working hours on total amount of alcohol consumed and on the incidence of, prevalence of or mortality from alcohol use disorders, compared with the theoretical minimum risk exposure level (i.e., worked 35-40 h/week). STUDY APPRAISAL AND SYNTHESIS METHODS: At least two review authors will independently screen titles and abstracts at a first stage and full texts of potentially eligible records at a second stage, followed by extraction of data from qualifying studies. At least two review authors will assess risk of bias and quality of evidence, using the most suited tools currently available. For Systematic Review 2, if feasible, we will combine relative risks using meta-analysis. We will report results using the guidelines for accurate and transparent health estimates reporting (GATHER) for Systematic Review 1 and the preferred reporting items for systematic reviews and meta-analyses guidelines (PRISMA) for Systematic Review 2. PROSPERO registration number: CRD42018084077.

Abordagem terapêutica dos distúrbios respiratórios do sono tratamento com ventilação não-invasiva (CPAP, BiPAP e AUTO-CPAP / Therapeutic approach of respiratory sleep disorders treatment with non-invasive ventilation (CPAP, BiPAP and AUTO-CPAP)

RESUMO: A abordagem dos distúrbios respiratórios do sono com uso de pressão positiva contínua nas vias aéreas é considerada a forma mais eficiente de tratamento. É feita por meio de aparelho apropriado, chamado CPAP que se adapta a um tubo flexível através do qual o ar liberado pelo aparelho é conduzido até uma máscara firmemente adaptada ao nariz do paciente. Os portadores de distúrbios graves bem como os moderados sintomáticos, aderem facilmente a essa forma de tratamento. A adesão ao tratamento pode ser melhorada com medidas simples em alguns casos. As complicações são previsíveis e raras. Outras modalidades de dispositivos de pressão positiva ocasionalmente são mais bem toleradas e mais eficazes para o tratamento de hipoventilação alveolar e apnéias centrais.