Melatonin and agomelatine for preventing seasonal affective disorder.

Nussbaumer-Streit B ，Greenblatt A ，Kaminski-Hartenthaler A ，Van Noord MG ，Forneris CA ，Morgan LC ，Gaynes BN ，Wipplinger J ，Lux LJ ，Winkler D ，Gartlehner G ... -  《Cochrane Database of Systematic Reviews》

Psychological therapies for preventing seasonal affective disorder.

Forneris CA ，Nussbaumer-Streit B ，Morgan LC ，Greenblatt A ，Van Noord MG ，Gaynes BN ，Wipplinger J ，Lux LJ ，Winkler D ，Gartlehner G ... -  《Cochrane Database of Systematic Reviews》

Exercise therapy for chronic fatigue syndrome.

Editorial note (19 December 2024; amended 31 January 2025): Larun L, Brurberg KG, Odgaard‐Jensen J, Price JR. Exercise therapy for chronic fatigue syndrome. Cochrane Database of Systematic Reviews 2019, Issue 10. Art. No.: CD003200. DOI: 10.1002/14651858.CD003200.pub8. Accessed 18 December 2024. This Editorial Note is for the above article, published online on 2 October 2019 on the Cochrane Library (https://www.cochranelibrary.com/), and has been issued by the Publisher, John Wiley & Sons Ltd, in agreement with the Cochrane Collaboration. The Editorial note has been agreed to inform readers that Cochrane is ceasing the production of a full update of this Cochrane review. A pilot project for engaging interest holders in the development of this Cochrane review was initiated on 2 October 2019 (see Editorial Note below) and has now been disbanded. Cochrane maintains its decision to publish this Cochrane review in 2019, which includes studies from searches up to 9 May 2014. Editorial note (2 October 2019): A statement from the Editor in Chief about this review and its planned update is available at https://www.cochrane.org/news/cfs Chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME) is a serious disorder characterised by persistent postexertional fatigue and substantial symptoms related to cognitive, immune and autonomous dysfunction. There is no specific diagnostic test, therefore diagnostic criteria are used to diagnose CFS. The prevalence of CFS varies by type of diagnostic criteria used. Existing treatment strategies primarily aim to relieve symptoms and improve function. One treatment option is exercise therapy. The objective of this review was to determine the effects of exercise therapy for adults with CFS compared with any other intervention or control on fatigue, adverse outcomes, pain, physical functioning, quality of life, mood disorders, sleep, self-perceived changes in overall health, health service resources use and dropout. We searched the Cochrane Common Mental Disorders Group controlled trials register, CENTRAL, and SPORTDiscus up to May 2014, using a comprehensive list of free-text terms for CFS and exercise. We located unpublished and ongoing studies through the World Health Organization International Clinical Trials Registry Platform up to May 2014. We screened reference lists of retrieved articles and contacted experts in the field for additional studies. We included randomised controlled trials (RCTs) about adults with a primary diagnosis of CFS, from all diagnostic criteria, who were able to participate in exercise therapy. Two review authors independently performed study selection, 'Risk of bias' assessments and data extraction. We combined continuous measures of outcomes using mean differences (MDs) or standardised mean differences (SMDs). To facilitate interpretation of SMDs, we re-expressed SMD estimates as MDs on more common measurement scales. We combined dichotomous outcomes using risk ratios (RRs). We assessed the certainty of evidence using GRADE. We included eight RCTs with data from 1518 participants. Exercise therapy lasted from 12 weeks to 26 weeks. The studies measured effect at the end of the treatment and at long-term follow-up, after 50 weeks or 72 weeks. Seven studies used aerobic exercise therapies such as walking, swimming, cycling or dancing, provided at mixed levels in terms of intensity of the aerobic exercise from very low to quite rigorous, and one study used anaerobic exercise. Control groups consisted of passive control, including treatment as usual, relaxation or flexibility (eight studies); cognitive behavioural therapy (CBT) (two studies); cognitive therapy (one study); supportive listening (one study); pacing (one study); pharmacological treatment (one study) and combination treatment (one study). Most studies had a low risk of selection bias. All had a high risk of performance and detection bias. Exercise therapy compared with 'passive' control Exercise therapy probably reduces fatigue at end of treatment (SMD -0.66, 95% CI -1.01 to -0.31; 7 studies, 840 participants; moderate-certainty evidence; re-expressed MD -3.4, 95% CI -5.3 to -1.6; scale 0 to 33). We are uncertain if fatigue is reduced in the long term because the certainty of the evidence is very low (SMD -0.62, 95 % CI -1.32 to 0.07; 4 studies, 670 participants; re-expressed MD -3.2, 95% CI -6.9 to 0.4; scale 0 to 33). We are uncertain about the risk of serious adverse reactions because the certainty of the evidence is very low (RR 0.99, 95% CI 0.14 to 6.97; 1 study, 319 participants). Exercise therapy may moderately improve physical functioning at end of treatment, but the long-term effect is uncertain because the certainty of the evidence is very low. Exercise therapy may also slightly improve sleep at end of treatment and at long term. The effect of exercise therapy on pain, quality of life and depression is uncertain because evidence is missing or of very low certainty. Exercise therapy compared with CBT Exercise therapy may make little or no difference to fatigue at end of treatment (MD 0.20, 95% CI -1.49 to 1.89; 1 study, 298 participants; low-certainty evidence), or at long-term follow-up (SMD 0.07, 95% CI -0.13 to 0.28; 2 studies, 351 participants; moderate-certainty evidence). We are uncertain about the risk of serious adverse reactions because the certainty of the evidence is very low (RR 0.67, 95% CI 0.11 to 3.96; 1 study, 321 participants). The available evidence suggests that there may be little or no difference between exercise therapy and CBT in physical functioning or sleep (low-certainty evidence) and probably little or no difference in the effect on depression (moderate-certainty evidence). We are uncertain if exercise therapy compared to CBT improves quality of life or reduces pain because the evidence is of very low certainty. Exercise therapy compared with adaptive pacing Exercise therapy may slightly reduce fatigue at end of treatment (MD -2.00, 95% CI -3.57 to -0.43; scale 0 to 33; 1 study, 305 participants; low-certainty evidence) and at long-term follow-up (MD -2.50, 95% CI -4.16 to -0.84; scale 0 to 33; 1 study, 307 participants; low-certainty evidence). We are uncertain about the risk of serious adverse reactions (RR 0.99, 95% CI 0.14 to 6.97; 1 study, 319 participants; very low-certainty evidence). The available evidence suggests that exercise therapy may slightly improve physical functioning, depression and sleep compared to adaptive pacing (low-certainty evidence). No studies reported quality of life or pain. Exercise therapy compared with antidepressants We are uncertain if exercise therapy, alone or in combination with antidepressants, reduces fatigue and depression more than antidepressant alone, as the certainty of the evidence is very low. The one included study did not report on adverse reactions, pain, physical functioning, quality of life, sleep or long-term results. Exercise therapy probably has a positive effect on fatigue in adults with CFS compared to usual care or passive therapies. The evidence regarding adverse effects is uncertain. Due to limited evidence it is difficult to draw conclusions about the comparative effectiveness of CBT, adaptive pacing or other interventions. All studies were conducted with outpatients diagnosed with 1994 criteria of the Centers for Disease Control and Prevention or the Oxford criteria, or both. Patients diagnosed using other criteria may experience different effects.

Larun L ，Brurberg KG ，Odgaard-Jensen J ，Price JR ... -  《Cochrane Database of Systematic Reviews》

Conservative, physical and surgical interventions for managing faecal incontinence and constipation in adults with central neurological diseases.

People with central neurological disease or injury have a much higher risk of both faecal incontinence (FI) and constipation than the general population. There is often a fine line between the two symptoms, with management intended to ameliorate one risking precipitating the other. Bowel problems are observed to be the cause of much anxiety and may reduce quality of life in these people. Current bowel management is largely empirical, with a limited research base. The review is relevant to individuals with any disease directly and chronically affecting the central nervous system (post-traumatic, degenerative, ischaemic or neoplastic), such as multiple sclerosis, spinal cord injury, cerebrovascular disease, Parkinson's disease and Alzheimer's disease. This is an update of a Cochrane Review first published in 2001 and subsequently updated in 2003, 2006 and 2014. To assess the effects of conservative, physical and surgical interventions for managing FI and constipation in people with a neurological disease or injury affecting the central nervous system. We searched the Cochrane Incontinence Specialised Register (searched 27 March 2023), which includes searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE In-Process, MEDLINE Epub Ahead of Print, ClinicalTrials.gov, WHO ICTRP as well as handsearching of journals and conference proceedings; and all reference lists of relevant articles. We included randomised, quasi-randomised (where allocation is not strictly random), cross-over and cluster-randomised trials evaluating any type of conservative, physical or surgical intervention against placebo, usual care or no intervention for the management of FI and constipation in people with central neurological disease or injury. At least two review authors independently assessed the risk of bias in eligible trials using Cochrane's 'Risk of bias' tool and independently extracted data from the included trials using a range of prespecified outcome measures. We produced summary of findings tables for our main outcome measures and assessed the certainty of the evidence using GRADE. We included 25 studies with 1598 participants. The studies were generally at high risk of bias due to lack of blinding of participants and personnel to the intervention. Half of the included studies were also at high risk of bias in terms of selective reporting. Outcomes were often reported heterogeneously across studies, making it difficult to pool data. We did not find enough evidence to be able to analyse the effects of interventions on individual central neurological diseases. Additionally, very few studies reported on the primary outcomes of self-reported improvement in FI or constipation, or Neurogenic Bowel Dysfunction Score. Conservative interventions compared with usual care, no active treatment or placebo Thirteen studies assessed this comparison. The interventions included assessment-based nursing, holistic nursing, probiotics, psyllium, faecal microbiota transplantation, and a stepwise protocol of increasingly invasive evacuation methods. Conservative interventions may result in a large improvement in faecal incontinence (standardised mean difference (SMD) -1.85, 95% confidence interval (CI) -3.47 to -0.23; 3 studies; n = 410; low-certainty evidence). We interpreted SMD ≥ 0.80 as a large effect. It was not possible to pool all data from studies that assessed improvement in constipation, but the evidence suggested that conservative interventions may improve constipation symptoms (data not pooled; 8 studies; n = 612; low-certainty evidence). Conservative interventions may lead to a reduction in mean time taken on bowel care (data not pooled; 5 studies; n = 526; low-certainty evidence). The evidence is uncertain about the effects of conservative interventions on condition-specific quality of life and adverse events. Neurogenic Bowel Dysfunction Score was not reported. Physical therapy compared with usual care, no active treatment or placebo Twelve studies assessed this comparison. The interventions included massage therapy, standing, osteopathic manipulative treatment, electrical stimulation, transanal irrigation, and conventional physical therapy with visceral mobilisation. Physical therapies may make little to no difference to self-reported faecal continence assessed using the St Mark's Faecal Incontinence Score, where the minimally important difference is five, or the Cleveland Constipation Score (MD -2.60, 95% CI -4.91 to -0.29; 3 studies; n = 155; low-certainty evidence). Physical therapies may result in a moderate improvement in constipation symptoms (SMD -0.62, 95% CI -1.10 to -0.14; 9 studies; n = 431; low-certainty evidence). We interpreted SMD ≥ 0.5 as a moderate effect. However, physical therapies may make little to no difference in Neurogenic Bowel Dysfunction Score as the minimally important difference for this tool is 3 (MD -1.94, 95% CI -3.36 to -0.51; 7 studies; n = 358; low-certainty evidence). We are very uncertain about the effects of physical therapies on the time spent on bowel care, condition-specific quality of life and adverse effects (all very low-certainty evidence). Surgical interventions compared with usual care, no active treatment or placebo No studies were found for surgical interventions that met the inclusion criteria for this review. There remains little research on this common and, for patients, very significant issue of bowel management. The available evidence is almost uniformly of low methodological quality. The clinical significance of some of the research findings presented here is difficult to interpret, not least because each intervention has only been addressed in individual trials, against control rather than compared against each other, and the interventions are very different from each other. Understanding whether there is a clinically-meaningful difference from the results of available trials is largely hampered by the lack of uniform outcome measures. This is due to an absence of core outcome sets, and development of these needs to be a research priority to allow studies to be compared directly. Some studies used validated constipation, incontinence or condition-specific measures; however, others used unvalidated analogue scales to report effectiveness. Some studies did not use any patient-reported outcomes and focused on physiological outcome measures, which is of relatively limited significance in terms of clinical implementation. There was evidence in favour of some conservative interventions, but these findings need to be confirmed by larger, well-designed controlled trials, which should include evaluation of the acceptability of the intervention to patients and the effect on their quality of life.

Todd CL ，Johnson EE ，Stewart F ，Wallace SA ，Bryant A ，Woodward S ，Norton C ... -  《Cochrane Database of Systematic Reviews》

Tamoxifen for adults with hepatocellular carcinoma.

Hepatocellular carcinoma is the most common type of liver cancer, accounting for 70% to 85% of individuals with primary liver cancer. Tamoxifen has been evaluated in randomised clinical trials in people with hepatocellular cancer. The reported results have been inconsistent. To evaluate the benefits and harms of tamoxifen or tamoxifen plus any other anticancer drugs compared with no intervention, placebo, any type of standard care, or alternative treatment in adults with hepatocellular carcinoma, irrespective of sex, administered dose, type of formulation, and duration of treatment. We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, three other databases, and major trials registries, and handsearched reference lists up to 26 March 2024. Parallel-group randomised clinical trials including adults (aged 18 years and above) diagnosed with advanced or unresectable hepatocellular carcinoma. Had we found cross-over trials, we would have included only the first trial phase. We did not consider data from quasi-randomised trials for analysis. Our critical outcomes were all-cause mortality, serious adverse events, and health-related quality of life. Our important outcomes were disease progression, and adverse events considered non-serious. We assessed risk of bias using the RoB 2 tool. We used standard Cochrane methods and Review Manager. We meta-analysed the outcome data at the longest follow-up. We presented the results of dichotomous outcomes as risk ratios (RR) and continuous data as mean difference (MD), with 95% confidence intervals (CI) using the random-effects model. We summarised the certainty of evidence using GRADE. We included 10 trials that randomised 1715 participants with advanced, unresectable, or terminal stage hepatocellular carcinoma. Six were single-centre trials conducted in Hong Kong, Italy, and Spain, while three were conducted as multicentre trials in single countries (France, Italy, and Spain), and one trial was conducted in nine countries in the Asia-Pacific region (Australia, Hong Kong, Indonesia, Malaysia, Myanmar, New Zealand, Singapore, South Korea, and Thailand). The experimental intervention was tamoxifen in all trials. The control interventions were no intervention (three trials), placebo (six trials), and symptomatic treatment (one trial). Co-interventions were best supportive care (three trials) and standard care (one trial). The remaining six trials did not provide this information. The number of participants in the trials ranged from 22 to 496 (median 99), mean age was 63.7 (standard deviation 4.18) years, and mean proportion of men was 74.7% (standard deviation 42%). Follow-up was three months to five years. Ten trials evaluated oral tamoxifen at five different dosages (ranging from 20 mg per day to 120 mg per day). All trials investigated one or more of our outcomes. We performed meta-analyses when at least two trials assessed similar types of tamoxifen versus similar control interventions. Eight trials evaluated all-cause mortality at varied follow-up points. Tamoxifen versus the control interventions (i.e. no treatment, placebo, and symptomatic treatment) results in little to no difference in mortality between one and five years (RR 0.99, 95% CI 0.92 to 1.06; 8 trials, 1364 participants; low-certainty evidence). In total, 488/682 (71.5%) participants died in the tamoxifen groups versus 487/682 (71.4%) in the control groups. The separate analysis results for one, between two and three, and five years were comparable to the analysis result for all follow-up periods taken together. The evidence is very uncertain about the effect of tamoxifen versus no treatment on serious adverse events at one-year follow-up (RR 0.44, 95% CI 0.19 to 1.06; 1 trial, 36 participants; very low-certainty evidence). A total of 5/20 (25.0%) participants in the tamoxifen group versus 9/16 (56.3%) participants in the control group experienced serious adverse events. One trial measured health-related quality of life at baseline and at nine months' follow-up, using the Spitzer Quality of Life Index. The evidence is very uncertain about the effect of tamoxifen versus no treatment on health-related quality of life (MD 0.03, 95% CI -0.45 to 0.51; 1 trial, 420 participants; very low-certainty evidence). A second trial found no appreciable difference in global health-related quality of life scores. No further data were provided. Tamoxifen versus control interventions (i.e. no treatment, placebo, or symptomatic treatment) results in little to no difference in disease progression between one and five years' follow-up (RR 1.02, 95% CI 0.91 to 1.14; 4 trials, 720 participants; low-certainty evidence). A total of 191/358 (53.3%) participants in the tamoxifen group versus 198/362 (54.7%) participants in the control group had progression of hepatocellular carcinoma. Tamoxifen versus control interventions (i.e. no treatment or placebo) may have little to no effect on adverse events considered non-serious during treatment, but the evidence is very uncertain (RR 1.17, 95% CI 0.45 to 3.06; 4 trials, 462 participants; very low-certainty evidence). A total of 10/265 (3.8%) participants in the tamoxifen group versus 6/197 (3.0%) participants in the control group had adverse events considered non-serious. We identified no trials with participants diagnosed with early stages of hepatocellular carcinoma. We identified no ongoing trials. Based on the low- and very low-certainty evidence, the effects of tamoxifen on all-cause mortality, disease progression, serious adverse events, health-related quality of life, and adverse events considered non-serious in adults with advanced, unresectable, or terminal stage hepatocellular carcinoma when compared with no intervention, placebo, or symptomatic treatment could not be established. Our findings are mostly based on trials at high risk of bias with insufficient power (fewer than 100 participants), and a lack of trial data on clinically important outcomes. Therefore, firm conclusions cannot be drawn. Trials comparing tamoxifen administered with any other anticancer drug versus standard care, usual care, or alternative treatment as control interventions were lacking. Evidence on the benefits and harms of tamoxifen in participants at the early stages of hepatocellular carcinoma was also lacking. This Cochrane review had no dedicated funding. Protocol available via DOI: 10.1002/14651858.CD014869.

Naing C ，Ni H ，Aung HH 《Cochrane Database of Systematic Reviews》