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Background: Major depressive disorder (MDD) is the most prevalent, disabling form of depression, with a high economic effect.Purpose: To assess evidence on cost-effectiveness of pharmacologic and nonpharmacologic interventions as first- and second-step treatments in patients with MDD.Data Sources: Multiple electronic databases limited to English language were searched (1 January 2015 to 29 November 2022).Study Selection: Two investigators independently screened the literature. Seven economic modeling studies fulfilled the eligibility criteria.Data Extraction: Data abstraction by a single investigator was confirmed by a second; 2 investigators independently rated risk of bias. One investigator determined certainty of evidence, and another checked for plausibility.Data Synthesis: Seven modeling studies met the eligibility criteria. In a U.S. setting over a 5-year time horizon, cognitive behavioral therapy (CBT) was cost-effective compared with second-generation antidepressants (SGAs) as a first-step treatment from the societal and health care sector perspectives. However, the certainty of evidence is low, and the findings should be interpreted cautiously. For second-step treatment, only switch strategies between SGAs were assessed. The evidence is insufficient to draw any conclusions.Limitations: Methodologically heterogeneous studies, which compared only CBT and some SGAs, were included. No evidence on other psychotherapies or complementary and alternative treatments as first-step treatment or augmentation strategies as second-step treatment was available.Conclusion: Although CBT may be cost-effective compared with SGAs as a first-step treatment at a 5-year time horizon from the societal and health care sector perspectives, the certainty of evidence is low, and the findings need to be interpreted cautiously. For other comparisons, the evidence was entirely missing or insufficient to draw conclusions.Primary Funding Source:American College of Physicians.

Background: Primary care patients and clinicians may prefer alternative options to second-generation antidepressants for major depressive disorder (MDD). Purpose: To compare the benefits and harms of nonpharmacologic treatments with second-generation antidepressants as first-step interventions for acute MDD, and to compare second-step treatment strategies for patients who did not achieve remission after an initial attempt with antidepressants. Data Sources: English-language studies from several electronic databases from 1 January 1990 to 8 August 2022, trial registries, gray literature databases, and reference lists to identify unpublished research. Study Selection: 2 investigators independently selected randomized trials of at least 6 weeks' duration. Data Extraction: Reviewers abstracted data about study design and conduct, participants, interventions, and outcomes. They dually rated the risk of bias of studies and the certainty of evidence for outcomes of interest. Data Synthesis: 65 randomized trials met the inclusion criteria; eligible data from nonrandomized studies were not found. Meta-analyses and network meta-analyses indicated similar benefits of most nonpharmacologic treatments and antidepressants as first-step treatments. Antidepressants had higher risks for discontinuation because of adverse events than most other treatments. For second-step therapies, different switching and augmentation strategies provided similar symptomatic relief. The certainty of evidence for most comparisons is low; findings should be interpreted cautiously. Limitations: Many studies had methodological limitations or dosing inequalities; publication bias might have affected some comparisons. In some cases, conclusions could not be drawn because of insufficient evidence. Conclusion: Although benefits seem to be similar among first- and second-step MDD treatments, the certainty of evidence is low for most comparisons. Clinicians and patients should focus on options with the most reliable evidence and take adverse event profiles and patient preferences into consideration.

After concussion, approximately 30% of adolescents experience symptoms that persist beyond 1 month postinjury. For some, these symptoms affect functioning, development, and quality of life. Somatization, where psychological distress contributes to physical symptoms, may contribute to persistent symptoms after concussion in some adolescents. Understanding how clinicians identify somatization in adolescents with persistent symptoms after concussion in practice is a critical next step in improving our understanding, identification, and subsequent treatment of somatization in this patient population. To address this, the investigators assessed and compared characteristics of adolescents with persistent symptoms after concussion with and without clinician-identified somatization.Participants were adolescents (N=94) referred for persistent symptoms after concussion to a specialty youth concussion clinic between January 2016 and May 2018. A retrospective chart review extracted demographic and injury characteristics, symptoms after concussion, school attendance, premorbid experiences, mental health, and medical service use. Participants with physician-identified somatization were compared with those without physician-identified somatization on these measures.Adolescents with identified somatization had more severe and atypical neurological and psychiatric symptoms after concussion and more postinjury impairment in school attendance, were more likely to have a history of premorbid chronic pain or medically unexplained symptoms, and obtained more neuroimaging and health care after injury compared with those unaffected by somatization. They did not differ in mood or anxiety symptom self-reports.This study identified characteristic differences and similarities in adolescents with and without clinician-identified somatization after a prolonged concussion recovery. These findings have the potential to improve clinical identification of somatization in youths following a concussion and may aid in treatment among this demographic group.

Emotions are at the core of all human experiences, but talking about emotions is challenging, particularly in the context of medical encounters focused on somatic symptoms. Transparent, normalizing, and validating communication about the mind-body connection opens the door for respectful, open dialogue between the family and members of the care team, acknowledging the lived experience that is brought to the table in understanding the problem and co-creating a solution.

Background: Developers of clinical practice guidelines need to take patient values and preferences into consideration when weighing benefits and harms of treatment options for depressive disorder.Purpose: To assess patient values and preferences regarding pharmacologic and nonpharmacologic treatments of depressive disorder.Data Sources: MEDLINE (Ovid) and PsycINFO (EBSCO) were searched for eligible studies published from 1 January 2014 to 30 November 2022.Study Selection: Pairs of reviewers independently screened 30% of search results. The remaining 70% of the abstracts were screened by single reviewers; excluded abstracts were checked by a second reviewer. Pairs of reviewers independently screened full texts.Data Extraction: One reviewer extracted data and assessed the certainty of evidence, and a second reviewer checked for completeness and accuracy. Two reviewers independently assessed risk of bias.Data Synthesis: The review included 11 studies: 4 randomized controlled trials, 5 cross-sectional studies, and 2 qualitative studies. In 1 randomized controlled trial, participants reported at the start of therapy that they expected supportive-expressive psychotherapy and antidepressants to yield similar improvements. A cross-sectional study reported that non-Hispanic White participants and men generally preferred antidepressants over talk therapy, whereas Hispanic and non-Hispanic Black participants and women generally did not have a preference. Another cross-sectional study reported that the most important nonserious adverse events for patients treated with antidepressants were insomnia, anxiety, fatigue, weight gain, agitation, and sexual dysfunction. For other comparisons and outcomes, no conclusions could be drawn because of the insufficient certainty of evidence.Limitations: The main limitation of this review is the low or insufficient certainty of evidence for most outcomes. No evidence was available on second-step depression treatment or differences in values and preferences based on gender, race/ethnicity, age, and depression severity.Conclusion: Low-certainty evidence suggests that there may be some differences in preferences for talk therapy or pharmacologic treatment of depressive disorders based on gender or race/ethnicity. In addition, low-certainty evidence suggests that insomnia, anxiety, fatigue, weight gain, agitation, and sexual dysfunction may be the most important nonserious adverse events for patients treated with antidepressants. Evidence is lacking or insufficient to draw any further conclusions about patients' weighing or valuation of the benefits and harms of depression treatments.

Background The COVID-19 pandemic led to rapid changes in clinical service delivery across hospital systems nationally. Local realities and resources were key driving factors impacting workflow changes, including for pediatric consultation-liaison psychiatry service (PCLPS) providers. Objective This study aims to describe the early changes implemented by 22 PCLPSs from the United States and Canada during the COVID-19 pandemic. Understanding similarities and differences in adaptations made to PCLPS care delivery can inform best practices and future models of care. Methods A 20-point survey relating to PCLPS changes during the COVID-19 pandemic was sent to professional listservs. Baseline hospital demographics, hospital and PCLPS workflow changes, and PCLPS experience were collected from March 20 to April 28, 2020, and from August 18 to September 10, 2020. Qualitative data were collected from responding sites. An exploratory thematic analysis approach was used to analyze the qualitative data that were not dependent on predetermined coding themes. Descriptive statistics were calculated using Microsoft Excel. Results Twenty-two academic hospitals in the United States and Canada responded to the survey, with an average of 303 beds/hospital. Most respondents (18/22) were children's hospitals. Despite differences in regional impact of COVID-19 and resource availability, there was significant overlap in respondent experiences. Restricted visitation to one caregiver, use of virtual rounding, ongoing trainee involvement, and an overall low number of COVID-positive pediatric patients were common. While there was variability in PCLPS care delivery occurring virtually versus in person, all respondents maintained some level of on-site presence. Technological limitations and pediatric provider preference led to increased on-site presence. Conclusions To our knowledge, this is the first multicenter study exploring pandemic-related PCLPS changes in North America. Findings of this study demonstrate that PCLPSs rapidly adapted to COVID-19 realities. Common themes emerged that may serve as a model for future practice. However, important gaps in understanding their effectiveness and acceptability need to be addressed. This multisite survey highlights the importance of establishing consensus through national professional organizations to inform provider and hospital practices.

Background Dyspnea is a common and often debilitating symptom with a complex diagnostic work-up. Purpose To evaluate the benefits, harms, and diagnostic test accuracy of point-of-care ultrasonography (POCUS) in patients with acute dyspnea. (PROSPERO: CRD42019126419). Data sources Searches of multiple electronic databases without language limitations (January 2004 to August 2020) and reference lists of pertinent articles and reviews. Study selection Five randomized controlled trials (RCTs) and 44 prospective cohort-type studies in patients with acute dyspnea evaluated POCUS as a diagnostic tool to determine the underlying cause of dyspnea. Two investigators independently screened the literature for inclusion. Data extraction Data abstraction by a single investigator was confirmed by a second investigator; 2 investigators independently rated risk of bias and determined certainty of evidence. Data synthesis Point-of-care ultrasonography, when added to a standard diagnostic pathway, led to statistically significantly more correct diagnoses in patients with dyspnea than the standard diagnostic pathway alone. In-hospital mortality and length of hospital stay did not differ significantly between patients who did or did not receive POCUS in addition to standard diagnostic tests. Finally, POCUS consistently improved the sensitivities of standard diagnostic pathways to detect congestive heart failure, pneumonia, pulmonary embolism, pleural effusion, or pneumothorax; specificities increased in most but not all studies. Limitations Most studies assessed diagnostic test accuracy, which has limited utility for clinical decision making. Studies rarely reported on the proportion of indeterminate sonography results, and no evidence is available on adverse health outcomes of false-positive or false-negative POCUS results. Conclusion Point-of-care ultrasonography can improve the correctness of diagnosis in patients with acute dyspnea. Primary funding source American College of Physicians.

Objective: To evaluate clinical utility and feasibility of universal somatization screening in the pediatric emergency department (ED) using a standardized approach of (1) identifying potential somatizing symptoms within the ED, (2) introducing these patients and their caregivers to the concept of the ‘mind-body connection’, (3) corroborating the likelihood of a somatization diagnosis via brief psychiatric assessment, and (4) inviting families to a psychoeducational follow-up session. Methods: We conducted a cross-sectional study to carry out this approach with families visiting a pediatric ED. Our primary outcome of screening utility was measured as the proportion of youth who screened positive for somatization by the ED clinician. Our secondary outcome of screening feasibility was measured as the proportion of patients with positives who (1) agreed to meet with the study psychiatrist, (2) consented to an ED psychiatric assessment, (3) were assessed by the study psychiatrist as likely experiencing somatization, and (4) were invited for follow-up and attended. Results: Of the 344 screened patients, 27 (7.8%) screened positive for somatization. Of these, 25 (92.6%) families verbally consented to meet the study psychiatrist to learn about the mind-body connection, and 21 (77.8%) consented to further psychiatric assessment. Upon assessment, the somatization likelihood was supported for all 21 youth. Twenty families were invited to follow-up and ultimately two (10%) attended. Conclusions: Somatization can be detected through ED-based universal screening. Few families attended psychoeducational follow-up. Further research is needed to determine appropriate ED-initiated pediatric somatization intervention.

ObjectivesPain and other physical symptoms commonly co-occur in childhood. There is debate about the relevance of somatization in understanding pain. The present review critically appraised and synthesized the extant literature on the relationship between pediatric pain and somatization.MethodsA systematic review (PROSPERO registration #95956) was conducted in Medline, PsycINFO, EMBASE, and CINAHL using search terms related to pain and somatization in children and adolescents. A total of 156 articles were eligible for inclusion in the review. For studies that measured somatization using a symptom questionnaire, descriptions of “somatization” were extracted. Data regarding the relationship between pain and somatization were extracted for studies measuring somatization using a diagnostic category (e.g., Somatic Symptom and Related Disorders [SSRDs]).ResultsWhile many studies using somatic symptom questionnaires described somatization as having a psychological component, this was not always captured in measurement tools. Pain was reported as a common symptom in patients with an SSRD diagnosis, though rates varied depending on the specific diagnosis and pain location. Rates of SSRD diagnoses among pain patients were less frequent than rates of pain amongst SSRD patients.ConclusionsSSRDs and pain commonly co-occur, though rates differ depending on diagnosis and pain location. Understanding the relationship between pain and somatization is complicated by the discrepancy between how somatization is defined and measured in questionnaire studies. A comprehensive and measurable definition of somatization is needed so researchers can better identify the shared and unique contributions of pain and somatization in pediatric populations.

Objective To summarize the evidence on the effectiveness of soil remediation to prevent or reduce lead exposure. Methods We systematically searched MEDLINE, the Agricultural & Environmental Science Database, Web of Science, and Scopus from 1980 to February 15, 2021. We also performed reference list checking, hand-searched websites, and contacted experts. Eligible studies evaluated the effect of soil remediation to prevent or reduce lead exposure in humans of any age. We screened all records dually; one investigator performed the data extraction; a second checked for completeness and accuracy. Two investigators independently rated the risk of bias of included studies and graded the certainty of evidence. We synthesized findings narratively. Results We identified 6614 potentially relevant publications, all focused on children, of which five studies (six records) fulfilled our prespecified inclusion criteria. The number of evaluated participants ranged from 31 to 1425, with follow-up periods of 11 months to one year. The primary soil remediation method was the replacement of the upper layer with clean soil. Outcomes were limited to blood lead levels (BLL), dust lead levels, and soil lead levels. The largest study, a controlled before– after study (n = 1425) reported favorable effects of soil remediation compared to no intervention. This finding was consistent with results from two cross-sectional studies and one uncontrolled before–after study. One year post-remediation, the mean reduction in BLL was 2.1 μg/dL (p, Graphical abstract Unlabelled Image, Highlights • Lead exposure from contaminated soil is an important public health issue, concerning both children and adults. • Soil remediation alone or in combination with other interventions appears to reduce the blood lead levels in children. • The effect of soil remediation on health outcomes, in high lead exposure areas or in low/middle-income countries is unclear.

Background Seasonal affective disorder (SAD) is a seasonal pattern of recurrent depressive episodes that is often treated with second-generation antidepressants (SGAs), light therapy, or psychotherapy. Objectives To assess the efficacy and safety of second-generation antidepressants (SGAs) for the treatment of seasonal affective disorder (SAD) in adults in comparison with placebo, light therapy, other SGAs, or psychotherapy. Search methods This is an update of an earlier review first published in 2011. We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 1) in the Cochrane Library (all years), Ovid MEDLINE, Embase, and PsycINFO (2011 to January 2020), together with the Cochrane Common Mental Disorders Controlled Trials Register (CCMDCTR) (all available years), for reports of randomised controlled trials (RCTs). We hand searched the reference lists of all included studies and other systematic reviews. We searched ClinicalTrials.gov for unpublished/ongoing trials. We ran a separate update search for reports of adverse events in the Ovid databases. SELECTION CRITERIA: For efficacy we included RCTs of SGAs compared with other SGAs, placebo, light therapy, or psychotherapy in adult participants with SAD. For adverse events we also included non-randomised studies. Data collection and analysis Two review authors independently screened abstracts and full-text publications against the inclusion criteria. Data extraction and 'Risk of bias' assessment were conducted individually. We pooled data for meta-analysis where the participant groups were similar, and the studies assessed the same treatments with the same comparator and had similar definitions of outcome measures over a similar duration of treatment. Main results In this update we identified no new RCT on the effectiveness of SGAs in SAD patients. We included 2 additional single-arm observational studies that reported on adverse events of SGAs. For efficacy we included three RCTs of between five and eight weeks' duration with a total of 204 participants. For adverse events we included two RCTs and five observational (non-randomised) studies of five to eight weeks' duration with a total of 249 participants. All participants met the DSM (Diagnostic and Statistical Manual of Mental Disorders) criteria for SAD. The average age ranged from 34 to 42 years, and the majority of participants were female (66% to 100%). Results from one trial with 68 participants showed that fluoxetine (20/36) was numerically superior to placebo (11/32) in achieving clinical response; however, the confidence interval (CI) included both a potential benefit as well as no benefit of fluoxetine (risk ratio (RR) 1.62, 95% CI 0.92 to 2.83, very low-certainty evidence). The number of adverse events was similar in both groups (very low-certainty evidence). Two trials involving a total of 136 participants compared fluoxetine versus light therapy. Meta-analysis showed fluoxetine and light therapy to be approximately equal in treating seasonal depression: RR of response 0.98 (95% CI 0.77 to 1.24, low-certainty evidence), RR of remission 0.81 (95% CI 0.39 to 1.71, very low-certainty evidence). The number of adverse events was similar in both groups (low-certainty evidence). We did not identify any eligible study comparing SGA with another SGA or with psychotherapy. Two RCTs and five non-randomised studies reported adverse event data on a total of 249 participants who received bupropion, fluoxetine, escitalopram, duloxetine, nefazodone, reboxetine, light therapy, or placebo. We were only able to obtain crude rates of adverse events, therefore caution is advised regarding interpretation of this information. Between 0% and 100% of participants who received an SGA suffered an adverse event, and between 0% and 25% of participants withdrew from the study due to adverse events. Authors' conclusions Evidence for the effectiveness of SGAs is limited to one small trial of fluoxetine compared with placebo showing a non-significant effect in favour of fluoxetine, and two small trials comparing fluoxetine against light therapy suggesting equivalence between the two interventions. The lack of available evidence precluded us from drawing any overall conclusions on the use of SGAs for SAD. Further, larger RCTs are required to expand and strengthen the evidence base on this topic, and should also include comparisons with psychotherapy and other SGAs. Data on adverse events were sparse, and a comparative analysis was not possible. The data we obtained on adverse events is therefore not robust, and our confidence in the data is limited. Overall, up to 25% of participants treated with SGAs for SAD withdrew from the study early due to adverse events.

Background Coronavirus disease 2019 (COVID‐19) is a rapidly emerging disease classified as a pandemic by the World Health Organization (WHO). To support the WHO with their recommendations on quarantine, we conducted a rapid review on the effectiveness of quarantine during severe coronavirus outbreaks. Objectives To assess the effects of quarantine (alone or in combination with other measures) of individuals who had contact with confirmed or suspected cases of COVID‐19, who travelled from countries with a declared outbreak, or who live in regions with high disease transmission. Search methods An information specialist searched the Cochrane COVID‐19 Study Register, and updated the search in PubMed, Ovid MEDLINE, WHO Global Index Medicus, Embase, and CINAHL on 23 June 2020. Selection criteria Cohort studies, case‐control studies, time series, interrupted time series, case series, and mathematical modelling studies that assessed the effect of any type of quarantine to control COVID‐19. We also included studies on SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome) as indirect evidence for the current coronavirus outbreak. Data collection and analysis Two review authors independently screened abstracts and titles in duplicate. Two review authors then independently screened all potentially relevant full‐text publications. One review author extracted data, assessed the risk of bias and assessed the certainty of evidence with GRADE and a second review author checked the assessment. We used three different tools to assess risk of bias, depending on the study design: ROBINS‐I for non‐randomised studies of interventions, a tool provided by Cochrane Childhood Cancer for non‐randomised, non‐controlled studies, and recommendations from the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) for modelling studies. We rated the certainty of evidence for the four primary outcomes: incidence, onward transmission, mortality, and costs. Main results We included 51 studies; 4 observational studies and 28 modelling studies on COVID‐19, one observational and one modelling study on MERS, three observational and 11 modelling studies on SARS, and three modelling studies on SARS and other infectious diseases. Because of the diverse methods of measurement and analysis across the outcomes of interest, we could not conduct a meta‐analysis and undertook a narrative synthesis. We judged risk of bias to be moderate for 2/3 non‐randomized studies of interventions (NRSIs) and serious for 1/3 NRSI. We rated risk of bias moderate for 4/5 non‐controlled cohort studies, and serious for 1/5. We rated modelling studies as having no concerns for 13 studies, moderate concerns for 17 studies and major concerns for 13 studies. Quarantine for individuals who were in contact with a confirmed/suspected COVID‐19 case in comparison to no quarantine Modelling studies consistently reported a benefit of the simulated quarantine measures, for example, quarantine of people exposed to confirmed or suspected cases may have averted 44% to 96% of incident cases and 31% to 76% of deaths compared to no measures based on different scenarios (incident cases: 6 modelling studies on COVID‐19, 1 on SARS; mortality: 2 modelling studies on COVID‐19, 1 on SARS, low‐certainty evidence). Studies also indicated that there may be a reduction in the basic reproduction number ranging from 37% to 88% due to the implementation of quarantine (5 modelling studies on COVID‐19, low‐certainty evidence). Very low‐certainty evidence suggests that the earlier quarantine measures are implemented, the greater the cost savings may be (2 modelling studies on SARS). Quarantine in combination with other measures to contain COVID‐19 in comparison to other measures without quarantine or no measures When the models combined quarantine with other prevention and control measures, such as school closures, travel restrictions and social distancing, the models demonstrated that there may be a larger effect on the reduction of new cases, transmissions and deaths than measures without quarantine or no interventions (incident cases: 9 modelling studies on COVID‐19; onward transmission: 5 modelling studies on COVID‐19; mortality: 5 modelling studies on COVID‐19, low‐certainty evidence). Studies on SARS and MERS were consistent with findings from the studies on COVID‐19. Quarantine for individuals travelling from a country with a declared COVID‐19 outbreak compared to no quarantine Very low‐certainty evidence indicated that the effect of quarantine of travellers from a country with a declared outbreak on reducing incidence and deaths may be small for SARS, but might be larger for COVID‐19 (2 observational studies on COVID‐19 and 2 observational studies on SARS). Authors' conclusions The current evidence is limited because most studies on COVID‐19 are mathematical modelling studies that make different assumptions on important model parameters. Findings consistently indicate that quarantine is important in reducing incidence and mortality during the COVID‐19 pandemic, although there is uncertainty over the magnitude of the effect. Early implementation of quarantine and combining quarantine with other public health measures is important to ensure effectiveness. In order to maintain the best possible balance of measures, decision makers must constantly monitor the outbreak and the impact of the measures implemented. This review was originally commissioned by the WHO and supported by Danube‐University‐Krems. The update was self‐initiated by the review authors., Plain language summary Does quarantine, alone or in combination with other public health measures, control coronavirus (COVID‐19)? Background Coronavirus disease 2019 (COVID‐19) is caused by a new virus that has spread quickly throughout the world. Most infected people either experience no symptoms or suffer mild, flu‐like symptoms, but some become seriously ill, and may die. There is no vaccine (a medicine that stops people catching a specific disease) for COVID‐19, so other ways of slowing its spread are needed. One way of controlling the disease is quarantine. This means separating healthy people from other healthy people, who may have the virus after being in close contact with an infected person, or because they have returned from an area with high infection rates. Similar recommendations include isolation (like quarantine, but for people who tested positive for COVID‐19) and physical distancing (people without symptoms keep a distance from each other). What did we want to find out? We wanted to find out whether and how effectively quarantine stops COVID‐19 spreading and if it prevents death. We wanted to know if it was more effective when combined with other measures, and how much it costs. Study characteristics COVID‐19 is spreading rapidly, so we needed to answer these questions as quickly as possible. This meant we shortened some steps of the normal Cochrane Review process. Nevertheless, we are confident that these changes do not affect our overall conclusions. We looked for studies that assessed the effect of any type of quarantine, anywhere, on the spread and severity of COVID‐19. We also looked for studies that assessed quarantine alongside other measures, such as isolation, physical distancing or school closures. COVID‐19 is a new disease, so, to find as much evidence as possible, we also looked for studies on similar viruses, such as SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome). Studies measured the number of COVID‐19, SARS or MERS cases, how many people were infected, how quickly the virus spread, how many people died, and the costs of quarantine. Key results We included 51 studies. Thirty‐two studies focused on COVID‐19, 14 on SARS, three on SARS plus other viruses, and two on MERS. Most studies combined existing data from multiple sources and assumptions to create a model (a simulation) for predicting how events might occur over time, for people in different situations (called modelling studies). Four COVID‐19 studies observed the effects of quarantine (observational studies) on 6064 individuals in China, Greece and Singapore. Twenty‐eight COVID‐19 studies simulated outbreaks in Algeria, China, Canada, Italy, Kazakhstan, Nepal, UK, USA, Singapore, South Korea, on the cruise ship Diamond Princess, and in a general population. Four studies looked back on the effect of quarantine on 178,122 people involved in SARS and MERS outbreaks. The remaining 15 studies modelled SARS and MERS outbreaks. The modelling studies all found that simulated quarantine measures reduce the number of people with COVID‐19 and the number of deaths. With quarantine, estimates showed a minimum reduction in the number of people with COVID‐19 of 44%, and a maximum reduction of 96%. Similarly, with quarantine, estimates of the number of deaths showed a minimum reduction of 31%, and a maximum reduction of 76%. Combining quarantine with other measures, such as closing schools or physical distancing, may be more effective at reducing the spread of COVID‐19 than quarantine alone. The SARS and MERS studies agreed with the studies on COVID‐19. Two SARS modelling studies assessed costs. They found that the costs may be lower when quarantine measures start earlier. Reliability of the evidence We are uncertain about the evidence we found for several reasons. The observational studies on COVID‐19 did not include a comparison group without quarantine. The COVID‐19 studies based their models on limited data and made different assumptions about the virus (e.g. how quickly it would spread). The other studies investigated SARS and MERS so they only provide indirect evidence. Conclusion Despite limited evidence, all the studies found quarantine to be important in reducing the number of people infected and the number of deaths. Results suggest that quarantine was most effective, and cost less, when it started earlier. Combining quarantine with other prevention and control measures may have a greater effect than quarantine alone. This review includes evidence published up to 23 June 2020.

Somatic symptom and related disorders (SSRDs) are commonly encountered in pediatric hospital settings. There is, however, a lack of standardization of care across institutions for youth with these disorders. These patients are diagnostically and psychosocially complex, posing significant challenges for medical and behavioral health care providers. SSRDs are associated with significant health care use, cost to families and hospitals, and risk for iatrogenic interventions and missed diagnoses. With sponsorship from the American Academy of Child and Adolescent Psychiatry and input from multidisciplinary stakeholders, we describe the first attempt to develop a clinical pathway and standardize the care of patients with SSRDs in pediatric hospital settings by a working group of pediatric consultation-liaison psychiatrists from multiple institutions across North America. The authors of the SSRD clinical pathway outline 5 key steps from admission to discharge and include practical, evidence-informed approaches to the assessment and management of children and adolescents who are medically hospitalized with SSRDs.

Background Abdominal pain-related functional gastrointestinal disorders (FGIDs) are among the most common medical problems in paediatric medicine. Frequently, physicians prescribe antidepressants as a second-line treatment for children and adolescents with FGIDs. To date, the evidence on the benefits and harms of antidepressants for the treatment of abdominal pain-related FGIDs has not been assessed systematically. Objectives The primary objectives were to conduct a systematic review to evaluate the efficacy and safety of antidepressants for the treatment of abdominal pain-related FGIDs in children and adolescents. Search methods We searched The Cochrane Library, PubMed, EMBASE, IPA, CINAHL, PsycINFO, ISI Web of Science, Biosis Previews and the International Clinical Trials Registry Platform of the World Health Organization with appropriate filters (from inception to January 31, 2011). Selection criteria For efficacy we included double-blind, randomised controlled trials (RCTs) of antidepressants for treatment of abdominal pain-related FGIDs in children and adolescents 18 years or younger. Open-label and uncontrolled experimental studies, as well as observational studies were eligible for the assessment of harms. The minimum study duration was 4 weeks. The minimum study size was 30 participants. Data collection and analysis Two authors independently assessed all abstracts and full text articles, and rated the risk of bias for included studies. Data were extracted independently by one author and checked for accuracy by another author. Data were analysed using RevMan 5. Main results Two RCTs (123 participants), both using amitriptyline, met the pre-specified inclusion criteria. These studies provided mixed findings on the efficacy of amitriptyline for the treatment of abdominal pain-related FGIDs. The larger, publicly-funded study reported no statistically significant difference in efficacy between amitriptyline and placebo in 90 children and adolescents with FGIDs after 4 weeks of treatment. On intention-to-treat (ITT)- analysis, 59% of the children reported feeling better in the amitriptyline group compared with 53% in the placebo group (RR 1.12; 95% CI: 0.77 to 1.63; P = 0.54). The risk of bias for this study was rated as low. The second RCT enrolled 33 adolescents with irritable bowel syndrome. Patients receiving amitriptyline experienced greater improvements in the primary outcome, overall quality of life, at weeks 6, 10, and 13 compared with those on placebo (P= 0.019, 0.004, and 0.013, respectively). No effect estimates were calculated for the quality of life outcome because mean quality of life scores and standard deviations were not reported. For most secondary outcomes no statistically significant differences between amitriptyline and placebo could be detected. The risk of bias for this study was rated as unclear for most items. However, it was rated as high for other bias due to multiple testing. The results of this study should be interpreted with caution due to the small number of patients and multiple testing. The larger study reported mild adverse events including fatigue, rash and headache and dizziness. On ITT analysis, 4% of the amitriptyline group experienced at least one adverse event compared to 2% of the placebo group. There was no statistically significant difference in the proportion of patients who experienced at least one adverse event (RR 1.91; 95% CI 0.18 to 20.35; P = 0.59). The smaller study reported no adverse events. The methods of adverse effects assessment was poorly reported in both studies and no clear conclusions on the risks of harms of amitriptyline can be drawn. Authors' conclusions Clinicians must be aware that for the majority of antidepressant medications no evidence exists that supports their use for the treatment of abdominal pain-related FGIDs in children and adolescents. The existing randomised controlled evidence is limited to studies on amitriptyline and revealed no statistically significant differences between amitriptyline and placebo for most efficacy outcomes. Amitriptyline does not appear to provide any benefit for the treatment of FGIDs in children and adolescents. Studies in children with depressive disorders have shown that antidepressants can lead to substantial, sometimes life-threatening adverse effects. Until better evidence evolves, clinicians should weigh the potential benefits of antidepressant treatment against known risks of antidepressants in paediatric patients. Plain Language Summary Antidepressants for the treatment of children and adolescents with functional abdominal pain Abdominal pain-related functional gastrointestinal disorders (FGIDs) are common in childhood and adolescence. In most cases no medical reason for the pain can be found. Various drug treatment approaches for the different types of abdominal pain-related FGIDs exist. These drug treatments include: prokinetics and antisecretory agents for functional dyspepsia; pizotifen, propranolol, cyproheptadine or sumatriptane for abdominal migraine; and antispasmodic and antidiarrhoeal regimen for irritable bowel syndrome. Antidepressants have been shown to be effective in some studies of adults with functional gastrointestinal disorders. As a result young patients with similar complaints are sometimes treated with antidepressants. The purpose of this review was to examine the evidence assessing the advantages and disadvantages of such an approach. Only two studies met the inclusion criteria. Both of these studies were randomised controlled trials and assessed the effectiveness and safety of amitriptyline in children with FGIDs. Amitriptyline is a first generation antidepressant (tricyclic antidepressant). Amitriptyline is no longer an agent of first choice for the treatment of depressive disorders because of potentially serious side effects including overdose. Amitriptyline has not been approved for the treatment of functional abdominal pain in children or adolescents. The larger study (n = 90) showed no difference in the proportion of patients feeling better between the treatment - and the placebo (sugar pill) groups. Side effects were mild and included fatigue, rash and headache and dizziness.The authors of the other, much smaller study (n = 33) reported a significant improvement in overall quality of life and a reduction in pain for specific areas of the abdomen and certain follow up times. However, the results of this study should be interpreted with caution due to poor methodological quality and the small number of patients enrolled. Amitriptyline does not appear to provide any benefit for the treatment of FGIDs in children and adolescents. At present, the evidence for the treatment of children and adolescents with abdominal pain-related diseases with antidepressants does not support the use of antidepressant agents in this group of patients. We suggest considering alternative treatments that are supported by stronger evidence. There is need for larger, well-conducted trials with adequate patient relevant outcomes such as quality of life and pain relief to provide more information regarding this common condition.

The National Lung Screening Trial (NLST) is a randomized multicenter study comparing low-dose helical computed tomography (CT) with chest radiography in the screening of older current and former heavy smokers for early detection of lung cancer, which is the leading cause of cancer-related death in the United States. Five-year survival rates approach 70% with surgical resection of stage IA disease; however, more than 75% of individuals have incurable locally advanced or metastatic disease, the latter having a 5-year survival of less than 5%. It is plausible that treatment should be more effective and the likelihood of death decreased if asymptomatic lung cancer is detected through screening early enough in its preclinical phase. For these reasons, there is intense interest and intuitive appeal in lung cancer screening with low-dose CT. The use of survival as the determinant of screening effectiveness is, however, confounded by the well-described biases of lead time, length, and overdiagnosis. Despite previous attempts, no test has been shown to reduce lung cancer mortality, an endpoint that circumvents screening biases and provides a definitive measure of benefit when assessed in a randomized controlled trial that enables comparison of mortality rates between screened individuals and a control group that does not undergo the screening intervention of interest. The NLST is such a trial. The rationale for and design of the NLST are presented.

Background: To minimise retrieval bias, manual literature searches are a key part of the search process of any systematic review. Considering the need to have accurate information, valid results of the manual literature search are essential to ensure scientific standards; likewise efficient approaches that minimise the amount of personnel time required to conduct a manual literature search are of great interest. Objective: The objective of this project was to determine the validity and efficiency of a new manual search method that utilises the scopus™ database. Methods: We used the traditional manual search approach as the gold standard to determine the validity and efficiency of the proposed scopus method. Outcome measures included completeness of article detection and personnel time involved. Using both methods independently, we compared the results based on accuracy of the results, validity and time spent conducting the search, efficiency. Results: Regarding accuracy, the scopus method identified the same studies as the traditional approach indicating its validity. In terms of efficiency, using scopus led to a time saving of 62.5% compared with the traditional approach (3 h versus 8 h). Conclusions: The scopus method can significantly improve the efficiency of manual searches and thus of systematic reviews.

PurposeThe aim of this study is to benchmark the impact of the Crisis Resolution Home Treatment Team (CRHTT) on the elderly admission rate as well as the duration of admissionDesign/methodology/approachData were collected for a period of one year before (August 2006 to July 2007) and after (August 2007 to July 2008) the extension of CRHTT input into elderly services.FindingsThere was an overall reduction in the number of admissions after CRHTT got involved with the elderly.Research limitations/implicationsThis study only considered individuals with functional disorders who were admitted to the in‐patient services or referred to the CRHTT. However, these only make up a proportion of the elderly in‐patients.Practical implicationsThe study will help identify areas which may further help in reducing the admissions.Originality/valueThis is an original study that acknowledges the reduction in admission following the introduction of a crisis resolution home treatment team in Trafford, Manchester.

Background Screening with mammography has the ability to detect breast cancer at an early stage but misses some cancers. Supporters of adjunct ultrasonography to the screening regimen argue that it might be a safe and inexpensive approach to reduce the false-negative rates of screening. Critics are concerned that adjunct ultrasonography will also increase the rate of false-positive findings and can lead to unnecessary biopsies and treatments in women at average risk. Aims The purpose of this review was to systematically assess the comparative benefits and harms of mammography with adjunct breast ultrasonography and mammography only in breast cancer screening. Methods We searched multiple electronic databases and the Cochrane Breast Cancer Group's Specialised Register (from 1995 to February 2012). To detect ongoing or unpublished studies, we searched trial registries and multiple sources of grey literature. Two researchers independently reviewed all abstracts and full-text articles against pre-defined eligibility criteria. We dually rated the risk of bias of studies and the strength of evidence based on established guidance. Results We did not detect any controlled studies that provide evidence for (or against) the use of adjunct ultrasonography for screening in women at average risk for breast cancer. Extrapolations of results from women at elevated risk for breast cancer indicate that the false-positive rates in women at average risk who were recalled because of positive ultrasonographies will exceed 98%. In women with dense or very dense breast tissue, the evidence regarding the use of adjunct ultrasonography is not conclusive. Conclusions No methodologically sound evidence is available justifying the routine use of ultrasonography as an adjunct screening tool in women at average risk for breast cancer. Implications for practice Clinicians should not use ultrasonography as a screening tool for breast cancer screening on a routine basis. The use should be limited to women with dense breasts for whom the accuracy of mammography is low, or for diagnostic purposes.

Background Breast cancer is the most common malignant disease diagnosed in women worldwide. Screening with mammography has the ability to detect breast cancer at an early stage. The diagnostic accuracy of mammography screening largely depends on the radiographic density of the imaged breasts. In radiographically dense breasts, non-calcified breast cancers are more likely to be missed than in fatty breasts. As a consequence, some cancers are not detected by mammography screening. Supporters of adjunct ultrasonography to the screening regimen for breast cancer argue that it might be a safe and inexpensive approach to reduce the false negative rates of the screening process. Critics, however, are concerned that performing supplemental ultrasonography on women at average risk will also increase the rate of false positive findings and can lead to unnecessary biopsies and treatments. Objectives To assess the comparative effectiveness and safety of mammography in combination with breast ultrasonography versus mammography for breast cancer screening for women at average risk of breast cancer. Search methods We searched the Cochrane Breast Cancer Group's Specialised Register, MEDLINE (via OvidSP) and EMBASE up until February 2012. To detect ongoing or unpublished studies, we searched the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), ClinicalTrials.gov and the National Cancer Institute's clinical trial database until June 2012. In addition, we conducted grey literature searches using the following sources: OpenGrey; National Institute of Health RePORTER; Health Services Research Projects in Progress (HSRPROJ); Hayes, Inc. Health Technology Assessment; The New York Academy of Medicine’s Grey Literature Index and Conference Papers Index. Selection criteria For efficacy, we considered randomised controlled trials (RCTs), with either individual or cluster randomisation, and prospective, controlled non-randomised studies with a low risk of bias and a sample size of at least 500 participants. In addition to studies eligible for efficacy, we considered any controlled, non-randomised study with a low risk of bias and a study size of at least 500 participants for the assessment of harms. Our population of interest were women between the ages of 40 and 75 years who were at average risk for breast cancer. Data collection and analysis Two review authors screened abstracts and full-text publications against the inclusion criteria. None of the studies met our inclusion criteria. Main results Our review did not detect any controlled studies on the use of adjunct ultrasonography for screening in women at average risk for breast cancer. One ongoing randomised controlled trial was identified (J-START, Japan). Authors' conclusions Presently, there is no methodologically sound evidence available justifying the routine use of ultrasonography as an adjunct screening tool in women at average risk for breast cancer.

BACKGROUND: Seasonal affective disorder (SAD) is a seasonal pattern of recurrent depressive episodes that is often treated with second‐generation antidepressants (SGAs), light therapy, or psychotherapy. OBJECTIVES: To assess the efficacy and safety of second‐generation antidepressants (SGAs) for the treatment of seasonal affective disorder (SAD) in adults in comparison with placebo, light therapy, other SGAs, or psychotherapy. SEARCH METHODS: This is an update of an earlier review first published in 2011. We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 1) in the Cochrane Library (all years), Ovid MEDLINE, Embase, and PsycINFO (2011 to January 2020), together with the Cochrane Common Mental Disorders Controlled Trials Register (CCMDCTR) (all available years), for reports of randomised controlled trials (RCTs). We hand searched the reference lists of all included studies and other systematic reviews. We searched ClinicalTrials.gov for unpublished/ongoing trials. We ran a separate update search for reports of adverse events in the Ovid databases. SELECTION CRITERIA: For efficacy we included RCTs of SGAs compared with other SGAs, placebo, light therapy, or psychotherapy in adult participants with SAD. For adverse events we also included non‐randomised studies. DATA COLLECTION AND ANALYSIS: Two review authors independently screened abstracts and full‐text publications against the inclusion criteria. Data extraction and 'Risk of bias' assessment were conducted individually. We pooled data for meta‐analysis where the participant groups were similar, and the studies assessed the same treatments with the same comparator and had similar definitions of outcome measures over a similar duration of treatment. MAIN RESULTS: In this update we identified no new RCT on the effectiveness of SGAs in SAD patients. We included 2 additional single‐arm observational studies that reported on adverse events of SGAs. For efficacy we included three RCTs of between five and eight weeks' duration with a total of 204 participants. For adverse events we included two RCTs and five observational (non‐randomised) studies of five to eight weeks' duration with a total of 249 participants. All participants met the DSM (Diagnostic and Statistical Manual of Mental Disorders) criteria for SAD. The average age ranged from 34 to 42 years, and the majority of participants were female (66% to 100%). Results from one trial with 68 participants showed that fluoxetine (20/36) was numerically superior to placebo (11/32) in achieving clinical response; however, the confidence interval (CI) included both a potential benefit as well as no benefit of fluoxetine (risk ratio (RR) 1.62, 95% CI 0.92 to 2.83, very low‐certainty evidence). The number of adverse events was similar in both groups (very low‐certainty evidence). Two trials involving a total of 136 participants compared fluoxetine versus light therapy. Meta‐analysis showed fluoxetine and light therapy to be approximately equal in treating seasonal depression: RR of response 0.98 (95% CI 0.77 to 1.24, low‐certainty evidence), RR of remission 0.81 (95% CI 0.39 to 1.71, very low‐certainty evidence). The number of adverse events was similar in both groups (low‐certainty evidence). We did not identify any eligible study comparing SGA with another SGA or with psychotherapy. Two RCTs and five non‐randomised studies reported adverse event data on a total of 249 participants who received bupropion, fluoxetine, escitalopram, duloxetine, nefazodone, reboxetine, light therapy, or placebo. We were only able to obtain crude rates of adverse events, therefore caution is advised regarding interpretation of this information. Between 0% and 100% of participants who received an SGA suffered an adverse event, and between 0% and 25% of participants withdrew from the study due to adverse events. AUTHORS' CONCLUSIONS: Evidence for the effectiveness of SGAs is limited to one small trial of fluoxetine compared with placebo showing a non‐significant effect in favour of fluoxetine, and two small trials comparing fluoxetine against light therapy suggesting equivalence between the two interventions. The lack of available evidence precluded us from drawing any overall conclusions on the use of SGAs for SAD. Further, larger RCTs are required to expand and strengthen the evidence base on this topic, and should also include comparisons with psychotherapy and other SGAs. Data on adverse events were sparse, and a comparative analysis was not possible. The data we obtained on adverse events is therefore not robust, and our confidence in the data is limited. Overall, up to 25% of participants treated with SGAs for SAD withdrew from the study early due to adverse events.

Background Abdominal pain-related functional gastrointestinal disorders (FGIDs) are among the most common medical problems in paediatric medicine. Frequently, physicians prescribe antidepressants as a second-line treatment for children and adolescents with FGIDs. To date, the evidence on the benefits and harms of antidepressants for the treatment of abdominal pain-related FGIDs has not been assessed systematically. Objectives The primary objectives were to conduct a systematic review to evaluate the efficacy and safety of antidepressants for the treatment of abdominal pain-related FGIDs in children and adolescents. Search methods We searched The Cochrane Library, PubMed, EMBASE, IPA, CINAHL, PsycINFO, ISI Web of Science, Biosis Previews and the International Clinical Trials Registry Platform of the World Health Organization with appropriate filters (from inception to January 31, 2011). Selection criteria For efficacy we included double-blind, randomised controlled trials (RCTs) of antidepressants for treatment of abdominal pain-related FGIDs in children and adolescents 18 years or younger. Open-label and uncontrolled experimental studies, as well as observational studies were eligible for the assessment of harms. The minimum study duration was 4 weeks. The minimum study size was 30 participants. Data collection and analysis Two authors independently assessed all abstracts and full text articles, and rated the risk of bias for included studies. Data were extracted independently by one author and checked for accuracy by another author. Data were analysed using RevMan 5. Main results Two RCTs (123 participants), both using amitriptyline, met the pre-specified inclusion criteria. These studies provided mixed findings on the efficacy of amitriptyline for the treatment of abdominal pain-related FGIDs. The larger, publicly-funded study reported no statistically significant difference in efficacy between amitriptyline and placebo in 90 children and adolescents with FGIDs after 4 weeks of treatment. On intention-to-treat (ITT)- analysis, 59% of the children reported feeling better in the amitriptyline group compared with 53% in the placebo group (RR 1.12; 95% CI: 0.77 to 1.63; P = 0.54). The risk of bias for this study was rated as low. The second RCT enrolled 33 adolescents with irritable bowel syndrome. Patients receiving amitriptyline experienced greater improvements in the primary outcome, overall quality of life, at weeks 6, 10, and 13 compared with those on placebo (P= 0.019, 0.004, and 0.013, respectively). No effect estimates were calculated for the quality of life outcome because mean quality of life scores and standard deviations were not reported. For most secondary outcomes no statistically significant differences between amitriptyline and placebo could be detected. The risk of bias for this study was rated as unclear for most items. However, it was rated as high for other bias due to multiple testing. The results of this study should be interpreted with caution due to the small number of patients and multiple testing. The larger study reported mild adverse events including fatigue, rash and headache and dizziness. On ITT analysis, 4% of the amitriptyline group experienced at least one adverse event compared to 2% of the placebo group. There was no statistically significant difference in the proportion of patients who experienced at least one adverse event (RR 1.91; 95% CI 0.18 to 20.35; P = 0.59). The smaller study reported no adverse events. The methods of adverse effects assessment was poorly reported in both studies and no clear conclusions on the risks of harms of amitriptyline can be drawn. Authors' conclusions Clinicians must be aware that for the majority of antidepressant medications no evidence exists that supports their use for the treatment of abdominal pain-related FGIDs in children and adolescents. The existing randomised controlled evidence is limited to studies on amitriptyline and revealed no statistically significant differences between amitriptyline and placebo for most efficacy outcomes. Amitriptyline does not appear to provide any benefit for the treatment of FGIDs in children and adolescents. Studies in children with depressive disorders have shown that antidepressants can lead to substantial, sometimes life-threatening adverse effects. Until better evidence evolves, clinicians should weigh the potential benefits of antidepressant treatment against known risks of antidepressants in paediatric patients.

Amyloidosis is an idiopathic disease that is characterized by the extracellular deposition of fibrillar proteins. The disease can be categorized as primary or secondary where deposits occur in conjunction with chronic diseases such as rheumatoid arthritis or tuberculosis. The deposits can be localized or systemically distributed. It can mimic, and also be associated with underlying malignancy. Primary amyloidosis is a rare cause of a nasopharyngeal lesion, and less so of a secondary middle ear effusion. Its association with underlying chronic and malignant disease must not be over-looked if serious complications are to be avoided. It is, therefore, important to consider this as a differential diagnosis in such patients.

Being male or female is an important determinant of risks for certain diseases, patterns of illness and life expectancy. Although differences in risks for and prognoses of several diseases have been well documented, sex-based differences in responses to pharmaceutical treatments and accompanying risks of adverse events are less clear. The objective of this umbrella review was to determine whether clinically relevant differences in efficacy and safety of commonly prescribed medications exist between men and women. We retrieved all available systematic reviews of the Oregon Drug Effectiveness Review Project published before January 2010. Two persons independently reviewed each report to identify relevant studies. We dually abstracted data from the original publications into standardized forms. We synthesized the available evidence for each drug class and rated its quality applying the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Findings, based on 59 studies and data of more than 250,000 patients suggested that for the majority of drugs no substantial differences in efficacy and safety exist between men and women. Some clinically important exceptions, however, were apparent: women experienced substantially lower response rates with newer antiemetics than men (45% vs. 58%; relative risk 1.49, 95% confidence interval 1.35-1.64); men had higher rates of sexual dysfunction than women while on paroxetine for major depressive disorder; women discontinued lovastatin more frequently than men because of adverse events. Overall, for the majority of drugs sex does not appear to be a factor that has to be taken into consideration when choosing a drug treatment. The available body of evidence, however, was limited in quality and quantity, confining the range and certainty of our conclusions.

Background Bach Flower Remedies are thought to help balance emotional state and are commonly recommended by practitioners for psychological problems and pain. We assessed whether Bach Flower Remedies (BFRs) are safe and efficacious for these indications by performing a systematic review of the literature. Methods We searched MEDLINE®, Embase, AMED, and the Cochrane Library from inception until June 2008 and performed a hand-search of references from relevant key articles. For efficacy, we included all prospective studies with a control group. For safety, we also included retrospective, observational studies with more than 30 subjects. Two authors abstracted data and determined risk of bias using a recognised rating system of trial quality. Results Four randomised controlled trials (RCTs) and two additional retrospective, observational studies were identified and included in the review. Three RCTs of BFRs for students with examination anxiety, and one RCT of BFRs for children with attention-deficit hyperactivity disorder (ADHD) showed no overall benefit in comparison to placebo. Due to the number and quality of the studies the strength of the evidence is low or very low. We did not find any controlled prospective studies regarding the efficacy of BFRs for pain. Only four of the six studies included for safety explicitly reported adverse events. Conclusion Most of the available evidence regarding the efficacy and safety of BFRs has a high risk of bias. We conclude that, based on the reported adverse events in these six trials, BFRs are probably safe. Few controlled prospective trials of BFRs for psychological problems and pain exist. Our analysis of the four controlled trials of BFRs for examination anxiety and ADHD indicates that there is no evidence of benefit compared with a placebo intervention.