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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 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.

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.

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.