Systemic therapy in children and adolescents with mental disorders: a systematic review and meta-analysis.

BACKGROUND: Systemic therapy (ST) is a psychotherapeutic intervention in complex human systems (both psychological and interpersonal). Cognitive behavioural therapy (CBT) is an established treatment for children and adolescents with mental disorders. As methodologically rigorous systematic reviews on ST in this population are lacking, we conducted a systematic review and meta-analysis to compare the benefit and harm of ST (and ST as an add-on to CBT) with CBT in children and adolescents with mental disorders. METHODS: We searched MEDLINE, Embase, PsycINFO and other sources for randomised controlled trials in 14 mental disorder classes for the above comparisons in respect of effects on patient-relevant outcomes (search date: 7/2022). Where possible, meta-analyses were performed and results were graded into 3 different evidence categories: "proof", "indication", or "hint" (or none of these categories). PRISMA standards were followed. RESULTS: Fifteen studies in 5 mental disorder classes with usable data were identified. 2079 patients (mean age: 10 to 19 years) were analysed. 12/15 studies and 29/30 outcomes showed a high risk of bias. In 2 classes, statistically significant and clinically relevant effects in favour of ST were found, supporting the conclusion of a hint of greater benefit of ST for mental and behavioural disorders due to psychoactive substance use and of ST as an add-on to CBT for obsessive-compulsive disorders. In 2 other classes (eating disorders; hyperkinetic disorders), there was no evidence of greater benefit or harm of ST. For affective disorders, a statistically significant effect to the disadvantage of ST was found for 1 outcome, supporting the conclusion of a hint of lesser benefit of ST. CONCLUSIONS: Our results show a hint of greater benefit of ST (or ST as an add-on to CBT) compared with CBT for 2 mental disorder classes in children and adolescents (mental and behavioural disorders due to psychoactive substance use, obsessive compulsive disorders). Given the importance of CBT as a control intervention, ST can therefore be considered a beneficial treatment option for children and adolescents with certain mental disorders. Limitations include an overall high risk of bias of studies and outcomes and a lack of data for several disorders.

Single-fraction stereotactic radiosurgery versus microsurgical resection for the treatment of vestibular schwannoma: a systematic review and meta-analysis.

BACKGROUND: Vestibular schwannomas are benign tumours for which various treatments are available. We performed a systematic review of prospective controlled trials comparing the patient-relevant benefits and harms of single-fraction stereotactic radiosurgery (sfSRS) with microsurgical resection (MR) in patients with vestibular schwannoma. METHODS: We searched for randomized controlled trials (RCTs) and non-randomized prospective controlled trials in MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and study registries (last search: 09/2021) and also screened reference lists of relevant systematic reviews. Manufacturers were asked to provide unpublished data. Eligible studies investigated at least one patient-relevant outcome. We assessed the risk of bias (high or low) at the study and outcome level. If feasible, meta-analyses were performed. We graded the results into different categories (hint, indication, or proof of greater benefit or harm). RESULTS: We identified three non-randomized prospective controlled trials of generally low quality with evaluable data on 339 patients with unilateral vestibular schwannoma. There was an indication of greater benefit of sfSRS compared with MR for facial palsy (OR 0.06, 95% CI 0.02-0.21, p < 0.001, 2 studies), hearing function (no pooled estimate available, 2 studies), and length of hospital stay (no pooled estimate available, 2 studies). We found no clinically relevant differences for mortality, vertigo, headaches, tinnitus, balance function, work disability, adverse events, and health-related quality of life. CONCLUSIONS: Our systematic review indicates that sfSRS has greater benefits than MR in patients with unilateral vestibular schwannoma. However, it is unclear whether this conclusion still holds after 2 years, as long-term studies are lacking. It is also unclear whether the effects of sfSRS are similar in patients with bilateral vestibular schwannomas. Long-term prospective studies including patients with this condition would therefore be useful. SYSTEMATIC REVIEW REGISTRATION: The full (German language) protocol and report (Commission No. N20-03) are available on the institute's website: www.iqwig.de/en/projects/n20-03.html.

Screening for sickle cell disease in newborns: a systematic review.

BACKGROUND: Sickle cell disease (SCD) is an inherited autosomal recessive disorder caused by the replacement of normal haemoglobin (HbA) by mutant Hb (sickle Hb, HbS). The sickle-shaped red blood cells lead to haemolysis and vaso-occlusion. Especially in the first years of life, patients with SCD are at high risk of life-threatening complications. SCD prevalence shows large regional variations; the disease predominantly occurs in sub-Saharan Africa. We aimed to systematically assess the evidence on the benefit of newborn screening for SCD followed by an earlier treatment start. METHODS: We systematically searched bibliographic databases (MEDLINE, EMBASE, Cochrane Databases, and the Health Technology Assessment Database), trial registries, and other sources to identify systematic reviews and randomised controlled trials (RCTs) or non-randomised trials on newborn screening for SCD. The last search was in 07/2020. Two reviewers independently reviewed abstracts and full-text articles and assessed the risk of bias of the studies included. Data were extracted by one person and checked by another. As meta-analyses were not possible, a qualitative summary of results was performed. RESULTS: We identified 1 eligible study with direct evidence: a Jamaican retrospective study evaluating newborn screening for SCD followed by preventive measures (prevention of infections and education of parents). The study included 500 patients with SCD (intervention group, 395; historical control group, 105). Although the results showed a high risk of bias, the difference between the intervention and the control group was very large: mortality in children decreased by a factor of about 10 in the first 5 years of life (0.02% in the intervention group vs. 0.19% in the control group, odds ratio 0.09; 95% confidence interval [0.04; 0.22], p < 0.001). CONCLUSION: The results are based on a single retrospective study including historical controls. However, the decrease of mortality by a factor of 10 is unlikely to be explained by bias alone. Therefore, in terms of mortality, data from this single retrospective study included in our systematic review suggest a benefit of newborn screening for SCD (followed by preventive measures) versus no newborn screening for SCD (weak certainty of conclusions).

[GRADE: Evidence to Decision (EtD) framework for coverage decisions]. / GRADE: Von der Evidenz zur Empfehlung oder Entscheidung ­ Entscheidungen zur Kostenerstattung.

BACKGROUND: Coverage decisions are decisions by third party payers about whether and how much to pay for technologies or services, and under what conditions. Given their complexity, a systematic and transparent approach is needed. The DECIDE project, a GRADE working group initiative funded by the European Union, has developed GRADE Evidence to Decision (EtD) frameworks for different types of decisions, including coverage ones. METHODS: We used an iterative approach, including brainstorming to generate ideas, consultation with stakeholders, user testing, and pilot testing of the framework. RESULTS: The general structure of the EtD includes formulation of the question, an assessment using 12 criteria, and conclusions. Criteria that are relevant for coverage decisions are similar to those for clinical recommendations from a population perspective. Important differences between the two include the decision-making processes, accountability, and the nature of the judgments that need to be made for some criteria. Although cost-effectiveness is a key consideration when making coverage decisions, it may not be the determining factor. Strength of recommendation is not directly linked to the type of coverage decisions, but when there are important uncertainties, it may be possible to cover an intervention for a subgroup, in the context of research, with price negotiation, or with restrictions. CONCLUSION: The EtD provides a systematic and transparent approach for making coverage decisions. It helps ensure consideration of key criteria that determine whether a technology or service should be covered and that judgments are informed by the best available evidence.

Exercise for women receiving adjuvant therapy for breast cancer.

BACKGROUND: A huge clinical research database on adjuvant cancer treatment has verified improvements in breast cancer outcomes such as recurrence and mortality rates. On the other hand, adjuvant and neoadjuvant therapy with chemotherapy and radiotherapy impacts on quality of life due to substantial short- and long-term side effects. A number of studies have evaluated the effect of exercise interventions on those side effects. This is an updated version of the original Cochrane review published in 2006. The original review identified some benefits of physical activity on physical fitness and the resulting capacity for performing activities of daily life. It also identified a lack of evidence for other outcomes, providing clear justification for an updated review. OBJECTIVES: To assess the effect of aerobic or resistance exercise interventions during adjuvant treatment for breast cancer on treatment-related side effects such as physical deterioration, fatigue, diminished quality of life, depression, and cognitive dysfunction. SEARCH METHODS: We carried out an updated search in the Cochrane Breast Cancer Group Specialised Register (30 March 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2, 2015), MEDLINE (1966 to 30 March 2015), and EMBASE (1966 to 30 March 2015). We did not update the original searches in CINAHL (1982 to 2004), SPORTDiscus (1975 to 2004), PsycINFO (1872 to 2003), SIGLE (1880 to 2004), and ProQuest Digital Dissertations (1861 to 2004). We searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov for ongoing trials on 30 March 2015. We screened references in relevant reviews and published clinical trials. SELECTION CRITERIA: We included randomised controlled trials that examined aerobic or resistance exercise or both in women undergoing adjuvant treatment for breast cancer. Published and unpublished trials were eligible. DATA COLLECTION AND ANALYSIS: Two review authors independently performed data extraction, assessed trials, and graded the methodological quality using Cochrane's 'Risk of bias' tool. Any disagreements were resolved through discussion or by consulting the third review author. We entered data into Review Manager for analysis. For outcomes assessed with a variety of instruments, we used the standardised mean difference (SMD) as a summary statistic for meta-analysis; for those assessed with the same instrument, we used the mean difference (MD). MAIN RESULTS: For this 2015 update we included a total of 32 studies with 2626 randomised women, 8 studies from the original search and 24 studies from the updated search. We found evidence that physical exercise during adjuvant treatment for breast cancer probably improves physical fitness (SMD 0.42, 95% confidence interval (CI) 0.25 to 0.59; 15 studies; 1310 women; moderate-quality evidence) and slightly reduces fatigue (SMD -0.28, 95% CI -0.41 to -0.16; 19 studies; 1698 women; moderate-quality evidence). Exercise may lead to little or no improvement in health-related quality of life (MD 1.10, 95% CI -5.28 to 7.48; 1 study; 68 women; low-quality evidence), a slight improvement in cancer site-specific quality of life (MD 4.24, 95% CI -1.81 to 10.29; 4 studies; 262 women; low-quality evidence), and an improvement in cognitive function (MD -11.55, 95% CI -22.06 to -1.05; 2 studies; 213 women; low-quality evidence). Exercise probably leads to little or no difference in cancer-specific quality of life (SMD 0.12, 95% CI 0.00 to 0.25; 12 studies; 1012 women; moderate-quality evidence) and little or no difference in depression (SMD -0.15, 95% CI -0.30 to 0.01; 5 studies; 674 women; moderate-quality evidence). Evidence for other outcomes ranged from low to moderate quality. Seven trials reported a very small number of adverse events. AUTHORS' CONCLUSIONS: Exercise during adjuvant treatment for breast cancer can be regarded as a supportive self care intervention that probably results in less fatigue, improved physical fitness, and little or no difference in cancer-specific quality of life and depression. Exercise may also slightly improve cancer site-specific quality of life and cognitive function, while it may result in little or no difference in health-related quality of life. This review is based on trials with a considerable degree of clinical heterogeneity regarding adjuvant cancer treatments and exercise interventions. Due to the difficulty of blinding exercise trials, all included trials were at high risk for performance bias. Furthermore, the majority of trials were at high risk for detection bias, largely due to most outcomes being self reported.The findings of the updated review have enabled us to make a more precise conclusion that both aerobic and resistance exercise can be regarded as beneficial for individuals with adjuvant therapy-related side effects. Further research is required to determine the optimal type, intensity, and timing of an exercise intervention. Furthermore, long-term evaluation is required due to possible long-term side effects of adjuvant treatment.