Adjuvant therapy and recurrence risk in non-myoinvasive high-grade (stage IC) endometrial cancer: A systematic review and meta-analysis.

Anastasio MK ，Nolin A ，Penvose KN ，Lambert K ，Li J ，Ledbetter L ，Davidson BA ，Havrilesky LJ ，Albright BB ... -  《-》

Falls prevention interventions for community-dwelling older adults: systematic review and meta-analysis of benefits, harms, and patient values and preferences.

About 20-30% of older adults (≥ 65 years old) experience one or more falls each year, and falls are associated with substantial burden to the health care system, individuals, and families from resulting injuries, fractures, and reduced functioning and quality of life. Many interventions for preventing falls have been studied, and their effectiveness, factors relevant to their implementation, and patient preferences may determine which interventions to use in primary care. The aim of this set of reviews was to inform recommendations by the Canadian Task Force on Preventive Health Care (task force) on fall prevention interventions. We undertook three systematic reviews to address questions about the following: (i) the benefits and harms of interventions, (ii) how patients weigh the potential outcomes (outcome valuation), and (iii) patient preferences for different types of interventions, and their attributes, shown to offer benefit (intervention preferences). We searched four databases for benefits and harms (MEDLINE, Embase, AgeLine, CENTRAL, to August 25, 2023) and three for outcome valuation and intervention preferences (MEDLINE, PsycINFO, CINAHL, to June 9, 2023). For benefits and harms, we relied heavily on a previous review for studies published until 2016. We also searched trial registries, references of included studies, and recent reviews. Two reviewers independently screened studies. The population of interest was community-dwelling adults ≥ 65 years old. We did not limit eligibility by participant fall history. The task force rated several outcomes, decided on their eligibility, and provided input on the effect thresholds to apply for each outcome (fallers, falls, injurious fallers, fractures, hip fractures, functional status, health-related quality of life, long-term care admissions, adverse effects, serious adverse effects). For benefits and harms, we included a broad range of non-pharmacological interventions relevant to primary care. Although usual care was the main comparator of interest, we included studies comparing interventions head-to-head and conducted a network meta-analysis (NMAs) for each outcome, enabling analysis of interventions lacking direct comparisons to usual care. For benefits and harms, we included randomized controlled trials with a minimum 3-month follow-up and reporting on one of our fall outcomes (fallers, falls, injurious fallers); for the other questions, we preferred quantitative data but considered qualitative findings to fill gaps in evidence. No date limits were applied for benefits and harms, whereas for outcome valuation and intervention preferences we included studies published in 2000 or later. All data were extracted by one trained reviewer and verified for accuracy and completeness. For benefits and harms, we relied on the previous review team's risk-of-bias assessments for benefit outcomes, but otherwise, two reviewers independently assessed the risk of bias (within and across study). For the other questions, one reviewer verified another's assessments. Consensus was used, with adjudication by a lead author when necessary. A coding framework, modified from the ProFANE taxonomy, classified interventions and their attributes (e.g., supervision, delivery format, duration/intensity). For benefit outcomes, we employed random-effects NMA using a frequentist approach and a consistency model. Transitivity and coherence were assessed using meta-regressions and global and local coherence tests, as well as through graphical display and descriptive data on the composition of the nodes with respect to major pre-planned effect modifiers. We assessed heterogeneity using prediction intervals. For intervention-related adverse effects, we pooled proportions except for vitamin D for which we considered data in the control groups and undertook random-effects pairwise meta-analysis using a relative risk (any adverse effects) or risk difference (serious adverse effects). For outcome valuation, we pooled disutilities (representing the impact of a negative event, e.g. fall, on one's usual quality of life, with 0 = no impact and 1 = death and ~ 0.05 indicating important disutility) from the EQ-5D utility measurement using the inverse variance method and a random-effects model and explored heterogeneity. When studies only reported other data, we compared the findings with our main analysis. For intervention preferences, we used a coding schema identifying whether there were strong, clear, no, or variable preferences within, and then across, studies. We assessed the certainty of evidence for each outcome using CINeMA for benefit outcomes and GRADE for all other outcomes. A total of 290 studies were included across the reviews, with two studies included in multiple questions. For benefits and harms, we included 219 trials reporting on 167,864 participants and created 59 interventions (nodes). Transitivity and coherence were assessed as adequate. Across eight NMAs, the number of contributing trials ranged between 19 and 173, and the number of interventions ranged from 19 to 57. Approximately, half of the interventions in each network had at least low certainty for benefit. The fallers outcome had the highest number of interventions with moderate certainty for benefit (18/57). For the non-fall outcomes (fractures, hip fracture, long-term care [LTC] admission, functional status, health-related quality of life), many interventions had very low certainty evidence, often from lack of data. We prioritized findings from 21 interventions where there was moderate certainty for at least some benefit. Fourteen of these had a focus on exercise, the majority being supervised (for > 2 sessions) and of long duration (> 3 months), and with balance/resistance and group Tai Chi interventions generally having the most outcomes with at least low certainty for benefit. None of the interventions having moderate certainty evidence focused on walking. Whole-body vibration or home-hazard assessment (HHA) plus exercise provided to everyone showed moderate certainty for some benefit. No multifactorial intervention alone showed moderate certainty for any benefit. Six interventions only had very-low certainty evidence for the benefit outcomes. Two interventions had moderate certainty of harmful effects for at least one benefit outcome, though the populations across studies were at high risk for falls. Vitamin D and most single-component exercise interventions are probably associated with minimal adverse effects. Some uncertainty exists about possible adverse effects from other interventions. For outcome valuation, we included 44 studies of which 34 reported EQ-5D disutilities. Admission to long-term care had the highest disutility (1.0), but the evidence was rated as low certainty. Both fall-related hip (moderate certainty) and non-hip (low certainty) fracture may result in substantial disutility (0.53 and 0.57) in the first 3 months after injury. Disutility for both hip and non-hip fractures is probably lower 12 months after injury (0.16 and 0.19, with high and moderate certainty, respectively) compared to within the first 3 months. No study measured the disutility of an injurious fall. Fractures are probably more important than either falls (0.09 over 12 months) or functional status (0.12). Functional status may be somewhat more important than falls. For intervention preferences, 29 studies (9 qualitative) reported on 17 comparisons among single-component interventions showing benefit. Exercise interventions focusing on balance and/or resistance training appear to be clearly preferred over Tai Chi and other forms of exercise (e.g., yoga, aerobic). For exercise programs in general, there is probably variability among people in whether they prefer group or individual delivery, though there was high certainty that individual was preferred over group delivery of balance/resistance programs. Balance/resistance exercise may be preferred over education, though the evidence was low certainty. There was low certainty for a slight preference for education over cognitive-behavioral therapy, and group education may be preferred over individual education. To prevent falls among community-dwelling older adults, evidence is most certain for benefit, at least over 1-2 years, from supervised, long-duration balance/resistance and group Tai Chi interventions, whole-body vibration, high-intensity/dose education or cognitive-behavioral therapy, and interventions of comprehensive multifactorial assessment with targeted treatment plus HHA, HHA plus exercise, or education provided to everyone. Adding other interventions to exercise does not appear to substantially increase benefits. Overall, effects appear most applicable to those with elevated fall risk. Choice among effective interventions that are available may best depend on individual patient preferences, though when implementing new balance/resistance programs delivering individual over group sessions when feasible may be most acceptable. Data on more patient-important outcomes including fall-related fractures and adverse effects would be beneficial, as would studies focusing on equity-deserving populations and on programs delivered virtually. Not registered.

Pillay J ，Gaudet LA ，Saba S ，Vandermeer B ，Ashiq AR ，Wingert A ，Hartling L ... -  《Systematic Reviews》

Impact of residual disease as a prognostic factor for survival in women with advanced epithelial ovarian cancer after primary surgery.

Ovarian cancer is the seventh most common cancer among women and a leading cause of death from gynaecological malignancies. Epithelial ovarian cancer is the most common type, accounting for around 90% of all ovarian cancers. This specific type of ovarian cancer starts in the surface layer covering the ovary or lining of the fallopian tube. Surgery is performed either before chemotherapy (upfront or primary debulking surgery (PDS)) or in the middle of a course of treatment with chemotherapy (neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS)), with the aim of removing all visible tumour and achieving no macroscopic residual disease (NMRD). The aim of this review is to investigate the prognostic impact of size of residual disease nodules (RD) in women who received upfront or interval cytoreductive surgery for advanced (stage III and IV) epithelial ovarian cancer (EOC). To assess the prognostic impact of residual disease after primary surgery on survival outcomes for advanced (stage III and IV) epithelial ovarian cancer. In separate analyses, primary surgery included both upfront primary debulking surgery (PDS) followed by adjuvant chemotherapy and neoadjuvant chemotherapy followed by interval debulking surgery (IDS). Each residual disease threshold is considered as a separate prognostic factor. We searched CENTRAL (2021, Issue 8), MEDLINE via Ovid (to 30 August 2021) and Embase via Ovid (to 30 August 2021). We included survival data from studies of at least 100 women with advanced EOC after primary surgery. Residual disease was assessed as a prognostic factor in multivariate prognostic models. We excluded studies that reported fewer than 100 women, women with concurrent malignancies or studies that only reported unadjusted results. Women were included into two distinct groups: those who received PDS followed by platinum-based chemotherapy and those who received IDS, analysed separately. We included studies that reported all RD thresholds after surgery, but the main thresholds of interest were microscopic RD (labelled NMRD), RD 0.1 cm to 1 cm (small-volume residual disease (SVRD)) and RD > 1 cm (large-volume residual disease (LVRD)). Two review authors independently abstracted data and assessed risk of bias. Where possible, we synthesised the data in meta-analysis. To assess the adequacy of adjustment factors used in multivariate Cox models, we used the 'adjustment for other prognostic factors' and 'statistical analysis and reporting' domains of the quality in prognosis studies (QUIPS) tool. We also made judgements about the certainty of the evidence for each outcome in the main comparisons, using GRADE. We examined differences between FIGO stages III and IV for different thresholds of RD after primary surgery. We considered factors such as age, grade, length of follow-up, type and experience of surgeon, and type of surgery in the interpretation of any heterogeneity. We also performed sensitivity analyses that distinguished between studies that included NMRD in RD categories of < 1 cm and those that did not. This was applicable to comparisons involving RD < 1 cm with the exception of RD < 1 cm versus NMRD. We evaluated women undergoing PDS and IDS in separate analyses. We found 46 studies reporting multivariate prognostic analyses, including RD as a prognostic factor, which met our inclusion criteria: 22,376 women who underwent PDS and 3697 who underwent IDS, all with varying levels of RD. While we identified a range of different RD thresholds, we mainly report on comparisons that are the focus of a key area of clinical uncertainty (involving NMRD, SVRD and LVRD). The comparison involving any visible disease (RD > 0 cm) and NMRD was also important. SVRD versus NMRD in a PDS setting In PDS studies, most showed an increased risk of death in all RD groups when those with macroscopic RD (MRD) were compared to NMRD. Women who had SVRD after PDS had more than twice the risk of death compared to women with NMRD (hazard ratio (HR) 2.03, 95% confidence interval (CI) 1.80 to 2.29; I2 = 50%; 17 studies; 9404 participants; moderate-certainty). The analysis of progression-free survival found that women who had SVRD after PDS had nearly twice the risk of death compared to women with NMRD (HR 1.88, 95% CI 1.63 to 2.16; I2 = 63%; 10 studies; 6596 participants; moderate-certainty). LVRD versus SVRD in a PDS setting When we compared LVRD versus SVRD following surgery, the estimates were attenuated compared to NMRD comparisons. All analyses showed an overall survival benefit in women who had RD < 1 cm after surgery (HR 1.22, 95% CI 1.13 to 1.32; I2 = 0%; 5 studies; 6000 participants; moderate-certainty). The results were robust to analyses of progression-free survival. SVRD and LVRD versus NMRD in an IDS setting The one study that defined the categories as NMRD, SVRD and LVRD showed that women who had SVRD and LVRD after IDS had more than twice the risk of death compared to women who had NMRD (HR 2.09, 95% CI 1.20 to 3.66; 310 participants; I2 = 56%, and HR 2.23, 95% CI 1.49 to 3.34; 343 participants; I2 = 35%; very low-certainty, for SVRD versus NMRD and LVRD versus NMRD, respectively). LVRD versus SVRD + NMRD in an IDS setting Meta-analysis found that women who had LVRD had a greater risk of death and disease progression compared to women who had either SVRD or NMRD (HR 1.60, 95% CI 1.21 to 2.11; 6 studies; 1572 participants; I2 = 58% for overall survival and HR 1.76, 95% CI 1.23 to 2.52; 1145 participants; I2 = 60% for progression-free survival; very low-certainty). However, this result is biased as in all but one study it was not possible to distinguish NMRD within the < 1 cm thresholds. Only one study separated NMRD from SVRD; all others included NMRD in the SVRD group, which may create bias when comparing with LVRD, making interpretation challenging. MRD versus NMRD in an IDS setting Women who had any amount of MRD after IDS had more than twice the risk of death compared to women with NMRD (HR 2.11, 95% CI 1.35 to 3.29, I2 = 81%; 906 participants; very low-certainty). In a PDS setting, there is moderate-certainty evidence that the amount of RD after primary surgery is a prognostic factor for overall and progression-free survival in women with advanced ovarian cancer. We separated our analysis into three distinct categories for the survival outcome including NMRD, SVRD and LVRD. After IDS, there may be only two categories required, although this is based on very low-certainty evidence, as all but one study included NMRD in the SVRD category. The one study that separated NMRD from SVRD showed no improved survival outcome in the SVRD category, compared to LVRD. Further low-certainty evidence also supported restricting to two categories, where women who had any amount of MRD after IDS had a significantly greater risk of death compared to women with NMRD. Therefore, the evidence presented in this review cannot conclude that using three categories applies in an IDS setting (very low-certainty evidence), as was supported for PDS (which has convincing moderate-certainty evidence).

Bryant A ，Hiu S ，Kunonga PT ，Gajjar K ，Craig D ，Vale L ，Winter-Roach BA ，Elattar A ，Naik R ... -  《Cochrane Database of Systematic Reviews》

Defining the optimum strategy for identifying adults and children with coeliac disease: systematic review and economic modelling.

Elwenspoek MM ，Thom H ，Sheppard AL ，Keeney E ，O'Donnell R ，Jackson J ，Roadevin C ，Dawson S ，Lane D ，Stubbs J ，Everitt H ，Watson JC ，Hay AD ，Gillett P ，Robins G ，Jones HE ，Mallett S ，Whiting PF ... -  《-》

Mobile apps to reduce depressive symptoms and alcohol use in youth: A systematic review and meta-analysis: A systematic review.

Among youth, symptoms of depression, anxiety, and alcohol use are associated with considerable illness and disability. Youth face many personal and health system barriers in accessing mental health care. Mobile applications (apps) offer youth potentially accessible, scalable, and anonymous therapy and other support. Recent systematic reviews on apps to reduce mental health symptoms among youth have reported uncertain effectiveness, but analyses based on the type of app-delivered therapy are limited. We conducted this systematic review with youth co-researchers to ensure that this review addressed the questions that were most important to them. The objective of this review is to synthesize the best available evidence on the effectiveness of mobile apps for the reduction of depressive symptoms (depression, generalized anxiety, psychological distress) and alcohol use among youth. We conducted electronic searches of the following bibliographic databases for studies published between January 1, 2008, and July 1, 2022: MEDLINE (via Ovid), Embase (via Ovid), PsycINFO (via Ovid), CINAHL (via EBSCOHost), and CENTRAL (via the Cochrane Library). The search used a combination of indexed terms, free text words, and MeSH headings. We manually screened the references of relevant systematic reviews and included randomized controlled trials (RCTs) for additional eligible studies, and contacted authors for full reports of identified trial registries or protocols. We included RCTs conducted among youth aged 15-24 years from any setting. We did not exclude populations on the basis of gender, socioeconomic status, geographic location or other personal characteristics. We included studies which assessed the effectiveness of app-delivered mental health support or therapy interventions that targeted the management of depressive disorders and/or alcohol use disorders. We excluded apps that targeted general wellness, apps which focused on prevention of psychological disorders and apps that targeted bipolar disorder, psychosis, post-traumatic stress disorder, attention-deficit hyperactivity disorder, substance use disorders (aside from alcohol), and sleep disorders. Eligible comparisons included usual care, no intervention, wait-list control, alternative or controlled mobile applications. We included studies which reported outcomes on depressive symptoms, anxiety symptoms, alcohol use and psychological distress over any follow-up period. We standardized the PICO definitions (population, intervention, comparison, and outcome) of each included study and grouped studies by the type of therapy or support offered by the app. Whenever app design and clinical homogeneity allowed, we meta-analyzed outcomes using a random-effects model. Outcome data measured using categorical scales were synthesized using odds ratios. Outcome data measured using continuous scales were synthesized as the standardized mean difference. We assessed the methodological quality of each included study using the Cochrane Risk of Bias 2.0 tool and we assessed certainty of the evidence using the GRADE approach. From 5280 unique citations, we included 36 RCTs published in 37 reports and conducted in 15 different countries (7984 participants). Among the 36 included trials, we assessed two with an overall low risk of bias, 8 trials with some concern regarding risk of bias, and 26 trials with a high risk of bias. Interventions varied in the type of therapy or supports offered. The most common intervention designs employed mindfulness training, cognitive behavioral therapy (CBT), or a combination of the two (mindfulness + CBT). However, other interventions also included self-monitoring, medication reminders, cognitive bias modification or positive stimulation, dialectical behavioral therapy, gamified health promotion, or social skill building. Mindfulness apps led to short term improvements in depressive symptoms when compared to a withheld control (SMD = -0.36; 95% CI [-0.63, -0.10]; p = 0.007, n = 3 RCTs, GRADE: very low certainty) and when compared to an active control (SMD = -0.27; 95% CI [-0.53, -0.01]; p = 0.04, n = 2 RCTs, GRADE: very low). Apps delivering this type of support also significantly improved symptoms of anxiety when compared to a withheld control (SMD = -0.35; 95% CI [-0.60, -0.09]; p = 0.008, n = 3 RCTs, GRADE: very low) but not when compared to an active control (SMD = -0.24; 95% CI [-0.50, 0.02]; p = 0.07, n = 2 RCTs, GRADE: very low). Mindfulness apps showed improvements in psychological stress that approached statistical significance among participants receiving the mindfulness mobile apps compared to those in the withheld control (SMD = -0.27; 95% CI [-0.56, 0.03]; p = .07, n = 4 RCTs, GRADE: very low). CBT apps also led to short-term improvements in depressive symptoms when compared to a withheld control (SMD = -0.40; 95% CI [-0.80, 0.01]; p = 0.05, n = 2 RCTs, GRADE: very low) and when compared to an active control (SMD = -0.59; 95% CI [-0.98, -0.19]; p = 0.003, n = 2 RCTs, GRADE: very low). CBT-based apps also improved symptoms of anxiety compared to a withheld control (SMD = -0.51; 95% CI [-0.94, -0.09]; p = 0.02, n = 3 RCTs, GRADE: very low) but not when compared to an active control (SMD = -0.26; 95% CI [-1.11, 0.59]; p = 0.55, n = 3 RCTs, GRADE: very low). Apps which combined mindfulness and CBT did not significantly improve symptoms of depression (SMD = -0.20; 95% CI [-0.42, 0.02]; p = 0.07, n = 2 RCTs, GRADE: very low) or anxiety (SMD = -0.21; 95% CI [-0.49, 0.07]; p = 0.14, n = 2 RCTs, GRADE: very low). However, these apps did improve psychological distress (SMD = -0.43; 95% CI [-0.74, -0.12]; p = 0.006, n = 2 RCTs, GRADE: very low). The results of trials on apps to reduce alcohol use were inconsistent. We did not identify any harms associated with the use of apps to manage mental health concerns. All effectiveness results had a very low certainty of evidence rating using the GRADE approach, meaning that apps which deliver therapy or other mental health support may reduce symptoms of depression, anxiety and psychological distress but the evidence is very uncertain. We reviewed evidence from 36 trials conducted among youth. According to our meta-analyses, the evidence is very uncertain about the effect of apps on depression, anxiety, psychological distress, and alcohol use. Very few effects were interpreted to be of clinical importance. Most of the RCTs were small studies focusing on efficacy for youth at risk for depressive symptoms. Larger trials are needed to evaluate effectiveness and allow for further analysis of subgroup differences. Longer trials are also needed to better estimate the clinical importance of these apps over the long term.

Magwood O ，Saad A ，Ranger D ，Volpini K ，Rukikamirera F ，Haridas R ，Sayfi S ，Alexander J ，Tan Y ，Pottie K ... -  《-》