Non-clotting factor therapies for preventing bleeds in people with congenital hemophilia A or B.

BACKGROUND: Management of congenital hemophilia A and B is by prophylactic or on-demand replacement therapy with clotting factor concentrates. The effects of newer non-clotting factor therapies such as emicizumab, concizumab, marstacimab, and fitusiran compared with existing standards of care are yet to be systematically reviewed. OBJECTIVES: To assess the effects (clinical, economic, patient-reported, and adverse outcomes) of non-clotting factor therapies for preventing bleeding and bleeding-related complications in people with congenital hemophilia A or B compared with prophylaxis with clotting factor therapies, bypassing agents, placebo, or no prophylaxis. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register, electronic databases, conference proceedings, and reference lists of relevant articles and reviews. The date of the last search was 16 August 2023. SELECTION CRITERIA: Randomized controlled trials (RCTs) evaluating people with congenital hemophilia A or B with and without inhibitors, who were treated with non-clotting factor therapies to prevent bleeds. DATA COLLECTION AND ANALYSIS: Two review authors independently reviewed studies for eligibility, assessed risk of bias, and extracted data for the primary outcomes (bleeding rates, health-related quality of life (HRQoL), adverse events) and secondary outcomes (joint health, pain scores, and economic outcomes). We assessed the mean difference (MD), risk ratio (RR), 95% confidence interval (CI) of effect estimates, and evaluated the certainty of the evidence using GRADE. MAIN RESULTS: Six RCTs (including 397 males aged 12 to 75 years) were eligible for inclusion. Prophylaxis versus on-demand therapy in people with inhibitors Four trials (189 participants) compared emicizumab, fitusiran, and concizumab with on-demand therapy in people with inhibitors. Prophylaxis using emicizumab likely reduced annualized bleeding rates (ABR) for all bleeds (MD -22.80, 95% CI -37.39 to -8.21), treated bleeds (MD -20.40, 95% CI -35.19 to -5.61), and annualized spontaneous bleeds (MD -15.50, 95% CI -24.06 to -6.94), but did not significantly reduce annualized joint and target joint bleeding rates (AjBR and AtjBR) (1 trial; 53 participants; moderate-certainty evidence). Fitusiran also likely reduced ABR for all bleeds (MD -28.80, 95% CI -40.07 to -17.53), treated bleeds (MD -16.80, 95% CI -25.80 to -7.80), joint bleeds (MD -12.50, 95% CI -19.91 to -5.09), and spontaneous bleeds (MD -14.80, 95% CI -24.90 to -4.71; 1 trial; 57 participants; moderate-certainty evidence). No evidence was available on the effect of bleed prophylaxis using fitusiran versus on-demand therapy on AtjBR. Concizumab may reduce ABR for all bleeds (MD -12.31, 95% CI -19.17 to -5.45), treated bleeds (MD -10.10, 95% CI -17.74 to -2.46), joint bleeds (MD -9.55, 95% CI -13.55 to -5.55), and spontaneous bleeds (MD -11.96, 95% CI -19.89 to -4.03; 2 trials; 78 participants; very low-certainty evidence), but not target joint bleeds (MD -1.00, 95% CI -3.26 to 1.26). Emicizumab prophylaxis resulted in an 11.31-fold increase, fitusiran in a 12.5-fold increase, and concizumab in a 1.59-fold increase in the proportion of participants with no bleeds. HRQoL measured using the Haemophilia Quality of Life Questionnaire for Adults (Haem-A-QoL) physical and total health scores was improved with emicizumab, fitusiran, and concizumab prophylaxis (low-certainty evidence). Non-serious adverse events were higher with non-clotting factor therapies versus on-demand therapy, with injection site reactions being the most frequently reported adverse events. Transient antidrug antibodies were reported for fitusiran and concizumab. Prophylaxis versus on-demand therapy in people without inhibitors Two trials (208 participants) compared emicizumab and fitusiran with on-demand therapy in people without inhibitors. One trial assessed two doses of emicizumab (1.5 mg/kg weekly and 3.0 mg/kg bi-weekly). Fitusiran 80 mg monthly, emicizumab 1.5 mg/kg/week, and emicizumab 3.0 mg/kg bi-weekly all likely resulted in a large reduction in ABR for all bleeds, all treated bleeds, and joint bleeds. AtjBR was not reduced with either of the emicizumab dosing regimens. The effect of fitusiran prophylaxis on target joint bleeds was not assessed. Spontaneous bleeds were likely reduced with fitusiran (MD -20.21, 95% CI -32.12 to -8.30) and emicizumab 3.0 mg/kg bi-weekly (MD -15.30, 95% CI -30.46 to -0.14), but not with emicizumab 1.5 mg/kg/week (MD -14.60, 95% CI -29.78 to 0.58). The percentage of participants with zero bleeds was higher following emicizumab 1.5 mg/kg/week (50% versus 0%), emicizumab 3.0 mg/kg bi-weekly (40% versus 0%), and fitusiran prophylaxis (40% versus 5%) compared with on-demand therapy. Emicizumab 1.5 mg/kg/week did not improve Haem-A-QoL physical and total health scores, EQ-5D-5L VAS, or utility index scores (low-certainty evidence) when compared with on-demand therapy at 25 weeks. Emicizumab 3.0 mg/kg bi-weekly may improve HRQoL measured by the Haem-A-QoL physical health score (MD -15.97, 95% CI -29.14 to -2.80) and EQ-5D-5L VAS (MD 9.15, 95% CI 2.05 to 16.25; 1 trial; 43 participants; low-certainty evidence). Fitusiran may result in improved HRQoL shown as a reduction in Haem-A-QoL total score (MD -7.06, 95% CI -11.50 to -2.62) and physical health score (MD -19.75, 95% CI -25.76 to -11.94; 1 trial; 103 participants; low-certainty evidence). The risk of serious adverse events in participants without inhibitors also likely did not differ following prophylaxis with either emicizumab or fitusiran versus on-demand therapy (moderate-certainty evidence). Transient antidrug antibodies were reported in 4% (3/80) participants to fitusiran, with no observed effect on antithrombin lowering. A comparison of the different dosing regimens of emicizumab identified no differences in bleeding, safety, or patient-reported outcomes. No case of treatment-related cancer or mortality was reported in any study group. None of the included studies assessed our secondary outcomes of joint health, clinical joint function, and economic outcomes. None of the included studies evaluated marstacimab. AUTHORS' CONCLUSIONS: Evidence from RCTs shows that prophylaxis using non-clotting factor therapies compared with on-demand treatment may reduce bleeding events, increase the percentage of individuals with zero bleeds, increase the incidence of non-serious adverse events, and improve HRQoL. Comparative assessments with other prophylaxis regimens, assessment of long-term joint outcomes, and assessment of economic outcomes will improve evidence-based decision-making for the use of these therapies in bleed prevention.

The use and effects of telemedicine on complementary, alternative, and integrative medicine practices: a scoping review.

BACKGROUND: Telemedicine includes the delivery of health-care services and sharing of health information across distances. Past research has found that telemedicine can play a role in enhancing complementary, alternative, and integrative medicine (CAIM) while allowing the maintenance of cultural values and ancestral knowledge. This scoping review synthesized evidence regarding the use of telemedicine in the context of CAIM. METHODS: Following Arksey and O'Malley's scoping review framework, CINAHL, PsycINFO, MEDLINE, EMBASE and AMED databases were searched systematically. The CADTH website was also searched for grey literature. Eligible articles included a CAIM practice or therapy offered through telemedicine, with no restrictions placed on the type of telemedicine technology used. Inductive thematic analysis was conducted to synthesise common themes among the included studies. RESULTS: Sixty-two articles were included in this synthesis. The following themes emerged: 1) the practitioner view of CAIM delivered through telemedicine, 2) the patient view of CAIM delivered through telemedicine, and 3) the technological impacts of telemedicine delivery of CAIM. CONCLUSIONS: Studies have shown that telemedicine delivery of CAIM is feasible, acceptable, and results in positive health outcomes. Some barriers remain such as the presence of chronic illness and morbidity, inability to form strong patient-provider relationships relative to face-to-face approaches, and technological difficulties. Future intervention research should focus on reducing such barriers, as well as explore which patient population would realize the greatest benefit from CAIM delivered via telemedicine, and the impact of interventions on providers and caregivers.

A global systematic scoping review of literature on the sexual exploitation of boys.

BACKGROUND: Sexual exploitation of children (SEC) is a widespread crime which impacts the child victim across developmental, health and well-being domains. As victims, boys have received much less clinical and research attention. While context-specific factors likely shape the SEC risk, under-recognized gender norms can deny boys' vulnerability. Professional failures to recognize and respond adequately to boys' sexual exploitation may prevent access to support. OBJECTIVE: This systematic scoping review updates and broadens a previous review of literature addressing prevalence, victim/offender/facilitator characteristics, control mechanisms, as well as the health correlates and outcomes regarding sexual exploitation of boys. This review included international peer-reviewed and gray literature from 38 countries in 14 languages. PARTICIPANTS AND SETTING: Studies from the years 2000 to 2022 that included samples of boys under age 18, or sex-disaggregated data for children under 18, were included. Case studies, systematic reviews, and those reporting on retrospective experiences by adults over 18 were excluded. A total of 254,744 boys were represented across 81 studies. METHODS: A systematic scoping review considered qualitative and quantitative peer-reviewed publications from eight, English-language databases. English and non-English non-peer reviewed publications ('gray literature') was identified by both ECPAT International's global network of member organizations and citation chaining. RESULTS: Overall, 81 peer-reviewed (n = 51) and gray literature (n = 30) documents from 38 countries were included. In total, 254,744 youth participated in peer-reviewed studies (N = 217,726) and gray literature (N = 37,018). General prevalence of sexual exploitation of boys was reported at up to 5 %, with higher rates noted in specifically vulnerable sub-populations (e.g., 10 %, trans youth; 26 %, street-connected youth). The literature indicates that sexual exploitation of boys is reported as occurring primarily between 12 and 18 years old. Multi-level factors are linked to SEC, including individual (e.g., disability status), relationship (e.g., child maltreatment, dating violence), community (e.g., community violence), and societal domains (e.g., discriminatory beliefs). SEC victimization is linked with youth mental and physical health concerns, particularly sexual health. Post-traumatic stress symptomatology or disorder was rarely evaluated. Evidence-based treatments were not available, which may be related to a lack of gender-based theoretical models for understanding SEC specifically. CONCLUSION: The sexual exploitation of boys is a prevalent public health, child rights, and clinical issue. All young people experiencing sexual exploitation face sex- and gender-specific challenges, and this remains the case for boys with indications including family rejection, implicit community tolerance for abuse to service accessibility barriers. Actioning our duty to care for all children requires gender- and trauma-informed lenses. Ongoing surveillance of all forms of violence against children, with gender disaggregation, is essential for practice and policy advancement.

Indigenous Youth and Resilience in Canada and the USA: a Scoping Review.

Relative to non-Indigenous youth, Indigenous youth have been under-represented when studying pathways to mental wellness. Yet, a broad range of adversity is acknowledged, from intergenerational and ongoing trauma arising from colonial policies. This scoping review explores resilience definitions, measures, key stressors, and what Indigenous youth identify as pathways to their wellness, based on quantitative and qualitative peer-reviewed literature in Canada and the Continental United States. Eight databases (EBSCO, PsycINFO, Science Direct, Social Science Citation Index, Web of Science, PsycARTICLES, and EMBASE) and hand searches of 7 relevant journals were conducted to ensure literature coverage. Two independent reviewers screened each article, with one Indigenous screener per article. The final scoping review analysis included 44 articles. In articles, no Indigenous term for resilience was found, but related concepts were identified ("walking a good path," "good mind," Grandfathers' teachings on 7 values, decision-making for 7 generations into the future, etc.). Few Indigenous-specific measures of resilience exist, with studies relying on Western measures of psychological resilience. Qualitative approaches supporting youth-led resilience definitions yielded important insights. Youth stressors included the following: substance use, family instability, and loss of cultural identity. Youth resilience strategies included the following: having a future orientation, cultural pride, learning from the natural world, and interacting with community members (e.g., relationship with Elders, being in community and on the land). Indigenous traditional knowledge and cultural continuity serve as prominent pathways to Indigenous youth resilience. More research is needed to yield a holistic, youth-centered measure of resilience that includes traditional practices.

Risk factors for bleeding in people living with hemophilia A and B treated with regular prophylaxis: A systematic review of the literature.

BACKGROUND: Knowledge about the risk for bleeding in patients with hemophilia (PWH) would be relevant for patients, stakeholders, and policy makers. OBJECTIVES: To perform a systematic review of the literature on risk assessment models (RAMs) and risk factors for bleeding in PWH on regular prophylaxis. METHODS: We searched Medline, Embase, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews from inception through August 2019. In duplicate, reviewers screened the articles for inclusion, extracted data, and assessed the risk for bias using the Quality in Prognostic Studies (QUIPS) tool. A qualitative synthesis of the results was not performed due to high heterogeneity in risk factors, outcomes definition and measurement, and statistical analysis of the results. RESULTS: From 1843 search results, 10 studies met the inclusion criteria. No RAM for the risk for bleeding in PWH was found. Most studies included only PWH A or both PWH A and B and were conducted in North America or Europe. Only one study had a low risk for bias in all the domains. Eight categories of risk factors were identified. The risk for bleeding was increased when factor levels were lower and in people with a significant history of bleeding or who engaged in physical activities involving contact. CONCLUSIONS: Our findings suggest that plasma factor levels, history of bleeds, and physical activity should be considered for the derivation analysis when building a RAM for bleeding in PWH, and the role of other risk factors, including antithrombotic treatment and obesity, should be explored.

Accuracy and Acceptability of Wrist-Wearable Activity-Tracking Devices: Systematic Review of the Literature.

BACKGROUND: Numerous wrist-wearable devices to measure physical activity are currently available, but there is a need to unify the evidence on how they compare in terms of acceptability and accuracy. OBJECTIVE: The aim of this study is to perform a systematic review of the literature to assess the accuracy and acceptability (willingness to use the device for the task it is designed to support) of wrist-wearable activity trackers. METHODS: We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and SPORTDiscus for studies measuring physical activity in the general population using wrist-wearable activity trackers. We screened articles for inclusion and, for the included studies, reported data on the studies' setting and population, outcome measured, and risk of bias. RESULTS: A total of 65 articles were included in our review. Accuracy was assessed for 14 different outcomes, which can be classified in the following categories: count of specific activities (including step counts), time spent being active, intensity of physical activity (including energy expenditure), heart rate, distance, and speed. Substantial clinical heterogeneity did not allow us to perform a meta-analysis of the results. The outcomes assessed most frequently were step counts, heart rate, and energy expenditure. For step counts, the Fitbit Charge (or the Fitbit Charge HR) had a mean absolute percentage error (MAPE) <25% across 20 studies. For heart rate, the Apple Watch had a MAPE <10% in 2 studies. For energy expenditure, the MAPE was >30% for all the brands, showing poor accuracy across devices. Acceptability was most frequently measured through data availability and wearing time. Data availability was ≥75% for the Fitbit Charge HR, Fitbit Flex 2, and Garmin Vivofit. The wearing time was 89% for both the GENEActiv and Nike FuelBand. CONCLUSIONS: The Fitbit Charge and Fitbit Charge HR were consistently shown to have a good accuracy for step counts and the Apple Watch for measuring heart rate. None of the tested devices proved to be accurate in measuring energy expenditure. Efforts should be made to reduce the heterogeneity among studies.