Correction: Jansa et al. Hospitalisation Is Prognostic of Survival in Chronic Thromboembolic Pulmonary Hypertension. J. Clin. Med. 2022, 11, 6189.

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Impacts of a social and behavior change communication program implemented at scale on infant and young feeding practices in Nigeria: Results of a cluster-randomized evaluation.

BACKGROUND: Infant and young child feeding (IYCF) practices are important for child survival and healthy growth, but IYCF practices remain suboptimal in Nigeria. The objective of this study was to measure the impact of Alive & Thrive's IYCF social and behavior change communication intervention on early initiation of breastfeeding, exclusive breastfeeding, and minimum dietary diversity in Kaduna and Lagos States. METHODS: Local government areas were randomly allocated to intervention or comparison. Cross-sectional surveys of households with children aged 0-23 months were conducted [N = 6,266 baseline (2017), N = 7,320 endline (2020)]. Logistic regression was used to calculate difference-in-differences estimates (DDEs) of impact on IYCF practices and to assess within group changes from baseline to endline. Associations between intervention exposures and IYCF practices were tested in both study groups combined. RESULTS: In Kaduna, a positive differential effect of the intervention was found for exclusive breastfeeding (adjusted DDE 8.9 pp, P<0.099). Increases in both study groups from baseline to endline were observed in Kaduna for early initiation of breastfeeding (intervention 12.2 pp, P = 0.010; comparison 6.4 pp, P = 0.118) and minimum dietary diversity (intervention 20.0 pp, P<0.001; comparison 19.7 pp, P<0.001), which eliminated differential effects. In Lagos, no differential intervention impacts were found on IYCF practices because changes in early initiation of breastfeeding from baseline to endline were small in both study groups and increases in both study groups from baseline to endline were observed for exclusive breastfeeding (intervention 8.9 pp, P = 0.05; comparison 6.6 pp, P<0.001) and minimum dietary diversity (intervention 18.9 pp, P<0.001; comparison 24.3 pp, P<0.001). Odds of all three IYCF practices increased with exposure to facility-based interpersonal communication in both states and with community mobilization or mass media exposure in Kaduna. CONCLUSIONS: This evaluation found weak impacts of the Alive & Thrive intervention on IYCF practices in the difference-in-differences analysis because of suspected intervention spillover to the comparison group. Substantial within group increases in IYCF practices from baseline to endline are likely attributable to the intervention, which was the major IYCF promotion activity in both states. This is supported by the association between intervention exposures and IYCF practices. TRIAL REGISTRATION: The study was registered with clinicaltrials.gov (NCT02975063).

Divergent Pathways of Ammonia and Urea Production and Excretion during the Life Cycle of the Sea Lamprey.

Little is known about nitrogenous waste (N waste) handling and excretion (JN waste) during the complex life cycle of the sea lamprey (Petromyzon marinus), an extant jawless fish that undergoes a complete metamorphosis from a filter-feeding larva (ammocoete) into a parasitic juvenile that feeds on the blood of larger, jawed fishes. Here, we investigate the ammonia- and urea-handling profiles of sea lampreys before, during, and after metamorphosis. The rates of ammonia excretion (Jamm) and urea excretion (Jurea) significantly decreased after the onset of metamorphosis, with the lowest rates observed during midmetamorphosis. Near the completion of metamorphosis, rates of JN waste (JN waste=Jamm+Jurea) significantly increased as sea lampreys entered the juvenile period. Feeding juvenile lampreys had greater than 10- to 15-fold higher Jamm and fivefold higher Jurea compared to nonfed juveniles, which corresponded to higher postprandial (postfeeding) concentrations of plasma ammonia and urea. The routes of Jamm and Jurea completely diverged following metamorphosis. In larvae, Jamm was equally split between branchial (gills) and extrabranchial (skin plus renal) pathways, but following metamorphosis, >80% of ammonia was excreted via the gills in nonfeeding juvenile lampreys, and >95% of ammonia was excreted via the gills in adult sea lampreys. Urea, on the other hand, was predominantly excreted via extrabranchial routes and, to a lesser extent, the gills in larvae and in nonfeeding juveniles. In adults, however, virtually all urea was excreted via urine. Reverse transcription polymerase chain reaction and in silico analyses also indicated that a urea transporter encoded by a slc4a2-like gene is present in lampreys. The branchial expression of this transporter is modulated throughout sea lamprey life history, as it is higher in the larvae and steadily decreases until the adult stage. We conclude that the divergent pathways of Jamm and Jurea during the sea lamprey life cycle reflect changes in their habitat, lifestyle, and diet. Further, the near-complete reliance on renal routes for Jurea in adult sea lampreys is unique among fishes and may reflect the ancestral condition of how this N waste product was handled and excreted by the earliest vertebrates.

Hospitalisation Is Prognostic of Survival in Chronic Thromboembolic Pulmonary Hypertension.

This analysis investigated the prognostic value of hospitalisation in chronic thromboembolic pulmonary hypertension (CTEPH) using data from the Czech Republic, wherein pulmonary endarterectomy (PEA) was the only targeted treatment option until 2015. Using a landmark method, this analysis quantified the association between a first CTEPH-related hospitalisation event occurring before 3-, 6-, 9-, and 12-month landmark timepoints and subsequent all-cause mortality in adult CTEPH patients diagnosed between 2003 and 2016 in the Czech Republic. Patients were stratified into operable and inoperable, according to PEA eligibility. CTEPH-related hospitalisations were defined as non-elective. Hospitalisations related to CTEPH diagnosis, PEA, balloon pulmonary angioplasty, or clinical trial participation were excluded. Of 436 patients who survived to ≥3 months post diagnosis, 309 were operable, and 127 were inoperable. Sex- and age-adjusted hazard ratios (HRs) showed CTEPH-related hospitalisation was a statistically significant prognostic indicator of mortality at 3, 9, and 12 months in inoperable patients, with an approximately 2-fold increased risk of death in the hospitalisation group (HRs [95% CI] ranging from 1.98 [1.06-3.70] to 2.17 [1.01-4.63]). There was also a trend of worse survival probabilities in the hospitalisation groups for operable patients, with the difference most pronounced at 3 months, with a 76% increased risk of death (adjusted HR [95% CI] 1.76 [1.15-2.68]). This first analysis on the prognostic value of CTEPH-related hospitalisations demonstrates that a first CTEPH-related hospitalisation is prognostic of mortality in CTEPH, particularly for inoperable patients. These patients may benefit from medical and/or interventional therapy.

Five year risk assessment and treatment patterns in patients with chronic thromboembolic pulmonary hypertension.

AIMS: Repeated risk assessments and treatment patterns over long time are sparsely studied in chronic thromboembolic pulmonary hypertension (CTEPH); thus, we aimed to investigate changes in risk status and treatment patterns in incident patients with CTEPH over a 5 year period. METHODS AND RESULTS: Descriptive and explorative study including 311 patients diagnosed with CTEPH 2008-2019 from the Swedish pulmonary hypertension registry, stratified by pulmonary endarterectomy surgery (PEA). Risk and PH-specific treatment were assessed in surgically treated (PEA) and medically treated (non-PEA) patients at diagnosis and up to 5 years follow-up. Data are presented as median (Q1-Q3), count or per cent. Prior to surgery, 63% in the PEA-group [n = 98, age 64 (51-71) years, 37% female] used PH-specific treatment and 20, 69, and 10% were assessed as low, intermediate or high risk, respectively. After 1 year post-surgery, 34% had no PH-specific treatment or follow-up visit registered despite being alive at 5 years. Of patients with a 5 year visit (n = 23), 46% were at low and 54% at intermediate risk, while 91% used PH-specific treatment. In the non-PEA group [n = 213, age 72 (65-77) years, 56% female], 28% were assessed as low, 61% as intermediate and 11% as high risk. All patients at high risk versus 50% at low risk used PH-specific treatment. The 1 year mortality was 6%, while the risk was unchanged in 57% of the patients; 14% improved from intermediate to low risk, and 1% from high to low risk. At 5 years, 27% had a registered visit and 28% had died. Of patients with a 5 year visit (n = 58), 38% were at low, 59% at intermediate and 1% at high risk, and 86% used PH-specific treatment. CONCLUSIONS: Risk status assessed pre-surgery did not foresee long-term post-PEA risk and pre-surgery PH-specific treatment did not foresee long-term post-PEA treatment. Medically treated CTEPH patients tend to remain at the same risk over time, suggesting a need for improved treatment strategies in this group.

Complementary Feeding Social and Behavior Change Communication for Fathers and Mothers Improves Children's Consumption of Fish and Eggs and Minimum Meal Frequency in Kaduna State, Nigeria.

Background: Fathers are key influencers of complementary feeding practices, but few studies in low- and middle-income countries have measured the effects of complementary feeding social and behavior change communication (SBCC) targeted at both fathers and mothers. Objectives: The aims of this study were to measure the effects of an SBCC intervention on children's dietary diversity (primary outcome) and other complementary feeding indicators, fathers' and mothers' complementary feeding knowledge, and fathers' support for complementary feeding (secondary outcomes). Methods: The 12-mo intervention in Kaduna State, Nigeria, engaged parents through community meetings, religious services, home visits from community health extension workers (CHEWs), mobile phone messages (fathers only), and mass media. Cross-sectional population-based surveys of cohabiting fathers and mothers with a child aged 6-23 mo were conducted, and regression models were used to compare results at baseline (n = 497) and endline (n = 495). Results: Children's minimum dietary diversity did not change from baseline to endline (62% to 65%, P = 0.441). Children's consumption of fish (36% to 44%, P = 0.012) and eggs (8% to 20%, P = 0.004) and minimum meal frequency (58% to 73%, P < 0.001) increased. Fathers' and mothers' knowledge of the timing of introduction of different foods and meal frequency improved. Fathers' support for child feeding by providing money for food increased (79% to 90%, P < 0.001). Fathers' and mothers' reported intervention exposure was low (11-26% across types of SBCC). Child feeding outcomes were not associated with fathers' exposure. Children's odds of both fish and egg consumption increased significantly with mothers' exposure to community meetings, religious services, home visits, and television spots, and children's odds of minimum meal frequency increased significantly with mothers' exposure to home visits. Conclusions: A multipronged SBCC intervention improved complementary feeding practices, fathers' and mothers' knowledge of complementary feeding, and fathers' support for complementary feeding, despite low levels of reported exposure, which may have been influenced by coronavirus disease 2019 (COVID-19) disruptions. This trial was registered at ClinicalTrials.gov as NCT04835662.

Dining on the dead in the deep: Active NH4 + excretion via Na+ /H+ (NH4 + ) exchange in the highly ammonia tolerant Pacific hagfish, Eptatretus stoutii.

AIM: Pacific hagfish are exceptionally tolerant to high environmental ammonia (HEA). Here, we elucidated a cellular mechanism that enables hagfish to actively excrete ammonia against steep ammonia gradients expected to be found inside a decomposing whale carcass. METHODS: Hagfish were exposed to varying concentrations of HEA in the presence or absence of environmental Na+ , while plasma ammonia levels were tracked. 14 C-methylammonium was used as a proxy for NH4 + to measure efflux in whole animals and in isolated gill pouches; the latter allowed us to assess the effects of amiloride specifically on Na+ /H+ exchangers (NHEs) in gill cells. Western blotting and immunohistochemistry were utilized to evaluate the abundance and sub-cellular localization of Rhesus glycoprotein (Rh) channels in the response to HEA. RESULTS: Hagfish actively excreted NH4 + against steep inwardly directed ENH4 + (ΔENH4 + ~ 35 mV) and pNH3 (ΔpNH3 ~ 2000 µtorr) gradients. Active NH4 + excretion and plasma ammonia hypo-regulation were contingent on the presence of environmental Na+ , indicating a Na+ /NH4 + exchange mechanism. Active NH4 + excretion across isolated gill pouches was amiloride-sensitive. Exposure to HEA resulted in decreased abundance of Rh channels in the apical membrane of gill ionocytes. CONCLUSIONS: During HEA exposure, hagfish can actively excrete ammonia against a steep concentration gradient using apical NHEs energized by Na+ -K+ -ATPase in gill ionocytes. Additionally, apical Rh channels are removed from the apical membrane, presumably to reduce ammonia loading from the environment. We suggest that this mechanism allows hagfish to maintain tolerable ammonia levels while feeding inside decomposing carrion, allowing them to exploit nutrient-rich food-falls.

Comparing the Learning Effectiveness of Three Virtual Simulation Tools With Nursing Students During the Coronavirus Disease (COVID-19) Pandemic.

Background: We explored the learning effectiveness of three virtual simulation tools used in the Coronavirus Disease pandemic environment. Sample: Study participants consisted of students from two nursing classes, a junior and a senior class. Method: A mixed-methods approach compared three tools' performance across five learning domains. Descriptive statistics and analysis of variance compared mean ratings for learning domains. Open-ended questions were included for qualitative evaluation. Results: Thirty-six respondents rated the Resource Simulation Center (RSC), based on the observation of videos of students undergoing simulation exercises, as superior to the other two. There were no differences between the other two tools. Qualitative findings echoed preference by students for "RSC". Conclusion: "RSC" was preferred over a commercial product based on computer generated graphics, and a free-online product based on clinical scenarios acted out in short videos. Differences in debriefing practices may have influenced the results, thereby emphasizing the role of debriefing with virtual simulation tools.

Promoting deceased organ and tissue donation registration in family physician waiting rooms (RegisterNow-1): a pragmatic stepped-wedge, cluster randomized controlled registry trial.

BACKGROUND: The shortage of available organs for life-saving transplants persists worldwide. While a majority support donating their organs or tissue when they die, many have not registered their wish to do so. When registered, next of kin are much more likely to follow-through with the decision to donate. In many countries, most people visit their family physician office each year and this setting is a promising, yet underused, site where more people could register for deceased organ donation. Our primary aim was to evaluate the effectiveness of an intervention to promote organ donation registration in family physician's offices. METHODS: We developed an intervention to address barriers and enablers to organ donation registration that involved physician office reception staff inviting patients to register on a tablet in the waiting room while they waited for their appointment. We conducted a cross-sectional stepped-wedge cluster randomized controlled registry trial to evaluate the intervention. We recruited six family physician offices in Canada. All offices began with usual care and then every two weeks, one office (randomly assigned) started the intervention until all offices delivered the intervention. The primary outcome was registration for deceased organ donation in the provincial organ registration registry, assessed within the 7 days of the physician visit. At the end of the trial, we also conducted interviews with clinic staff to assess any barriers and enablers to delivering the intervention. RESULTS: The trial involved 24,616 patient visits by 13,562 unique patients: 12,484 visits in the intervention period and 12,132 in the control period. There was no statistically significant difference in the percentage of patients registered for deceased organ donation in the intervention versus control period (48.0% vs 46.2%; absolute difference after accounting for the secular trend: 0.12%; 95% CI: - 2.30, 2.54; p=0.92). Interviews with clinic staff indicated location of the tablet within a waiting room, patient rapport, existing registration, confidence and motivation to deliver the intervention and competing priorities as barriers and enablers to delivery. CONCLUSIONS: Our intervention did not increase donor registration. Nonetheless, family physician offices may still remain a promising setting to develop and evaluate better interventions to increase organ donation registration. TRIAL REGISTRATION: NCT03213171.

Breastfeeding Interpersonal Communication, Mobile Phone Support, and Mass Media Messaging Increase Exclusive Breastfeeding at 6 and 24 Weeks Among Clients of Private Health Facilities in Lagos, Nigeria.

BACKGROUND: Although most health facilities in urban Nigeria are privately owned, interventions to promote optimal breastfeeding practices in private facilities have not previously been implemented. OBJECTIVES: We tested the impact of a breastfeeding promotion intervention on early initiation of breastfeeding and exclusive breastfeeding among clients of private facilities in Lagos, Nigeria. METHODS: The intervention included training for health-care providers on the Baby-Friendly Hospital Initiative and breastfeeding counseling skills, provision of interpersonal communication and support to women at facilities and on WhatsApp, distribution of behavior change communication materials, and mobile phone and mass media messaging. We used logistic regression models adjusted for clustering to measure intervention impact in a cohort of women (n = 1200) at 10 intervention and 10 comparison facilities interviewed during their third trimester and at 6 and 24 weeks postpartum. RESULTS: The intervention significantly increased the percentage of infants who were exclusively breastfed at 6 weeks (83% intervention; 76% comparison; P = 0.02) and 24 weeks (66% intervention; 52% comparison; P < 0.001), but had no impact on early initiation of breastfeeding (35% intervention; 33% comparison; P = 0.65). Among infants who were exclusively breastfed at 6 weeks, the odds of continued exclusive breastfeeding at 24 weeks were higher in the intervention arm than in the comparison arm (OR, 1.6; 95% CI: 1.2-2.1). Infants had increased odds of being exclusively breastfed at 6 weeks if their mothers discussed breastfeeding with a private health provider (OR, 2.3; 95% CI: 1.5-3.4), received text or WhatsApp messages about breastfeeding (OR, 1.7; 95% CI: 1.0-2.7), or heard breastfeeding radio spots (OR, 4.2; 95% CI: 1.2-14.7). Infants had increased odds of exclusive breastfeeding at 24 weeks if their mothers participated in a WhatsApp breastfeeding support group (OR, 1.5; 95% CI: 1.0-2.2). CONCLUSIONS: A breastfeeding intervention in private health facilities in Lagos increased exclusive breastfeeding. Implementation of breastfeeding interventions in private facilities could extend the reach of breastfeeding promotion programs in urban Nigeria. This trial was registered at clinicaltrials.gov as NCT04835051.

A Field Test of Opportunities for Teen Dating Violence Disclosure in School-Based Relationship Education Programs.

School-based relationship education programs offer an opportunity to identify youth who are experiencing teen dating violence (TDV), support their safety, and connect them with individualized services or referrals. However, no research has tested the feasibility or accuracy of approaches to create opportunities for TDV disclosure in the context of school-based programs. The current study presents the results of a field test comparing three tools used to provide opportunities for TDV disclosure (two questionnaire-style tools and one universal education discussion guide). High school students from two federally funded healthy marriage and relationship education (HMRE) program sites (N = 648) were offered the three tools in random order over the course of the HMRE program, which lasted between 3 weeks and 3 months and took place during the school day. Onsite qualitative interviews with HMRE program staff and their local domestic violence program partners assessed how service providers saw the tools and the process of implementing them. Latent class models examined the accuracy of the tools in identifying TDV. Sensitivities of the tools were low and specificities were high; the questionnaire-style tools tended to have higher sensitivities and fewer classification errors than the universal education tool. Several three-item combinations from across the tools performed better than any intact tool, suggesting that shorter assessments may be effective, provided they include items on sexual coercion and physical violence. Qualitative findings suggested that implementation of TDV assessment and universal education in school settings is a viable strategy, provided programs are able to gain support from school staff, adapt to tight time constraints, and plan procedures for protecting student privacy and confidentiality.

The Epidemiology of Persons Living with Fontan in 2020 and Projections for 2030: Development of an Epidemiology Model Providing Multinational Estimates.

INTRODUCTION: Fontan surgery is a palliative procedure performed in children with a functionally univentricular heart. Improvements in surgical technique over the past 30 years have increased life expectancy in this rare population. However, the epidemiology of persons living with Fontan is poorly understood. This study aimed to estimate the 2020 and 2030 prevalence of persons living with a Fontan circulation in 11 countries across the US, Europe, Australia and New Zealand, by procedure type: [atriopulmonary connection (AP), lateral tunnel total cavopulmonary connection (LT-TCPC) or extracardiac total cavopulmonary connection (EC-TCPC)]; and age group: [children (< 12 years), adolescents (12-17 years), and adults (≥ 18 years old)] by building an epidemiologic model. METHODS: The annual number of Fontan surgeries by country in 2010-2020 were extracted from hospital or claims databases, via procedure codes. The epidemiology of persons living with Fontan was modelled by applying these surgery frequencies to mid-year populations from 1972 to 2020 and overlaying an uptake curve. A literature search identified: 30-day mortality rates, long-term survival, and median age at surgery. Averages of these estimates were inputted into the model to project prevalence in 2030. RESULTS: The number of persons living with Fontan in 2020 across the 11 countries was estimated to be 47,881 [66 people per million (ppm)], rising to 59,777 (79 ppm) by 2030. In 2020, this population was 55% adults, 17% adolescents and 28% children shifting to 64%, 13% and 23%, respectively, in 2030. Among all persons living with Fontan, 74%/18%/9% are estimated to have EC-TCPC/LT-TCPC/AP, respectively, in 2020, and 83%/14%/4% in 2030. CONCLUSIONS: According to this epidemiology model, the Fontan population is growing, partly driven by increased survival rates with the more recent LT-TCPC and EC-TCPC procedures (compared with AP). The 2020/2030 prevalence of persons living with Fontan is 66/79 ppm.

Rationale, Design and Methods Protocol for Participatory Design of an Online Tool to Support Industry Service Provision Regarding Digital Technology Use 'with, by and for' Young Children.

Adults who educate and care for young children are exposed to mixed-messages about what is in the best interests of young children in digital society. Such mixed-messaging makes adult decision-making about technology use in the best interests of young children hard to achieve. This project addresses this problem by working with leading organisations providing services related to quality digital media production, online-safety education, digital play and digital parenting. Using a Participatory Design approach, families, educators, industry partners and researchers will conduct mixed-methods investigations concerning: Relationships; Health and Well-being; Citizenship; and Play and Pedagogy to identify practices concerning technology use 'with, by and for' young children. Iterative design cycles will develop an Online Tool to support organisations providing services to young children and the adults responsible for their education and care. As society becomes more digital families and educators need new knowledge about what people do in digital society to inform their decision-making. This project will support organisations to use an empirically informed approach to service provision regarding using technologies in the best interests of young children.

Reducing the Burden of Complex Medication Regimens: SImplification of Medications Prescribed to Long-tErm care Residents (SIMPLER) Cluster Randomized Controlled Trial.

OBJECTIVE: To assess the application of a structured process to consolidate the number of medication administration times for residents of aged care facilities. DESIGN: A nonblinded, matched-pair, cluster randomized controlled trial. SETTING AND PARTICIPANTS: Permanent residents who were English-speaking and taking at least 1 regular medication, recruited from 8 South Australian residential aged care facilities (RACFs). METHODS: The intervention involved a clinical pharmacist applying a validated 5-step tool to identify opportunities to reduce medication complexity (eg, by administering medications at the same time or through use of longer-acting or combination formulations). Residents in the comparison group received routine care. The primary outcome at 4-month follow-up was the number of administration times per day for medications charted regularly. Resident satisfaction and quality of life were secondary outcomes. Harms included falls, medication incidents, hospitalizations, and mortality. The association between the intervention and primary outcome was estimated using linear mixed models. RESULTS: Overall, 99 residents participated in the intervention arm and 143 in the comparison arm. At baseline, the mean resident age was 86 years, 74% were female, and medications were taken an average of 4 times daily. Medication simplification was possible for 62 (65%) residents in the intervention arm, with 57 (62%) of 92 simplification recommendations implemented at follow-up. The mean number of administration times at follow-up was reduced in the intervention arm in comparison to usual care (-0.36, 95% confidence interval -0.63 to -0.09, P = .01). No significant changes in secondary outcomes or harms were observed. CONCLUSIONS AND IMPLICATIONS: One-off application of a structured tool to reduce regimen complexity is a low-risk intervention to reduce the burden of medication administration in RACFs and may enable staff to shift time to other resident care activities.

Efficacy of emicizumab prophylaxis versus factor VIII prophylaxis for treatment of hemophilia A without inhibitors: network meta-analysis and sub-group analyses of the intra-patient comparison of the HAVEN 3 trial.

Objectives: To compare the efficacy of emicizumab prophylaxis with that of factor VIII (FVIII) prophylaxis in patients with hemophilia A without inhibitors using two approaches: network meta-analyses (NMA) and additional sub-group analyses from the HAVEN 3 trial.Methods: The NMA used data from trials identified using a systematic literature review and compared bleed rates in patients receiving emicizumab prophylaxis and patients receiving FVIII prophylaxis using a Bayesian, random effects generalized linear model with log link Poisson likelihood. Additional sub-groups of the HAVEN 3 trial included here were defined as patients whose dose-taking behavior met either European label or World Federation of Hemophilia guidelines. A negative binomial regression model was used to conduct an intra-patient comparison of bleed rates within the sub-groups, during treatment with FVIII prophylaxis before entering HAVEN 3 and treatment with emicizumab prophylaxis during HAVEN 3.Results: Four studies were included in the base-case NMA. Evidence showed that the total treated bleed rate was lower with emicizumab prophylaxis compared with FVIII prophylaxis (rate ratio [RR] = 0.36 [95% credible interval (CrI) = 0.13-0.95]). Similar associations were observed in sensitivity analyses. The additional HAVEN 3 analyses also showed lower rates of treated bleeds with emicizumab prophylaxis than with FVIII prophylaxis (RRs [95% confidence interval (CI)] = 0.380 [0.186-0.790] and 0.472 [0.258-0.866] in two sub-groups). These results confirm the original HAVEN 3 intra-patient comparison findings.Conclusions: Combined findings from NMA and additional sub-group analyses of HAVEN 3 support the superiority of emicizumab prophylaxis over FVIII prophylaxis in patients with hemophilia A without inhibitors.

Key stakeholder opinions for a national learner education handover.

BACKGROUND: Sharing information about learners during training is seen as an important component supporting learner progression and relevant to patient safety. Shared information may cover topics from accommodation requirements to unprofessional behavior. The purpose of this study was to determine the views of key stakeholders on a proposed national information sharing process during the transition from undergraduate to postgraduate medical education in Canada, termed the Learner Education Handover (LEH). METHOD: Key stakeholder groups including medical students, resident physicians, residency program directors, medical regulatory authority representatives, undergraduate medical education deans, student affairs leaders, postgraduate medical education deans participated in focus groups conducted via teleconference. Data were transcribed and coded independently by two coders, then analyzed for themes informed by principles of constructivist grounded theory. RESULTS: Sixty participants (33 males and 27 females) from 16 focus groups representing key stakeholder groups participated. Most recognized value in a national LEH that would facilitate a smooth learner transition from medical school to residency. Potential risks and benefits of the LEH were identified. Themes significant to the content, process and format of the LEH also emerged. Guiding principles of the LEH process were determined to include that it be learner-centered while supporting patient safety, resident wellness and professional behavior. The learner and representatives from their undergraduate medical education environment would each contribute to the LEH. CONCLUSIONS: The LEH must advocate for the learner with respect for learner privacy, while promoting professionalism, patient safety and learner wellness.

Systematic review and network meta-analysis comparing ocrelizumab with other treatments for relapsing multiple sclerosis.

BACKGROUND: Ocrelizumab was approved for the treatment of relapsing multiple sclerosis (RMS) and primary progressive multiple sclerosis (PPMS) by the US Food and Drug Administration in March 2017 and by the European Medicines Agency in January 2018. These approvals were based on two pivotal randomized controlled trials (RCTs), OPERA I and OPERA II, comparing ocrelizumab 600 mg with an active comparator, interferon ß-1a 44 µg (Rebif), and the first trial with positive results in patients with PPMS, which compared ocrelizumab with placebo. However, direct evidence of the efficacy and safety of ocrelizumab in RMS compared with other disease-modifying therapies (DMTs) approved for RMS is not available from RCTs. In the absence of such RCTs, network meta-analyses (NMAs) were conducted to compare indirectly the relative efficacy and safety of ocrelizumab with all other approved DMTs for the treatment of RMS. METHODS: Systematic literature searches were conducted in MEDLINE, Embase, the Cochrane Library, trial registers, relevant conference websites and health technology assessment agency websites. Eligible RCTs evaluated approved treatments for multiple sclerosis (MS) in which more than 75% of patients had a relapsing form of MS. NMAs were conducted for four efficacy and three safety outcomes, and treatment hierarchies were generated for each outcome using surface under the cumulative ranking curve (SUCRA) values. RESULTS: Results suggest that ocrelizumab has superior efficacy to 10 of the 17 treatments in the 12-week confirmed disability progression network and 12 of the 17 treatments in the annualized relapse rate network (both including placebo). The efficacy of ocrelizumab was comparable with the other treatments in both networks. In the serious adverse events and discontinuation due to adverse events networks, ocrelizumab demonstrated a safety profile comparable with all other treatments (including placebo). SUCRA values consistently ranked ocrelizumab among the most effective or tolerable treatments across all outcomes. CONCLUSIONS: Results suggest that ocrelizumab has an efficacy superior to or comparable with all other currently approved DMTs across all endpoints analyzed, and a similar safety profile, indicating it offers a valuable package for the treatment of patients with RMS.

Moving beyond orientations: a multiple case study of the residency experiences of Canadian-born and immigrant international medical graduates.

Many international medical graduates (IMGs) enter North American residency programs every year. The Canadian IMG physician pool increasingly includes Canadian-born IMGs (C-IMGs) along with Immigrant-IMGs (I-IMGs). Similar trends exist in the United States. Our objective was to understand the similarities and differences in the challenges faced by both I-IMGs and C-IMGs during residency to identify actionable recommendations to support them during this critical time. We performed a multiple case study of IMGs' experiences at a large Canadian university. Within our two descriptive cases (I-IMGs, C-IMGs) we iteratively conducted twenty-two semi-structured interviews; we thematically analyzed our data within, between, and across both cases to understand challenges to IMGs' integration and opportunities for curricular innovations to facilitate their adaptation process. Research team members with different perspectives contributed reflexively to the thematic analysis. Participants identified key differences between medical culture and knowledge expected in Canada and the health systems and curricula in which they originally trained. I-IMG and C-IMG participants perceived two major challenges: discrimination because of negative labelling as IMGs and difficulties navigating their initial residency months. C-IMGs described a third challenge: frustration around the focus on the needs of I-IMGs. Participants from both groups identified two major opportunities: their desire to help other IMGs and a need for mentorship. I-IMGs and C-IMGs face diverse challenges during their training, including disorientation and discrimination. We identified specific objectives to inform the design of curriculum and support services that residency programs can offer trainees as well as important targets for resident education and faculty development.