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Abstract Background Adverse childhood experiences (ACEs) are important factors for population mental and physical health. While considerable public health literature demonstrates the global relevance of ACEs, more recent research shows that benevolent childhood experiences (BCEs) might be important to consider in their direct and mitigating roles for psychological distress and other mental health outcomes. There is little evidence of latent class examinations involving both ACEs and BCEs among adults in western nations. The present study sought to replicate and extend prior literature by: (1) assessing the extent to which past latent class groupings reproduce in present samples, and (2) analyzing the association of latent classes of childhood experiences with psychological distress and suicidal thoughts and behaviours (STBs). We examined psychological distress (i.e., depression, anxiety, post-traumatic stress, general wellbeing) and STBs (i.e., suicidal ideation, self-harm ideation and behaviour, entrapment, and defeat). Method Data were drawn from two nationwide cross-sectional online survey studies in the United Kingdom. The first sample (N = 488) was drawn from a study on suicidal behaviour, and the second sample (N = 447) was from a study concerning risk for interpersonal violence. Results Results largely replicated an existing four class solution of childhood experiences: Class 1 (Moderate ACEs/High BCEs; 17.6%), Class 2 (High ACEs/Moderate BCEs; 15.3%), Class 3 (Low ACEs/High BCEs; 48.3%), and Class 4 (Low ACEs/Moderate BCEs; 18.8%). Class 2 (High ACEs/Moderate BCEs) was associated with consistently worse psychological distress and STBs. Classes containing high BCEs (1 and 3) were characterized by generally lower levels of psychological distress and STBs. Conclusions Results affirm the potential value for jointly considering ACEs and BCEs to understand psychological distress and STBs. ACEs and BCEs may serve foundational roles in theories of suicide. The protective role of BCEs hypothesized in resiliency theory may be supported. Prevention practice and research implications are discussed.

Abstract Background It has not been clearly established if skin cancer or melanoma are manifestations of BRCA1 or BRCA2 mutation carrier status. Estimating the risk of skin cancer is an important step towards developing screening recommendations. Methods We report the findings of a prospective cohort study of 6,207 women from North America who carry BRCA1 or BRCA2 mutations. Women were followed from the date of baseline questionnaire to the diagnosis of skin cancer, to age 80 years, death from any cause, or the date of last follow-up. Results During the mean follow-up period of eight years, 3.7% of women with a BRCA1 mutation (133 of 3,623) and 3.8% of women with a BRCA2 mutation (99 of 2,584) reported a diagnosis of skin cancer (including both keratinocyte carcinomas and melanoma). The cumulative risk of all types of skin cancer from age 20 to 80 years was 14.1% for BRCA1 carriers and 10.7% for BRCA2 carriers. The cumulative risk of melanoma was 2.5% for BRCA1 carriers and 2.3% for BRCA2 carriers, compared to 1.5% for women in the general population in the United States. The strongest risk factor for skin cancer was a prior diagnosis of skin cancer. Conclusion The risk of non-melanoma skin cancer in women who carry a mutation in BRCA1 or BRCA2 is similar to that of non-carrier women. The risk of melanoma appears to be slightly elevated. We suggest that a referral to a dermatologist or primary care provider for BRCA mutation carriers for annual skin examination and counselling regarding limiting UV exposure, the use of sunscreen and recognizing the early signs of melanoma might be warranted, but further studies are necessary.

Delivering COVID-19 vaccines with 4–6 weeks shelf life remains one of Africa’s most pressing challenges. The Africa Centres for Disease Control and Prevention (Africa CDC) leadership recognised that COVID-19 vaccines donated to many African countries were at risk of expiry considering the short shelf life on delivery in the Member States and slow vaccine uptake rates. Thus, a streamlined rapid response system, the urgent support mechanism, was developed to assist countries accelerate COVID-19 vaccine uptake. We describe the achievements and lessons learnt during implementation of the urgent support mechanism in eight African countries. An Africa CDC team was rapidly deployed to meet with the Ministry of Health of each country alerted for COVID-19 vaccine expiry and identified national implementing partners to quickly develop operational work plans and strategies to scale up the urgent use of the vaccines. The time between the initiation of alerts to the start of the implementation was typically within 2 weeks. A total of approximately 2.5 million doses of vaccines, costing $900 000, were prevented from expiration. The urgent support has also contributed to the increased COVID-19 vaccination coverage in the Member States from 16.1% at the initiation to 25.3% at the end of the urgent support. Some of the effective strategies used by the urgent support mechanism included coordination between Africa CDC and country vaccine task forces, establishment of vaccination centres, building the capacity of routine and surge health workforce, procurement and distribution of vaccine ancillaries, staff training, advocacy and sensitisation events, and use of trusted religious scriptures and community influencers to support public health messages. The urgent support mechanism demonstrated a highly optimised process and serves as a successful example for acceleration and integration of vaccination into different healthcare delivery points.

There are many items in Wikidata representing scholarly articles. However, these items have been created mostly by volunteer Wikidata editors and not systematically by journal publishers or editors, which can lead to gaps and inconsistencies in the datasets. This article presents findings from a survey investigating practices of library and information studies (LIS) journals in Wikidata item creation. Believing that a significant number of LIS journal editors would be aware of Wikidata and some would be creating Wikidata items for their publications, the authors sent a survey asking 138 English-language LIS journal editors if they created Wikidata items for materials published in their journal and follow-up questions. With a response rate of 41 percent, respondents overwhelmingly indicated that they did not create Wikidata items for materials published in their journal and were completely unaware of or only somewhat familiar with Wikidata. Respondents indicated that more familiarity with Wikidata and its benefits for scholarly journals as well as institutional support for the creation of Wikidata items could lead to greater participation; however, a campaign of education about Wikidata, documentation of benefits, and support for creation would be a necessary first step. The article presents and discusses the results of the survey, but the conclusions that can be drawn are minimal; therefore, the authors also discuss the benefits of creating Wikidata items for LIS journals as a first step in this educational campaign for editors and publishers.

Abstract Background Antibiotic resistance is a significant public health problem and is responsible for high mortality in children and new-borns. Strengthening the rational use of antibiotics and improving the quality and access to existing antibiotics are important factors in the fight against antibiotic resistance. This study aims to provide knowledge on the use of antibiotics in children in resource-limited countries in order to identify problems and possible avenues for improvement of antibiotics use. Methods We conducted a retrospective study in July 2020 and collected quantitative clinical and therapeutic data on antibiotic prescriptions between January and December 2019 in 4 hospitals or health centres in both Uganda and Niger, respectively from January to December 2019. Semi-structured interviews and focus groups were conducted among healthcare personnel and carers for children under 17 years of age, respectively. Results A total of 1,622 children in Uganda and 660 children in Niger (mean age of 3.9 years (SD 4.43)) who received at least one antibiotic were included in the study. In hospital settings, 98.4 to 100% of children prescribed at least one antibiotic received at least one injectable antibiotic. Most hospitalized children received more than one antibiotic in both Uganda (52.1%) and Niger (71.1%). According to the WHO-AWaRe index, the proportion of prescriptions of antibiotics belonging to the Watch category was 21.8% (432/1982) in Uganda and 32.0% (371/1158) in Niger. No antibiotics from the Reserve category were prescribed. Health care provider’s prescribing practices are rarely guided by microbiological analyses. Prescribers are faced with numerous constraints, such as lack of standard national guidelines, unavailability of essential antibiotics at the level of hospital pharmacies, the limited financial means of the families, and pressure to prescribe antibiotics from caregivers as well as from drug company representatives. The quality of some antibiotics provided by the National Medical Stores to the public and private hospitals has been questioned by some health professionals. Self-medication is a widespread practice for the antibiotic treatment of children for economic and access reasons. Conclusion The study findings indicate that an intersection of policy, institutional norms and practices including individual caregiver or health provider factors, influence antibiotic prescription, administration and dispensing practices.

Educational opportunities for investigators and staff to promote inclusive research practices are a critical piece of the effort to increase diversity in study participation and promote health equity. However, few trainings to date have empirically been shown to result in behavior changes. We present preliminary evaluation findings for the Just Research workshop offered at the University of Wisconsin–Madison between October 2022 and August 2023. These sessions included 80 participants who made up 4 cohorts. Data was collected through a retrospective pre/post-test survey administered 0–7 days following the workshop (n = 70), and a follow-up survey administered 9–12 months following the workshop (n = 21). Participants demonstrate significant increases in knowledge and self-efficacy regarding implementing inclusive practices post-intervention (p < .001). 85.7% of participants who completed the follow-up survey reported implementing inclusive practices.

Despite the growing availability of effective COVID-19 vaccines in rural communities in the United States, widespread vaccine hesitancy delays COVID-19 vaccine coverage in rural communities and threatens to worsen pre-pandemic rural–urban disparities in other vaccination rates, including influenza and routine pediatric immunizations. Therefore, there is an urgent need to develop communication-based interventions to improve vaccine confidence in rural America. This study demonstrates the efficacy of a community-engaged approach to developing social media campaign messages in promoting COVID-19 vaccine uptake and pro-vaccine social diffusion among rural adults. Using a community-engaged approach, we developed social media campaign videos varying in (a) featured messengers (clinicians versus community leaders) and (b) the presence of personal testimonials. We conducted a national online experiment (N = 1,364 rural adults) in spring 2022. We found that videos featuring clinicians serving rural communities and their testimonials increased (a) vaccination intentions in the unvaccinated group (4-point scale, b = 0.23, p =.015) and (b) intention to discuss the messages with others (4-point scale, b = 0.14, p =.037), share the message (4-point scale, b = 0.15, p =.026), and promote the vaccines to others (9-point scale, b = 0.48, p =.013). Results suggest that vaccine promotional social media campaigns targeting rural populations can benefit from including clinician testimonials.

With the aim of achieving a method to develop and increase the social, communication, and daily life skills of independent children, the present researcher investigated the effect of the applied behavior analysis method on these children’s social and emotional skills. In terms of purpose and data acquisition, the research was applied and semi-experimental, with control and experimental groups and a covariance analysis model. This study’s statistical population consisted of 48 volunteer boys aged 4 to 11 years old who resided in Tehran between 2020 and 2021. Of this population, 24 boys were selected and assigned to two control and experimental groups (12 individuals in each group). For data collection, the Social and Emotional Skills Questionnaire for Preschoolers (KIST) was utilized. Individually, the applied behavior analysis program was administered to the experimental group in 8 one-hour sessions twice per week. Using SPSS-24 software and multivariate covariance analysis, the data were analyzed. The results demonstrated that the applied behavior analysis program improved the social and communication skills of bereaved children as well as their day-to-day functioning (p

Abstract Lung cancer is the leading cause of cancer‐related deaths worldwide. Surgery and chemoradiation are the standard of care in early stages of non‐small cell lung cancer (NSCLC), while immunotherapy is the standard of care in late‐stage NSCLC. The immune composition of the tumor microenvironment (TME) is recognized as an indicator for responsiveness to immunotherapy, although much remains unknown about its role in responsiveness to surgery or chemoradiation. In this pilot study, we characterized the NSCLC TME using mass cytometry (CyTOF) and bulk RNA sequencing (RNA‐Seq) with deconvolution of RNA‐Seq being performed by Kassandra, a recently published deconvolution tool. Stratification of patients based on the intratumoral abundance of B cells identified that the B‐cell rich patient group had increased expression of CXCL13 and greater abundance of PD1+ CD8 T cells. The presence of B cells and PD1+ CD8 T cells correlated positively with the presence of intratumoral tertiary lymphoid structures (TLS). We then assessed the predictive and prognostic utility of these cell types and TLS within publicly available stage 3 and 4 lung adenocarcinoma (LUAD) RNA‐Seq datasets. As previously described by others, pre‐treatment expression of intratumoral 12‐chemokine TLS gene signature is associated with progression free survival (PFS) in patients who receive treatment with immune checkpoint inhibitors (ICI). Notably and unexpectedly pre‐treatment percentages of intratumoral B cells are associated with PFS in patients who receive surgery, chemotherapy, or radiation. Further studies to confirm these findings would allow for more effective patient selection for both ICI and non‐ICI treatments.

Abstract Background Survivorship care plans (SCPs) communicate cancer‐related information from oncology providers to patients and primary care providers. SCPs may limit overuse testing by specifying necessary follow‐up care. From a randomized, controlled trial of SCP delivery, we examined whether cancer‐related tests not specified in SCPs, but conducted after SCP receipt, were appropriate or consistent with overuse. Methods Survivors of breast, colorectal, or prostate cancer treated at urban‐academic or rural‐community health systems were randomized to one of three SCP delivery arms. Tests during 18 months after SCP receipt were classified as consistent with overuse if they were (1) not included in SCPs and (2) on a guideline‐based predetermined list of “not recommended surveillance.” After chart abstraction, physicians performed review and adjudication of potential overuse. Descriptive analyses were conducted of tests consistent with overuse. Negative binomial regression models determined if testing consistent with overuse differed across study arms. Results Among 316 patients (137 breast, 67 colorectal, 112 prostate), 140 individual tests were identified as potential overuse. Upon review, 98 were deemed to be consistent with overuse: 78 tumor markers and 20 imaging tests. The majority of overuse testing was breast cancer‐related (95%). Across sites, 27 patients (9%) received ≥1 test consistent with overuse; most were breast cancer patients (22/27). Exploratory analyses of overuse test frequency by study arm showed no significant difference. Conclusions This analysis identified practice patterns consistent with overuse of surveillance testing and can inform efforts to improve guideline‐concordant care. Future interventions may include individual practice patterns and provider education.

Introduction Several factors have been associated with excess weight gain in adolescents, including loss of sleep. Objective The purpose of this study is to examine the effects of sleep factors on appetite, dietary intake, and the body weights of adolescent youth. Methods A prospective correlational study design was used. Male and female adolescents (N = 76) ages 12–18 years completed a 5-night study. Sleep was assessed using Fitbits (88.5% accuracy) and the Pittsburgh Sleep Quality Index (PSQI) (test-retest reliability = .81); appetite was assessed by a Visual Analog Scale (α = 0.84); dietary intake was assessed by the Block Kids Food Screener (reliability up to .88); sleep hygiene was assessed using the Adolescent Sleep Hygiene Practice Scale (α = .67). Results Poor sleep quality was reported by 39.5% of participants, and 75% of participants had inadequate sleep time (7.33 h). Participants’ age significantly correlated with PSQI scores (r = .28, p

IntroductionQ fever, caused by the intracellular bacterium Coxiella burnetii, is considered an occupational and biodefense hazard and can result in debilitating long-term complications. While natural infection and vaccination induce humoral and cellular immune responses, the exact nature of cellular immune responses to C. burnetii is incompletely understood. The current study seeks to investigate more deeply the nature of long-term cellular recall responses in naturally exposed individuals by both cytokine release assessment and cytometry profiling.MethodsIndividuals exposed during the 2007-2010 Dutch Q fever outbreak were grouped in 2015, based on a C. burnetii-specific IFNγ release assay (IGRA), serological status, and self-reported clinical symptoms during initial infection, into asymptomatic IGRA-negative/seronegative controls, and three IGRA-positive groups (seronegative/asymptomatic; seropositive/asymptomatic and seropositive/symptomatic). Recall responses following in vitro re-stimulation with heat-inactivated C. burnetii in whole blood, were assessed in 2016/2017 by cytokine release assays (n=55) and flow cytometry (n=36), and in blood mononuclear cells by mass cytometry (n=36).ResultsCytokine release analysis showed significantly elevated IL-2 responses in all seropositive individuals and elevated IL-1β responses in those recovered from symptomatic infection. Comparative flow cytometry analysis revealed significantly increased IFNγ, TNFα and IL-2 recall responses by CD4 T cells and higher IL-6 production by monocytes from symptomatic, IGRA-positive/seropositive individuals compared to controls. Mass cytometry profiling and unsupervised clustering analysis confirmed recall responses in seropositive individuals by two activated CD4 T cell subsets, one characterized by a strong Th1 cytokine profile (IFNγ+IL-2+TNFα+), and identified C. burnetii-specific activation of CD8 T cells in all IGRA-positive groups. Remarkably, increased C. burnetii-specific responses in IGRA-positive individuals were also observed in three innate cell subpopulations: one characterized by an IFNγ+IL-2+TNFα+ Th1 cytokine profile and lack of canonical marker expression, and two IL-1β-, IL-6- and IL-8-producing CD14+ monocyte subsets that could be the drivers of elevated secretion of innate cytokines in pre-exposed individuals.DiscussionThese data highlight that there are long-term increased responses to C. burnetii in both adaptive and innate cellular compartments, the latter being indicative of trained immunity. These findings warrant future studies into the protective role of these innate responses and may inform future Q fever vaccine design.

Abstract While several artificial nanodrugs have been approved for clinical treatment of breast tumor, their long-term applications are restricted by unsatisfactory therapeutic outcomes, side reactions and high costs. Conversely, edible plant-derived natural nanotherapeutics (NTs) are source-widespread and cost-effective, which have been shown remarkably effective in disease treatment. Herein, we extracted and purified exosome-like NTs from tea leaves (TLNTs), which had an average diameter of 166.9 nm and a negative-charged surface of − 28.8 mV. These TLNTs contained an adequate slew of functional components such as lipids, proteins and pharmacologically active molecules. In vitro studies indicated that TLNTs were effectively internalized by breast tumor cells (4T1 cells) and caused a 2.5-fold increase in the amount of intracellular reactive oxygen species (ROS) after incubation for 8 h. The high levels of ROS triggered mitochondrial damages and arrested cell cycles, resulting in the apoptosis of tumor cells. The mouse experiments revealed that TLNTs achieved good therapeutic effects against breast tumors regardless of intravenous injection and oral administration through direct pro-apoptosis and microbiota modulation. Strikingly, the intravenous injection of TLNTs, not oral administration, yielded obvious hepatorenal toxicity and immune activation. These findings collectively demonstrate that TLNTs can be developed as a promising oral therapeutic platform for the treatment of breast cancer. Graphic Abstract

Abstract Background Multiple Sclerosis is an autoimmune inflammatory disease of the central nervous system that often leads to premature incapacity for work. Therefore, the MSnetWork project implements a new form of care and pursues the goal of maintaining or even improving the state of health of MS patients and having a positive influence on their ability to work as well as their participation in social life. A network of neurologists, occupational health and rehabilitation physicians, psychologists, and social insurance suppliers provide patients with targeted services that have not previously been part of standard care. According to the patient’s needs treatment options will be identified and initiated. Methods The MSnetWork study is designed as a multicenter randomized controlled trial, with two parallel groups (randomization at the patient level with 1:1 allocation ratio, planned N = 950, duration of study participation 24 months). After 12 months, the patients in the control group will also receive the interventions. The primary outcome is the number of sick leave days. Secondary outcomes are health-related quality of life, physical, affective and cognitive status, fatigue, costs of incapacity to work, treatment costs, out-of-pocket costs, self-efficacy, and patient satisfaction with therapy. Intervention effects are analyzed by a parallel-group comparison between the intervention and the control group. Furthermore, the long-term effects within the intervention group will be observed and a pre-post comparison of the control group, before and after receiving the intervention in MSnetWork, will be performed. Discussion Due to the multiple approaches to patient-centered, multidisciplinary MS care, MSnetWork can be considered a complex intervention. The study design and linkage of comprehensive, patient-specific primary and secondary data in an outpatient setting enable the evaluation of this complex intervention, both on a qualitative and quantitative level. The basic assumption is a positive effect on the prevention or reduction of incapacity for work as well as on the patients’ quality of life. If the project proves to be a success, MSnetWork could be adapted for the treatment of other chronic diseases with an impact on the ability to work and quality of life. Trial registration The trial MSnetWork has been retrospectively registered in the German Clinical Trials Register (DRKS) since 08.07.2022 with the ID DRKS00025451 .

Abstract Background Public resources to answer pertinent research questions about the impact of illness and treatment on people with mental health problems are limited. To target funds effectively and efficiently and maximize the health benefits to populations, prioritizing research areas is needed. Research agendas are generally driven by researcher and funder priorities, however, there is growing recognition of the need to include user‐defined research priorities to make research more relevant, needs‐based and efficient. Objective To gain consensus on top priorities for research into early intervention in psychosis through a robust, democratic process for prioritization enlisting the views of key stakeholders including users, carers and healthcare professionals. We also sought to determine which user‐prioritized questions were supported by scientific evidence. Design and Methods We used a modified nominal group technique to gain consensus on unanswered questions that were obtained by survey and ranked at successive stages by a steering group comprising users, carer representatives and clinicians from relevant disciplines and stakeholder bodies. We checked each question posed in the survey was unanswered in research by reviewing evidence in five databases (Medline, Cinahl, PsychInfo, EMBASE and Cochrane Database). Results Two hundred and eighty‐three questions were submitted by 207 people. After checking for relevance, reframing and examining for duplicates, 258 questions remained. We gained consensus on 10 priority questions; these largely represented themes around access and engagement, information needs before and after treatment acceptance, and the influence of service‐user (SU) priorities and beliefs on treatment choices and effectiveness. A recovery SUtheme identified specific self‐management questions and more globally, a need to fully identify factors that impact recovery. Discussion and Conclusions Published research findings indicated that the priorities of service users, carers and healthcare professionals were aligned with researchers' and funders' priorities in some areas and misaligned in others providing vital opportunities to develop research agendas that more closely reflect users' needs. Patient and Public Contribution Initial results were presented at stakeholder workshops which included service‐users, carers, health professionals and researchers during a consensus workshop to prioritize research questions and allow the opportunity for feedback. Patient and public representatives formed part of the steering group and were consulted regularly during the research process.

Background: Previous analyses describing the relationship between SARS-CoV-2 infection and Staphylococcus aureus have focused on hospital-onset S. aureus infections occurring during COVID-19 hospitalizations. Because most invasive S. aureus (iSA) infections are community-onset (CO), we characterized CO iSA cases with a recent positive SARS-CoV-2 test (coinfection). Methods: We analyzed CDC Emerging Infections Program active, population- and laboratory-based iSA surveillance data among adults during March 1–December 31, 2020, from 11 counties in 7 states. The iSA cases (S. aureus isolation from a normally sterile site in a surveillance area resident) were considered CO if culture was obtained 73 years, LTCF residence 3 days before iSA culture, and/or CVC present any time during the 2 days before iSA culture. More often, iSA cases with SARS-CoV-2 coinfection were admitted to the intensive care unit ≤2 days after iSA culture (37.7% vs 23.3%, P

Abstract We present a 67‐year‐old woman who developed progressive pancytopenia over 10 months, concomitant with administration of severe adult respiratory syndrome coronavirus‐2 (SARS‐CoV‐2), pneumococcal and influenza vaccines. She developed mild leukopenia ∼2 weeks after the SARS‐CoV‐2 mRNA vaccine sequence, with progressive symptoms after subsequent vaccines, eventually developing severe aplastic anaemia (SAA). While there have been several reports of vaccine‐related SAA, at time of submission, our case is the first reported to develop after the Moderna mRNA SARS‐CoV‐2 vaccine, as well as the first to document the gradual development of SAA over the course of many vaccine exposures. Physicians should be cognizant of vaccine‐associated SAA, considering current widespread coronavirus disease 2019 vaccination efforts.

Objective This open pilot study examines the feasibility, acceptability, and qualitative outcomes of an interactive web- and text message-delivered personalized feedback intervention aimed at cultivating motivation and tolerance of distress for adults initiating outpatient buprenorphine treatment. Methods Patients ( n = 10) initiating buprenorphine within the past 8 weeks first completed a web-based intervention focused on enhancing motivation and providing psychoeducation on distress tolerance skills. Participants then received 8 weeks of daily personalized text messages that provided reminders of salient motivational factors and recommended distress tolerance-oriented coping skills. Participants completed self-report measures to assess intervention satisfaction, perceived usability, and preliminary efficacy. Additional perspectives were captured via qualitative exit interviews. Results In total, 100% of retained participants ( n = 9) engaged with the text messages throughout the entire 8-week period. Mean scores of 27 (SD = 5.05) on the Client Satisfaction Questionnaire at the end of 8-week period indicated a high degree of satisfaction with the text-based intervention. The average rating on the System Usability Scale was 65.3 at the end of the 8-week program, suggesting that the intervention was relatively easy to use. Participants also endorsed positive experiences with the intervention during qualitative interviews. Clinical improvements were observed across the intervention period. Conclusions Preliminary findings from this pilot suggest that the content and delivery method of this combined web- and text message-based personalized feedback intervention is perceived by patients as feasible and acceptable. Leveraging digital health platforms to augment buprenorphine has potential for high scalability and impact to reduce opioid use, increase adherence/retention to treatment, and prevent future incidence of overdose. Future work will evaluate the efficacy of the intervention in a randomized clinical trial design.

BackgroundOccupational therapists (OTs) and physiotherapists (PTs) are expected to provide evidence-based services to individuals living with disabilities. Despite the emphasis on evidence-based practice (EBP) by professional entry-level programs and professional bodies, little is known about their EBP competencies upon entry to practice and over time or what factors impact EBP use. The aim of the study was to measure and understand how EBP evolves over the first three years after graduation among Canadian OTs and PTs, and how individual and organizational factors impact the continuous use of EBP.MethodsA longitudinal, mixed methods sequential explanatory study. We administered a survey questionnaire measuring six EBP constructs (knowledge, attitudes, confidence, resources, use of EBP and evidence-based activities) annually, followed by focus group discussions with a subset of survey participants. We performed group-based trajectory modeling to identify trajectories of EBP over time, and a content analysis of qualitative data guided by the Theoretical Domains Framework.ResultsOf 1700 graduates in 2016-2017, 257 (response rate = 15%) responded at baseline (T0) (i.e., at graduation), and 83 (retention rate = 32%), 75 (retention rate = 29%), and 74 (retention rate = 29%) participated at time point 1 (T1: one year into practice), time point 2 (T2: two years into practice, and time point 3 (T3: three years into practice) respectively. Group-based trajectory modeling showed four unique group trajectories for the use of EBP. Over 64% of participants (two trajectories) showed a decline in the use of EBP over time. Fifteen practitioners (7 OTs and 8 PTs) participated in the focus group discussions. Personal and peer experiences, client needs and expectations, and availability of resources were perceived to influence EBP the most.ConclusionsThough a decline in EBP may be concerning, it is unclear if this decline is clinically meaningful and whether professional expertise can offset such declines. Stakeholder-concerted efforts towards the common goal of promoting EBP in education, practice and policy are needed.

A major limitation of current reports on insect declines is the lack of standardized, long-term, and taxonomically broad time series. Here, we demonstrate the utility of environmental DNA from archived leaf material to characterize plant-associated arthropod communities. We base our work on several multi-decadal leaf time series from tree canopies in four land use types, which were sampled as part of a long-term environmental monitoring program across Germany. Using these highly standardized and well-preserved samples, we analyze temporal changes in communities of several thousand arthropod species belonging to 23 orders using metabarcoding and quantitative PCR. Our data do not support widespread declines of α-diversity or genetic variation within sites. Instead, we find a gradual community turnover, which results in temporal and spatial biotic homogenization, across all land use types and all arthropod orders. Our results suggest that insect decline is more complex than mere α-diversity loss, but can be driven by β-diversity decay across space and time.

In response to the COVID-19 pandemic, the American Board of Obstetrics and Gynecology canceled the 2020 in-person subspecialty certifying examinations and developed remote administration of 4 subspecialty certifying examinations in 2021 for both examiners and candidates. Because of the continued risks of the COVID-19 pandemic, the 2021 specialty certifying examinations and the 2022 subspecialty certifying examinations were also administered remotely for candidates. For these examinations, examiners participated remotely in 2021 and were at the American Board of Obstetrics and Gynecology testing center in 2022. Overall, the American Board of Obstetrics and Gynecology remote certifying examinations have been well-received by candidates and examiners according to posttest survey data. Candidate performance has been comparable to that observed in the previous in-person examinations. In this review, we describe our implementation, process modifications, successes, and challenges with remote testing. During this process, the American Board of Medical Specialties approval was required, and the Standards for Educational and Psychological Testing served as our testing-industry guideline to ensure valid interpretation of scores and fairness to candidates.

BackgroundThe cumulative body of research on suicidality in later life describes its unique and complex features in older people when compared with that in other population groups. Yet significant gaps exist in how research informs the further development of suitable interventions. The perspectives of older people are also limited in research findings.AimsTherefore, this exploratory study aimed to (1) identify potential barriers and enablers in discussing suicidal thoughts and their expression in later life from the perspectives of lay older people and (2) explore where opportunities might occur in approach, place, relationships, and language with older people to discuss suicidal thoughts and their expression.MethodWe conducted in-depth qualitative individual interviews with 15 people aged 70–89 years. This method helped explore older peoples' own lay perspectives on suicidal thoughts in later life and how these are expressed, and their understanding of where and how people might seek support.ResultsA total of three themes were generated from the dataset: (1) intergenerational and socio-cultural differences in suicide expression, (2) the normalization of suicidal thoughts in later life, and (3) the importance and difficulties of everyday discussion and opportunities to express suicidal thoughts.ConclusionSuicidal thoughts and their expression appear commonly and are normalized in later life yet remain taboo and hidden. The participants revealed how such thoughts and behaviors are typically expressed through colloquial or “off-hand” remarks and comments and the importance of authentic listening. The findings highlight the importance of more informal discussions around these topics and how care professionals, practitioners, and providers might frame opportunities for dialogue with people who may want to access support. Further engagement with community-informed participatory research methods in which older people provide their own perspectives and experiences is important in addressing these gaps. There is a need for co-designing in developing screening, assessment, and signposting outside of clinical settings that can be used in everyday caring relationships with people in later life.

This article explores diasporic experiences and reflections on religious conversion through analyzing visitational, predictive/generative, and inspirational dreams recalled and related by Kabyle immigrant converts in France, which prompted their earlier conversion from Islam in their home region of Kabylie in Algeria, North Africa, prior to their migration to France. There is an approach to dreaming as both self-psychoanalysis and social practice in which visions in visitational dreams illuminate complex cultural identity and belonging in contexts of believed soul travel in dream time and transcultural migration over space. Useful in this analysis is Mikhail Bakhtin’s concept of the chronotope, referring to how configurations of time and space are represented in language—in the present case, dreams—analyzed here in terms of how converts’ dreaming, cultural theories of dreams, and dream-sharing construct ambiguous, changing, and ambivalent meanings of conversion in bringing together, but also highlighting contrasts between, cultural and religious distances over time and space. Pre- and post-conversion disruptions emerge in dreams that reveal both religious change and cultural continuity in ways these diasporic converts forge new meanings of identity and belonging as they cope with remembered political violence in Algeria and ongoing economic precarity, political discrimination, and social ambiguity in France. More broadly, an approach inspired by a Bakhtinian (1981) “chronotopic” metaphor hopefully opens up rich perspectives in the study of diasporic spaces and entangled religions in contexts of both conjunctions and disjunctions between dreaming and waking lifeworlds of contradictions and dilemmas over time.

Introduction: Permanent genital hair removal is required before gender-affirming vaginoplasty to prevent hair-related complications. No previous studies have directly compared the relative efficacy, costs, and patient experiences with laser hair removal (LHR) vs electrolysis treatments. Food and Drug Administration (FDA) oversight of medical devices is poorly understood and commonly misrepresented, adversely affecting patient care. Aim: This study compares treatment outcomes of electrolysis and LHR for genital hair removal and investigates FDA regulation of electrolysis and LHR devices. Methods: Penile-inversion vaginoplasty and shallow-depth vaginoplasty patients completed surveys about their preoperative hair removal, including procedure type, number/frequency of sessions, cost, and discomfort. Publicly available FDA-review documents and databases were reviewed. Main Outcomes Measure: Compared to electrolysis, LHR was associated with greater efficiency, decreased cost, decreased pain, and improved patient satisfaction. Results: Of 52 total (44 full-depth and 8 shallow-depth) vaginoplasty patients, 22 of 52 underwent electrolysis only, 15 of 52 underwent laser only, and 15 of 52 used both techniques. Compared to patients that underwent LHR only, patients that underwent only electrolysis required a significantly greater number of treatment sessions (mean 24.3 electrolysis vs 8.1 LHR sessions, P < .01) and more frequent sessions (every 2.4 weeks for electrolysis vs 5.3 weeks for LHR, P < .01) to complete treatment (defined as absence of re-growth over 2 months). Electrolysis sessions were significantly longer than LHR sessions (152 minutes vs 26 minutes, P < .01). Total treatment costs for electrolysis ($5,161) were significantly greater than for laser ($981, P < .01). Electrolysis was associated with greater pain and significantly increased need for pretreatment analgesia, which further contributed to higher net costs for treatment with electrolysis vs laser. Many LHR and electrolysis devices have been FDA-cleared for safety, but the FDA does not assess or compare clinical efficacy or efficiency. Clinical Implications: For patients with dark-pigmented hair, providers should consider LHR as the first-line treatment option for preoperative hair removal before gender-affirming vaginoplasty. Strength and Limitations: This is the first study to compare electrolysis and LHR for genital hair removal. The discussion addresses FDA review/oversight of devices, which is commonly misrepresented. Limitations include the survey format for data collection. Conclusion: When compared with electrolysis, LHR showed greater treatment efficiency (shorter and fewer treatment sessions to complete treatment), less pain, greater tolerability, and lower total cost. Our data suggests that, for patients with dark genital hair, providers should consider recommending laser as the first-line treatment for permanent genital hair removal before vaginoplasty.Yuan N, Feldman A, Chin P, et al. Comparison of Permanent Hair Removal Procedures before Gender-Affirming Vaginoplasty: Why We Should Consider Laser Hair Removal as a First-Line Treatment for Patients Who Meet Criteria. Sex Med 2022;10:100545.

Background: Despite the extensive benefits of implementing Medications for Opioid Use Disorder (MOUD) in jail/prison, criminal justice-involved populations face significant challenges when transitioning back to the community following a period of incarceration. These risk factors are associated with increased drug use and discontinuation of evidence-based care. Novel intervention strategies are needed to support this high-risk period of transition. The primary objective of this protocol was to gather perspectives from the target population to optimize feasibility and acceptability of a combined in-person and text message-delivered intervention designed to support community reentry and continuation of MOUD. Methods: Participants (n = 8), who had prior experience engaging in MOUD while in jail/prison, were recruited from an outpatient primary care clinic in Rhode Island. A semi-structured interview was conducted to assess barriers/facilitators to technology following release, experiences of community reentry and OUD treatment, perceptions of continuum of care, and feasibility/acceptability of the intervention. All interviews were coded independently by 2 research assistants. Results: Participants reacted positively toward an intervention designed to support the transition to community-based care. Most participants denied any apprehension about using this type of platform. Obtaining a cell phone following release was endorsed as generally viable; however, special consideration must be paid to the consistency of cell phone service as well as digital literacy. Participants readily agreed on the utility of structured, daily text messages that provide motivational reminders and distress tolerance skill suggestions as well as the opportunity to access “on-demand” support. Conclusion: Overall, individuals engaged in MOUD while in jail/prison were receptive to a motivational- and distress tolerance-based digital health intervention to support recovery. Incorporating thematic results on suggested structural changes may increase the usability of this intervention to promote continuation of MOUD following release from jail/prison.

Abstract Next-generation sequencing (NGS) technologies have facilitated multi-gene panel (MGP) testing to detect germline DNA variants in hereditary cancer patients. This sensitive technique can uncover unexpected, non-germline incidental findings indicative of mosaicism, clonal hematopoiesis (CH), or hematologic malignancies. A retrospective chart review was conducted to identify cases of incidental findings from NGS-MGP testing. Inclusion criteria included: 1) multiple pathogenic variants in the same patient; 2) pathogenic variants at a low allele fraction; and/or 3) the presence of pathogenic variants not consistent with family history. Secondary tissue analysis, complete blood count (CBC) and medical record review were conducted to further delineate the etiology of the pathogenic variants. Of 6060 NGS-MGP tests, 24 cases fulfilling our inclusion criteria were identified. Pathogenic variants were detected in TP53, ATM, CHEK2, BRCA1 and APC. 18/24 (75.0%) patients were classified as CH, 3/24 (12.5%) as mosaic, 2/24 (8.3%) related to a hematologic malignancy, and 1/24 (4.2%) as true germline. We describe a case-specific workflow to identify and interpret the nature of incidental findings on NGS-MGP. This workflow will provide oncology and genetic clinics a practical guide for the management and counselling of patients with unexpected NGS-MGP findings.

Abstract A model‐informed drug development approach was used to select ceftaroline fosamil high‐dose regimens for pediatric patients with complicated skin and soft‐tissue infections caused by Staphylococcus aureus with a ceftaroline minimum inhibitory concentration (MIC) of 2 or 4 mg/L. Steady‐state ceftaroline concentrations were simulated using a population pharmacokinetics (PK) model for ceftaroline fosamil and ceftaroline including data from 304 pediatric subjects and 944 adults. Probability of target attainment (PTA) for various simulated pediatric high‐dose regimens and renal function categories were calculated based on patients achieving 35% fT>MIC (S. aureus PK/pharmacodynamic target for 2‐log10 bacterial killing). For extrapolation of efficacy, simulated exposures and PTA were compared to adults with normal renal function receiving high‐dose ceftaroline fosamil (600 mg 2‐h infusions every 8 h). For safety, predicted ceftaroline exposures were compared with observed pediatric and adult data. Predicted ceftaroline exposures for the approved pediatric high‐dose regimens (12, 10, or 8 mg/kg by 2‐h infusions every 8 h for patients aged >2 to 99% and ≥81% for MICs of 2 and 4 mg/L, respectively) matched or exceeded the adult predictions. Simulated Cmax,ss values were below the maximum observed data in other indications, including a high‐dose pediatric pneumonia trial, which reported no adverse events related to high exposure.

Gastrointestinal (GI) cancers are among the main reasons for cancer death globally. The deadliest types of GI cancer include colon, stomach, and liver cancers. Multiple lines of evidence have shown that angiogenesis has a key role in the growth and metastasis of all GI tumors. Abnormal angiogenesis also has a critical role in many non-malignant diseases. Therefore, angiogenesis is considered to be an important target for improved cancer treatment. Despite much research, the mechanisms governing angiogenesis are not completely understood. Recently, it has been shown that angiogenesis-related non-coding RNAs (ncRNAs) could affect the development of angiogenesis in cancer cells and tumors. The broad family of ncRNAs, which include long non-coding RNAs, microRNAs, and circular RNAs, are related to the development, promotion, and metastasis of GI cancers, especially in angiogenesis. This review discusses the role of ncRNAs in mediating angiogenesis in various types of GI cancers and looks forward to the introduction of mimetics and antagonists as possible therapeutic agents.

Disentangling the impacts of non-pharmaceutical interventions on COVID-19 transmission is challenging as they have been used in different combinations across time and space. This study shows that, early in the epidemic, school/daycare closures and stopping nursing home visits were associated with the biggest reduction in transmission in the United States.

Background: Incidence of methicillin-sensitive Staphylococcus aureus (MSSA) bloodstream infections (BSIs) in the United States during 2012–2017 has been reported to have been stable for hospital-onset BSIs and to have increased 3.9% per year for community-onset BSIs. We sought to determine whether these trends continued in more recent years and whether there were further differences within subgroups of community-onset BSIs. Methods: We analyzed CDC Emerging Infections Program active, population- and laboratory-based surveillance data during 2016–2019 for MSSA BSIs from 8 counties in 5 states. BSI cases were defined as isolation of MSSA from blood in a surveillance area resident. Cases were considered hospital onset (HO) if culture was obtained >3 days after hospital admission and healthcare-associated community-onset (HACO) if culture was obtained on or after day 3 of hospitalization and was associated with dialysis, hospitalization, surgery, or long-term care facility residence within 1 year prior or if a central venous catheter was present ≤2 days prior. Cases were otherwise considered community-associated (CA). Annual rates per 100,000 census population were calculated for each epidemiologic classification; rates of HACO cases among chronic dialysis patients per 100,000 dialysis patients were calculated using US Renal Data System data. Annual increases were modeled using negative binomial or Poisson regression and accounting for changes in the overall population age group, and sex. Descriptive analyses were performed. Results: Overall, 8,344 MSSA BSI cases were reported. From 2016–2019 total MSSA BSI rates increased from 23.9 per 100,000 to 28.5 per 100,000 (6.6% per year; P < .01). MSSA BSI rates also increased significantly among all epidemiologic classes. HO cases increased from 2.5 per 100,000 to 3.2 per 100,000 (7.9% per year; P = .01). HACO cases increased from 12.7 per 100,000 to 14.7 per 100,000 (7.0% per year; P = .01). CA cases increased from 8.4 per 100,000 to 10.4 per 100,000 (6.7% per year; P < .01) (Fig. 1). Significant increases in MSSA BSI rates were also observed for nondialysis HACO cases (9.3 per 100,000 to 11.1 per 100,000; 7.8% per year; P < .01) but not dialysis HACO cases (1,823.2 per 100,000 to 1,857.4 per 100,000; 1.4% per year; P = .59). Healthcare risk factors for HACO cases were hospitalization in the previous year (82%), surgery (31%), dialysis (27%), and long-term care facility residence (19%). Conclusions: MSSA BSI rates increased from 2016–2019 overall, among all epidemiologic classes, and among nondialysis HACO cases. Efforts to prevent MSSA BSIs among individuals with healthcare risk factors, particularly those related to hospitalization, might have an impact on MSSA BSI rates.

Q fever is a zoonotic disease caused by the highly infectious Gram-negative coccobacillus, Coxiella burnetii (C. burnetii). The Q fever vaccine Q-VAX® is characterised by high reactogenicity, requiring individuals to be pre-screened for prior exposure before vaccination. To date it remains unclear whether vaccine side effects in pre-exposed individuals are associated with pre-existing adaptive immune responses to C. burnetii or are also a function of innate responses to Q-VAX®. In the current study, we measured innate and adaptive cytokine responses to C. burnetii and compared these among individuals with different pre-exposure status. Three groups were included: n=98 Dutch blood bank donors with unknown exposure status, n=95 Dutch village inhabitants with known natural exposure status to C. burnetii during the Dutch Q fever outbreak of 2007-2010, and n=96 Australian students receiving Q-VAX® vaccination in 2021. Whole blood cytokine responses following ex vivo stimulation with heat-killed C. burnetii were assessed for IFNγ, IL-2, IL-6, IL-10, TNFα, IL-1β, IP-10, MIP-1α and IL-8. Serological data were collected for all three cohorts, as well as data on skin test and self-reported vaccine side effects and clinical symptoms during past infection. IFNγ, IP-10 and IL-2 responses were strongly elevated in individuals with prior C. burnetii antigen exposure, whether through infection or vaccination, while IL-1β, IL-6 and TNFα responses were slightly increased in naturally exposed individuals only. High dimensional analysis of the cytokine data identified four clusters of individuals with distinct cytokine response signatures. The cluster with the highest levels of adaptive cytokines and antibodies comprised solely individuals with prior exposure to C. burnetii, while another cluster was characterized by high innate cytokine production and an absence of C. burnetii-induced IP-10 production paired with high baseline IP-10 levels. Prior exposure status was partially associated with these signatures, but could not be clearly assigned to a single cytokine response signature. Overall, Q-VAX® vaccination and natural C. burnetii infection were associated with comparable cytokine response signatures, largely driven by adaptive cytokine responses. Neither individual innate and adaptive cytokine responses nor response signatures were associated retrospectively with clinical symptoms during infection or prospectively with side effects post-vaccination.

This study compares knowledge, experience and understanding of genetic testing, and psychological outcomes among breast and ovarian cancer patients undergoing multi-gene panel testing via genetic counselor-mediated (GMT) or oncologist-mediated (OMT) testing models. A pragmatic, prospective survey of breast and ovarian cancer patients pursuing genetic testing between January 2017 and August 2019 was conducted at the Princess Margaret Cancer Centre in Toronto, Canada. A total of 120 (80 GMT; 40 OMT) individuals completed a survey administered one week following consent to genetic testing. Compared to OMT, the GMT cohort had higher median knowledge (8 vs. 9; p = 0.025) and experience/understanding scores (8.5 vs. 10; p < 0.001) at the time of genetic testing. Significant differences were noted in the potential psychological concerns experienced, with individuals in the GMT cohort more likely to screen positive in the hereditary predisposition domain of the Psychosocial Aspects of Hereditary Cancer tool (55% vs. 27.5%; p = 0.005), and individuals in the OMT cohort more likely to screen positive in the general emotions domain (65.0% vs. 38.8%; p = 0.007). The results of this study suggest that OMT can be implemented to streamline genetic testing; however, post-test genetic counseling should remain available to all individuals undergoing genetic testing, to ensure any psychologic concerns are addressed and that individuals have a clear understanding of relevant implications and limitations of their test results.

Purpose – The author offers two challenges and four principles to teaching in the tertiary sector during this pandemic. While others may focus on the challenge of technical delivery, the author notes the challenges of systemic student disengagement. The author attempts to correct for this in four ways. She argues that the challenges she identifies and the principles that can be deployed in response are applicable across a range of teaching contexts and can be adapted for a post-COVID-19 era. Design/methodology/approach – This paper draws on the author's phenomenological experience teaching in the context of COVID-19 and draws as well on the sociological literature of higher education teaching. Findings – Four principles emerged from a year of successful teaching during COVID-19. First, the author embraces a pedagogy of care, which reflects a genuine concern for student well-being. Second, the author utilizes a variety of technological approaches to keep students engaged. Third, she retains a flexible approach to teaching. Fourth, she considers carefully the extent to which COVID-19 is included, and excluded, from topical discussions. On this point she argues that COVID-19 should neither be the center point of any material, nor should it be ignored completely. Originality/value – Shocks to the tertiary education system will continue to recur, as will instances of systemic student disengagement. Effective correctives to such disengagement, drawn from both education theory and empirical experience, will continue to be of value.

Abstract Background Our aim was to conduct a post participation survey of respondent experiences with in-home remote patient monitoring via telehealth for blood pressure monitoring of women with postpartum hypertension. We hypothesized that the in-home remote patient monitoring application will be implemented with strong fidelity and have positive patient acceptability. Methods This analysis was a planned secondary analysis of a non-randomized controlled trial of telehealth with remote blood pressure patient monitoring for postpartum hypertension compared to standard outpatient monitoring in women with a hypertension-related diagnosis during pregnancy. In collaboration with survey experts, we developed a 41-item web-based survey to assess 1) perception of quality of care received, 2) ease of use/ease to learn the telehealth program, 3) effective orientation of equipment, 4) level of perceived security/privacy utilizing telehealth and 5) problems encountered. The survey included multiple question formats including Likert scale responses, dichotomous Yes/No responses, and free text. We performed a descriptive analysis on all responses and then performed regression analysis on a subset of questions most relevant to the domains of interest. The qualitative data collected through open ended responses was analyzed to determine relevant categories. Intervention participants who completed the study received the survey at the 6-week study endpoint. Results Sixty six percent of respondents completed the survey. The majority of women found the technology fit easily into their lifestyle. Privacy concerns were minimal and factors that influenced this included age, BMI, marital status, and readmissions. 95% of women preferred remote care for postpartum follow-up, in which hypertensive type, medication use and ethnicity were found to be significant factors in influencing location of follow-up. Most women were satisfied with the devices, but rates varied by hypertensive type, infant discharge rates and BMI. Conclusions Postpartum women perceived the telehealth remote intervention was a safe, easy to use method that represented an acceptable burden of care and an overall satisfying method for postpartum blood pressure monitoring. Trial registration ClinicalTrials.gov identification number: NCT03111095 Date of registration: April 12, 2017.

Abstract Background After the US Surgeon General declared youth electronic cigarette (e-cigarette) use an epidemic in 2018, the number of youth e-cigarette users continued to surge, growing from 3.8 million in 2018 to over 5 million 2019. Youth who use e-cigarettes are at a substantially higher risk of transitioning to traditional cigarettes, becoming regular cigarette smokers, and increasing their risk of developing tobacco-related cancer. A majority of youth are misinformed about e-cigarettes, often believing they are not harmful or contain no nicotine. Middle school students using e-cigarettes have been affected by its normalization leading to influence by their peers. However, social and group dynamics can be leveraged for a school-based peer-led intervention to identify and recruit student leaders to be anti-e-cigarette champions to prevent e-cigarette initiation. This study outlines a project to use social network analysis to identify student opinion-leaders in schools and train them to conduct anti-e-cigarette programming to their peers. Methods In the 2019–2020 academic school year, 6th grade students from nine schools in the Pittsburgh area were recruited. A randomized controlled trial (RCT) was conducted with three arms—expert, elected peer-leader, and random peer-leader—for e-cigarette programming. Sixth grade students in each school completed a network survey that assessed the friendship networks in each class. Students also completed pre-intervention and post-intervention surveys about their intention-to-use, knowledge, and attitudes towards e-cigarettes. Within each peer-led arm, social network analysis was conducted to identify peer-nominated opinion leaders. An e-cigarette prevention program was administered by (1) an adult content-expert, (2) a peer-nominated opinion leader to assigned students, or (3) a peer-nominated opinion leader to random students. Discussion This study is the first to evaluate the feasibility of leveraging social network analysis to identify 6th grade opinion leaders to lead a school-based e-cigarette intervention. Trial registration ClinicalTrials.gov NCT04083469 . Registered on September 10, 2019.

The research conducted by this researcher intends to analyze the effect of trust and ease of use on purchase decisions and repurchase intention. The data collection method in this study uses a questionnaire with 130 consumers who have purchased at an online store. The analytical method used is descriptive analysis, and the test instrument uses SEM AMOS. in this study using four variables, thirteen dimensions and twenty-six indicators. The results show that trust and ease of use have a significant effect on buying decisions and also have a significant effect on repurchase intention, and purchase decisions have a significant and significant effect on repurchase intention. so it can be said that trust and ease of use are the entry points that make consumers start to move to the next stage, therefore online store marketers need to pay attention.

T cell-mediated immunity plays a central role in the control and clearance of intracellular Coxiella burnetii infection, which can cause Q fever. Therefore, we aimed to develop a novel T cell-targeted vaccine that induces pathogen-specific cell-mediated immunity to protect against Q fever in humans while avoiding the reactogenicity of the current inactivated whole cell vaccine. Human HLA class II T cell epitopes from C. burnetii were previously identified and selected by immunoinformatic predictions of HLA binding, conservation in multiple C. burnetii isolates, and low potential for cross-reactivity with the human proteome or microbiome. Epitopes were selected for vaccine inclusion based on long-lived human T cell recall responses to corresponding peptides in individuals that had been naturally exposed to the bacterium during a 2007-2010 Q fever outbreak in the Netherlands. Multiple viral vector-based candidate vaccines were generated that express concatemers of selected epitope sequences arranged to minimize potential junctional neo-epitopes. The vaccine candidates caused no antigen-specific reactogenicity in a sensitized guinea pig model. A subset of the vaccine epitope peptides elicited antigenic recall responses in splenocytes from C57BL/6 mice previously infected with C. burnetii. However, immunogenicity of the vaccine candidates in C57BL/6 mice was dominated by a single epitope and this was insufficient to confer protection against an infection challenge, highlighting the limitations of assessing human-targeted vaccine candidates in murine models. The viral vector-based vaccine candidates induced antigen-specific T cell responses to a broader array of epitopes in cynomolgus macaques, establishing a foundation for future vaccine efficacy studies in this large animal model of C. burnetii infection.

Introduction The high demand for genetic tests and limited supply of genetics professionals has created a need for alternative service delivery models. Digital tools are increasingly being used to support multiple points in the genetic testing journey; however, none are transferable across multiple clinical specialties and settings nor do they encompass the entire trajectory of the journey. We aim to evaluate the effectiveness of the Genetics Adviser, an interactive, patient-facing, online digital health tool that delivers pre-test counselling, provides support during the waiting period for results, and returns results with post-test counselling, encompassing the entire patient genetic testing journey.Methods and analysis We will compare the Genetics Adviser paired with a brief genetic counselling session to genetic counselling alone in a randomised controlled trial. One hundred and forty patients who previously received uninformative genetic test results for their personal and family history of cancer will be recruited from familial cancer clinics in Toronto and offered all clinically significant results from genomic sequencing. Participants randomised into the intervention arm will use the Genetics Adviser to learn about genomic sequencing, receive pre-test counselling, support during the waiting period and results, supplemented with brief counselling from a genetic counsellor. Participants in the control arm will receive standard pre-test and post-test counselling for genomic sequencing from a genetic counsellor. Our primary outcome is decisional conflict following pre-test counselling from the Genetics Adviser+genetic counsellor or counsellor alone. Secondary outcomes include: knowledge, satisfaction with decision-making, anxiety, quality of life, psychological impact of results, empowerment, acceptability and economic impact for patients and the health system. A subset of patients will be interviewed to assess user experience.Ethics and dissemination This study has been approved by Clinical Trials Ontario Streamlined Research Ethics Review System (REB#20–035). Results will be shared through stakeholder workshops, national and international conferences and peer-reviewed journals.Trial registration number NCT04725565.

BackgroundPatient body weight is a frequently used measure in biomedical studies, yet there are no standard methods for processing and cleaning weight data. Conflicting documentation on constructing body weight measurements presents challenges for research and program evaluation. ObjectiveIn this study, we aim to describe and compare methods for extracting and cleaning weight data from electronic health record databases to develop guidelines for standardized approaches that promote reproducibility. MethodsWe conducted a systematic review of studies published from 2008 to 2018 that used Veterans Health Administration electronic health record weight data and documented the algorithms for constructing patient weight. We applied these algorithms to a cohort of veterans with at least one primary care visit in 2016. The resulting weight measures were compared at the patient and site levels. ResultsWe identified 496 studies and included 62 (12.5%) that used weight as an outcome. Approximately 48% (27/62) included a replicable algorithm. Algorithms varied from cutoffs of implausible weights to complex models using measures within patients over time. We found differences in the number of weight values after applying the algorithms (71,961/1,175,995, 6.12% to 1,175,177/1,175,995, 99.93% of raw data) but little difference in average weights across methods (93.3, SD 21.0 kg to 94.8, SD 21.8 kg). The percentage of patients with at least 5% weight loss over 1 year ranged from 9.37% (4933/52,642) to 13.99% (3355/23,987). ConclusionsContrasting algorithms provide similar results and, in some cases, the results are not different from using raw, unprocessed data despite algorithm complexity. Studies using point estimates of weight may benefit from a simple cleaning rule based on cutoffs of implausible values; however, research questions involving weight trajectories and other, more complex scenarios may benefit from a more nuanced algorithm that considers all available weight data.

Introduction Ebola virus disease (EVD) continues to be a significant public health problem in sub-Saharan Africa, especially in the Democratic Republic of the Congo (DRC). Large-scale vaccination during outbreaks may reduce virus transmission. We established a large population-based clinical trial of a heterologous, two-dose prophylactic vaccine during an outbreak in eastern DRC to determine vaccine effectiveness.Methods and analysis This open-label, non-randomised, population-based trial enrolled eligible adults and children aged 1 year and above. Participants were offered the two-dose candidate EVD vaccine regimen VAC52150 (Ad26.ZEBOV, Modified Vaccinia Ankara (MVA)-BN-Filo), with the doses being given 56 days apart. After vaccination, serious adverse events (SAEs) were passively recorded until 1 month post dose 2. 1000 safety subset participants were telephoned at 1 month post dose 2 to collect SAEs. 500 pregnancy subset participants were contacted to collect SAEs at D7 and D21 post dose 1 and at D7, 1 month, 3 months and 6 months post dose 2, unless delivery was before these time points. The first 100 infants born to these women were given a clinical examination 3 months post delivery. Due to COVID-19 and temporary suspension of dose 2 vaccinations, at least 50 paediatric and 50 adult participants were enrolled into an immunogenicity subset to examine immune responses following a delayed second dose. Samples collected predose 2 and at 21 days post dose 2 will be tested using the Ebola viruses glycoprotein Filovirus Animal Non-Clinical Group ELISA. For qualitative research, in-depth interviews and focus group discussions were being conducted with participants or parents/care providers of paediatric participants.Ethics and dissemination Approved by Comité National d’Ethique et de la Santé du Ministère de la santé de RDC, Comité d'Ethique de l'Ecole de Santé Publique de l’Université de Kinshasa, the LSHTM Ethics Committee and the MSF Ethics Review Board. Findings will be presented to stakeholders and conferences. Study data will be made available for open access.Trial registration number NCT04152486.

Abstract Background Buprenorphine-naloxone is an evidence-based treatment for Opioid Use Disorder. However, despite its efficacy, nearly half of participants are unsuccessful in achieving stabilization (i.e., period of time following medication induction in which medication dose is adjusted to be effective in reducing cravings/withdrawal, minimize potential side effects, and eliminate illicit substance use). This paper presents the study design and protocol for a digital health intervention designed to promote engagement in and adherence to buprenorphine treatment, offered through an outpatient addiction treatment center, through motivational enhancement and distress tolerance skills training. Personalized feedback interventions represent a promising method to effectively motivate engagement in and adherence to buprenorphine treatment. These interventions are generally brief, individually tailored, and have the potential to be delivered via mobile platforms. Distress tolerance, a transdiagnostic vulnerability factor, has been implicated in the development and maintenance of substance use. Targeting distress tolerance may improve substance use treatment outcomes by promoting the ability to persist in goal-directed activity even when experiencing physical or emotional distress. Methods The study aims are to: (1) develop and refine an interactive computer- and text message-delivered personalized feedback intervention that incorporates distress tolerance skills training for persons who have elected to initiate outpatient buprenorphine treatment (iCOPE); (2) examine the feasibility, acceptability, and preliminary efficacy of iCOPE for increasing abstinence, adherence, and retention in treatment compared to a treatment as usual comparison condition; and, (3) examine potential mechanisms that may underlie the efficacy of iCOPE in improving outcomes, including motivation, distress tolerance, self-regulation, and negative affect. Discussion Results of this study will be used to determine whether to proceed with further testing through a large-scale trial. This work has the potential to improve treatment outcomes by reducing illicit opioid use, increasing adherence/retention, and preventing future overdose and other complications of illicit opioid use. Trial Registration NCT03842384

Abstract Introduction: The lack of diversity in health research participation has serious consequences for science as well as ethics. While there is growing interest in solving the problem, much of the work to date focuses on attitudes of distrust among members of underrepresented communities. However, there is also a pressing need to understand existing barriers within the cultural and structural context of researchers and research staff. Methods: This study adopted a sequential exploratory mixed-methods design to allow for a focused examination of barriers to inclusive research recruitment among researchers and staff. Barriers first identified from an initial quantitative investigation (web-based survey; n = 279) were further explored through qualitative methods (key informant interviews; n = 26). Participants were investigators and research team members in both phases of the study. Results: The survey revealed a paradoxical disconnect between participants’ reported belief in the abstract value of diversity in research participation (87.1% important/extremely important) and belief in it as an important goal in their own specific research (38.3% important/extremely important). Interviews reveal that researchers and staff perceive many barriers to the recruitment of members of underrepresented groups and hold a general view of diversity in research as an impractical, even unattainable, goal. Conclusions: It is crucial that principal investigators not only understand the consequences of the continued exclusion of marginalized groups from research but also implement strategies to reverse this trend and communicate with research staff on the issue. While individual bias does play a role (ex: a priori assumptions about the willingness or ability of members of underrepresented groups to participate), these behaviors are part of a larger context of systemic racism.