Diagnostic delay of sarcoidosis: an integrated systematic review.

BACKGROUND: Sarcoidosis is a chronic inflammatory granulomatous disease of unknown cause. Delays in diagnosis can result in disease progression and poorer outcomes for patients. Our aim was to review the current literature to determine the overall diagnostic delay of sarcoidosis, factors associated with diagnostic delay, and the experiences of people with sarcoidosis of diagnostic delay. METHODS: Three databases (PubMed/Medline, Scopus, and ProQuest) and grey literature sources were searched. Random effects inverse variance meta-analysis was used to pool mean diagnostic delay in all types of sarcoidosis subgroup analysis. Diagnostic delay was defined as the time from reported onset of symptoms to diagnosis of sarcoidosis. RESULTS: We identified 374 titles, of which 29 studies were included in the review, with an overall sample of 1531 (694 females, 837 males). The overall mean diagnostic delay in all types of sarcoidosis was 7.93 months (95% CI 1.21 to 14.64 months). Meta-aggregation of factors related to diagnostic delay in the included studies identified three categories: (1) the complex and rare features of sarcoidosis, (2) healthcare factors and (3) patient-centred factors. Meta-aggregation of outcomes reported in case studies revealed that the three most frequent outcomes associated with diagnostic delay were: (1) incorrect diagnosis, (2) incorrect treatment and (3) development of complications/disease progression. There was no significant difference in diagnostic delay between countries with gatekeeper health systems (where consumers are referred from a primary care clinician to specialist care) and countries with non-gatekeeper systems. No qualitative studies examining people's experiences of diagnostic delay were identified. CONCLUSION: The mean diagnostic delay for sarcoidosis is almost 8 months, which has objective consequences for patient management. On the other hand, there is a paucity of evidence about the experience of diagnostic delay in sarcoidosis and factors related to this. Gaining an understanding of people's experiences while seeking a diagnosis of sarcoidosis is vital to gain insight into factors that may contribute to delays, and subsequently inform strategies, tools and training activities aimed at increasing clinician and public awareness about this rare condition. TRIAL REGISTRATION: PROSPERO Registration number: CRD42022307236.

Intergroup Contact Improves Medical Student Attitudes and Skill in Transgender Health Care.

Purpose: Poorer health outcomes for transgender and gender diverse (TGD) individuals have been associated with lack of health care provider knowledge and personal bias. Training at all levels of medical education has been positioned as one strategy to combat these inequities. This study sought to characterize preclinical medical student attitude, skill, and knowledge pre- and post-teaching with TGD community volunteers. Methods: This matched pre- and post-test study was conducted from July 2020 to August 2021 capturing two preclinical medical student cohorts exposed to the same teaching intervention. Students completed the Transgender Attitudes and Beliefs Scale (TABS) and the Transgender Development of Clinical Skills Scale (T-DOCSS) at baseline, 1 week, and 1 month after the clinical skills session. Tutors' attitudes to TGD health were measured before facilitating teaching, using the Attitudes Toward Transgender Patients and Beliefs and Knowledge about Treating Transgender Patients scales. Results: Fifty-nine students completed questionnaires at three time points and were included in this study. Total TABS and T-DOCCS scores increased from preintervention to 1-week follow-up, maintained at 1 month, with significant changes in Interpersonal Comfort and Sex and Gender Beliefs subscales. Scores on the Human Value subscale did not change, remaining consistently high. Postintervention knowledge-question scores were high. Nine of 13 tutors completed surveys, demonstrating overall positive attitudes toward gender diversity and TGD health. Conclusion: This study demonstrates improvement in preclinical medical student attitudes and self-reported skill toward gender health care sustained at 1 month after small-group teaching with TGD community volunteers.

The Impact of Monetary Incentives on Delay Discounting Within a Year-Long Physical Activity Intervention.

BACKGROUND: Delay discounting is the depreciation in a reward's perceived value as a function of the time until receipt. Monetary incentive programs that provide rewards contingent on meeting daily physical activity (PA) goals may change participants' delay discounting preferences. PURPOSE: Determine if monetary incentives provided in close temporal proximity to meeting PA goals changed delay discounting, and if such changes mediated intervention effects. METHODS: Inactive adults (n = 512) wore accelerometers during a 12-month intervention where they received proximal monetary incentives for meeting daily moderate-to-vigorous PA (MVPA) goals or delayed incentives for study participation. Delay discount rate and average MVPA were assessed at baseline, end of intervention, and a 24-month follow-up. Using structural equation modeling, we tested effects of proximal versus delayed rewards on delay discounting and whether any changes mediated intervention effects on MVPA. PA self-efficacy was also evaluated as a potential mediator, and both self-efficacy and delay discounting were assessed as potential moderators of intervention effects. RESULTS: Proximal rewards significantly increased participants' delay discounting (ß = 0.238, confidence interval [CI]: -0.078, 0.380), indicating greater sensitivity to reinforcement timing. This change did not mediate incentive-associated increases in MVPA at the end of the 12-month intervention (ß = -0.016, CI: -0.053, 0.019) or at a 24-month follow-up (ß = -0.020, CI: -0.059, 0.018). Moderation effects were not found. CONCLUSIONS: Incentive-induced increases in delay discounting did not deleteriously impact MVPA. This finding may help assuage concerns about using monetary incentives for PA promotion, but further research regarding the consequences of changes in delay discounting is warranted.

This study examined the effects of providing proximal monetary incentives for meeting daily exercise goals on people's tendency to value immediate versus delayed rewards. Inactive adults (n = 512) participated in a year-long program where they wore an accelerometer each day and received either (i) small monetary rewards in close temporal proximity to instances of meeting daily exercise goals or (ii) larger rewards at 2-month intervals for ongoing participation. Those receiving proximal incentives showed an increased preference for immediate rewards, yet this reported change did not compromise long-term physical activity gains. In a comparison analysis, we found that proximal monetary incentives were not associated with changes in exercise self-efficacy. Overall, the findings suggest that monetary incentives for exercise do not negatively impact people's activity levels, though more research is needed to fully understand the implications of changes in reward timing preferences.

Tisagenlecleucel utilisation and outcomes across refractory, first relapse and multiply relapsed B-cell acute lymphoblastic leukemia: a retrospective analysis of real-world patterns.

Background: Tisagenlecleucel was approved by the Food and Drug Administration (FDA) in 2017 for refractory B-cell acute lymphoblastic leukemia (B-ALL) and B-ALL in ≥2nd relapse. Outcomes of patients receiving commercial tisagenlecleucel upon 1st relapse have yet to be established. We aimed to report real-world tisagenlecleucel utilisation patterns and outcomes across indications, specifically including patients treated in 1st relapse, an indication omitted from formal FDA approval. Methods: We conducted a retrospective analysis of real-world tisagenlecleucel utilisation patterns across 185 children and young adults treated between August 30, 2017 and March 6, 2020 from centres participating in the Pediatric Real-World CAR Consortium (PRWCC), within the United States. We described definitions of refractory B-ALL used in the real-world setting and categorised patients by reported Chimeric Antigen Receptor (CAR) T-cell indication, including refractory, 1st relapse and ≥2nd relapse B-ALL. We analysed baseline patient characteristics and post-tisagenlecleucel outcomes across defined cohorts. Findings: Thirty-six percent (n = 67) of our cohort received tisagenlecleucel following 1st relapse. Of 66 evaluable patients, 56 (85%, 95% CI 74-92%) achieved morphologic complete response. Overall-survival (OS) and event-free survival (EFS) at 1-year were 69%, (95% CI 58-82%) and 49%, (95% CI 37-64%), respectively, with survival outcomes statistically comparable to remaining patients (OS; p = 0.14, EFS; p = 0.39). Notably, toxicity was increased in this cohort, warranting further study. Interestingly, of 30 patients treated for upfront refractory disease, 23 (77%, 95% CI 58-90%) had flow cytometry and/or next-generation sequencing (NGS) minimum residual disease (MRD)-only disease at the end of induction, not meeting the historic morphologic definition of refractory. Interpretation: Our findings suggested that tisagenlecleucel response and survival rates overlap across patients treated with upfront refractory B-ALL, B-ALL ≥2nd relapse and B-ALL in 1st relapse. We additionally highlighted that definitions of refractory B-ALL are evolving beyond morphologic measures of residual disease. Funding: St. Baldrick's/Stand Up 2 Cancer, Parker Institute for Cancer Immunotherapy, Virginia and D.K. Ludwig Fund for Cancer Research.

Mediport use as an acceptable standard for CAR T cell infusion.

Introduction: Mediport use as a clinical option for the administration of chimeric antigen receptor T cell (CAR T cell) therapy in patients with B-cell malignancies has yet to be standardized. Concern for mediport dislodgement, cell infiltration, and ineffective therapy delivery to systemic circulation has resulted in variable practice with intravenous administration of CAR T cell therapy. With CAR T cell commercialization, it is important to establish practice standards for CAR T cell delivery. We conducted a study to establish usage patterns of mediports in the clinical setting and provide a standard of care recommendation for mediport use as an acceptable form of access for CAR T cell infusions. Methods: In this retrospective cohort study, data on mediport use and infiltration rate was collected from a survey across 34 medical centers in the Pediatric Real-World CAR Consortium, capturing 504 CAR T cell infusion routes across 489 patients. Data represents the largest, and to our knowledge sole, report on clinical CAR T cell infusion practice patterns since FDA approval and CAR T cell commercialization in 2017. Results: Across 34 sites, all reported tunneled central venous catheters, including Broviac® and Hickman® catheters, as accepted standard venous options for CAR T cell infusion. Use of mediports as a standard clinical practice was reported in 29 of 34 sites (85%). Of 489 evaluable patients with reported route of CAR T cell infusion, 184 patients were infused using mediports, with no reported incidences of CAR T cell infiltration. Discussion/Conclusion: Based on current clinical practice, mediports are a commonly utilized form of access for CAR T cell therapy administration. These findings support the safe practice of mediport usage as an accepted standard line option for CAR T cell infusion.

'A human face and voice': transgender patient-educator and medical student perspectives on gender-diversity teaching.

BACKGROUND: Transgender and gender diverse (TGD) people face many obstacles in accessing health care, including discrimination, institutional bias, and clinician knowledge deficits. We developed a clinical skills and education module on gender-affirming care for pre-clinical medical students, in collaboration with a TGD-led civil society organisation. The module consisted of an educational session followed by preceptor-facilitated small group tutorials, led by TGD patient-educators (n = 22) who used their lived experience to explore medical history-taking and broader issues related to TGD healthcare with students (n = 199). This study aimed to explore the views of students and TGD patient-educators on the structure, delivery and impact of the module. METHODS: Analysis of responses of TGD patient-educators and students to the module (2020 and 2021), in post-intervention surveys using open-ended questions for TGD patient-educators (18 responses from 22 educators) and free text comments as part of a quantitative survey for medical students (89 responses). RESULTS: Responses from students and patient-educators to the session were highly positive. Students and patient-educators emphasised that the teaching session succeeded through elevating the centrality of shared experience and creating a safe space for learning and teaching. Safety was experienced by patient-educators through the recognition of their own expertise in a medical environment, while students reported a non-judgemental teaching space which allowed them to explore and redress recognised limitations in knowledge and skill. Patient-educators described their motivation to teach as being driven by a sense of responsibility to their community. Preceptor attitudes may function as a barrier to the effectiveness of this teaching, and further attention should be paid to supporting the education of clinical facilitators in TGD health. CONCLUSION: The experiences of TGD patient-educators and medical students in this study suggest that this model of teaching could serve as a transferable template for TGD health and the inclusion of other historically marginalised groups in medical education.

Anxiety management in Australian general practice: an analysis of encounters from 2006 - 2016.

BACKGROUND: Anxiety disorders are highly prevalent mental health conditions managed predominantly by general practitioners (GPs). This study aimed to examine the management of anxiety by Australian GPs since the introduction of the Better Access to Psychiatrists, Psychologists and General Practitioners initiative in 2006. METHODS: We conducted secondary analysis of Bettering the Evaluation and Care of Health data on GP encounters for anxiety from 2006 to 2016 (N = 28,784). We calculated point estimates and used multivariate logistic regression to explore the effect of GP and patient characteristics on rates and types of management. RESULTS: The management rate of anxiety increased from 2.3% of GP encounters in 2006 to 3.2% in 2016. Over the 10-year period, increases were seen in referrals to psychologists (AOR = 1.09, 95%CI = 1.07-1.11, p < .0001) and selective serotonin / serotonin-noradrenalin reuptake inhibitors (AOR = 1.05, 95%CI = 1.03-1.06, p < .0001), and benzodiazepines decreased (AOR = 0.94, 95%CI = 0.92-0.95, p < .0001). Systematic differences in management were found for patient and GP characteristics, including high rates of benzodiazepines in certain groups. CONCLUSIONS: Anxiety is accounting for more of the GP workload, year on year. GP management of anxiety has become more closely aligned with practice guidelines since 2006. However, high rates of benzodiazepine prescribing in certain groups remains a concern. Further research is needed into GP treatment decision making for anxiety.

The moderating impact of neighborhood walkability on mHealth interventions to increase moderate to vigorous physical activity for insufficiently active adults in a randomized trial.

BACKGROUND: Ecological models suggest that interventions targeting specific behaviors are most effective when supported by the environment. This study prospectively examined the interactions between neighborhood walkability and an mHealth intervention in a large-scale, adequately powered trial to increase moderate-to-vigorous physical activity (MVPA). METHODS: Healthy, insufficiently active adults (N = 512) were recruited purposefully from census block groups ranked on walkability (high/low) and socioeconomic status (SES, high/low). Participants were block-randomized in groups of four to WalkIT Arizona, a 12-month, 2 × 2 factorial trial evaluating adaptive versus static goal setting and immediate versus delayed financial reinforcement delivered via text messages. Participants wore ActiGraph GT9X accelerometers daily for one year. After recruitment, a walkability index was calculated uniquely for every participant using a 500-m street network buffer. Generalized linear mixed-effects hurdle models tested for interactions between walkability, intervention components, and phase (baseline vs. intervention) on: (1) likelihood of any (versus no) MVPA and (2) daily MVPA minutes, after adjusting for accelerometer wear time, neighborhood SES, and calendar month. Neighborhood walkability was probed at 5th, 25th, 50th, 75th, and 95th percentiles to explore the full range of effects. RESULTS: Adaptive goal setting was more effective in increasing the likelihood of any MVPA and daily MVPA minutes, especially in lower walkable neighborhoods, while the magnitude of intervention effect declined as walkability increased. Immediate reinforcement showed a greater increase in any and daily MVPA compared to delayed reinforcement, especially relatively greater in higher walkable neighborhoods. CONCLUSIONS: Results partially supported the synergy hypotheses between neighborhood walkability and PA interventions and suggest the potential of tailoring interventions to individuals' neighborhood characteristics. TRIAL REGISTRATION: Preregistered at clinicaltrials.gov (NCT02717663).

Heatwaves and wildfires suffocate our healthy start to life: time to assess impact and take action.

Adverse environmental exposures in utero and early childhood are known to programme long-term health. Climate change, by contributing to severe heatwaves, wildfires, and other natural disasters, is plausibly associated with adverse pregnancy outcomes and an increase in the future burden of chronic diseases in both mothers and their babies. In this Personal View, we highlight the limitations of existing evidence, specifically on the effects of severe heatwave and wildfire events, and compounding syndemic events such as the COVID-19 pandemic, on the short-term and long-term physical and mental health of pregnant women and their babies, taking into account the interactions with individual and community vulnerabilities. We highlight a need for an international, interdisciplinary collaborative effort to systematically study the effects of severe climate-related environmental crises on maternal and child health. This will enable informed changes to public health policy and clinical practice necessary to safeguard the health and wellbeing of current and future generations.

Feasibility of a pilot dyadic randomized controlled trial testing the effects of three behavioral interventions on older adults' cognitive, physical and everyday function.

Introduction: Maintaining functional abilities is critical for optimizing older adults' well-being and independence. This randomized controlled trial (RCT) pilot examined the feasibility of testing the effects of three commercially available interventions on function-related outcomes in older adults. Methods: Pairs of community-dwelling older adults (N=55, Mage=71.4) were randomized to a 10-week intervention (cognitive-COG, physical-EX, combined exergame-EXCOG, or control-CON). Cognitive, physical, and everyday function were assessed at baseline, immediately post-intervention, and 6-months post-intervention. Feasibility was evaluated using recruitment, enrollment, training adherence, and retention metrics. Variability and patterns of change in functional outcomes were examined descriptively. Results: A total of 208 individuals were screened, with 26% subsequently randomized. Across training arms, 95% of training sessions were completed and 89% of participants were retained at immediate post-test. Variability in functional outcomes and patterns of change differed across study arms. Discussion: Results support a fully powered RCT, with several modifications to the pilot study design, to investigate short- and long-term training impacts.

Male pediatric, adolescent, and young adult reproductive survivorship.

As pediatric, adolescent, and young adult cancer survival rates increase, emphasis is placed on reducing late effects, including reproductive complications and potential impact to fertility. Male survivors are at risk of abnormalities in sperm, hormone deficiencies, and sexual dysfunction. This can impact one's progression into puberty and ability to have a biological child and impacts quality of life following treatment. Access to reproductive care is important and requires patient assessment and appropriate referral to reproductive specialists. This review addresses reproductive complications associated with therapy, standard-of-care testing, and therapeutic interventions. The psychologic impact on psychosexual functioning is also addressed.

Driven by need, shaped by access: Heterogeneity in patient profiles and patterns of service utilization in patients with alcohol use disorders.

BACKGROUND: Patients with alcohol-use disorders (AUDs) are highly heterogenous and account for an increasing proportion of general medical hospital visits. However, many patients with AUDs do not present with severe medical or psychiatric needs requiring immediate attention. There may be a mismatch between some patients' needs and the available services, potentially driving re-admissions and re-encounters. The current study aims to identify subgroups of AUD patients and predict differences in patterns of healthcare service use (HSU) over time. METHODS: Latent class analysis (LCA) was conducted using hospital data incorporating sociodemographic, health behavior, clinical, and service use variables to identify subtypes of AUD patients, then class membership was used to predict patterns of HSU. RESULTS: Four classes were identified with the following characteristics: (1) Patients with acute medical injuries (30 %); (2) Patients with socioeconomic and psychiatric risk factors, (11 %); (3) Patients with chronic AUD with primarily non-psychiatric medical needs (18 %); and (4) Patients with primary AUDs with low medical-treatment complexity (40 %). Negative binomial models showed that Class 4 patients accounted for the highest frequency of service use, including significantly higher rates of emergency department reencounters at 30 days and 12 months. CONCLUSIONS: The profile and patterns of HSU exhibited by patients in class 4 suggest that these patients have needs which are not currently being addressed in the emergency department. These have implications for how resources are allocated to meet the needs of patients with AUDs, including those who make frequent visits to the emergency department without high acuity medical needs.

Durable remissions achieved with reinfusion of CD19-directed CAR-T despite failure to induce or maintain B-cell aplasia and single-center experience with reinfusion of tisagenlecleucel.

CD19-directed chimeric antigen receptor T lymphocytes (CAR-T) have led to durable remissions in children with refractory and/or multiply relapsed B-lymphoblastic leukemia. For those who relapse or lose B-cell aplasia post CAR-T, the role of CAR-T reinfusion is unclear. We report two cases of durable remission with tisagenlecleucel reinfusion despite failure to achieve or maintain B-cell aplasia, and compare these cases to six additional children who received multiple tisagenlecleucel infusions at our institution. Our experience suggests that reinfusion is safe and may be a definitive therapy for a small subset of patients. Reinfusion can also reintroduce remission and/or B-cell aplasia, allowing for subsequent therapies.

The Choice of Either Conventional Chemotherapy or Inotuzumab Ozogamicin as Bridging Regimen Does Not Appear To Impact Clinical Response to CD19-Directed CAR-T Therapy in Pediatric B-ALL.

Bridging therapy (BT) given during the period between T-cell collection and initiation of lymphodepleting chemotherapy is indicated for most children with B-cell acute lymphoblastic leukemia (B-ALL) undergoing treatment with tisagenlecleucel (tisa-cel), a CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy. Both conventional chemotherapy agents and B-cell directed antibody-based therapies such as antibody-drug conjugates and bispecific T-cell engagers have been used as systemic forms of BT. The purpose of this retrospective study was to evaluate if there are detectable differences in clinical outcomes based on the type of BT given (conventional chemotherapy or inotuzumab). A retrospective analysis was performed on all patients treated with tisa-cel at Cincinnati Children's Hospital Medical Center for B-ALL with bone marrow disease (with or without extramedullary disease). Patients who did not receive systemic BT were excluded. Only 1 patient received blinatumomab as BT and was therefore not included in this analysis to focus the analysis on the use of inotuzumab. Pre-infusion characteristics and post-infusion outcomes were collected. Fisher's exact test was used for categorical variables, and t-test or Mann-Whitney test was used for continuous parametric and non-parametric variables respectively. Mantel-Cox was used for survival analyses. Thirty-two patients received BT before CD19 CAR-T for medullary leukemia; 24 received conventional chemotherapy, and 8 received inotuzumab ozogamicin (InO). Cohorts were evenly matched regarding CAR-T indication, recipient age, and median CAR-T cell dose. There were no significant differences between the groups for attaining a minimal residual disease (MRD)-negative complete response after CAR-T, the percentage of patients who maintained prolonged B-cell aplasia, or the median duration of B-cell aplasia. Thirty-seven percent of patients in the conventional chemotherapy group and 43% in the antibody-based therapy group relapsed, with a median time to relapse in both groups of 5 months. No differences in event-free survival, the cumulative incidence of relapse, or overall survival were seen between the two groups. Initial response to tisa-cel, relapse rate, and survival were similar between patients who received BT with conventional chemotherapy or InO therapy. Because low disease burden at the time of infusion is a positive prognostic factor, choice of bridging regimen should focus on therapy that is anticipated to effectively lower disease burden and minimize treatment-related toxicity. Given the limitations associated with the single center retrospective analysis, a larger, multicenter study is needed to further explore these findings.

Diagnostic delay of sarcoidosis: Protocol for an integrated systematic review.

INTRODUCTION: Sarcoidosis is a rare systemic inflammatory granulomatous disease of unknown cause. It can manifest in any organ. The incidence of sarcoidosis varies across countries, and by ethnicity and gender. Delays in the diagnosis of sarcoidosis can lead to extension of the disease and organ impairment. Diagnosis delay is attributed in part to the lack of a single diagnostic test or unified commonly used diagnostic criteria, and to the diversity of disease manifestations and symptom load. There is a paucity of evidence examining the determinants of diagnostic delay in sarcoidosis and the experiences of people with sarcoidosis related to delayed diagnosis. We aim to systematically review available evidence about diagnostic delay in sarcoidosis to elucidate the factors associated with diagnostic delay for this disease in different contexts and settings, and the consequences for people with sarcoidosis. METHODS AND ANALYSIS: A systematic search of the literature will be conducted using PubMed/Medline, Scopus, and ProQuest databases, and sources of grey literature, up to 25th of May 2022, with no limitations on publication date. We will include all study types (qualitative, quantitative, and mixed methods) except review articles, examining diagnostic delay, incorrect diagnosis, missed diagnosis or slow diagnosis of all types of sarcoidosis across all age groups. We will also examine evidence of patients' experiences associated with diagnostic delay. Only studies in English, German and Indonesian will be included. The outcomes we examine will be diagnostic delay time, patients' experiences, and factors associated with diagnostic delay in sarcoidosis. Two people will independently screen the titles and abstracts of search results, and then the remaining full-text documents against the inclusion criteria. Disagreements will be resolved with a third reviewer until consensus is reached. Selected studies will be appraised using the Mixed Methods Appraisal Tool (MMAT). A meta-analysis and subgroup analyses of quantitative data will be conducted. Meta-aggregation methods will be used to analyse qualitative data. If there is insufficient data for these analyses, a narrative synthesis will be conducted. DISCUSSION: This review will provide systematic and integrated evidence on the diagnostic delay, associated factors, and experiences of diagnosis delay among people with all types of sarcoidosis. This knowledge may shed light on ways to improve diagnosis delays in diagnosis across different subpopulations, and with different disease presentations. ETHICS AND DISSEMINATION: Ethical approval will not be required as no human recruitment or participation will be involved. Findings of the study will be disseminated through publications in peer-reviewed journals, conferences, and symposia. TRIAL REGISTRATION: PROSPERO Registration number: CRD42022307236. URL of the PROSPERO registration: https://www.crd.york.ac.uk/PROSPEROFILES/307236_PROTOCOL_20220127.pdf.

Tocilizumab for Treatment of Children and Young Adults With Severe Acute COVID-19: Experience at a Quaternary-care Children's Hospital.

We describe the clinical characteristics and outcomes of 16 children and young adults with severe acute COVID-19 who were treated with tocilizumab. Patients who were discharged by day 28 were more likely to be treated with tocilizumab earlier in their COVID-19 illness and had lower ferritin and interleukin-6 levels compared with those who were not discharged by day 28.

Toward Diabetes Device Development That Is Mindful to the Needs of Young People Living With Type 1 Diabetes: A Data- and Theory-Driven Qualitative Study.

BACKGROUND: An important strategy to understand young people's needs regarding technologies for type 1 diabetes mellitus (T1DM) management is to examine their day-to-day experiences with these technologies. OBJECTIVE: This study aimed to examine young people's and their caregivers' experiences with diabetes technologies in an exploratory way and relate the findings to the existing technology acceptance and technology design theories. On the basis of this procedure, we aimed to develop device characteristics that meet young people's needs. METHODS: Overall, 16 in-person and web-based face-to-face interviews were conducted with 7 female and 9 male young people with T1DM (aged between 12 and 17 years) and their parents between December 2019 and July 2020. The participants were recruited through a pediatric diabetes clinic based at Canberra Hospital. Data-driven thematic analysis was performed before theory-driven analysis to incorporate empirical data results into the unified theory of acceptance and use of technology (UTAUT) and value-sensitive design (VSD). We used the COREQ (Consolidated Criteria for Reporting Qualitative Research) checklist for reporting our research procedure and findings. In this paper, we summarize the key device characteristics that meet young people's needs. RESULTS: Summarized interview themes from the data-driven analysis included aspects of self-management, device use, technological characteristics, and feelings associated with device types. In the subsequent theory-driven analysis, the interview themes aligned with all UTAUT and VSD factors except for one (privacy). Privacy concerns or related aspects were not reported throughout the interviews, and none of the participants made any mention of data privacy. Discussions around ideal device characteristics focused on reliability, flexibility, and automated closed loop systems that enable young people with T1DM to lead an independent life and alleviate parental anxiety. However, in line with a previous systematic review by Brew-Sam et al, the analysis showed that reality deviated from these expectations, with inaccuracy problems reported in continuous glucose monitoring devices and technical failures occurring in both continuous glucose monitoring devices and insulin pumps. CONCLUSIONS: Our research highlights the benefits of the transdisciplinary use of exploratory and theory-informed methods for designing improved technologies. Technologies for diabetes self-management require continual advancement to meet the needs and expectations of young people with T1DM and their caregivers. The UTAUT and VSD approaches were found useful as a combined foundation for structuring the findings of our study.

Opportunities for primary health care: a qualitative study of perinatal health and wellbeing during bushfire crises.

BACKGROUND: During the summer of 2019/2020, Australia experienced a catastrophic wildfire season that affected nearly 80% of Australians either directly or indirectly. The impacts of climate crisis on perinatal health have only recently begun to receive attention. The objective of this study was to understand experiences of perinatal women during the bushfire and smoke events of 2019-2020 regarding health, health care, and public health messaging. METHODS: Semistructured interviews were conducted by phone or web conferencing platforms with 43 participants living in the south-east of Australia who were either pregnant or who had recently had a baby during the 2019/2020 fires. RESULTS: The health impacts on participants of the fires, associated smoke, and evacuations for some, were both physical and psychological. Many participants sought information regarding how to protect their own health and that of their unborn/recently born children, but reported this difficult to find. CONCLUSIONS: Pregnant women and new mothers exposed to bushfire events are a risk group for adverse physical and psychological outcomes. At the time of the 2019/2020 Australian bushfires, exposed women could not easily access evidence-based information to mitigate this risk. Family practitioners are well placed to provide pregnant women and new mothers with this sought-after information, but they need to be prepared well in advance of future similar events.

Reduced-Intensity Conditioning Mitigates Risk for Primary Ovarian Insufficiency but Does Not Decrease Risk for Infertility in Pediatric and Young Adult Survivors of Hematopoietic Stem Cell Transplantation.

Hematopoietic stem cell transplantation (HSCT) is a curative therapy for many pediatric malignant and nonmalignant conditions. Gonadal insufficiency or infertility is present in almost all HSCT survivors who received a myeloablative conditioning (MAC) regimen. Reduced-intensity conditioning (RIC) regimens are being increasingly used in medically fragile patients or in patients with nonmalignant diagnoses to limit the toxicities associated with HSCT; however, the short-term and long-term gonadal toxicity of RIC regimens in pediatric and young adult survivors remains unknown. In this study, we compared the prevalence of gonadal insufficiency and infertility among pubertal and postpubertal pediatric and young adult survivors of HSCT who received a RIC regimen versus those who received a MAC regimen. Twenty-three females (RIC, n = 8; MAC, n = 15) and 35 males (RIC, n = 19; MAC, n = 16) were included in this single-center, retrospective cross-sectional study. Eligible patients were those with available laboratory results who were ≥1 year post-HSCT, age <40 years, and pubertal or postpubertal as assessed by an endocrinologist. Follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, and anti-Müllerian hormone (AMH) levels were measured in females, and FSH, LH, total testosterone, and inhibin B (InhB) levels were measured in males. Twenty-one males (RIC, n = 11; MAC, n = 10) underwent semen analysis through a separate consent. Parametric and nonparametric analyses were undertaken to compare the RIC and MAC groups. Female patients who received RIC were less likely than those who received MAC to develop primary ovarian insufficiency, as demonstrated by elevated FSH (P = .02) and low estradiol (P = .01) or elevated LH (P = .09). Most females in the RIC (75%) and MAC (93%) groups had low AMH levels, indicating low or absent ovarian reserve, with no significant difference between the groups (P = .53). In males, there were no significant differences between the 2 groups in the prevalence of abnormal FSH, LH, testosterone, or InhB levels. Ten of 11 RIC males (91%) and 10 of 10 MAC males (100%) had azoospermia or oligospermia, at a median time to semen analysis from HSCT of 3.7 years (range, 1.3 to 12.2 years). RIC may pose less risk than MAC for primary ovarian insufficiency among female survivors of HSCT; however, both female and male recipients of either RIC or MAC regimens are at high risk for infertility. In the largest reported series of semen analyses of pediatric and young adult male recipients of RIC, azoospermia or oligospermia was found in nearly all (91%) RIC survivors. All patients undergoing HSCT should receive counseling about the high risk of gonadal toxicity, and efforts should be made to preserve fertility in patients undergoing either RIC or MAC.

Higher doses of tisagenlecleucel are associated with improved outcomes: a report from the pediatric real-world CAR consortium.

Remarkable complete response rates have been shown with tisagenlecleucel, a chimeric antigen receptor (CAR) T-cell therapy targeting CD19, in patients up to age 26 years with refractory/relapsed B-cell acute lymphoblastic leukemia; it is US Food and Drug Administration approved for this indication. Currently, patients receive a single dose of tisagenlecleucel across a wide dose range of 0.2 to 5.0 × 106 and 0.1 to 2.5 × 108 CAR T cells per kg for patients ≤50 and >50 kg, respectively. The effect of cell dose on survival and remission is not yet well established. Our primary goal was to determine if CAR T-cell dose affects overall survival (OS), event-free survival (EFS), or relapse-free-survival (RFS) in tisagenlecleucel recipients. Retrospective data were collected from Pediatric Real World CAR Consortium member institutions and included 185 patients infused with commercial tisagenlecleucel. The median dose of viable transduced CAR T cells was 1.7 × 106 CAR T cells per kg. To assess the impact of cell dose, we divided responders into dose quartiles: 0.134 to 1.300 × 106 (n = 48 [27%]), 1.301 to 1.700 × 106 (n = 46 [26%]), 1.701 to 2.400 × 106 (n = 43 [24%]), and 2.401 to 5.100 × 106 (n = 43 [24%]). OS, EFS, and RFS were improved in patients who received higher doses of tisagenlecleucel (P = .031, .0079, and .0045, respectively). Higher doses of tisagenlecleucel were not associated with increased toxicity. Because the current tisagenlecleucel package insert dose range remains broad, this work has implications in regard to targeting higher cell doses, within the approved dose range, to optimize patients' potential for long-standing remission.