Blending Behavioural Theory and Narrative Analysis to Explore the Lived Experience of Obesity and Assess Potential Engagement in a UK Weight Management Service: Theory and Narrative Approaches in Weight Management.

BACKGROUND: Current treatments for people with obesity emphasise the need for person-centred approaches that consider complex biopsychosocial factors and value the lived experience of people when attempting to lose weight. METHODS: Narrative interviews (n = 20) were conducted with people living with obesity to explore the causes of their weight gain and their expectations and engagement with treatment at a Weight Management Clinic. A mixed inductive and deductive qualitative analysis identified utterances that represented psychological constructs used to understand self-appraisal and health behaviour. A narrative analysis was used to situate these findings in the context of a participant's life story. RESULTS: Locus of control was a dominant construct evidenced through a person's attributional style and self-efficacy. Transcripts represented a heightened sense of self-understanding and shifts in control, and styles of attribution and efficacy resulted in either stasis or self-actualisation. The Stages of Change model could be applied to narratives to ascertain a patient's motivation to access treatment. Importantly, narrative interviews also allowed for the consideration of how a person's systemic context influenced their weight. CONCLUSION: Narrative interaction supports both self- and shared understandings of the causes and consequences of obesity for individuals, in a non-blaming or shaming manner. It provides an opportunity to enhance engagement through tailored, person-centred treatments.

Evolution of endosymbiosis-mediated nuclear calcium signaling in land plants.

The ability of fungi to establish mycorrhizal associations with plants and enhance the acquisition of mineral nutrients stands out as a key feature of terrestrial life. Evidence indicates that arbuscular mycorrhizal (AM) association is a trait present in the common ancestor of land plants,1,2,3,4 suggesting that AM symbiosis was an important adaptation for plants in terrestrial environments.5 The activation of nuclear calcium signaling in roots is essential for AM within flowering plants.6 Given that the earliest land plants lacked roots, whether nuclear calcium signals are required for AM in non-flowering plants is unknown. To address this question, we explored the functional conservation of symbiont-induced nuclear calcium signals between the liverwort Marchantia paleacea and the legume Medicago truncatula. In M. paleacea, AM fungi penetrate the rhizoids and form arbuscules in the thalli.7 Here, we demonstrate that AM germinating spore exudate (GSE) activates nuclear calcium signals in the rhizoids of M. paleacea and that this activation is dependent on the nuclear-localized ion channel DOES NOT MAKE INFECTIONS 1 (MpaDMI1). However, unlike flowering plants, MpaDMI1-mediated calcium signaling is only required for the thalli colonization but not for the AM penetration within rhizoids. We further demonstrate that the mechanism of regulation of DMI1 has diverged between M. paleacea and M. truncatula, including a key amino acid residue essential to sustain DMI1 in an inactive state. Our study reveals functional evolution of nuclear calcium signaling between liverworts and flowering plants and opens new avenues of research into the mechanism of endosymbiosis signaling.

The Impact of Adjustment on Workplace Attitudes and Behaviors Among Health Care Workers During the COVID-19 Pandemic.

OBJECTIVE: We examined the impact of health care workers' (HCWs) adjustment to the COVID-19 pandemic on their work-related attitudes and behaviors. METHODS: HCWs ( n = 1468) participated in an observational longitudinal study in which they completed surveys of anxiety and occupational health between 2020 and 2021. RESULTS: Most HCWs reported anxiety that was consistently below the diagnostic threshold (68%) or fell below the threshold within a year (16%). Others reported consistently high (14%) or increasing (2%) anxiety, especially women, younger HCWs, those with a weakened immune system, and allied health professionals. Consistently high or increasing anxiety was associated with poorer job satisfaction, work engagement, perceived supervisor support, burnout, and turnover intentions. CONCLUSIONS: Resources to support HCWs may be focused on those who report consistently high or increasing anxiety to minimize the effects of crises and disasters on the workforce.

A review of evidence for pneumococcal vaccination in adults at increased risk of pneumococcal disease: risk group definitions and optimization of vaccination coverage in the United Kingdom.

INTRODUCTION: Pneumococcal disease (PD) significantly contributes to morbidity and mortality, carrying substantial economic and public health burden. This article is a targeted review of evidence for pneumococcal vaccination in the UK, the definitions of groups at particular risk of PD and vaccine effectiveness. AREAS COVERED: Relevant evidence focusing on UK data from surveillance systems, randomized controlled trials, observational studies and publicly available government documents is collated and reviewed. Selected global data are included where appropriate. EXPERT OPINION: National vaccination programs have reduced the incidence of vaccine-type PD, despite the rising prominence of non-vaccine serotypes in the UK. The introduction of higher-valency conjugate vaccines provides an opportunity to improve protection against PD for adults in risk groups. Several incentives are in place to encourage general practitioners to vaccinate risk groups, but uptake is low-suboptimal particularly among at-risk individuals. Wider awareness and understanding among the public and healthcare professionals may increase vaccination uptake and coverage. National strategies targeting organizational factors are urgently needed to achieve optimal access to vaccines. Finally, identifying new risk factors and approaches to risk assessment for PD are crucial to ensure those at risk of PD can benefit from pneumococcal vaccination.

Healthcare interventions for sex workers: protocol for a scoping review.

INTRODUCTION: Sex workers, who provide sexual or erotic acts in exchange for payment, often experience multiple disadvantages, including mental ill health and substance misuse. Mainstream healthcare services are generally not configured to facilitate engagement with sex workers and therefore, services are needed that are accessible to this population. The aim of this scoping review is to understand the evidence base for approaches, services and interventions that are aimed at addressing sex workers' health needs. METHODS AND ANALYSIS: Nine databases, CINAHL, Embase, EThOS, Google Scholar, Health Management Information Consortium, MEDLINE, ProQuest Dissertations and Theses, PsycINFO and Web of Science (Core Collection), will be searched, with results limited to English language publications and those published from 2003 onwards. De-duplication, study selection and data extraction will be conducted using Covidence software. Included studies will describe or evaluate approaches, services or interventions that address the health needs of sex workers who offer services that involve physical contact with a client. ETHICS AND DISSEMINATION: No ethical review is needed. The final report will be shared with Birmingham City Council as part of ongoing work and will be disseminated by peer-reviewed publication. STUDY REGISTRATION: Open Science Framework (doi: 10.17605/OSF.IO/N7WSX).

Online Patient-Reported Outcome Measure Engagement Is Dependent on Demographics and Locality: Findings From an Observational Cohort.

OBJECTIVE: Online patient-reported outcome measures (PROMs) enable remote collection of perceptions of health status, function, and well-being. We aimed to explore patterns of PROM completion in patients with early inflammatory arthritis (EIA) recruited to the National Early Inflammatory Arthritis Audit (NEIAA). METHODS: NEIAA is an observational cohort study design; we included adults from this cohort with a new diagnosis of EIA from May 2018 to March 2020. The primary outcome was PROM completion at baseline, 3 months, and 12 months. Mixed effects logistic regression and spatial regression models were used to identify associations between demographics (age, gender, ethnicity, deprivation, smoking, and comorbidity), clinical commissioning groups, and PROM completion. RESULTS: Eleven thousand nine hundred eighty-six patients with EIA were included, of whom 5331 (44.5%) completed at least 1 PROM. Patients from ethnic minority backgrounds were less likely to return a PROM (adjusted odds ratio [aOR] 0.57, 95% CI 0.48-0.66). Greater deprivation (aOR 0.73, 95% CI 0.64-0.83), male gender (aOR 0.86, 95% CI 0.78-0.94), higher comorbidity burden (aOR 0.95, 95% CI 0.91-0.99), and current smoker status (aOR 0.73, 95% CI 0.64-0.82) also reduced odds of PROM completion. Spatial analysis identified 2 regions with high (North of England) and low (Southeast of England) PROM completion. CONCLUSION: We define key patient characteristics (including ethnicity) that influence PROM engagement using a national clinical audit. We observed an association between locality and PROM completion, with varying response rates across regions of England. Completion rates could benefit from targeted education for these groups.

A double-blind, sham-controlled, trial of home-administered rhythmic 10-Hz median nerve stimulation for the reduction of tics, and suppression of the urge-to-tic, in individuals with Tourette syndrome and chronic tic disorder.

Tourette syndrome (TS) and chronic tic disorder (CTD) are neurological disorders of childhood onset characterized by the occurrence of tics; repetitive, purposeless, movements or vocalizations of short duration which can occur many times throughout a day. Currently, effective treatment for tic disorders is an area of considerable unmet clinical need. We aimed to evaluate the efficacy of a home-administered neuromodulation treatment for tics involving the delivery of rhythmic pulse trains of median nerve stimulation (MNS) delivered via a wearable 'watch-like' device worn at the wrist. We conducted a UK-wide parallel double-blind sham-controlled trial for the reduction of tics in individuals with tic disorder. The device was programmed to deliver rhythmic (10 Hz) trains of low-intensity (1-19 mA) electrical stimulation to the median nerve for a pre-determined duration each day, and was intended to be used by each participant in their home once each day, 5 days each week, for a period of 4 weeks. Between 18th March 2022 and 26th September 2022, 135 participants (45 per group) were initially allocated, using stratified randomization, to one of the following groups; active stimulation; sham stimulation or to a waitlist (i.e. treatment as usual) control group. Recruited participants were individuals with confirmed or suspected TS/CTD aged 12 years of age or upward with moderate to severe tics. Researchers involved in the collection or processing of measurement outcomes and assessing the outcomes, as well as participants in the active and sham groups and their legal guardians were all blind to the group allocation. The primary outcome measure used to assess the 'offline' or treatment effect of stimulation was the Yale Global Tic Severity Scale-Total Tic Severity Score (YGTSS-TTSS) assessed at the conclusion of 4 weeks of stimulation. The primary outcome measure used to assess the 'online' effects of stimulation was tic frequency, measured as the number of tics per minute (TPM) observed, based upon blind analysis of daily video recordings obtained while stimulation was delivered. The results demonstrated that after 4-week stimulation, tic severity (YGTSS-TTSS) had reduced by 7.1 points (35 percentile reduction) for the active stimulation group compared to 2.13/2.11 points for the sham stimulation and waitlist control groups. The reduction in YGTSS-TTSS for the active stimulation group was substantially larger, clinically meaningful (effect size = .5) and statistically significant (p = .02) compared to both the sham stimulation and waitlist control groups, which did not differ from one another (effect size = -.03). Furthermore, blind analyses of video recordings demonstrated that tic frequency (tics per minute) reduced substantially (-15.6 TPM) during active stimulation compared to sham stimulation (-7.7 TPM). This difference represents a statistically significant (p < .03) and clinically meaningful reduction in tic frequency (>25 percentile reduction: effect size = .3). These findings indicate that home-administered rhythmic MNS delivered through a wearable wrist-worn device has the potential to be an effective community-based treatment for tic disorders.

Prevalence of oral and blood oncogenic human papillomavirus biomarkers among an enriched screening population: Baseline results of the MOUTH study.

BACKGROUND: Human papillomavirus (HPV)-related oropharyngeal cancer screening is being explored in research studies, but strategies to identify an appropriate population are not established. The authors evaluated whether a screening population could be enriched for participants with oncogenic HPV biomarkers using risk factors for oral HPV. METHODS: Participants were enrolled at Johns Hopkins Hospitals and Mount Sinai Icahn School of Medicine. Eligible participants were either men aged 30 years or older who had two or more lifetime oral sex partners and a personal history of anogenital dysplasia/cancer or partners of patients who had HPV-related cancer. Oral rinse and serum samples were tested for oncogenic HPV DNA, RNA, and E6 or E7 antibodies, respectively. Participants with any biomarker were considered at-risk. RESULTS: Of 1108 individuals, 7.3% had any oncogenic oral HPV DNA, and 22.9% had serum antibodies for oncogenic HPV E6 or E7. Seventeen participants (1.5%) had both oral and blood biomarkers. HPV type 16 (HPV16) biomarkers were rarer, detected in 3.7% of participants, including 20 with oral HPV16 DNA and 22 with HPV16 E6 serum antibodies (n = 1 had both). In adjusted analysis, living with HIV (adjusted odds ratio, 2.65; 95% CI, 1.60-4.40) and older age (66-86 vs. 24-45 years; adjusted odds ratio, 1.70; 95% CI, 1.07-2.70) were significant predictors of being at risk. Compared with the general population, the prevalence of oral HPV16 (1.8% vs. 0.9%), any oncogenic oral HPV DNA (7.3% vs. 3.5%), and HPV16 E6 antibodies (2.2% vs. 0.3%) was significantly elevated. CONCLUSIONS: Enrichment by the eligibility criteria successfully identified a population with higher biomarker prevalence, including HPV16 biomarkers, that may be considered for screening trials. Most in this group are still expected to have a low risk of oropharyngeal cancer.

The COSI trial: a study protocol for a multi-centre, randomised controlled trial to explore the clinical and cost-effectiveness of the Circle of Security-Parenting Intervention in community perinatal mental health services in England.

BACKGROUND: Perinatal mental health difficulties affect up to 27% of birthing parents during pregnancy and the first postnatal year, and if untreated are associated with difficulties in bonding and long-term adverse outcomes to children. There are large evidence gaps related to psychological treatment, particularly in group therapy approaches and parent-infant interventions. One intervention showing preliminary efficacious findings and user acceptability is Circle of Security-Parenting (COS-P), which is a brief, weekly, group programme. However, these studies were underpowered and predominantly non-randomised, and there has never been a research trial in England or with birthing parents experiencing severe and complex perinatal mental health difficulties. The aim of the research is to conduct a randomised control trial to test whether COS-P will reduce perinatal mental health symptoms in birthing parents accessing NHS perinatal mental health services, compared to treatment as usual (TAU). Secondary objectives include exploring whether the intervention improves parenting sensitivity, emotion regulation skills, attachment security and infant development. Additionally, the project aims to examine whether the intervention is acceptable to parents and NHS staff, and whether it is cost-effective. METHODS: COSI is an individually randomised, single-blind parallel arm controlled trial with an embedded internal pilot aiming to recruit 369 participants in a 2:1 ratio (intervention: TAU). Participants will be recruited from ten NHS community perinatal mental health services in England and screened based on clinical levels of both mental health symptoms (average CORE-OM score ≥ 1.1) and postnatal bonding difficulties (total PBQ score ≥ 12). This trial has 90% power to detect a MCID of 5 points on the CORE-OM. Primary and secondary outcomes will be measured at baseline, 3, 7 and 12 months after baseline. Service use and quality of life measures will also be collected alongside a process evaluation of parents' and interveners' views and experiences. DISCUSSION: This will be the first large pragmatic trial to test whether COS-P is effective for birthing parents with severe and complex perinatal mental health difficulties in improving their mental health symptoms. If shown to be effective, the intervention could be delivered widely across the NHS and other similar services globally. TRIAL REGISTRATION: ISRCTN, ISRCTN18308962. Registered 18 February 2022.

Moral injury and psychosocial functioning in health care workers during the COVID-19 pandemic.

Studies of moral injury among nonmilitary samples are scarce despite repeated calls to examine the prevalence and outcomes of moral injury among civilian frontline workers. The purpose of this study was to describe the prevalence of moral injury and to examine its association with psychosocial functioning among health care workers during the COVID-19 pandemic. We surveyed health care workers (N = 480), assessing exposure to potentially morally injurious events (PMIEs) and psychosocial functioning. Data were analyzed using latent class analysis (LCA) to explore patterns of PMIE exposure (i.e., classes) and corresponding psychosocial functioning. The minimal exposure class, who denied PMIE exposure, accounted for 22% of health care workers. The moral injury-other class included those who had witnessed PMIEs for which others were responsible and felt betrayed (26%). The moral injury-self class comprised those who felt they transgressed their own values in addition to witnessing others' transgressions and feeling betrayed (11%). The betrayal-only class included those who felt betrayed by government and community members but otherwise denied PMIE exposure (41%). Those assigned to the moral injury-self class were the most impaired on a psychosocial functioning composite, followed by those assigned to the moral injury-other and betrayal-only classes, and finally the minimal exposure class. Moral injury is prevalent and impairing for health care workers, which establishes a need for interventions with health care workers in organized care settings. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Exposure to potentially morally injurious events and mental health outcomes among frontline workers affected by the coronavirus pandemic.

OBJECTIVE: The current studies explored associations between exposure to potentially morally injurious events (PMIEs) and mental health outcomes among frontline workers affected by the coronavirus pandemic. METHOD: We administered online self-report surveys to emergency responders (N = 473) and hospital personnel (N = 854) in the Rocky Mountain region of the United States between April and June of 2020. Surveys assessed frequency and intensity of exposure to PMIEs alongside psychological and functional outcomes. RESULTS: Between 20% and 30% of frontline workers reported exposure to PMIEs of at least moderate frequency and intensity. Exposure to more intense PMIEs was associated with greater psychological symptoms (i.e., stress, depression, and anxiety) and functional impairment (i.e., professional burnout), especially among emergency responders who reported frequent exposure but also hospital workers who reported few exposures. CONCLUSION: Efforts to facilitate and maintain the well-being of the public health workforce should specifically address critical incidents encountered by frontline workers that have embedded moral and ethical challenges. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Long term outcome of antegrade colonic enema (ACE) stoma for treatment of constipation and fecal incontinence in children.

AIM: To determine the long term outcome of antegrade colonic enema (ACE) stoma for treatment of chronic constipation and soiling in children. METHOD: We reviewed patients prospectively who underwent formation of ACE stoma after failure of maximum medical treatment of chronic constipation and soiling from September 2008 to October 2020. All patients had anorectal manometry, endosonography and colonic transit study. A validated symptom severity (SS) score questionnaire was used pre operatively and during follow up. The sum of SS score ranged between 0 (best) and 65 (worst). Data was expressed as median(range) and Wilcoxon rank sum test was used and p value < 0.05 was considered significant. RESULTS: 58 patients had formation of ACE stoma, laparoscopic appendicostomy 56, cecostomy 1, and open procedure 1. The main indications for the ACE stoma were chronic functional constipation (FC) 50(86%), anorectal malformations (ARM) 6(11%) and Hirschsprung disease (HD) 2(3%). 41(71%) of patients had previous intrasphincteric botulinum toxin (BT) treatment. Age at operation was 11(range 4-15) years and follow up was 36(3-84) months. 47(81%) patients were continent of stool within three months postoperatively. The preoperative SS score improved from 34/65 (26-47) to 8/65 (4-12) at 12 months and 5/65 (2-11) at 24 months follow up, p ≤ 0.05. OVERALL: complication rate was 15(26%), wound infection 5, granulation tissue 4, stoma prolapse 4, retraction 1, abscess formation and fistula 1. 15 (26%) adolescents had transition of their care to adult services. CONCLUSION: There is a significant improvement of constipation, soiling and general health of patients following formation of ACE stoma. Adolescents benefits an orderly transition of their care to adult services. LEVEL OF EVIDENCE: Level 2, Therapeutic study.

Laparoscopic Complete Mesocolic Excision Without Routine Gastro-Pancreatico-Colic Trunk Dissection: Survival Outcomes and Morbidity for 567 Cases.

Purpose: It is unclear whether the principles of open complete mesocolic excision (CME) can be safely applied to laparoscopic surgery. Furthermore, definitions vary over how radical optimal CME surgery should be. We report morbidity and oncological outcomes for laparoscopic CME without routine gastro-pancreatico-colic trunk (GPCT) dissection. Materials and Methods: An observational study with consecutive data for patients with Union for International Cancer Control (UICC) stage I-III colon adenocarcinoma who underwent elective laparoscopic resection between 2006 and 2015. Data were retrieved for demographics, tumor characteristics, treatment, and histology from prospectively maintained databases. Standardized, routinely video recorded, laparoscopic resections were performed in two United Kingdom centers from The National Training Programme for Laparoscopic Colorectal Surgery. Overall survival and disease-free survival (DFS) were reported using Kaplan-Meier curves and Cox regression. Results: Laparoscopic CME was performed in 567 patients, 52.7% (288/546) women, median (interquartile range [IQR]) age 73 (65-80) years. Median (IQR) length of stay was 4 (3-5) days with 4.0 (2.2-5.7)-year follow-up. Significant DFS predictors (hazard ratio [HR]) by multivariable Cox regression were age >80 years (1.9), American Society of Anesthesiologists (ASA) 3 and 4 (HR = 1.1), right colon cancer (1.7), UICC stage III (3.4), and intramesocolic grade (2.2). Overall 4-year DFS (95% confidence interval) was 81.3% (77-85). Four-year DFS by UICC grades I, II, and III was 94.6% (89-99), 83.4% (77-88), and 72.2% (66-78), respectively (log-rank P = .001). Morbidity by Clavien-Dindo grade was III 18 (3.2%), IV 4 (0.7%) and V 7 (1.2%). Conclusion: This large series suggests standardized laparoscopic CME without routine GPCT dissection has a low morbidity and achieves equivalent outcomes to the most radical open CME techniques.

Hospitalization costs of adult community-acquired pneumonia in England.

OBJECTIVE: Accurate and up-to-date figures of the cost of community-acquired pneumonia (CAP) hospitalization are needed to understand the associated economic burden for public health decision-makers. Recent estimates are lacking, and previously published estimates differ markedly. Our objective was to estimate the current mean cost to the UK National Health Service (NHS) for adult hospitalized CAP. METHODS: All CAP hospitalizations in 2019 for those aged ≥18 years were identified from English Hospital Episode Statistics (HES). Each hospitalization was mapped to the tariff cost paid to the care provider within the NHS, including critical care costs and accounting for length of stay and complexity of the case. Mean hospitalization costs were estimated in total and in individuals with defined underlying comorbidities. RESULTS: A mean cost of £3,904 was estimated for 187,251 CAP admissions providing a total cost of approximately £731 million per annum. The mean cost was £3,402, excluding critical care costs, and £11,654 for critical care episodes in the 4.4% of admissions receiving this care. Groups at high risk of CAP had higher mean costs, ranging from £4,458 for people with diabetes to £5,215 for those with heart disease aged <65 years and £4,356 for those with heart disease to £4,751 for those with liver disease aged >65 years who comprised 74.3% of admissions overall. CONCLUSION: This estimate of the cost of hospitalization for CAP from the total population and in those with certain underlying comorbidities will allow a valid understanding of the cost-benefit of vaccination and evidence-based prioritization of pneumococcal vaccination to those at highest risk.

Community-acquired pneumonia (CAP) is a disease that is most commonly caused in England by the bacterium Streptococcus pneumoniae, which infects patients outside of a hospital. Patients who suffer from CAP often require hospitalization, which incurs a cost to the UK National Health Service (NHS). The goal of this study was to establish the annual cost of hospitalized CAP.The researchers used England's national healthcare database, known as Hospital Episodes Statistics (HES), to select all adults in England who were hospitalized for CAP in 2019. For the 187,251 patients hospitalized, an average cost of £3,904 per person was estimated, amounting to a total cost of £731 million per year to the NHS. Most people admitted to hospital with CAP were at risk for the disease (due to factors such as increased age or presence of another disease) and the cost of treatment for this subgroup was disproportionately larger than that for treatment of patients not at risk. Furthermore, while approximately 5% of patients admitted for CAP received critical care during treatment, the average cost for these patients was over £8,000 higher than for those outside this subsection.The costs of hospitalization reported in this analysis were higher than previously estimated. The researchers highlighted weaknesses in other studies and limitations of the current study which could explain the difference. This work provides up-to-date figures for the cost of treating CAP in hospital in England. Public health decision-makers can use these estimates to determine the cost-benefit of vaccines that can help protect against important causes of CAP, particularly vaccines that target S. pneumoniae.

X-Linked Agammaglobulinemia: Infection Frequency and Infection-Related Mortality in the USIDNET Registry.

X-linked agammaglobulinemia (XLA) is a primary immunodeficiency disorder caused by mutations in the Bruton tyrosine kinase (BTK) gene leading to B lymphocyte deficiency and susceptibility to infection. A potential benefit of earlier diagnosis and treatment initiation on morbidity and mortality in XLA is incompletely understood. In the USIDNET Registry, we describe infection frequency and infection-related mortality in patients with XLA and their relationship to age of diagnosis and treatment initiation. Among the 231 XLA patients enrolled in the Registry, respiratory infections (N = 203, 88%) were the most commonly reported. Among those deceased (N = 20) where cause of death was known (N = 17), mortality was attributed to infection in most (N = 12, 71%). Chronic lung disease, often a consequence of repeated lower respiratory tract infection (LRTI), was also a frequent complication associated with mortality (N = 9, 53%). Age of diagnosis in years was lower for those without LRTI compared to those with (median 1.5 [IQR 0.5-3.3] vs. median 3.0 [IQR 1.0-5.0], p = 0.0026) and among living patients compared to deceased (median 1.8 [IQR 0.5-5.0] vs. median 2.7 [IQR 1.6-6.0], p = 0.04). Age at treatment initiation in years was lower among those without LRTIs compared to those with (median 1.0 [IQR 0.4-2.4] vs. median 2.8 [IQR 1.0-5.4], p = 0.0006). For every year increase in age at start of therapy, the odds of experiencing a LRTI was 1.216 (OR 1.216, 95% CI 1.048-1.411, p = 0.01). Given the expected finding of reduced LRTIs and mortality among those with earlier age at diagnosis, our study findings support inclusion of XLA in newborn screening programs.

Morbidity, Mortality, and Therapeutics in Combined Immunodeficiency: Data From the USIDNET Registry.

BACKGROUND: Optimal management of patients with combined immunodeficiency, especially pertaining to hematopoietic stem cell transplantation (HSCT), remains unclear. OBJECTIVE: To identify factors influencing HSCT and mortality in the population with combined immunodeficiency in North America. METHODS: We identified 337 participants in the United States Immunodeficiency Network database with diverse forms of combined immunodeficiency and their characteristics, including demographic characteristics, laboratory values, infectious history, comorbidities, and treatment strategies. Univariate analysis was performed using logistic regression, whereas multivariate analysis was performed using multiple Cox proportional hazards. RESULTS: On univariate analysis, disseminated invasive viral infections and variants in STAT3, GATA2, and, DOCK8 were associated with increased odds of HSCT. Mucocutaneous fungal infections and variants in STAT3 were associated with increased odds of survival, whereas disseminated/invasive fungal infections, disseminated/invasive viral infections, and parasitic infections were associated with decreased odds of survival. On multiple variable Cox proportional hazards analysis, variants in ZAP70, nonspecific bacterial, and disseminated/invasive viral infections were associated with increased hazards of transplantation, whereas variants in multiple genes (RMRP, NEMO, DOCK8, CD40L, and CARD9), disseminated/invasive viral infections, autoimmune disease, and higher absolute lymphocyte count were associated with increased hazards of death. Importantly, demographic characteristics, basic lymphocyte subset counts, and absence of genetic diagnosis were not associated with HSCT or mortality. CONCLUSIONS: We determined that specific genetic diagnoses and infection burden impacts the decision to undergo HSCT in this cohort. In addition, certain genetic diagnoses and invasive viral infections carry an increased risk of mortality.

Social cognitive mechanisms in healthcare worker resilience across time during the pandemic.

PURPOSE: Healthcare workers are at increased risk for mental health problems during disasters such as the COVID-19 pandemic. Identifying resilience mechanisms can inform development of interventions for this population. The current study examined pathways that may support healthcare worker resilience, specifically testing enabling (social support enabled self-efficacy) and cultivation (self-efficacy cultivating support) models. METHODS: Healthcare workers (N = 828) in the Rocky Mountain West completed self-report measures at four time points (once per month from April to July of 2020). We estimated structural equation models to explore the potential mediating effects that received social support and coping self-efficacy had (at time 2 and time 3) between traumatic stress symptom severity (at time 1 and time 4). Models included covariates gender, age, minority status, and time lagged co-variations between the proposed mediators (social support and coping self-efficacy). RESULTS: The full model fit the data well, CFI = .993, SRMR = .027, RMSEA = .036 [90% CIs (0.013, 0.057)]. Tests of sequential mediation supported enabling model dynamics. Specifically, the effects of time 1 traumatic stress severity were mediated through received social support at time 2 and time 3 coping self-efficacy, in sequential order to reduce time 4 traumatic stress severity. CONCLUSIONS: Findings show the importance of received social support and coping self-efficacy in mitigating psychopathology risk. Interventions can support mental health by focusing on social resource engagement that facilitates coping empowerment, which may decrease risk for mental health job-related problems among frontline healthcare workers exposed to highly stressful events.