Maladaptive health factors as potential mediators for the association between posttraumatic stress disorder and cardiovascular disease: A sex-stratified analysis in the U.S. adult population.

OBJECTIVES: This study examined sex differences for health risk factors as potential mediators in the association between posttraumatic stress disorder (PTSD) and cardiovascular disease (CVD). METHODS: Secondary data from the 2012-2013 National Epidemiological Survey on Alcohol and Related Conditions Wave 3 was used. This cross-sectional survey contains a nationally representative sample of 36,309 U.S. adults (nfemales = 20,447, Mage = 47.16, 95% CI = [46.74, 47,57]; nmales = 15,682, Mage = 45.88, 95% CI = [45.42, 46.34]). Natural effect models and logistic regression analyses were conducted to evaluate health risk factors (smoking, substance use, low physical activity, high body mass index [BMI], binge eating, and multiple health risk factors) as potential mediators for the PTSD-CVD relationship in females and males. RESULTS: High BMI (indirect AOR = 1.05, 95% CI = [1.02, 1.07]) and substance use (indirect AOR = 0.93, 95% CI = [0.88, 0.98], p = 0.005) were potential mediators in females and males respectively. Binge eating, smoking, and low physical activity were not mediators in either sex. The number of health risk factors was also a potential mediator in females (indirect AOR = 1.12, 95% CI = [1.07, 1.19], p = <0.001) though not males (indirect AOR = 1.09, 95% CI = [1.00, 1.19], p = .059). CONCLUSIONS: The results inform prevention strategies, such as screening for health risk factors to mitigate the adverse effect of PTSD on CVD risk. Findings also inform important directions for future longitudinal research to establish causal pathways.

Kids+ Parent Infant Program (PIP): a community model for supporting partnerships in early developmental follow-up and support.

High-risk infants are discharged home from hospital with increased care needs and the potential for the emergence of developmental disabilities, contributing to high levels of parental stress and anxiety. To enable optimal outcomes for high-risk infants and their families, developmental follow-up programs need to continue following hospital discharge. However, current follow-up care for high-risk infants is variable in terms of type, access and equity, and there seems to be a gap in existing services such as supporting the transition home, parental support, and inclusion of all at-risk infants regardless of causality. Routine follow-up that identifies developmental delays or neuromotor concerns can facilitate timely referral and access to targeted intervention during critical periods of development. The Kids+ Parent Infant Program (PIP) is a unique model of developmental follow-up that shares some characteristics with established programs, but also includes additional key elements for a seamless, wrap-around service for all high-risk infants and their families living in a regional area of Australia. This community-based program provides integrated assessment and intervention of infants, alongside parent support and education, embracing a holistic model that accounts for the complexity and interrelatedness of infant, parent, medical and developmental factors. By prioritising the well-being of high-risk infants and their families, the Kids+ PIP paves the way for improved developmental outcomes and provides an innovative model for developmental follow-up, with the potential for reproduction in other healthcare settings.

Sustained Retinal Defocus Increases the Effect of Induced Myopia on the Retinal Astrocyte Template.

The aim of this article is to describe sustained myopic eye growth's effect on astrocyte cellular distribution and its association with inner retinal layer thicknesses. Astrocyte density and distribution, retinal nerve fiber layer (RNFL), ganglion cell layer, and inner plexiform layer (IPL) thicknesses were assessed using immunochemistry and spectral-domain optical coherence tomography on seventeen common marmoset retinas (Callithrix jacchus): six induced with myopia from 2 to 6 months of age (6-month-old myopes), three induced with myopia from 2 to 12 months of age (12-month-old myopes), five age-matched 6-month-old controls, and three age-matched 12-month-old controls. Untreated marmoset eyes grew normally, and both RNFL and IPL thicknesses did not change with age, with astrocyte numbers correlating to RNFL and IPL thicknesses in both control age groups. Myopic marmosets did not follow this trend and, instead, exhibited decreased astrocyte density, increased GFAP+ spatial coverage, and thinner RNFL and IPL, all of which worsened over time. Myopic changes in astrocyte density, GFAP+ spatial coverage and inner retinal layer thicknesses suggest astrocyte template reorganization during myopia development and progression which increased over time. Whether or not these changes are constructive or destructive to the retina still remains to be assessed.

Early Alterations in Inner-Retina Neural and Glial Saturated Responses in Lens-Induced Myopia.

Purpose: Myopic marmosets are known to exhibit significant inner retinal thinning compared to age-matched controls. The purpose of this study was to assess inner retinal activity in marmosets with lens-induced myopia compared to age-matched controls and evaluate its relationship with induced changes in refractive state and eye growth. Methods: Cycloplegic refractive error (Rx), vitreous chamber depth (VCD), and photopic full-field electroretinogram were measured in 14 marmosets treated binocularly with negative contact lenses compared to 9 untreated controls at different stages throughout the experimental period (from 74 to 369 days of age). The implicit times of the a-, b-, d-, and photopic negative response (PhNR) waves, as well as the saturated amplitude (Vmax), semi-saturation constant (K), and slope (n) estimated from intensity-response functions fitted with Naka-Rushton equations were analyzed. Results: Compared to controls, treated marmosets exhibited attenuated b-, d-, and PhNR waves Vmax amplitudes 7 to 14 days into treatment before compensatory changes in refraction and eye growth occurred. At later time points, when treated marmosets had developed axial myopia, the amplitudes and implicit times of the b-, d-, and PhNR waves were similar between groups. In controls, the PhNR wave saturated amplitude increased as the b + d-wave Vmax increased. This trend was absent in treated marmosets. Conclusions: Marmosets induced with negative defocus exhibit early alterations in inner retinal saturated amplitudes compared to controls, prior to the development of compensatory myopia. These early ERG changes are independent of refraction and eye size and may reflect early changes in bipolar, ganglion, amacrine, or glial cell physiology prior to myopia development. Translational Relevance: The early changes in retinal function identified in the negative lens-treated marmosets may serve as clinical biomarkers to help identify children at risk of developing myopia.

Immune checkpoint blockers in solid organ transplant recipients and cancer: the INNOVATED cohort.

BACKGROUND: Patients with solid organ transplant (SOT) and solid tumors are usually excluded from clinical trials testing immune checkpoint blockers (ICB). As transplant rates are increasing, we aimed to evaluate ICB outcomes in this population, with a special focus on lung cancer. METHODS: We conducted a multicenter retrospective cohort study collecting real data of ICB use in patients with SOT and solid tumors. Clinical data and treatment outcomes were assessed by using retrospective medical chart reviews in every participating center. Study endpoints were: overall response rate (ORR), 6-month progression-free survival (PFS), and grade ≥3 immune-related adverse events. RESULTS: From August 2016 to October 2022, 31 patients with SOT (98% kidney) and solid tumors were identified (36.0% lung cancer, 19.4% melanoma, 13.0% genitourinary cancer, 6.5% gastrointestinal cancer). Programmed death-ligand 1 expression was positive in 29% of tumors. Median age was 61 years, 69% were males, and 71% received ICB as first-line treatment. In the whole cohort the ORR was 45.2%, with a 6-month PFS of 56.8%. In the lung cancer cohort, the ORR was 45.5%, with a 6-month PFS of 32.7%, and median overall survival of 4.6 months. The grade 3 immune-related adverse events rate leading to ICB discontinuation was 12.9%. Allograft rejection rate was 25.8%, and risk of rejection was similar regardless of the type of ICB strategy (monotherapy or combination, 28% versus 33%, P = 1.0) or response to ICB treatment. CONCLUSIONS: ICB could be considered a feasible option for SOT recipients with some advanced solid malignancies and no alternative therapeutic options. Due to the risk of allograft rejection, multidisciplinary teams should be involved before ICB therapy.

Priorities when designing a service-focused delivery model for mobility devices: a systematic review.

PURPOSE: Throughout the world, mobility devices are usually distributed using product-based business models, where a device is provided to a user, and serviced or replaced when the user returns to the clinic with an issue. Moving to a service-based business model can provide continuous and customised support for the user, and provide the clinicians and manufacturers with better data to base their decisions on. This study reviews papers on assistive technology service-based business models and considerations in designing such a model to optimise economic and social value. It then applies the findings to the mobility device space. METHOD: A systematic literature search was undertaken in PubMed, Web of Science, and OVID databases to analyse studies that discuss service delivery models used to provide assistive products. Inductive thematic analysis determined the themes, facilitators and barriers associated with providing a service. Findings were applied to mobility device service provision. RESULTS AND CONCLUSION: Themes from the 29 relevant papers were grouped into four categories: Access (affordability/availability/education), Utility (customisability/usability/adaptability), Integrity (quality/sustainability/impact), and Compliance (policy/privacy/security). The most common themes were customisability, affordability, availability, and education. There is a need for service-based delivery models to replace conventional product-based models, and many considerations to optimise their design. No publications discussed the design and implementation of a service-based model for mobility device provision that uses modern sensors, software and other digital technologies to optimise the service. Service-based models that use modern digital technologies are new for the mobility device field, but much can be learnt from other fields.

Service-based business models that make use of modern digital technologies are likely to improve ongoing individual rehabilitation, but they are new for the mobility device field and currently lack research and evidence-based practice.The systematic review found that modern digital technologies like sensors, apps, and AI might be useful for providing ongoing support and more personalised rehabilitation for users of assistive products.To provide ongoing support for end-users, a successful design of service-based business model for assistive products should be accessible, both physically and financially, as well as easy to customise and adapt over time.

Glial-mediated dysregulation of neurodevelopment in Fragile X Syndrome.

Astrocytes are highly involved in a multitude of developmental processes that are known to be dysregulated in Fragile X Syndrome. Here, we examine these processes individually and review the roles astrocytes play in contributing to the pathology of this syndrome. As a growing area of interest in the field, new and exciting insight is continually emerging. Understanding these glial-mediated roles is imperative for elucidating the underlying molecular mechanisms at play, not only in Fragile X Syndrome, but also other ASD-related disorders. Understanding these roles will be central to the future development of effective, clinically-relevant treatments of these disorders.

Effects of high incubation temperature on tight junction proteins in the yolk sac and small intestine of embryonic broilers.

During the transition from incubation to hatch, the chicks shift from obtaining nutrients from the yolk sac to the intestine. The yolk sac tissue (YST) and small intestine serve as biological barriers between the yolk or gut contents and the blood circulation. These barriers must maintain structural integrity for optimal nutrient uptake as well as protection from pathogens. The objective of this study was to investigate the effect of high incubation temperature on mRNA abundance of the tight junction (TJ) proteins zona occludens 1 (ZO1), occludin (OCLN), claudin 1 (CLDN1), and junctional adhesion molecules A and 2 (JAMA, JAM2) and the heat shock proteins (HSP70 and HSP90) in the YST and small intestine of embryonic broilers. Broiler eggs were incubated at 37.5°C. On embryonic day 12 (E12), half of the eggs were switched to 39.5°C. YST samples were collected from E7 to day of hatch (DOH), while small intestinal samples were collected from E17 to DOH. The temporal expression of TJ protein mRNA from E7 to DOH at 37.5°C and the effect of incubation temperature from E13 to DOH were analyzed by one-way and two-way ANOVA, respectively and Tukey's test. Significance was set at P < 0.05. The temporal expression pattern of ZO1, OCLN, and CLDN1 mRNA showed a pattern of decreased expression from E7 to E13 followed by an increase to DOH. High incubation temperature caused an upregulation of ZO1 and JAM2 mRNA in the YST and small intestine. Using in situ hybridization, OCLN and JAMA mRNA were detected in the epithelial cells of the YST. In addition, JAMA mRNA was detected in epithelial cells of the small intestine, whereas JAM2 mRNA was detected in the vascular system of the villi and lamina propria. In conclusion, the YST expressed mRNA for TJ proteins and high incubation temperature increased ZO1 and JAM2 mRNA. This suggests that the TJ in the vasculature of the YST and intestine is affected by high incubation temperature.

Effect of dermatological consultation on survival in patients with checkpoint inhibitor-associated cutaneous toxicity.

BACKGROUND: Cutaneous immune-related adverse events (cirAEs) are a common side-effect of immune checkpoint inhibitors (ICIs). However, prior work examining these toxicities in detail has considered only the fraction of events evaluated by dermatologists. Associations between dermatology referral, cirAE treatment and survival outcomes remain underexplored across care settings. OBJECTIVES: To comprehensively categorize cirAE patterns among all patients treated with immunotherapy at our institution, and to evaluate: (i) the effect of dermatology referral on cirAE treatment and (ii) the impact of cirAE treatment on survival. METHODS: This was a retrospective cohort analysis of patients with cancer who initiated ICI therapy between 1 January 2016 and 8 March 2019 and developed one or more cirAEs, as screened for using International Classification of Diseases 10th revision codes and confirmed via manual chart review (n = 358). All relevant information documented prior to 31 March 2020 was included. RESULTS: CirAEs evaluated by dermatologists were significantly more likely to be treated than cirAEs that were not referred (odds ratio 6·08, P < 0·001). Patients who received any cirAE treatment had improved progression-free survival [hazard ratio (HR) 0·59, P = 0·001] and overall survival (HR 0·58, P = 0·007) compared with those who did not. CONCLUSIONS: CirAEs evaluated by dermatologists were significantly more likely to be treated than cirAEs that were not referred, and patients who received any treatment for a cirAE had improved survival outcomes.

Development of a core outcome set for cutaneous squamous cell carcinoma trials: identification of core domains and outcomes.

BACKGROUND: The lack of uniformity in the outcomes reported in clinical studies of the treatment of cutaneous squamous cell carcinoma (cSCC) complicates efforts to compare treatment effectiveness across trials. OBJECTIVES: To develop a core outcome set (COS), a minimum set of agreed-upon outcomes to be measured in all clinical trials of a given disease or outcome, for the treatment of cSCC. METHODS: One hundred and nine outcomes were identified via a systematic literature review and interviews with 28 stakeholders. After consolidation of this long list, 55 candidate outcomes were rated by 19 physician and 10 patient stakeholders, in two rounds of Delphi exercises. Outcomes scored 'critically important' (score of 7, 8 or 9) by ≥ 70% of patients and ≥ 70% of physicians were provisionally included. At the consensus meeting, after discussion and voting of 44 international experts and patients, the provisional list was reduced to a final core set, for which consensus was achieved among all meeting participants. RESULTS: A core set of seven outcomes was finalized at the consensus meeting: (i) serious or persistent adverse events, (ii) patient-reported quality of life, (iii) complete response, (iv) partial response, (v) recurrence-free survival, (vi) progression-free survival and (vii) disease-specific survival. CONCLUSIONS: In order to increase the comparability of results across trials and to reduce selective reporting bias, cSCC researchers should consider reporting these core outcomes. Further work needs to be performed to identify the measures that should be reported for each of these outcomes.

Comparison of electric hand dryers and paper towels for hand hygiene: a critical review of the literature.

Numerous studies are published on the benefits of electric hand dryers vs paper towels (PT) for drying hands after washing. Data are conflicting and lacking key variables needed to assess infection risks. We provide a rapid scoping review on hand-drying methods relative to hygiene and health risks. Controlled vocabulary terms and keywords were used to search PubMed (1946-2018) and Embase (1947-2018). Multiple researchers independently screened abstracts for relevance using predetermined criteria and created a quality assessment scoring system for relative study comparisons. Of 293 papers, 23 were included in the final analysis. Five studies did not compare multiple methods; however, 2 generally favoured electric dryers (ED); 7 preferred PT; and 9 had mixed or statistically insignificant results (among these, 3 contained scenarios favourable to ED, 4 had results supporting PT, and the remaining studies had broadly conflicting results). Results were mixed among and within studies and many lacked consistent design or statistical analysis. The breadth of data does not favour one method as being more hygienic. However, some authors extended generalizable recommendations without sufficient scientific evidence. The use of tools in quantitative microbial risk assessment is suggested to evaluate health exposure potentials and risks relative to hand-drying methods. We found no data to support any human health claims associated with hand-drying methods. Inconclusive and conflicting results represent data gaps preventing the advancement of hand-drying policy or practice recommendations.

Supporting individuals with intellectual and developmental disability during the first 100 days of the COVID-19 outbreak in the USA.

BACKGROUND: It is unknown how the novel Coronavirus SARS-CoV-2, the cause of the current acute respiratory illness COVID-19 pandemic that has infected millions of people, affects people with intellectual and developmental disability (IDD). The aim of this study is to describe how individuals with IDD have been affected in the first 100 days of the COVID-19 pandemic. METHODS: Shortly after the first COVID-19 case was reported in the USA, our organisation, which provides continuous support for over 11 000 individuals with IDD, assembled an outbreak committee composed of senior leaders from across the health care organisation. The committee led the development and deployment of a comprehensive COVID-19 prevention and suppression strategy, utilising current evidence-based practice, while surveilling the global and local situation daily. We implemented enhanced infection control procedures across 2400 homes, which were communicated to our employees using multi-faceted channels including an electronic resource library, mobile and web applications, paper postings in locations, live webinars and direct mail. Using custom-built software applications enabling us to track patient, client and employee cases and exposures, we leveraged current public health recommendations to identify cases and to suppress transmission, which included the use of personal protective equipment. A COVID-19 case was defined as a positive nucleic acid test for SARS-CoV-2 RNA. RESULTS: In the 100-day period between 20 January 2020 and 30 April 2020, we provided continuous support for 11 540 individuals with IDD. Sixty-four per cent of the individuals were in residential, community settings, and 36% were in intermediate care facilities. The average age of the cohort was 46 ± 12 years, and 60% were male. One hundred twenty-two individuals with IDD were placed in quarantine for exhibiting symptoms and signs of acute infection such as fever or cough. Sixty-six individuals tested positive for SARS-CoV-2, and their average age was 50. The positive individuals were located in 30 different homes (1.3% of total) across 14 states. Fifteen homes have had single cases, and 15 have had more than one case. Fifteen COVID-19-positive individuals were hospitalised. As of 30 April, seven of the individuals hospitalised have been discharged back to home and are recovering. Five remain hospitalised, with three improving and two remaining in intensive care and on mechanical ventilation. There have been three deaths. We found that among COVID-19-positive individuals with IDD, a higher number of chronic medical conditions and male sex were characteristics associated with a greater likelihood of hospitalisation. CONCLUSIONS: In the first 100 days of the COVID-19 outbreak in the USA, we observed that people with IDD living in congregate care settings can benefit from a coordinated approach to infection control, case identification and cohorting, as evidenced by the low relative case rate reported. Male individuals with higher numbers of chronic medical conditions were more likely to be hospitalised, while most younger, less chronically ill individuals recovered spontaneously at home.

Changes with age in density of goblet cells in the small intestine of broiler chicks.

Goblet cells secrete mucin 2 (Muc2), which is a major component of the mucus that lines the intestinal tract and creates a protective barrier between pathogens and the intestinal epithelial cells and thus are important for chick health. The objectives of this study were to determine the age-specific and intestinal segment-specific expression of Muc2 mRNA and changes in the number of goblet cells from late embryogenesis to early after hatch. Small intestinal samples from the duodenum, jejunum, and ileum were collected from Cobb 500 broilers at embryonic day 19 (e19), day of hatch (doh), and day 2 and 4 after hatch. Cells expressing Muc2 mRNA and mucin glycoprotein were detected by in situ hybridization or alcian blue and periodic acid-Schiff staining, respectively. Along the villi, there were many more cells expressing Muc2 mRNA than those stained for mucin glycoprotein. In the crypt, cells expressing Muc2 mRNA did not stain for mucin glycoprotein. There was an increase in the density of goblet cells in the villi and Muc2 mRNA expressing cells in the crypts of the jejunum and ileum from e19 to doh and day 2 to day 4, with no change between doh and day 2. In contrast, in the duodenum, the density of goblet cells in the villi and Muc2 mRNA expressing cells in the crypts remained constant from e19 to day 4. At day 4, the villi in the ileum had a greater density of goblet cells than the duodenum. In the crypt, the ileum had a greater density of Muc2 mRNA expressing cells than the duodenum at doh, and the ileum and jejunum both had greater densities of Muc2 mRNA expressing cells than the duodenum at day 4. These results indicate that the population of goblet cells has reached a steady state by doh in the duodenum, whereas in the jejunum and ileum, a steady-state population was not reached until after hatch.

Clinical characteristics of exposures to liquid laundry detergent packets.

INTRODUCTION: Our objective was to describe the characteristics of liquid laundry detergent packet (LDP) exposures and to develop referral and treatment recommendations. METHODS: This retrospective cohort study investigated LDP exposures reported to the National Poison Data System from January 1, 2013 through June 30, 2014. Three medical toxicologists reviewed the most significant exposures (n = 450). RESULTS: Of 17,857 reported LDP exposures, 13,307 involved only an LDP (no other substance) and were followed to a known medical outcome. The median age was 2 years (range 12 days to 100 years). Approximately 10% of exposures reported a major or moderate effect. The most common symptom was vomiting (51.7%; n = 6875), but stridor or aspiration pneumonia and respiratory depression secondary to central nervous system effects also occurred. Two pediatric and two adult deaths occurred, but no causal mechanism leading to death could be identified in any of the deaths. CONCLUSIONS: LDPs occasionally produce a toxidrome of vomiting, stridor, hypoxia, and sedation with metabolic acidosis and respiratory failure. These symptoms and the availability of LDPs highlight the need for referral and treatment recommendations and efforts to minimize unintentional exposures. Review of data from US poison centers may provide referral and treatment recommendations that improve patient outcomes.

A comparison of two models of follow-up care for adult survivors of childhood cancer.

PURPOSE: Few studies have compared follow-up-care models for adult survivors of childhood cancer (ASCCs), though choice of model could impact medical test adherence, and health-related quality of life (QOL). This study compared two follow-up-care models, cancer-center-based versus community-based, for ASCCs in Alberta, Canada, to determine which model would demonstrate greater ASCC adherence to guideline-recommended medical screening tests for late effects, QOL, physical symptoms, and adherence to yearly follow-up. METHODS: ASCC discharged to a community model (over 15 years) and those with comparable birth years (1973-1993) currently followed in a cancer center model were recruited via direct contact or multimedia campaign. Chart review identified chemotherapeutic and radiation exposures, and required medical late effect screening tests. ASCCs also completed questionnaires assessing QOL, physical symptoms, and follow-up behavior. RESULTS: One hundred fifty-six survivors participated (community (n = 86); cancer center (n = 70)). Primary analysis indicated that cancer center ASCCs guideline-recommended total test adherence percentage (Mdn = 85.4%) was significantly higher than the community model (Mdn = 29.2%, U = 3996.50, p < 0.0001). There was no significant difference in QOL for cancer center ASCCs (M = 83.85, SD = 20.55 versus M = 77.50, SD = 23.94; t (154) = 1.77, p = 0.078) compared to community-based ASCCs. Cancer center-based ASCCs endorsed from 0.4-7.1% fewer physical symptom clusters, and higher adherence to follow-up behavior in comparisons using effect sizes without p values. CONCLUSION: This study highlights the cancer center model's superiority for adherence to exposure-based medical late effect screening guidelines, cancer-specific follow-up behaviors, and the reporting of fewer physical complaints in ASCCs. IMPLICATIONS FOR CANCER SURVIVORS: ASCCs followed in a cancer center model likely benefit from earlier late-effects detection and opportunities for early intervention.

Floor and environmental contamination during glove disposal.

BACKGROUND: Evidence suggests that doffing and possibly disposal of used personal protective equipment (PPE) can lead to environmental contamination. AIM: To ascertain the potential for site and floor contamination when medical gloves are inappropriately disposed. METHODS: Fifteen healthcare workers (HCWs) disposed of gloves inoculated with bacteriophage and a chemical dye into a wastebasket, located 1.22 m away. Following each trial, designated sample areas were visually inspected with a blacklight for fluorescent dye stains and swabbed with a 3M Letheen Broth sponge to quantify the bacteriophage. FINDINGS: The area closest to the participant (<0.30 m) had the highest bacteriophage concentrations (geomean: 6.9 × 103 pfu/100 cm2; range: 8.07 to 3.93 × 107 pfu/100 cm2). Bacteriophage concentrations were significantly higher (P < 0.05) in areas ≤0.61 m compared to >0.61 m from the HCWs. Although the farthest distances (1.22-1.52 m) resulted in 14% bacteriophage- and 4% fluorescent dye-positive occurrences, there was no significant difference (P = 0.069) between the tracers. The bacteriophage and chemical dye indicate highest environmental contamination nearest the HCWs and both tracers could be appropriate for PPE disposal training. CONCLUSION: HCWs use gloves every workday and potentially could contaminate surrounding surfaces and floors, during improper disposal practices. Therefore, proper disposal techniques are required to minimize pathogen transmission by establishing industry-wide policies, adequate training, and education to HCWs.