Seasonal changes in physiological and psychological parameters of stress in collegiate swimmers.

To investigate the seasonal changes in physiological and psychological parameters of stress in collegiate swimmers. Fifteen NCAA Division I swimmers (8 men) participated in a tethered anaerobic swim test to determine physiological responses in an ecologically-relevant, graded exercise test. Wisconsin Upper Respiratory Symptom Survey (WURSS-21), Activation-Deactivation Adjective Check List (AD-ACL), Daily Analysis of Life Demands of Athletes (DALDA), and Pittsburgh Sleep Quality Index were assessed at post-season in April (V1), the end of off-season in June (V2), and pre-season in October (V3). The percent change was determined from V2-V1 (off-season phase), V3-V2 (pre-season phase), V1-V3 (in-season phase). Spearman's rho correlation was used to examine associations between change in physiological and psychological outcomes. All data results showed a better swim performance occurred at V2. Men tended to have faster speed (p = 0.07) in fewer strokes (p = 0.10) and greater work per stroke (p = 0.10) at V2 than V1. Women were faster during V2 compared to V1 (p = 0.02) and V3 (p = 0.05). Women had fewer strokes (p = 0.02) and greater work per stroke (p = 0.01) at V2 compared to V3. Women had the lowest HR and lactate concentration at V3 compared to other visits (p < 0.05). During the in-season phase, swim speed decreased the greatest extent and stress sources and symptoms assessed by DALDA had greatest elevation (p < 0.05). An increased in stress sources and symptoms assessed by DALDA was associated with an increase in upper respiratory illness from WURSS-21 (rho = 0.44, p = 0.009), being less energetic (rho = - 0.35, p = 0.04) and greater tension state (rho = 0.49, p = 0.003; AD-ACL), and a decrease in swim speed (rho =- 0.38, p = 0.03). Swim performance peaked at off-season when psychological stress was at its lowest. The relationship between DALDA scores with psychological parameters and swim performance suggested physiological and psychological parameters of stress is an important aspect to avoid overtraining when approaching high swim performance.

Influenza vaccination reveals and partly reverses sex dimorphic immune imprints associated with prior mild COVID-19

Viral infections can have profound and durable functional impacts on the immune system. There is an urgent need to characterize the long-term immune effects of SARS-CoV-2 infection given the persistence of symptoms in some individuals and the continued threat of novel variants. Here we use systems immunology, including longitudinal multimodal single cell analysis (surface proteins, transcriptome, and V(D)J sequences) from 33 previously healthy individuals after recovery from mild, non-hospitalized COVID-19 and 40 age- and sex-matched healthy controls with no history of COVID-19 to comparatively assess the post-infection immune status (mean: 151 days after diagnosis) and subsequent innate and adaptive responses to seasonal influenza vaccination. Identification of both sex-specific and -independent temporally stable changes, including signatures of T-cell activation and repression of innate defense/immune receptor genes (e.g., Toll-like receptors) in monocytes, suggest that mild COVID-19 can establish new post-recovery immunological set-points. COVID-19-recovered males had higher innate, influenza-specific plasmablast, and antibody responses after vaccination compared to healthy males and COVID-19-recovered females, partly attributable to elevated pre-vaccination frequencies of a GPR56 expressing CD8+ T-cell subset in male recoverees that are "poised" to produce higher levels of IFN{gamma} upon inflammatory stimulation. Intriguingly, by day 1 post-vaccination in COVID-19-recovered subjects, the expression of the repressed genes in monocytes increased and moved towards the pre-vaccination baseline of healthy controls, suggesting that the acute inflammation induced by vaccination could partly reset the immune states established by mild COVID-19. Our study reveals sex-dimorphic immune imprints and in vivo functional impacts of mild COVID-19 in humans, suggesting that prior COVID-19, and possibly respiratory viral infections in general, could change future responses to vaccination and in turn, vaccines could help reset the immune system after COVID-19, both in an antigen-agnostic manner.

Alcohol use disorder in active duty service members: Incidence rates over a 19-year period.

Background: Alcohol use is a concerning issue for the military given its potential negative impact on human performance. Limited data are available regarding the incidence of alcohol use disorder in the military, which is critical to understand to evaluate force readiness, as well as for preventative initiatives and treatment planning. The aim was to examine the alcohol use disorder incidence rates (overall and across demographics) among active duty service members from 2001 to 2018. Methods: Data on 208,870 active duty service members between 2001 and 2018 from the Defense Medical Epidemiology Database was examined. Incidence rates were analyzed to determine the diagnostic rates of AUD (including both alcohol abuse and dependence), which were then examined by sex, age, service branch, military pay grade, marital status, and race. Results: Incidence rates of AUD in active duty service members (per 1,000 service members) ranged from 6.45 to 10.50 for alcohol abuse and 5.21 to 7.11 for alcohol dependence. Initial diagnoses of new-onset AUD occurred most frequently within 20-24 year-old, white, male, and non-married U.S. Army service members in the enlisted pay grades of E-1 to E-4. Statistically significant differences (p <.001) were found between observed and expected counts across all examined demographic variables. Conclusions: To our knowledge, this is the first study to provide a comprehensive examination of AUD incidence rates in an active-duty military population over an extended 18-year period and during the last decade. Incidence rates were higher than expected for alcohol dependence and lower than expected for alcohol abuse. Given the untoward effects of AUD on overall health and force readiness, active-duty service members may benefit from more advanced preventative interventions to decrease incidence rates of AUD over time. Future research should use these data to develop targeted interventions for the demographics at greatest risk.

British Association of Dermatologists National Clinical Audit on the Management of Hidradenitis Suppurativa in the UK.

BACKGROUND: The first UK guidelines for the management of hidradenitis suppurativa (HS) were published by the British Association of Dermatologists (BAD) in 2018. The guidelines contained a set of audit criteria. AIM: To evaluate current HS management against the audit standards in the BAD guidelines. METHODS: BAD members were invited to complete audit questionnaires between January and May 2020 for five consecutive patients with HS per department. RESULTS: In total, 88 centres participated, providing data for 406 patients. Disease staging using the Hurley system and disease severity using a validated tool during follow-ups was documented in 75% and 56% of cases, respectively, while quality of life and pain were documented in 49% and 50% of cases, respectively. Screening for cardiovascular disease risk factors was as follows: smoking 75%, body mass index 27% and others such as lipids and diabetes 57%. Screening for depression and anxiety was performed in 40% and 25% of cases, respectively. Support for smokers or obese patients was documented in 35% and 23% of cases. In total, 182 patients were on adalimumab, of whom 68% had documentation of baseline disease severity, and 76% were reported as having inadequate response or contraindications to systemic treatments; 44% of patients continued on adalimumab despite having < 25% improvement in lesion count. CONCLUSION: UK dermatologists performed well against several audit standards, including documenting disease staging at baseline and smoking status. However, improvements are needed, particularly with regard to screening and management of comorbidities that could reduce the long-term complications associated with HS. A re-audit is required to evaluate changes in practice in the future.

An international survey on the impact of COVID-19 in individuals with Down syndrome

BackgroundHealth conditions and immune dysfunction associated with trisomy 21 (Down syndrome, DS) may impact the clinical course of COVID-19 once infected by SARS-CoV-2. MethodsThe T21RS COVID-19 Initiative launched an international survey for clinicians or caregivers/family members on patients with COVID-19 and DS (N=1046). De-identified survey data collected between April and October 2020 were analysed and compared with the UK ISARIC4C survey of hospitalized COVID-19 patients with and without DS. COVID-19 patients with DS from the ISARIC4C survey (ISARIC4C DS cases=100) were matched to a random set of patients without DS (ISARIC4C controls=400) and hospitalized DS cases in the T21RS survey (T21RS DS cases=100) based on age, gender, and ethnicity. FindingThe mean age in the T21RS survey was 29 years (SD=18), 73% lived with their family. Similar to the general population, the most frequent signs and symptoms of COVID-19 were fever, cough, and shortness of breath. Pain and nausea were reported less frequently (p<0.01), whereas altered consciousness/confusion were reported more frequently (p<0.01). Risk factors for hospitalization and mortality were similar to the general population (age, male gender, diabetes, obesity, dementia) with the addition of congenital heart defects as a risk factor for hospitalization. Mortality rates showed a rapid increase from age 40 and were higher than for controls (T21RS DS versus controls: risk ratio (RR)=3.5 (95%-CI=2.6;4.4), ISARIC4C DS versus controls: RR=2.9 (95%-CI=2.1;3.8)) even after adjusting for known risk factors for COVID-19 mortality. InterpretationLeading signs/symptoms of COVID-19 and risk factors for severe disease course are similar to the general population. However, individuals with DS present significantly higher rates of mortality, especially from age 40. FundingDown Syndrome Affiliates in Action, Down Syndrome Medical Interest Group-USA, GiGis Playhouse, Jerome Lejeune Foundation, LuMind IDSC Foundation, Matthews Foundation, National Down Syndrome Society, National Task Group on Intellectual Disabilities and Dementia Practices.

British Association of Dermatologists (BAD) National Audit on Non-Melanoma Skin Cancer Excision 2016 in collaboration with the Royal College of Pathologists.

BACKGROUND: We conducted a re-audit of the surgical practice of UK dermatologists for the treatment of nonmelanoma skin cancer and examined changes with reference to our previous audit in 2014. The audit was supplemented by a detailed assessment of completeness of the histopathology reports for each tumour. METHODS: UK dermatologists collected data on 10 consecutive nonmicrographic excisions for basal cell carcinoma (BCC) and 5 for squamous cell carcinoma (SCC). Data were collected on site, preoperative diagnosis, histological diagnosis, proximity to previous scars, and histological deep and peripheral margins. RESULTS: In total, 222 responses were received from 135 centres, reporting on 3290 excisions. Excisions from the head and neck accounted for 56.7% of cases. Tumour diameter (mean ± SD) was 11.4 ± SD 7.1 mm (maximum size 100 mm) and 97% of cases were primary excisions. BCCs and SCCs respectively accounted for 65.7% and 26.8% of total cases. Of the suspected BCCs and SCCs, 95.8% and 80.4%, respectively, were confirmed histologically. All margins for any tumour were clear in 97.0% of cases, and complication rate in the audit was < 1%. Of the 2864 histology reports evaluated, only 706 (24.6%) contained all core data items; 95% of these were structure (synoptic) reports. Commonly omitted items were level of invasion, risk and T stage, which were absent from 35.7%, 64.2% and 44.1% of reports, respectively. CONCLUSIONS: Diagnostic accuracy and complete excision rates remain high. Complication rates may be under-reported owing to lack of follow-up. Histopathology reporting has a greater chance of being complete if reports are generated on a field-based platform (synoptic reporting).

Caregiver Choice and Caregiver Outcomes: A Longitudinal Study of Irish Spousal Dementia Caregivers.

BACKGROUND: The perception of choice in becoming a caregiver may impact on caregiver psychological and physical health. We determined the proportion of spousal dementia caregivers who felt they had a choice, and examined whether lack of choice in taking up the caregiving role and the perceived degree of choice in caregiving predicted caregiver health and wellbeing and care-recipient placement in long-term care at 1-year follow-up. METHODS: We performed secondary analyses of data from DeStress, a longitudinal study of 251 spousal dementia caregivers in Ireland. We used multivariate logistic and linear regression analyses to examine whether lack of choice (a dichotomous item) and/or the perceived degree of choice (a 9-point scale) at baseline predicted caregiver health (number of chronic health conditions; self-reported health) and wellbeing (e.g., burden, anxiety, depression, stress, and positive aspects of caregiving) and care status (continued care at home or placement in long-term care) at follow-up. RESULTS: The vast majority of caregivers (82%) reported that they had no choice in taking up the caregiving role. Nevertheless, nearly three-quarters (74%) responded above the midpoint on the rating scale (Mean = 6.82, SD = 3.22; Median = 9; Mode = 9), indicating they provided care voluntarily. Caregivers who reported a greater degree of choice were more likely to still be providing care at home at follow-up and to identify benefits from providing care. Neither choice nor degree of choice predicted any other caregiver outcomes. CONCLUSION: For the vast majority of spousal dementia caregivers, taking up the caregiving role is not perceived as a choice; yet, most report performing this role voluntarily. Thus, facilitating greater choice may not necessarily diminish the key contribution family caregivers make to the care system. Although we found no evidence that caregiver choice predicted more positive caregiver health and wellbeing, the perception of choice is important in and of itself, and may benefit caregivers by facilitating the identification of positive aspects of care and be a factor in delaying care-recipient placement in long-term care. Future research should be especially mindful of how caregiver choice is assessed and how this may affect the resulting prevalence of choice.

Compliance with national guidelines on isotretinoin: where are we 2 years since the last audit? Results of the National Isotretinoin Re-Audit 2014.

BACKGROUND: In 2010, the British Association of Dermatologists (BAD) published clinical guidelines for the safe introduction and continued use of isotretinoin in patients with acne in the UK. The BAD provides UK dermatologists with a facility for national audit, and it undertook an audit on compliance with these guidelines in 2012. AIM: To determine current clinical practices relating to use of isotretinoin among dermatologists in the UK (including geographical variations) as measured against BAD standards, and to ascertain any improvement since the 2012 audit. METHODS: The 2012 isotretinoin audit proforma was used, with additional questions on clinical setting, complaints and litigation. A web-based survey tool was used for data entry and submission, with email invitation to working, UK-based BAD members (n = 1226) in December 2013 and weekly reminders during the 8.5-week data collection period. Responders were requested to enter data for the three most recent consecutive patients (including one male and one female patient) who had completed treatment within the previous 6 months. RESULTS: In total, 338 (27.6%) respondents provided data on 1013 patients. Serum lipids were checked in 93.4% of patients and documentation of mental health and/or mood state was recorded in 82.1%. Regarding the Pregnancy Prevention Programme (PPP), 91.6% of female patients of childbearing potential had signed the PPP information form, while 93.3% who had followed the PPP had taken pregnancy tests both before and during treatment, and 54.7% had taken a pregnancy test 5 weeks post-treatment. CONCLUSION: Overall, there is currently good compliance with standards. Certain aspects of care that are less frequently preformed, such as pregnancy testing post-treatment, are highlighted.

British Association of Dermatologists' national audit on nonmelanoma skin cancer excision, 2014.

BACKGROUND: Diagnosis and management of nonmelanoma skin cancer (NMSC) represents a large part of the dermatology workload, and complete excision is a required surgical standard for treatment. AIM: To conduct an audit of the surgical practice for the treatment of NMSC by dermatologists in the UK. METHODS: Data on 10 consecutive nonmicrographic excisions of nonmelanoma skin cancer by UK dermatologists. Data collected included site, preoperative diagnosis, histological diagnosis, proximity to previous scars, and histological deep and peripheral margins. RESULTS: A total of 227 responses from 135 centres reported 2739 excisions. Excisions on the head and neck accounted for 58.3% of cases. Tumour diameter (mean ± SD) was 10.61 ± 6.9 mm (maximum 130 mm), and 96.7% of cases were primary excisions, with 3.3% being re-excisions. Basal cell carcinomas (BCCs) accounted for 79.1% (n = 2167) of the total cases and squamous cell carcinomas (SCCs) for 17.9% n = 491). Of the suspected BCCs and SCCS, 94.4% (n = 2045) and 66.8% (328), respectively, were confirmed histologically to be the respective carcinomas. Similar proportions of BCC and SCC cases were within 10 mm of a previous excision. Lateral and deep margins were clear in 98.3% and 99.2% of BCC cases, respectively, and in 98.4% and 97.1% of SCC cases, respectively. Reported surgical complication rate in the audit was 3.4%. CONCLUSIONS: The majority of excisions for NMSC are for BCC and SCC. Our figures for diagnostic accuracy are at the upper range of previously published figures. Most patients were not followed up in secondary care, hence complication rates may be under-reported.

Comparing disease activity indices in ulcerative colitis.

BACKGROUND: Comparisons between disease activity indices for ulcerative colitis (UC) are few. This study evaluates three indices, to determine the potential impact of inter-observer variation on clinical trial recruitment or outcome as well as their clinical relevance. METHODS: One hundred patients with UC were prospectively evaluated, each by four specialists, followed by videosigmoidoscopy, which was later scored by each specialist. The Simple Clinical Colitis Activity (SCCAI), Mayo Clinic and Seo indices were compared by assigning a disease activity category from published thresholds for remission, mild, moderate and severe activity. Inter-observer variation was evaluated using Kappa statistics and its effect for each patient on recruitment and outcome measures for representative clinical trials calculated. Clinical relevance was assessed by comparing an independently assigned clinical category, taking all information into account as if in clinic, with the disease activity assigned by the indices. RESULTS: Inter-observer agreement for SCCAI (κ=0.75, 95% CI 0.70-0.81), Mayo Clinic (κ=0.72, 95% CI 0.67-0.78) and Seo (κ=0.89, 95% CI 0.83-0.95) indices was good or very good as was the agreement for rectal bleeding (κ=0.77) and stool frequency (κ=0.90). Endoscopy in the Mayo Clinic index had the greatest variation (κ=0.38). Inter-observer variation alone would have excluded up to 1 in 5 patients from recruitment or remission criteria in representative trials. Categorisation by the SCCAI, Mayo Clinic and Seo indices agreed with the independently assigned clinical category in 61%, 67% and 47% of cases respectively. CONCLUSIONS: Trial recruitment and outcome measures are affected by inter-observer variation in UC activity indices, and endoscopic scoring was the component most susceptible to variation.

Motives for smoking in movies affect future smoking risk in middle school students: an experimental investigation.

BACKGROUND: Exposure to smoking in movies has been linked to adolescent smoking uptake. However, beyond linking amount of exposure to smoking in movies with adolescent smoking, whether the way that smoking is portrayed in movies matters for influencing adolescent smoking has not been investigated. This study experimentally examined how motivation for smoking depicted in movies affects self-reported future smoking risk (a composite measure with items that assess smoking refusal self-efficacy and smoking intentions) among early adolescents. METHODS: A randomized laboratory experiment was used. Adolescents were exposed to movie scenes depicting one of three movie smoking motives: social smoking motive (characters smoked to facilitate social interaction); relaxation smoking motive (characters smoked to relax); or no smoking motive (characters smoked with no apparent motive, i.e., in neutral contexts and/or with neutral affect). Responses to these movie scenes were contrasted (within subjects) to participants' responses to control movie scenes in which no smoking was present; these control scenes matched to the smoking scenes with the same characters in similar situations but where no smoking was present. A total of 358 adolescents, aged 11-14 years, participated. RESULTS: Compared with participants exposed to movie scenes depicting characters smoking with no clear motive, adolescents exposed to movie scenes depicting characters smoking for social motives and adolescents exposed to movie scenes depicting characters smoking for relaxation motives had significantly greater chances of having increases in their future smoking risk. CONCLUSIONS: Exposure to movies that portray smoking motives places adolescents at particular risk for future smoking.

Structure of vesicles formed from non-ionic dialkylglycerol poly(oxyethylene) ether surfactants: effect of electrolyte and cholesterol.

Five non-ionic dialkylglycerol poly(oxyethylene) ether surfactants, designated 2C(m)E(n) (where m, the number of carbons in each alkyl chain=16 or 18, and n, the number of oxyethylene units=12, 16 or 17) have been examined for their ability to form vesicles when dispersed in water or in an aqueous solution of 154 mM NaCl, alone or in the presence of 50 mol% cholesterol. Freeze fracture electron microscopy and light scattering showed that regardless of the hydrating fluid, all the non-ionic surfactants, with the exception of 2C(16)E(17) and 2C(18)E(17), formed vesicles in the absence of cholesterol - 2C(16)E(17) and 2C(18)E(17) instead formed micellar aggregates. All surfactants, however, formed vesicles in the presence of 50 mol% cholesterol. Small angle neutron scattering studies of the surfactant vesicles enabled the bilayer thickness and repeat distance (d-spacing) to be determined. The bilayers formed by all the non-ionic surfactants in the absence of cholesterol were surprisingly thin (∼50 Å for the E(12) containing surfactants and ∼64 Å for 2C(18)E(16)) most likely due to the intrusion of oxyethylene groups into the hydrophobic core of the bilayers. In contrast, however, the non-ionic surfactants exhibited a relatively large d-spacing of around ∼130-150 Å. The addition of 50 mol% cholesterol had a dramatic effect on the thickness of the vesicle bilayer, increasing its size by 10-20 Å, most probably because of an extrusion of oxyethylene from the hydrophobic region of the bilayer and/or a reduction in the tilt on the surfactant alkyl chains. Additionally the presence of cholesterol in a vesicle tended to reduce slightly both the d-spacing and the thickness of the water layer separating the bilayers. The presence of NaCl, even at the low concentrations used in the study, did affect the properties of the bilayer such that it reduced the d-spacing and, in the case of cholesterol-containing systems, also reduced bilayer thickness.

Risk reducing mastectomy: outcomes in 10 European centres.

BACKGROUND: Increasingly women at high risk of breast cancer are opting for risk reducing surgery. The aim of this study was to assess the effectiveness of this approach in women at high risk in both carriers and non-carriers of BRCA1/2. METHODS: Data from 10 European centres that offer a genetic counselling and screening service to women at risk were obtained prospectively from 1995. Breast cancer risks were estimated from life tables and a control group of women at risk who did not undergo surgery. RESULTS: The combined centres have data on 550 women who have undergone risk reducing mastectomy with greater than 3334 women years of follow-up. Operations were carried out on women with lifetime risks of 25-80%, with an average expected incidence rate of 1% per year. No breast cancers have occurred in this cohort in the "at risk" unaffected breast, whereas >34 would have been expected. A high rate (2-3.6%) of occult disease was identified in the at risk breast at the time of surgery. INTERPRETATION: We conclude that risk reducing surgery is highly effective.

Surgical decisions made by 158 women with hereditary breast cancer aged <50 years.

AIM: To establish the uptake of contralateral risk reducing mastectomy in women informed of their risks and options at time of diagnosis of their primary unilateral breast cancer. METHODS: We have assessed the surgical choices of 70 women diagnosed with breast cancer <50 years as part of a family history surveillance program and fully informed about their contralateral risks and surgical options. We have compared this to women from other surgical clinics who were subsequently found to harbour a pathogenic BRCA1/2 mutation. RESULTS: Sixty-five percent (13/20) of BRCA1/2 mutation carriers and 59% (n=20/34) of those at the highest level of risk pre-diagnosis (33+% lifetime risk) opted for contra-lateral mastectomy in the study sample. In contrast only 10% (n=9/88) women identified as mutation carriers from other clinics opted for such surgery. CONCLUSIONS: We would suggest that women with a significant family history and therefore a high contra-lateral breast cancer risk, should have these risks and management options discussed at the time of diagnosis of breast cancer.