A cross-sectional study on gender differences in body dysmorphic concerns in patients with skin conditions in relation to sociodemographic, clinical and psychological variables.

BACKGROUND: Dysmorphic concern is an overconcern with an imagined or slight defect in physical appearance that can be a symptom of body dysmorphic disorder (BDD). Appearance-related concerns are frequently reported by people with dermatological conditions. However, relatively little remains known about the relationship between dysmorphic concern and other variables within persons with different skin conditions. OBJECTIVES: The aim of this multicentre, cross-sectional study was to investigate gender differences regarding dysmorphic concern and the prevalence of BDD in a large sample of patients with skin conditions, in relation to sociodemographic, clinical and psychological variables. METHODS: Participants aged ≥18 years with skin conditions were consecutively enrolled in dermatological clinics of 22 European centres. Dysmorphic concern and the possible presence of BDD were measured using the Dysmorphic Concern Questionnaire (DCQ) and compared between men and women in relation to sociodemographic, clinical and psychological variables, and separately for each skin condition. RESULTS: The DCQ questionnaire was completed by 5290 dermatological patients. In all categories, mean scores were significantly higher in women than in men. Mean DCQ scores were also higher in women for most skin conditions, with the highest effect size in vitiligo. The percentage of patients who screened positive for BDD on the DCQ was 10.5%, 7.7% of men and 12.7% of women. The prevalence of BDD positive was 6.9% in patients with mild clinical severity, 11.1% for moderate and 19.1% for severe condition. In the multivariate model in patients with mild skin condition, the presence of BDD was positively associated with stress and stigma both in men and in women. CONCLUSIONS: Dysmorphic concern and BDD were more frequent in women than in men with skin conditions. Both received and actual stigmatization might have an impact on body-related concerns, in particular in women, who may be more at risk for sociocultural reasons.

Stroke Risk Reduction in Atrial Fibrillation Through Pharmacist Prescribing: A Randomized Clinical Trial.

Importance: Major gaps in the delivery of appropriate oral anticoagulation therapy (OAC) exist, leaving a large proportion of persons with atrial fibrillation (AF) unnecessarily at risk for stroke and its sequalae. Objective: To investigate whether pharmacist-led OAC prescription can increase the delivery of stroke risk reduction therapy in individuals with AF. Design, Setting, and Participants: This prospective, open-label, patient-level randomized clinical trial of early vs delayed pharmacist intervention from January 1, 2019, to December 31, 2022, was performed in 27 community pharmacies in Alberta, Canada. Pharmacists identified patients 65 years or older with 1 additional stroke risk factor and known, untreated AF (OAC nonprescription or OAC suboptimal dosing) or performed screening using a 30-second single-lead electrocardiogram to detect previously unrecognized AF. Patients with undertreated or newly diagnosed AF eligible for OAC therapy were considered to have actionable AF. Data were analyzed from April 3 to November 30, 2023. Interventions: In the early intervention group, pharmacists prescribed OAC using guideline-based algorithms with follow-up visits at 1 and 3 months. In the delayed intervention group, which served as the usual care control, the primary care physician (PCP) was sent a notification of actionable AF along with a medication list (both enhancement over usual care). After 3 months, patients without OAC optimization in the control group underwent delayed pharmacist intervention. Main Outcomes and Measures: The primary outcome was the difference in the rate of guideline-concordant OAC use in the 2 groups at 3-month follow-up ascertained by a research pharmacist blinded to treatment allocation. Results: Eighty patients were enrolled with actionable AF (9 [11.3%] newly diagnosed in 235 individuals screened). The mean (SD) age was 79.7 (7.4) years, and 45 patients (56.3%) were female. The median CHADS2 (congestive heart failure, hypertension, age, diabetes, and stroke or transient ischemic attack) score was 2 (IQR, 2-3). Seventy patients completed follow-up. Guideline-concordant OAC use at 3 months occurred in 36 of 39 patients (92.3%) in the early intervention group vs 23 of 41 (56.1%) in the control group (P < .001), with an absolute increase of 34% and number needed to treat of 3. Of the 23 patients who received appropriate OAC prescription in the control group, the PCP called the pharmacist for prescribing advice in 6 patients. Conclusions and Relevance: This randomized clinical trial found that pharmacist OAC prescription is a potentially high-yield opportunity to effectively close gaps in the delivery of stroke risk reduction therapy for AF. Scalability and sustainability of pharmacist OAC prescription will require larger trials demonstrating effectiveness and safety. Trial Registration: ClinicalTrials.gov Identifier: NCT03126214.

DIETARY SODIUM INTAKE AND OUTCOMES: A SECONDARY ANALYSIS FROM SODIUM-HF: Sodium Intake and Outcomes in Heart Failure.

OBJECTIVES: This post-hoc analysis of SODIUM-HF assessed the association between baseline dietary sodium intake and change at 6 months with a composite of cardiovascular (CV) hospitalizations, emergency department visits, and all-cause death at 12 and 24 months. BACKGROUND: Dietary sodium restriction is common advice for patients with heart failure (HF). Randomized clinical trials have not shown a beneficial effect of dietary sodium restriction on clinical outcomes. METHODS: Multivariable Cox proportional hazard regression model was used to assess the association of dietary sodium intake measured at randomization with primary and secondary endpoints. RESULTS: 792 participants were included. Baseline sodium intake was ≤1500 mg/day in 19.9% (n=158), 1501-3000 mg/day in 56.5% (n=448), and >3000 mg/day in 23.4% (n=186) of participants. The factors associated with higher baseline sodium intake were higher calorie consumption, higher body mass index and recruitment from Canada. Multivariable analyses showed no association between baseline sodium intake nor magnitude of 6 months change and 12 or 24-month outcomes. In a responder analysis, participants achieving a sodium intake <1500 mg at 6 months showed an association with a decreased risk for the composite outcome (adjusted HR 0.52 [95% CI 0.25, 1.07] P=0.08) and CV hospitalization (adjusted HR 0.51 [95% CI 0.24, 1.09] P=0.08) at 12 months. CONCLUSION: There was no association between dietary sodium intake and clinical outcomes over 24 months in patients with HF. Responder analyses suggest the need for further investigation of the effects of sodium reduction in those who achieve the targeted dietary sodium reduction level.

Quality of life measurement in urticaria: Position statement of the European Academy of Dermatology and Venereology Task Forces on Quality of Life and Patient-Oriented Outcomes and Urticaria and Angioedema.

The European Academy of Dermatology and Venereology (EADV) Task Forces on quality of life (QoL) and patient-oriented outcomes and on urticaria and angioedema recommendations for the assessment of Health-related (HR) QoL in all patients with urticaria in research and practice are as follows: to use the DLQI for adults and the CDLQI for children as dermatology-specific and the CU-Q2oL as a disease-specific HRQoL instruments in urticaria; to use generic instruments to provide comparison of data on urticaria with non-dermatologic diseases, or to compare with healthy volunteers or the general population; to select validated HRQoL instruments with appropriate age limits; to present exact numeric data for HRQoL results; correct title of any HRQoL instrument should be used, along with its correct abbreviation and the reference to its original publication, where possible. The EADV TFs discourage the use of non-validated HRQoL instruments and modified HRQoL instruments that have not undergone standard validation.

Ambulatory Cardiology or General Internal Medicine Assessment Prior to Scheduled Major Vascular Surgery is Associated with Improved Outcomes.

OBJECTIVE: To characterize the association between ambulatory cardiology or general internal medicine (GIM) assessment prior to surgery and outcomes following scheduled major vascular surgery. BACKGROUND: Cardiovascular risk assessment and management prior to high-risk surgery remains an evolving area of care. METHODS: This is population-based retrospective cohort study of all adults who underwent scheduled major vascular surgery in Ontario, Canada, April 1, 2004-March 31, 2019. Patients who had an ambulatory cardiology and/or GIM assessment within 6 months prior to surgery were compared to those who did not. The primary outcome was 30-day mortality. Secondary outcomes included: composite of 30-day mortality, myocardial infarction or stroke; 30-day cardiovascular death; 1-year mortality; composite of 1-year mortality, myocardial infarction or stroke; and 1-year cardiovascular death. Cox proportional hazard regression using inverse probability of treatment weighting (IPTW) was used to mitigate confounding by indication. RESULTS: Among 50,228 patients, 20,484 (40.8%) underwent an ambulatory assessment prior to surgery: 11,074 (54.1%) with cardiology, 8,071 (39.4%) with GIM and 1,339 (6.5%) with both. Compared to patients who did not, those who underwent an assessment had a higher Revised Cardiac Risk Index (N with Index over 2= 4,989[24.4%] vs. 4,587[15.4%], P<0.001) and more frequent pre-operative cardiac testing (N=7,772[37.9%] vs. 6,113[20.6%], P<0.001) but, lower 30-day mortality (N=551[2.7%] vs. 970[3.3%], P<0.001). After application of IPTW, cardiology or GIM assessment prior to surgery remained associated with a lower 30-day mortality (weighted Hazard Ratio [95%CI] = 0.73 [0.65-0.82]) and a lower rate of all secondary outcomes. CONCLUSIONS: Major vascular surgery patients assessed by a cardiology or GIM physician prior to surgery have better outcomes than those who are not. Further research is needed to better understand potential mechanisms of benefit.

Systematic large-scale application of ClinGen InSiGHT APC -specific ACMG/AMP variant classification criteria substantially alleviates the burden of variants of uncertain significance in ClinVar and LOVD databases.

Background: Pathogenic constitutional APC variants underlie familial adenomatous polyposis, the most common hereditary gastrointestinal polyposis syndrome. To improve variant classification and resolve the interpretative challenges of variants of uncertain significance (VUS), APC-specific ACMG/AMP variant classification criteria were developed by the ClinGen-InSiGHT Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel (VCEP). Methods: A streamlined algorithm using the APC -specific criteria was developed and applied to assess all APC variants in ClinVar and the InSiGHT international reference APC LOVD variant database. Results: A total of 10,228 unique APC variants were analysed. Among the ClinVar and LOVD variants with an initial classification of (Likely) Benign or (Likely) Pathogenic, 94% and 96% remained in their original categories, respectively. In contrast, 41% ClinVar and 61% LOVD VUS were reclassified into clinically actionable classes, the vast majority as (Likely) Benign. The total number of VUS was reduced by 37%. In 21 out of 36 (58%) promising APC variants that remained VUS despite evidence for pathogenicity, a data mining-driven work-up allowed their reclassification as (Likely) Pathogenic. Conclusions: The application of APC -specific criteria substantially reduced the number of VUS in ClinVar and LOVD. The study also demonstrated the feasibility of a systematic approach to variant classification in large datasets, which might serve as a generalisable model for other gene-/disease-specific variant interpretation initiatives. It also allowed for the prioritization of VUS that will benefit from in-depth evidence collection. This subset of APC variants was approved by the VCEP and made publicly available through ClinVar and LOVD for widespread clinical use.

Measurement of the major ignored burden of multiple myeloma, pernicious anaemia and of other haematological conditions on partners and family members: A cross-sectional study.

BACKGROUND: Having a haematological condition can adversely affect the quality of life (QoL) of family members/partners of patients. It is important to measure this often ignored burden in order to implement appropriate supportive interventions. OBJECTIVE: To measure current impact of haematological conditions on the QoL of family members/partners of patients, using the Family Reported Outcome Measure-16 (FROM-16). METHODS: A cross-sectional study, recruited online through patient support groups, involved UK family members/partners of people with haematological conditions completing the FROM-16. RESULTS: 183 family members/partners (mean age = 60.5 years, SD = 13.2; females = 62.8%) of patients (mean age = 64.1, SD = 12.8; females = 46.4%) with 12 haematological conditions completed the FROM-16. The FROM-16 mean total score was 14.0 (SD = 7.2), meaning 'a moderate effect on QoL'. The mean FROM-16 scores of family members of people with multiple myeloma (mean = 15.8, SD = 6.3, n = 99) and other haematological malignancies (mean = 13.9, SD = 7.8, n = 29) were higher than of people with pernicious anaemia (mean = 10.7, SD = 7.5, n = 47) and other non-malignant conditions (mean = 11, SD = 7.4, n = 56, p < .01). Over one third (36.1%, n = 183) of family members experienced a 'very large effect' (FROM-16 score>16) on their quality of life. CONCLUSIONS: Haematological conditions, in particular those of malignant type, impact the QoL of family members/partners of patients. Healthcare professionals can now, using FROM-16, identify those most affected and should consider how to provide appropriate holistic support within routine practice.

Applicability and impact of the COMPASS trial in a Canadian population of patients with atherosclerotic disease.

BACKGROUND AND AIMS: In the COMPASS trial, low-dose rivaroxaban with aspirin improved cardiovascular outcomes in patients with atherosclerotic cardiovascular disease (ASCVD). We aimed to assess the potential clinical implications of this therapy in a generalizable population. METHODS AND RESULTS: A retrospective cohort of adults with ASVCD was formed using healthcare administrative databases in Alberta, Canada (population 4.4 million). Patients with a new diagnosis between 2008 and 2019 formed the epidemiological cohort (n = 224,600) and those with long-term follow-up (>5 years) formed the outcomes cohort (n = 232,460). The primary outcome of major adverse cardiovascular events (MACE) was assessed and categorized based on the COMPASS trial eligibility. In the outcomes cohort, 77% had only coronary artery disease, 15% had only peripheral artery disease, and 8% had both. Of those, 37% met the COMPASS trial eligibility criteria, 36% met exclusion criteria and 27% did not meet inclusion criteria. Over a median of 7.8 years, the COMPASS exclusion group demonstrated the highest rate of MACE (5.9 per 100 person-years), following by the eligible group and the group that did not meet COMPASS inclusion criteria (3.1 and 1.4 per 100 person-years respectively). The expected net clinical benefit of antithrombotic therapy in the eligible group was 5.6 fewer events per 1000 person-years. CONCLUSIONS: In a real-world population of 4.4 million adults, there are roughly 20,000 new cases of ASVCD diagnosed yearly, with ∼40% being eligible for the addition of low-dose rivaroxaban therapy to antiplatelet therapy. The theoretical implementation of dual antithrombotic treatment in this population could result in a substantial reduction in cardiovascular morbidity and mortality.

Uptake of SGLT2i and Outcomes in Patients with Diabetes and Heart Failure: A Population-Based Cohort and a Specialized Clinic Cohort.

BACKGROUND: Sodium-glucose cotransporter-2 (SGLT2) inhibitors are effective in adults with diabetes mellitus (DM) and heart failure (HF) based on randomized clinical trials. We compared SGLT2 inhibitor uptake and outcomes in two cohorts: a population-based cohort of all adults with DM and HF in Alberta, Canada and a specialized heart function clinic (HFC) cohort. METHODS: The population-based cohort was derived from linked provincial healthcare datasets. The specialized clinic cohort was created by chart review of consecutive patients prospectively enrolled in the HFC between February 2018 and August 2022. We examined the association between SGLT2 inhibitor use (modeled as a time-varying covariate) and all-cause mortality or deaths/cardiovascular hospitalizations. RESULTS: Of the 4,885 individuals from the population-based cohort, 64.2% met the eligibility criteria of the trials proving the effectiveness of SGLT2 inhibitors. Utilization of SGLT2 inhibitors increased from 1.2% in 2017 to 26.4% by January 2022. In comparison, of the 530 patients followed in the HFC, SGLT2 inhibitor use increased from 9.8% in 2019 to 49.1 % by March 2022. SGLT2 inhibitor use in the population-based cohort was associated with fewer all-cause mortality (aHR 0.51, 95%CI 0.41-0.63) and deaths/cardiovascular hospitalizations (aHR 0.65, 95%CI 0.54-0.77). However, SGLT2 inhibitor usage rates were far lower in HF patients without DM (3.5% by March 2022 in the HFC cohort). CONCLUSIONS: Despite robust randomized trial evidence of clinical benefit, the uptake of SGLT2 inhibitors in patients with HF and DM remains low, even in the specialized HFC. Clinical care strategies are needed to enhance the use of SGLT2 inhibitors and improve implementation.

Increased frequency and mortality in persons with neurological disorders during COVID-19.

Determining the frequency and outcomes of neurological disorders associated with coronavirus disease 2019 (COVID-19) is imperative for understanding risks and for recognition of emerging neurological disorders. We investigated the susceptibility and impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among persons with premorbid neurological disorders, in addition to the post-infection incidence of neurological sequelae, in a case-control population-based cohort. Using health service data collected between 1 March 2020 and 30 June 2021, we constructed a cohort of SARS-CoV-2 RNA-positive (n = 177 892) and -negative (n = 177 800) adults who were age, sex and comorbidity matched and underwent RT-PCR testing at similar times. COVID-19-associated mortality rates were examined within the cohort. Neurological sequelae were analysed during the acute (<3 months) and the post-acute (3-9 months) phases post-infection. The risk of death was significantly greater in the SARS-CoV-2 RNA-positive (2140 per 100 000 person years) compared with RNA-negative (922 per 100 000 person years) over a follow-up of 9 months, particularly amongst those with premorbid neurological disorders: adjusted odds ratios (95% confidence interval) in persons with a prior history of parkinsonism, 1.65 (1.15-2.37); dementia, 1.30 (1.11-1.52); seizures, 1.91 (1.26-2.87); encephalopathy, 1.82 (1.02-3.23); and stroke, 1.74 (1.05-2.86). There was also a significantly increased risk for diagnosis of new neurological sequelae during the acute time phase after COVID-19, including encephalopathy, 2.0 (1.10-3.64); dementia, 1.36 (1.07-1.73); seizure, 1.77 (1.22-2.56); and brain fog, 1.96 (1.20-3.20). These risks persisted into the post-acute phase after COVID-19, during which inflammatory myopathy (2.57, 1.07-6.15) and coma (1.87, 1.22-2.87) also became significantly increased. Thus, persons with SARS-CoV-2 infection and premorbid neurological disorders are at greater risk of death, and SARS-CoV-2 infection was complicated by increased risk of new-onset neurological disorders in both the acute and post-acute phases of COVID-19.

Iron Deficiency, Anemia, and Iron Supplementation in Patients With Heart Failure: A Population-Level Study.

BACKGROUND: Studies have shown an association between iron deficiency (ID) and clinical outcomes in patients with heart failure (HF), irrespective of the presence of ID anemia (IDA). The current study used population-level data from a large, single-payer health care system in Canada to investigate the epidemiology of ID and IDA in patients with acute HF and those with chronic HF, and the iron supplementation practices in these settings. METHODS: All adult patients with HF in Alberta between 2012 and 2019 were identified and categorized as acute or chronic HF. HF subtypes were determined through echocardiography data, and ID (serum ferritin concentration <100 µg/L, or ferritin concentration between 100 and 300 µg/L along with transferrin saturation <20%), and IDA through laboratory data. Broad eligibility for 3 clinical trials (AFFIRM-AHF [Study to Compare Ferric Carboxymaltose With Placebo in Patients With Acute HF and ID], IRONMAN [Intravenous Iron Treatment in Patients With Heart Failure and Iron Deficiency], and HEART-FID [Randomized Placebocontrolled Trial of Ferric Carboxymaltose as Treatment for HF With ID]) was determined. RESULTS: Among the 17 463 patients with acute HF, 38.5% had iron studies tested within 30 days post-index-HF episode (and 34.2% of the 11 320 patients with chronic HF). Among tested patients, 72.6% of the acute HF and 73.9% of the chronic HF were iron-deficient, and 51.4% and 49.0% had IDA, respectively. Iron therapy was provided to 41.8% and 40.5% of patients with IDA and acute or chronic HF, respectively. Of ID patients without anemia, 19.9% and 21.7% were prescribed iron therapy. The most common type of iron therapy was oral (28.1% of patients). Approximately half of the cohort was eligible for each of the AFFIRM-AHF, intravenous iron treatment in patients with HF and ID, and HEART-FID trials. CONCLUSIONS: Current practices for investigating and treating ID in patients with HF do not align with existing guideline recommendations. Considering the gap in care, innovative strategies to optimize iron therapy in patients with HF are required.

Dermatological patients with itch report more stress, stigmatization experience, anxiety and depression compared to patients without itch: Results from a European multi-centre study.

BACKGROUND: Itch as the most common symptom in dermatology has been shown to be related to psychological factors such as stress, anxiety and depression. Moreover, associations were found between perceived stigmatization and itch. However, studies investigating the differences between patients with dermatoses with and without itch regarding perceived stress, stigmatization, anxiety and depression are missing. Therefore, one of the aims of the second study of the European Society for Dermatology and Psychiatry (ESDaP study II) was to investigate these relationships in a large cohort of patients with different itchy dermatoses. RESULTS: 3399 patients with 14 different itchy dermatoses were recruited at 22 centres in 17 European countries. They filled in questionnaires to assess perceived stigmatization, stress, signs of clinically relevant anxiety or depression, itch-related quality of life, the overall health status, itch duration, frequency and intensity. The most significant association between the severity of itching and the perception of stress was observed among individuals with rosacea (correlation coefficient r = 0.314). Similarly, the strongest links between itch intensity and experiences of stigmatization, anxiety, and depression were found in patients with seborrheic dermatitis (correlation coefficients r = 0.317, r = 0.356, and r = 0.400, respectively). Utilizing a stepwise linear regression analysis, it was determined that within the entire patient cohort, 9.3% of the variation in itch intensity could be accounted for by factors including gender, levels of anxiety, depression, and perceived stigmatization. Females and individuals with elevated anxiety, depression, and perceived stigmatization scores reported more pronounced itch intensities compared to those with contrary attributes. CONCLUSION: This study underscores the connection between experiencing itch and its intensity and the psychological strain it places on individuals. Consequently, psychological interventions should encompass both addressing the itch itself and the interconnected psychological factors. In specific cases, it becomes imperative for dermatologists to direct individuals towards suitable healthcare resources to undergo further psychological assessment.

Targeted Coaching to Improve Osteoporosis Therapy Adherence: A Single Arm Variation of the C-STOP Study.

BACKGROUND: In this pre-planned variation of the Comparing Strategies Targeting Osteoporosis to Prevent Fractures After an Upper Extremity Fracture (C-STOP) trial, we investigated whether adherence-specific coaching by the case manager (CM) further improved the adherence and persistence rates compared to those seen in the C-STOP trial. METHODS: We conducted a prospective observational cohort study of community-dwelling adults 50 years or older who suffered an upper-extremity fracture and were not previously treated with osteoporosis medications, to assess whether a well-trained CM can partner with patients to improve adherence to and persistence with oral bisphosphonate intake. The primary outcome was adherence (taking > 80% of prescribed doses) to oral bisphosphonate intake at 12 months after study enrollment. Secondary outcomes included primary adherence to and 12-month persistence with oral bisphosphonate and calcium and vitamin D supplement intake at 12 months. RESULTS: The study cohort consisted of 84 participants, of which 30 were prescribed an oral bisphosphonate. Twenty-two (73.3%) started treatment within 3 months. The adherence rate at 12 months was 77.3%. The persistence rate at 12 months was 95.5%. Of those not prescribed an oral bisphosphonate, 62.8% were taking supplemental calcium and 93.0% were taking supplemental vitamin D at 12 months. Depression was a significant predictor of 12-month non-adherence (adjusted odds ratio, 9.8; 95% confidence interval, 1.2-81.5). CONCLUSIONS: Adherence-specific coaching by a CM did not further improve the level of medication adherence achieved in the original C-STOP study. Importantly, these results can inform adherence in future intervention studies.

Responsiveness and minimal important change of the Family Reported Outcome Measure (FROM-16).

BACKGROUND: The FROM-16 is a generic family quality of life (QoL) instrument that measures the QoL impact of patients' disease on their family members/partners. The study aimed to assess the responsiveness of FROM-16 to change and determine Minimal Important Change (MIC). METHODS: Responsiveness and MIC for FROM-16 were assessed prospectively with patients and their family members recruited from outpatient departments of the University Hospital Wales and University Hospital Llandough, Cardiff, United Kingdom. Patients completed the EQ-5D-3L and a global severity question (GSQ) online at baseline and at 3-month follow-up. Family members completed FROM-16 at baseline and a Global Rating of Change (GRC) in addition to FROM-16 at follow-up. Responsiveness was assessed using the distribution-based (effect size-ES, standardized response mean -SRM) and anchor-based (area under the receiver operating characteristics curve ROC-AUC) approaches and by testing hypotheses on expected correlation strength between FROM-16 change score and patient assessment tools (GSQ and EQ-5D). Cohen's criteria were used for assessing ES. The AUC ≥ 0.7 was considered a good measure of responsiveness. MIC was calculated using anchor-based (ROC analysis and adjusted predictive modelling) and distribution methods based on standard deviation (SD) and standard error of the measurement (SEM). RESULTS: Eighty-three patients with 15 different health conditions and their relatives completed baseline and follow-up questionnaires and were included in the responsiveness analysis. The mean FROM-16 change over 3 months = 1.43 (SD = 4.98). The mean patient EQ-5D change over 3 months = -0.059 (SD = 0.14). The responsiveness analysis showed that the FROM-16 was responsive to change (ES = 0.2, SRM = 0.3; p < 0.01). The ES and SRM of FROM-16 change score ranged from small (ES = 0.2; SRM = 0.3) for the distribution-based method to large (ES = 0.8, SRM = 0.85) for anchor-based methods. The AUC value was above 0.7, indicating good responsiveness. There was a significant positive correlation between the FROM-16 change scores and the patient's disease severity change scores (p < 0.001). The MIC analysis was based on data from 100 family members of 100 patients. The MIC value of 4 was suggested for FROM-16. CONCLUSIONS: The results of this study confirm the longitudinal validity of FROM-16 which refers to the degree to which an instrument is able to measure change in the construct to be measured. The results yield a MIC value of 4 for FROM-16. These psychometric attributes of the FROM-16 instrument are useful in both clinical research as well as clinical practice.

Mapping of Family Reported Outcome Measure (FROM-16) scores to EQ-5D: algorithm to calculate utility values.

OBJECTIVE: Although decision scientists and health economists encourage inclusion of family member/informal carer utility in health economic evaluation, there is a lack of suitable utility measures comparable to patient utility measures such those based on the EQ-5D. This study aims to predict EQ-5D-3L utility values from Family Reported Outcome Measure (FROM-16) scores, to allow the use of FROM-16 data in health economic evaluation when EQ-5D data is not available. METHODS: Data from 4228 family members/partners of patients recruited to an online cross-sectional study through 58 UK-based patient support groups, three research support platforms and Welsh social services departments were randomly divided five times into two groups, to derive and test a mapping model. Split-half cross-validation was employed, resulting in a total of ten multinomial logistic regression models. The Monte Carlo simulation procedure was used to generate predicted EQ-5D-3L responses, and utility scores were calculated and compared against observed values. Mean error and mean absolute error were calculated for all ten validation models. The final model algorithm was derived using the entire sample. RESULTS: The model was highly predictive, and its repeated fitting using multinomial logistic regression demonstrated a stable model. The mean differences between predicted and observed health utility estimates ranged from 0.005 to 0.029 across the ten modelling exercises, with an average overall difference of 0.015 (a 2.2% overestimate, not of clinical importance). CONCLUSIONS: The algorithm developed will enable researchers and decision scientists to calculate EQ-5D health utility estimates from FROM-16 scores, thus allowing the inclusion of the family impact of disease in health economic evaluation of medical interventions when EQ-5D data is not available.

Intratumoral presence of the genotoxic gut bacteria pks+ E. coli, Enterotoxigenic Bacteroides fragilis, and Fusobacterium nucleatum and their association with clinicopathological and molecular features of colorectal cancer.

BACKGROUND: This study aimed to investigate clinicopathological and molecular tumour features associated with intratumoral pks+ Escherichia coli (pks+E.coli+), pks+E.coli- (non-E.coli bacteria harbouring the pks island), Enterotoxigenic Bacteroides fragilis (ETBF) and Fusobacterium nucleatum (F. nucleatum). METHODS: We screened 1697 tumour-derived DNA samples from the Australasian Colorectal Cancer Family Registry, Melbourne Collaborative Cohort Study and the ANGELS study using targeted PCR. RESULTS: Pks+E.coli+ was associated with male sex (P < 0.01) and APC:c.835-8 A > G somatic mutation (P = 0.03). The association between pks+E.coli+ and APC:c.835-8 A > G was specific to early-onset CRCs (diagnosed<45years, P = 0.02). The APC:c.835-A > G was not associated with pks+E.coli- (P = 0.36). F. nucleatum was associated with DNA mismatch repair deficiency (MMRd), BRAF:c.1799T>A p.V600E mutation, CpG island methylator phenotype, proximal tumour location, and high levels of tumour infiltrating lymphocytes (Ps < 0.01). In the stratified analysis by MMRd subgroups, F. nucleatum was associated with Lynch syndrome, MLH1 methylated and double MMR somatic mutated MMRd subgroups (Ps < 0.01). CONCLUSION: Intratumoral pks+E.coli+ but not pks+E.coli- are associated with CRCs harbouring the APC:c.835-8 A > G somatic mutation, suggesting that this mutation is specifically related to DNA damage from colibactin-producing E.coli exposures. F. nucleatum was associated with both hereditary and sporadic MMRd subtypes, suggesting the MMRd tumour microenvironment is important for F. nucleatum colonisation irrespective of its cause.

Inherited BRCA1 and RNF43 pathogenic variants in a familial colorectal cancer type X family.

Genetic susceptibility to familial colorectal cancer (CRC), including for individuals classified as Familial Colorectal Cancer Type X (FCCTX), remains poorly understood. We describe a multi-generation CRC-affected family segregating pathogenic variants in both BRCA1, a gene associated with breast and ovarian cancer and RNF43, a gene associated with Serrated Polyposis Syndrome (SPS). A single family out of 105 families meeting the criteria for FCCTX (Amsterdam I family history criteria with mismatch repair (MMR)-proficient CRCs) recruited to the Australasian Colorectal Cancer Family Registry (ACCFR; 1998-2008) that underwent whole exome sequencing (WES), was selected for further testing. CRC and polyp tissue from four carriers were molecularly characterized including a single CRC that underwent WES to determine tumor mutational signatures and loss of heterozygosity (LOH) events. Ten carriers of a germline pathogenic variant BRCA1:c.2681_2682delAA p.Lys894ThrfsTer8 and eight carriers of a germline pathogenic variant RNF43:c.988 C > T p.Arg330Ter were identified in this family. Seven members carried both variants, four of which developed CRC. A single carrier of the RNF43 variant met the 2019 World Health Organization (WHO2019) criteria for SPS, developing a BRAF p.V600 wildtype CRC. Loss of the wildtype allele for both BRCA1 and RNF43 variants was observed in three CRC tumors while a LOH event across chromosome 17q encompassing both genes was observed in a CRC. Tumor mutational signature analysis identified the homologous recombination deficiency (HRD)-associated COSMIC signatures SBS3 and ID6 in a CRC for a carrier of both variants. Our findings show digenic inheritance of pathogenic variants in BRCA1 and RNF43 segregating with CRC in a FCCTX family. LOH and evidence of BRCA1-associated HRD supports the importance of both these tumor suppressor genes in CRC tumorigenesis.

Quality of life measurement in teledermatology. Position statement of the European Academy of Dermatology and Venereology Task Forces on Quality of Life and Patient Oriented Outcomes and Teledermatology.

Many events, including the COVID-19 pandemic, have accelerated the implementation of teledermatology pathways within dermatology departments and across healthcare organizations. Quality of Life (QoL) assessment in dermatology is also a rapidly developing field with a gradual shift from theory to practice. The purpose of this paper organized jointly by the European Academy of Dermatology and Venereology (EADV) Task Force (TF) on QoL and patient-oriented outcomes and the EADV TF on teledermatology is to present current knowledge about QoL assessment during the use of teledermatology approaches, including data on health-related (HR) QoL instruments used in teledermatology, comparison of influence of different treatment methods on HRQoL after face-to-face and teledermatology consultations and to make practical recommendations concerning the assessment of QoL in teledermatology. The EADV TFs made the following position statements: HRQoL assessment may be an important part in most of teledermatology activities; HRQoL assessment may be easily and effectively performed during teledermatology consultations. It is especially important to monitor HRQoL of patients with chronic skin diseases during lockdowns or in areas where it is difficult to reach a hospital for face-to-face consultation; regular assessment of HRQoL of patients with skin diseases during teledermatology consultations may help to monitor therapy efficacy and visualize individual patient's needs; we recommend the use of the DLQI in teledermatology, including the use of the DLQI app which is available in seven languages; it is important to develop apps for dermatology-specific HRQoL instruments for use in children (for example the CDLQI and InToDermQoL) and for disease-specific instruments.

Gene-specific ACMG/AMP classification criteria for germline APC variants: Recommendations from the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel.

PURPOSE: The Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel (VCEP) was established by the International Society for Gastrointestinal Hereditary Tumours and the Clinical Genome Resource, who set out to develop recommendations for the interpretation of germline APC variants underlying Familial Adenomatous Polyposis, the most frequent hereditary polyposis syndrome. METHODS: Through a rigorous process of database analysis, literature review, and expert elicitation, the APC VCEP derived gene-specific modifications to the ACMG/AMP (American College of Medical Genetics and Genomics and Association for Molecular Pathology) variant classification guidelines and validated such criteria through the pilot classification of 58 variants. RESULTS: The APC-specific criteria represented gene- and disease-informed specifications, including a quantitative approach to allele frequency thresholds, a stepwise decision tool for truncating variants, and semiquantitative evaluations of experimental and clinical data. Using the APC-specific criteria, 47% (27/58) of pilot variants were reclassified including 14 previous variants of uncertain significance (VUS). CONCLUSION: The APC-specific ACMG/AMP criteria preserved the classification of well-characterized variants on ClinVar while substantially reducing the number of VUS by 56% (14/25). Moving forward, the APC VCEP will continue to interpret prioritized lists of VUS, the results of which will represent the most authoritative variant classification for widespread clinical use.

Quantifying hospital environmental ventilation using carbon dioxide monitoring - a multicentre study.

The COVID-19 pandemic has highlighted the importance of environmental ventilation in reducing airborne pathogen transmission. Carbon dioxide monitoring is recommended in the community to ensure adequate ventilation. Dynamic measurements of ventilation quantifying human exhaled waste gas accumulation are not conducted routinely in hospitals. Instead, environmental ventilation is allocated using static hourly air change rates. These vary according to the degree of perceived hazard, with the highest change rates reserved for locations where aerosol-generating procedures are performed, where medical/anaesthetic gases are used and where a small number of high-risk infective or immunocompromised patients may be isolated to reduce cross-infection. We aimed to quantify the quality and distribution of ventilation in hospital by measuring carbon dioxide levels in a two-phased prospective observational study. First, under controlled conditions, we validated our method and the relationship between human occupancy, ventilation and carbon dioxide levels using non-dispersive infrared carbon dioxide monitors. We then assessed ventilation quality in patient-occupied (clinical) and staff break and office (non-clinical) areas across two hospitals in Scotland. We selected acute medical and respiratory wards in which patients with COVID-19 are cared for routinely, as well as ICUs and operating theatres where aerosol-generating procedures  are performed routinely. Between November and December 2022, 127,680 carbon dioxide measurements were obtained across 32 areas over 8 weeks. Carbon dioxide levels breached the 800 ppm threshold for 14% of the time in non-clinical areas vs. 7% in clinical areas (p < 0.001). In non-clinical areas, carbon dioxide levels were > 800 ppm for 20% of the time in both ICUs and wards, vs. 1% in operating theatres (p < 0.001). In clinical areas, carbon dioxide was > 800 ppm for 16% of the time in wards, vs. 0% in ICUs and operating theatres (p < 0.001). We conclude that staff break, office and clinical areas on acute medical and respiratory wards frequently had inadequate ventilation, potentially increasing the risks of airborne pathogen transmission to staff and patients. Conversely, ventilation was consistently high in the ICU and operating theatre clinical environments. Carbon dioxide monitoring could be used to measure and guide improvements in hospital ventilation.