Symptom burden and work-related impairment among patients with PTSD and complex PTSD

Background: The 11th revision of the International Classification of Diseases includes a newchapter of stress-related disorders and presents two distinct sibling conditions:Posttraumatic stress disorder (PTSD) and complex PTSD (CPTSD). Studies show that PTSDand CPTSD are associated with different levels of symptom burden, comorbidity andfunctional impairment, but have not yet addressed the qualitative and quantitative differences in work-related impairment between the two diagnoses.Objective: The aim of this study was to replicate differences in symptom severity, globaldistress, and the number of comorbid diagnoses between three groups that suffer from noPTSD, PTSD, or CPTSD. More importantly, we evaluated whether the three groups differ inindicators of functional impairment such as qualitative and quantitative working capacity.Finally, this study supplies information on prevalence rates of PTSD and CPTSD in a clinicalsample suffering from psychosomatic complaints.Methods: Participants were 662 patients of a Psychosomatic Rehabilitation Clinic (ageM= 50.99,SD8.99 years; 70.1% female). Self-report screening instruments were adminis-tered to participants at the beginning of their inpatient psychotherapy. Multivariate analysisof variance and Chi Square tests were utilized to assess group differences in symptomseverity, comorbidity and work-related impairment.Results: A prevalence of 13.3% CPTSD and 9.5% PTSD was found among the current sample.CPTSD was associated with heightened symptom burden and more comorbid diagnoses.More importantly, CPTSD was associated with a significantly lowered qualitative and quan-titative working capacity compared to PTSD and no-PTSD.Conclusions: The high prevalence, greater psychopathological burden and work-relatedimpairments in CPTSD compared to PTSD highlight the need for developing and evaluatingnew interventions in rehabilitation that address the complexity of the new disorder

Die Effekte einer Ärzte-Kurzschulung zur Raucherentwöhnung in einer pneumologischen Akutklinik eines Universitätsklinikums

Objective: The objective was to evaluate the effect of a short physician training in smoking cessation on the physicians’ performance of smoking cessation interventions. The effects on patients’ cessation rates were analyzed as well. A further aim was to identify barriers for providing cessation interventions. The study was conducted in an acute care pulmonology department of a German university hospital. Methods: 24 physicians of the pulmonology department of a German university hospital received a two-hour training in smoking cessation. 109 pre- and 89 post-training group patients were compared with regard to the frequencies of received smoking cessation interventions (Ask, Advise, Assist) and three- and six-month abstinence rates. Physicians estimated their intervention frequencies and gave reasons for not providing cessation interventions. Results: In a multivariable analysis (p<0.05), the physicians’ application of “Ask” (OR 3.28, 95% CI 1.13–9.53) and the six-month abstinence rates (OR 2.70, 95% CI 1.24–5.84) were significantly higher in the post-training group. The univariate analysis also showed a significant effect on “Assist” (OR 2.05, 95% CI 1.09–3.87). No significant effect was seen on “Advise to quit”. Physicians overestimated their intervention frequencies and reported the patients’ low motivation to stop, an oncological disease and palliative care situation as barriers to performing smoking cessation. Conclusion: A short physician training in a hospital department of pulmonology increases the use of guideline-based cessation strategies and may improve cessation rates. The findings show that hospital-based strategies such as physician trainings could be useful in the improvement of smoking cessation. Strategies for overcoming barriers for providing smoking cessation interventions are needed.Ziel: Das Ziel war die Evaluation der Effekte einer Ärzte-Kurzschulung zur Raucherentwöhnung auf die Anwendungshäufigkeit der Entwöhnungsstrategien durch die Ärzte. Ebenso wurden die Effekte auf die Abstinenzraten der Patienten untersucht. Außerdem sollten die Barrieren für die Durchführung von Raucherentwöhnungsmaßnahmen ermittelt werden. Die Studie wurde in einer pneumologischen Akutklinik eines deutschen Universitätsklinikums durchgeführt. Methoden: 24 Ärzte erhielten eine zweistündige Schulung zur Raucherentwöhnung. 109 Kontrollgruppenpatienten, die vor der Schulung in der Klinik behandelt wurden, wurden mit 89 nach der Schulung behandelten Studiengruppenpatienten hinsichtlich der Häufigkeit der ärztlichen Raucherentwöhnungsinterventionen (Ask, Advise, Assist) und ihrer Abstinenzraten drei und sechs Monate nach Klinikaufenthalt verglichen. Die Ärzte schätzten ihre Interventionshäufigkeiten und gaben Gründe an, warum sie in manchen Fällen keine Entwöhnungsinterventionen durchführten. Ergebnisse: Die Anwendung von „Ask“ (OR 3.28, 95% KI 1.13–9.53) durch die Ärzte und die Sechsmonats-Abstinenzraten (OR 2.70, 95% KI 1.24–5.84) waren in der Studiengruppe im multivariablen Modell signifikant höher (p<0.05). Bei „Assist“ zeigte nur das univariable Modell einen signifikanten Einfluss der Schulung (OR 2.05, 95% KI 1.09–3.87). Es wurde kein signifikanter Effekt der Schulung auf die Anwendung von „Advise“ festgestellt. Die Ärzte überschätzten ihre Interventionshäufigkeiten und nannten als Gründe für die Nicht-Durchführung einer Raucherentwöhnung eine wahrgenommene geringe Aufhörmotivation der Patienten und das Vorliegen einer onkologischen oder palliativen Krankheitssituation. Fazit: Eine Ärztekurzschulung zur Raucherentwöhnung in einer pneumologischen Akutklinik erhöht den Einsatz von leitlinienbasierten Raucherentwöhnungsstrategien und könnte einen positiven Effekt auf die Abstinenzraten haben. Implikationen: Die Ergebnisse zeigen, dass Krankenhaus-basierte Strategien wie Ärzteschulungen zur Verbesserung der Raucherentwöhnung nützlich sein können. Strategien zur Überwindung von Hindernissen für die Bereitstellung von Maßnahmen zur Raucherentwöhnung sind erforderlich

Efficacy of pembrolizumab in advanced cancer of the vulva: a systematic review and single-arm meta-analysis

IntroductionVulvar cancer carries a favourable prognosis in early stages. However, therapeutic options for advanced or recurrent cases are limited despite a variety of therapeutic modalities, such as extensive surgical resection, chemotherapy, and radiotherapy. The most important emerging treatment modalities are immune checkpoint inhibitors. This systematic review and meta-analysis aims to assess the efficacy and safety of pembrolizumab, an immune checkpoint inhibitor, in women with advanced vulvar cancer.Materials and methodsFollowing a comprehensive search, review, and appraisal, two relevant single-arm studies were included. Meta-analysis was conducted using R4.3.0 software and RStudio 2023.03.0, presenting the overall effect size with a 95% confidence interval. Heterogeneity was assessed using I2 and the Cochrane Q χ2 statistics.ResultsOut of 154 studies screened for eligibility, two single-arm studies involving 119 patients receiving pembrolizumab for advanced vulvar cancer were included. The pooled objective response rate (ORR) was overall 10% (95% CI: 0.00-0.84) and 9% (95% CI: 0.00-0.89) in the PD-L1 positive subgroup. In the intention-to-treat (ITT) population, 31% (95% CI: 0.04-0.85) exhibited any clinical benefit (complete response, partial response, or stable disease). In the ITT population at six months, progression-free survival (PFS) was 19% (95% CI: 0.01-0.82), and overall survival (OS) was 48% (95% CI: 0.08-0.90). At 12 months, PFS decreased to 9% (95% CI: 0.00-0.85), and OS was 33% (95% CI: 0.04-0.85). No statistically significant heterogeneity was observed in PFS and OS analyses.Discussion and conclusionThis study suggests that one-third of women with advanced or recurrent vulvar cancer may, without the influence of PD-L1 status, benefit from pembrolizumab treatment despite a decline in both PFS and OS at 12 months. These findings provide support for considering pembrolizumab in the treatment paradigm for this specific subset of cancer patients.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD4202339188

Discovery of common and rare genetic risk variants for colorectal cancer.

To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 × 10-8, bringing the number of known independent signals for CRC to ~100. New signals implicate lower-frequency variants, Krüppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.Goncalo R Abecasis has received compensation from 23andMe and Helix. He is currently an employee of Regeneron Pharmaceuticals. Heather Hampel performs collaborative research with Ambry Genetics, InVitae Genetics, and Myriad Genetic Laboratories, Inc., is on the scientific advisory board for InVitae Genetics and Genome Medical, and has stock in Genome Medical. Rachel Pearlman has participated in collaborative funded research with Myriad Genetics Laboratories and Invitae Genetics but has no financial competitive interest

Physical activity and risks of breast and colorectal cancer: a Mendelian randomisation analysis

Abstract: Physical activity has been associated with lower risks of breast and colorectal cancer in epidemiological studies; however, it is unknown if these associations are causal or confounded. In two-sample Mendelian randomisation analyses, using summary genetic data from the UK Biobank and GWA consortia, we found that a one standard deviation increment in average acceleration was associated with lower risks of breast cancer (odds ratio [OR]: 0.51, 95% confidence interval [CI]: 0.27 to 0.98, P-value = 0.04) and colorectal cancer (OR: 0.66, 95% CI: 0.48 to 0.90, P-value = 0.01). We found similar magnitude inverse associations for estrogen positive (ER+ve) breast cancer and for colon cancer. Our results support a potentially causal relationship between higher physical activity levels and lower risks of breast cancer and colorectal cancer. Based on these data, the promotion of physical activity is probably an effective strategy in the primary prevention of these commonly diagnosed cancers

Genetic architectures of proximal and distal colorectal cancer are partly distinct.

OBJECTIVE: An understanding of the etiologic heterogeneity of colorectal cancer (CRC) is critical for improving precision prevention, including individualized screening recommendations and the discovery of novel drug targets and repurposable drug candidates for chemoprevention. Known differences in molecular characteristics and environmental risk factors among tumors arising in different locations of the colorectum suggest partly distinct mechanisms of carcinogenesis. The extent to which the contribution of inherited genetic risk factors for CRC differs by anatomical subsite of the primary tumor has not been examined. DESIGN: To identify new anatomical subsite-specific risk loci, we performed genome-wide association study (GWAS) meta-analyses including data of 48 214 CRC cases and 64 159 controls of European ancestry. We characterised effect heterogeneity at CRC risk loci using multinomial modelling. RESULTS: We identified 13 loci that reached genome-wide significance (p<5×10-8) and that were not reported by previous GWASs for overall CRC risk. Multiple lines of evidence support candidate genes at several of these loci. We detected substantial heterogeneity between anatomical subsites. Just over half (61) of 109 known and new risk variants showed no evidence for heterogeneity. In contrast, 22 variants showed association with distal CRC (including rectal cancer), but no evidence for association or an attenuated association with proximal CRC. For two loci, there was strong evidence for effects confined to proximal colon cancer. CONCLUSION: Genetic architectures of proximal and distal CRC are partly distinct. Studies of risk factors and mechanisms of carcinogenesis, and precision prevention strategies should take into consideration the anatomical subsite of the tumour

Feedback models for gambling control: the use and efficacy of online responsible gambling tools

Social responsibility in gambling has become a major issue for the gaming industry. This has been coupled with the rise of behavioural tracking technologies that allow companies to track every behavioural decision and action made by gamblers on online gambling sites, slot machines, and/or any type of gambling that utilizes player cards. This chapter has a number of distinct but related aims including: (a) a brief overview of behavioral tracking technologies accompanied by a critique of both advantages and disadvantages of such technologies for both the gaming industry and researchers; and (b) results from a series of studies completed using behavioral tracking data to evaluate the efficacy of online responsible gambling tools (particularly in relation to data concerning the use of social responsibility tools such as limit setting, pop-up messaging, and personalized feedback to gamblers)

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030