A Precision Treatment Model for Internet-Delivered Cognitive Behavioral Therapy for Anxiety and Depression among University Students:A Secondary Analysis of a Randomized Clinical Trial

Importance: Guided internet-delivered cognitive behavioral therapy (i-CBT) is a low-cost way to address high unmet need for anxiety and depression treatment. Scalability could be increased if some patients were helped as much by self-guided i-CBT as guided i-CBT. Objective: To develop an individualized treatment rule using machine learning methods for guided i-CBT vs self-guided i-CBT based on a rich set of baseline predictors. Design, Setting, and Participants: This prespecified secondary analysis of an assessor-blinded, multisite randomized clinical trial of guided i-CBT, self-guided i-CBT, and treatment as usual included students in Colombia and Mexico who were seeking treatment for anxiety (defined as a 7-item Generalized Anxiety Disorder [GAD-7] score of ≥10) and/or depression (defined as a 9-item Patient Health Questionnaire [PHQ-9] score of ≥10). Study recruitment was from March 1 to October 26, 2021. Initial data analysis was conducted from May 23 to October 26, 2022. Interventions: Participants were randomized to a culturally adapted transdiagnostic i-CBT that was guided (n = 445), self-guided (n = 439), or treatment as usual (n = 435). Main Outcomes and Measures: Remission of anxiety (GAD-7 scores of ≤4) and depression (PHQ-9 scores of ≤4) 3 months after baseline. Results: The study included 1319 participants (mean [SD] age, 21.4 [3.2] years; 1038 women [78.7%]; 725 participants [55.0%] came from Mexico). A total of 1210 participants (91.7%) had significantly higher mean (SE) probabilities of joint remission of anxiety and depression with guided i-CBT (51.8% [3.0%]) than with self-guided i-CBT (37.8% [3.0%]; P =.003) or treatment as usual (40.0% [2.7%]; P =.001). The remaining 109 participants (8.3%) had low mean (SE) probabilities of joint remission of anxiety and depression across all groups (guided i-CBT: 24.5% [9.1%]; P =.007; self-guided i-CBT: 25.4% [8.8%]; P =.004; treatment as usual: 31.0% [9.4%]; P =.001). All participants with baseline anxiety had nonsignificantly higher mean (SE) probabilities of anxiety remission with guided i-CBT (62.7% [5.9%]) than the other 2 groups (self-guided i-CBT: 50.2% [6.2%]; P =.14; treatment as usual: 53.0% [6.0%]; P =.25). A total of 841 of 1177 participants (71.5%) with baseline depression had significantly higher mean (SE) probabilities of depression remission with guided i-CBT (61.5% [3.6%]) than the other 2 groups (self-guided i-CBT: 44.3% [3.7%]; P =.001; treatment as usual: 41.8% [3.2%]; P &lt;.001). The other 336 participants (28.5%) with baseline depression had nonsignificantly higher mean (SE) probabilities of depression remission with self-guided i-CBT (54.4% [6.0%]) than guided i-CBT (39.8% [5.4%]; P =.07). Conclusions and Relevance: Guided i-CBT yielded the highest probabilities of remission of anxiety and depression for most participants; however, these differences were nonsignificant for anxiety. Some participants had the highest probabilities of remission of depression with self-guided i-CBT. Information about this variation could be used to optimize allocation of guided and self-guided i-CBT in resource-constrained settings. Trial Registration: ClinicalTrials.gov Identifier: NCT04780542.</p

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

ADHD Comorbidity Structure and Impairment: Results of the WHO World Mental Health Surveys International College Student Project (WMH-ICS)

Objective: To examine the prevalence of ADHD and the association of comorbid disorders, and multivariate disorder classes with role impairment in college students. Method: About 15,991 freshmen (24 colleges, 9 countries, WMH-ICS) (response rate = 45.6%) completed online WMH-CIDI-SC surveys for 6-month ADHD and six 12-month DSM-IV disorders. We examined multivariate disorder classes using latent class analysis (LCA) and simulated a population attributable risk proportions (PARPs) of ADHD-related impairment. Results: About 15.9% had ADHD, of which 58.4% had comorbidities. LCA classified ADHD respondents to pure (42.9%), internalizing (36.0%), bipolar comorbidities (11.3%), and externalizing disorder classes (9.8%). ADHD, comorbidities, and multivariate disorder classes independently predicted severe impairment. PARPs: eliminating ADHD hypothetically reduced severe impairment by 19.2%, 10.1% adjusted for comorbidities, 9.5% for multivariate disorder classes. Conclusions: ADHD and comorbid disorders are common and impairing in college students. Personalized transdiagnostic interventions guided by multivariate disorder classes should be explored

Correction: A new family of fullerene derivatives: Fullerene-curcumin conjugates for biological and photovoltaic applications (RSC Advances (2018) 8 (41692-41698) DOI: 10.1039/C8RA08334G)

The authors regret that the following funding information was mistakenly omitted from the acknowledgements in the original article: 'Research reported in this article was partially supported by the National Institute of General Medical Sciences of the National Institutes of Health under linked Award Numbers RL5GM118969, TL4GM118971, and UL1GM118970. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.' The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers

Socioeconomic, Clinical, and Molecular Features of Breast Cancer Influence Overall Survival of Latin American Women

Molecular profile of breast cancer in Latin-American women was studied in five countries: Argentina, Brazil, Chile, Mexico, and Uruguay. Data about socioeconomic characteristics, risk factors, prognostic factors, and molecular subtypes were described, and the 60-month overall cumulative survival probabilities (OS) were estimated. From 2011 to 2013, 1,300 eligible Latin-American women 18 years or older, with a diagnosis of breast cancer in clinical stage II or III, and performance status ≦̸1 were invited to participate in a prospective cohort study. Face-to-face interviews were conducted, and clinical and outcome data, including death, were extracted from medical records. Unadjusted associations were evaluated by Chi-squared and Fisher’s exact tests and the OS by Kaplan–Meier method. Log-rank test was used to determine differences between cumulative probability curves. Multivariable adjustment was carried out by entering potential confounders in the Cox regression model. The OS at 60 months was 83.9%. Multivariable-adjusted death hazard differences were found for women living in Argentina (2.27), Chile (1.95), and Uruguay (2.42) compared with Mexican women, for older (≥60 years) (1.84) compared with younger (≤40 years) women, for basal-like subtype (5.8), luminal B (2.43), and HER2-enriched (2.52) compared with luminal A subtype, and for tumor clinical stages IIB (1.91), IIIA (3.54), and IIIB (3.94) compared with stage IIA women. OS was associated with country of residence, PAM50 intrinsic subtype, age, and tumor stage at diagnosis. While the latter is known to be influenced by access to care, including cancer screening, timely diagnosis and treatment, including access to more effective treatment protocols, it may also influence epigenetic changes that, potentially, impact molecular subtypes. Data derived from heretofore understudied populations with unique geographic ancestry and sociocultural experiences are critical to furthering our understanding of this complexity. Copyright © 2022 de Almeida, Cortés, Vilensky, Valenzuela, Cortes-Sanabria, de Souza, Barbeito, Abdelhay, Artagaveytia, Daneri-Navarro, Llera, Müller, Podhajcer, Velazquez, Alcoba, Alonso, Bravo, Camejo, Carraro, Castro, Cataldi, Cayota, Cerda, Colombo, Crocamo, Del Toro-Arreola, Delgadillo-Cristerna, Delgado, Breitenbach, Fernández, Fernández, Fernández, Franco-Topete, Gaete, Gómez, Gonzalez-Ramirez, Guerrero, Gutierrez-Rubio, Jalfin, Lopez-Vazquez, Loria, Míguez, Moran-Mendoza, Morgan-Villela, Mussetti, Nagai, Oceguera-Villanueva, Reis, Retamales, Rodriguez, Rosales, Salas-Gonzalez, Segovia, Sendoya, Silva-Garcia, Viña, Zagame, Jones, Szklo and United States-Latin American Cancer Research Network (US-LACRN).Fil: de Almeida, Liz Maria. Instituto Nacional de Cáncer; BrasilFil: Cortés, Sandra. Pontificia Universidad Católica de Chile; ChileFil: Vilensky, Marta. Instituto de Oncología Angel Roffo; ArgentinaFil: Valenzuela, Olivia. Universidad de Sonora; MéxicoFil: Cortes-Sanabria, Laura. Hospital de Especialidades, CMNO-IMSS; MéxicoFil: de Souza, Mirian. Instituto Nacional de Cáncer; BrasilFil: Barbeito, Rafael Alonso. Facultad de Medicina; ArgentinaFil: Abdelhay, Eliana. Instituto Nacional de Cáncer; BrasilFil: Artagaveytia, Nora. Hospital de Clínicas Manuel Quintela. Universidad de la República; UruguayFil: Daneri-Navarro, Adrian. Universidad de Guadalajara; MéxicoFil: Llera, Andrea S. CONICET. Fundación Instituto Leloir; ArgentinaFil: Müller, Bettina. Instituto Nacional del Cáncer; ArgentinaFil: Podhajcer, Osvaldo L. CONICET. Fundación Instituto Leloir; ArgentinaFil: Velazquez, Carlos. Universidad de Sonora; MéxicoFil: Alcoba, Elsa. Hospital Municipal de Oncología María Curie; ArgentinaFil: Alonso, Isabel. Centro Hospitalario Pereira Rossell; ArgentinaFil: Bravo, Alicia I. Hospital Regional de Agudos Eva Perón; ArgentinaFil: Camejo, Natalia. Hospital de Clínicas Manuel Quintela. Universidad de la República; UruguayFil: Carraro, Dirce Maria. AC Camargo Cancer Center; BrasilFil: Castro, Mónica. Instituto de Oncología Angel Roffo; ArgentinaFil: Cataldi, Sandra. Instituto Nacional de Cáncer; UruguayFil: Cayota, Alfonso. Institut Pasteur de Montevideo; UruguayFil: Cerda, Mauricio. Universidad de Chile; ChileFil: Colombo, Alicia. Universidad de Chile; ChileFil: Crocamo, Susanne. Instituto Nacional de Cáncer; BrasilFil: Del Toro-Arreola, Alicia. Universidad de Guadalajara; MéxicoFil: Delgadillo-Cristerna, Raul. Hospital de Especialidades. CMNO-IMSS; MéxicoFil: Delgado, Lucia. Hospital de Clínicas Manuel Quintela; UruguayFil: Breitenbach, Marisa Dreyer. Universidade do Estado do Rio de Janeiro; BrasilFil: Fernández, Elmer. Universidad Católica de Córdoba. CONICET. Centro de Investigaciones en Bioquímica Clínica e Inmunologia; ArgentinaFil: Fernández, Jorge. Instituto de Salud Pública; ChileFil: Fernández, Wanda. Hospital San Borja Arriarán; ChileFil: Franco-Topete, Ramon A. OPD Hospital Civil de Guadalajara. Universidad de Guadalajara; MéxicoFil: Gaete, Fancy. Hospital Luis Tisne; ChileFil: Gómez, Jorge. Texas A&M University; Estados UnidosFil: Gonzalez-Ramirez, Leivy P. Universidad de Guadalajara; MéxicoFil: Guerrero, Marisol. Hospital San José; ChileFil: Gutierrez-Rubio, Susan A. Universidad de Guadalajara; MéxicoFil: Jalfin, Beatriz. Hospital Regional de Agudos Eva Perón; ArgentinaFil: Lopez-Vazquez, Alejandra. Universidad de Sonora; MéxicoFil: Loria, Dora. Instituto de Oncología Angel Roffo; ArgentinaFil: Míguez, Silvia. Hospital Municipal de Oncología María Curie; ArgentinaFil: Moran-Mendoza, Andres de J. Hospital de Gineco-Obstetricia CMNO-IMSS; MéxicoFil: Morgan-Villela, Gilberto. Hospital de Especialidades. CMNO-IMSS; MéxicoFil: Mussetti, Carina. Registro Nacional de Cancer; UruguayFil: Nagai, Maria Aparecida. Instituto de Câncer de São Paulo; BrasilFil: Oceguera-Villanueva, Antonio. Instituto Jalisciense de Cancerologia; MéxicoFil: Reis, Rui M. Hospital de Câncer de Barretos; BrasilFil: Retamales, Javier. Grupo Oncológico Cooperativo Chileno de Investigación; ChileFil: Rodriguez, Robinson. Hospital Central de las Fuerzas Armadas; UruguayFil: Rosales, Cristina, Hospital Municipal de Oncología María Curie; ArgentinaFil: Salas-Gonzalez, Efrain. Hospital San José; ChileFil: Segovia, Laura. Hospital Barros Luco Trudeau; ChileFil: Sendoya, Juan M. CONICET. Fundación Instituto Leloir,; ArgentinaFil: Silva-Garcia, Aida A. OPD Hospital Civil de Guadalajara. Universidad de Guadalajara; MéxicoFil: Viña, Stella. Instituto de Oncología Angel Roffo; ArgentinaFil: Zagame, Livia. Instituto Jalisciense de Cancerologia; MéxicoFil: Jones, Beth. Yale University. Yale School of Public Health; Estados UnidosFil: Szklo, Moysés. Johns Hopkins University. Johns Hopkins Bloomberg School of Public Health; Estados Unido

Weaning from mechanical ventilation in intensive care units across 50 countries (WEAN SAFE): a multicentre, prospective, observational cohort study

International audienceBackground: Current management practices and outcomes in weaning from invasive mechanical ventilation are poorly understood. We aimed to describe the epidemiology, management, timings, risk for failure, and outcomes of weaning in patients requiring at least 2 days of invasive mechanical ventilation. Methods: WEAN SAFE was an international, multicentre, prospective, observational cohort study done in 481 intensive care units in 50 countries. Eligible participants were older than 16 years, admitted to a participating intensive care unit, and receiving mechanical ventilation for 2 calendar days or longer. We defined weaning initiation as the first attempt to separate a patient from the ventilator, successful weaning as no reintubation or death within 7 days of extubation, and weaning eligibility criteria based on positive end-expiratory pressure, fractional concentration of oxygen in inspired air, and vasopressors. The primary outcome was the proportion of patients successfully weaned at 90 days. Key secondary outcomes included weaning duration, timing of weaning events, factors associated with weaning delay and weaning failure, and hospital outcomes. This study is registered with ClinicalTrials.gov, NCT03255109. Findings: Between Oct 4, 2017, and June 25, 2018, 10 232 patients were screened for eligibility, of whom 5869 were enrolled. 4523 (77·1%) patients underwent at least one separation attempt and 3817 (65·0%) patients were successfully weaned from ventilation at day 90. 237 (4·0%) patients were transferred before any separation attempt, 153 (2·6%) were transferred after at least one separation attempt and not successfully weaned, and 1662 (28·3%) died while invasively ventilated. The median time from fulfilling weaning eligibility criteria to first separation attempt was 1 day (IQR 0–4), and 1013 (22·4%) patients had a delay in initiating first separation of 5 or more days. Of the 4523 (77·1%) patients with separation attempts, 2927 (64·7%) had a short wean (≤1 day), 457 (10·1%) had intermediate weaning (2–6 days), 433 (9·6%) required prolonged weaning (≥7 days), and 706 (15·6%) had weaning failure. Higher sedation scores were independently associated with delayed initiation of weaning. Delayed initiation of weaning and higher sedation scores were independently associated with weaning failure. 1742 (31·8%) of 5479 patients died in the intensive care unit and 2095 (38·3%) of 5465 patients died in hospital. Interpretation: In critically ill patients receiving at least 2 days of invasive mechanical ventilation, only 65% were weaned at 90 days. A better understanding of factors that delay the weaning process, such as delays in weaning initiation or excessive sedation levels, might improve weaning success rates. Funding: European Society of Intensive Care Medicine, European Respiratory Society

Heavy flavour decay muon production at forward rapidity in proton–proton collisions at √s=7 TeV

The production of muons from heavy flavour decays is measured at forward rapidity in proton–proton collisions at √s=7 TeV collected with the ALICE experiment at the LHC. The analysis is carried out on a data sample corresponding to an integrated luminosity Lint=16.5 nb−1. The transverse momentum and rapidity differential production cross sections of muons from heavy flavour decays are measured in the rapidity range 2.5<y<4, over the transverse momentum range 2<pt<12 GeV/c. The results are compared to predictions based on perturbative QCD calculations