Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 234
Filtrar
1.
Eur J Prev Cardiol ; 2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34893801

RESUMO

AIMS: We prospectively assessed and compared the accuracy of cardiovascular risk scores in people living with HIV (PLWH) and individuals from the general population. METHODS AND RESULTS: The Systematic Coronary Risk Evaluation Score 2 (SCORE2), the Pooled Cohort Equations (PCE), and the HIV-specific Data Collection on Adverse events of Anti-HIV Drugs (D:A:D) score were calculated in participants free from atherosclerotic cardiovascular disease (ASCVD) between 2003 and 2009. In total, 6373 [mean age, 40.6 years (SD, 9.9)] PLWH from the Swiss HIV Cohort Study (SHCS) and 5403 [52.8 years (SD, 10.7)] individuals from the CoLaus|PsyCoLaus study were eligible for analysis. We tested discrimination and calibration, and the value of adding HIV-specific factors to scores using the net reclassification improvement (NRI). During mean follow-ups of 13.5 (SD, 4.1) in SHCS and 9.9 (SD, 2.3) years in CoLaus|PsyCoLaus study, 533 (8.4%) and 374 (6.9%) people developed an incident ASCVD, respectively. This translated into age-adjusted incidence rates of 12.9 and 7.5 per 1000 person-year, respectively. In SHCS, SCORE2, PCE, and D:A:D presented comparable discriminative capacities [area under the receiver operating characteristic curve of 0.745 (95% confidence interval, CI, 0.723-0.767), 0.757 (95% CI, 0.736-0.777), and 0.763 (95% CI, 0.743-0.783)]. Adding HIV-specific variables (CD4 nadir and abacavir exposure) to SCORE2 and PCE resulted in an NRI of -0.1% (95% CI, -1.24 to 1, P = 0.83) and of 2.7% (95% CI, 0.3-5.1, P = 0.03), respectively. CONCLUSIONS: PLWH present a two-fold higher rate of incident ASCVD compared to individuals from the general population. SCORE2 and PCE, which are clinically easier to use (reduced set of variables without adding HIV-specific factors), are valid to predict ASCVD in PLWH.

2.
Fam Pract ; 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34611715

RESUMO

BACKGROUND: Clinical findings do not accurately predict laboratory diagnosis of influenza. Early identification of influenza is considered useful for proper management decisions in primary care. OBJECTIVE: We evaluated the diagnostic value of the presence and the severity of symptoms for the diagnosis of laboratory-confirmed influenza infection among adults presenting with influenza-like illness (ILI) in primary care. METHODS: Secondary analysis of patients with ILI who participated in a clinical trial from 2015 to 2018 in 15 European countries. Patients rated signs and symptoms as absent, minor, moderate, or major problem. A nasopharyngeal swab was taken for microbiological identification of influenza and other microorganisms. Models were generated considering (i) the presence of individual symptoms and (ii) the severity rating of symptoms. RESULTS: A total of 2,639 patients aged 18 or older were included in the analysis. The mean age was 41.8 ± 14.7 years, and 1,099 were men (42.1%). Influenza was microbiologically confirmed in 1,337 patients (51.1%). The area under the curve (AUC) of the model for the presence of any of seven symptoms for detecting influenza was 0.66 (95% confidence interval [CI]: 0.65-0.68), whereas the AUC of the symptom severity model, which included eight variables-cough, fever, muscle aches, sweating and/or chills, moderate to severe overall disease, age, abdominal pain, and sore throat-was 0.70 (95% CI: 0.69-0.72). CONCLUSION: Clinical prediction of microbiologically confirmed influenza in adults with ILI is slightly more accurate when based on patient reported symptom severity than when based on the presence or absence of symptoms.

3.
J Am Heart Assoc ; 10(20): e020488, 2021 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-34622666

RESUMO

Background It remains unclear whether the novel biomarker cysteine-rich angiogenic inducer 61 (CCN1) adds incremental prognostic value to the GRACE 2.0 (Global Registry of Acute Coronary Events) risk score and biomarkers high-sensitivity Troponin T, hsCRP (high-sensitivity C-reactive protein), and NT-proBNP (N-terminal pro-B-type natriuretic peptide) in patients with acute coronary syndromes. Methods and Results Patients referred for coronary angiography with a primary diagnosis of acute coronary syndromes were enrolled in the Special Program University Medicine - Acute Coronary Syndromes and Inflammation cohort. The primary/secondary end points were 30-day/1-year all-cause mortality and the composite of all-cause mortality or myocardial infarction as used in the GRACE risk score. Associations between biomarkers and outcome were assessed using log-transformed biomarker values and the GRACE risk score (versions 1.0 and 2.0). The incremental value of CCN1 beyond a reference model was assessed using Harrell's C-statistics calculated from a Cox proportional-hazard model. The P value of the C-statistics was derived from a likelihood ratio test. Among 2168 patients recruited, 1732 could be analyzed. CCN1 was the strongest single predictor of all-cause mortality at 30 days (hazard ratio [HR], 1.77 [1.31, 2.40]) and 1 year (HR, 1.81 [1.47, 2.22]). Adding CCN1 alone to the GRACE 2.0 risk score improved C-statistics for prognostic accuracy of all-cause mortality at 30 days (0.87-0.88) and 1 year (0.81-0.82) and when combined with high-sensitivity Troponin T, hsCRP, NT-proBNP for 30 days (0.87-0.91), and for 1-year follow-up (0.81-0.84). CCN1 also increased the prognostic value for the composite of all-cause mortality or myocardial infarction. Conclusions CCN1 predicts adverse outcomes in patients with acute coronary syndromes adding incremental information to the GRACE risk score, suggesting distinct underlying molecular mechanisms. Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT01000701.

4.
Trials ; 22(1): 724, 2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34674742

RESUMO

BACKGROUND: Late 2019, a new highly contagious coronavirus SARS-CoV-2 has emerged in Wuhan, China, causing within 2 months a pandemic with the highest disease burden in elderly and people with pre-existing medical conditions. The pandemic has highlighted that new and more flexible clinical trial approaches, such as trial platforms, are needed to assess the efficacy and safety of interventions in a timely manner. The two existing Swiss cohorts of immunocompromised patients (i.e., Swiss HIV Cohort Study (SHCS) and Swiss Transplant Cohort Study (STCS)) are an ideal foundation to set-up a trial platform in Switzerland leveraging routinely collected data. Within a newly founded trial platform, we plan to assess the efficacy of the first two mRNA SARS-CoV-2 vaccines that reached market authorization in Switzerland in the frame of a pilot randomized controlled trial (RCT) while at the same time assessing the functionality of the trial platform. METHODS: We will conduct a multicenter randomized controlled, open-label, 2-arm sub-study pilot trial of a platform trial nested into two Swiss cohorts. Patients included in the SHCS or the STCS will be eligible for randomization to either receiving the mRNA vaccine Comirnaty® (Pfizer/BioNTech) or the COVID-19 mRNA Vaccine Moderna®. The primary clinical outcome will be change in pan-lg antibody response (pan-Ig anti-S1-RBD; baseline vs. 3 months after first vaccination; binary outcome, considering ≥ 0.8 units/ml as a positive antibody response). The pilot study will also enable us to assess endpoints related to trial conduct feasibility (i.e., duration of RCT set-up; time of patient recruitment; patient consent rate; proportion of missing data). Assuming vaccine reactivity of 90% in both vaccine groups, we power our trial, using a non-inferiority margin such that a 95% two-sided confidence interval excludes a difference in favor of the reference group of more than 10%. A sample size of 380 (190 in each treatment arm) is required for a statistical power of 90% and a type I error of 0.025. The study is funded by the Swiss National Science Foundation (National Research Program NRP 78, "COVID-19"). DISCUSSION: This study will provide crucial information about the efficacy and safety of the mRNA SARS-CoV-2 vaccines in HIV patients and organ transplant recipients. Furthermore, this project has the potential to pave the way for further platform trials in Switzerland. TRIAL REGISTRATION: ClinicalTrials.gov NCT04805125 . Registered on March 18, 2021.


Assuntos
COVID-19 , Vacinas Virais , Idoso , Vacinas contra COVID-19 , Humanos , Hospedeiro Imunocomprometido , Estudos Multicêntricos como Assunto , Projetos Piloto , RNA Mensageiro , Ensaios Clínicos Controlados Aleatórios como Assunto , SARS-CoV-2
5.
BMJ Open ; 11(9): e045239, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34475143

RESUMO

INTRODUCTION: The emphasis on aesthetic outcomes and quality of life (QoL) has motivated surgeons to develop skin-sparing or nipple-sparing mastectomy (SSM/ NSM) for breast cancer treatment or prevention. During the same operation, a so-called immediate breast reconstruction is performed. The breast can be reconstructed by positioning of a breast implant above (prepectoral) or below (subpectoral) the pectoralis major muscle or by using the patients' own tissue (autologous reconstruction). The optimal positioning of the implant prepectoral or subpectoral is currently not clear. Subpectoral implant-based breast reconstruction (IBBR) is still standard care in many countries, but prepectoral IBBR is increasingly performed. This heterogeneity in breast reconstruction practice is calling for randomised clinical trials (RCTs) to guide treatment decisions. METHODS AND ANALYSIS: International, pragmatic, multicentre, randomised, superiority trial. The primary objective of this trial is to test whether prepectoral IBBR provides better QoL with respect to long-term (24 months) physical well-being (chest) compared with subpectoral IBBR for patients undergoing SSM or NSM for prevention or treatment of breast cancer. Secondary objectives will compare prepectoral versus subpectoral IBBR in terms of safety, QoL and patient satisfaction, aesthetic outcomes and burden on patients. Total number of patients to be included: 372 (186 per arm). ETHICS AND DISSEMINATION: This study will be conducted in compliance with the Declaration of Helsinki. Ethical approval has been obtained for the lead investigator's site by the Ethics Committee 'Ethikkommission Nordwest- und Zentralschweiz' (2020-00256, 26 March 2020). The results of this study will be published in a peer-reviewed medical journal, independent of the results, following the Consolidated Standards of Reporting Trials standards for RCTs and good publication practice. Metadata describing the type, size and content of the datasets will be shared along with the study protocol and case report forms on public repositories adhering to the FAIR (Findability, Accessibility, Interoperability, and Reuse) principles. TRIAL REGISTRATION NUMBER: NCT04293146.


Assuntos
Implante Mamário , Implantes de Mama , Neoplasias da Mama , Mamoplastia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Mastectomia , Mamilos/cirurgia
6.
Eur J Surg Oncol ; 47(6): 1324-1331, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33895025

RESUMO

BACKGROUND: In 2013 Swiss health authorities implemented annual hospital caseload requirements (CR) for five areas of visceral surgery. We assess the impact of the implementation of CR on indication for surgery in esophageal, pancreatic and rectal cancer. MATERIALS AND METHODS: Retrospective analysis of national registry data of all inpatient admissions between January 1st, 2005 and December 31st, 2015. Primary end-point was the age-adjusted resection rate for esophageal, pancreatic and rectal cancer among patients with at least one cancer-specific hospitalization per year. We calculated age-adjusted rate ratios for period effects before and after implementation of CR and odds ratios (OR) based on a generalized estimation equation. A relative increase of 5% in age-adjusted relative risk was set a priori as relevant from a health policy perspective. RESULTS: Age-adjusted resection rates before and after the implementation of CR were 0.12 and 0.13 (Relative Risk [RR] 1.08; 95%-Confidence Interval [CI] 0.85-1.36) in esophageal cancer, 0.22 and 0.26 (RR 1.17; 95%-CI 0.85-1.58) in pancreatic cancer and 0.38 and 0.43 (RR 1.14; 95%-CI 0.99-1.30) in rectal cancer. In adjusted models OR for resection after the implementation of CR were 1.40 (95%-CI 1.24-1.58) in esophageal cancer, 1.05 (95%-CI 0.96-1.15) in pancreatic cancer and 0.92 (95%-CI 0.87-0.97) in rectal cancer. CONCLUSION: Implementation of CR was associated with an increase of resection rates above the a priori set margins in all resections groups. In adjusted models, odds for resection were significantly higher for esophageal cancer, while they remained unchanged for pancreatic and decreased for rectal cancer.


Assuntos
Neoplasias Esofágicas/cirurgia , Política de Saúde/legislação & jurisprudência , Hospitais/estatística & dados numéricos , Neoplasias Pancreáticas/cirurgia , Neoplasias Retais/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Esofágicas/epidemiologia , Esofagectomia/estatística & dados numéricos , Feminino , Humanos , Incidência , Legislação Hospitalar , Masculino , Pessoa de Meia-Idade , Razão de Chances , Pancreatectomia/estatística & dados numéricos , Neoplasias Pancreáticas/epidemiologia , Protectomia/estatística & dados numéricos , Neoplasias Retais/epidemiologia , Sistema de Registros , Estudos Retrospectivos , Suíça/epidemiologia , Adulto Jovem
7.
BMC Pregnancy Childbirth ; 21(1): 339, 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33910502

RESUMO

BACKGROUND: Mother-to-child HIV transmission (MTCT) has substantially declined since the scale-up of prevention programs around the world, including Rwanda. To achieve full elimination of MTCT, it is important to understand the risk factors associated with residual HIV transmission, defined as MTCT at the population-level that still occurs despite universal access to PMTCT. METHODS: We performed a case control study of children born from mothers with HIV with known vital status at 18 months from birth, who were followed in three national cohorts between October and December 2013, 2014, and 2015 in Rwanda. Children with HIV were matched in a ratio of 1:2 with HIV-uninfected children and a conditional logistic regression model was used to investigate risk factors for MTCT. RESULTS: In total, 84 children with HIV were identified and matched with 164 non-infected children. The median age of mothers from both groups was 29 years (interquartile range (IQR): 24-33). Of these mothers, 126 (51.4 %) initiated antiretroviral therapy (ART) before their pregnancy on record. In a multivariable regression analysis, initiation of ART in the third trimester (Adjusted Odds Ratio [aOR]: 9.25; 95 % Confidence Interval [95 % CI]: 2.12-40.38) and during labour or post-partum (aOR: 8.87; 95 % CI: 1.92-40.88), compared to initiation of ART before pregnancy, increased the risk of MTCT. Similarly, offspring of single mothers (aOR: 7.15; 95 % CI: 1.15-44.21), and absence of postpartum neonatal ART prophylaxis (aOR: 7.26; 95 % CI: 1.66-31.59) were factors significantly associated with MTCT. CONCLUSIONS: Late ART initiation for PMTCT and lack of postpartum infant prophylaxis are still the most important risk factors to explain MTCT in the era of universal access. Improved early attendance at antenatal care, early ART initiation, and enhancing the continuum of care especially for single mothers is crucial for MTCT elimination in Rwanda.


Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/prevenção & controle , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Complicações Infecciosas na Gravidez/tratamento farmacológico , Adulto , Aleitamento Materno/efeitos adversos , Estudos de Casos e Controles , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/transmissão , Humanos , Lactente , Modelos Logísticos , Masculino , Análise Multivariada , Período Pós-Parto , Gravidez , Fatores de Risco , Ruanda , Adulto Jovem
8.
Clin Otolaryngol ; 46(5): 1050-1056, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33866681

RESUMO

OBJECTIVE: Antibiotics are largely overprescribed for acute rhinosinusitis in primary care, mainly due to the lack of diagnostic tests to confirm or rule out bacterial infection. The study objective was to assess the on-site applicability and safety of the newly developed JGG endoscope® for the diagnosis of acute bacterial rhinosinusitis in primary care. DESIGN: Five Swiss primary care centres and one university-affiliated ENT unit participated in this single-arm pilot study. PARTICIPANTS: Adults with acute suspected bacterial rhinosinusitis. The newly developed JGG endoscope® , which is attached to a pocket otoscope, was used to inspect after local anaesthesia the nasal cavity and middle meatus and to gain material for bacterial culture from paranasal sinuses draining ostium. MAIN OUTCOME MEASURES: Applicability and safety. RESULTS: The visualisation of the middle meatus was successful in 16 of 21 patients (13 in both sides and three in one side), and unclear or unsuccessful in five patients. Sample collection from the middle meatus was successful in 10 patients (six on both and four on one side) and unclear or unsuccessful in the remaining patients. Only one culture-confirmed bacterial rhinosinusitis and 11 PCR-confirmed viral infections were identified from collected samples. After a 2-week follow-up, no serious adverse events were observed. CONCLUSIONS: The on-site use of the JGG endoscope® in daily primary care routine is feasible and safe and was well accepted by the trial physicians and patients (assessed with structured questionnaires). The JGG endoscope® may support general practitioners to differentiate between bacterial and viral rhinosinusitis.

9.
BMJ Open ; 11(4): e045702, 2021 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-33888530

RESUMO

INTRODUCTION: In the field of arthroscopic rotator cuff repair (ARCR), reporting standards of published studies differ dramatically, notably concerning adverse events (AEs). In addition, prognostic studies are overall methodologically poor, based on small data sets and explore only limited numbers of influencing factors. We aim to develop prognostic models for individual ARCR patients, primarily for the patient-reported assessment of shoulder function (Oxford Shoulder Score (OSS)) and the occurrence of shoulder stiffness 6 months after surgery. We also aim to evaluate the use of a consensus core event set (CES) for AEs and validate a severity classification for these events, considering the patient's perspective. METHODS AND ANALYSIS: A cohort of 970 primary ARCR patients will be prospectively documented from several Swiss and German orthopaedic clinics up to 24 months postoperatively. Patient clinical examinations at 6 and 12 months will include shoulder range of motion and strength (Constant Score). Tendon repair integrity status will be assessed by ultrasound at 12 months. Patient-reported questionnaires at 6, 12 and 24 months will determine functional scores (subjective shoulder value, OSS), anxiety and depression scores, working status, sports activities, and quality of life (European Quality of Life 5 Dimensions 5 Level questionnaire). AEs will be documented according to a CES. Prognostic models will be developed using an internationally supported regression methodology. Multiple prognostic factors, including patient baseline demographics, psychological, socioeconomic and clinical factors, rotator cuff integrity, concomitant local findings, and (post)operative management factors, will be investigated. ETHICS AND DISSEMINATION: This project contributes to the development of personalised risk predictions for supporting the surgical decision process in ARCR. The consensus CES may become an international reference for the reporting of complications in clinical studies and registries. Ethical approval was obtained on 1 April 2020 from the lead ethics committee (EKNZ, Basel, Switzerland; ID: 2019-02076). All participants will provide informed written consent before enrolment in the study. TRIAL REGISTRATION NUMBER: NCT04321005. PROTOCOL VERSION: Version 2 (13 December 2019).


Assuntos
Lesões do Manguito Rotador , Manguito Rotador , Artroscopia , Estudos de Coortes , Humanos , Estudos Multicêntricos como Assunto , Qualidade de Vida , Manguito Rotador/diagnóstico por imagem , Manguito Rotador/cirurgia , Lesões do Manguito Rotador/cirurgia , Suíça , Resultado do Tratamento
10.
BMJ ; 373: n808, 2021 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-33910882

RESUMO

OBJECTIVE: To assess the overall effect of delayed antibiotic prescribing on average symptom severity for patients with respiratory tract infections in the community, and to identify any factors modifying this effect. DESIGN: Systematic review and individual patient data meta-analysis. DATA SOURCES: Cochrane Central Register of Controlled Trials, Ovid Medline, Ovid Embase, EBSCO CINAHL Plus, and Web of Science. ELIGIBILITY CRITERIA FOR STUDY SELECTION: Randomised controlled trials and observational cohort studies in a community setting that allowed comparison between delayed versus no antibiotic prescribing, and delayed versus immediate antibiotic prescribing. MAIN OUTCOME MEASURES: The primary outcome was the average symptom severity two to four days after the initial consultation measured on a seven item scale (ranging from normal to as bad as could be). Secondary outcomes were duration of illness after the initial consultation, complications resulting in admission to hospital or death, reconsultation with the same or worsening illness, and patient satisfaction rated on a Likert scale. RESULTS: Data were obtained from nine randomised controlled trials and four observational studies, totalling 55 682 patients. No difference was found in follow-up symptom severity (seven point scale) for delayed versus immediate antibiotics (adjusted mean difference -0.003, 95% confidence interval -0.12 to 0.11) or delayed versus no antibiotics (0.02, -0.11 to 0.15). Symptom duration was slightly longer in those given delayed versus immediate antibiotics (11.4 v 10.9 days), but was similar for delayed versus no antibiotics. Complications resulting in hospital admission or death were lower with delayed versus no antibiotics (odds ratio 0.62, 95% confidence interval 0.30 to 1.27) and delayed versus immediate antibiotics (0.78, 0.53 to 1.13). A significant reduction in reconsultation rates (odds ratio 0.72, 95% confidence interval 0.60 to 0.87) and an increase in patient satisfaction (adjusted mean difference 0.09, 0.06 to 0.11) were observed in delayed versus no antibiotics. The effect of delayed versus immediate antibiotics and delayed versus no antibiotics was not modified by previous duration of illness, fever, comorbidity, or severity of symptoms. Children younger than 5 years had a slightly higher follow-up symptom severity with delayed antibiotics than with immediate antibiotics (adjusted mean difference 0.10, 95% confidence interval 0.03 to 0.18), but no increased severity was found in the older age group. CONCLUSIONS: Delayed antibiotic prescribing is a safe and effective strategy for most patients, including those in higher risk subgroups. Delayed prescribing was associated with similar symptom duration as no antibiotic prescribing and is unlikely to lead to poorer symptom control than immediate antibiotic prescribing. Delayed prescribing could reduce reconsultation rates and is unlikely to be associated with an increase in symptoms or illness duration, except in young children. STUDY REGISTRATION: PROSPERO CRD42018079400.


Assuntos
Antibacterianos/uso terapêutico , Padrões de Prática Médica , Infecções Respiratórias/tratamento farmacológico , Esquema de Medicação , Humanos , Tempo para o Tratamento
11.
Contemp Clin Trials Commun ; 21: 100712, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33665467

RESUMO

Introduction: Antibiotic consumption is highest in primary care, and antibiotic overuse furthers antimicrobial resistance. In our recently published pilot-RCT, we used monthly aggregated claims data to provide personalized antibiotic prescription feedback to general practitioners (GPs). The pilot-RCT has shown that personalized prescription feedback is a feasible and promising low-cost intervention to reduce antibiotic prescribing. Here, we describe the rationale and design of the follow-up RCT with 3426 GPs in Switzerland. We now have access to pseudonymized patient-level data from routinely collected health insurance data of the three largest health insurers in Switzerland. Methods and analysis: 1713 GPs randomized to the intervention group received once evidence-based treatment guidelines at the beginning, including region-specific antibiotic resistance information from the community and personalized feedback of their antibiotic prescribing, followed by quarterly personalized prescription feedback for two years. The first and the last mailings were sent out in December 2017 and September 2019, respectively. The 1713 GPs randomized to the control group were not notified about the study and they received no guidelines and no prescription feedback. The personalized prescription feedbacks and the analyses of the primary and secondary outcomes are entirely based on pseudonymized patient-level data from routinely collected health insurance data. The primary outcome is prescribed antibiotics per 100 patient consultations during the second year of intervention. The secondary outcomes include antibiotic use during the entire two-year trial period, use of broad-spectrum antibiotics, hospitalization rates (all-cause and infection-related), and antibiotic use in different age groups. If the feedback intervention proves to be efficacious, the intervention could be continued systemwide. Ethics and dissemination: The trial is publicly funded by the Swiss National Science Foundation (SNSF, grant number 407240_167066). The trial was approved by the ethics committee "Ethikkommission Nordwest-und Zentralschweiz" (EKNZ Project-ID 2017-00888). Results will be disseminated in peer-reviewed journals and international conferences.

12.
Ann Intern Med ; 174(6): 768-776, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33721519

RESUMO

BACKGROUND: Immediate initiation of antiretroviral therapy (ART) regardless of CD4 cell count reduces risk for AIDS and non-AIDS-related events in asymptomatic, HIV-positive persons and is the standard of care. However, most HIV-positive persons initiate ART when their CD4 count decreases below 500 × 109 cells/L. Consequences of delayed ART on risk for non-AIDS-defining and AIDS-defining cancer, one of the most common reasons for death in HIV, are unclear. OBJECTIVE: To estimate the long-term risk difference for cancer with the immediate ART strategy. DESIGN: Multinational prospective cohort study. SETTING: The D:A:D (Data collection on Adverse events of anti-HIV Drugs) study, which included HIV-positive persons from Europe, Australia, and the United States. PARTICIPANTS: 8318 HIV-positive persons with at least 1 measurement each of CD4 cell count and viral load while ART-naive (study period, 2006 to 2016). MEASUREMENTS: The parametric g-formula was used, with adjustment for baseline and time-dependent confounders (CD4 cell count and viral load), to assess the 10-year risk for non-AIDS-defining and AIDS-defining cancer of immediate versus deferred (at CD4 counts <350 and <500 × 109 cells/L) ART initiation strategies. RESULTS: During 64 021 person-years of follow-up, 231 cases of non-AIDS-defining cancer and 272 of AIDS-defining cancer occurred among HIV-positive persons with a median age of 36 years (interquartile range, 29 to 43 years). With immediate ART, the 10-year risk for non-AIDS-defining cancer was 2.97% (95% CI, 2.37% to 3.50%) and that for AIDS-defining cancer was 2.50% (CI, 2.37% to 3.38%). Compared with immediate ART initiation, the 10-year absolute risk differences when deferring ART to CD4 counts less than 500 × 109 cells/L and less than 350 × 109 cells/L were 0.12 percentage point (CI, -0.01 to 0.26 percentage point) and 0.29 percentage point (CI, -0.03 to 0.73 percentage point), respectively, for non-AIDS-defining cancer and 0.32 percentage point (CI, 0.21 to 0.44 percentage point) and 1.00 percentage point (CI, 0.67 to 1.44 percentage points), respectively, for AIDS-defining cancer. LIMITATION: Potential residual confounding due to observational study design. CONCLUSION: In this young cohort, effects of immediate ART on 10-year risk for cancer were small, and further supportive data are needed for non-AIDS-defining cancer. PRIMARY FUNDING SOURCE: Highly Active Antiretroviral Therapy Oversight Committee.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Neoplasias/epidemiologia , Tempo para o Tratamento , Adulto , Contagem de Linfócito CD4 , Feminino , Infecções por HIV/imunologia , Infecções por HIV/virologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Carga Viral
13.
Atherosclerosis ; 320: 31-37, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33524907

RESUMO

BACKGROUND AND AIMS: Residual inflammatory risk (RIR) after acute coronary syndromes (ACS) may identify patients likely to benefit from anti-inflammatory therapies. METHODS: Patients from the Special Program University Medicine ACS cohort were divided into four groups according to level of hsCRP at baseline and after 12 months: persistently high RIR, increased RIR (first low, then high hsCRP), attenuated RIR (first high, then low hsCRP), or persistently low RIR. High RIR was defined as hsCRP ≥ 2 mg/L. An independently adjudicated incident of combined adverse events was defined as the composite of myocardial infarction, clinically indicated coronary revascularization or cerebrovascular events. RESULTS: Among 1209 patients with available hsCRP, clinical and demographic data, 295 (24.4%) patients had persistently high RIR (delta hsCRP median (IQR): 2.3 (-9.9; 0.3) (mg/L) and 72 (5.96%) patients had increased RIR (delta hsCRP median (IQR): +2.45 (1.2; 8.35) (mg/L). A total of 390 (32.26%) patients had attenuated RIR (delta hsCRP median (IQR): 3.55 (-10; -2) (mg/L) and 452 (37.38%) patients had persistently low RIR (delta hsCRP median (IQR): 0.2 (-0.6; 0.1) (mg/L). Of 90 combined adverse events, 31 (10.5%) occurred in the persistently high (multivariable adjusted OR: 1.71, (95% CI 1.08-2.7), p = 0.022) compared with the three other groups combined (increased RIR: 3 (4.2%), attenuated RIR 30 (7.7%), persistently low RIR 26 (5.8%). CONCLUSIONS: Persistently elevated hsCRP after ACS is found in a quarter of patients with the highest risk of combined adverse events. This underlines the need to perform anti-inflammatory intervention trials in RIR patients.


Assuntos
Síndrome Coronariana Aguda , Infarto do Miocárdio , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/epidemiologia , Síndrome Coronariana Aguda/terapia , Anti-Inflamatórios/uso terapêutico , Biomarcadores , Proteína C-Reativa/análise , Humanos , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/epidemiologia
14.
Clin Infect Dis ; 73(7): e2323-e2333, 2021 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-33354721

RESUMO

BACKGROUND: Limited data exist that compare clinical outcomes of 2-drug regimens (2DRs) and 3-drug regimens (3DRs) in people living with human immunodeficiency virus. METHODS: Antiretroviral treatment-experienced individuals in the International Cohort Consortium of Infectious Diseases (RESPOND) who switched to a new 2DR or 3DR from 1 January 2012-1 October 2018 were included. The incidence of clinical events (AIDS, non-AIDS cancer, cardiovascular disease, end-stage liver and renal disease, death) was compared between regimens using Poisson regression. RESULTS: Of 9791 individuals included, 1088 (11.1%) started 2DRs and 8703 (88.9%) started 3DRs. The most common 2DRs were dolutegravir plus lamivudine (22.8%) and raltegravir plus boosted darunavir (19.8%); the most common 3DR was dolutegravir plus 2 nucleoside reverse transcriptase inhibitors (46.9%). Individuals on 2DRs were older (median, 52.6 years [interquartile range, 46.7-59.0] vs 47.7 [39.7-54.3]), and a higher proportion had ≥1 comorbidity (81.6% vs 73.9%). There were 619 events during 27 159 person-years of follow-up (PYFU): 540 (incidence rate [IR] 22.5/1000 PYFU; 95% confidence interval [CI]: 20.7-24.5) on 3DRs and 79 (30.9/1000 PYFU; 95% CI: 24.8-38.5) on 2DRs. The most common events were death (7.5/1000 PYFU; 95% CI: 6.5-8.6) and non-AIDS cancer (5.8/1000 PYFU; 95% CI: 4.9-6.8). After adjustment for baseline demographic and clinical characteristics, there was a similar incidence of events on both regimen types (2DRs vs 3DRs IR ratio, 0.92; 95% CI: .72-1.19; P = .53). CONCLUSIONS: This is the first large, international cohort to assess clinical outcomes on 2DRs. After accounting for baseline characteristics, there was a similar incidence of events on 2DRs and 3DRs. 2DRs appear to be a viable treatment option with regard to clinical outcomes. Further research on resistance barriers and long-term durability of 2DRs is needed.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Preparações Farmacêuticas , Fármacos Anti-HIV/uso terapêutico , Antirretrovirais/uso terapêutico , HIV , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos
15.
Clin Infect Dis ; 73(7): e2145-e2152, 2021 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-32634832

RESUMO

BACKGROUND: Prevalence of potential drug-drug interactions (PDDIs) between antiretroviral drugs (ARVs) and co-medications was high in 2008 in a Swiss HIV Cohort Study (SHCS) survey. We reassessed the prevalence of PDDIs in the era of human immunodeficiency virus (HIV) integrase inhibitors (INIs), characterized by more favorable interaction profiles. METHODS: The prevalence of PDDIs in treated HIV-positive individuals was assessed for the period 01-12/2018 by linkage of the Liverpool HIV drug interactions and SHCS databases. PDDIs were categorized as harmful (red flagged), of potential clinical relevance (amber flagged), or of weak clinical significance (yellow flagged). RESULTS: In 9298 included individuals, median age was 51 years (IQR, 43-58), and 72% were males. Individuals received unboosted INIs (40%), boosted ARVs (30%), and nonnucleoside reverse transcriptase inhibitor (NNRTIs) (32%)-based regimens. In the entire cohort, 68% received ≥1 co-medication, 14% had polypharmacy (≥5 co-medications) and 29% had ≥1 PDDI. Among individuals with co-medication, the prevalence of combined amber and yellow PDDIs was 43% (33% amber-mostly with cardiovascular drugs-and 20% yellow-flagged PDDIs) compared to 59% in 2008. Two percent had red-flagged PDDIs (mostly with corticosteroids), the same as in the 2008 survey. Compared with 2008, fewer individuals received boosted ARVs (-24%) and NNRTIs (-13%) but the use of co-medications was higher. CONCLUSIONS: Prevalence of PDDIs was lower with more widespread use of INIs in 2018 than in 2008. Continued use of boosted regimens and increasing needs for co-medications in this aging population impeded lower rates of PDDIs.


Assuntos
Infecções por HIV , Inibidores de Integrase de HIV , Preparações Farmacêuticas , Idoso , Estudos de Coortes , Interações Medicamentosas , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Inibidores de Integrase de HIV/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Suíça/epidemiologia
16.
JAMA Netw Open ; 3(11): e2024406, 2020 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-33170262

RESUMO

Importance: Clinical trial evidence used to support drug approval is typically the only information on benefits and harms that patients and clinicians can use for decision-making when novel cancer therapies become available. Various evaluations have raised concern about the uncertainty surrounding these data, and a systematic investigation of the available information on treatment outcomes for cancer drugs approved by the US Food and Drug Administration (FDA) is warranted. Objective: To describe the clinical trial data available on treatment outcomes at the time of FDA approval of all novel cancer drugs approved for the first time between 2000 and 2016. Design, Setting, and Participants: This comparative effectiveness study analyzed randomized clinical trials and single-arm clinical trials of novel drugs approved for the first time to treat any type of cancer. Approval packages were obtained from drugs@FDA, a publicly available database containing information on drug and biologic products approved for human use in the US. Data from January 2000 to December 2016 were included in this study. Main Outcomes and Measures: Regulatory and clinical trial characteristics were described. For randomized clinical trials, summary treatment outcomes for overall survival, progression-free survival, and tumor response across all therapies were calculated, and median absolute survival increases were estimated. Tumor types and regulatory characteristics were assessed separately. Results: Between 2000 and 2016, 92 novel cancer drugs were approved by the FDA for 100 indications based on data from 127 clinical trials. The 127 clinical trials included a median of 191 participants (interquartile range [IQR], 106-448 participants). Overall, 65 clinical trials (51.2%) were randomized, and 95 clinical trials (74.8%) were open label. Of 100 indications, 44 indications underwent accelerated approval, 42 indications were for hematological cancers, and 58 indications were for solid tumors. Novel drugs had mean hazard ratios of 0.77 (95% CI, 0.73-0.81; I2 = 46%) for overall survival and 0.52 (95% CI, 0.47-0.57; I2 = 88%) for progression-free survival. The median tumor response, expressed as relative risk, was 2.37 (95% CI, 2.00-2.80; I2 = 91%). The median absolute survival benefit was 2.40 months (IQR, 1.25-3.89 months). Conclusions and Relevance: In this study, data available at the time of FDA drug approval indicated that novel cancer therapies were associated with substantial tumor responses but with prolonging median overall survival by only 2.40 months. Approval data from 17 years of clinical trials suggested that patients and clinicians typically had limited information available regarding the benefits of novel cancer treatments at market entry.


Assuntos
Antineoplásicos/uso terapêutico , Aprovação de Drogas/métodos , Neoplasias/tratamento farmacológico , United States Food and Drug Administration/organização & administração , Biomarcadores Tumorais/metabolismo , Ensaios Clínicos como Assunto , Intervalo Livre de Doença , Neoplasias Hematológicas/tratamento farmacológico , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Taxa de Sobrevida , Resultado do Tratamento , Estados Unidos/epidemiologia
17.
Syst Rev ; 9(1): 238, 2020 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-33038929

RESUMO

BACKGROUND: Negative pressure wound therapy (NPWT) is a widely used method of wound treatment. We performed a systematic review of randomised controlled trials (RCTs) comparing the patient-relevant benefits and harms of NPWT with standard wound therapy (SWT) in patients with wounds healing by secondary intention. METHODS: We searched for RCTs in MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and study registries (last search: July 2018) and screened reference lists of relevant systematic reviews and health technology assessments. Manufacturers and investigators were asked to provide unpublished data. Eligible studies investigated at least one patient-relevant outcome (e.g. wound closure). We assessed publication bias and, if feasible, performed meta-analyses, grading the results into different categories (hint, indication or proof of a greater benefit or harm). RESULTS: We identified 48 eligible studies of generally low quality with evaluable data for 4315 patients and 30 eligible studies with missing data for at least 1386 patients. Due to potential publication bias (proportion of inaccessible data, 24%), we downgraded our conclusions. A meta-analysis of all wound healing data showed a significant effect in favour of NPWT (OR 1.56, 95% CI 1.15 to 2.13, p = 0.008). As further analyses of different definitions of wound closure did not contradict that analysis, we inferred an indication of a greater benefit of NPWT. A meta-analysis of hospital stay (in days) showed a significant difference in favour of NPWT (MD - 4.78, 95% CI - 7.79 to - 1.76, p = 0.005). As further analyses of different definitions of hospital stay/readmission did not contradict that analysis, we inferred an indication of a greater benefit of NPWT. There was neither proof (nor indication nor hint) of greater benefit or harm of NPWT for other patient-relevant outcomes such as mortality and adverse events. CONCLUSIONS: In summary, low-quality data indicate a greater benefit of NPWT versus SWT for wound closure in patients with wounds healing by secondary intention. The length of hospital stay is also shortened. The data show no advantages or disadvantages of NPWT for other patient-relevant outcomes. Publication bias is an important problem in studies on NPWT, underlining that all clinical studies need to be fully reported.


Assuntos
Tratamento de Ferimentos com Pressão Negativa , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Cicatrização
19.
BMJ ; 370: m2917, 2020 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-32843333

RESUMO

OBJECTIVE: To prospectively assess the construct and criterion validity of ClassIntra version 1.0, a newly developed classification for assessing intraoperative adverse events. DESIGN: International, multicentre cohort study. SETTING: 18 secondary and tertiary centres from 12 countries in Europe, Oceania, and North America. PARTICIPANTS: The cohort study included a representative sample of 2520 patients in hospital having any type of surgery, followed up until discharge. A follow-up to assess mortality at 30 days was performed in 2372 patients (94%). A survey was sent to a representative sample of 163 surgeons and anaesthetists from participating centres. MAIN OUTCOME MEASURES: Intraoperative complications were assessed according to ClassIntra. Postoperative complications were assessed daily until discharge from hospital with the Clavien-Dindo classification. The primary endpoint was construct validity by investigating the risk adjusted association between the most severe intraoperative and postoperative complications, measured in a multivariable hierarchical proportional odds model. For criterion validity, inter-rater reliability was evaluated in a survey of 10 fictitious case scenarios describing intraoperative complications. RESULTS: Of 2520 patients enrolled, 610 (24%) experienced at least one intraoperative adverse event and 838 (33%) at least one postoperative complication. Multivariable analysis showed a gradual increase in risk for a more severe postoperative complication with increasing grade of ClassIntra: ClassIntra grade I versus grade 0, odds ratio 0.99 (95% confidence interval 0.69 to 1.42); grade II versus grade 0, 1.39 (0.97 to 2.00); grade III versus grade 0, 2.62 (1.31 to 5.26); and grade IV versus grade 0, 3.81 (1.19 to 12.2). ClassIntra showed high criterion validity with an intraclass correlation coefficient of 0.76 (95% confidence interval 0.59 to 0.91) in the survey (response rate 83%). CONCLUSIONS: ClassIntra is the first prospectively validated classification for assessing intraoperative adverse events in a standardised way, linking them to postoperative complications with the well established Clavien-Dindo classification. ClassIntra can be incorporated into routine practice in perioperative surgical safety checklists, or used as a monitoring and outcome reporting tool for different surgical disciplines. Future studies should investigate whether the tool is useful to stratify patients to the appropriate postoperative care, to enhance the quality of surgical interventions, and to improve long term outcomes of surgical patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT03009929.


Assuntos
Complicações Intraoperatórias/classificação , Complicações Pós-Operatórias/classificação , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Complicações Intraoperatórias/epidemiologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Estudos Prospectivos , Reprodutibilidade dos Testes , Procedimentos Cirúrgicos Operatórios/estatística & dados numéricos , Inquéritos e Questionários , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...