518 research outputs found
Inadequate Reporting of Cointerventions, Other Methodological Factors, and Treatment Estimates in Cardiovascular Trials: A Meta-Epidemiological Study.
OBJECTIVE
To assess how inadequate reporting of cointerventions influences estimated treatment effects in recent cardiovascular trials.
METHODS
Medline/Embase were systematically searched from January 1, 2011 to July 1, 2021 for trials evaluating pharmacologic interventions on clinical cardiovascular outcomes published in 5 high-impact journals. Information on adequate vs inadequate reporting of cointerventions, blinding, risk of bias due to deviations of intended interventions (low vs high/some concerns), funding (nonindustry vs industry), design (superiority vs noninferiority), and results were assessed by 2 reviewers. The association with effect sizes was assessed using meta-regression random-effect analysis, expressed as ratios of odds ratios (ROR). RORs of >1.0 indicated that trials with the methodological factor pointing to lower quality report larger treatment estimates.
RESULTS
In total, 164 trials were included. Of the 164 trials, 124 (74%) did not adequately report cointerventions; 89 of the 164 trials (54%) provided no information regarding cointerventions, and 70 of the 164 (43%) were at risk of bias due to inadequate blinding. Moreover, 86 of the 164 (53%) were at risk of bias due to deviation of intended interventions. Of the 164 trials, 144 (88%) were funded by the industries. Trials with inadequate reporting of cointerventions had larger treatment estimates for the primary end point (ROR, 1.08; 95% CI, 1.01-1.15; I2=0%). No significant association with results for blinding (ROR, 0.97; 95% CI, 0.91-1.03; I2=66%), deviation of intended interventions (ROR, 0.98; 95% CI, 0.92-1.04; I2=0%), or funding (ROR, 1.01; 95% CI, 0.93-1.09; I2=0%) was found.
CONCLUSION
We conclude that trials with inadequate reporting of cointerventions showed larger treatment effect estimates, potentially indicating overestimation of therapeutic benefit.
TRIAL REGISTRATION
Prospero Identifier: CRD42017072522
Impact of PGL-I Seropositivity on the Protective Effect of BCG Vaccination among Leprosy Contacts: A Cohort Study
Although leprosy has become a neglected disease, it is an important cause of disability, and 250,000 new cases are still diagnosed worldwide every year. The current study was carried out in Brazil, where almost 40,000 new cases of leprosy are diagnosed every year. The study targeted contacts of leprosy patients, who are at the highest risk of contracting the disease. We studied 2,135 contacts who were diagnosed at the Leprosy Outpatient Clinic at the Oswaldo Cruz Foundation in Rio de Janeiro, RJ, Brazil, between 1987 and 2007. The presence of antibodies against a specific Mycobacterium leprae antigen (PGL-I) at the first examination and BCG vaccination status were evaluated. PGL-I-positive contacts had a higher risk of developing leprosy than PGL-I-negative contacts. Among the former, vaccinated contacts were at higher risk than unvaccinated contacts. Our results indicate that contact examination combined with PGL-I testing and BCG vaccination appears to justify the targeting of PGL-I-positive individuals for enhanced surveillance. Furthermore, it is highly recommended that PGL-I-positive contacts and contacts with a high familial bacterial index (i.e., the sum of results from index and co-prevalent cases), regardless of serological response, should be monitored. This group could be considered as a target for chemoprophylaxis
Safety and Short-term Outcomes of High-Dose Erythropoietin in Preterm Infants With Intraventricular Hemorrhage: The EpoRepair Randomized Clinical Trial.
IMPORTANCE
Intraventricular hemorrhage (IVH) is a major cause of neonatal morbidity and mortality in preterm infants without a specific medical treatment to date.
OBJECTIVE
To assess the safety and short-term outcomes of high-dose erythropoietin in preterm infants with IVH.
DESIGN, SETTING, AND PARTICIPANTS
Between April 1, 2014, and August 3, 2018, a randomized double-blind clinical trial enrolled 121 preterm infants (gestational age <32 weeks or birth weight <1500 g) aged 8 or less days with moderate to severe IVH identified by cerebral ultrasonography from 8 Swiss and Austrian tertiary neonatal units. Statistical analyses were performed between October 1, 2019, and September 12, 2022.
INTERVENTIONS
Infants received intravenous high-dose erythropoietin (2000 units/kg body weight) or placebo at 4 time points between weeks 1 and 4 of life.
MAIN OUTCOMES AND MEASURES
Secondary outcomes included (1) mortality and morbidity rates and (2) brain magnetic resonance imaging findings at term-equivalent age (TEA). The primary outcome was the composite intelligence quotient at 5 years of age (not available before 2023).
RESULTS
Sixty infants (48% male [n = 29]) were randomly assigned to receive erythropoietin, and 61 infants (61% male [n = 37]) were randomly assigned to receive placebo. The median birth weight was 832 g (IQR, 687-990 g) in the erythropoietin group and 870 g (IQR, 680-1110 g) in the placebo group. Median gestation was 26.1 weeks (IQR, 24.8-27.3 weeks) in the erythropoietin group and 27.0 weeks (24.9-28.1 weeks) in the placebo group. The 2 groups had similar baseline characteristics and morbidities. Up to TEA, 10 newborns died (16.7%) in the erythropoietin group, and 5 newborns (8.2%) died in the placebo group (adjusted odds ratio, 2.24 [95% CI, 0.74-7.66]; P = .15). Infants receiving erythropoietin had higher mean hematocrit levels. Conventional magnetic resonance imaging at TEA for 100 infants showed no significant differences in global or regional brain injury scores.
CONCLUSIONS AND RELEVANCE
This preliminary report of a randomized clinical trial found no evidence that high-dose erythropoietin in preterm infants with IVH affects brain injury scores on conventional magnetic resonance imaging at TEA. Higher mortality in the erythropoietin group was not significant but should be reassessed based on future results from similar trials.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02076373
Safety and Short-term Outcomes of High-Dose Erythropoietin in Preterm Infants With Intraventricular Hemorrhage: The EpoRepair Randomized Clinical Trial
IMPORTANCE
Intraventricular hemorrhage (IVH) is a major cause of neonatal morbidity and mortality in preterm infants without a specific medical treatment to date.
OBJECTIVE
To assess the safety and short-term outcomes of high-dose erythropoietin in preterm infants with IVH.
DESIGN, SETTING, AND PARTICIPANTS
Between April 1, 2014, and August 3, 2018, a randomized double-blind clinical trial enrolled 121 preterm infants (gestational age <32 weeks or birth weight <1500 g) aged 8 or less days with moderate to severe IVH identified by cerebral ultrasonography from 8 Swiss and Austrian tertiary neonatal units. Statistical analyses were performed between October 1, 2019, and September 12, 2022.
INTERVENTIONS
Infants received intravenous high-dose erythropoietin (2000 units/kg body weight) or placebo at 4 time points between weeks 1 and 4 of life.
MAIN OUTCOMES AND MEASURES
Secondary outcomes included (1) mortality and morbidity rates and (2) brain magnetic resonance imaging findings at term-equivalent age (TEA). The primary outcome was the composite intelligence quotient at 5 years of age (not available before 2023).
RESULTS
Sixty infants (48% male [n = 29]) were randomly assigned to receive erythropoietin, and 61 infants (61% male [n = 37]) were randomly assigned to receive placebo. The median birth weight was 832 g (IQR, 687-990 g) in the erythropoietin group and 870 g (IQR, 680-1110 g) in the placebo group. Median gestation was 26.1 weeks (IQR, 24.8-27.3 weeks) in the erythropoietin group and 27.0 weeks (24.9-28.1 weeks) in the placebo group. The 2 groups had similar baseline characteristics and morbidities. Up to TEA, 10 newborns died (16.7%) in the erythropoietin group, and 5 newborns (8.2%) died in the placebo group (adjusted odds ratio, 2.24 [95% CI, 0.74-7.66]; P = .15). Infants receiving erythropoietin had higher mean hematocrit levels. Conventional magnetic resonance imaging at TEA for 100 infants showed no significant differences in global or regional brain injury scores.
CONCLUSIONS AND RELEVANCE
This preliminary report of a randomized clinical trial found no evidence that high-dose erythropoietin in preterm infants with IVH affects brain injury scores on conventional magnetic resonance imaging at TEA. Higher mortality in the erythropoietin group was not significant but should be reassessed based on future results from similar trials.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02076373
Cancer Predisposition Cascade Screening for Hereditary Breast/Ovarian Cancer and Lynch Syndromes in Switzerland: Study Protocol
Background : Breast, colorectal, ovarian, and endometrial cancers constitute approximately 30% of newly diagnosed cancer cases in Switzerland, affecting more than 12,000 individuals annually. Hundreds of these patients are likely to carry germline pathogenic variants associated with hereditary breast ovarian cancer (HBOC) or Lynch syndrome (LS). Genetic services (counseling and testing) for hereditary susceptibility to cancer can prevent many cancer diagnoses and deaths through early identification and risk management. Objective : Cascade screening is the systematic identification and testing of relatives of a known mutation carrier. It determines whether asymptomatic relatives also carry the known variant, needing management options to reduce future harmful outcomes. Specific aims of the CASCADE study are to (1) survey index cases with HBOC or LS from clinic-based genetic testing records and determine their current cancer status and surveillance practices, needs for coordination of medical care, psychosocial needs, patient-provider and patient-family communication, quality of life, and willingness to serve as advocates for cancer genetic services to blood relatives, (2) survey first- and second-degree relatives and first-cousins identified from pedigrees or family history records of HBOC and LS index cases and determine their current cancer and mutation status, cancer surveillance practices, needs for coordination of medical care, barriers and facilitators to using cancer genetic services, psychosocial needs, patient-provider and patient-family communication, quality of life, and willingness to participate in a study designed to increase use of cancer genetic services, and (3) explore the influence of patient-provider communication about genetic cancer risk on patient-family communication and the acceptability of a family-based communication, coping, and decision support intervention with focus group(s) of mutation carriers and relatives. Methods: CASCADE is a longitudinal study using surveys (online or paper/pencil) and focus groups, designed to elicit factors that enhance cascade genetic testing for HBOC and LS in Switzerland. Repeated observations are the optimal way for assessing these outcomes. Focus groups will examine barriers in patient-provider and patient-family communication, and the acceptability of a family-based communication, coping, and decision-support intervention. The survey will be developed in English, translated into three languages (German, French, and Italian), and back-translated into English, except for scales with validated versions in these languages. Results: Descriptive analyses will include calculating means, standard deviations, frequencies, and percentages of variables and participant descriptors. Bivariate analyses (Pearson correlations, chi-square test for differences in proportions, and t test for differences in means) will assess associations between demographics and clinical characteristics. Regression analyses will incorporate generalized estimating equations for pairing index cases with their relatives and explore whether predictors are in direct, mediating, or moderating relationship to an outcome. Focus group data will be transcribed verbatim and analyzed for common themes. Conclusions: Robust evidence from basic science and descriptive population-based studies in Switzerland support the necessity of cascade screening for genetic predisposition to HBOC and LS. CASCADE is designed to address translation of this knowledge into public health interventions. Trial Registration: ClinicalTrials.gov NCT03124212; https://clinicaltrials.gov/ct2/show/NCT03124212 (Archived by WebCite at http://www.webcitation.org/6tKZnNDBt
Critical exponents and equation of state of the three-dimensional Heisenberg universality class
We improve the theoretical estimates of the critical exponents for the
three-dimensional Heisenberg universality class. We find gamma=1.3960(9),
nu=0.7112(5), eta=0.0375(5), alpha=-0.1336(15), beta=0.3689(3), and
delta=4.783(3). We consider an improved lattice phi^4 Hamiltonian with
suppressed leading scaling corrections. Our results are obtained by combining
Monte Carlo simulations based on finite-size scaling methods and
high-temperature expansions. The critical exponents are computed from
high-temperature expansions specialized to the phi^4 improved model. By the
same technique we determine the coefficients of the small-magnetization
expansion of the equation of state. This expansion is extended analytically by
means of approximate parametric representations, obtaining the equation of
state in the whole critical region. We also determine a number of universal
amplitude ratios.Comment: 40 pages, final version. In publication in Phys. Rev.
Current Approaches to the Management of Sentinel Node Procedures in Early Vulvar Cancer in Germany : A Web-Based Nationwide Analysis of Practices
Background: Lymph node involvement is the most important prognostic factor for recurrence and survival in vulvar cancer. Sentinel node (SN) procedure can be offered in well-selected
patients with early vulvar cancer. This study aimed to assess current management practices with
respect to the sentinel node procedure in women with early vulvar cancer in Germany. Methods: A
Web-based survey was conducted. Questionnaires were e-mailed to 612 gynecology departments.
Data were summarized as frequencies and analyzed using the chi-square test. Results: A total of
222 hospitals (36.27%) responded to the invitation to participate. Among the responders, 9.5% did
not offer the SN procedure. However, 79.5% evaluated SNs by ultrastaging. In vulvar cancer of the
midline with unilateral localized positive SN, 49.1% and 48.6% of respondents, respectively, would
perform ipsilateral or bilateral inguinal lymph node dissection. Repeat SN procedure was performed
by 16.2% of respondents. For isolated tumor cells (ITCs) or micrometastases, 28.1% and 60.5% of
respondents, respectively, would perform inguinal lymph node dissection, whereas 19.3% and 23.8%,
respectively, would opt for radiation without further surgical intervention. Notably, 50.9% of respondents would not initiate any further therapy and 15.1% would opt for expectant management.
Conclusions: The majority of German hospitals implement the SN procedure. However, only 79.5%
of respondents performed ultrastaging and only 28.1% were aware that ITC may affect survival in
vulvar cancer. There is a need to ensure that the management of vulvar cancer follows the latest
recommendations and clinical evidence. Deviations from state-of-the-art management should only
be after a detailed discussion with the concerned patient
Measurement of the cross-section and charge asymmetry of bosons produced in proton-proton collisions at TeV with the ATLAS detector
This paper presents measurements of the and cross-sections and the associated charge asymmetry as a
function of the absolute pseudorapidity of the decay muon. The data were
collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with
the ATLAS experiment at the LHC and correspond to a total integrated luminosity
of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements
varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the
1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured
with an uncertainty between 0.002 and 0.003. The results are compared with
predictions based on next-to-next-to-leading-order calculations with various
parton distribution functions and have the sensitivity to discriminate between
them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables,
submitted to EPJC. All figures including auxiliary figures are available at
https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13
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