Transcatheter or Surgical Treatment of Aortic-Valve Stenosis

Eurosurveillance

Background Women are overrepresented among individuals with post-acute sequelae of SARS-CoV-2 infection (PASC). Biological (sex) as well as sociocultural (gender) differences between women and men might account for this imbalance, yet their impact on PASC is unknown. Aim We assessed the impact of sex and gender on PASC in a Swiss population. Method Our multicentre prospective cohort study included 2,856 (46% women, mean age 44.2 ± 16.8 years) outpatients and hospitalised patients with PCR-confirmed SARS-CoV-2 infection. Results Among those who remained outpatients during their first infection, women reported persisting symptoms more often than men (40.5% vs 25.5% of men; p < 0.001). This sex difference was absent in hospitalised patients. In a crude analysis, both female biological sex (RR = 1.59; 95% CI: 1.41–1.79; p < 0.001) and a score summarising gendered sociocultural …

Journal of Cardiovascular Magnetic Resonance

Background: The presence of myocardial scar is associated with poor prognosis in several settings. Clinically silent “unrecognized myocardial scar”(UMS) can be revealed by Late-gadolinium-enhancement (LGE) cardiovascular magnetic resonance (CMR) imaging. This population-based CMR study evaluated risk factors and patterns of UMS.Methods: Participants of the Hamburg City Health study without a history of coronary heart disease or myocarditis were consecutively included between February 8 th, 2016, and November 7 th, 2018. Presences and patterns of UMS were assessed by standard-phase-sensitive-inversion-recovery (PSIR) LGE CMR. Risk factors for the presence of UMS were assessed by multivariable, logistic regression analyses.Results: The final study population consisted of 1064 individuals (median age 66 [quartiles 59; 71] years, 37% females). UMS was detected in 244 (23%) subjects …

Scientific Reports

" Open Access funding enabled and organized by Projekt DEAL. We acknowledge financial support from the Open Access Publication Fund of UKE—Universitätsklinikum Hamburg-Eppendorf and DFG—German Research Foundation. The HCHS is supported by the Innovative medicine initiative (Grant number 116074), by the Joachim Herz Foundation, by the Foundation Leducq (Grant number 16 CVD 03), by the euCanSHare grant agreement (Grant number 825903-euCanSHare H2020), and the Deutsche Forschungsgemeinschaft (Grant number TH1106/5-1; AA93/2-1). Furthermore, it is supported by the participating institutes and departments from the University Medical Centre Hamburg-Eppendorf, which contribute with individual and scaled budgets to the overall funding. Technical equipment is provided by SIEMENS according to a contract for 12 years, the Schiller AG on a loan basis for six years, and Topcon …

Journal of Cardiovascular Magnetic Resonance

Background: The presence of myocardial scar is associated with poor prognosis in several settings. Clinically silent “unrecognized myocardial scar”(UMS) can be revealed by Late-gadolinium-enhancement (LGE) cardiovascular magnetic resonance (CMR) imaging. This population-based CMR study evaluated risk factors and patterns of UMS.Methods: Participants of the Hamburg City Health study without a history of coronary heart disease or myocarditis were consecutively included between February 8 th, 2016, and November 7 th, 2018. Presences and patterns of UMS were assessed by standard-phase-sensitive-inversion-recovery (PSIR) LGE CMR. Risk factors for the presence of UMS were assessed by multivariable, logistic regression analyses.Results: The final study population consisted of 1064 individuals (median age 66 [quartiles 59; 71] years, 37% females). UMS was detected in 244 (23%) subjects …

Die Diagnostik eines Myokardinfarktes ist mittels laborchemischer Analysen kardialer Marker, vor allem des hochsensitiven kardialen Troponins, mit hoher Spezifität und Sensitivität möglich und in Zusammenschau mit der entsprechenden Symptomatik und EKG-Veränderungen etabliert. Nach herzchirurgischen Eingriffen kann eine Troponinfreisetzung als Ausdruck einer prozeduralen Myokardschädigung auftreten. Ursachen hierfür sind beispielsweise Manipulation am Myokard oder die Verwendung von Kardioplegie bei Herzoperationen. Hierdurch ist die Diagnose eines perioperativen Myokardinfarktes jedoch herausfordernd, aber von höchster klinischer Relevanz. Studien zeigten, dass erhöhte Troponinwerte innerhalb der ersten 48 h postoperativ mit einer erhöhten Mortalität nach herzchirurgischem Eingriff korrelieren. Die B‑ACS-Pilotstudie untersuchte die Troponindynamik von 412 kardiochirurgischen …

medRxiv

Lipoprotein (a) [LP(a)] is a risk factor for cardiovascular diseases and mainly regulated by the complex LPA gene. We investigated the types of variation in the LPA gene and their predictive performance on LP(a) concentration. We determined the Kringle IV-type 2 (KIV-2) copy number (CN) using the DRAGEN LPA Caller (DLC) and a read-depth based CN estimator in 8351 whole genome sequencing samples from the GENESIS-HD study. The pentanucleotide repeat in the promoter region was genotyped with GangSTR and ExpansionHunter. LP(a) concentration was available in 4861 population-based subjects. Predictive performance on LP(a) concentration was investigated using random forests. The agreement of the KIV-2 CN between the two specialized callers was high (r=0.9966; 95% confidence interval [CI] 0.9965-0.9968). Allele-specific KIV-2 CN could be determined in 47.0% of the subjects using the DLC. Lp(a) concentration can be better predicted from allele-specific KIV-2 CN than total KIV-2 CN. Two single nucleotide variants 4925G>A and rs41272114 further improved prediction. The genetically complex LPA gene can be analyzed with excellent agreement between different callers. The allele-specific KIV-2 CN is more important for predicting LP(a) concentration than the total KIV-2 CN. It would be important that the allele-specific KIV-2 CN is determinable in all subjects.

Journal of Cardiovascular Magnetic Resonance

Background: The left atrial volume (LAV) is a crucial cardiac parameter in several clinical settings such as in atrial fibrillation or heart failure for the assessment of diastolic dysfunction and cardiac risk. Currently available LAV reference values were defined by 2d transthoracic echocardiography (2d-TTE). However, LAV measurements are routine part of CMR protocols, though data on the interchangeability of LAV values between CMR and 2d-TTE remain scarce.Methods: We performed CMR (3 T scanner MAGNETOM™ Skyra, Siemens Healthineers, Erlangen, Germany) and 2d-TTE in 2126 participants of the Hamburg City Health Study (HCHS), a population-based cohort study of the middle-aged population in Hamburg. LAV was assessed in TTE from the 4-and 2-chamber view by the method of disk summation. In CMR, LAV was also measured in cine images from the 2-and 4-chamber orientation, employing the …

Elife

The link between metabolic syndrome (MetS) and neurodegenerative as well as cerebrovascular conditions holds substantial implications for brain health in at-risk populations. This study elucidates the complex relationship between MetS and brain health by conducting a comprehensive examination of cardiometabolic risk factors, brain morphology, and cognitive function in 40,087 individuals. Multivariate, data-driven statistics identified a latent dimension linking more severe MetS to widespread brain morphological abnormalities, accounting for up to 71% of shared variance in the data. This dimension was replicable across sub-samples. In a mediation analysis, we could demonstrate that MetS-related brain morphological abnormalities mediated the link between MetS severity and cognitive performance in multiple domains. Employing imaging transcriptomics and connectomics, our results also suggest that MetS-related morphological abnormalities are linked to the regional cellular composition and macroscopic brain network organization. By leveraging extensive, multi-domain data combined with a dimensional stratification approach, our analysis provides profound insights into the association of MetS and brain health. These findings can inform effective therapeutic and risk mitigation strategies aimed at maintaining brain integrity.

European Heart Journal: Acute Cardiovascular Care

Aims High-sensitivity cardiac troponin (hs-cTn) assays are used for detection of myocardial infarction (MI). Ninety-ninth percentiles show wide inter-assay variation. The use of sex-specific cut-offs is recommended as definitory cut-off for MI. We compared diagnostic performance and prognostic value of sex-specific 99th percentiles of four hs-cTn assays in patients with suspected MI. Methods and results Concentrations of four hs-cTn assays were measured at presentation and after 3 h in patients with suspected MI. Final diagnoses were adjudicated according to the 4th Universal Definition of MI. Unisex and sex-specific 99th percentiles were evaluated as diagnostic cut-offs following the ESC 0/3 h algorithm. These cut-offs were used in Cox-regression analyses to investigate the association with a composite endpoint of MI, revascularization, cardiac rehospitalization, and death …

Journal of Cardiovascular Magnetic Resonance

BackgroundThe presence of myocardial scar is associated with poor prognosis in several underlying diseases. Late-gadolinium-enhancement (LGE) cardiovascular magnetic resonance (CMR) imaging reveals clinically silent “unrecognized myocardial scar” (UMS), but the etiology of UMS often remains unclear. This population-based CMR study evaluated prevalence, localization, patterns and risk factors of UMS.MethodsThe study population consisted of 1064 consecutive Hamburg City Health study participants without a history of coronary heart disease or myocarditis. UMS was assessed by standard-phase-sensitive-inversion-recovery LGE CMR.ResultsMedian age was 66 [quartiles 59,71] years and 37% were females. UMS was detected in 244 (23%) participants. Twenty-five participants (10%) had ischemic, and 217 participants (89%) had non-ischemic scar patterns, predominantly involving the basal …

Imaging Neuroscience

We aimed to replicate recent findings on the association between the extent of cerebral small vessel disease (cSVD), functional brain network dedifferentiation, and cognitive impairment. We analyzed demographic, imaging, and behavioral data from the prospective population-based Hamburg City Health Study. Using a fully prespecified analysis pipeline, we estimated discrete brain states from structural and resting-state functional magnetic resonance imaging (MRI). In a multiverse analysis, we varied brain parcellations and functional MRI confound regression strategies. The severity of cSVD was operationalized as the volume of white matter hyperintensities of presumed vascular origin. Processing speed and executive dysfunction were quantified using the Trail Making Test (TMT). We hypothesized a) that a greater volume of supratentorial white matter hyperintensities would be associated with less …

ESC Heart Failure

Aims Cardiomyopathies (CMPs) are a heterogeneous group of diseases that are defined by structural and functional abnormalities of the cardiac muscle. Dilated cardiomyopathy (DCM), the most common CMP, is defined by left ventricular dilation and impaired contractility and represents a common cause of heart failure. Different phenotypes result from various underlying genetic and acquired causes with variable effects on disease development and progression, prognosis, and response to medical treatment. Current treatment algorithms do not consider these different aetiologies, due to lack of insights into treatable drivers of cardiac failure in patients with DCM. Our study aims to precisely phenotype and genotype the various subtypes of DCM and hereby lay the foundation for individualized therapy. Methods and results The Geno‐ And Phenotyping of PrImary Cardiomyopathy (GrAPHIC) is a currently ongoing …

Plos one

Considering sex as a biological variable in modern digital health solutions, we investigated sex-specific differences in the trajectory of four physiological parameters across a COVID-19 infection. A wearable medical device measured breathing rate, heart rate, heart rate variability, and wrist skin temperature in 1163 participants (mean age = 44.1 years, standard deviation [SD] = 5.6; 667 [57%] females). Participants reported daily symptoms and confounders in a complementary app. A machine learning algorithm retrospectively ingested daily biophysical parameters to detect COVID-19 infections. COVID-19 serology samples were collected from all participants at baseline and follow-up. We analysed potential sex-specific differences in physiology and antibody titres using multilevel modelling and t-tests. Over 1.5 million hours of physiological data were recorded. During the symptomatic period of infection, men demonstrated larger increases in skin temperature, breathing rate, and heart rate as well as larger decreases in heart rate variability than women. The COVID-19 infection detection algorithm performed similarly well for men and women. Our study belongs to the first research to provide evidence for differential physiological responses to COVID-19 between females and males, highlighting the potential of wearable technology to inform future precision medicine approaches.

Plos one

Background Non-communicable diseases (NCDs) are responsible for many deaths. They are associated with several modifiable and metabolic risk factors and are therefore prone to significant regional variations on different scales. However, only few intra-urban studies examined spatial variation in NCDs and its association with social circumstances, especially in Germany. Thus, the present study aimed to identify associations of personal risk factors and local social conditions with NCDs in a large German city. Methods This study is based on a population-based cohort of the Hamburg City Health Study including 10,000 probands. Six NCDs were analyzed (chronic obstructive pulmonary disease [COPD], coronary heart disease [CHD], diabetes mellitus, heart failure, depression, and hypertension) in 68 city district clusters. As risk factors, we considered socio-demographic variables (age, sex, education) and risk behaviour variables (smoking, alcohol consumption). Logistic regression analyses identified associations between the district clusters and the prevalence rates for each NCD. Regional variation was detected by Gini coefficients and spatial cluster analyses. Local social condition indexes were correlated with prevalence rates of NCDs on city district level and hot-spot analyses were performed for significant high or low values. Results The analyses included 7,308 participants with a mean age of 63.1 years (51.5% female). The prevalence of hypertension (67.6%) was the highest. Risk factor associations were identified between smoking, alcohol consumption and education and the prevalence of NCDs (hypertension, diabetes, and COPD …

Frontiers in Immunology

In search for immunological correlates of protection against acute coronavirus disease 2019 (COVID-19) there is a need for high through-put assays for cell-mediated immunity (CMI) to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We established an interferon-γ release assay -based test for detection of CMI against SARS-CoV-2 spike (S) or nucleocapsid (NC) peptides. Blood samples obtained from 549 healthy or convalescent individuals were measured for interferon-γ (IFN-γ) production after peptide stimulation using a certified chemiluminescence immunoassay. Test performance was calculated applying cutoff values with the highest Youden indices in receiver-operating-characteristics curve analysis and compared to a commercially available serologic test. Potential confounders and clinical correlates were assessed for all test systems. 522 samples obtained from 378 convalescent in median 298 days after PCR-confirmed SARS-CoV-2 infection and 144 healthy control individuals were included in the final analysis. CMI testing had a sensitivity and specificity of up to 89% and 74% for S peptides and 89% and 91% for NC peptides, respectively. High white blood cell counts correlated negatively with IFN-γ responses but there was no CMI decay in samples obtained up to one year after recovery. Severe clinical symptoms at time of acute infection were associated with higher measures of adaptive immunity and reported hair loss at time of examination. This laboratory-developed test for CMI to SARS-CoV-2 NC peptides exhibits excellent test performance, is suitable for high through-put routine diagnostics, and should …

American journal of respiratory and critical care medicine

Rationale: Coronavirus disease 2019 (COVID-19) can lead to acute respiratory distress syndrome with fatal outcomes. Evidence suggests that dysregulated immune responses, including autoimmunity, are key pathogenic factors. Objectives: To assess whether IgA autoantibodies target lung-specific proteins and contribute to disease severity. Methods: We collected 147 blood, 9 lung tissue, and 36 BAL fluid samples from three tertiary hospitals in Switzerland and one in Germany. Severe COVID-19 was defined by the need to administer oxygen. We investigated the presence of IgA autoantibodies and their effects on pulmonary surfactant in COVID-19 using the following methods: immunofluorescence on tissue samples, immunoprecipitations followed by mass spectrometry on BAL fluid samples, enzyme-linked immunosorbent assays on blood samples, and surface tension measurements with medical surfactant …

Diseases of the heart and brain are strongly linked to each other, and cardiac dysfunction is associated with cognitive decline and dementia. This link between cardiovascular disease and dementia offers opportunities for dementia prevention through prevention and treatment of cardiovascular risk factors and heart disease. Increasing evidence suggests the clinical utility of cardiac biomarkers as risk markers for structural brain changes and cognitive impairment. We propose the hypothesis that structural brain changes are the link between impaired cardiac function, as captured by blood‐based cardiac biomarkers, and cognitive impairment. This review provides an overview of the literature and illustrates emerging insights into the association of markers of hemodynamic stress (natriuretic peptides) and markers of myocardial injury (cardiac troponins) with imaging findings of brain damage and cognitive impairment …

Journal of the American Heart Association

Background High‐sensitivity cardiac troponin (hs‐cTn)‐based diagnostic algorithms are recommended for the management of patients with suspected myocardial infarction (MI) without ST elevation. Although mirroring different phases of myocardial injury, falling and rising troponin patterns (FPs and RPs, respectively) are equally considered by most algorithms. We aimed to compare the performance of diagnostic protocols for RPs and FPs, separately. Methods and Results We pooled 2 prospective cohorts of patients with suspected MI and stratified patients to stable, FP, and RP during serial sampling separately for hs‐cTnI and hs‐cTnT and applied the European Society of Cardiology 0/1‐ and 0/3‐hour algorithms comparing the positive predictive values to rule in MI. Overall, 3523 patients were included in the hs‐cTnI study population. The positive predictive value for patients with an FP was significantly reduced …

Annals of emergency medicine

Study objectiveThe diagnostic performance of T-wave amplitudes for the detection of myocardial infarction is largely unknown. We aimed to address this knowledge gap.MethodsT-wave amplitudes were automatically measured in 12-lead ECGs of patients presenting with acute chest discomfort to the emergency department within a prospective diagnostic multicenter study. The final diagnosis was centrally adjudicated by 2 independent cardiologists. Patients with left ventricular hypertrophy, complete left bundle branch block, or paced ventricular depolarization were excluded. The performance for lead-specific 95th-percentile thresholds were reported as likelihood ratios (lr), specificity, and sensitivity.ResultsMyocardial infarction was the final diagnosis in 445 (18%) of 2457 patients. In most leads, T-wave amplitudes tended to be greater in patients without myocardial infarction than those with myocardial infarction …

New England Journal of Medicine

Background Most trials that have shown a benefit of beta-blocker treatment after myocardial infarction included patients with large myocardial infarctions and were conducted in an era before modern biomarker-based diagnosis of myocardial infarction and treatment with percutaneous coronary intervention, antithrombotic agents, high-intensity statins, and renin–angiotensin–aldosterone system antagonists. Methods In a parallel-group, open-label trial performed at 45 centers in Sweden, Estonia, and New Zealand, we randomly assigned patients with an acute myocardial infarction who had undergone coronary angiography and had a left ventricular ejection fraction of at least 50% to receive either long-term treatment with a beta-blocker (metoprolol or bisoprolol) or no beta-blocker treatment. The primary end point was a composite of death from any cause or new myocardial infarction. Results From September …

New England Journal of Medicine

Background Electronic nicotine-delivery systems — also called e-cigarettes — are used by some tobacco smokers to assist with quitting. Evidence regarding the efficacy and safety of these systems is needed. Methods In this open-label, controlled trial, we randomly assigned adults who were smoking at least five tobacco cigarettes per day and who wanted to set a quit date to an intervention group, which received free e-cigarettes and e-liquids, standard-of-care smoking-cessation counseling, and optional (not free) nicotine-replacement therapy, or to a control group, which received standard counseling and a voucher, which they could use for any purpose, including nicotine-replacement therapy. The primary outcome was biochemically validated, continuous abstinence from smoking at 6 months. Secondary outcomes included participant-reported abstinence from tobacco and from any nicotine (including smoking …

New England Journal of Medicine

Background Food allergies are common and are associated with substantial morbidity; the only approved treatment is oral immunotherapy for peanut allergy. Methods In this trial, we assessed whether omalizumab, a monoclonal anti-IgE antibody, would be effective and safe as monotherapy in patients with multiple food allergies. Persons 1 to 55 years of age who were allergic to peanuts and at least two other trial-specified foods (cashew, milk, egg, walnut, wheat, and hazelnut) were screened. Inclusion required a reaction to a food challenge of 100 mg or less of peanut protein and 300 mg or less of the two other foods. Participants were randomly assigned, in a 2:1 ratio, to receive omalizumab or placebo administered subcutaneously (with the dose based on weight and IgE levels) every 2 to 4 weeks for 16 to 20 weeks, after which the challenges were repeated. The primary end point was ingestion of peanut …

New England Journal of Medicine

The Journal’s Historical “Indian Problem” Racism against Indigenous people infected Journal articles about civilization, Indigenous medicines, disease susceptibility, and possible Indigenous extinction, but the erasures are equally striking.

New England Journal of Medicine

Background Studies evaluating surgical-site infection have had conflicting results with respect to the use of alcohol solutions containing iodine povacrylex or chlorhexidine gluconate as skin antisepsis before surgery to repair a fractured limb (i.e., an extremity fracture). Methods In a cluster-randomized, crossover trial at 25 hospitals in the United States and Canada, we randomly assigned hospitals to use a solution of 0.7% iodine povacrylex in 74% isopropyl alcohol (iodine group) or 2% chlorhexidine gluconate in 70% isopropyl alcohol (chlorhexidine group) as preoperative antisepsis for surgical procedures to repair extremity fractures. Every 2 months, the hospitals alternated interventions. Separate populations of patients with either open or closed fractures were enrolled and included in the analysis. The primary outcome was surgical-site infection, which included superficial incisional infection within 30 days or …

New England Journal of Medicine

A Woman with Falls and Cognitive Decline An 82-year-old woman was admitted because of difficulty walking, falls, and cognitive decline. Light touch of the right hand, right knee, and both feet caused pain. A diagnosis was made.

New England Journal of Medicine

The Public Good on the Docket The Supreme Court has imposed new legal principles that impede the ability of states, Congress, and agencies to use evidence to protect the public. It now has the opportunity to reconsider this approach.

New England Journal of Medicine

Background The cardiovascular safety of testosterone-replacement therapy in middle-aged and older men with hypogonadism has not been determined. Methods In a multicenter, randomized, double-blind, placebo-controlled, noninferiority trial, we enrolled 5246 men 45 to 80 years of age who had preexisting or a high risk of cardiovascular disease and who reported symptoms of hypogonadism and had two fasting testosterone levels of less than 300 ng per deciliter. Patients were randomly assigned to receive daily transdermal 1.62% testosterone gel (dose adjusted to maintain testosterone levels between 350 and 750 ng per deciliter) or placebo gel. The primary cardiovascular safety end point was the first occurrence of any component of a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, assessed in a time-to-event analysis. A secondary cardiovascular end …

New England Journal of Medicine

Background Effective treatments for patients with primary biliary cholangitis are limited. Seladelpar, a peroxisome proliferator–activated receptor delta agonist, has potential benefits. Methods In this phase 3, 12-month, double-blind, placebo-controlled trial, we randomly assigned (in a 2:1 ratio) patients who had had an inadequate response to or who had a history of unacceptable side effects with ursodeoxycholic acid to receive oral seladelpar at a dose of 10 mg daily or placebo. The primary end point was a biochemical response, which was defined as an alkaline phosphatase level less than 1.67 times the upper limit of the normal range, with a decrease of 15% or more from baseline, and a normal total bilirubin level at month 12. Key secondary end points were normalization of the alkaline phosphatase level at month 12 and a change in the score on the pruritus numerical rating scale (range, 0 [no itch] to 10 …

New England Journal of Medicine

Background Food allergies are common and are associated with substantial morbidity; the only approved treatment is oral immunotherapy for peanut allergy. Methods In this trial, we assessed whether omalizumab, a monoclonal anti-IgE antibody, would be effective and safe as monotherapy in patients with multiple food allergies. Persons 1 to 55 years of age who were allergic to peanuts and at least two other trial-specified foods (cashew, milk, egg, walnut, wheat, and hazelnut) were screened. Inclusion required a reaction to a food challenge of 100 mg or less of peanut protein and 300 mg or less of the two other foods. Participants were randomly assigned, in a 2:1 ratio, to receive omalizumab or placebo administered subcutaneously (with the dose based on weight and IgE levels) every 2 to 4 weeks for 16 to 20 weeks, after which the challenges were repeated. The primary end point was ingestion of peanut …

New England Journal of Medicine

Background The addition of vancomycin to beta-lactam prophylaxis in arthroplasty may reduce surgical-site infections; however, the efficacy and safety are unclear. Methods In this multicenter, double-blind, superiority, placebo-controlled trial, we randomly assigned adult patients without known methicillin-resistant Staphylococcus aureus (MRSA) colonization who were undergoing arthroplasty to receive 1.5 g of vancomycin or normal saline placebo, in addition to cefazolin prophylaxis. The primary outcome was surgical-site infection within 90 days after surgery. Results A total of 4239 patients underwent randomization. Among 4113 patients in the modified intention-to-treat population (2233 undergoing knee arthroplasty, 1850 undergoing hip arthroplasty, and 30 undergoing shoulder arthroplasty), surgical-site infections occurred in 91 of 2044 patients (4.5%) in the vancomycin group and in 72 of 2069 patients (3 …

New England Journal of Medicine

Background Household air pollution is associated with stunted growth in infants. Whether the replacement of biomass fuel (e.g., wood, dung, or agricultural crop waste) with liquefied petroleum gas (LPG) for cooking can reduce the risk of stunting is unknown. Methods We conducted a randomized trial involving 3200 pregnant women 18 to 34 years of age in four low- and middle-income countries. Women at 9 to less than 20 weeks’ gestation were randomly assigned to use a free LPG cookstove with continuous free fuel delivery for 18 months (intervention group) or to continue using a biomass cookstove (control group). The length of each infant was measured at 12 months of age, and personal exposures to fine particulate matter (particles with an aerodynamic diameter of ≤2.5 μm) were monitored starting at pregnancy and continuing until the infants were 1 year of age. The primary outcome for which data are …

New England Journal of Medicine

Background Household air pollution is associated with stunted growth in infants. Whether the replacement of biomass fuel (e.g., wood, dung, or agricultural crop waste) with liquefied petroleum gas (LPG) for cooking can reduce the risk of stunting is unknown. Methods We conducted a randomized trial involving 3200 pregnant women 18 to 34 years of age in four low- and middle-income countries. Women at 9 to less than 20 weeks’ gestation were randomly assigned to use a free LPG cookstove with continuous free fuel delivery for 18 months (intervention group) or to continue using a biomass cookstove (control group). The length of each infant was measured at 12 months of age, and personal exposures to fine particulate matter (particles with an aerodynamic diameter of ≤2.5 μm) were monitored starting at pregnancy and continuing until the infants were 1 year of age. The primary outcome for which data are …

New England Journal of Medicine

Background Trials of surgical evacuation of supratentorial intracerebral hemorrhages have generally shown no functional benefit. Whether early minimally invasive surgical removal would result in better outcomes than medical management is not known. Methods In this multicenter, randomized trial involving patients with an acute intracerebral hemorrhage, we assessed surgical removal of the hematoma as compared with medical management. Patients who had a lobar or anterior basal ganglia hemorrhage with a hematoma volume of 30 to 80 ml were assigned, in a 1:1 ratio, within 24 hours after the time that they were last known to be well, to minimally invasive surgical removal of the hematoma plus guideline-based medical management (surgery group) or to guideline-based medical management alone (control group). The primary efficacy end point was the mean score on the utility-weighted modified Rankin …

New England Journal of Medicine

Background Nonalcoholic steatohepatitis (NASH) is a progressive liver disease with no approved treatment. Resmetirom is an oral, liver-directed, thyroid hormone receptor beta–selective agonist in development for the treatment of NASH with liver fibrosis. Methods We are conducting an ongoing phase 3 trial involving adults with biopsy-confirmed NASH and a fibrosis stage of F1B, F2, or F3 (stages range from F0 [no fibrosis] to F4 [cirrhosis]). Patients were randomly assigned in a 1:1:1 ratio to receive once-daily resmetirom at a dose of 80 mg or 100 mg or placebo. The two primary end points at week 52 were NASH resolution (including a reduction in the nonalcoholic fatty liver disease [NAFLD] activity score by ≥2 points; scores range from 0 to 8, with higher scores indicating more severe disease) with no worsening of fibrosis, and an improvement (reduction) in fibrosis by at least one stage with no worsening of …

New England Journal of Medicine

A Randomized Controlled Phase 3 Trial of Resmetirom in NASH with Liver Fibrosis - ePrints - Newcastle University Newcastle University Toggle Main Menu Toggle Search Home Browse Latest Policies About Home Browse Latest Policies About Open Access padlock ePrints Browse by author A Randomized Controlled Phase 3 Trial of Resmetirom in NASH with Liver Fibrosis Lookup NU author(s): Professor Pierre Bedossa, Professor Quentin AnsteeORCiD Downloads Full text for this publication is not currently held within this repository. Alternative links are provided below where available. Publication metadata Author(s): Harrison SA, Bedossa P, Guy CD, Schattenberg JM, Loomba R, Taub R, Labriola D, Moussa SE, Neff GW, Rinella ME, Anstee QM, Abdelmalek MF, Younossi Z, Baum S, Francque S, Charlton M, Newsome PN, Lanthier N, Schiefke I, Mangia A, Pericàs JM, Patil R, Sanyal AJ, Noureddin M, Bansal MB…

New England Journal of Medicine

HIV-1 Remission after Stem-Cell Transplantation A patient with a 33-year history of HIV-1 infection who underwent stem-cell transplantation for the treatment of acute myelogenous leukemia remained HIV-1 free nearly 5 years later.

New England Journal of Medicine

Background Reducing the levels of triglycerides and triglyceride-rich lipoproteins remains an unmet clinical need. Olezarsen is an antisense oligonucleotide targeting messenger RNA for apolipoprotein C-III (APOC3), a genetically validated target for triglyceride lowering. Methods In this phase 2b, randomized, controlled trial, we assigned adults either with moderate hypertriglyceridemia (triglyceride level, 150 to 499 mg per deciliter) and elevated cardiovascular risk or with severe hypertriglyceridemia (triglyceride level, ≥500 mg per deciliter) in a 1:1 ratio to either a 50-mg or 80-mg cohort. Patients were then assigned in a 3:1 ratio to receive monthly subcutaneous olezarsen or matching placebo within each cohort. The primary outcome was the percent change in the triglyceride level from baseline to 6 months, reported as the difference between each olezarsen group and placebo. Key secondary outcomes were …

New England Journal of Medicine

Background Subclinical atrial fibrillation is short-lasting and asymptomatic and can usually be detected only by long-term continuous monitoring with pacemakers or defibrillators. Subclinical atrial fibrillation is associated with an increased risk of stroke by a factor of 2.5; however, treatment with oral anticoagulation is of uncertain benefit. Methods We conducted a trial involving patients with subclinical atrial fibrillation lasting 6 minutes to 24 hours. Patients were randomly assigned in a double-blind, double-dummy design to receive apixaban at a dose of 5 mg twice daily (2.5 mg twice daily when indicated) or aspirin at a dose of 81 mg daily. The trial medication was discontinued and anticoagulation started if subclinical atrial fibrillation lasting more than 24 hours or clinical atrial fibrillation developed. The primary efficacy outcome, stroke or systemic embolism, was assessed in the intention-to-treat population (all the …

New England Journal of Medicine

Background Household air pollution is associated with stunted growth in infants. Whether the replacement of biomass fuel (e.g., wood, dung, or agricultural crop waste) with liquefied petroleum gas (LPG) for cooking can reduce the risk of stunting is unknown. Methods We conducted a randomized trial involving 3200 pregnant women 18 to 34 years of age in four low- and middle-income countries. Women at 9 to less than 20 weeks’ gestation were randomly assigned to use a free LPG cookstove with continuous free fuel delivery for 18 months (intervention group) or to continue using a biomass cookstove (control group). The length of each infant was measured at 12 months of age, and personal exposures to fine particulate matter (particles with an aerodynamic diameter of ≤2.5 μm) were monitored starting at pregnancy and continuing until the infants were 1 year of age. The primary outcome for which data are …