Credible Interval Research Articles

A Nationwide Physical Activity Intervention for 654,500 Adults in Singapore: Cost-Utility Analysis.

Increasing physical inactivity is a primary risk factor for diabetes and hypertension, contributing to rising health care expenditure and productivity losses. As Singapore's aging population grows, there is an increased disease burden on Singapore's health systems. Large-scale physical activity interventions could potentially reduce the disease burden but face challenges with the uncertainty of long-term health impact and high implementation costs, hindering their adoption. We examined the cost-effectiveness of the Singapore National Steps Challenge (NSC), an annual nationwide mobile health (mHealth) intervention to increase physical activity, from both the health care provider perspective, which only considers the direct costs, and the societal perspective, which considers both the direct and indirect costs. We used a Markov model to assess the long-term impact of increased physical activity from the NSC on adults aged 17 years and older. A Monte Carlo simulation with 1000 samples was conducted to compare two situations: the NSC conducted yearly for 10 years against a no-intervention situation with no NSC. The model projected inpatient and outpatient costs and mortality arising from diabetes and hypertension, as well as their complications. Health outcomes were expressed in terms of the quality-adjusted life-years (QALYs) gained. All future costs and QALYs were discounted at 3% per annum. Sensitivity analyses were done to test the robustness of our model results. We estimated that conducting the NSC yearly for 10 years with a mean cohort size of 654,500 participants was projected to prevent 6200 diabetes cases (95% credible interval 3700 to 9100), 10,500 hypertension cases (95% credible interval 6550 to 15,200), and 4930 deaths (95% credible interval 3260 to 6930). This led to a reduction in health care costs of SGD (Singapore dollar) 448 million (95% credible interval SGD 132 million to SGD 1.09 billion; SGD 1=US $0.73 for the year 2019). There would be 78,800 (95% credible interval 55,700 to 102,000) QALYs gained. Using a willingness-to-pay threshold of SGD 10,000 per QALY gained, the NSC would be cost-saving. When indirect costs were included, the NSC was estimated to reduce societal costs by SGD 1.41 billion (95% credible interval SGD 353 million to SGD 3.80 billion). The model was most sensitive to changes in the inpatient cost of treatment for diabetes complications, time horizon, and program compliance. In this modeling study, increasing physical activity by conducting a yearly nationwide physical activity intervention was cost-saving, preventing diabetes and hypertension and reducing mortality from these diseases. Our results provide important information for decision-making in countries that may consider introducing similar large-scale physical activity programs.

An Analysis of Type-I Generalized Progressive Hybrid Censoring for the One Parameter Logistic-Geometry Lifetime Distribution with Applications

Based on Type-I generalized progressive hybrid censored samples (GPHCSs), the parameter estimate for the unit-half logistic-geometry (UHLG) distribution is investigated in this work. Using maximum likelihood estimation (MLE) and Bayesian estimation, the parameters, reliability, and hazard functions of the UHLG distribution under GPHCSs have been assessed. Likewise, the computation is carried out for the asymptotic confidence intervals (ACIs). Furthermore, two bootstrap CIs, bootstrap-p and bootstrap-t, are mentioned. For symmetric loss functions, like squared error loss (SEL), and asymmetric loss functions, such as linear exponential loss (LL) and general entropy loss (GEL), there are specific Bayesian approximations. The Metropolis–Hastings samplers methodology were used to construct the credible intervals (CRIs). In conclusion, a genuine data set measuring the mortality statistics of a group of male mice with reticulum cell sarcoma is regarded as an application of the methods given.

A time-calibrated phylogeny of the diversification of Holoadeninae frogs.

The phylogeny of the major lineages of Amphibia has received significant attention in recent years, although evolutionary relationships within families remain largely neglected. One such overlooked group is the subfamily Holoadeninae, comprising 73 species across nine genera and characterized by a disjunct geographical distribution. The lack of a fossil record for this subfamily hampers the formulation of a comprehensive evolutionary hypothesis for their diversification. Aiming to fill this gap, we inferred the phylogenetic relationships and divergence times for Holoadeninae using molecular data and calibration information derived from the fossil record of Neobatrachia. Our inferred phylogeny confirmed most genus-level associations, and molecular dating analysis placed the origin of Holoadeninae in the Eocene, with subsequent splits also occurring during this period. The climatic and geological events that occurred during the Oligocene-Miocene transition were crucial to the dynamic biogeographical history of the subfamily. However, the wide highest posterior density intervals in our divergence time estimates are primarily attributed to the absence of Holoadeninae fossil information and, secondarily, to the limited number of sampled nucleotide sites.

Association Between Sex, Race, and Ethnicity and IVSedation Use in Patients Receiving Invasive Ventilation

BackgroundIntravenous sedation is an important tool for managing invasively ventilated patients, yet excess sedation is harmful, and dosing could be influenced by implicit bias. Research questionWhat is the association between sex, race and ethnicity, and sedation practices? MethodsWe performed a retrospective single-center cohort study of adults receiving invasive ventilation for 24 hours or more using the MIMIC-IV (2008-2019) database from Boston, USA. We used a repeated-measures design (4-hour intervals) to study the association between sex (female, male) or race and ethnicity (Asian, Black, Hispanic, White) and sedation outcomes. Sedation outcomes included sedative use (propofol, benzodiazepine, dexmedetomidine) and minimum sedation score. We categorized sedative use as follows: no sedative, then lowest, second, third, and highest quartiles of sedative dose. We adjusted for covariates with multilevel Bayesian proportional odds modeling and reported odds ratios (OR) with 95% credible intervals (CrI). ResultsWe studied 6,764 patients: 43% female; 3.5% Asian, 12% Black, 4.5% Hispanic and 80% White. Benzodiazepines were administered to 2,334 (36%) patients. Black patients received benzodiazepines less often and at lower doses than White patients (OR for more benzodiazepine 0.66, CrI 0.49-0.92). Propofol was administered to 3,865 (57%) patients. Female patients received propofol less often and at lower doses than male patients (OR for more propofol 0.72, CrI 0.61-0.86). Dexmedetomidine was administered to 1,439 (21%) patients, and use was similar across sex or race and ethnicity. Female patients were less sedated than male patients (OR for deeper sedation 0.71, CrI 0.62 to 0.81), and Black patients were more sedated than White patients (OR for more sedated 1.28, CrI 1.05 to 1.55). InterpretationAmong patients invasively ventilated for at least 24 hours, intravenous sedation and attained sedation levels varied by sex and race and ethnicity. Adherence to sedation guidelines may improve equity in sedation management for critically ill patients.

Retention processed placental membrane versus standard of care in treating diabetic foot ulcers.

Diabetic foot ulcers (DFUs) are a severe complication for diabetic patients, significantly impacting patient quality of life and healthcare system efficiency. Traditional standard of care (SOC) treatments are inadequate for many patients, necessitating the use of advanced wound care products, such as human placental membranes. We studied a real-world population of large, hard-to-heal and complicated wounds, otherwise under-studied in the wound care literature. To this end, we conducted a retrospective cohort analysis to compare the effectiveness of a human placental amnion/chorion membrane product using retention-based processing (RE-AC) and SOC in managing chronic DFUs. During the study period of September 2021 through April 2024, we collected retrospective observational data from electronic health records of 21 patients treated with RE-AC at three outpatient wound care centres. Additionally, 21 control SOC patients were matched from a wound registry using Coarsened Exact Matching. Patients were categorized into two cohorts based on whether they received RE-AC or SOC. Key metrics included wound size progression and wound closure. The analysis employed Bayesian regression and Hurdle Gamma Analysis of Covariance models. Despite their rather large size (average of 13.8 cm2), our results indicated that RE-AC achieved almost a 10% higher expected wound closure rate compared to SOC at 12 weeks (8.53% [credible interval: 5.60%-10.7%]). Further, for wounds that did not close, RE-AC resulted in a 93.6% (credible interval: 147.7%-41.6) improvement in expected Percent Area Reduction over the SOC group at 12 weeks. We noted that on average, SOC wounds stalled or grew larger. In terms of a risk ratio comparing the study group with SOC, we found a 52% benefit in the RE-AC group (RR = 1.52). The findings suggest that even with larger DFUs, R-AC is superior to SOC for wound closure and expected Percent Area Reduction by 12 weeks. This benefit likely leads to reduced treatment costs, optimized resource utilization and improved outcomes in the DFU patient population; ultimately resulting in improved patient care.

Estimating the impact of sarcoptic mange epidemic on the population size of wild raccoon dogs (Nyctereutes procyonoides) from wildlife rescue data

The impact of infectious diseases on host populations is often not quantified because it is difficult to observe the host population and infectious disease dynamics. To address this problem, we developed a state-space model to simultaneously estimate host population and disease dynamics using wildlife rescue data. Using this model, we aimed to quantify the impact of sarcoptic mange on a Japanese raccoon dog population by estimating the change in their relative population size. We classified the status of rescued raccoon dogs into four categories: i) rescued due to infection with mange, ii) rescued due to traffic accidents without mange, iii) rescued due to traffic accidents with mange, and iv) rescued due to causes other than traffic accidents or mange. We modelled the observation process for each category and fitted the model to the reported number of raccoon dogs rescued between 1990 and 2010 at three wildlife rescue facilities in Kanagawa Prefecture, Japan. The mortality rate induced by mange was estimated to be 1.09 (95% credible interval (CI): 0.47–1.72) per year. The estimated prevalence of sarcoptic mange ranged between 4–80% in the study period. When a substantial prevalence of mange was observed (1995 to 2002), the host population size decreased by 91.2% (95% credible intervals: 86.3–94.7). We show that the impact of infectious disease outbreak on the wildlife population can be estimated from the time-series data of wildlife rescue events due to multiple causes. Our estimates suggest that sarcoptic mange triggered a substantial decrease in the Japanese wild raccoon dog populations.

Epidemiologic Quantities for Monkeypox Virus Clade I from Historical Data with Implications for Current Outbreaks, Democratic Republic of the Congo.

We used published data from outbreak investigations of monkeypox virus clade I in the Democratic Republic of the Congo to estimate the distributions of critical epidemiological parameters. We estimated a mean incubation period of 9.9 days (95% credible interval [CrI] 8.5-11.5 days) and a mean generation time of 17.2 days (95% CrI 14.1-20.9 days) or 11.3 days (95% CrI 9.4-14.0 days), depending on the considered dataset. Presymptomatic transmission was limited. Those estimates suggest generally slower transmission dynamics in clade I than in clade IIb. The time-varying reproduction number for clade I in the Democratic Republic of the Congo was estimated to be below the epidemic threshold in the first half of 2024. However, in the South Kivu Province, where the newly identified subclade Ib has been associated with sustained human-to-human transmission, we estimated an effective reproduction number above the epidemic threshold (95% CrI 0.96-1.27).

Immuno-persistence after the 4th and 5th dose of inactivated polio vaccines in school-aged children

ObjectiveThis study aimed to assess the long-term persistence of neutralising antibodies (nAb) titres and seroprotection proportions after the 4th and 5th doses of inactivated polio vaccine (IPV). MethodsSerum samples from 299 children in Hong Kong were collected and used to estimate the persistence of nAb titres and seroprotection proportions by neutralisation test. ResultsThe mean nAb titres against polioviruses type 1, 2 and 3 (PV1, PV2 and PV3) one month after receiving the 4th dose of IPV at 19 months of age were 2,068 (95% credible interval: 1,517 – 2,864), 4,705 (3,439 – 6,436) and 2,758 (1,894 – 4,086), but declined substantially in 4 years to 268 (222 – 325), 751 (630 – 900), and 411 (323 – 521), respectively. Administration of the 5th dose of IPV restored nAb titres among children aged 6-7 years, and the decline in nAb titres was slightly slower with the estimated mean titres of 355 (272 – 462), 538 (427 – 681), and 548 (378 – 786) against PV1, PV2, and PV3 at 4 years post the 5th dose. We estimated that the proportion of children who were seroprotected against PV1, PV2 and PV3 would drop below 90% at: (i) 8.2, 10.8, 8.7 years after the 4th dose; and (ii) 11.6, 11.2, 11.0 years after the 5th dose. ConclusionsThe results revealed the immuno-persistence after the 4th and 5th dose of IPV and highlighted the importance of completing immunization series to ensure high vaccination coverage, particularly among children in the developing countries affected by the COVID-19 pandemic.

Outcomes with revascularisation versus conservative management of participants with 3-vessel coronary artery disease in the ISCHEMIA trial.

Whether revascularisation (REV) improves outcomes in patients with three-vessel coronary artery disease (3V-CAD) is uncertain. Our objective was to evaluate outcomes with REV (percutaneous coronary intervention [PCI] or coronary artery bypass graft surgery [CABG]) versus medical therapy in patients with 3V-CAD. ISCHEMIA participants with 3V-CAD on coronary computed tomography angiography without prior CABG were included. Outcomes following initial invasive management (INV) with REV (PCI or CABG) versus initial conservative management (CON) with medical therapy alone were evaluated. Regression modelling was used to estimate the outcomes if all participants were to undergo prompt REV versus those assigned to CON. Outcomes were cardiovascular (CV) death/myocardial infarction (MI), death, CV death, and quality of life. Bayesian posterior probability for benefit (Pr [benefit]) for 1 percentage point lower 4-year rates with REV versus CON were evaluated. Among 1,236 participants with 3V-CAD (612 INV/624 CON), REV was associated with lower 4-year CV death/MI (adjusted 4-year difference: -4.4, 95% credible interval [CrI] -8.7 to -0.3 percentage points, Pr [benefit]=94.8%) when compared with CON, with similar results for PCI versus CON (-5.8, 95% CrI: -10.8 to -0.5 percentage points, Pr [benefit]=96.4%) and CABG versus CON (-3.7, 95% CrI: -8.8 to 1.5 percentage points, Pr [benefit]=84.7%). Adjusted 4-year REV versus CON differences were as follows: death -1.2 (95% CrI: -4.7 to 2.2) percentage points, CV death -2.3 (95% CrI: -5.5 to 0.8) percentage points, with similar results for PCI and for CABG. The Pr (benefit) for death with REV (PCI or CABG) versus CON was 49-63%. The adjusted 12-month Seattle Angina Questionnaire-7 summary score differences favoured REV: REV versus CON 4.6 (95% CrI: 2.7-6.4) percentage points; PCI versus CON 3.6 (95% CrI: 1.2-5.8) percentage points and CABG versus CON 4.3 (95% CrI: 1.5-6.9) percentage points with high Pr (benefit). In participants with 3V-CAD, REV (either PCI or CABG) was associated with a lower 4-year CV death/MI rate and improved quality of life, with similar results for PCI versus CON and CABG versus CON. The differences in all-cause mortality between REV and CON were small with wide confidence intervals. (ClinicalTrials.gov: NCT01471522).

Multistructured Accretion Flow of Sgr A*. I. Examination of a Radiatively Inefficient Accretion Flow Model

The extreme low-luminosity supermassive black hole Sgr A* provides a unique laboratory in which to test models of radiatively inefficient accretion flows (RIAFs). Previous fits to the quiescent Chandra ACIS-S spectrum found that a RIAF model with an equal inflow–outflow balance works well. In this work, we apply the RIAF model to the Chandra HETG-S spectrum obtained through the Chandra X-ray Visionary Program, which displays features suggestive of temperature and velocity structures within the plasma. A comprehensive forward model analysis accounting for the accretion flow geometry and HETG-S instrumental effects is required for a full interpretation of the quiescent Chandra HETG-S spectrum. We present a RIAF model that takes these effects into account. Our fits to the high-resolution grating spectrum indicate an inflow balanced by an outflow (s ∼ 1) alongside a temperature profile that appears shallower than what would be expected from a gravitational potential following 1/r. The data require that the abundance of iron relative to solar is Z Fe < 0.32 Z ⊙ (90% credible interval), much lower than the 2 Z ⊙ metallicity measured in nearby late-type giants. While future missions like NewAthena will provide higher spectral resolution, source separation will continue to be a problem. Leveraging Chandra’s unparalleled spatial resolution, which is not expected to be surpassed for decades, remains essential for detailed investigations of the densely populated Galactic center in X-rays.

Cardiac Resynchronization Therapy in Ischemic Versus Nonischemic Cardiomyopathy: Patient-Level Meta-Analysis of 7 Randomized Clinical Trials

BackgroundData on whether cardiac resynchronization therapy (CRT) results in better clinical and echocardiographic outcomes in patients with nonischemic cardiomyopathy (NICM) vs ischemic cardiomyopathy (ICM) are conflicting. ObjectivesThe authors conducted this meta-analysis of 7 clinical trials of CRT to determine the association between etiology of cardiomyopathy and clinical and echocardiographic outcomes. MethodsThe authors analyzed patient-level data using Bayesian Hierarchical Weibull survival regression modeling to determine the association between etiology of cardiomyopathy and time to all-cause death or heart failure hospitalization (HFH). Linear regression was used to assess the association between etiology of cardiomyopathy and echocardiographic measurements. ResultsOf 6,252 patients included, 4,717 (75%) were men, median age was 66 years (IQR: 58-73 years), 3,704 (59%) had ICM, and 3,778 (60%) received CRT. CRT increased the time to HFH or all-cause death (HR: 0.67; 95% credible interval [CrI]: 0.56-0.82; P < 0.001) with no difference by etiology of cardiomyopathy (HR ratio: 1.06 [95% CrI: 0.87-1.29]; P = 0.57). Likewise, CRT increased the time to all-cause death (HR: 0.71 [95% CrI: 0.55-0.93]; P = 0.019) with no difference by etiology of cardiomyopathy (HR ratio: 1.06 [95% CrI: 0.80-1.43]; P = 0.70). Echocardiographic data that were available for 2,430 (39%) patients showed that CRT improvements in left ventricular ejection fraction, left ventricular end-diastolic diameter, and left ventricular end-systolic diameter were larger for patients with NICM. ConclusionsAlthough CRT led to greater increases in left ventricular ejection fraction and reductions in ventricular dimensions for patients with NICM compared with those with ICM, CRT significantly increased the time to HFH or all-cause death independently of the etiology of cardiomyopathy. Further studies on improving patient selection for CRT are needed.

Institutional Variation in PatientRadiationDoses During Transcatheter Valve Interventions: A Statewide Experience.

Little is known about institutional radiation doses during transcatheter valve interventions. The authors sought to evaluate institutional variability in radiation doses during transcatheter valve interventions. Using a large statewide registry, transcatheter edge-to-edge mitral valve repair, transcatheter mitral valve replacement, and transcatheter aortic valve replacement procedures between January 1, 2020, and December 31, 2022, with an air kerma (AK) recorded were analyzed. Patient and procedural characteristics were compared between cases with AK≥2 and<2 Gy. Associations of variables with AK≥2Gy were investigated using Bayesian random effects modeling and median ORs for the performing hospital. Among 9,446 procedures across 30 hospitals, median (Q1-Q3) procedural AK was 0.592Gy (0.348-0.989 Gy) with AK≥2Gy in 533 cases (5.6%). Wide variation in procedural AK was observed, with an institutional frequency of AK≥2Gy ranging from 0.0% to 29.5%. Bayesian modeling identified the performing hospital as more strongly associated with the odds of a procedural AK≥2Gy than any patient or procedural factors (hospital median OR: 3.54 [95% credible interval: 2.52-16.66]). In a large, multicenter state-wide registry, there is wide institutional variability in patient-level radiation doses during transcatheter valve interventions, with the performing hospital having a higher odds of an AK≥2Gy than any patient or procedural factors. Future interventions are warranted to reduce procedural-related variation in radiation exposure.

Use of a Liaison-Mediated Referral Strategy and Participation in Cardiac Rehabilitation After Percutaneous Coronary Intervention.

Cardiac rehabilitation (CR) improves outcomes following percutaneous coronary intervention (PCI) but remains underutilized. A liaison-mediated referral (LMR), where a health care professional explains CR's benefits, addresses barriers to participation, and places a referral before discharge, may promote CR use. Our objective was to assess the impact of an LMR on CR participation after PCI. This was a retrospective study of patients who underwent PCI across 48 hospitals in Michigan between January 2021 and April 2022 and referred to CR before discharge. Clinical registry data were linked to administrative claims to identify the primary outcome, CR participation, defined as ≥1 CR session within 90 days of discharge. Bayesian hierarchical logistic regression was used to compare CR participation between patients with and without an LMR. For the secondary outcome, frailty proportional hazard modeling compared days elapsed between discharge and first CR session between liaison cohorts. Among 9023 patients referred to CR after PCI, 4323 (47.9%) underwent an LMR (mean age, 69.3 [SD=11] years; 68.3% male) and 3390 (36.7%) attended ≥1 CR session within 90 days of discharge. The LMR cohort had a higher unadjusted CR participation rate (43.1% [95% CI, 41.5%-44.6%] versus 32.4% [95% CI, 31.1%-33.8%]; P<0.001), a higher adjusted odds ratio of attending ≥1 CR session (adjusted odds ratio, 1.21; 95% credible interval, 1.07-1.38), and a shorter delay in attending the first CR session compared with the non-LMR cohort (28 [interquartile range, 19-42] versus 33 [interquartile range, 21-47] days; P<0.001). An LMR was associated with higher odds of CR participation and may mitigate delays in CR enrollment. This referral strategy may improve CR participation and patient outcomes after PCI.

Modeling movements improves capture–recapture estimates for mobile species with sparse data: Polar bears (Ursus maritimus) in Viscount Melville sound

AbstractWildlife management requires estimates of demographic parameters that are difficult to obtain for mobile species at low densities. Biased parameter estimates often result from capture–recapture (CR) studies due to small sample sizes and unequal recapture probabilities, the latter of which can be caused by animal movements with respect to the sampling area. We developed a multistate CR model designed to minimize biases by including multiple data types (capture, harvest, natural mortality, and telemetry) and accounting for temporary emigration. We applied the model to data collected intensively from 2012 to 2014, and intermittently since the 1970s, for the Viscount Melville (VM) subpopulation of polar bears (Ursus maritimus) in the Canadian Arctic. The number of bears within the VM subpopulation boundary likely increased from an average of 145 (Bayesian 95% credible interval [CRI] [109, 221]) in 1989–1992 to 235 (95% CRI [148, 569]) in 2012–2014. Survival probability increased for all sex and age classes except adult females, for which estimates declined due to unknown reasons. Polar bear movements exhibited Markovian dependence with approximately 28% of the subpopulation located outside of the sampling area each spring. This contributed to inaccurate parameter estimates when using a simpler, single‐state CR model that only included capture data. Although the interpretation of demographic status was complicated by statistical uncertainty and changes in study design, our findings suggest that—as of 2014—the VM polar bear subpopulation had likely recovered from an earlier period of overharvest, was stable, and had not exhibited detectable negative effects of climate warming.

Incorporating multi-source uncertainties in fast building wall thermal resistance estimation through physics-based and multi-fidelity statistical learning models

Meta-modeling and Bayesian inversion technique are proposed for fast and accurate in-situ estimation of the total thermal resistance (RTot) of walls using non-intrusive wall instrumentation. Various sources of uncertainties are taken into account to provide an enhanced credible interval for the thermal resistance estimate. In the considered protocol, a small zone of the internal surface of the wall is excited by a prototype to get faster in situ estimation and to limit the influence of external weather conditions. To be independent of the heat transfer coefficients and of the misknown layer thicknesses, which are difficult to estimate, we use herein the measurements of internal and external surface temperatures as boundary conditions in a thermal direct problem reformulated. A meta-model of the thermal model is created based on a statistical multi-fidelity approach with two levels of fidelity, Resistance-Capacitance (RC) and 1D models, to achieve the Bayesian estimation of the total thermal resistance in a reasonable computation time. The RTot estimation method is applied to realistic internal insulated walls (IIW), from poorly to highly insulated, under different weather conditions. Several numerical tests are carried out and credible intervals are provided to study the importance of the wall initial condition, the excitation time and the instrumentation. Finally, an experimental application is conducted using real measurements on an internal insulated wall (IIW) in Nancy (France). The obtained experimental results show that, in a short excitation time (10h) with a reduced instrumentation, the proposed method accurately estimates the minimum wall thermal resistance. For a standard wall of about 4 m2.K/W, a relevant estimate of RTot with a relative deviation less than 10% can be achieved by using a polynomial initial temperature profile proposed in this study, sufficient measurements and an excitation time of 3 days. This study thus offers prospects for improved energy assessment of buildings before and after renovation.

Time to Sustained Recovery Among Outpatients With COVID-19 Receiving Montelukast vs Placebo

The effect of montelukast in reducing symptom duration among outpatients with mild to moderate COVID-19 is uncertain. To assess the effectiveness of montelukast compared with placebo in treating outpatients with mild to moderate COVID-19. This randomized clinical trial (Accelerating COVID-19 Therapeutic Interventions and Vaccines [ACTIV]-6) was conducted from January 27 through June 23, 2023, during the circulation of Omicron subvariants. Participants aged 30 years or older with confirmed SARS-CoV-2 infection and 2 or more acute COVID-19 symptoms for less than 7 days were included across 104 US sites. Participants were randomized 1:1 to receive montelukast, 10 mg once daily, or matched placebo for 14 days. The primary outcome was time to sustained recovery (defined as ≥3 consecutive days without symptoms). Secondary outcomes included time to death; time to hospitalization or death; a composite of health care utilization events (hospitalization, urgent care clinic visit, emergency department visit, or death); COVID-19 clinical progression scale score; and difference in mean time unwell. A modified intention-to-treat approach was used for the analysis. Among 1250 participants who were randomized and received the study drug or placebo, the median age was 53 years (IQR, 42-62 years), 753 (60.2%) were female, and 704 (56.3%) reported receiving 2 or more doses of a SARS-CoV-2 vaccine. Among 628 participants who received montelukast and 622 who received placebo, differences in time to sustained recovery were not observed (adjusted hazard ratio [AHR], 1.02; 95% credible interval [CrI], 0.92-1.12; P = .63 for efficacy). Unadjusted median time to sustained recovery was 10 days (95% CI, 10-11 days) in both groups. No deaths occurred, and hospitalizations were reported for 2 participants (0.3%) in each group; the composite of health care utilization events was reported for 18 participants (2.9%) in the montelukast group and 18 (2.9%) in the placebo group (AHR, 1.01; 95% CrI, 0.45-1.84; P = .48 for efficacy). Five participants (0.4%) experienced serious adverse events (3 [0.5%] in the montelukast group and 2 [0.3%] in the placebo group). In this randomized clinical trial of outpatients with mild to moderate COVID-19, treatment with montelukast did not reduce duration of COVID-19 symptoms. These findings do not support the use of montelukast for the treatment of mild to moderate COVID-19. ClinicalTrials.gov Identifier: NCT04885530.

Analyzing the dynamics of complicated and uncomplicated appendicitis during the COVID-19 pandemic in Seoul: a multifaceted time series approach.

This study investigated the impact of the COVID-19 pandemic and associated control strategies on the incidence of appendicitis in Seoul, using data from 2018 to 2020 from South Korea's National Health Insurance. We analyzed records of total, complicated, and uncomplicated appendicitis cases, as well as the ratio of complicated to uncomplicated appendicitis, using natural spline and piecewise regression models to identify trends and breakpoints. Bayesian structural time-series (BSTS) models were used to evaluate the causal impact of social distancing on appendicitis incidences. The spline regression analysis indicated decreasing trends in both total and uncomplicated appendicitis cases. Conversely, the incidence of complicated appendicitis and the ratio of complicated to uncomplicated cases increased. Breakpoints for a decline in uncomplicated appendicitis and a rise in the ratio occurred at 31 weeks in 2020 (95% confidence interval [CI], 23.2 to 38.8) and at 33.9 weeks (95% CI, 28.3 to 39.6), respectively. The BSTS model demonstrated a 7.8% reduction in total appendicitis cases (95% credible interval [CrI], -12.0% to -3.3%). It also showed a 17% decrease in uncomplicated cases (95% CrI, -22% to -12%) and increases of 13% (95% CrI, 4.9% to 22.0%) in complicated cases and 39% (95% CrI, 27.0% to 53.0%) in the ratio of complicated to uncomplicated appendicitis. The COVID-19 pandemic resulted in a decrease in both total and uncomplicated appendicitis cases, while the number of complicated cases increased. Reduced medical visits likely accounted for these changes. Strategies are needed to manage changes in disease pathophysiology resulting from altered healthcare utilization during health crises.

Vanilla inflation predicts negative running

We show that the simplest, and currently favoured, theoretical realizations of cosmic inflation yield a sharp prediction for the running of the spectral index . Using latest cosmological data, we compute its marginalized posterior probability distribution over the space of nearly 300 models of single-field slow-roll inflation. The most probable value is , lying within the credible interval . Within the landscape of all the proposed slow-roll inflationary models, positive values for the running are therefore disfavoured at more than three-sigma.

The herd-level prevalence of caprine arthritis-encephalitis and genetic characteristics of small ruminant lentivirus in the Lithuanian goat population

Caprine arthritis-encephalitis (CAE) is a progressive disease of goats caused by small ruminant lentivirus (SRLV) and is considered as one of the most important threats for goat farming in developed countries. The disease prevalence has never been investigated in the Lithuanian goat population. Therefore, a descriptive cross-sectional study was carried out in 2021-2022 to determine if SRLV infection was present in the Lithuanian goat population and, in the case of a positive result, to estimate the true herd-level prevalence of SRLV infection and specify genotypes and subtypes of SRLV responsible for the infection. Thirty goat herds counting >5 adult goats were randomly selected and, in each herd, a representative sample of adult goats was blood-sampled and tested serologically for SRLV infection using a commercial ELISA. The herd was considered infected if at least one goat tested positive and the true herd-level prevalence of SRLV infection was estimated using the Bayesian approach. Seropositive animals were found in 17 / 30 herds (57%; 95% confidence interval: 39%, 73%). The true herd-level prevalence was 56% (95% credible interval: 36%, 76%). In 10 / 17 seropositive herds whose owners consented for resampling of seropositive goats, 1 to 5 seropositive goats were tested using the nested real-time PCR (nRT-PCR). Goats from 9 seropositive herds tested positive in the nRT-PCR: in 4 herds for genotype A, in 4 herds for genotype B, and in 1 herd – 2 goats for genotype B and 1 goat for genotype A. From each of 9 nRT-PCR-positive herds, 1 PCR product of each genotype was sequenced using Sanger method and the phylogenic tree was constructed using the neighbor-joining method in the Molecular Evolutionary Genetics Analysis software. Four herds turned out to be infected with B1 subtype (91% identity with the prototypic strain), 3 herds with A2 subtype (90%-92% identity), and a herd with mixed infection was infected with B1 (91% identity) and A2 subtype (90% identity). In one herd, the only seropositive goat was found to be infected with the strain most closely related to the A1 subtype (80% identity). This study shows for the first time that SRLV infection is present and widespread in the Lithuanian goat population and both classical SRLV genotypes, represented by quite typical subtypes A2 and B1, appear to be responsible for the infection.

Patient- and Areal-Level Risk Factors Associated With Lung Cancer Mortality in Victoria, Australia: A Bayesian Spatial Survival Analysis.

In Australia, lung cancer is the leading cause of cancer-related deaths. In Victoria, the mortality risk is assumed to vary across Local Government Areas (LGAs) due to variations in socioeconomic advantage, remoteness, and healthcare accessibility. Thus, we applied Bayesian spatial survival models to examine the geographic variation in lung cancer survival in Victoria. Data on lung cancer cases were extracted from the Victorian Lung Cancer Registry (VLCR). To account for spatial dependence and risk factors of survival in lung cancer patients, we employed a Bayesian spatial survival model. Conditional Autoregressive (CAR) prior was assigned to model the spatial dependence. Deviance Information Criterion (DIC), Watanabe Akaike Information Criterion (WAIC), and Log Pseudo Marginal Likelihood (LPML) were used for model comparison. In the final best-fitted model, the Adjusted Hazard Ratio (AHR) with the 95% Credible Interval (CrI) was reported. The outcome variable was the survival status of lung cancer patients, defined as whether they survived or died during the follow-up period (death was our interest). Our study revealed substantial variations in lung cancer mortality in Victoria. Poor Eastern Cooperative Oncology Group (ECOG) performance status, diagnosed at a regional hospital, Small Cell Lung Cancer (SCLC), advanced age, and advanced clinical stage were associated with a higher risk of mortality, whereas being female, presented at Multidisciplinary Team (MDT) meeting, and diagnosed at a metropolitan private hospital were significantly associated with a lower risk of mortality. Identifying geographical disparities in lung cancer survival may help shape healthcare policy to implement more targeted and effective lung cancer care services.