Nonparametric Bootstrap Method Research Articles

Inference on the common mean direction of several Fisher-von Mises-Langevin populations with unknown concentration parameters

The problem of combining information from several samples for estimating or testing a common mean for normal populations has been extensively studied in the statistical literature. In this paper, we take up this problem in the context of the common mean direction of several Fisher-von Mises-Langevin (FvML) distributions. The concentration parameters are taken to be unknown and heterogeneous. A non-iterative combined estimator is proposed and is seen to have substantially better risk performance than individual sample mean directions and a grand mean direction in a simulation study. Further, a test based on this non-iterative estimator is proposed, and nonparametric bootstrap and permutation resampling methods are developed for its implementation. Two more alternative tests are proposed and their implementation is carried out using nonparametric bootstrap resampling. A detailed simulation study shows that these test procedures achieve the nominal size and have good power performance. An ‘R’ package is developed for the implementation of the tests. A real data set is considered for illustrating the procedures.

Quality-adjusted time without symptoms of disease or toxicity (Q-TWiST) analysis of fruquintinib + best supportive care (BSC) compared with placebo + BSC in metastatic colorectal cancer (mCRC): Results from the FRESCO-2 trial.

e15554 Background: As mCRC and its treatment can adversely impact quality of life (QoL), maintaining QoL is an important treatment goal in addition to improving survival outcomes, particularly as patients progress through lines of therapy. In the global, randomized, double-blind, phase 3 FRESCO-2 trial (NCT04322539), fruquintinib (F) + BSC vs placebo (P) + BSC demonstrated significantly improved overall survival (OS) (median 7.4 months vs 4.8 months; HR 0.66, 95% confidence interval [CI] 0.55–0.80) and progression-free survival, with a manageable safety profile and without deterioration of QoL in heavily pretreated patients with refractory mCRC. The objective of this post-hoc Q-TWiST analysis was to assess the quality-adjusted survival benefit of F + BSC in the context of the FRESCO-2 trial. Methods: The Q-TWiST analysis was applied to all 691 randomized patients from FRESCO-2 (F + BSC n = 461 vs P + BSC n = 230). Survival time of each patient was partitioned into 3 health states: time spent with treatment-emergent adverse events of CTCAE grade 3 or 4 before disease progression (TOX), time before disease progression without toxicity (TWiST), and time between disease progression and death or censoring (REL). Assuming utility coefficients of 1 for TWIST and 0.5 for TOX and REL, Q-TWiST was calculated as the utility-weighted sum of the time spent in each health state. The mean time spent in each of the 3 health states was calculated for each treatment group using Kaplan-Meier analysis, and a 95% CI for the difference between treatment was calculated using the nonparametric bootstrap method. Results: Q-TWiST was 6.25 months for F + BSC and 4.21 months for P + BSC, a difference of 2.04 (95% CI 1.51–2.57) months longer with F + BSC vs P + BSC. This difference in Q-TWiST was mainly driven by the difference in the TWiST component (2.14 months [95% CI 1.78–2.49]; F + BSC 4.06 months vs P + BSC 1.92 months). The relative Q-TWiST gain, calculated as the difference in Q-TWiST divided by the mean OS time of the P + BSC group, was 31.4% in favor of F + BSC. Conclusions: In the FRESCO-2 trial, F + BSC demonstrated a clinically meaningful quality-adjusted survival benefit compared with P + BSC in heavily pretreated patients with refractory mCRC. Clinical trial information: NCT04322539 .

Cost-effectiveness of outpatient adherence to recommendations for monitoring of patients hospitalized for heart failure.

A set of indicators to assess the quality of care for patients hospitalized for heart failure was developed by an expert working group of the Italian Health Ministry. Because a better performance profile measured using these indicators does not necessarily translate to better outcomes, a study to validate these indicators through their relationship with measurable clinical outcomes and healthcare costs supported by the Italian National Health System was carried out. Residents of four Italian regions (Lombardy, Marche, Lazio, and Sicily) who were newly hospitalized for heart failure (irrespective of stage and New York Heart Association class) during 2014-2015 entered in the cohort and followed up until 2019. Adherence to evidence-based recommendations [i.e. renin-angiotensin-aldosterone system (RAS) inhibitors, beta-blockers, mineralocorticoid receptor antagonists (MRAs), and echocardiograms (ECCs)] experienced during the first year after index discharge was assessed. Composite clinical outcomes (cardiovascular hospital admissions and all-cause mortality) and healthcare costs (hospitalizations, drugs, and outpatient services) were assessed during the follow-up. The restricted mean survival time at 5years (denoted as the number of months free from clinical outcomes), the hazard of clinical outcomes (according to the Cox model), and average annual healthcare cost (expressed in euros per person-year) were compared between adherent and non-adherent patients. A non-parametric bootstrap method based on 1000 resamples was used to account for uncertainty in cost-effectiveness estimates. A total of 41406 patients were included in this study (46.3% males, mean age 76.9±9.4years). Adherence to RAS inhibitors, beta-blockers, MRAs, and ECCs were 64%, 57%, 62%, and 20% among the cohort members, respectively. Compared with non-adherent patients, those who adhered to ECCs, RAS inhibitors, beta-blockers, and MRAs experienced (i) a delay in the composite outcome of 1.6, 1.9, 1.6, and 0.6months and reduced risks of 9% (95% confidence interval, 2-14%), 11% (7-14%), 8% (5-11%), and 4% (-1-8%), respectively; and (ii) lower (€262, €92, and €571 per year for RAS inhibitors, beta-blockers, and MRAs, respectively) and higher costs (€511 per year for ECC). Adherence to RAS inhibitors, beta-blockers, and MRAs showed a delay in the composite outcome and a saving of costs in 98%, 84%, and 93% of the 1000 bootstrap replications, respectively. Strict monitoring of patients with heart failure through regular clinical examinations and drug therapies should be considered the cornerstone of national guidelines and audits.

Mean Square Error Estimation of Small Area Predictors by Use of Parametric and Nonparametric Bootstrap

In this article, we propose and compare some old and new parametric and nonparametric bootstrap methods for MSE estimation in small area estimation, restricting to the case of the widely used Fay-Herriot model. The parametric method consists of generating parametrically a large number of area bootstrap samples from the model fitted to the original data, re-estimating the model parameters for each bootstrap sample and then estimating the separate components of the MSE. The use of double-bootstrap is also considered. The nonparametric method generates the samples by bootstrapping standardized residuals, estimated from the original sample data. The bootstrap procedures are compared to other methods proposed in the literature in a simulation study, which also examines the robustness of the various methods to non-normality of the model error terms. A design-based MSE estimator for the Fay-Herriot model-dependent predictor is also described and its performance is investigated in a separate simulation study. AMS subject classification: 62F10, 62F40

A study on the quantity, type, economic value and reasons for pharmaceutical waste returned to pharmacies in Finland

IntroductionSome medicines purchased are not used, resulting in pharmaceutical waste. Finland, among many other countries, is seeking to reduce the amount of pharmaceutical waste, but little information on this is currently available. This study aimed to evaluate the quantity, type, economic value, and reasons for returning pharmaceutical waste from households to community pharmacies in Finland. MethodsCommunity pharmacies (n = 82) quantified and qualified the amount of pharmaceutical waste returned to them over three days in May 2022. The data was collected using an electronic form. The reasons for returning medicines were asked from customers who returned medicines using a paper questionnaire. The data was analyzed for frequencies and percentages. To estimate the economic value, we used the Finnish medicines prices at the end of June 2022. The annual economic value was calculated by means of a pharmacy size-weighted average. The confidence intervals were estimated using the non-parametric bootstrap method. Sensitivity analyses were conducted to examine the reliability of the results. ResultsIn total, 5173 medicines were returned to pharmacies, of which 66 % were prescription medicines. The most common medicines group returned were medicines for nervous system (18 %), respiratory system (16 %), and alimentary tract and metabolism (12 %). The estimated annual economic value of the medicines returned was 81 million euros (CI 95 % M€61–M€103), of which the cost to society was 43 million euros (CI 95 % M€30–M€60). 799 customers responded to the questionnaire (Response rate 81.9 %). The limited shelf life of the medicine after opening (36 %), improvement of the medical condition or symptom (25 %), and the unnecessarily large pack size (22 %) were common reasons for returning. ConclusionA considerable amount of pharmaceutical waste is returned to pharmacies, causing unnecessary costs to both individuals and society, indicating the need to reduce waste. The limited shelf life and large pack sizes of medicines account for a large proportion of causes for household pharmaceutical waste. Reducing pharmaceutical waste requires action from all actors in the pharmaceutical chain.

Quality-adjusted time without symptoms of disease or toxicity (Q-TWiST) analysis of fruquintinib + best supportive care (BSC) compared with placebo + BSC in metastatic colorectal cancer (mCRC): Results from the FRESCO-2 trial.

116 Background: As mCRC and its treatment can adversely impact quality of life (QoL), maintaining QoL is an important treatment goal in addition to improving survival outcomes, particularly as patients progress through lines of therapy. In the global, randomized, double-blind, phase 3 FRESCO-2 trial (NCT04322539), fruquintinib (F) + BSC vs placebo (P) + BSC demonstrated significantly improved overall survival (OS) (median 7.4 months vs 4.8 months; HR 0.66, 95% confidence interval [CI] 0.55–0.80) and progression-free survival, with a manageable safety profile and without deterioration of QoL in heavily pretreated patients with refractory mCRC. The objective of this post-hoc Q-TWiST analysis was to assess the quality-adjusted survival benefit of F + BSC in the context of the FRESCO-2 trial. Methods: The Q-TWiST analysis was applied to all 691 randomized patients from FRESCO-2 (F + BSC n=461 vs P + BSC n=230). Survival time of each patient was partitioned into 3 health states: time spent with treatment-emergent adverse events of CTCAE grade 3 or 4 before disease progression (TOX), time before disease progression without toxicity (TWiST), and time between disease progression and death or censoring (REL). Assuming utility coefficients of 1 for TWIST and 0.5 for TOX and REL, Q-TWiST was calculated as the utility-weighted sum of the time spent in each health state. The mean time spent in each of the 3 health states was calculated for each treatment group using Kaplan-Meier analysis, and a 95% CI for the difference between treatment was calculated using the nonparametric bootstrap method. Results: Q-TWiST was 6.25 months for F + BSC and 4.21 months for P + BSC, a difference of 2.04 (95% CI 1.51–2.57) months longer with F + BSC vs P + BSC. This difference in Q-TWiST was mainly driven by the difference in the TWiST component (2.14 months [95% CI 1.78–2.49]; F + BSC 4.06 months vs P + BSC 1.92 months). The relative Q-TWiST gain, calculated as the difference in Q-TWiST divided by the mean OS time of the P + BSC group, was 31.4% in favor of F + BSC. Conclusions: In the FRESCO-2 trial, F + BSC demonstrated a clinically meaningful quality-adjusted survival benefit compared with P + BSC in heavily pretreated patients with refractory mCRC. Clinical trial information: NCT04322539 .

A study on the effect of school and family environments and self-efficacy on health literacy of college students.

Health literacy is an important means to improve health outcomes and reduce health disparities. It plays an important role in promoting multiple health-related behaviors of individuals. Numerous studies have demonstrated a number of sociodemographic and school characteristics, and family related factors were related to health literacy among college students. However, these characteristics and factors were relatively unchangeable. Research on the relationship between factors, that can be intervened, and health literacy remains scarce. This study aims to explore the association between personal and changeable environmental factors, and the level of health literacy in college students. A cross-sectional study, which used a stratified random sampling method, was conducted at a university in Wuhan (N = 447). The survey questionnaire included sociodemographic characteristics, the School Environment Questionnaire, the Family Environment Questionnaire, the General Self-Efficacy Scale Questionnaire, and the Health Literacy Questionnaire. We used Spearman correlation tests, and Student's tests or analyses of variance to describe the relationship among continuous variables. In addition, we employed linear regression analysis to test the mediating effect based on the bias-corrected nonparametric percentile Bootstrap method. Factors related to socioeconomic status, such as living costs (p = 0.011), residential area (p = 0.003), annual household income (p = 0.001), and parents' education level (fathers: p = 0.001; mothers: p = 0.01) and occupation type (fathers: p < 0.001; mothers: p = 0.044), had close correlations with health literacy. School and family environments and self-efficacy had a positive impact on college students' health literacy (β = 0.235, p < 0.001; β = 0.323, p < 0.001; β = 0.489, p < 0.001). Self-efficacy had a mediating effect on the relationship between school and family environments, as well as health literacy. The total, direct, and indirect effects of the school environment on health literacy were 0.235, 0.157, and 0.078, respectively. The total, direct, and indirect effects of the family environment on health literacy were 0.323, 0.189, and 0.134, respectively. This study confirms that improving school and family environments could directly or indirectly increase college students' health literacy through promoting their self-efficacy. Socioeconomic status has a significant impact on their health literacy. Moreover, other factors that affect students' health literacy and relationships among self-efficacy, surrounding environments, and health literacy may need to be explored in the future.

Nonparametric bootstrap methods for hypothesis testing in the event of double-censored data

&lt;abstract&gt;&lt;p&gt;This paper illustrated how nonparametric bootstrap methods for double-censored data can be used to conduct some hypothesis tests, such as quartiles' hypothesis tests. Through simulation studies, the smoothed bootstrap (SB) method performed better results than Efron's method in most scenarios, particularly for small datasets. The SB method provided smaller discrepancies between the actual and nominal error rates.&lt;/p&gt;&lt;/abstract&gt;

Assessing torrentiality in catchments of the tropical Andes: A morphometric approach

Torrential flows represent one of the most catastrophic natural hazards in the Andes, and Colombia is not an exception. We computed and analyzed ten morphometric indexes, classified by the catchment geometry and relief characteristics, for 149 torrential catchments across Colombian Andes three branches (Western, Central, and Eastern cordilleras). We divided the study area into six tectonic-stratigraphic regions, and employed statistical tests such as the Shapiro-Wilk and ANOVA One-Way Permutation tests to assess index distributions within each region. The ANOVA One-Way Permutation test results revealed significant differences in the distributions of form factor (p-value 0.048), mean gradient (p-value 0.009), relief ratio (p-value 0.003), Melton ratio (p-value 0.006), and hypsometric integral (p-value 0.000) indices among regions. Likewise, the pairwise comparison tests identified that the following regions are different between them for Melton ratio: Central Cordillera and Plateau Antioqueño (p-value 0.032), Garzón Massif and Plateau Antioqueño (p-value 0.015), Garzón Massif and Santander Massif (p-value 0.05), and Plateau Antioqueño and Western Cordillera (p-value 0.032); for relief ratio: Central Cordillera and Plateau Antioqueño (p-value 0.0219), Estern Cordillera and Plateau Antioqueño (p-value 0.0425), Garzón Massif and Plateau Antioqueño (p-value 0.0058), Plateau Antioqueño and Western Cordillera (p-value 0.053); for hypsometric integral: Central Cordillera and Western Cordillera (p-value 0.0004), Eastern Cordillera and Western Cordillera (p-value 0.0004), Garzón Massif and Western Cordillera (p-value 0.0004), Plateau Antioqueño and Western Cordillera (p-value 0.0161), and Santander Massif and Western Cordillera (p-value 0.002). Based on the findings we computed confidence intervals for the population median of the studied morphometric parameters according to the region employing a non-parametric bootstrapping method. The statistical analysis highlights the importance of the geological and geomorphological features in the morphometric indices analysis as part of the torrential flow susceptibility assessment.Applying our findings, we tested proposed thresholds in a case study of the Santander Massif (Eastern Cordillera of Colombia), focusing on the 2020 Piedecuesta Flow. In the study case, we demonstrated the relevance of identifying the feeder catchments where the morphometric indices would be calculated from, especially in areas where significant hydrologic changes occur. Volumetric concentration variations along the Piedecuesta Flow path highlight the need to prioritize the recognition of feeder catchments as an imperative part of the susceptibility assessment. Our approach enriches the knowledge base for identifying torrential-prone basins and has important implications for natural hazard management, aiming at mitigating the impact of torrential flows in the Andes.

Reference intervals for serum immunoglobulins G, M and E levels in Brazilian children aged 1 to 10 years: a population-based study

ObjectiveTo determine the reference intervals (RI) for serum levels of IgG, IgM, and IgE in healthy children aged 1–10 years living in central Brazil. MethodA sample of 1743 healthy children was randomly selected from kindergartens and public schools. Reference intervals were defined by non-parametric rank (Clinical Laboratory Standards Institute, USA), bootstrapping, and Horn's robust methods. ResultsBy the rank method, the IgG RI was 792–1771 mg/dL for children of both sexes aged 1–10 years. IgM RI were different for gender and age groups, being 45–196 mg/dL and 34–190 mg/dL for boys aged 1–2 years and 3–10 years, respectively. For girls, the IgM RI were 50–212 mg/dL and 39–212 mg/dL, for ages 1–4 and 5–10 years, respectively. The IgE RI for both sexes and ages 1–10 years was 6–1005 mg/dL. The bootstrap method showed RI similar to the rank method but with slightly different confidence intervals. Horn's robust method determined RI different from those obtained by previous methods. ConclusionRI for serum concentrations of IgG, IgM, and IgE were established for Brazilian children aged 1–10 years. This definition will be useful for Brazilian physicians, who will have more adequate parameters for their clinical decision-making.

Nonparametric bootstrap methods for interval estimation of the area under the ROC curve with correlated diagnostic test data: application to whole-virus ELISA testing in swine.

Developing and evaluating novel diagnostic assays are crucial components of contemporary diagnostic research. The receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC) are frequently used to evaluate diagnostic assays' performance. The variation in AUC estimation can be quantified nonparametrically using resampling methods, such as bootstrapping, and then used to construct interval estimation for the AUC. When multiple observations are observed from the same subject, which is very common in veterinary diagnostic tests evaluation experiments, a traditional bootstrap-based method can fail to provide valid interval estimations of AUC. In particular, the traditional method does not account for the correlation among data observations and could result in interval estimation that fails to cover the true AUC adequately at the desired confidence level. In this paper, we proposed two novel methods to calculate the confidence interval of the AUC for correlated diagnostic test data based on cluster bootstrapping and hierarchical bootstrapping, respectively. Our simulation studies showed that both proposed methods had adequate coverage probabilities which were higher than the existing traditional method when there were intra-subject correlations. We also discussed applying the proposed methods to evaluate a novel whole-virus ELISA (wv-ELISA) diagnostic assay in detecting porcine parainfluenza virus type-1 antibodies in swine serum.

Variability of Vairimorpha (=Nosema) ceranae infection level in individual honey bees and its implications on the pooled sample size

Nosemosis is caused by two microsporidian species of the genus recently renamed Vairimorpha (=Nosema) that parasitize the midgut of Apis mellifera. Usually, pooled samples of 60 bees are used for diagnosis. Reported differences in the efficiency of treatments against Vairimorpha sp. led us to wonder if the sample size may be one of the causes of these unpredictable results. This study focuses on the distribution of the spore load of V. ceranae among forager bees within a colony using statistical approaches in relation to sample size. Spore counts per bee were used to describe the spore distribution and to test whether they fit different statistical distributions. Standard errors were calculated and two-sided 95% confidence intervals were constructed for the spore count means, using standard (Student’s t) and non-parametric bootstrap methods (Percentil and bias-corrected and accelerated-BCa). Bees with a high degree of infection appear in low percentage but are very influential on the mean value. Data showed a poor fit to all of the distributions evaluated. To obtain a relative standard error below 10% of the mean, pooled samples should have more than 1,500 bees. The BCa interval showed better coverage than others being acceptable starting at 100 data of individual foragers. Results show that, when using the traditional sample size (pooled samples n = 60), the accuracy for estimating the mean spore load is low in V. ceranae infected hives, regardless of the statistical method applied. Thus, this work could justify some erratic results reported for treatments with commercial products.

A composite semiparametric homogeneity test for the distributions of multigroup interval-bounded longitudinal data

ABSTRACT Motivated by comparing the distribution of longitudinal quality of life (QoL) data among different treatment groups from a cancer clinical trial, we propose a semiparametric test statistic for the homogeneity of the distributions of multigroup longitudinal measurements, which are bounded in a closed interval with excess observations taking the boundary values. Our procedure is based on a three-component mixed density ratio model and a composite empirical likelihood for the longitudinal data taking values inside the interval. A nonparametric bootstrap method is applied to calculate the p-value of the proposed test. Simulation studies are conducted to evaluate the proposed procedure, which show that the proposed test is effective in controlling type I errors and more powerful than the procedure which ignores the values on the boundaries. It is also robust to the model mispecification than the parametric test. The proposed procedure is also applied to compare the distributions of the scores of Physical Function subscale and Global Heath Status between the patients randomized to two treatment groups in a cancer clinical trial.

Revised Definition of Free Light Chains in Serum and Light Chain Monoclonal Gammopathy of Undetermined Significance: Results of the Istopmm Study

Background: Serum free light chain (FLC) measurement, consisting of serum free kappa, serum free lambda, and a calculated FLC ratio (kappa/lambda), plays a pivotal role in the diagnosis, risk stratification and management of plasma cell disorders. Light chain monoclonal gammopathy of undetermined significance (LC-MGUS), is defined as abnormal FLC ratio with elevation of the involved FLC without evidence of heavy chain M protein or end-organ damage attributed to the plasma cell disorder. Several years ago, reference intervals for serum kappa (3.3-19.4 mg/L) and lambda (5.7-26.3 mg/L) FLC and FLC ratio (0.26-1.65) were defined in a small retrospective cohort (N = 282) of healthy individuals. Limitation of these reference intervals include inaccurate distributions among individuals with impaired kidney function. Recently, we addressed this matter in a large population-based study focusing on individuals with estimated glomerular filtration rate (eGFR) &amp;lt; 60 mL/min/1.73m 2, the results of which led to redefined reference intervals for patients with chronic kidney disease (Long et al, Blood Cancer J. 2022). Here, using a large cohort (N=41,882) of screened individuals, we aimed to determine FLC reference intervals in individuals with normal kidney function (eGFR ≥ 60 mL/min/1.73m 2). Methods: Data were collected from the ongoing Iceland Screens, Treats, or Prevents Multiple Myeloma (iStopMM) study, which focuses on population-based screening for MGUS. A total of 75,422 individuals aged ≥ 40 years (representing 51% of this age group in the Icelandic population) were screened for MGUS by serum protein electrophoresis, immunofixation, and serum FLC assay (Freelite®), and two-thirds of MGUS cases were randomized to active follow-up. Participants' eGFR was calculated using serum creatinine (CKD-EPI) closest to the time of screening. Participants with heavy chain M protein, known lymphoproliferative disorder, unknown eGFR or eGFR &amp;lt; 60 mL/min/1.73m 2, were excluded. The 0.5 and 99.5 percentiles of kappa FLC, lambda FLC, and the FLC ratio distributions were assessed for the whole group, and subgroups of age, sex, and different levels of eGFR. A nonparametric bootstrapping method was used to calculate the 95% confidence intervals. Partitioning was determined based on the proportion of subgroups (age, sex and eGFR) outside the whole group reference interval. Results: After application of the exclusion criteria, 41,882 participants were included for further analysis. The median (interquartile range, IQR) serum free kappa was 14.3 (11.6-17.8) mg/L, serum free lambda 14.2 (11.6-17.5) mg/L, and the FLC ratio was 1.02 (0.85-1.21). The median (IQR) age was 60 (52-68) years, eGFR 84 (74-94) mL/min/1.73 m 2, and 43% were male. A strong correlation was found between age and serum kappa FLC (ρ = 0.27, p &amp;lt; 0.001), lambda FLC (ρ = 0.14, p &amp;lt; 0.001), and the FLC ratio (ρ = 0.16, p &amp;lt; 0.001). Use of standard reference intervals yielded abnormal results for 17.5%, 3.9%, and 4.5% of serum kappa, lambda, and FLC ratio determinations, respectively, and a prevalence of LC-MGUS of 2.0% (96% kappa and 4% lambda). Based on these findings, we established new reference intervals for serum kappa and lambda FLC and FLC ratio, partitioned by age &amp;lt; 70 years and ≥ 70 years (Table). Utilizing the new reference intervals the crude prevalence of LC-MGUS was 0.3% (54% kappa and 46% lambda), yielding a relative decrease of 83%. Among the group of individuals diagnosed with LC-MGUS based on standard reference intervals who did not meet the diagnostic criteria using our revised reference intervals - none had progressed to a lymphoproliferative disorder after a median follow-up time of 42 months. Conclusion: Based on prospective screening of more than 40,000 individuals and after 3.5 years of follow-up, we show that standard reference intervals for serum FLC and FLC ratio appear inaccurate for persons with preserved kidney function. We propose a revision of the reference intervals for serum FLC and FLC ratio, and a new definition of LC MGUS (Figure). Implementation of new reference intervals will decrease the rate of false positive diagnosis of LC-MGUS in individuals with preserved kidney function by more than 80%. This, in turn, will reduce the unnecessary psychological and financial burden driven by clinical evaluation and lifelong monitoring of these individuals.

Medico-economic impact of thoracoscopy versus thoracotomy in lung cancer: multicentre randomised controlled trial (Lungsco01)

BackgroundLungsco01 is the first study assessing the real benefits and the medico-economic impact of video-thoracoscopy versus open thoracotomy for non-small cell lung cancer in the French context.MethodsTwo hundred and fifty nine adult patients from 10 French centres were randomised in this prospective multicentre randomised controlled trial, between July 29, 2016, and November 24, 2020. Survival from surgical intervention to day 30 and later was compared with the log-rank test. Total quality-adjusted-life-years (QALYs) were calculated using the EQ-5D-3L®. For medico-economic analyses at 30 days and at 3 months after surgery, resources consumed were valorised (€ 2018) from a hospital perspective. First, since mortality was infrequent and not different between the two arms, cost-minimisation analyses were performed considering only the cost differential. Second, based on complete cases on QALYs, cost-utility analyses were performed taking into account cost and QALY differential. Acceptability curves and the 95% confidence intervals for the incremental ratios were then obtained using the non-parametric bootstrap method (10,000 replications). Sensitivity analyses were performed using multiple imputations with the chained equation method.ResultsThe average cumulative costs of thoracotomy were lower than those of video-thoracoscopy at 30 days (€9,730 (SD = 3,597) vs. €11,290 (SD = 4,729)) and at 3 months (€9,863 (SD = 3,508) vs. €11,912 (SD = 5,159)). In the cost-utility analyses, the incremental cost-utility ratio was €19,162 per additional QALY gained at 30 days (€36,733 at 3 months). The acceptability curve revealed a 64% probability of efficiency at 30 days for video-thoracoscopy, at a widely-accepted willingness-to-pay threshold of €25,000 (34% at 3 months). Ratios increased after multiple imputations, implying a higher cost for video-thoracoscopy for an additional QALY gain (ratios: €26,015 at 30 days, €42,779 at 3 months).ConclusionsGiven our results, the economic efficiency of video-thoracoscopy at 30 days remains fragile at a willingness-to-pay threshold of €25,000/QALY. The economic efficiency is not established beyond that time horizon. The acceptability curves given will allow decision-makers to judge the probability of efficiency of this technology at other willingness-to-pay thresholds.Trial registrationNCT02502318.

Path Analysis of Self-Efficacy, Coping Style and Resilience on Depression in Patients with Recurrent Schizophrenia.

Based on the two mediating variables of self-efficacy and coping style, a multiple mediating model was constructed to explore the mechanism by which psychological resilience affects depression in patients with recurrent schizophrenia. A total of 210 patients with recurrent schizophrenia who were hospitalized in a tertiary hospital in Hunan Province, China, were enrolled. The Connor Davidson Resilience Scale (CD-RISC), Self-rating Depression Scale (SDS), General Self-Efficacy Energy Scale (GSES) and Simplified Coping Style Questionnaire (SCSQ) were used to evaluate resilience, self-efficacy, coping style and depression. Path analysis was performed by constructing a structural equation model, and the mediating effect between variables was verified by the bias-corrected nonparametric percentile bootstrap method. Resilience, self-efficacy and positive coping together explained 53.2% of the variance in depression. (1) The total scores of self-efficacy, coping style, resilience and depression in patients with recurrent schizophrenia were 2.54±0.61, 31.73±9.62, 58.06±17.26 and 50.48±12.55, respectively. (2) Pearson analysis showed that the scores of self-efficacy, positive coping, resilience and depression were significantly correlated with depression (r=-0.24-0.51, P<0.01). (3) The path analysis showed that resilience directly affects depression (β=-0.401); additionally, resilience indirectly affects depression through self-efficacy (β=-0.179) and through the chain mediating effect of self-efficacy and positive coping style (β=-0.024). There is a high incidence of depression in patients with recurrent schizophrenia in China, and intervention is needed. This research revealed that resilience directly affects depression in patients with recurrent schizophrenia and that self-efficacy and positive coping play a part in mediating resilience and depression in patients with recurrent schizophrenia in China. Implementing targeted interventions based on action paths to improve the level of resilience and reduce the incidence of depression has guiding significance in the field of occupational rehabilitation of patients with recurrent schizophrenia.

The influence of media use degree on public depressive symptoms: mediating role of big five personality

BackgroundMixed results have been found regarding the relationship between media use degree and depressive symptoms. The purpose of this study is to explore the relationship between media use degree, big five personality and depressive symptoms with a mediation model.MethodThis was a cross-sectional study. With 9-item Patient Health Questionnaire (PHQ-9), 10-item Big Five Inventory (BFI-10) and self-designed media usage scale, 11,031 participants aged 12 and above in 120 cities in China were collected. Pearson correlation analysis and regression analysis were performed on the data. The Process plug-in was used to construct the mediation model and explore the relationship among media use degree, big five personality and depressive symptoms. The nonparametric percentile Bootstrap method was used to test the mediating effect of personality traits.ResultsThe degree of media use was positively correlated with depressive symptoms (r = 0.20, P < 0.001), and big five personality played a mediating role between the degree of media use and depressive symptoms. Among five traits, extroversion (r=-0.12, P < 0.001), conscientiousness (r=-0.23, P < 0.001), openness (r=-0.03, P < 0.01) and agreeableness (r=-0.22, P < 0.001) were negatively correlated with depressive symptoms, and neuroticism (r = 0.25, P < 0.001) were positively correlated with depressive symptoms. In addition, extraversion (-0.004, -0.001), conscientiousness (-0.015, -0.008), agreeableness (-0.008, -0.001) and neuroticism (-0.015, -0.007) in big five personality played a mediating role between media use and depressive symptoms.ConclusionThe degree of media use positively predicted depressive symptoms, and excessive media use may bring risks to mental health. People with high neuroticism, low agreeableness, low conscientiousness and low extroversion are more likely to suffer from depressive symptoms.

Effect of Intolerance of Uncertainty on Fear of Childbirth in Primiparas : A Moderated Mediating Model

To explore the mediating effect of childbirth self-efficacy on the impact pathway of intolerance of uncertainty on the fear of childbirth in primiparas in the second and third trimesters and the potential moderating effect of perceived partner responsiveness. A total of 429 primiparas in their second and third trimesters completed the survey, which included general information questionnaire, Intolerance of Uncertainty Scale, Childbirth Self-Efficacy Inventory, Perceived Partner Responsiveness Scale, and Childbirth Attitudes Questionnaire. Rank sum test was used to compare the scores for the fear of childbirth among different groups and Spearman's correlation was used to analyze the scores for all the scales. In addition, the data were centrally processed by using PROCESS V3.4.1 Model 4 (a simple mediation model), Model 5 (the direct path of the mediation model was regulated), and non-parametric Bootstrap method to test the mediation effect and moderation effect. The study showed that 54.31% of the participants experienced fear of childbirth. Their scores for intolerance of uncertainty, childbirth self-efficacy, and perceived partner responsiveness were 15.00 (8.00), 240.00 (75.00), and 72.00 (19.00), respectively. There were significant differences in the scores for the fear of childbirth scale among pregnant women of different age groups, gestational weeks, employment statuses, and average per capita monthly income of the family ( P<0.05). According to our findings, intolerance of uncertainty directly and positively impacted on fear of childbirth ( β=0.76, P<0.001), with childbirth self-efficacy playing partial mediation role between them, its indirect effect being 0.05 and the contribution rate being 6.17%. In addition, after the scores of Perceived Partner Responsiveness Scale were added to the model, perceived partner responsiveness had no significant predictive effect for fear of childbirth, but the product term of the scores for Perceived Partner Responsiveness Scale and Intolerability Uncertainty Scale had significant predictive effect for fear of childbirth ( β=0.01, P<0.05), which suggested that perceived partner responsiveness also played a moderating role between intolerance of uncertainty and fear of childbirth. Health care providers can help primiparas reduce fear of childbirth and improve their childbirth experience by reducing perceived intolerance of uncertainty, improving family support, and teaching coping strategies.

Safety of monovalent and bivalent BNT162b2 mRNA COVID-19 vaccine boosters in at-risk populations in Israel: a large-scale, retrospective, self-controlled case series study

COVID-19 continues to be a major health threat, particularly among at-risk groups, including individuals aged 60 years or older and people with particular medical conditions. Nevertheless, the absence of sufficient vaccine safety information is one of the key contributors to vaccine refusal. We aimed to assess the short-term safety profile of the BNT162b2 mRNA COVID-19 vaccine booster doses. In this self-controlled case series study, we used a database of members of the largest health-care organisation in Israel. We analysed the medical records of individuals at risk of COVID-19 complications who had received two doses of the monovalent BNT162b2 mRNA COVID-19 vaccine (tozinameran, Pfizer-BioNTech) as their primary course of vaccination and then also received BNT162b2 mRNA COVID-19 vaccine boosters between July 30, 2021, and Nov 28, 2022, as a monovalent first or second booster, or as a bivalent first, second, or third booster, or a combination of these. We included individuals who had active membership of the health-care organisation and who were alive (excluding COVID-19 deaths) throughout the entire study period. We excluded individuals who, during the study period, were either not active Clalit Health Services members or died of non-COVID-19 causes, and those who were infected with COVID-19 during the 7-day period after vaccination. Individuals' at-risk status was assessed on the day before the baseline period started. The primary outcome was non-COVID-19 hospitalisation for 29 adverse events that might be associated with vaccination. For each adverse event, we compared the risk difference of hospitalisation during a 28-day pre-vaccination baseline period versus during a 28-day post-vaccination period, using a non-parametric percentile bootstrap method. Of the 3 574 243 members of the health-care organisation, 1 073 110 received a first monovalent booster, 394 251 received a second monovalent booster, and 123 084 received a bivalent first, second, or third booster. Overall, we found no indication of an elevated risk of non-COVID-19 hospitalisation following administration of any of the booster vaccines (risk difference in events per 100 000 individuals: first monovalent booster -37·1 [95% CI -49·8 to -24·2]; second monovalent booster -37·8 [-62·2 to -13·2]; and bivalent booster -18·7 [-53·6 to 15·4]). Except for extremely rare elevated risks after the first monovalent booster-of myocarditis (risk difference 0·7 events per 100 000 individuals [95% CI 0·3-1·3]), seizures (2·2 [0·4-4·1]), and thrombocytopenia (2·6 [0·7-4·7])-we found no safety signals in other adverse events, including ischaemic stroke. This study provides the necessary vaccine safety assurances for at-risk populations to receive timed roll-out booster vaccinations. These assurances could reduce vaccine hesitancy and increase the number of at-risk individuals who opt to become vaccinated, and thereby prevent the severe outcomes associated with COVID-19. Israel Science Foundation and Israel Precision Medicine Partnership programme.

Reference intervals for serum immunoglobulin A levels in Brazilian children aged 1 to 10 years: a population-based study

ObjectiveTo determine reference intervals (RI) for serum immunoglobulin A (IgA) levels in healthy children aged 1 to 1 0 years residing in the central region of Brazil. MethodsThis cross-sectional study was conducted on 1,743 healthy children randomly selected from kindergartens and public schools in Cuiabá, MT, Brazil. The IgA RIs were defined using the statistical methods postulated by the guidelines of the United States Clinical and Laboratory Standards Institute, the nonparametric bootstrap method, and Horn's robust method after the correction of discrepancies by Tukey's, Dixon's, and Horn's methods, respectively. The results were defined based on the values contained between the 2.5th and 97.5th percentiles and their respective 95% confidence intervals. ResultsPartition by sex was not necessary to determine the IgA RI of the studied children. Homogeneous subgroups were identified among children aged 1–<2, 2–<5, and 5–<11 years, whose IgA-specific RIs were determined. ConclusionThe serum IgA RIs were established for three groups of Brazilian children aged 1–11 years, which differed from those currently applied in Brazilian pediatric practice and from those defined by international studies. This definition will help Brazilian pediatricians formulate an accurate diagnosis and facilitate decision-making.