Category: Statistics

Biometrics. 2021 Aug 27. doi: 10.1111/biom.13555. Online ahead of print.

ABSTRACT

Censored survival data are common in clinical trial studies. We propose a unified framework for sensitivity analysis to censoring at random in survival data using multiple imputation and martingale, called SMIM. The proposed framework adopts the δ-adjusted and control-based models, indexed by the sensitivity parameter, entailing censoring at random and a wide collection of censoring not at random assumptions. Also, it targets a broad class of treatment effect estimands defined as functionals of treatment-specific survival functions, taking into account missing data due to censoring. Multiple imputation facilitates the use of simple full-sample estimation; however, the standard Rubin’s combining rule may overestimate the variance for inference in the sensitivity analysis framework. We decompose the multiple imputation estimator into a martingale series based on the sequential construction of the estimator and propose the wild bootstrap inference by resampling the martingale series. The new bootstrap inference has a theoretical guarantee for consistency and is computationally efficient compared to the non-parametric bootstrap counterpart. We evaluate the finite-sample performance of the proposed SMIM through simulation and an application on an HIV clinical trial. This article is protected by copyright. All rights reserved.

PMID:34453313 | DOI:10.1111/biom.13555

Ther Innov Regul Sci. 2021 Aug 27. doi: 10.1007/s43441-021-00335-3. Online ahead of print.

ABSTRACT

BACKGROUND: In 2016, the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use updated its efficacy guideline for good clinical practice and introduced quality tolerance limits (QTLs) as a quality control in clinical trials. Previously, TransCelerate proposed a framework for QTL implementation and parameters. Historical data can be important in helping to determine QTL thresholds in new clinical trials.

METHODS: This article presents results of historical data analyses for the previously proposed parameters based on data from 294 clinical trials from seven TransCelerate member companies. The differences across therapeutic areas were assessed by comparing Alzheimer’s disease (AD) and oncology trials using a separate dataset provided by Medidata.

RESULTS: TransCelerate member companies provided historical data on 11 QTL parameters with data sufficient for analysis for parameters. The distribution of values was similar for most parameters with a relatively small number of outlying trials with high parameter values. Medidata provided values for three parameters in a total of 45 AD and oncology trials with no obvious differences between the therapeutic areas.

CONCLUSION: Historical parameter values can provide helpful benchmark information for quality control activities in future trials.

PMID:34453269 | DOI:10.1007/s43441-021-00335-3

Biol Trace Elem Res. 2021 Aug 27. doi: 10.1007/s12011-021-02897-7. Online ahead of print.

ABSTRACT

The existing evidence on the relationships of serum zinc, copper, and zinc/copper ratio with sleep duration is limited and conflicting. The present cross-sectional study aimed to investigate these associations in general adults by utilizing data from the 2011-2016 National Health and Nutrition Examination Survey. The concentrations of zinc and copper were measured in serum samples. Sleep duration (self-reported usual sleep duration) was categorized as < 7 h/night (short sleep duration), 7-8 h/night (optimal sleep duration), and > 8 h/night (long sleep duration). Multinomial logistic regression models and restricted cubic splines were constructed to examine the associations of serum zinc, copper, and zinc/copper ratio with sleep duration. A total of 5067 adults were included. After multivariate adjustment, compared with the optimal sleep duration group, the odds ratios (ORs) (95% confidence intervals, CIs) in the long sleep duration group for the highest versus lowest quartile of serum zinc concentration and zinc/copper ratio were 0.61 (0.39-0.96) and 0.58 (0.38-0.89), respectively. Furthermore, among males, the OR (95% CI) of long sleep duration for the highest versus lowest quartile of serum copper concentration was 2.23 (1.15-4.32). Finally, the dose-response trends suggested that participants with optimal sleep duration had the highest serum zinc concentration and zinc/copper ratio and a slightly lower serum copper concentration. No significant association was found between serum zinc, copper concentrations and the zinc/copper ratio and short sleep duration. In conclusion, serum zinc and zinc/copper ratio were inversely related to long sleep duration in adults, while serum copper was positively associated with long sleep duration in males.

PMID:34453310 | DOI:10.1007/s12011-021-02897-7

Environ Sci Pollut Res Int. 2021 Aug 27. doi: 10.1007/s11356-021-16110-8. Online ahead of print.

ABSTRACT

Environmental challenges are as vast as the universe, allowing for numerous studies on their various dimensions. Using 17 data sets from Asia-Pacific countries between 2000 and 2017, this study attempted to investigate the economic factors influencing the ecological footprint of the fishing sector. The primary contribution of this study is to examine the effects of nine economic freedom indicators, as well as other control variables, on the status of fishery resources due to environmental pressure. The findings confirm the environmental Kuznets curve (EKC) hypothesis in the fishing grounds footprint, indicating that GDP per capita growth has a positive and significant effect, even though its squared form coefficient is negative. Other control variables, including natural resource rents, urbanization, and energy intensity, do not significantly affect the fishing footprint. The different components of economic freedom show different effects, while their cumulative effects in the form of the total economic freedom index positively affect the footprint of fishing and lead to increased extraction from fishing resources. The results show that the government integrity, tax burden, business freedom, and monetary freedom indices increase the fishing footprint. In contrast, indices of trade freedom and investment freedom, by highlighting the adverse effects of fishing on the environment, help countries reduce pressure on their aquatic resources. The findings of this study highlight the importance of examining how various dimensions of economic freedom affect the ability to manage fishery resources effectively.

PMID:34453249 | DOI:10.1007/s11356-021-16110-8

J Immigr Minor Health. 2021 Aug 28. doi: 10.1007/s10903-021-01265-w. Online ahead of print.

ABSTRACT

Considering the critical role of oral health on people’s well-being, access to regular dental care to improve oral health may be a useful medium for improving immigrant integration and settlement in Canada. Using the 2013-14 Canadian Community Health Survey, this study contributes to the literature and policy by examining if there are disparities in regular utilization of dental care among recent immigrants, established immigrants, and the native-born in Ontario, Canada. Adopting Andersen’s behavioural model of health services use as a conceptual framework, we introduce three sets of variables in our statistical analysis including predisposing, need, and enabling factors. At the bivariate level, recent (OR = 0.42, p < 0.001) and established immigrants (OR = 0.81, p < 0.001) are less likely to use dental care at least once a year than their native-born counterparts. Once accounting for enabling characteristics, however, we observe that the direction of the association becomes positive for established immigrants (OR = 1.15, p < 0.05). The difference between recent immigrants and the native-born is partially attenuated when we control for enabling characteristics but remains statistically significant (OR = 0.73, p < 0.05). Based on these findings, we provide several implications for policymakers and future research.

PMID:34453263 | DOI:10.1007/s10903-021-01265-w

Clin Res Cardiol. 2021 Aug 28. doi: 10.1007/s00392-021-01925-9. Online ahead of print.

ABSTRACT

OBJECTIVES: To evaluate associations of omega-3 fatty acid (O3-FA) blood levels with cardiometabolic risk markers, functional capacity and cardiac function/morphology in patients with heart failure with preserved ejection fraction (HFpEF).

BACKGROUND: O3-FA have been linked to reduced risk for HF and associated phenotypic traits in experimental/clinical studies.

METHODS: This is a cross-sectional analysis of data from the Aldo-DHF-RCT. From 422 patients, the omega-3-index (O3I = EPA + DHA) was analyzed at baseline in n = 404 using the HS-Omega-3-Index^® methodology. Patient characteristics were; 67 ± 8 years, 53% female, NYHA II/III (87/13%), ejection fraction ≥ 50%, E/e’ 7.1 ± 1.5; median NT-proBNP 158 ng/L (IQR 82-298). Pearson’s correlation coefficient and multiple linear regression analyses, using sex and age as covariates, were used to describe associations of the O3I with metabolic phenotype, functional capacity, echocardiographic markers for LVDF, and neurohumoral activation at baseline/12 months.

RESULTS: The O3I was below (< 8%), within (8-11%), and higher (> 11%) than the target range in 374 (93%), 29 (7%), and 1 (0.2%) patients, respectively. Mean O3I was 5.7 ± 1.7%. The O3I was inversely associated with HbA1c (r = – 0.139, p = 0.006), triglycerides-to-HDL-C ratio (r = – 0.12, p = 0.017), triglycerides (r = – 0.117, p = 0.02), non-HDL-C (r = – 0.101, p = 0.044), body-mass-index (r = – 0.149, p = 0.003), waist circumference (r = – 0.121, p = 0.015), waist-to-height ratio (r = – 0.141, p = 0.005), and positively associated with submaximal aerobic capacity (r = 0.113, p = 0.023) and LVEF (r = 0.211, p < 0.001) at baseline. Higher O3I at baseline was predictive of submaximal aerobic capacity (β = 15.614, p < 0,001), maximal aerobic capacity (β = 0.399, p = 0.005) and LVEF (β = 0.698, p = 0.007) at 12 months.

CONCLUSIONS: Higher O3I was associated with a more favorable cardiometabolic risk profile and predictive of higher submaximal/maximal aerobic capacity and lower BMI/truncal adiposity in HFpEF patients. Omega-3 fatty acid blood levels are inversely associated with cardiometabolic risk factors in HFpEF patients. Higher O3I was associated with a more favorable cardiometabolic risk profile and aerobic capacity (left) but did not correlate with echocardiographic markers for left ventricular diastolic function or neurohumoral activation (right). An O3I-driven intervention trial might be warranted to answer the question whether O3-FA in therapeutic doses (with the target O3I 8-11%) impact on echocardiographic markers for left ventricular diastolic function and neurohumoral activation in patients with HFpEF. This figure contains modified images from Servier Medical Art ( https://smart.servier.com ) licensed by a Creative Commons Attribution 3.0 Unported License.

PMID:34453204 | DOI:10.1007/s00392-021-01925-9

Acta Diabetol. 2021 Aug 27. doi: 10.1007/s00592-021-01789-5. Online ahead of print.

ABSTRACT

BACKGROUND: Automated insulin delivery aims to lower treatment burden and improve quality of life as well as glycemic outcomes.

METHODS: We present sub-study data from a dual-center, randomized, open-label, two-sequence crossover study in automated insulin delivery naïve users, comparing Medtronic MiniMed® Advanced Hybrid Closed-Loop (AHCL) to Sensor Augmented Pump therapy with Predictive Low Glucose Management (SAP + PLGM). At the end of each 4-week intervention, impacts on quality of life, sleep and treatment satisfaction were compared using seven age-appropriate validated questionnaires given to patients or caregivers.

RESULTS: 59/60 people completed the study (mean age 23.3 ± 14.4yrs). Statistically significant differences favoring AHCL were demonstrated in several scales (data shown as mean ± SE). In adults (≥ 18yrs), technology satisfaction favored AHCL over PLGM as shown by a higher score in the DTSQs during AHCL (n = 28) vs SAP + PLGM (n = 29) (30.9 ± 0.7 vs 27.9 ± 0.7, p = 0.004) and DTSQc AHCL (n = 29) vs SAP + PLGM (n = 30) (11.7 ± 0.9 vs 9.2 ± 0.8, p = 0.032). Adolescents (aged 13-17yrs) also showed a higher DTSQc score during AHCL (n = 16) versus SAP + PLGM (n = 15) (14.8 ± 0.7 vs 12.1 ± 0.8, p = 0.024). The DTQ “change” score (n = 59) favored AHCL over SAP + PLGM (3.5 ± 0.0 vs 3.3 ± 0.0, p < 0.001). PSQI was completed in those > 16 years (n = 36) and demonstrated improved sleep quality during AHCL vs SAP + PLGM (4.8 ± 0.3 vs 5.7 ± 0.3, p = 0.048) with a total score > 5 indicating poor quality sleep.

CONCLUSION: These data suggest that AHCL compared to SAP + PLGM mode has the potential to increase treatment satisfaction and improve subjective sleep quality in adolescents and adults with T1D.

PMID:34453208 | DOI:10.1007/s00592-021-01789-5

Jpn J Clin Oncol. 2021 Aug 27:hyab137. doi: 10.1093/jjco/hyab137. Online ahead of print.

ABSTRACT

OBJECTIVE: This study investigated whether the Dementia Assessment Sheet for the Community-based Integrated Care System is useful for decision-making or problem detection in the treatment and care of older patients with inoperable advanced non-small cell lung cancer compared with the current standard model using performance status.

METHODS: This study retrospectively examined 1595 cases admitted to the Department of Respiratory Medicine at the Tokyo Metropolitan Geriatric Hospital between 26 July 2016 and 28 January 2020. Among these, 29 and 31 patients who received pharmacotherapies and best supportive care were extracted, respectively. The performance in identifying best supportive care using the Dementia Assessment Sheet for the Community-based Integrated Care System was evaluated in comparison with performance status. The ability to detect impairments in each Dementia Assessment Sheet for the Community-based Integrated Care System domain was also assessed.

RESULTS: The Dementia Assessment Sheet for the Community-based Integrated Care System total score had an area under the curve of 0.831 (95% confidence interval, 0.694-0.914), which was statistically equivalent to performance status. The discriminatory cut-off value for identification of best supportive care was set at 29 with a sensitivity and specificity of 0.742 and 0.897, respectively. Dementia Assessment Sheet for the Community-based Integrated Care System total score showed good concordance with performance status especially when reported by family members or caregivers. Deficits other than activities of daily living were recognized (2.8-19.4%) in patients with good performance status. Impairments were more frequently detected when reported by family members or caregivers.

CONCLUSIONS: The Dementia Assessment Sheet for the Community-based Integrated Care System discriminates the best supportive care for older patients with inoperable advanced non-small cell lung cancer. Moreover, it can identify vulnerabilities especially when reported by family members or caregivers that cannot be detected by performance status.

PMID:34453179 | DOI:10.1093/jjco/hyab137

HNO. 2021 Aug 27. doi: 10.1007/s00106-021-01103-3. Online ahead of print.

ABSTRACT

BACKGROUND: Patients suffering from tinnitus require individualized clarification (counseling), sometimes going beyond the scope of the field of ENT and the initiation of specific interventions.

AIM: To investigate if patients who had a specific neurotological assessment including a psychosomatic medical history follow the recommendations provided to them. In addition, it should be examined whether compliance with the treatment suggestions has led to any psychological improvement in the suffering from tinnitus, evaluated by psychological tests.

MATERIAL AND METHOD: In295 out of 699 patients audiological tests were evaluated using the mini-questionnaire (TF 12) according to Hiller and Goebel and the German language version of the Hospitality Anxiety and Depression Scale (HADS) at 2 points in time with an interval of a least 6 months. The group of those who followed the recommendations were compared to the group of those who did not follow the recommendations.

RESULTS: A total of 180 patients (64.5%) followed at least 1 of the recommendations made to them. Patients who followed at least one recommendation benefited significantly more than the whole group in the TF 12 and in both HADS categories compared to the group that did not follow the recommendations.

CONCLUSION: In addition to counseling it was shown that the implementation of a specific measure has a positive effect, detectable for the Progressive Muscle Relaxation (PMR). Specific for ENT, a hearing aid can initiate an improvement even if no statistically significant difference to the comparison group was found.

PMID:34453187 | DOI:10.1007/s00106-021-01103-3

J Anim Sci. 2021 Aug 28:skab232. doi: 10.1093/jas/skab232. Online ahead of print.

ABSTRACT

The objective of this experiment was to determine if statistical process control (SPC) procedures coupled with remote continuous data collection could accurately differentiate between animals experimentally inoculated with a viral-bacterial (VB) challenge or phosphate buffer solution (PBS). Crossbred heifers (N = 38; BW = 230 ± 16.4 kg) were randomly assigned to treatments by initial weight, ADG, BHV-1 and MH serum titers. Feeding behavior, DMI, animal activity and rumen temperature were continuously monitored remotely prior to and following VB challenge. VB-challenged heifers exhibited decreased (P < 0.01) ADG and DMI, as well as increased (P < 0.01) neutrophils and rumen temperature consistent with a bovine respiratory disease (BRD) infection. However, none of the heifers displayed overt clinical signs of disease. Shewhart and cumulative summation (CUSUM) charts were evaluated, with sensitivity and specificity computed on the VB-challenged heifers (n = 19), and PBS-challenged heifers (n = 19) respectively, accuracy was determined as the average of sensitivity and specificity. To address the diurnal nature of rumen temperature responses, summary statistics (Mean, minimum, maximum) were computed for daily quartiles (6-h intervals), and these quartile temperature models were evaluated separately. In the Shewhart analysis, DMI was the most accurate (95%) at deciphering between PBS- or VB-challenged heifers, followed by rumen temperature (94%) collected in the 2 nd and 3 rd quartiles. Rest was most the accurate accelerometer-based traits (89%), and meal duration (87%) and bunk visit (BV) frequency (82%) were the most accurate feeding behavior traits. Rumen temperature collected in the 3 rd quartile signaled the earliest (2.5 d) of all the variables monitored with the Shewhart, followed by BV frequency (2.8 d), meal duration (2.8 d), DMI (3.0 d) and rest (4.0 d). Rumen temperature and DMI and remained the most accurate variables in the CUSUM at 80 and 79%, respectively. Meal duration (58%), BV frequency (71%) and rest (74%) were less accurate when monitored with the CUSUM analysis. Furthermore, signal day was greater for DMI, rumen temperature and meal duration (4.4, 5.0 and 3.7 d, respectively) in the CUSUM compared to Shewhart analysis. These results indicate that Shewhart and CUSUM charts can effectively identify deviations in feeding behavior, activity and rumen temperature patterns for the purpose of detecting sub-clinical BRD in beef cattle.

PMID:34453166 | DOI:10.1093/jas/skab232