Efficacy and safety of dolutegravir/lamivudine in virologically suppressed female participants: week 48 data from the pooled TANGO and SALSA studies.

OBJECTIVES: Women represent >50% of people with HIV globally but have historically been underrepresented in clinical trials. We evaluated the efficacy and safety of switching to dolutegravir/lamivudine (DTG/3TC) vs continuing their current antiretroviral regimen (CAR) by sex assigned at birth (female and male) in virologically suppressed adults with HIV-1 without prior virological failure in a pooled analysis of two randomized controlled trials. METHODS: This analysis included 48-week data from the phase 3 TANGO and SALSA studies. Primary and key secondary endpoints included proportions of participants with HIV-1 RNA ≥50 and <50 copies/mL at week 48, respectively. Safety was also assessed. RESULTS: Of 1234 participants, 250 (DTG/3TC, n = 133; CAR, n = 117) were female at birth. Week 48 proportions of participants with Snapshot HIV-1 RNA ≥50 copies/mL were similar regardless of sex at birth (DTG/3TC vs CAR: female, <1% [1/133] vs 2% [2/117]; male, <1% [1/482] vs <1% [3/502]). Proportions with HIV-1 RNA <50 copies/mL were high across sexes and treatment groups (DTG/3TC vs CAR: female, 91% [121/133] vs 89% [104/117]; male, 94% [455/482] vs 94% [471/502]). Immunological response with DTG/3TC was slightly higher in female participants. Incidences of adverse events leading to withdrawal and serious adverse events were low and comparable between treatment groups and across sexes. Weight gain was higher with DTG/3TC than with CAR among female participants aged ≥50 years (treatment difference 2.08 kg [95% confidence interval 0.40-3.75]). CONCLUSIONS: Results confirm the robustness of DTG/3TC as a switch option in virologically suppressed females with HIV-1, with outcomes similar to those in males.

Efficacy Assessment of Post-nephrectomy Adjuvant Therapies in Patients with Renal Cell Carcinoma.

OBJECTIVE: The objective of our study was to integrate the efficacy results of post-nephrectomy adjuvant therapies in renal cell carcinoma (RCC) patients with risk of recurrence, and attempt to determine the optimal intervention choice. METHODS: We performed standard meta-analysis procedures in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The PubMed, Embase, and Cochrane Library databases were searched from inception to 22 September 2022. Randomized controlled trials reporting overall survival (OS) or disease-free survival (DFS) of adjuvant therapies, including immune checkpoint inhibitors (ICIs) and targeted therapies, in adult post-nephrectomy RCC patients were eligible for inclusion. RESULTS: Seven studies involving 7548 participants were included in our analyses. In contrast with placebo, DFS benefit with ICIs was only observed in female RCC patients and RCC patients with high programmed death-ligand 1 (PD-L1) expression (≥ 1%), sarcomatoid features, and M0 intermediate-high risk. Network meta-analyses demonstrated that pembrolizumab exhibited both DFS and OS benefit compared with placebo, sunitinib, sorafenib, and girentuximab, and only DFS benefit compared with atezolizumab and nivolumab plus ipilimumab. CONCLUSIONS: Our results suggest that post-nephrectomy RCC patients with sarcomatoid differentiation and high PD-L1 expression were more responsive to ICIs. Furthermore, pembrolizumab monotherapy exhibited superior DFS and OS results over other adjuvant therapies.

COVID-19 in three waves in a tertiary referral hospital in Belgium: a comparison of patient characteristics, management, and outcome.

PURPOSE: Few studies have compared patient characteristics, clinical management, and outcome of patients with COVID-19 between the different epidemic waves. In this study, we describe patient characteristics, treatment, and outcome of patients admitted for COVID-19 in the Antwerp University Hospital over the first three epidemic waves of 2020-2021. METHODS: Retrospective observational study of COVID-19 patients in a Belgian tertiary referral hospital. All adult patients with COVID-19, hospitalized between February 29, 2020, and June 30, 2021, were included. Standardized routine medical data was collected from patient records. Risk factors were assessed with multivariable logistic regression. RESULTS: We included 722 patients, during the first (n = 179), second (n = 347) and third (n = 194) wave. We observed the lowest disease severity at admission during the first wave, and more elderly and comorbid patients during the second wave. Throughout the subsequent waves we observed an increasing use of corticosteroids and high-flow oxygen therapy. In spite of increasing number of complications throughout the subsequent waves, mortality decreased each wave (16.6%,15.6% 11.9% in 1st, 2nd and 3rd wave respectively). C-reactive protein above 150 mg/L was predictive for the need for intensive care unit admission (odds ratio (OR) 3.77, 95% confidence interval (CI) 2.32-6.15). A Charlson comorbidity index ≥ 5 (OR 5.68, 95% CI 2.54-12.70) and interhospital transfers (OR 3.78, 95% CI 2.05-6.98) were associated with a higher mortality. CONCLUSIONS: We observed a reduction in mortality each wave, despite increasing comorbidity. Evolutions in patient management such as high-flow oxygen therapy on regular wards and corticosteroid use may explain this favorable evolution.

Finding the best subgroup with differential treatment effect with multiple outcomes.

Precision medicine aims to identify specific patient subgroups that may benefit the most from a particular treatment than the whole population. Existing definitions for the best subgroup in subgroup analysis are based on a single outcome and do not consider multiple outcomes; specifically, outcomes of different types. In this article, we introduce a definition for the best subgroup under a multiple-outcome setting with continuous, binary, and censored time-to-event outcomes. Our definition provides a trade-off between the subgroup size and the conditional average treatment effects (CATE) in the subgroup with respect to each of the outcomes while taking the relative contribution of the outcomes into account. We conduct simulations to illustrate the proposed definition. By examining the outcomes of urinary tract infection and renal scarring in the RIVUR clinical trial, we identify a subgroup of children that would benefit the most from long-term antimicrobial prophylaxis.

In-depth analysis of data from the RAS-ALS study reveals new insights in rasagiline treatment for amyotrophic lateral sclerosis.

BACKGROUND AND PURPOSE: In 2016, we concluded a randomized controlled trial testing 1 mg rasagiline per day add-on to standard therapy in 252 amyotrophic lateral sclerosis (ALS) patients. This article aims at better characterizing ALS patients who could possibly benefit from rasagiline by reporting new subgroup analysis and genetic data. METHODS: We performed further exploratory in-depth analyses of the study population and investigated the relevance of single nucleotide polymorphisms (SNPs) related to the dopaminergic system. RESULTS: Placebo-treated patients with very slow disease progression (loss of Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised [ALSFRS-R] per month before randomization of ≤0.328 points) showed a per se survival probability after 24 months of 0.85 (95% confidence interval = 0.65-0.94). The large group of intermediate to fast progressing ALS patients showed a prolonged survival in the rasagiline group compared to placebo after 6 and 12 months (p = 0.02, p = 0.04), and a reduced decline of ALSFRS-R after 18 months (p = 0.049). SNP genotypes in the MAOB gene and DRD2 gene did not show clear associations with rasagiline treatment effects. CONCLUSIONS: These results underline the need to consider individual disease progression at baseline in future ALS studies. Very slow disease progressors compromise the statistical power of studies with treatment durations of 12-18 months using clinical endpoints. Analysis of MAOB and DRD2 SNPs revealed no clear relationship to any outcome parameter. More insights are expected from future studies elucidating whether patients with DRD2CC genotype (Rs2283265) show a pronounced benefit from treatment with rasagiline, pointing to the opportunities precision medicine could open up for ALS patients in the future.

Waistline to thigh circumference ratio as a predictor of MAFLD: a health care worker study with 2-year follow-up.

BACKGROUND: This study aimed to determine whether the waist-to-thigh ratio (WTTR) is associated with the incidence of metabolic-associated fatty liver disease (MAFLD) in health care workers. METHODS: There were 4517 health care workers with baseline data and results from 2 follow-up examinations. We divided the subjects into 3 groups according to baseline WTTR and used the Cox hazard regression model to estimate MAFLD risk. RESULTS: The WTTRs were categorized by tertiles at baseline using the values 1.58 and 1.66. Patients with higher WTTR tended to have significantly greater values for the following factors, body mass index (BMI), fasting blood glucose (FPG), systolic blood pressure, diastolic blood pressure, total cholesterol (TC), triglycerides (TG), low-density lipoprotein-cholesterol (LDL-C) and neck circumference. The incidence of MAFLD significantly increased with increasing WTTR tertiles (5.74%, 12.75% and 22.25% for the first, second and third tertiles, respectively, P < 0.05 for trend). Kaplan-Meier(K-M) survival analysis revealed a significant tendency towards increased MAFLD risk with increasing WTTR tertile. In the fully adjusted model, the hazard ratios (95% CIs) for MAFLD in the second, third WTTR tertiles compared with the first quartile were 2.17(1.58,2.98), 3.63(2.70,4.89), respectively, third neck circumference tertiles compared with the first quartile were 2.84(1.89,4.25), 8.95(6.00,13.35), respectively. Compared with those of individuals with a BMI > 23 kg/m2, the associations between WTTR and MAFLD incidence were more pronounced in subjects with a BMI < 23 kg/m2. Similarly, the difference in neck circumference was more pronounced in these patients with a BMI < 23 kg/m2. CONCLUSIONS: Our results revealed that the WTTR is an independent risk factor for MAFLD, and there was a dose‒response relationship between the WTTR and MAFLD risk. The neck circumference was significantly different in subjects with a BMI < 23 kg/m2. This approach provides a new way to predict the incidence rate of MAFLD.

Association between dietary riboflavin intake and cognitive decline in older adults: a cross-sectional analysis.

BACKGROUND: Research exploring the link between dietary riboflavin intake and cognitive decline in this demographic is limited. Our aim was to examine the association between riboflavin intake levels and cognitive decline. METHODS: The National Health and Nutrition Examination Survey (NHANES) data from 2011 to 2014 were utilized in this cross-sectional analysis. The Consortium to Establish a Registry for Alzheimer's Disease test Word Learning delayed recall trial (DR), Digit Symbol Substitution Test (DSST), Animal Fluency Test(AFT) and Z test were used to evaluate cognitive performance. Multivariate logistic regression, restricted cubic spline and subgroup analysis were performed to evaluate the associations between riboflavin intake and cognitive decline. RESULTS: The study included a total of 2255 patients, with 47.9% being male. The incidence of cognitive decline was 23.8%. After adjusting for all selected covariates, we found that high riboflavin intake was associated with a lower risk of cognitive impairment in adults in the United States. When riboflavin intake was used as a Categorical variable, compared to those with the lowest intake, the odds ratio (OR) of individuals with the highest riboflavin intake for DR test, AFT test, DSST test and Z test were 0.73 (95% CI: 0.53~1), 0.68(95% CI: 0.49-0.96),0.53(95% CI: 0.37-0.77) and 0.56(95% CI: 0.39-0.8). The study also found an L-shaped association between riboflavin intake and cognitive decline, with an inflection point at approximately 2.984 mg/d. CONCLUSIONS: Our cross-sectional study in a nationwide sample of American old adults suggests that dietary riboflavin intake was negative associated with cognitive decline.

Factors affecting responsiveness of vadadustat in patients with anemia associated with chronic kidney disease: a post-hoc subgroup analysis of Japanese phase 3 randomized studies.

BACKGROUND: Vadadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor developed for treating anemia in chronic kidney disease (CKD). The purpose of this post-hoc analysis was to investigate the factors affecting the responsiveness to vadadustat in anemia patients with nondialysis-dependent (NDD) or hemodialysis-dependent (HDD) CKD in two Japanese phase 3 studies. METHODS: Of 151 and 162 patients enrolled in NDD-CKD and HDD-CKD studies, 136 and 140 patients, respectively, were included and divided into subgroups for the analysis. To assess vadadustat responsiveness, the resistance index was defined as the mean body weight-adjusted dose of vadadustat (mg/kg) at weeks 20-24 divided by the mean hemoglobin (g/dL) at weeks 20-24. Multivariate analysis was performed to identify the variables affecting the resistance index. RESULTS: Independent factors identified as determinants for better response to vadadustat were as follows: high baseline hemoglobin, low baseline eGFR, high week-20-24 ferritin, and CKD not caused by autoimmune disease/glomerulonephritis/vasculitis in NDD-CKD; and male sex, high baseline C-reactive protein, and low baseline erythropoiesis-stimulating agent resistance index (ERI) in HDD-CKD. CONCLUSIONS: In this post-hoc analysis, several factors were identified as affecting the response to vadadustat. These results may provide useful information leading to an appropriate dose modification for vadadustat. CLINICAL TRIAL REGISTRATION: NCT03329196 (MT-6548-J01) and NCT03439137 (MT-6548-J03).

Associations of dexamethasone's effect on morphine consumption after total knee arthroplasty-Subgroup analyses.

The DEXamethasone twice for pain treatment after Total Knee Arthroplasty (DEX-2-TKA) trial showed that adding one and two doses of 24 mg intravenous dexamethasone to paracetamol, ibuprofen and local infiltration analgesia, reduced morphine consumption (primary outcome) within 48 h after TKA. We aimed to explore the differences in the effect of dexamethasone on morphine consumption in different subgroups. Quantile regression adjusted for site was used to test for significant interaction between the predefined dichotomised subgroups and treatment group. The subgroups were defined based on baseline data: sex (male/female), age (≤65 years/>65 years), American Society of Anaesthesiologists (ASA)-score (ASA I + II/III), visual analogue score of preoperative pain at rest (≤30 mm/>30 mm), pain during mobilisation (≤30 mm/>30 mm), type of anaesthesia (spinal anaesthesia/general anaesthesia and spinal converted to general anaesthesia), and prior daily use of analgesics (either paracetamol and/or NSAID/neither). These analyses were supplemented with post hoc multivariate linear regression analyses. Test of interaction comparing sex in the pairwise comparison between DX2 (dexamethasone [24 mg] + dexamethasone [24 mg]) versus placebo (p = .02), showed a larger effect of dexamethasone on morphine consumption in male patients compared to females. Test of interaction comparing age in the pairwise comparison between DX1 (dexamethasone [24 mg] + placebo) versus placebo (p = .04), showed a larger effect of dexamethasone on morphine consumption in younger patients (≤65 years) compared to older. All remaining subgroup analyses showed no evidence of a difference. The supplemental multivariate analyses did not support any significant interaction for sex (p = .256) or age (p = .730) but supported a significant interaction with the type of anaesthesia (p < .001). Our results from the quantile regression analyses indicate that the male sex and younger age (≤65 years) may be associated with a larger analgesic effect of dexamethasone than the effects in other types of patients. However, this is not supported by post-hoc multivariate linear regression analyses. The two types of analyses both supported a possible interaction with the type of anaesthesia.

Using Power Analysis to Choose the Unit of Randomization, Outcome, and Approach for Subgroup Analysis for a Multilevel Randomized Controlled Clinical Trial to Reduce Disparities in Cardiovascular Health.

We give examples of three features in the design of randomized controlled clinical trials which can increase power and thus decrease sample size and costs. We consider an example multilevel trial with several levels of clustering. For a fixed number of independent sampling units, we show that power can vary widely with the choice of the level of randomization. We demonstrate that power and interpretability can improve by testing a multivariate outcome rather than an unweighted composite outcome. Finally, we show that using a pooled analytic approach, which analyzes data for all subgroups in a single model, improves power for testing the intervention effect compared to a stratified analysis, which analyzes data for each subgroup in a separate model. The power results are computed for a proposed prevention research study. The trial plans to randomize adults to either telehealth (intervention) or in-person treatment (control) to reduce cardiovascular risk factors. The trial outcomes will be measures of the Essential Eight, a set of scores for cardiovascular health developed by the American Heart Association which can be combined into a single composite score. The proposed trial is a multilevel study, with outcomes measured on participants, participants treated by the same provider, providers nested within clinics, and clinics nested within hospitals. Investigators suspect that the intervention effect will be greater in rural participants, who live farther from clinics than urban participants. The results use published, exact analytic methods for power calculations with continuous outcomes. We provide example code for power analyses using validated software.

Bayesian Multivariate Logistic Regression for Superiority and Inferiority Decision-Making under Observable Treatment Heterogeneity.

The effects of treatments may differ between persons with different characteristics. Addressing such treatment heterogeneity is crucial to investigate whether patients with specific characteristics are likely to benefit from a new treatment. The current paper presents a novel Bayesian method for superiority decision-making in the context of randomized controlled trials with multivariate binary responses and heterogeneous treatment effects. The framework is based on three elements: a) Bayesian multivariate logistic regression analysis with a Pólya-Gamma expansion; b) a transformation procedure to transfer obtained regression coefficients to a more intuitive multivariate probability scale (i.e., success probabilities and the differences between them); and c) a compatible decision procedure for treatment comparison with prespecified decision error rates. Procedures for a priori sample size estimation under a non-informative prior distribution are included. A numerical evaluation demonstrated that decisions based on a priori sample size estimation resulted in anticipated error rates among the trial population as well as subpopulations. Further, average and conditional treatment effect parameters could be estimated unbiasedly when the sample was large enough. Illustration with the International Stroke Trial dataset revealed a trend toward heterogeneous effects among stroke patients: Something that would have remained undetected when analyses were limited to average treatment effects.

Investigating Stability in Subgroup Identification for Stratified Medicine.

Subgroup analysis may be used to investigate treatment effect heterogeneity among subsets of the study population defined by baseline characteristics. Several methodologies have been proposed in recent years and with these, statistical issues such as multiplicity, complexity, and selection bias have been widely discussed. Some methods adjust for one or more of these issues; however, few of them discuss or consider the stability of the subgroup assignments. We propose exploring the stability of subgroups as a sensitivity analysis step for stratified medicine to assess the robustness of the identified subgroups besides identifying possible factors that may drive this instability. After applying Bayesian credible subgroups, a nonparametric bootstrap can be used to assess stability at subgroup-level and patient-level. Our findings illustrate that when the treatment effect is small or not so evident, patients are more likely to switch to different subgroups (jumpers) across bootstrap resamples. In contrast, when the treatment effect is large or extremely convincing, patients generally remain in the same subgroup. While the proposed subgroup stability method is illustrated through Bayesian credible subgroups method on time-to-event data, this general approach can be used with other subgroup identification methods and endpoints.

Predicting subgroup treatment effects for a new study: Motivations, results and learnings from running a data challenge in a pharmaceutical corporation.

We present the motivation, experience, and learnings from a data challenge conducted at a large pharmaceutical corporation on the topic of subgroup identification. The data challenge aimed at exploring approaches to subgroup identification for future clinical trials. To mimic a realistic setting, participants had access to 4 Phase III clinical trials to derive a subgroup and predict its treatment effect on a future study not accessible to challenge participants. A total of 30 teams registered for the challenge with around 100 participants, primarily from Biostatistics organization. We outline the motivation for running the challenge, the challenge rules, and logistics. Finally, we present the results of the challenge, the participant feedback as well as the learnings. We also present our view on the implications of the results on exploratory analyses related to treatment effect heterogeneity.

Exploring Stratification Strategies for Population- Versus Randomization-Based Inference.

Stratification on important variables is a common practice in clinical trials, since ensuring cosmetic balance on known baseline covariates is often deemed to be a crucial requirement for the credibility of the experimental results. However, the actual benefits of stratification are still debated in the literature. Other authors have shown that it does not improve efficiency in large samples and improves it only negligibly in smaller samples. This paper investigates different subgroup analysis strategies, with a particular focus on the potential benefits in terms of inferential precision of prestratification versus both poststratification and post hoc regression adjustment. For each of these approaches, the pros and cons of population-based versus randomization-based inference are discussed. The effects of the presence of a treatment-by-covariate interaction and the variability in the patient responses are also taken into account. Our results show that, in general, prestratifying does not provide substantial benefit. On the contrary, it may be deleterious, in particular for randomization-based procedures in the presence of a chronological bias. Even when there is treatment-by-covariate interaction, prestratification may backfire by considerably reducing the inferential precision.

The impact of pre-stroke aspirin exposure on radiographic appearance and disability outcomes: A post-hoc analysis of the SPS3 trial: Aspirin Use and Small Subcortical Stroke.

OBJECTIVES: The effect of pre-stroke use of aspirin on small subcortical infarct dimensions or outcomes is not well described. We aimed to bridge this knowledge gap amongst a well-described and heterogeneous patient population. MATERIALS AND METHODS: We performed a post-hoc analysis of the Secondary Prevention of Small Subcortical Stroke (SPS3) trial. The primary exposure was aspirin use ≤7 days of index stroke. The primary outcomes were infarct dimensions. Functional outcomes by modified Rankin Scale (mRS) was a secondary outcome. Age restricted (≥55 years) subgroup analyses were performed as a sensitivity analysis. Descriptive statistical and regression modeling were performed for data analysis. RESULTS: We included 1423 participants of which 453(31.8 %) used aspirin. Aspirin use was associated with more cardiovascular risk diagnoses. Maximal infarct diameter did not differ with pre-stroke aspirin use (11.3±4.2 mm versus 11.8±4.1 mm, p=0.057) however infarct area was smaller with exposure (126.4±90.0 mm2 versus 137.4±97.0 mm2, p=0.037) regardless of aspirin strength. Participants ≥55 years had smaller infarct diameters (11.1±4.2 mm versus 11.9±4.4 mm, p=0.019) and area (123.4±87.1 mm2 versus 130.6±93.2 mm2, p=0.037) with aspirin use. mRS did not significantly differ in our analyses. CONCLUSIONS: In this post-hoc analysis of the SPS3 trial, pre-stroke aspirin use was associated with a smaller infarct area regardless of aspirin strength and without impact on functional outcomes. These findings were more pronounced in participants ≥55 years. REGISTRATION: https://clinicaltrials.gov/study/NCT00059306?term= %22sps3 %22&rank=1.

U-Shaped Association between Serum Chloride Levels and In-Hospital Mortality in Patients with Congestive Heart Failure in Intensive Care Units.

Serum chloride level has clinical significance in the prognosis of heart failure. Little is known regarding the association between serum chloride levels and in-hospital mortality in patients with heart failure.This retrospective study used clinical data obtained from the Medical Information Mart for Intensive Care Database. The study cohort comprised patients who were categorized on the basis of their serum chloride levels, and the primary endpoint was in-hospital mortality. To assess the impact of serum chloride levels at the time of intensive care unit admission on in-hospital mortality, we used various statistical approaches, including multivariable logistic regression models, a generalized additive model, and a two-piecewise linear regression model. In addition, subgroup analysis was conducted to examine the robustness of the main findings.This study comprised 15,983 participants. When compared with the reference group (Q5), the groups with the highest (Q7) and lowest (Q1) blood chloride levels exhibited increased in-hospital mortality, with fully adjusted odds ratios (ORs) of 1.36 [95% confidence interval (CI): 1.08-1.71] and 1.25 (95% CI: 1-1.56), respectively. A U-shaped relationship was observed between blood chloride levels and in-hospital mortality, with the lowest risk observed at a threshold of 105.017 mmol/L. The effect sizes and corresponding CIs below and above the threshold were 0.969 (95% CI: 0.957-0.982) and 1.039 (95% CI: 1.002-1.076), respectively. Stratified analyses demonstrated the robustness of this correlation.The relationship between serum chloride levels and in-hospital mortality in patients with heart failure was U-shaped, with an inflection point of 105.017 mmol/L.

Quantifying and reducing inequity in average treatment effect estimation.

BACKGROUND: Across studies of average treatment effects, some population subgroups consistently have lower representation than others which can lead to discrepancies in how well results generalize. METHODS: We develop a framework for quantifying inequity due to systemic disparities in sample representation and a method for mitigation during data analysis. Assuming subgroup treatment effects are exchangeable, an unbiased sample average treatment effect estimator will have lower mean-squared error, on average across studies, for subgroups with less representation when treatment effects vary. We present a method for estimating average treatment effects in representation-adjusted samples which enables subgroups to optimally leverage information from the full sample rather than only their own subgroup's data. Two approaches for specifying representation adjustment are offered-one minimizes average mean-squared error for each subgroup separately and the other balances minimization of mean-squared error and equal representation. We conduct simulation studies to compare the performance of the proposed estimators to several subgroup-specific estimators. RESULTS: We find that the proposed estimators generally provide lower mean squared error, particularly for smaller subgroups, relative to the other estimators. As a case study, we apply this method to a subgroup analysis from a published study. CONCLUSIONS: We recommend the use of the proposed estimators to mitigate the impact of disparities in representation, though structural change is ultimately needed.

Amikacin liposome inhalation suspension for Mycobacterium avium complex pulmonary disease: A subgroup analysis of Japanese patients in the randomized, phase 3, CONVERT study.

BACKGROUND: CONVERT, a randomized, active-controlled, global, Phase 3 trial demonstrated that patients with treatment-refractory Mycobacterium avium complex (MAC) pulmonary disease were more likely to achieve culture conversion with amikacin liposome inhalation suspension (ALIS) plus guideline-based therapy (GBT) versus those continuing on GBT alone. This subgroup analysis reports the efficacy and safety of ALIS in Japanese patients enrolled in CONVERT. METHODS: Japanese patients aged ≥20 years with treatment-refractory MAC pulmonary disease from Japanese sites were included. Patients were randomized to receive once-daily 590 mg ALIS + GBT or GBT alone; patients converting by Month 6 remained in the study to complete 12-month treatment followed by a 12-month off-treatment period. Nonconverters exited the study at Month 8. The primary endpoint was the proportion of patients achieving culture conversion by Month 6. RESULTS: Of the 59 Japanese patients screened, 48 were randomized to receive ALIS + GBT (n = 34) or GBT alone (n = 14), and 41/48 (85.4 %) were women. The mean (standard deviation) age of patients was 64.5 (8.6) years, and 83.3 % of patients had bronchiectasis at baseline. By Month 6, sputum culture conversion was cumulatively achieved in 9/34 (26.5 %) patients receiving ALIS + GBT versus none receiving GBT alone. Treatment-emergent adverse events were reported in 94.1 % and 100.0 % of patients receiving ALIS + GBT and GBT alone, respectively. No deaths were reported. CONCLUSIONS: The efficacy observed in the Japanese subpopulation was largely consistent with that in the overall CONVERT study population, with more patients achieving culture conversion with ALIS + GBT versus GBT alone. Safety profiles were similar between the overall population and the Japanese subpopulation. CLINICAL TRIAL REGISTRATION: NCT02344004.

Association between thiamine intake and depression: A national cross-sectional study.

BACKGROUND: Recent years have seen increasing attention to improving depressive symptoms through dietary intakes, yet the association between thiamine intake and depression remains unclear. The present study aimed to explore this association using data from an American cross-sectional study. METHODS: We explored the association of covariates, exposure, and outcome with logistic regression equations. Multivariable regression models were performed to further exclude confounding factors. To investigate nonlinear relationships, we employed restricted cubic splines. Recursive algorithms were utilized to identify inflection points. Additionally, we conducted stratified analyses by age and sex to uncover differences among subgroups. RESULTS: When all covariates were adjusted, the association between thiamine intake and depression was not statistically significant [0.93 (0.82, 1.07)]. In the linear trend test using Q1 as the reference, the ORs (95%CI) for Q2, Q3, and Q4 were 0.87 (0.73, 1.04), 0.83 (0.68, 1.00), and 0.92 (0.73, 1.16), which suggested that the association might be nonlinear. We then confirmed this nonlinear relationship with a restricted cubic spline, and the inflection point of 1.35 mg/day was calculated. Before the inflection point, the effect value of the relationship was 0.68 (0.53, 0.89). After the inflection point, no significant association was found [1.10 (0.92, 1.31)]. Stratified analyses revealed that this nonlinear relationship was consistent among women and individuals aged <60 years. DISCUSSION: In this cross-sectional study among American general adults, we found a nonlinear association between thiamine intake and depression and further observed differences by age and sex.

Impact of Humectants on Physicochemical and Functional Properties of Jerky: A Meta-Analysis.

This study aimed to determine the effects of humectants on moisture content, water activity, tenderness, color, microbiological analysis, protein denaturation, and oxidation of jerky. A thorough search for papers published in scientific journals that examined the impacts of humectants on jerky was carried out using Web of Science, Google Scholar, PubMed, and Science Direct. Only 14 studies matched inclusion requirements. They were used in the meta-analysis to synthesise quantitative findings. In the current investigation, jerky produced with beef, poultry, goat, or pork was used. The standardised mean difference (SMD) between treatments with humectants and controls was examined to investigate the effects of humectants using random-effects models. Heterogeneity was investigated using meta-regression. A subgroup analysis was carried out for significant factors. Results revealed that the addition of humectants had no significant impact on water activity, pH, fat, ash, CIE L*, or CIE a* (p>0.05). However, humectant addition significantly increased moisture (SMD=1.28, p<0.05), CIE b* (SMD=1.67, p<0.05), and overall acceptability (SMD=1.73, p<0.05). It significantly decreased metmyoglobin (SMD=-0.96, p<0.05), shear force (SMD=-0.84, p<0.05), and protein (SMD=-1.61, p<0.05). However, it was difficult to get a firm conclusion about how humectants affected the myofibrillar fragmentation index, total plate count, and 2-thiobarbituric acid-reactive substances because there were fewer than ten studies. To sum up, the proper use of humectants in jerky demands careful attention to both type and quantity, needing a delicate balancing act with other contributing factors.