Category: Statistics

JAMA Netw Open. 2024 Nov 4;7(11):e2445771. doi: 10.1001/jamanetworkopen.2024.45771.

ABSTRACT

IMPORTANCE: Being born either small for gestational age (SGA) or large for gestational age (LGA) and experiencing rapid or slow growth after birth are associated with later-life obesity. Understanding the associations of dietary quality during pregnancy with infant growth may inform obesity prevention strategies.

OBJECTIVE: To evaluate the associations of prenatal dietary quality according to the Healthy Eating Index (HEI) and the Empirical Dietary Inflammatory Pattern (EDIP) with infant size at birth and infant growth from birth to age 24 months.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from birthing parent-child dyads in 8 cohorts participating in the Environmental influences on Child Health Outcomes program between 2007 and 2021. Data were analyzed from March 2021 to August 2024.

EXPOSURES: The HEI and the EDIP dietary patterns.

MAIN OUTCOMES AND MEASURES: Outcomes of interest were infant birth weight, categorized as SGA, reference range, or LGA, and infant growth from birth to ages 6, 12, and 24 months, categorized as slow growth (weight-for-length z score [WLZ] score difference <-0.67), within reference range (WLZ score difference -0.67 to 0.67), or rapid (WLZ score difference, >0.67).

RESULTS: The study included 2854 birthing parent-child dyads (median [IQR] maternal age, 30 [25-34] years; 1464 [51.3%] male infants). The cohort was racially and ethnically diverse, including 225 Asian or Pacific Islander infants (7.9%), 640 Black infants (22.4%), 1022 Hispanic infants (35.8%), 664 White infants (23.3%), and 224 infants (7.8%) with other race or multiple races. A high HEI score (>80), indicative of a healthier diet, was associated with lower odds of LGA (adjusted odds ratio [aOR], 0.88 [95% CI, 0.79-0.98]), rapid growth from birth to age 6 months (aOR, 0.80 [95% CI, 0.37-0.94]) and age 24 months (aOR 0.82 [95% CI, 0.70- 0.96]), and slow growth from birth to age 6 months (aOR, 0.65 [95% CI, 0.50-0.84]), 12 months (aOR, 0.74 [95% CI, 0.65-0.83]), and 24 months (OR, 0.65 [95% CI, 0.56-0.76]) compared with an HEI score 80 or lower. There was no association between high HEI and SGA (aOR, 1.14 [95% CI, 0.95-1.35]). A low EDIP score (ie, ≤63.6), indicative of a less inflammatory diet, was associated with higher odds of LGA (aOR, 1.24 [95% CI, 1.13-1.36]) and rapid infant growth from birth to age 12 months (aOR, 1.50 [95% CI, 1.18-1.91]) and lower odds of rapid growth to age 6 months (aOR, 0.77 [95% CI, 0.71-0.83]), but there was no association with SGA (aOR, 0.80 [95% CI, 0.51-1.25]) compared with an EDIP score of 63.6 or greater.

CONCLUSIONS AND RELEVANCE: In this cohort study, a prenatal diet that aligned with the US Dietary Guidelines was associated with reduced patterns of rapid and slow infant growth, known risk factors associated with obesity. Future research should examine whether interventions to improve prenatal diet are also beneficial in improving growth trajectory in children.

PMID:39570591 | DOI:10.1001/jamanetworkopen.2024.45771

JAMA Netw Open. 2024 Nov 4;7(11):e2446243. doi: 10.1001/jamanetworkopen.2024.46243.

ABSTRACT

IMPORTANCE: Although intensive follow-up of patients after curative surgery for colorectal cancer is common in clinical practice, evidence for a long-term survival benefit of more frequent testing is limited.

OBJECTIVE: To examine overall and colorectal cancer-specific mortality rates in patients with stage II or III colorectal cancer who underwent curative surgery and underwent high-frequency or low-frequency follow-up testing.

DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial with posttrial prespecified follow-up was performed in 23 centers in Sweden and Denmark. The original study enrolled 2509 patients with stage II or III colorectal cancer from Sweden, Denmark, and Uruguay (1 center) who received treatment from January 1, 2006, through December 31, 2010, and were followed up for up to 5 years. The participants from Sweden and Denmark were then followed up for 10 years through population-based health registries. The 53 patients from Uruguay were not included in the posttrial follow-up. Statistical analysis was performed from March to June 2024.

INTERVENTIONS: Patients were randomly allocated to follow-up testing with computed tomography (CT) scans and serum carcinoembryonic antigen (CEA) screening at 6, 12, 18, 24, and 36 months after surgery (high-frequency group; 1227 patients), or at 12 and 36 months after surgery (low-frequency group, 1229 patients).

MAIN OUTCOMES AND MEASURES: The outcomes were 10-year overall mortality and colorectal cancer-specific mortality rates. Both intention-to-treat and per-protocol analyses were performed.

RESULTS: Of the 2555 patients who were randomly allocated, 2509 were included in the intention-to-treat analysis, of whom 2456 (97.9%) were included in this posttrial analysis (median age, 65 years [IQR, 59-70 years]; 1355 male patients [55.2%]). The 10-year overall mortality rate for the high-frequency group was 27.1% (333 of 1227; 95% CI, 24.7%-29.7%) compared with 28.4% (349 of 1229; 95% CI, 26.0%-31.0%) in the low-frequency group (risk difference, 1.3% [95% CI, -2.3% to 4.8%]). The 10-year colorectal cancer-specific mortality rate in the high-frequency group was 15.6% (191 of 1227; 95% CI, 13.6%-17.7%) compared with 16.0% (196 of 1229; 95% CI, 14.0%-18.1%) in the low-frequency group (risk difference, 0.4% [95% CI, -2.5% to 3.3%]). The same pattern resulted from the per-protocol analysis.

CONCLUSIONS AND RELEVANCE: Among patients with stage II or III colorectal cancer, more frequent follow-up testing with CT scans and CEA testing did not result in a significant reduction in 10-year overall mortality or colorectal cancer-specific mortality. The results of this trial should be considered as the evidence base for updating clinical guidelines.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00225641.

PMID:39570590 | DOI:10.1001/jamanetworkopen.2024.46243

JAMA Netw Open. 2024 Nov 4;7(11):e2446591. doi: 10.1001/jamanetworkopen.2024.46591.

ABSTRACT

IMPORTANCE: Health-related quality of life is a critical health outcome and a clinically important patient-reported outcome in clinical trials. Hearing loss is associated with poorer health-related quality-of-life in older adults.

OBJECTIVE: To investigate the 3-year outcomes of hearing intervention vs health education control on health-related quality of life.

DESIGN, SETTING, AND PARTICIPANTS: This secondary analysis of a randomized clinical trial included participants treated for hearing loss at multiple US centers between 2018 and 2019 with 3-year follow-up completed in 2022. Eligible participants were aged 70 to 84 years, had untreated hearing loss, and were without substantial cognitive impairment. Participants were randomized (1:1) to hearing intervention or health education control and followed every 6 months.

INTERVENTION: Hearing intervention (provision of hearing aids and related technologies, counseling, education) or health education control (individual sessions covering topics relevant to chronic disease, disability prevention).

MAIN OUTCOMES AND MEASURES: Three-year change in the RAND-36 physical and mental health component scores over 3 years. The 8 individual domains of health-related quality-of-life were additionally assessed. Outcomes measured at baseline and at 6-month, 1-year, 2-year, and 3-year follow-ups. Intervention effect sizes estimated using a 2-level linear mixed effects model under the intention-to-treat principle.

RESULTS: A total of 977 participants were analyzed (mean [SD] age, 76.8 [4.0] years; 523 female [53.5%]; 112 Black [11.5%], 858 White [87.8%]; 521 had a Bachelor’s degree or higher [53.4%]), with 490 in the hearing intervention and 487 in the control group. Over 3 years, hearing intervention (vs health education control) had no significant association with physical (intervention, -0.49 [95% CI, -3.05 to 2.08]; control, -0.92 [95% CI, -3.39 to 1.55]; difference, 0.43 [95% CI, -0.64 to 1.51]) or mental (intervention, 0.38 [95% CI, -1.58 to 2.34]; control, -0.09 [95% CI, -1.99 to 1.81]; difference, 0.47 [95% CI, -0.41 to 1.35]) health-related quality of life.

CONCLUSIONS AND RELEVANCE: In this secondary analysis of a randomized clinical trial, hearing intervention had no association with physical and mental health-related quality-of-life over 3 years among older adults with hearing loss. Additional intervention strategies may be needed to modify health-related quality among older adults with hearing loss.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03243422.

PMID:39570588 | DOI:10.1001/jamanetworkopen.2024.46591

Med Care. 2024 Nov 15. doi: 10.1097/MLR.0000000000002100. Online ahead of print.

ABSTRACT

OBJECTIVES: To provide population utility norms from the Health Utilities Index Mark 3 (HUI3) for the province of Quebec, Canada.

METHODS: This study used data from the Care Trajectories Enriched Data (TorSaDE) cohort, which combines data from the Canadian Community Health Survey (CCHS) and the Quebec Provincial Insurance Board [Régie de l’assurance maladie du Quebec (RAMQ)]. The CCHS is a multiround health-related survey conducted by Statistics Canada since 2007. For each round spanning over 2 years, respondents were randomly selected and completed an online questionnaire. Quebec data for the HUI3 were available in the CCHS for rounds 2007, 2009, and 2013. The RAMQ database is an administrative database that contains information on health care services use and medical diagnostics. HUI3 scores were stratified by sociodemographic variables, as well as by self-reported health problems in the CCHS and by medical diagnostics from the RAMQ. Medical diagnostics were retrieved for the CCHS completion year and the year before and identifiable with the ICD-9 code in the RAMQ database.

RESULTS: A total of 55,656 individuals were considered in this analysis. The mean (95% CI) and the median interquartile range of HUI3 were respectively 0.919 (0.918-0.919) and 0.973 (0.905-1) for the entire population. Individuals with lower scores were females, those aged 75 and over, divorced or widowed, unemployed during the last 12 months, less educated, or with a lower annual household income. Individuals born abroad and with normal weight of body mass index had higher utility scores. HUI3 score decreased with the number of diagnosed diseases from 0.946 (0.946-0946) for individuals without diagnosed disease to 0.682 (0.678-0.686) for individuals diagnosed with up to 18 diseases. Regardless of the number of diagnosed diseases in the RAMQ database, individuals who self-reported suffering from a single health problem presented a significantly lower HUI3 ranging from 0.944 (0.943-0.944) for Asthma to 0.789 (0.782-0.796) for Alzheimer compared with 0.956 (0.956-0.957) for individuals with no reported health problems. The same pattern was observed when considering individuals regardless of the diagnosed and self-reported diseases.

CONCLUSION: Utility score norms for HUI3 were produced in the general population of Quebec. Significant differences among various health problems were identified and norms can be used to compare populations in studies that do not have a control group.

PMID:39570579 | DOI:10.1097/MLR.0000000000002100

Int J Clin Pharm. 2024 Nov 21. doi: 10.1007/s11096-024-01836-5. Online ahead of print.

ABSTRACT

BACKGROUND: Neutropenia can easily progress to febrile neutropenia and is a risk factor for life-threatening infections. Predicting and preventing severe neutropenia can help avoid such infections.

AIM: This study aimed to develop an optimal model using advanced statistical methods to predict neutropenia after 5-fluorouracil/cisplatin chemotherapy for esophageal cancer and to create a nomogram for clinical application.

METHOD: Patients who received 5-fluorouracil/cisplatin chemotherapy at Chiba University Hospital, Japan, between January 2011 and March 2021 were included. Clinical parameters were measured before the first, second, and third chemotherapy cycles and were randomly divided by patient into a training cohort (60%) and test cohort (40%). The predictive performance of Logistic, Stepwise, Lasso, and GLMMLasso models was evaluated by the area under the receiver-operating characteristic curve (AUC). A nomogram based on GLMMLasso was developed, and the accuracy of probabilistic predictions was evaluated by the Brier score.

RESULTS: The AUC for the first cycle of chemotherapy was 0.781 for GLMMLasso, 0.751 for Lasso, 0.697 for Stepwise, and 0.669 for Logistic. The respective AUCs for GLMMLasso in the second and third cycles were 0.704 and 0.900. The variables selected by GLMMLasso were cisplatin dose, 5-fluorouracil dose, use of leucovorin, sex, cholinesterase, and platelets. A nomogram predicting neutropenia was created based on each regression coefficient. The Brier score for the nomogram was 0.139.

CONCLUSION: We have developed a predictive model with high performance using GLMMLasso. Our nomogram can represent risk visually and may facilitate the assessment of the probability of chemotherapy-induced severe neutropenia in clinical practice.

PMID:39570570 | DOI:10.1007/s11096-024-01836-5

Drug Saf. 2024 Nov 21. doi: 10.1007/s40264-024-01487-5. Online ahead of print.

ABSTRACT

INTRODUCTION: Risk minimisation measures (RMMs) aim to ensure safe use of medicines, but their implementation in clinical practice is complicated by the diversity of stakeholders whose clinical decision making they seek to inform. Clinical practice guidelines (CPGs) are considered integral in clinical decision making.

OBJECTIVES: To determine the extent to which RMMs are included in the relevant CPGs and to describe factors that determine RMM inclusion.

METHODS: A multi-case study design using quantitative document analysis of CPGs combined with qualitative interviews with informants from organisations that issue CPGs. Cases from five therapeutic areas (TAs) with a regulatory requirement for further RMMs were studied individually in six EU member states (Denmark, Greece, Latvia, Netherlands, Portugal and Slovenia). Clinical practice guidelines were analysed using pre-defined coding frameworks. Interviewees were sampled purposively for experience and knowledge about CPG development and RMM inclusion. Verbatim interview transcripts were analysed inductively.

RESULTS: In total, 136 CPGs were analysed, and RMM information about TAs was included in 25% of CPGs. Based on 71 interviews we found that factors that determine RMM inclusion in CPGs include clinicians’ low awareness of RMMs despite awareness of RMMs’ safety concern, low expectation of RMMs’ clinical utility, and unfamiliarity with pharmacovigilance data supporting RMMs and perceived incompatibility of CPGs’ scope and purpose and RMM information.

CONCLUSIONS: The inclusion of RMM information in relevant CPGs is remarkably limited. It may be explained by characteristics of CPGs and of RMMs as well as lack of connection between national regulators and organisations and authors developing CPGs. More collaboration between stakeholders, national regulators and the EMA may advance implementation.

PMID:39570566 | DOI:10.1007/s40264-024-01487-5

Adv Ther. 2024 Nov 21. doi: 10.1007/s12325-024-03050-1. Online ahead of print.

ABSTRACT

INTRODUCTION: There is no information on the incidence of severe hypoglycemia in real-world patients with diabetes receiving ultra-rapid lispro (URLi). This post-marketing, observational, safety study assessed the incidence proportion and incidence rate of the first severe hypoglycemia event requiring a hospital visit in URLi-treated patients. It also compared the risk of severe hypoglycemia between patients treated with URLi or other rapid-acting insulin analogs (RAIAs).

METHODS: Claims data were obtained from a nationwide hospital-based administrative database in Japan (Medical Data Vision). Adults with diabetes who initiated URLi or other RAIA on/after June 01, 2020, were followed up through May 31, 2023. Severe hypoglycemia was identified using a validated algorithm. Incidence proportion and incidence rate of the first severe hypoglycemia event requiring a hospital visit was described in URLi-treated patients (descriptive analysis). These outcomes were also compared against propensity score (PS)-matched other RAIA-treated patients (comparator; comparative analysis). Hazard ratio (HR) and 95% confidence interval (CI) was estimated with a Cox proportional hazards model.

RESULTS: The descriptive analysis’ URLi-treated cohort included 17,838 patients [mean (standard deviation, SD) age 65.9 (15.7) years; 58.3% male]. The majority had type 2 diabetes (75.7%). The incidence proportion of the first severe hypoglycemia event requiring a hospital visit was 0.6% (95% CI 0.5, 0.8) and the incidence rate was 1.7 per 100 person-years (95% CI 0.7, 4.3). The comparative analysis included 10,592 URLi-treated and 52,917 comparator-treated patients. The incidence rate of severe hypoglycemia did not significantly differ between these cohorts (HR 0.8; 95% CI 0.5, 1.1; p = 0.132;.

CONCLUSION: This study did not show a statistically significant increase in the incidence and risk of the first severe hypoglycemia event requiring a hospital visit in real-world URLi-treated patients in Japan, compared with a PS-matched cohort of other RAIA-treated patients.

PMID:39570544 | DOI:10.1007/s12325-024-03050-1

Sports Med. 2024 Nov 21. doi: 10.1007/s40279-024-02144-8. Online ahead of print.

ABSTRACT

BACKGROUND: Several factors such as acute symptom severity, premorbid anxiety, and depression have been associated with concussion recovery. Elevated kinesiophobia has been associated with recovery from musculoskeletal conditions, as well as increased reaction time and vestibular-ocular motor dysfunction following concussion. However, kinesiophobia has yet to be evaluated as a modifier of concussion recovery time.

OBJECTIVES: This study was designed to evaluate the role of acute kinesiophobia levels on days until clinical recovery in collegiate athletes with concussion. We hypothesized that collegiate athletes with elevated Tampa Scale of Kinesiophobia (TSK) scores would take a greater number of days to achieve clinical recovery compared with athletes with lower values.

METHODS: Division I collegiate athletes diagnosed with a concussion (N = 113, 19.9 ± 1.5 years, 42% female) participated in this descriptive laboratory study. Participants were assigned to high [≥ 37 (H-TSK, n = 54)] or low [< 37 (L-TSK, n = 59)] TSK groups on the basis of the first TSK values recorded within 72 h of their concussion. Participants were also administered the Revised Head Injury Scale (HIS-r) to assess symptom severity within 72 h of injury. The Immediate Postconcussion and Cognitive Test (ImPACT) battery was administered at baseline and used to gather demographic variables such as biological sex, age, history of anxiety/depression, and concussion history, and as part of the athletes’ symptom-free assessment. Days until clinical recovery between H-TSK and L-TSK groups were compared using a Mann-Whitney U test. Spearman’s rank correlation coefficients were calculated to determine the relationship between TSK and days until clinical recovery in addition to other modifiers of recovery. Multiple linear regression was used to evaluate days until clinical recovery as a function of the TSK total score, controlling for the HIS-r and ImPACT variables.

RESULTS: Days until clinical recovery was significantly longer in the H-TSK group (median difference = 2.5 days, p < 0.001) compared with the L-TSK group. A significant, moderate positive correlation between the TSK score and days to clinical recovery (ρ = 0.45, p < 0.001) was observed, which was also the strongest correlation among all variables. Our regression model demonstrated that for every point increase on the TSK, days until clinical recovery increased by 0.23 while controlling for total symptom severity, age, concussion history, psychiatric history, and biological sex (β = 0.23, p = 0.018). All other variables entered into the regression were not statistically significant.

CONCLUSIONS: Our data suggest that athletes with TSK scores above 37 within 72 h of a concussion had a greater number of days until clinical recovery when compared with athletes with TSK values below 37. The TSK score had the highest correlation with days until clinical recovery when compared with other known modifiers of recovery, including total symptom severity. The TSK score was also the strongest predictor of days until clinical recovery. Collectively, these findings suggest that the TSK score should be considered by healthcare professionals to help inform effective management strategies for collegiate athletes with concussion.

PMID:39570534 | DOI:10.1007/s40279-024-02144-8

Environ Sci Pollut Res Int. 2024 Nov 21. doi: 10.1007/s11356-024-35558-y. Online ahead of print.

ABSTRACT

The chemical behavior of mercury (Hg) and its interactions with naturally occurring ligands shape its environmental fate and impact. The neurotoxic properties of Hg are widely known and studied both in vitro and in vivo. However, there continues to be limited information on the influence of chelation with large organic ligands on the toxicity to marine macro-organisms. This work examined the effect of Hg complexed with various types of dissolved organic matter (DOM) on the mortality and hatching success of Artemia sp. nauplii under varying marine media conditions. The results confirmed both, an alleviating as well as additive, DOM-specific, effect on mortality. DOM coexposure resulted in a compound specific decreased or increased toxicity in comparison with single exposure in artificial seawater, with LC₅₀ values ranging from 2.11 to 62.89 µM. Hatching success under conditions of Hg exposure was almost two orders of magnitude more sensitive than toxicity in hatched individuals. Elevated DOM concentrations had no statistically significant impact on hatching success with computed EC₅₀ values ranging from 196 to 324 nM.

PMID:39570530 | DOI:10.1007/s11356-024-35558-y

Biochem Genet. 2024 Nov 21. doi: 10.1007/s10528-024-10949-5. Online ahead of print.

ABSTRACT

Cervical cancer (CC) remains a real public health problem in low- and middle-income countries, where technical resources and competent personnel are insufficient. Persistent cervix infection by high-risk human papillomavirus (Hr-HPV) is the main cause of CC development. In the current study, we examined the distribution of Hr-HPV in the general healthy Malian population using cervicovaginal self- sampling. A total of 354 women were recruited, with a median age of 34 ± 11.37 years, IQR (27-43). We found that 100% of participants agreed to self-sample at the health center. For result announcement 99.2% expressed their preference to be contacted by cell phone. Furthermore, 100% of study participants showed their willingness to undergo confirmatory CC test in case of Hr-HPV test proved positive, and to receive treatment in the event of the presence of cervical lesions. The overall prevalence of Hr-HPV was 21.2% (95% CI: 17-25.8). HPV31/35/33/52/58 with 11.9% (95% CI: 8.7-15.7) and HPV39/68/56/66 with 5.9% (95% CI: 3.7-8.9) were the most common Hr-HPV subtypes. We noted that Hr-HPV genotypes were more prevalent among women under 25 years, 36.1% (N = 61). In addition, the distribution of Hr-HPV was statistically associated with age, W = 12,374, p = 0.015. Our data showed that 25.3% (N = 19) of Hr-HPV-positive women were tested positive by VIA/VILI. Among the 19 VIA/VILI-positive women, histological examination showed that 4 were CIN1, 4 were CIN2, and 2 were CIN3 grades. In addition, the median age of participants with CIN2 and CIN3 was statistically higher than the median of those with CIN1 grade, 25 years IQR (21-26.75) versus 50 years, IQR (40.25-55), W = 24, p = 0.009. In sum, end-users are very satisfied with the cervicovaginal self-sampling device for identifying HR-HPV genotypes as part of CC screening. In addition, it enables hospital practitioners to take the necessary action after triaging women according to their HR-HPV genotype.

PMID:39570507 | DOI:10.1007/s10528-024-10949-5