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Background: The influence of inflammation on iron status among people living with HIV (PLWHIV) has not been well explored. We evaluated the trajectory of iron status among PLWHIV during the first year of highly active antiretroviral therapy (HAART), compared alternative approaches for inflammation correction, and assessed the associations of iron status with HIV‐1 viral load and anthropometric outcomes. Methods: We conducted a secondary analysis of data from a randomized trial among 400 adults initiating HAART in Tanzania. Ferritin and C‐reactive protein (CRP) were measured at baseline, 1, 6 or 12 months. Ferritin was considered in four ways: unadjusted, and adjusted for inflammation using higher cut‐off (HC), Thurnham‐corrected (TC) and regression‐corrected (RC) approaches. For unadjusted, TC and RC ferritin, iron deficiency (ID) was defined using ferritin < 15 μg/L and elevated iron status was defined using ferritin > 150 μg/L among females and > 200 μg/L among males. For HC ferritin, elevated iron status was defined based on serum ferritin > 500 μg/L, while ID was defined using ferritin < 70 μg/L in the presence of inflammation and < 15 μg/L in the absence of inflammation. Regression models evaluated the trajectory of ferritin concentration across categories of baseline characteristics, and assessed the association of iron status with viral and anthropometric outcomes. Results: The prevalence of iron deficiency at HAART initiation was 9% for unadjusted, 17% for HC, 12% for TC and 22% for RC ferritin. The prevalence of elevated iron status was 42% for unadjusted, 18% for HC, 31% for TC, and 15% for RC ferritin. The prevalence of iron deficiency for all three methods increased during the first year of HAART, while the prevalence of elevated iron status decreased. Baseline elevated iron status defined using HC ferritin was associated with a greater risk of HIV‐1 viral load > 1000 copies/mL [relative risk (RR) = 4.29, 95% CI: 1.38–13.3] and incidence of being underweight [body mass index (BMI) < 18.5 kg/m2, hazard ratio (HR) = 3.65, 95% confidence interval (CI): 1.38–9.67]. Neither baseline‐elevated iron status defined using TC or RC ferritin nor baseline iron deficiency defined using any of the three methods was associated with HIV‐1 viral load or anthropometric outcomes. Conclusions: Whether and how inflammation correction is done influences findings of studies of iron status among PLWHIV. [ABSTRACT FROM AUTHOR]

Propensity score matching is commonly used in observational studies to control for confounding and estimate the causal effects of a treatment or exposure. Frequently, in observational studies data are clustered, which adds to the complexity of using propensity score techniques. In this article, we give an overview of propensity score matching methods for clustered data, and highlight how propensity score matching can be used to account for not just measured confounders, but also unmeasured cluster level confounders. We also consider using machine learning methods such as generalized boosted models to estimate the propensity score and show that accounting for clustering when using these methods can greatly reduce the performance, particularly when there are a large number of clusters and a small number of subjects per cluster. In order to get around this we highlight scenarios where it may be possible to control for measured covariates using propensity score matching, while using fixed effects regression in the outcome model to control for cluster level covariates. Using simulation studies we compare the performance of different propensity score matching methods for clustered data across a number of different settings. Finally, as an illustrative example we apply propensity score matching methods for clustered data to study the causal effect of aspirin on hearing deterioration using data from the conservation of hearing study. [ABSTRACT FROM AUTHOR]

Background Although several dietary patterns have been associated with incident colorectal cancer (CRC), it is unclear which diet is optimal. Methods Participants included 48 409 men and 169 772 women from three USA-based prospective cohort studies. We compared the associations of 18 dietary patterns with CRC risk, including two reference scores. The reference scores were derived based on the dietary recommendations for cancer prevention and CRC-specific dietary risk factors mentioned in the 2018 World Cancer Research Fund/American Institute of Cancer Research (WCRF/AICR) Third Expert Report. Multivariable Cox proportional hazards models were fitted to estimate hazard ratios (HRs) and 95% CIs. Results Most dietary patterns showed moderate correlations with the WCRF dietary score (absolute values of Spearman correlation coefficients: 0.45–0.63), except the Plant-based diet index, low-carbohydrate diets, the Empirical dietary index for hyperinsulinemia (EDIH) and Empirical dietary inflammation pattern (EDIP). HR for the 10th–90th percentile difference in the score was 0.86 (95% CI: 0.78–0.94) for the Dietary Approaches to Stop Hypertension score (DASH), 1.15 (1.06–1.26) for Western dietary pattern, 1.20 (1.10–1.31) for EDIH and 1.23 (1.13–1.34) for EDIP. These associations between patterns and CRC risk persisted after adjusting for the two reference scores. Conclusions Although further research is needed to improve the WCRF/AICR dietary recommendations, our comprehensive assessment of dietary patterns revealed that the DASH, Western dietary pattern, EDIH and EDIP may be the most relevant diets for preventing CRC. [ABSTRACT FROM AUTHOR]

Background: Although colorectal cancer (CRC) incidence is declining among adults aged ≥65 years, CRC incidence in younger adults has been rising. The protective role of calcium in colorectal carcinogenesis has been well established, but evidence is lacking on whether the association varies by age at diagnosis. We investigated the association between total calcium intake and risk of overall CRC and CRC before age 55 years.Methods: In the Nurses' Health Study II (1991-2015), 94 205 women aged 25-42 years at baseline were included in the analysis. Diet was assessed every 4 years through validated food frequency questionnaires. Multivariable-adjusted hazard ratios (HRs) and 95% CIs for CRC were estimated using the Cox proportional hazards model.Results: We documented 349 incident CRC cases during 2 202 604 person-years of follow-up. Higher total calcium intake was associated with a reduced risk of CRC. Compared with those with <750 mg/day of total calcium intake, the HR of CRC was 0.61 (95% CI, 0.38-0.97) for those who consumed ≥1500 mg/day (P for trend = 0.01). The HR per 300 mg/day increase was 0.85 (95% CI, 0.76-0.95). There was a suggestive inverse association between total calcium intake and CRC before age 55 years (HR per 300 mg/day increase, 0.87; 95% CI, 0.75-1.00), suggesting the importance of calcium intake in the younger population.Conclusions: In a cohort of younger women, which reflects the birth cohorts, time periods and age ranges paralleling the recent rise in CRC, higher calcium intake was associated with a decreased risk of CRC. [ABSTRACT FROM AUTHOR]

Background: Persistent tinnitus is common, disabling, and difficult to treat. High-dose aspirin may precipitate tinnitus, but longitudinal data on typical dose aspirin and other analgesics are scarce.Objective: To investigate independent associations of aspirin, NSAIDs, and acetaminophen and risk of incident persistent tinnitus.Design: Longitudinal cohort study.Setting: Nurses' Health Study II (1995-2017).Participants: A total of 69,455 women, age 31-48 years, without tinnitus at baseline.Main Measures: Information on analgesic use and tinnitus obtained by biennial questionnaires.Key Results: After 1,120,936 person-years of follow-up, 10,452 cases of incident persistent tinnitus were reported. For low-dose aspirin, the risk of developing persistent tinnitus was not elevated among frequent low-dose aspirin users. For moderate dose aspirin, frequent use was associated with higher risk of tinnitus among women aged < 60 years, but not among older women (p-interactionage = 0.003). Compared with women aged < 60 using moderate-dose aspirin < 1 day/week, the multivariable-adjusted hazard ratio (MVHR, 95% CI) among women using moderate-dose aspirin 6-7 days per week was 1.16 (1.03, 1.32). Among all women, frequent non-aspirin non-steroidal anti-inflammatory drug (NSAID) or acetaminophen use was associated with higher risk. Compared with women using NSAIDs <1 day/week, the MVHR for use 4-5days/week was 1.17 (1.08, 1.28) and for 6-7days/week was 1.07 (1.00, 1.16) (p-trend=0.001). For acetaminophen, compared with use <1 day/week, the MVHR for use 6-7days/week was 1.18 (1.07, 1.29) (p-trend=0.002).Limitations: Information on tinnitus and analgesic use was self-reported. Information on indications for analgesic use was not available. Studies in non-White women and men are needed.Conclusion: The risk of developing persistent tinnitus was not elevated among frequent low-dose aspirin users. Among younger women, frequent moderate-dose aspirin use was associated with higher risk. Frequent NSAID use and frequent acetaminophen use were associated with higher risk of incident persistent tinnitus among all women, and the magnitude of the risks tended to be greater with increasing frequency of use. Our results suggest analgesic users are at higher risk for developing tinnitus and may provide insight into the precipitants of this challenging disorder, but additional investigation to determine whether there is a causal association is needed. [ABSTRACT FROM AUTHOR]

Marginal structural models (MSMs), which adopt inverse probability treatment weighting in the estimating equations, are powerful tools to estimate the causal effects of time-varying exposures in the presence of time-dependent confounders. Motivated by the Conservation of Hearing Study (CHEARS) Audiology Assessment Arm (AAA) where repeated hearing measurements were clustered by study participants, time, and testing sites, we propose two methods to account for the multilevel correlation structure when fitting the MSMs. The first method directly models the covariance of the repeated outcomes when solving the weighted generalized estimating equations for MSMs, while the second two-stage analysis approach fits cluster-specific MSMs first and then combines the estimated parameters using mixed-effects meta-analysis. Finite sample simulation results suggest that our methods can obtain less biased and more efficient estimates of the parameters by accounting for the multilevel correlation. Moreover, we explore the effects of using fixed- or mixed-effects model to estimate the treatment probability on the parameter estimates of the MSMs in the presence of unmeasured cluster-level confounders. Lastly, we apply our methods to the CHEARS AAA data set, to estimate the causal effects of aspirin use on hearing loss. [ABSTRACT FROM AUTHOR]

Background: Weight loss is crucial for disease prevention among individuals with overweight or obesity. This study aimed to examine associations of weight loss strategies (WLSs) with weight change and type 2 diabetes (T2D) risk among US health professionals. Methods and findings: This study included 93,110 participants (24 to 60 years old; 11.6% male) from the Nurses' Health Study (NHS), NHSII, and Health Professionals Follow-Up Study (HPFS) cohorts who were free of T2D, cardiovascular disease, and cancer at baseline (1988 for NHS/HPFS and 1989 for NHSII) for analyses of weight change and 104,180 (24 to 78 years old; 14.2% male) for T2D risk assessment. WLSs used to achieve an intentional weight loss of 4.5+ kg were collected in 1992 (NHS/HPFS)/1993 (NHSII) and grouped into 7 mutually exclusive categories, including low-calorie diet, exercise, low-calorie diet and exercise, fasting, commercial weight loss program (CWLP), diet pills, and FCP (selected at least 2 methods from fasting, CWLP, and pill). The reference group was participants who did not attempt to lose weight. Generalized estimating equations and Cox regression were applied to estimate up to 10-year weight change trajectory and incident T2D risk through 2016 (NHS/HPFS)/2017 (NHSII), respectively. The associations of WLSs with weight change and T2D risk were differential by baseline body weight (Pinteraction < 0.01). Among individuals with obesity, all WLSs tended to associate with less weight gain [ranging from −4.2% (95% confidence interval (CI), −5.1% to −3.2%; P < 0.001) for exercise to −0.3% (−1.2% to 0.7%; P > 0.99) for FCP] and a lower T2D risk [hazard ratios (HRs) ranging from 0.79 (0.66 to 0.95; P = 0.04) for exercise to 0.87 (0.66 to 1.13; P = 0.30) for pill]. Such a pattern was less clear among overweight individuals: the difference of weight change varied from −2.5% (−3.0% to −2.1%; P < 0.001) for exercise to 2.0% (1.3% to 2.7%; P < 0.001) for FCP, and HRs of T2D varied from 0.91 (0.77 to 1.07; P = 0.29) for exercise to 1.42 (1.11 to 1.81; P = 0.02) for pill. The pattern was further inverted among lean individuals in that weight change ranged from −0.4% (−0.6% to −0.1%; P = 0.02) for exercise to 3.7% (3.1% to 4.3%; P < 0.001) for FCP, and the HRs of T2D ranged from 1.09 (0.91 to 1.30; P = 0.33) for exercise to 1.54 (1.13 to 2.10; P = 0.008) for pill. Approximately 15.6% to 46.8% of the association between WLSs and the T2D risk was attributed to weight changes. This study was limited by a single assessment of WLSs, heterogeneity within each WLS, and potential misclassification of the timing of weight loss and weight regain. Conclusions: The current study showed that individuals with obesity who attempted to lose weight, regardless of the WLSs used, tended to gain less body weight and have a lower diabetes risk. In contrast, lean individuals who intentionally lost weight tended to gain more weight and have a higher diabetes risk. These data support the notion that intentional weight loss may not be beneficial for lean individuals and the use of WLSs for achieving weight loss shall be guided by medical indications only. Keyi Si and colleagues investigate associations of weight loss strategies with weight gain and type 2 diabetes in health professionals in the US. Author summary: Why was this study done?: Weight control is one of the primary and effective strategies for the prevention and management of obesity and related chronic diseases. Trying to lose weight is common not only among overweight individuals or those with obesity, but also among lean individuals. Long-term weight change and risks of developing type 2 diabetes (T2D) following various weight loss strategies (WLSs) are understudied. What did the researchers do and find?: Up to 10-year weight change and 24-year T2D risk were compared between individuals who lost 4.5+ kg (10+ lbs) through various WLSs (low-calorie diet, exercise, low-calorie diet and exercise, fasting, commercial weight loss program (CWLP), diet pills, or a combination of the last 3 strategies collectively named as FCP) and those who did not attempt to lose weight. Association of WLSs with weight change and T2D risk varied by baseline body mass index status: individuals with obesity who lost 4.5+ kg intentionally were likely to have less weight gain within 4 years since baseline and lower risk of T2D during 24 years of follow-up, regardless of WLS, but the beneficial associations were attenuated in individuals with overweight and even inverted in lean individuals. Of all WLSs, exercise was associated with the least weight gain and the lowest T2D risk among individuals with obesity. Approximately 15.6% to 46.8% of the association between WLSs and the T2D risk was attributable to body weight changes after weight loss attempts. What do these findings mean?: Individuals with obesity may benefit from intentional weight loss regardless of the methods used to achieve the weight loss, whereas lean individuals may not enjoy the same health benefits from intentionally losing a significant amount of body weight. These data suggest that the use of weight loss methods for achieving weight loss should be guided by medical or health indications. [ABSTRACT FROM AUTHOR]