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1.
Stat Med ; 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36125070

RESUMO

In epidemiological hearing studies, estimating the association between exposures and hearing loss using audiometrically-assessed hearing measurements is challenging due to the complex correlation structure in the clustered data, with clusters formed by the two ears of the same individual and the testing site and audiologist. We propose a linear mixed-effects model to take into account the multilevel correlation structures of the data. Both theoretically and in simulation studies, we compare single-ear linear regression models commonly used in published hearing loss studies with the proposed both-ears linear mixed models properly accounting for the multi-level correlations. Our findings include (1) when there are only participant-level covariates, the worse-ear linear regression models produce unbiased but typically less efficient estimators than the both-ear and average-ear approaches; (2) when there are ear-level confounders, the worse-ear method may lead to biased estimators and the average-ear method produces unbiased but typically less efficient estimators than the both-ear method; (3) the both-ear method may gain efficiency when additionally adjusting for testing sites and audiologists. As an illustrative example, we applied the single-ear and both-ear methods to assess aspirin-hearing association in the Nurses' Health Study II.

2.
Artigo em Inglês | MEDLINE | ID: mdl-36049216

RESUMO

Current recommendations for CRC screening have not accounted for type 2 diabetes (T2D) status. It remains unknown whether the CRC-preventive benefit of endoscopic screening and the recommended age for screening initiation differ by T2D. Among 166,307 women (Nurses' Health Study I and II, 1988-2017) and 42,875 men (Health Professionals Follow-up Study, 1988-2016), endoscopic screening and T2D diagnosis were biennially updated. We calculated endoscopic screening-associated hazard ratios (HRs) and absolute risk reductions (ARRs) for CRC incidence and mortality according to T2D, and age-specific CRC incidence according to T2D. During a median of 26 years of follow-up, we documented 3,457 CRC cases and 1,129 CRC deaths. Endoscopic screening was associated with a similar HR of CRC incidence in the T2D and non-T2D groups (P-multiplicative interaction=0.57). In contrast, the endoscopic screening-associated ARR for CRC incidence was higher in the T2D group (2.36%, 95%CI, 1.55-3.13%) than in the non-T2D group (1.73%, 95%CI, 1.29-2.16%) (P-additive interaction=0.01). Individuals without T2D attained a 10-year cumulative risk of 0.35% at the benchmark age of 45 years, whereas those with T2D reached this threshold risk level at the age of 36 years. Similar results were observed for CRC mortality. In conclusion, the absolute benefit of endoscopic screening for CRC prevention may be substantially higher for individuals with T2D compared to those without T2D. Although T2D is comparatively rare prior to the 5th decade of life, the rising incidence of young-onset T2D and heightened CRC risk associated with T2D support the consideration of earlier endoscopic screening in individuals with T2D.

3.
HIV Med ; 2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-36075691

RESUMO

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.

4.
Am J Clin Nutr ; 2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36130877

RESUMO

BACKGROUND: Gestational weight gain (GWG) below or above the Institute of Medicine (IOM) recommendations has been associated with adverse perinatal outcomes. Few studies have examined the effect of prenatal nutrient supplementations on GWG in low- and middle-income countries (LMICs). OBJECTIVES: To investigate the effects of multiple micronutrient supplements (MMS) and small-quantity lipid-based nutrient supplements (LNS) on GWG in LMICs. METHODS: A two-stage meta-analysis of individual participant data was conducted to examine the effects of MMS (45,507 women from 14 trials) and small-quantity LNS (6,237 women from 4 trials) on GWG compared to iron and folic acid supplements only. Percent adequacy of GWG and total weight gain at delivery were calculated according to the IOM 2009 guidelines. Binary outcomes included severely inadequate (% adequacy < 70%), inadequate (< 90%), and excessive (>125%) GWG. Results from individual trials were pooled using fixed-effects inverse-variance models. Heterogeneity was examined using I2, stratified analysis, and meta-regression. RESULTS: MMS resulted in a greater % adequacy of GWG (weighted mean difference (WMD): 0.86%; 95% CI: 0.28%,1.44%; P < 0.01) and higher GWG at delivery (WMD: 209 g; 95% CI: 139, 280; P < 0.01) than among those in the control arm. Women who received MMS had a 2.9% reduced risk of severely inadequate GWG (RR: 0.971; 95% CI: 0.956, 0.987; P < 0.01). No association was found between small-quantity LNS and GWG % adequacy (WMD: 1.51%; 95% CI: -0.38%, 3.40%; P = 0.21). Neither MMS nor small-quantity LNS was associated with excessive GWG. CONCLUSIONS: Maternal MMS was associated with a greater GWG % adequacy and total GWG at delivery compared to iron and folic acid only. This finding is consistent with previous results on birth outcomes and will inform policy development and local recommendation of switching routine prenatal iron and folic acid supplements to MMS.

5.
Iran J Pharm Res ; 21(1): e126919, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36060924

RESUMO

Berberine, an isoquinoline alkaloid purified from Chinese herbs, was verified to have antitumor effects. It has also been reported that berberine can enhance the anticancer effect of tamoxifen (TAM) in estrogen receptor (ER)-positive breast cancer cells; however, the involved underlying mechanism is still unclear. In the present study, the role of one variant of ER-α, ER-α36, in the TAM sensitizing effect of berberine was explored in TAM-resistant breast cancer cells. This study demonstrated that berberine potently sensitized TAM-resistant breast cancer cells, including TAM-resistant MCF7 and BT-474 cells, to TAM treatment. Additionally, this study showed that berberine could simultaneously suppress ER-α36 expression in TAM-resistant cells. However, when ER-α36 was knocked down in TAM-resistant cells, there was no significant TAM-sensitizing effect by berberine. Therefore, this study indicated that ER-α36 is involved in berberine's TAM-sensitizing effect on ER-positive breast cancer cells, which provided supporting data for the application of berberine in cancer therapy as an adjuvant agent for TAM treatment.

6.
J Acoust Soc Am ; 152(1): 214, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35931539

RESUMO

Statistical approaches that could be used as standardized methodology for evaluating reliability and validity of data obtained using remote audiometry are proposed. Using data from the Nurses' Health Study II (n = 31), the approaches to evaluate the reliability and validity of hearing threshold measurements obtained by a self-administered iPhone-based hearing assessment application (Decibel Therapeutics, Inc., Boston, MA) compared with measurements obtained by clinical (soundbooth) audiometry are described. These approaches use mixed-effects models to account for multilevel correlations, intraclass correlation coefficients (ICCs) of single and averaged measurements, and regression techniques with the generalized estimating equations (GEEs) to account for between-ear correlations. Threshold measurements obtained using the iPhone application were moderately reliable. The reliability was improved substantially by averaging repeated measurements; good reliability was achieved by averaging three repeated measurements. In the linear regression analyses that assessed validity, the range of intercepts (2.3-8.4) and range of slopes (0.4-0.7) indicated that the measurements from the application were likely biased from those obtained by clinical audiometry. When evaluating alternative hearing assessment tools, it is recommended to assess reliability through mixed-effects models and use ICCs to determine the number of repeated assessments needed to achieve satisfactory reliability. When evaluating validity, GEE methods are recommended to estimate regression coefficients.


Assuntos
Audiometria , Testes Auditivos , Audiometria/métodos , Boston , Audição , Humanos , Reprodutibilidade dos Testes
7.
BMJ Open ; 12(8): e061301, 2022 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-36038172

RESUMO

INTRODUCTION: Presently, there are few population-level strategies to address SARS-CoV-2 infection except preventive measures such as vaccination. Micronutrient deficiency, particularly vitamin D and zinc deficiency, has been associated with dysregulated host responses, and may play an important role in COVID-19. METHODS AND ANALYSIS: We have designed a 2×2 factorial, randomised, double-blind, multi-centre placebo-controlled trial to evaluate the effect of vitamin D and zinc on COVID-19 outcomes in Maharashtra, India. COVID-19 positive individuals are recruited from hospitals in Mumbai and Pune. Participants are provided (1) vitamin D3 bolus (180 000 IU) maintained by daily dose of 2000 IU and/or (2) zinc gluconate (40 mg daily), versus placebo for 8 weeks. Participants undergo a detailed assessment at baseline and at 8 weeks, and are monitored daily in hospital or every 3 days after leaving the hospital to assess symptoms and other clinical measures. A final follow-up telephone call occurs 12 weeks post-enrolment to assess long-term outcomes. The primary outcome of the study is to time to recovery, defined as time to resolution of all of fever, cough and shortness of breath. Secondary outcomes include: duration of hospital stay, all-cause mortality, necessity of assisted ventilation, change in blood biomarker levels and individual symptoms duration. Participant recruitment commenced on April 2021. ETHICS AND DISSEMINATION: Ethical approval was obtained from institutional ethical committees of all participating institutions. The study findings will be presented in peer-reviewed medical journals. TRIAL REGISTRATION NUMBERS: NCT04641195, CTRI/2021/04/032593, HMSC (GOI)-2021-0060.


Assuntos
COVID-19 , Suplementos Nutricionais , Humanos , Índia/epidemiologia , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , SARS-CoV-2 , Resultado do Tratamento , Vitamina D/uso terapêutico , Zinco/uso terapêutico
8.
Biostatistics ; 2022 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-35904119

RESUMO

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.

9.
Cancer Causes Control ; 33(8): 1107-1120, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35759080

RESUMO

Cancer heterogeneities hold the key to a deeper understanding of cancer etiology and progression and the discovery of more precise cancer therapy. Modern pathological and molecular technologies offer a powerful set of tools to profile tumor heterogeneities at multiple levels in large patient populations, from DNA to RNA, protein and epigenetics, and from tumor tissues to tumor microenvironment and liquid biopsy. When coupled with well-validated epidemiologic methodology and well-characterized epidemiologic resources, the rich tumor pathological and molecular tumor information provide new research opportunities at an unprecedented breadth and depth. This is the research space where Molecular Pathological Epidemiology (MPE) emerged over a decade ago and has been thriving since then. As a truly multidisciplinary field, MPE embraces collaborations from diverse fields including epidemiology, pathology, immunology, genetics, biostatistics, bioinformatics, and data science. Since first convened in 2013, the International MPE Meeting series has grown into a dynamic and dedicated platform for experts from these disciplines to communicate novel findings, discuss new research opportunities and challenges, build professional networks, and educate the next-generation scientists. Herein, we share the proceedings of the Fifth International MPE meeting, held virtually online, on May 24 and 25, 2021. The meeting consisted of 21 presentations organized into the three main themes, which were recent integrative MPE studies, novel cancer profiling technologies, and new statistical and data science approaches. Looking forward to the near future, the meeting attendees anticipated continuous expansion and fruition of MPE research in many research fronts, particularly immune-epidemiology, mutational signatures, liquid biopsy, and health disparities.


Assuntos
Neoplasias , Patologia Molecular , Humanos , Mutação , Neoplasias/epidemiologia , Neoplasias/genética , Neoplasias/terapia , Patologia Molecular/métodos , Microambiente Tumoral
10.
Cancers (Basel) ; 14(11)2022 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-35681763

RESUMO

Pooling biomarker data across multiple studies enables researchers to obtain precise estimates of the association between biomarker measurements and disease risks due to increased sample sizes. However, biomarker measurements often vary significantly across different assays and laboratories; therefore, calibration of the local laboratory measurements to a reference laboratory is necessary before pooling data. We propose two methods for estimating the dose-response curves that allow for a nonlinear association between the continuous biomarker measurements and log relative risk in pooling projects of matched/nested case-control studies. Our methods are based on full calibration and internalized calibration methods. The full calibration method uses calibrated biomarker measurements for all subjects, even for people with reference laboratory measurements, while the internalized calibration method uses the reference laboratory measurements when available and otherwise uses the calibrated biomarker measurements. We conducted simulation studies to compare these methods, as well as a naive method, where data are pooled without calibration. Our simulation and theoretical results suggest that, in estimating the dose-response curves for biomarker-disease relationships, the internalized and full calibration methods perform substantially better than the naive method, and the full calibration approach is the preferred method for calibrating biomarker measurements. We apply our methods in a pooling project of nested case-control studies to estimate the association of circulating Vitamin D levels with risk of colorectal cancer.

11.
Reprod Health ; 19(1): 140, 2022 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-35710384

RESUMO

BACKGROUND: Appropriate gestational weight gain (GWG) is important for optimal pregnancy outcomes. This study prospectively evaluated the associations between GWG during the second and third trimesters of pregnancy and adverse pregnancy outcomes in an urban Tanzanian pregnancy cohort. METHODS: We used data from a randomized clinical trial conducted among pregnant women recruited by 27 weeks of gestation in Dar es Salaam, Tanzania (N = 1230). Women's gestational weight was measured at baseline and at monthly antenatal visits. Weekly GWG rate during the second and third trimesters was calculated and characterized as inadequate, adequate, or excessive, in conjunction with measured or imputed early-pregnancy BMI status according to the 2009 Institute of Medicine (IOM) GWG guidelines. We used multivariable Poisson regression with a sandwich variance estimator to calculate risk ratios (RR) for associations of GWG with low birth weight, preterm birth, small for gestational age (SGA), and large for gestational age (LGA). Degree of appropriate GWG defined using additional metrics (i.e., percentage of adequacy, z-score) and potential effect modification by maternal BMI were additionally evaluated. RESULTS: According to the IOM guidelines, 517 (42.0%), 270 (22.0%), and 443 (36.0%) women were characterized as having inadequate, adequate, and excessive GWG, respectively. Overall, compared to women with adequate GWG, women with inadequate GWG had a lower risk of LGA births (RR = 0.54, 95% CI: 0.36-0.80) and a higher risk of SGA births (RR = 1.32, 95% CI: 0.95-1.81). Women with inadequate GWG as defined by percentage of GWG adequacy had a higher risk of LBW (OR = 1.93, 95% CI: 1.03-3.63). In stratified analyses by early-pregnancy BMI, excessive GWG among women with normal BMI was associated with a higher risk of preterm birth (RR = 1.59, 95% CI: 1.03-2.44). CONCLUSIONS: A comparatively high percentage of excessive GWG was observed among healthy pregnant women in Tanzania. Both inadequate and excessive GWGs were associated with elevated risks of poor pregnancy outcomes. Future studies among diverse SSA populations are warranted to confirm our findings, and clinical recommendations on optimal GWG should be developed to promote healthy GWG in SSA settings. TRIAL REGISTRATION: This trial was registered as "Prenatal Iron Supplements: Safety and Efficacy in Tanzania" (NCT01119612; http://clinicaltrials.gov/show/NCT01119612 ).


Pregnancy is a critical lifetime event for both mother and the offspring, with implications in short-term and long-term health consequences. Gestational weight gain (GWG) is an important modifiable factor for pregnancy outcomes related to infant body size and weight and prematurity. Countries in sub-Saharan Africa (SSA) have long had poor rates of insufficient GWG and pregnancy complications associated with insufficient GWG. Nevertheless, some SSA countries are experiencing economic transitions accompanied with changes in lifestyle and nutrition, which might impact pregnancy experiences, including GWG and pregnancy outcomes. This study aimed to characterize recent GWG patterns and the associations of both inadequate and excessive GWG with adverse pregnancy outcomes, using an urban pregnancy cohort in Tanzania. This study found that 42.0%. 22.0%, and 36.0% of women had insufficient, adequate, and excessive GWG, respectively. Insufficient GWG was associated with higher risks of small infant size and low infant body weight, and excessive GWG was associated with higher risk of preterm birth, particularly among women with body mass index 18.5­25.0 kg/m2. Results from the present study highlight that both insufficient and excessive GWG are of potential public health concerns in urban centers of SSA, concerning upward trends in obesity and possibly obesity-related pregnancy consequences. Local public health practitioners should continue to advocate longitudinal GWG monitoring and care among African pregnant women, and optimal GWG with feasible and effective clinical guidelines should be developed to prevent both over- and under-gaining of maternal weight during pregnancy.


Assuntos
Ganho de Peso na Gestação , Complicações na Gravidez , Nascimento Prematuro , Índice de Massa Corporal , Feminino , Retardo do Crescimento Fetal , Humanos , Recém-Nascido , Masculino , Gravidez , Complicações na Gravidez/epidemiologia , Resultado da Gravidez/epidemiologia , Terceiro Trimestre da Gravidez , Nascimento Prematuro/epidemiologia , Estudos Prospectivos , Tanzânia/epidemiologia , Aumento de Peso
12.
JAMA Netw Open ; 5(5): e2210450, 2022 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-35507343

RESUMO

Importance: Rotating night shift work is associated with higher mortality. Whether it is also associated with overall health among those who survive to older ages remains unclear. Objective: To examine whether rotating night shift work is associated with healthy aging after 24 years of follow-up in the Nurses' Health Study, a cohort study among registered female nurses. Design, Setting, and Participants: For this cohort study, a composite healthy aging phenotype was ascertained among 46 318 participants who were aged 46 to 68 years and free of major chronic diseases in 1988 when the history of night shift work was assessed. In a secondary analysis in which cognitive function decline was considered in the healthy aging definition, 14 273 nurses were involved. Data were analyzed from March 1 to September 30, 2021. Exposures: Duration of rotating night shift work. Main Outcomes and Measures: Healthy aging was defined as reaching at least 70 years of age and being free of 11 major chronic diseases, memory impairment, physical limitation, or deteriorated mental health. Results: Of 46 318 female nurses (mean [SD] age at baseline, 55.4 [6.1] years), 3695 (8.0%) achieved healthy aging after 24 years of follow-up. After adjusting for established and potential confounders, compared with women who never worked rotating night shifts, the odds of achieving healthy aging decreased significantly with increasing duration of night shift work. The odds ratios were 0.96 (95% CI, 0.89-1.03) for 1 to 5 years, 0.92 (95% CI, 0.79-1.07) for 6 to 9 years, and 0.79 (95% CI, 0.69-0.91) for 10 or more years of night shift work (P = .001 for trend). This association did not differ substantially by age and lifestyles and was consistent for 4 individual dimensions of healthy aging. Results were similar in a secondary analysis, with an odds ratio of 0.73 (95% CI, 0.60-0.89; P < .001 for trend) comparing 10 or more years of night shift work vs no night shift work. Conclusions and Relevance: In this cohort study, rotating night shift work was associated with decreased probability of healthy aging among US female nurses. These data support the notion that excess night shift work is a significant health concern that may also lead to deteriorated overall health among older individuals.


Assuntos
Envelhecimento Saudável , Enfermeiras e Enfermeiros , Jornada de Trabalho em Turnos , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Estudos Prospectivos , Jornada de Trabalho em Turnos/efeitos adversos , Tolerância ao Trabalho Programado
13.
JAMA Oncol ; 8(7): 986-993, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35511155

RESUMO

Importance: In the past 4 years, the American Cancer Society and the US Preventive Services Task Force updated recommendations to initiate colorectal cancer (CRC) screening at 45 years of age to address the increasing incidence of CRC among adults younger than 50 years. However, empirical evidence evaluating the potential benefits of screening in younger populations is scant. Objective: To examine the association between endoscopy initiation at different ages and risk of CRC among US women. Design, Setting, and Participants: This prospective cohort study used data from the Nurses' Health Study II, which included US female health professionals followed up from 1991 through 2017. Data analysis was performed from August 2020 to June 2021. Exposure: Age at initiation of sigmoidoscopy or colonoscopy for screening (routine screening or because of family history) or symptoms. Main Outcomes and Measures: Incident CRC, confirmed by medical records, pathology reports, and the National Death Index. Cumulative incidence of CRC in each group was estimated with age as the time scale, and the absolute risk reduction associated with endoscopy initiation at different ages through 60 years was calculated. Cox proportional hazards regression was used to calculate hazard ratios (HRs) and 95% CIs, stratified by age and calendar year of questionnaire cycle and adjusted for CRC risk factors in the multivariable models. Results: Among 111 801 women aged 26 to 46 years (median, 36 years) at enrollment, 519 incident CRC cases were documented over 26 years, encompassing 2 509 358 person-years of follow-up. In the multivariable analysis, compared with no endoscopy, undergoing endoscopy was associated with a significantly lower risk of incident CRC for age at initiation before 45 years (HR, 0.37; 95% CI, 0.26-0.53), 45 to 49 years (HR, 0.43; 95% CI, 0.29-0.62), 50 to 54 years (HR, 0.47; 95% CI, 0.35-0.62), and 55 years or older (HR, 0.46; 95% CI, 0.30-0.69). The absolute reduction in the estimated cumulative incidence of CRC through 60 years of age was 72 per 100 000 persons for initiation of endoscopy at 45 to 49 years of age vs 50 to 54 years of age. Compared with no endoscopy, initiation of endoscopy before 50 years of age was also associated with a reduced risk of CRC diagnosed before 55 years of age (<45 years: HR, 0.45 [95% CI, 0.29-0.70]; 45-49 years: HR, 0.43 [95% CI, 0.24-0.76]). Conclusions and Relevance: In this cohort study, compared with no endoscopy, initiation of endoscopy before 50 years of age was associated with a reduced risk of CRC, including CRC diagnosed before 55 years of age. Screening before 50 years of age was associated with greater absolute reduction in CRC risk compared with initiation of CRC screening at 50 years of age or later.


Assuntos
Neoplasias Colorretais , Sigmoidoscopia , Adulto , Estudos de Coortes , Colonoscopia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/patologia , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco
14.
Am J Clin Nutr ; 115(6): 1481-1489, 2022 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-35470384

RESUMO

BACKGROUND: Recent preclinical research strongly suggests that dietary sugars can enhance colorectal tumorigenesis by direct action, particularly in the proximal colon that unabsorbed fructose reaches. OBJECTIVES: We aimed to examine long-term consumption of sugar-sweetened beverages (SSBs) and total fructose in relation to incidence and mortality of colorectal cancer (CRC) by anatomic subsite. METHODS: We followed 121,111 participants from 2 prospective US cohort studies, the Nurses' Health Study (1984-2014) and Health Professionals Follow-Up Study (1986-2014), for incident CRC and related death. Cox proportional hazards regression was used to compute HRs and 95% CIs. RESULTS: During follow-up, we documented 2733 incident cases of CRC with a known anatomic location, of whom 901 died from CRC. Positive associations of SSB and total fructose intakes with cancer incidence and mortality were observed in the proximal colon but not in the distal colon or rectum (Pheterogeneity ≤ 0.03). SSB consumption was associated with a statistically significant increase in the incidence of proximal colon cancer (HR per 1-serving/d increment: 1.18; 95% CI: 1.03, 1.34; Ptrend = 0.02) and a more pronounced elevation in the mortality of proximal colon cancer (HR: 1.39; 95% CI: 1.13, 1.72; Ptrend = 0.002). Similarly, total fructose intake was associated with increased incidence and mortality of proximal colon cancer (HRs per 25-g/d increment: 1.18; 95% CI: 1.03, 1.35; and 1.42; 95% CI: 1.12, 1.79, respectively). Moreover, SSB and total fructose intakes during the most recent 10 y, rather than those from a more distant period, were associated with increased incidence of proximal colon cancer. CONCLUSIONS: SSB and total fructose consumption were associated with increased incidence and mortality of proximal colon cancer, particularly during later stages of tumorigenesis.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Bebidas Adoçadas com Açúcar , Bebidas/análise , Carcinogênese , Neoplasias do Colo/epidemiologia , Neoplasias do Colo/etiologia , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia , Açúcares da Dieta , Seguimentos , Frutose/efeitos adversos , Humanos , Incidência , Estudos Prospectivos , Bebidas Adoçadas com Açúcar/efeitos adversos , Açúcares
15.
PLoS Med ; 19(4): e1003973, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35427363

RESUMO

BACKGROUND: Observational studies suggest that vitamin D deficiency among people living with HIV is associated with a greater risk of disease progression and death. Low levels of vitamin D in pregnancy are also associated with poor fetal and infant growth. Therefore, vitamin D supplementation may improve clinical outcomes for pregnant women living with HIV and improve fetal and postnatal growth for their infants. METHODS AND FINDINGS: We conducted a randomized, triple-blind, placebo-controlled trial of vitamin D3 supplementation among pregnant and lactating women living with HIV in Dar es Salaam, Tanzania (ClinicalTrials.gov NCT02305927). Participants were randomized with 1:1 allocation stratified by study clinic to receive either daily 3,000 IU vitamin D3 supplements or matching placebo supplements from the second trimester of pregnancy (12-27 weeks) until 1 year postpartum. The primary outcomes were (i) maternal HIV progression or death, (ii) small-for-gestational-age (SGA) live births (<10th percentile), and (iii) infant stunting at 1 year of age (length-for-age z-score < -2). We also examined the effect of vitamin D3 supplementation on secondary maternal and infant health outcomes, maternal and infant serum 25-hydroxyvitamin D (25[OH]D) concentrations, and maternal hypercalcemia. An intent-to-treat analysis was used as the primary analytic approach. We enrolled 2,300 pregnant women between June 15, 2015, and April 17, 2018, and follow-up of mothers and infants was completed on October 20, 2019. There were 1,148 pregnant women randomly assigned to the vitamin D3 group, and 1,152 to the placebo group. The proportion of mothers lost to follow-up at 1 year postpartum was 6.6% in the vitamin D3 group (83 of 1,148) and 6.6% in the placebo group (76 of 1,152). The proportion of children lost to follow-up at 1 year of age was 5.5% in the vitamin D3 group (59 of 1,074 live births) and 5.2% in the placebo group (57 of 1,093 live births). There was no difference in the risk of maternal HIV progression or death, with 166 events during 1,461 person-years of follow-up in the vitamin D3 group and 141 events during 1,469 person-years of follow-up in the placebo group (hazard ratio 1.21, 95% CI 0.97 to 1.52, p = 0.09). There was no difference in the risk of SGA birth between the vitamin D3 (229 SGA births among 1,070 live births) and placebo groups (236 SGA births among 1,091 live births) (relative risk 1.03, 95% CI 0.87 to 1.22, p = 0.70). There was also no difference in the risk of infant stunting at 1 year of age between the vitamin D3 (407 events among 867 infants) and placebo groups (413 events among 873 infants) (relative risk 1.00, 95% CI 0.92 to 1.10, p = 0.95). In terms of adverse events, no cases of maternal hypercalcemia were identified. One hypersensitivity reaction to the trial supplements occurred for a pregnant woman in the placebo group. A limitation of our study is that our findings may not be generalizable to HIV-negative pregnant women or contexts where severe vitamin D deficiency is prevalent. CONCLUSIONS: The trial findings do not support routine vitamin D supplementation for pregnant and lactating women living with HIV in Tanzania. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02305927.


Assuntos
Infecções por HIV , Hipercalcemia , Deficiência de Vitamina D , Criança , Colecalciferol/uso terapêutico , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Transtornos do Crescimento/tratamento farmacológico , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Hipercalcemia/etiologia , Lactente , Lactação , Gravidez , Tanzânia/epidemiologia , Vitamina D/uso terapêutico , Deficiência de Vitamina D/tratamento farmacológico
16.
J Nutr ; 152(8): 1983-1990, 2022 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-35460249

RESUMO

BACKGROUND: Observational studies suggest that blood concentrations of 25-hydroxyvitamin D [25(OH)D] are associated with morbidity, viral suppression, and mortality among adults living with HIV. OBJECTIVES: We evaluated the effect of cholecalciferol (vitamin D3) supplementation on the risk of HIV disease progression, HIV-1 viral suppression, comorbidities, weight change, and depression among HIV-infected individuals that were initiating antiretroviral therapy (ART) in Dar es Salaam, Tanzania. METHODS: We conducted a randomized, double-blind, placebo-controlled trial of vitamin D3 supplementation among 4000 HIV-infected adult men and nonpregnant women initiating ART with insufficient serum 25(OH)D concentrations (<30 ng/mL). Participants were randomly assigned to receive either weekly 50,000-IU doses for 4 wk followed by daily 2000 IU vitamin D3 until 1 y or a matching placebo regimen given in weekly followed by daily doses until 1 y. Participants were followed up at weekly visits for the first month followed by monthly visits thereafter. We conducted intent-to-treat analyses to assess the effect of vitamin D3 supplementation on the secondary trial outcomes of HIV progression or death, viral suppression, comorbidities, change in BMI, >10% weight loss, incident wasting, and depression. RESULTS: During follow-up, 345 participants (17.2%) in the vitamin D3 group and 371 participants (18.6%) in the placebo group experienced HIV disease progression or death and there was no difference in risk between groups (RR: 0.91; 95% CI: 0.79, 1.06). Vitamin D3 supplementation did not affect the risk of an unsuppressed HIV-1 viral load (>1000 copies/mL) after 6 mo (RR: 1.10; 95% CI: 0.87, 1.41) and there was also no effect on change in BMI, risk of >10% weight loss, wasting, comorbidities, and depression (P values >0.05). CONCLUSIONS: Vitamin D supplementation did not affect the risk of HIV progression, viral suppression, common morbidities, weight-related indicators, or depression among adults initiating ART in Tanzania.This trial was registered at clinicaltrials.gov as NCT01798680.


Assuntos
Colecalciferol , Infecções por HIV , Adulto , Depressão , Suplementos Nutricionais , Progressão da Doença , Método Duplo-Cego , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Tanzânia/epidemiologia , Vitamina D , Redução de Peso
17.
Cancers (Basel) ; 14(7)2022 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-35406583

RESUMO

Molecular pathologic diagnosis is important in clinical (oncology) practice. Integration of molecular pathology into epidemiological methods (i.e., molecular pathological epidemiology) allows for investigating the distinct etiology of disease subtypes based on biomarker analyses, thereby contributing to precision medicine and prevention. However, existing approaches for investigating etiological heterogeneity deal with categorical subtypes. We aimed to fully leverage continuous measures available in most biomarker readouts (gene/protein expression levels, signaling pathway activation, immune cell counts, microbiome/microbial abundance in tumor microenvironment, etc.). We present a cause-specific Cox proportional hazards regression model for evaluating how the exposure-disease subtype association changes across continuous subtyping biomarker levels. Utilizing two longitudinal observational prospective cohort studies, we investigated how the association of alcohol intake (a risk factor) with colorectal cancer incidence differed across the continuous values of tumor epigenetic DNA methylation at long interspersed nucleotide element-1 (LINE-1). The heterogeneous alcohol effect was modeled using different functions of the LINE-1 marker to demonstrate the method's flexibility. This real-world proof-of-principle computational application demonstrates how the new method enables visualizing the trend of the exposure effect over continuous marker levels. The utilization of continuous biomarker data without categorization for investigating etiological heterogeneity can advance our understanding of biological and pathogenic mechanisms.

18.
Ear Hear ; 43(5): 1447-1455, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35302530

RESUMO

OBJECTIVE: Single-ear hearing measurements, such as better-ear, worse-ear or left/right ear, are often used as outcomes in auditory research, yet, measurements in the two ears of the same individual are often strongly but not perfectly correlated. We propose a both-ear method using the Generalized Estimating Equation approach for analysis of correlated binary ear data to evaluate determinants of ear-specific outcomes that includes information from both ears of the same individual. DESIGN: We first theoretically evaluated bias in odds ratio (OR) estimates based on worse-ear and better-ear hearing outcomes. A simulation study was conducted to compare the finite sample performances of single-ear and both-ear methods in logistic regression models. As an illustrative example, the single-ear and both-ear methods were applied to estimate the association of Dietary Approaches to Stop Hypertension adherence scores with hearing threshold elevation among 3135 women, aged 48 to 68 years, in the Nurses' Health Study II. RESULTS: Based on statistical theories, the worse-ear and better-ear methods could bias the OR estimates. The simulation results led to the same conclusion. In addition, the simulation results showed that the both-ear method had satisfactory finite sample performance and was more efficient than the single-ear method. In the illustrative example, the confidence intervals of the estimated ORs for the association of Dietary Approaches to Stop Hypertension scores and hearing threshold elevation using the both-ear method were narrower, indicating greater precision, than for those obtained using the other methods. CONCLUSIONS: The worse-ear and better-ear methods may lead to biased estimates, and the left/right ear method typically results in less-efficient estimates. In certain settings, the both-ear method using the Generalized Estimating Equation approach for analyses of audiometric data may be preferable to the single-ear methods.


Assuntos
Audição , Audiometria de Tons Puros , Limiar Auditivo , Feminino , Humanos
19.
Ann Nutr Metab ; 78(3): 156-165, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35124672

RESUMO

INTRODUCTION: Gestational weight gain (GWG) is associated with fetal and newborn health; however, data from sub-Saharan Africa are limited. METHODS: We used data from a prenatal micronutrient supplementation trial among a cohort of human immunodeficiency virus-negative pregnant women in Dar es Salaam, Tanzania to estimate the relationships between GWG and neonatal outcomes. GWG adequacy was defined as the ratio of the total observed weight gain over the recommended weight gain based on the Institute of Medicine body mass index-specific guidelines. Neonatal outcomes assessed were stillbirth, perinatal death, preterm birth, low birthweight, macrosomia, small-for-gestational age (SGA), large-for-gestational age (LGA), stunting at birth, and microcephaly. Modified Poisson regressions with robust standard error were used to estimate the relative risk of newborn outcomes as a function of GWG adequacy. RESULTS: Of 7,561 women included in this study, 51% had severely inadequate (<70%) or inadequate GWG (70 to <90%), 31% had adequate GWG (90 to <125%), and 18% had excessive GWG (≥125%). Compared to adequate GWG, severely inadequate GWG was associated with a higher risk of low birthweight, SGA, stunting at birth, and microcephaly, whereas excessive GWG was associated with a higher risk of LGA and macrosomia. CONCLUSION: Interventions to support optimal GWG are needed and may contribute to preventing adverse neonatal outcomes.


Assuntos
Ganho de Peso na Gestação , Microcefalia , Nascimento Prematuro , Peso ao Nascer , Índice de Massa Corporal , Feminino , Macrossomia Fetal/epidemiologia , Transtornos do Crescimento , Humanos , Recém-Nascido , Gravidez , Resultado da Gravidez , Nascimento Prematuro/epidemiologia , Tanzânia/epidemiologia , Aumento de Peso
20.
J Gen Intern Med ; 2022 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-35132561

RESUMO

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.

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