Thyroid cancer mortality is higher in Filipinos in the United States: An analysis using national mortality records from 2003 through 2012.

BACKGROUND: Well-differentiated thyroid carcinoma has a favorable prognosis, but patients with multiple recurrences have drastically lower survival. Filipinos in the United States are known to have high rates of thyroid cancer incidence and disease recurrence. To the authors' knowledge, it is unknown whether Filipinos also have higher thyroid cancer mortality rates. METHODS: The authors studied thyroid cancer mortality in Filipino, non-Filipino Asian (NFA), and non-Hispanic white (NHW) adults using US death records (2003-2012) and US Census data. Age-adjusted mortality rates and proportional mortality ratios (PMRs) were calculated. Sex, nativity status, age at death, and educational attainment also were examined. RESULTS: The authors examined 19,940,952 deaths. The age-adjusted mortality rates due to thyroid cancer were highest in Filipinos (1.72 deaths per 100,000 population; 95% confidence interval [95% CI], 1.51-1.95) compared with NFAs (1.03 per 100,000 population; 95% CI, 0.95-1.12) and NHWs (1.17 per 100,000 population; 95% CI, 1.16-1.18). Compared with NHWs, higher proportionate mortality was observed in Filipino women (3-5 times higher) across all age groups, and among Filipino men, the PMR was 2 to 3 times higher in the subgroup aged >55 years. Filipinos who completed a higher educational level had a notably higher PMR (5.0) compared with their counterparts who had not (3.5). CONCLUSIONS: Negative prognostic factors for thyroid cancer traditionally include age >45 years and male sex. The results of the current study demonstrate that Filipinos die of thyroid cancer at higher rates than NFA and NHW individuals of similar ages. Highly educated Filipinos and Filipino women may be especially at risk of poor thyroid cancer outcomes. Filipino ethnicity should be factored into clinical decision making in the management of patients with thyroid cancer. Cancer 2017;123:4860-7. © 2017 American Cancer Society.

Estimating inverse-probability weights for longitudinal data with dropout or truncation: The xtrccipw command.

Individuals may drop out of a longitudinal study, rendering their outcomes unobserved but still well defined. However, they may also undergo truncation (for example, death), beyond which their outcomes are no longer meaningful. Kurland and Heagerty (2005, Biostatistics 6: 241-258) developed a method to conduct regression conditioning on nontruncation, that is, regression conditioning on continuation (RCC), for longitudinal outcomes that are monotonically missing at random (for example, because of dropout). This method first estimates the probability of dropout among continuing individuals to construct inverse-probability weights (IPWs), then fits generalized estimating equations (GEE) with these IPWs. In this article, we present the xtrccipw command, which can both estimate the IPWs required by RCC and then use these IPWs in a GEE estimator by calling the glm command from within xtrccipw. In the absence of truncation, the xtrccipw command can also be used to run a weighted GEE analysis. We demonstrate the xtrccipw command by analyzing an example dataset and the original Kurland and Heagerty (2005) data. We also use xtrccipw to illustrate some empirical properties of RCC through a simulation study.

Plasma Micronutrient Concentrations Are Altered by Antiretroviral Therapy and Lipid-Based Nutrient Supplements in Lactating HIV-Infected Malawian Women.

BACKGROUND: Little is known about the influence of antiretroviral therapy with or without micronutrient supplementation on the micronutrient concentrations of HIV-infected lactating women in resource-constrained settings. OBJECTIVE: We examined associations of highly active antiretroviral therapy (HAART) and lipid-based nutrient supplements (LNS) with concentrations of selected micronutrients in HIV-infected Malawian women at 24 wk postpartum. METHODS: Plasma micronutrient concentrations were measured in a subsample (n = 690) of Breastfeeding, Antiretrovirals, and Nutrition (BAN) study participants who were randomly assigned at delivery to receive HAART, LNS, HAART+LNS, or no HAART/no LNS (control). HAART consisted of protease inhibitor-based triple therapy. LNS (140 g/d) met energy and micronutrient requirements of lactation. Multivariable linear regression tested the association of HAART and LNS, plus their interaction, with micronutrient concentrations, controlling for season, baseline viral load, and baseline CD4 count. RESULTS: We found significant HAART by LNS interactions for folate (P = 0.051), vitamin B-12 (P < 0.001), and transferrin receptors (TfRs) (P = 0.085). HAART was associated with lower folate (with LNS: -27%, P < 0.001; without LNS: -12%, P = 0.040) and higher TfR concentrations (with LNS: +14%, P = 0.004; without LNS: +28%, P < 0.001), indicating iron deficiency. LNS increased folate (with HAART: +17%, P = 0.037; without HAART: +39%, P < 0.001) and decreased TfR concentrations (with HAART only: -12%, P = 0.023). HAART was associated with lower vitamin B-12 concentrations only when LNS was present (-18%, P = 0.001), whereas LNS increased vitamin B-12 only when no HAART was present (+27%, P < 0.001). HAART, but not LNS, was associated with higher retinol-binding protein (RBP; +10%, P = 0.007). We detected no association of HAART or LNS with selenium, ferritin, or hemoglobin. CONCLUSION: The association of HAART with lower folate, iron deficiency, and higher RBP plus the attenuation of LNS effects on folate and vitamin B-12 when combined with HAART has implications for the health of lactating HIV-infected women taking HAART in prevention of mother-to-child transmission programs. This trial was registered at clinicaltrials.gov as NCT00164736.

Integrating group counseling, cell phone messaging, and participant-generated songs and dramas into a microcredit program increases Nigerian women's adherence to international breastfeeding recommendations.

In northern Nigeria, interventions are urgently needed to narrow the large gap between international breastfeeding recommendations and actual breastfeeding practices. Studies of integrated microcredit and community health interventions documented success in modifying health behaviors but typically had uncontrolled designs. We conducted a cluster-randomized controlled trial in Bauchi State, Nigeria, with the aim of increasing early breastfeeding initiation and exclusive breastfeeding among female microcredit clients. The intervention had 3 components. Trained credit officers led monthly breastfeeding learning sessions during regularly scheduled microcredit meetings for 10 mo. Text and voice messages were sent out weekly to a cell phone provided to small groups of microcredit clients (5-7 women). The small groups prepared songs or dramas about the messages and presented them at the monthly microcredit meetings. The control arm continued with the regular microcredit program. Randomization occurred at the level of the monthly meeting groups. Pregnant clients were recruited at baseline and interviewed again when their infants were aged ≥6 mo. Logistic regression models accounting for clustering were used to estimate the odds of performing recommended behaviors. Among the clients who completed the final survey (n = 390), the odds of exclusive breastfeeding to 6 mo (OR: 2.4; 95% CI: 1.4, 4.0) and timely breastfeeding initiation (OR: 2.6; 95% CI: 1.6, 4.1) were increased in the intervention vs. control arm. Delayed introduction of water explained most of the increase in exclusive breastfeeding among clients receiving the intervention. In conclusion, a breastfeeding promotion intervention integrated into microcredit increased the likelihood that women adopted recommended breastfeeding practices. This intervention could be scaled up in Nigeria, where local organizations provide microcredit to >500,000 clients. Furthermore, the intervention could be adopted more widely given that >150 million women, many of childbearing age, are involved in microfinance globally.

Changes in soluble transferrin receptor and hemoglobin concentrations in Malawian mothers are associated with those values in their exclusively breastfed, HIV-exposed infants.

Infant iron status at birth is influenced by maternal iron status during pregnancy; however, there are limited data on the extent to which maternal iron status is associated with infant iron status during exclusive breastfeeding. We evaluated how maternal and infant hemoglobin and iron status [soluble transferrin receptors (TfR) and ferritin] were related during exclusive breastfeeding in HIV-infected women and their infants. The Breastfeeding, Antiretrovirals, and Nutrition Study was a randomized controlled trial in Lilongwe, Malawi, in which HIV-infected women were assigned with a 2 × 3 factorial design to a lipid-based nutrient supplement (LNS), or no LNS, and maternal, infant, or no antiretroviral drug, and followed for 24 wk. Longitudinal models were used to relate postpartum maternal hemoglobin (n = 1926) to concurrently measured infant hemoglobin, adjusting for initial infant hemoglobin values. In a subsample, change in infant iron status (hemoglobin, log ferritin, log TfR) between 2 (n = 352) or 6 wk (n = 167) and 24 wk (n = 519) was regressed on corresponding change in the maternal indicator, adjusting for 2 or 6 wk values. A 1 g/L higher maternal hemoglobin at 12, 18, and 24 wk was associated with a 0.06 g/L (P = 0.01), 0.10 g/L (P < 0.001), and 0.06 g/L (P = 0.01), respectively, higher infant hemoglobin. In the subsample, a reduction in maternal log TfR and an increase in hemoglobin from initial measurement to 24 wk were associated with the same pattern in infant values (log TfR ß = -0.18 mg/L, P < 0.001; hemoglobin ß = 0.13 g/L, P = 0.01). Given the observed influence of maternal and initial infant values, optimizing maternal iron status in pregnancy and postpartum is important to protect infant iron status. This trial was registered at clinicaltrials.gov as NCT00164736.

Patient and Physician Perspectives on the Use of a Connected Ecosystem for Diabetes Management: International Cross-Sectional Observational Study.

BACKGROUND: Collaboration between people with type 2 diabetes (T2DM) and their health care teams is important for optimal control of the disease and outcomes. Digital technologies could potentially tie together several health care-related devices and platforms into connected ecosystems (CES), but attitudes about CES are unknown. OBJECTIVE: We surveyed convenience samples of patients and physicians to better understand which patient characteristics are associated with higher likelihoods of (1) participating in a potential CES program, as self-reported by patients with T2DM and (2) clinical benefit from participation in a potential CES program, as reported by physicians. METHODS: Adults self-reporting a diagnosis of T2DM and current insulin use (n=197), and 33 physicians whose practices included ≥20% of such patients, were enrolled in the United States, France, and Germany. We surveyed both groups about the likelihood of patient participation in a CES. We then examined the associations between patients' clinical and sociodemographic characteristics and this likelihood. We also described characteristics of patients likely to clinically benefit from CES use, according to physicians. RESULTS: Compared with patients in Germany and France, US patients were younger (mean age 45.3 [SD 11.9] years vs 61.9 [SD 9.2] and 65.8 [SD 9.4] years, respectively), more often female, more highly educated, and more often working full-time. In all, 51 (44.7%) US patients, 16 (36.4%) German patients, and 18 (46.3%) French patients indicated strong interest in a CES program, and 115 (78.7%) reported currently using ≥1 connected device or app. However, physicians believed that only 11.3%-19.2% of their patients were using connected devices or apps to manage their disease. Physicians also reported infrequently recommending or prescribing connected devices to their patients, although ≥80% (n=28) of them thought that a CES could help support their patients in managing their disease. The factors most predictive of patient likelihood of participating in a CES program were cost, inclusion of medication reminders, and linking blood glucose levels to behaviors such as eating and exercise. In all countries, the most common patient expectations for a CES program were that it could help them eat more healthfully, increase their physical activity, increase their understanding of how blood glucose relates to behavior such as exercise and eating, and reduce stress. Physicians thought that newly diagnosed patients, sicker patients-those who had been hospitalized for diabetes, were currently using insulin, or who had any comorbid condition-and patients who were nonadherent to treatment were most likely to benefit from CES use. CONCLUSIONS: In this study, there was a high degree of interest in the future use of CES, although additional education is needed among both patients with T2DM and their physicians to achieve the full potential of such systems to improve self-management and clinical care for the disease.

What possibly affects nighttime heart rate? Conclusions from N-of-1 observational data.

Background: Heart rate (HR), especially at nighttime, is an important biomarker for cardiovascular health. It is known to be influenced by overall physical fitness, as well as daily life physical or psychological stressors like exercise, insufficient sleep, excess alcohol, certain foods, socialization, or air travel causing physiological arousal of the body. However, the exact mechanisms by which these stressors affect nighttime HR are unclear and may be highly idiographic (i.e. individual-specific). A single-case or "n-of-1" observational study (N1OS) is useful in exploring such suggested effects by examining each subject's exposure to both stressors and baseline conditions, thereby characterizing suggested effects specific to that individual. Objective: Our objective was to test and generate individual-specific N1OS hypotheses of the suggested effects of daily life stressors on nighttime HR. As an N1OS, this study provides conclusions for each participant, thus not requiring a representative population. Methods: We studied three healthy, nonathlete individuals, collecting the data for up to four years. Additionally, we evaluated model-twin randomization (MoTR), a novel Monte Carlo method facilitating the discovery of personalized interventions on stressors in daily life. Results: We found that physical activity can increase the nighttime heart rate amplitude, whereas there were no strong conclusions about its suggested effect on total sleep time. Self-reported states such as exercise, yoga, and stress were associated with increased (for the first two) and decreased (last one) average nighttime heart rate. Conclusions: This study implemented the MoTR method evaluating the suggested effects of daily stressors on nighttime heart rate, sleep time, and physical activity in an individualized way: via the N-of-1 approach. A Python implementation of MoTR is freely available.

Estimating the Burden of Influenza-like Illness on Daily Activity at the Population Scale Using Commercial Wearable Sensors.

Importance: The severity of viral infections can vary widely, from asymptomatic cases to complications leading to hospitalizations and death. Milder cases, despite being more prevalent, often go undocumented, and their public health burden is not accurately estimated. Objective: To estimate the true burden of influenza-like illness (ILI) in the US population using a surrogate measure of daily steps lost as measured by commercial wearable sensors. Design, Setting, and Participants: This cohort study modeled data from 15 122 US adults who reported ILI symptoms during the 2018-2019 influenza season (before the COVID-19 pandemic) and who had a sufficient density of wearable sensor data at symptom onset. Participants' minute-level step data as measured by commercial wearable sensors were collected from October 1, 2018, through June 30, 2019. Minute-level activity time series were transformed into day-level time series per user, indicating the total number of steps daily. Main Outcomes and Measures: The primary end point was the number of steps lost during the period of 4 days before symptom onset (the latent phase) through 11 days after symptom onset (the symptomatic phase). The association between covariates and steps lost during this interval was also examined. Results: Of the 15 122 participants in this study, 13 108 (86.7%) were women, and the median age was 32 years (IQR, 27-38 years). For their ILI event, 2836 of 15 080 participants (18.8%) sought medical attention, and only 61 (0.4%) were hospitalized. Over the course of an ILI lasting 10 days, the mean cumulative loss was 4437 steps (95% CI, 4143-4731 steps). After weighting, there was an estimated overall nationwide reduction in mobility equivalent to 255.2 billion steps (95% CI, 232.9-277.6 billion steps) lost because of ILI symptoms during the study period. This finding reflects significant changes in routines, mobility, and employment and is equivalent to 15% of the active US population becoming completely immobilized for 1 day. Moreover, 60.6% of this reduction in steps (154.6 billion steps [95% CI, 138.1-171.2 billion steps]) occurred among persons who sought no medical care. Age and educational level were positively associated with steps lost. Conclusions and Relevance: These findings suggest that most of the burden of ILI in this study would have been invisible to health care and public health reporting systems. This approach has applications for public health, health care, and clinical research, from estimating costs of lost productivity at population scale, to measuring effectiveness of anti-ILI treatments, to monitoring recovery after acute viral syndromes such as during long COVID-19.

Causal Analysis of Self-tracked Time Series Data Using a Counterfactual Framework for N-of-1 Trials.

Many of an individual's historically recorded personal measurements vary over time, thereby forming a time series (e.g., wearable-device data, self-tracked fitness or nutrition measurements, regularly monitored clinical events or chronic conditions). Statistical analyses of such n-of-1 (i.e., single-subject) observational studies (N1OSs) can be used to discover possible cause-effect relationships to then self-test in an n-of-1 randomized trial (N1RT). However, a principled way of determining how and when to interpret an N1OS association as a causal effect (e.g., as if randomization had occurred) is needed.Our goal in this paper is to help bridge the methodological gap between risk-factor discovery and N1RT testing by introducing a basic counterfactual framework for N1OS design and personalized causal analysis.We introduce and characterize what we call the average period treatment effect (APTE), i.e., the estimand of interest in an N1RT, and build an analytical framework around it that can accommodate autocorrelation and time trends in the outcome, effect carryover from previous treatment periods, and slow onset or decay of the effect. The APTE is loosely defined as a contrast (e.g., difference, ratio) of averages of potential outcomes the individual can theoretically experience under different treatment levels during a given treatment period. To illustrate the utility of our framework for APTE discovery and estimation, two common causal inference methods are specified within the N1OS context. We then apply the framework and methods to search for estimable and interpretable APTEs using six years of the author's self-tracked weight and exercise data, and report both the preliminary findings and the challenges we faced in conducting N1OS causal discovery.Causal analysis of an individual's time series data can be facilitated by an N1RT counterfactual framework. However, for inference to be valid, the veracity of certain key assumptions must be assessed critically, and the hypothesized causal models must be interpretable and meaningful.

A Bayesian approach to the g-formula.

Epidemiologists often wish to estimate quantities that are easy to communicate and correspond to the results of realistic public health interventions. Methods from causal inference can answer these questions. We adopt the language of potential outcomes under Rubin's original Bayesian framework and show that the parametric g-formula is easily amenable to a Bayesian approach. We show that the frequentist properties of the Bayesian g-formula suggest it improves the accuracy of estimates of causal effects in small samples or when data are sparse. We demonstrate an approach to estimate the effect of environmental tobacco smoke on body mass index among children aged 4-9 years who were enrolled in a longitudinal birth cohort in New York, USA. We provide an algorithm and supply SAS and Stan code that can be adopted to implement this computational approach more generally.

Likelihood of Unemployed Smokers vs Nonsmokers Attaining Reemployment in a One-Year Observational Study.

IMPORTANCE: Studies in the United States and Europe have found higher smoking prevalence among unemployed job seekers relative to employed workers. While consistent, the extant epidemiologic investigations of smoking and work status have been cross-sectional, leaving it underdetermined whether tobacco use is a cause or effect of unemployment. OBJECTIVE: To examine differences in reemployment by smoking status in a 12-month period. DESIGN, SETTING, AND PARTICIPANTS: An observational 2-group study was conducted from September 10, 2013, to August 15, 2015, in employment service settings in the San Francisco Bay Area (California). Participants were 131 daily smokers and 120 nonsmokers, all of whom were unemployed job seekers. Owing to the study's observational design, a propensity score analysis was conducted using inverse probability weighting with trimmed observations. Including covariates of time out of work, age, education, race/ethnicity, and perceived health status as predictors of smoking status. MAIN OUTCOMES AND MEASURES: Reemployment at 12-month follow-up. RESULTS: Of the 251 study participants, 165 (65.7) were men, with a mean (SD) age of 48 (11) years; 96 participants were white (38.2%), 90 were black (35.9%), 24 were Hispanic (9.6%), 18 were Asian (7.2%), and 23 were multiracial or other race (9.2%); 78 had a college degree (31.1%), 99 were unstably housed (39.4%), 70 lacked reliable transportation (27.9%), 52 had a criminal history (20.7%), and 72 had received prior treatment for alcohol or drug use (28.7%). Smokers consumed a mean (SD) of 13.5 (8.2) cigarettes per day at baseline. At 12-month follow-up (217 participants retained [86.5%]), 60 of 108 nonsmokers (55.6%) were reemployed compared with 29 of 109 smokers (26.6%) (unadjusted risk difference, 0.29; 95% CI, 0.15-0.42). With 6% of analysis sample observations trimmed, the estimated risk difference indicated that nonsmokers were 30% (95% CI, 12%-48%) more likely on average to be reemployed at 1 year relative to smokers. Results of a sensitivity analysis with additional covariates of sex, stable housing, reliable transportation, criminal history, and prior treatment for alcohol or drug use (25.3% of observations trimmed) reduced the difference in employment attributed to smoking status to 24% (95% CI, 7%-39%), which was still a significant difference. Among those reemployed at 1 year, the average hourly wage for smokers was significantly lower (mean [SD], $15.10 [$4.68]) than for nonsmokers (mean [SD], $20.27 [$10.54]; F(1,86) = 6.50, P = .01). CONCLUSIONS AND RELEVANCE: To our knowledge, this is the first study to prospectively track reemployment success by smoking status. Smokers had a lower likelihood of reemployment at 1 year and were paid significantly less than nonsmokers when reemployed. Treatment of tobacco use in unemployment service settings is worth testing for increasing reemployment success and financial well-being.

Online Patient-Provider E-cigarette Consultations: Perceptions of Safety and Harm.

INTRODUCTION: E-cigarettes are popular and unregulated. Patient-provider communications concerning e-cigarettes were characterized to identify patient concerns, provider advice and attitudes, and research needs. METHODS: An observational study of online patient-provider communications was conducted January 2011-June 2015 from a network providing free medical advice, and analyzed July 2014-May 2016. Patient and provider themes, and provider attitudes toward e-cigarettes (positive, negative, or neutral) were coded qualitatively. Provider attitudes were analyzed with cumulative logit modeling to account for clustering. Patient satisfaction with provider responses was expressed via a Thank function. RESULTS: An increase in e-cigarette-related questions was observed over time. Patient questions (N=512) primarily concerned specific side effects and harms (34%); general safety (27%); e-cigarettes as quit aids (19%); comparison of e-cigarette harms relative to combusted tobacco (18%); use with pre-existing medical conditions (18%); and nicotine-free e-cigarettes (14%). Half of provider responses discussed e-cigarettes as a harm reduction option (48%); 26% discussed them as quit aids. Overall, 47% of providers' responses represented a negative attitude toward e-cigarettes; 33% were neutral (contradictory or non-committal); and 20% were positive. Attitudes did not differ statistically by medical specialty; provider responses positive toward e-cigarettes received significantly more Thanks. CONCLUSIONS: Examination of online patient-provider communications provides insight into consumer health experience with emerging alternative tobacco products. Patient concerns largely related to harms and safety, and patients preferred provider responses positively inclined toward e-cigarettes. Lacking conclusive evidence of e-cigarette safety or efficacy, healthcare providers encouraged smoking cessation and recommended first-line cessation treatment approaches.

Plasma and breast-milk selenium in HIV-infected Malawian mothers are positively associated with infant selenium status but are not associated with maternal supplementation: results of the Breastfeeding, Antiretrovirals, and Nutrition study.

BACKGROUND: Selenium is found in soils and is essential for human antioxidant defense and immune function. In Malawi, low soil selenium and dietary intakes coupled with low plasma selenium concentrations in HIV infection could have negative consequences for the health of HIV-infected mothers and their exclusively breastfed infants. OBJECTIVE: We tested the effects of lipid-based nutrient supplements (LNS) that contained 1.3 times the Recommended Dietary Allowance of sodium selenite and antiretroviral drugs (ARV) on maternal plasma and breast-milk selenium concentrations. DESIGN: HIV-infected Malawian mothers in the Breastfeeding, Antiretrovirals, and Nutrition study were randomly assigned at delivery to receive: LNS, ARV, LNS and ARV, or a control. In a subsample of 526 mothers and their uninfected infants, we measured plasma and breast-milk selenium concentrations at 2 or 6 (depending on the availability of infant samples) and 24 wk postpartum. RESULTS: Overall, mean (± SD) maternal (range: 81.2 ± 20.4 to 86.2 ± 19.9 µg/L) and infant (55.6 ± 16.3 to 61.0 ± 15.4 µg/L) plasma selenium concentrations increased, whereas breast-milk selenium concentrations declined (14.3 ± 11.5 to 9.8 ± 7.3 µg/L) from 2 or 6 to 24 wk postpartum (all P < 0.001). Compared with the highest baseline selenium tertile, low and middle tertiles were positively associated with a change in maternal plasma or breast-milk selenium from 2 or 6 to 24 wk postpartum (both P < 0.001). With the use of linear regression, we showed that LNS that contained selenium and ARV were not associated with changes in maternal plasma and breast-milk selenium, but maternal selenium concentrations were positively associated with infant plasma selenium at 2 or 6 and 24 wk postpartum (P < 0.001) regardless of the study arm. CONCLUSIONS: Selenite supplementation of HIV-infected Malawian women was not associated with a change in their plasma or breast-milk selenium concentrations. Future research should examine effects of more readily incorporated forms of selenium (ie, selenomethionine) in HIV-infected breastfeeding women.