Firefighter occupational factors and the risk of preterm birth: results from a survey of women firefighters in the USA.

OBJECTIVES: Previous research has suggested that women firefighters may have a greater risk of adverse reproductive outcomes compared with non-firefighting women. In this study, we investigated the association between firefighter occupational factors and risk of preterm birth. METHODS: This cross-sectional analysis of US firefighters surveyed in 2017 compared preterm birth among firefighters to non-firefighters using age-at-pregnancy-standardised prevalence ratios. Generalised estimating equations estimated relative risks and 95% CIs between firefighter occupational factors (career or volunteer, wildland status, shift schedule, fire responses, work restriction) and preterm birth risk. We adjusted for age-at-pregnancy, education, gravidity, BMI, and smoking and considered effect modification by age-at-pregnancy and career versus volunteer status. RESULTS: Among 934 women who reported 1356 live births, 12% were preterm (n=161). Preterm birth prevalence among firefighters was 1.41 times greater than non-firefighters (95% CI 1.18 to 1.68). Among wildland and combination wildland/structural firefighters, volunteers had 2.82 times the risk of preterm birth (95% CI 1.19 to 6.67) compared with career firefighters. Firefighters who started restricting their work in the 2nd trimester had a nonsignificant 0.67 times lower risk of preterm birth than those who started in the 3rd trimester or did not restrict work at all (95% CI 0.43 to 1.03). CONCLUSIONS: Firefighters may have greater risk of preterm birth than non-firefighters, which could be influenced by roles in the fire service and work restrictions taken.

Anxiety, depression, and concentration in cancer survivors: National Health and Nutrition Examination Survey results.

PURPOSE: We report on prevalence of anxiety, depression, and concentration difficulties and their associations in survivors of cancer in a nationally representative sample up to 25 years after diagnosis. METHODS: Using the National Health and Nutrition Examination Survey (NHANES) data from 2015 to 2018, participants between the ages of 18 and 79 self-reported on cancer history, symptoms of anxiety, depression, and difficulties with concentration. RESULTS: Of 10,337 participants, 691 (6.7%) reported a previous diagnosis of cancer; the median time since diagnosis was 8 years. Prevalence was similar between those with and without cancer for anxiety (45.8% versus 46.9%) and depression (19.7% versus 20.0%). Concentration difficulties were more common (11.3% versus 9.0%) for those with a history of cancer compared to those without (adjusted OR = 1.38, 95% CI: 1.00-1.90). Prevalence of mental health symptoms was not related to time since diagnosis. Anxiety and depression were highly correlated (r = 0.81, 95% CI: 0.74-0.86) and moderately correlated with difficulty with concentration (r = 0.52, 95%CI: 0.40-0.64 and r = 0.64, 95% CI: 0.53-0.74 respectively). CONCLUSIONS: Difficulty with concentration was more commonly reported by participants with than without a cancer history. Report of anxiety and depression was no different between participants with and without a history of cancer. Anxiety, depression, and difficulties with concentration were strongly related. Further research is needed to explore if there is a causal association, and if so, the direction of these correlations, so that interventions may be appropriately targeted.

Laparoscopically Confirmed Endometriosis and Risk of Incident Stroke: A Prospective Cohort Study.

BACKGROUND: Prior research suggests that women with endometriosis are at greater risk of coronary heart disease. Therefore, our objective was to prospectively investigate the association between laparoscopically confirmed endometriosis and risk of incident stroke during 28 years of follow-up. METHODS: Participants in the NHSII cohort study (Nurses' Health Study II) were followed from 1989 when they were between the ages of 25 to 42 until 2017 for development of incident stroke (ischemic and hemorrhagic). Cox proportional hazard models were used to calculate hazard ratios and 95% CI, with adjustment for potential confounding variables (alcohol intake, body mass index at age 18, current body mass index, age at menarche, menstrual cycle pattern in adolescence, current menstrual cycle pattern, parity, oral contraceptive use history, smoking history, diet quality, physical activity, NSAID use, aspirin use, race/ethnicity, and income). We estimated the proportion of the total association mediated by history of hypertension, hypercholesterolemia, hysterectomy/oophorectomy, and hormone therapy. We also tested for effect modification by age (<50, ≥50 years), infertility history, body mass index (<25, ≥25 kg/m2), and menopausal status. RESULTS: We documented 893 incident cases of stroke during 2 770 152 person-years of follow-up. Women with laparoscopically confirmed endometriosis had a 34% greater risk of stroke in multivariable-adjusted models (hazard ratio, 1.34 [95% CI, 1.10-1.62]), compared to those without a history of endometriosis. Of the total association of endometriosis with risk of stroke, the largest proportion was attributed to hysterectomy/oophorectomy (39% mediated [95% CI, 14%-71%]) and hormone therapy (16% mediated [95% CI, 5%-40%]). We observed no differences in the relationship between endometriosis and stroke by age, infertility history, body mass index, or menopausal status. CONCLUSIONS: We observed that women with endometriosis were at elevated risk of stroke. Women and their health care providers should be aware of endometriosis history, maximize primary cardiovascular prevention, and discuss signs and symptoms of cardiovascular disease.

The relationship between sleep and weight change among women diagnosed with breast cancer participating in the Women's Health Initiative.

PURPOSE: Short and long sleep duration and poor sleep quality are risk factors for weight gain and cancer mortality. The purpose of this study is to investigate the relationship between sleep and weight change among postmenopausal breast cancer survivors. METHODS: Women participating in the Women's Health Initiative who were diagnosed with incident breast cancer between year one and year three were included. Self-reported sleep duration was categorized as ≤ 5 h (short), 6 h, 7-8 h (optimal), and ≥ 9 h (long). Self-reported sleep quality was categorized as poor, average, and above average. Post-diagnosis weight change was the difference of weight closest to, but preceding diagnosis, and year 3 weight. We used linear regression to evaluate sleep duration and sleep quality associations with post-diagnosis weight change adjusted for potential confounders. RESULTS: Among 1156 participants, 63% were weight stable after diagnosis; average weight gain post cancer diagnosis was 3.2 kg. Six percent of women reported sleeping ≤ 5 h, 26% reported 6 h, 64% reported 7-8 h, and 4% reported ≥ 9 h. There were no differences in adjusted estimates of weight change among participants with short duration (0.37 kg; 95% CI - 0.88, 1.63), or long duration (- 0.56 kg; 95% CI - 2.03, 0.90) compared to optimal duration, nor was there a difference among poor quality (- 0.51 kg; 95% CI - 1.42, 0.41) compared to above average quality. CONCLUSION: Among postmenopausal breast cancer survivors, sleep duration and quality were not associated with weight change after breast cancer diagnosis. Future studies should consider capturing change in adiposity and to expand beyond self-reported sleep.

Screening for cognitive symptoms among cancer patients during chemotherapy: Sensitivity and specificity of a single item self-report cognitive change score.

OBJECTIVES: Cognitive symptoms are commonly reported among cancer patients and survivors, yet guidance on when self-reported cognitive symptoms warrant follow-up is lacking. We sought to establish cut-off scores for identifying patients with perceived low cognitive functioning on widely used self-report measures of cognition and a novel single item Cognitive Change Score. METHODS: Adult patients diagnosed with invasive cancer who had completed at least one cycle of chemotherapy completed a questionnaire containing the EORTC-Cognitive Function (CF) subscale, Functional Assessment of Cancer Therapy-Cognitive Function (FACT-COG) Perceived Cognitive Impairment (PCI) and our Cognitive Change Score (CCS). We used receiver operating characteristic analyses to establish the discriminative ability of these measures against the Patient's Assessment of Own Functioning Inventory (PAOFI) as our reference standard. We chose cut-off scores on each measure that maximised both sensitivity and specificity for identifying patients with self-reported low CF. RESULTS: We recruited 294 participants (55.8% women, mean age 56.6 years) with mixed cancer diagnoses (25.5 months since diagnosis). On the CCS, 77.6% reported some cognitive change since starting chemotherapy. On the PAOFI 36% had low CF. The following cut-off scores identified cases of low CF: ≥28.5 on the CCS (75.5% sensitivity, 67.6% specificity); ≤75.0 on the European Organisation for Research and Treatment of Cancer, QLQ-C30 Cognitive Functioning scale (90.9% sensitivity, 57.1% specificity); ≤55.1 on the FACT-COG PCI-18 (84.8% sensitivity, 76.2% specificity), and ≤59.5 on the FACT-COG PCI-20 (78.8% sensitivity, 84.1% specificity). CONCLUSIONS: We found a single item question asking about cognitive change has acceptable discrimination between patients with self-reported normal and low CF when compared to other more comprehensive self-report measures of cognitive symptoms. Further validation work is required.

Managing missing items in the Fagerström Test for Nicotine Dependence: a simulation study.

BACKGROUND: The Fagerström Test for Nicotine Dependence (FTND) is frequently used to assess the level of smokers' nicotine dependence; however, it is unclear how to manage missing items. The aim of this study was to investigate different methods for managing missing items in the FTND. METHODS: We performed a simulation study using data from the Arizona Smokers' Helpline. We randomly sampled with replacement from the complete data to simulate 1000 datasets for each parameter combination of sample size, proportion of missing data, and type of missing data (missing at random and missing not at random). Then for six methods for managing missing items on the FTND (two involving no imputation and four involving single imputation), we assessed the accuracy (via bias) and precision (via bias of standard error) of the total FTND score itself and of the regression coefficient for the total FTND score regressed on a covariate. RESULTS: When using the total FTND score as a descriptive statistic or in analysis for both types of missing data and for all levels of missing data, proration performed the best in terms of accuracy and precision. Proration's accuracy decreased with the amount of missing data; for example, at 9% missing data proration's maximum bias for the mean FTND was only - 0.3%, but at 35% missing data its maximum bias for the mean FTND increased to - 6%. CONCLUSIONS: For managing missing items on the FTND, we recommend proration, because it was found to be accurate and precise, and it is easy to implement. However, because proration becomes less accurate with more missing data, if more than ~ 10% of data are missing, we recommend performing a sensitivity analysis with a different method of managing missing data.

Persisting gastrointestinal symptoms and post-infectious irritable bowel syndrome following SARS-CoV-2 infection: results from the Arizona CoVHORT.

In this study, we aimed to examine the association between gastrointestinal (GI) symptom presence during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the prevalence of GI symptoms and the development of post-infectious irritable bowel syndrome (PI-IBS). We used data from a prospective cohort and logistic regression to examine the association between GI symptom status during confirmed SARS-CoV-2 infection and prevalence of persistent GI symptoms at ≥45 days. We also report the incidence of PI-IBS following SARS-CoV-2 infection. Of the 1475 participants in this study, 33.8% (n = 499) had GI symptoms during acute infection. Cases with acute GI symptoms had an odds of persisting GI symptoms 4 times higher than cases without acute GI symptoms (odds ratio (OR) 4.29, 95% confidence interval (CI) 2.45-7.53); symptoms lasted on average 8 months following infection. Of those with persisting GI symptoms, 67% sought care for their symptoms and incident PI-IBS occurred in 3.0% (n = 15) of participants. Those with acute GI symptoms after SARS-CoV-2 infection are likely to have similar persistent symptoms 45 days and greater. These data indicate that attention to a potential increase in related healthcare needs is warranted.

Comorbidities and perceived health status in persons with history of cancer in the USA.

PURPOSE: Comorbidities can further challenge prognosis and general wellbeing of cancer patients. This study aimed to assess the association between comorbidities and perceived health status (PHS) of US persons with cancer. METHODS: This cross-sectional study used 2019 Medical Expenditure Panel Survey (MEPS) data and included individuals who were alive throughout the year, aged 18 to 84 years, and had diagnosis for cancer. Using adjusted logistic regression models, we estimated the association of comorbidities (no, few [1/2], and more [3 or more] comorbidities) with PHS. Analyses accounted for the complex design of MEPS. RESULTS: The dataset included 28,512 participants, 1739 of which were eligible for the study. Of these, 11.16% (95% CI 9.64, 12.59%); 41.73% (95% CI 39.21, 43.96%); and 47.10% (95% CI 44.86, 49.73%) reported having no, few, and more comorbidities, respectively. While breast (N = 356), prostate (N = 276), and melanoma (N = 273) were the most common cancers, hypertension (88.3%), hypercholesterolemia (49.5%), and arthritis (48%) were the most prevalent comorbidities. Adjusted logistic regression showed that, compared with those with no comorbidities, persons with few and more comorbidities had 1.58 (95% CI = 0.79, 3.15) and 2.27 (95% CI = 1.19, 4.32) times greater odds of poor PHS. Younger or male patients, those with less formal education, low-income, pain, functional limitation, or poor perception of mental health were more likely to regard their health as poor. CONCLUSION: About 88% of persons with history of cancer in the USA aged 18-84 years reported at least one comorbidity. Having more comorbidities, along with several other variables, was associated with poor PHS. Comorbidities management must be given special consideration to improve the prognosis and general wellbeing of persons with cancer.

Perceived Normalization of Drug Trafficking and Adolescent Substance Use on the US-Mexico Border.

Background: Historically marginalized youth are at risk for daily substance use. Daily use may be associated with social and environmental factors. Methods: In March 2018, we surveyed primarily Latino adolescents ages 14-18 who lived on the US-Mexico border and assessed associations between daily substance use, neighborhood stress, border community and immigration stress, and family support. Results: Of 443 surveyed adolescents, 41 (9%) reported daily use. Those who used daily were more likely to be older, identify as male, and reported lower social support and higher neighborhood and border community stress compared to those who did not use daily. Perceived neighborhood stress (OR = 1.95, 95% CI 1.37-2.80) and border community and immigration stress (OR = 1.55, 95% CI 1.12-2.02) were associated with increased odds of daily substance use. Discussion: Latino adolescents who live near the US-Mexico border experience unique socioenvironmental stress which is associated with daily substance use.

Correlates of cognitive impairment in adult cancer survivors who have received chemotherapy and report cognitive problems.

OBJECTIVE: Cognitive impairment negatively affects some cancer survivors who have completed chemotherapy; however, factors underlying this cognitive impairment remain poorly understood. We aimed to investigate (1) the relative importance of demographics, medical, and psychological characteristics associated with cognitive impairment and (2) the specific variables associated with cognitive impairment in adult cancer survivors who completed adjuvant chemotherapy. METHODS: We performed post hoc analyses of baseline data from early-stage cancer survivors with cognitive complaints who received adjuvant chemotherapy 0.5-5 years earlier and volunteered for a trial designed to improve cognition. The primary outcome of self-reported cognitive impairment was measured using a questionnaire; secondary outcome of objective cognitive impairment was measured using a computerized neuropsychological test battery. Hierarchical linear regression determined the relative importance of demographics, medical, and psychological characteristics in associations with both self-reported and objective cognitive impairment. RESULTS: The sample was 95% female and 89% breast cancer patients. The final model accounted for 33% of variation in self-reported cognitive impairment (n = 212, demographics 5%, medical 3%, and psychological 25%), with fatigue and stress as significant individual correlates (p values ≤ 0.0001). For the secondary analysis, the final model accounted for 19% of variation in objective cognitive impairment (n = 206, demographics 10%, medical 5%, and psychological 4%), with age, smoking history, and number of chemotherapy cycles as significant individual correlates. CONCLUSION: We found that psychological characteristics are more important than demographic and medical characteristics in self-reported cognitive impairment, whereas other characteristics are more important in objective cognitive impairment. This suggests clinicians should investigate possible psychological problems in cancer survivors who self-report cognitive impairment.

Occupational factors and miscarriages in the US fire service: a cross-sectional analysis of women firefighters.

BACKGROUND: Evidence from previous studies suggests that women firefighters have greater risk of some adverse reproductive outcomes. The purpose of this study was to investigate whether women firefighters had greater risk of miscarriage compared to non-firefighters and whether there were occupational factors associated with risk of miscarriage among firefighters. METHODS: We studied pregnancies in the United States fire service using data from the Health and Wellness of Women Firefighters Study (n = 3181). We compared the prevalence of miscarriage among firefighters to published rates among non-firefighters using age-standardized prevalence ratios. We used generalized estimating equations to estimate relative risks (RRs) and 95% confidence intervals (CIs) between occupational factors (employment (career/volunteer), wildland firefighter status (wildland or wildland-urban-interface/structural), shift schedule, fire/rescue calls at pregnancy start) and risk of miscarriage, adjusted for age at pregnancy, education, gravidity, BMI, and smoking. We evaluated if associations varied by age at pregnancy or employment. RESULTS: Among 1074 firefighters and 1864 total pregnancies, 404 pregnancies resulted in miscarriages (22%). Among most recent pregnancies, 138 resulted in miscarriage (13%). Compared to a study of US nurses, firefighters had 2.33 times greater age-standardized prevalence of miscarriage (95% CI 1.96-2.75). Overall, we observed that volunteer firefighters had an increased risk of miscarriage which varied by wildland status (interaction p-value< 0.01). Among structural firefighters, volunteer firefighters had 1.42 times the risk of miscarriage (95% CI 1.11-1.80) compared to career firefighters. Among wildland/wildland-urban-interface firefighters, volunteer firefighters had 2.53 times the risk of miscarriage (95% CI 1.35-4.78) compared to career firefighters. CONCLUSIONS: Age-standardized miscarriage prevalence among firefighters may be greater than non-firefighters and there may be variation in risk of miscarriage by fire service role. Further research is needed to clarify these associations to inform policy and decision-making.

The estimand framework and its application in substance use disorder clinical trials: a case study.

Relapse rates among individuals with substance use disorder (SUD) remain high and new treatment approaches are needed, which require evaluation in randomized controlled trials (RCTs). Measurement and interpretation challenges for SUD RCT data are often ignored or presented only in statistical analysis plans. Since different analytic approaches may result in different estimates and thus interpretations of the treatment effect, it is important to present this clearly throughout the trial. Inconsistencies between study analyses and objectives present further challenges for interpretation and cross-study comparisons. The recent International Council for Harmonization (ICH) addendum provides standardized language and a common framework for aligning trial objectives, design, conduct, and analysis. The framework focuses on estimands, which describe the treatment effect and link the trial objective with the scientific question and the analytic approach. The use of estimands offers SUD researchers and clinicians the opportunity to explicitly address events that affect measurement and interpretation at the outset of the trial. Furthermore, the use of standard terminology can lead to clearer interpretations of SUD trials and the treatments evaluated in SUD trials. Resources for understanding and applying estimands are needed to optimize the use of this new, helpful framework. This Perspective provides this resource for SUD researchers. Specifically, it highlights the relevance of estimands for SUD trials. Furthermore, it demonstrates how estimands can be used to develop clinically relevant analyses to address challenges in SUD trials. It also shows how a standardized framework can be employed to improve the interpretation and presentation of SUD study findings.

Power difference in a χ2 test vs generalized linear mixed model in the presence of missing data - a simulation study.

BACKGROUND: Longitudinal randomized controlled trials (RCTs) often aim to test and measure the effect of treatment between arms at a single time point. A two-sample χ2 test is a common statistical approach when outcome data are binary. However, only complete outcomes are used in the analysis. Missing responses are common in longitudinal RCTs and by only analyzing complete data, power may be reduced and estimates could be biased. Generalized linear mixed models (GLMM) with a random intercept can be used to test and estimate the treatment effect, which may increase power and reduce bias. METHODS: We simulated longitudinal binary RCT data to compare the performance of a complete case χ2 test to a GLMM in terms of power, type I error, relative bias, and coverage under different missing data mechanisms (missing completely at random and missing at random). We considered how the baseline probability of the event, within subject correlation, and dropout rates under various missing mechanisms impacted each performance measure. RESULTS: When outcome data were missing completely at random, both χ2 and GLMM produced unbiased estimates; however, the GLMM returned an absolute power gain up to from 12.0% as compared to the χ2 test. When outcome data were missing at random, the GLMM yielded an absolute power gain up to 42.7% and estimates were unbiased or less biased compared to the χ2 test. CONCLUSIONS: Investigators wishing to test for a treatment effect between treatment arms in longitudinal RCTs with binary outcome data in the presence of missing data should use a GLMM to gain power and produce minimally unbiased estimates instead of a complete case χ2 test.

Effects of HIV status on non-metastatic cervical cancer progression among patients in Lusaka, Zambia.

INTRODUCTION: Sub-Saharan Africa has the highest global incidence of cervical cancer. Cervical cancer is the most common cause of cancer morbidity and mortality among women in Zambia. HIV increases the risk for cervical cancer and with a national Zambian adult HIV prevalence of 16%, it is important to investigate the impact of HIV on the progression of cervical cancer. We measured differences in cervical cancer progression between HIV-positive and HIV-negative patients in Zambia. METHODS: This study included 577 stage I and II cervical cancer patients seen between January 2008 and December 2012 at the Cancer Diseases Hospital in Lusaka, Zambia. The inclusion criteria for records during the study period included known HIV status and FIGO stage I and II cervical cancer at initial date of registration in the Cancer Diseases Hospital. Medical records were abstracted for clinical and epidemiological data. Cancer databases were linked to the national HIV database to assess HIV status among cervical cancer patients. Logistic regression examined the association between HIV and progression, which was defined as metastatic or residual tumor after 3 months of initial treatment. RESULTS: A total of 2451 cervical cancer cases were identified, and after exclusion criteria were performed the final analysis population totaled 537 patients with stage I and II cervical cancer with known HIV status (224 HIV-positive and 313 HIV-negative). HIV-positive women were, on average, 10 years younger than HIV-negative women who had a median age of 42, ranging between 25 and 72. A total of 416 (77.5%) patients received external beam radiation, and only 249 (46.4%) patients received the recommended treatment of chemotherapy, external beam radiation, and brachytherapy. Most patients were stage II (85.7%) and had squamous cell carcinoma (74.7%). HIV-positive patients were more likely to receive lower doses of external beam radiation than HIV-negative patients (47% vs 37%; P<0.05, respectively). The median total dose of external beam radiation for HIV-positive and HIV-negative patients was 46 Gy and 50 Gy, respectively. HIV positivity did not lead to tumor progression (25.4% in HIV-positive vs 23.9% in HIV-negative, OR 1.04, 95% CI [0.57, 1.92]). However, among a subset of HIV-positive patients, longer duration of infection was associated with lower odds of progression. CONCLUSION: There was no significant impact on non-metastatic cervical cancer progression by HIV status among patients in Lusaka, Zambia. The high prevalence of HIV among cervical cancer patients suggest that HIV-positive patients should be a primary target group for HPV vaccinations, screening, and early detection.

Predictors of Tobacco Cessation Among American Indian/Alaska Native Adults Enrolled in a State Quitline.

Background: High rates of smoking are documented among some American Indian and Alaska Native (AI/AN) communities, with potential variability by region and urban/rural settings. Quitlines are a cost-effective strategy for providing evidence-based cessation treatment, but little is known about the effectiveness of quitline services for the AI/AN population. Objectives: This study compared demographic characteristics, tobacco use, and cessation and program utilization behaviors between AI/AN (n = 297) and Non-Hispanic White (NHW; n = 13,497) quitline callers. The study also identified predictors of 30-day cessation at 7-month follow-up among AI/AN callers and determined if predictors were different between AI/AN and NHW callers. Methods: Data from callers to the Arizona Smokers' Helpline between January 2011 and June 2016 were analyzed. Results: At enrollment, AI/AN callers were less likely to use tobacco daily and were less dependent on nicotine compared to NHW callers. Both groups reported similar rates of 30-day cessation at 7-month follow-up (37.3% and 39.7% for AI/AN and NHW callers, respectively). For AI/AN callers, 30-day cessation was significantly associated with tobacco cessation medication use (OR = 2.24, 95% CI: 1.02-4.93), number of coaching sessions (OR = 1.14, 95% CI: 1.04-1.26), and other smokers in the home (OR = 0.41, 95% CI: 0.19-0.91). The effect of other smokers in the home was significantly different between AI/AN and NHW callers (p = .007). Conclusions: Different individual characteristics and predictors of cessation among AI/AN callers compared to NHW callers were documented. Findings may be used to inform the development of culturally-tailored strategies and protocols for AI/AN quitline callers.

Baseline quality of life is associated with survival among people with advanced lung cancer.

INTRODUCTION: Lung cancer patients presenting with advanced cancer face low survival rates and a high symptom burden. There have been mixed findings for the association between survival and various patient reported outcomes (PROs). METHODS: We used prospective data from 111 lung cancer patients with advanced stage III/IV disease to investigate the association of survival with PROs (European Organization for Research and Treatment of Cancer Core-30 and Lung Module). Cox proportional hazard models were used to examine the individual association between several PRO measures and survival. RESULTS: Pain in chest and global quality of life (QoL) were found to have the strongest association with survival with a 20% increased hazard of death per 10% increase in pain in chest and 14% decrease in hazard of death per 10% increase in global QoL. CONCLUSION: Our results provide more evidence for the value of PRO data to inform clinical and patient decision-making.

Imputation strategies when a continuous outcome is to be dichotomized for responder analysis: a simulation study.

BACKGROUND: In many clinical trials continuous outcomes are dichotomized to compare proportions of patients who respond. A common and recommended approach to handling missing data in responder analysis is to impute as non-responders, despite known biases. Multiple imputation is another natural choice but when a continuous outcome is ultimately dichotomized, the specifications of the imputation model come into question. Practitioners can either impute the missing outcome before dichotomizing or dichotomize then impute. In this study we compared multiple imputation of the continuous and dichotomous forms of the outcome, and imputing responder status as non-response in responder analysis. METHODS: We simulated four response profiles representing a two-arm randomized controlled trial with a continuous outcome at four time points. We omitted data using six missing at random mechanisms, and imputed missing observations three ways: 1) replacing as non-responder; 2) multiply imputing before dichotomizing; and 3) multiply imputing the dichotomized response. Imputation models included the continuous response at all timepoints, and additional auxiliary variables for some scenarios. We assessed bias, power, coverage of the 95% confidence interval, and type 1 error. Finally, we applied these methods to a longitudinal trial for patients with major depressive disorder. RESULTS: Both forms of multiple imputation performed better than non-response imputation in terms of bias and type 1 error. When approximately 30% of responses were missing, bias was less than 7.3% for multiple imputation scenarios but when 50% of responses were missing, imputing before dichotomizing generally had lower bias compared to dichotomizing before imputing. Non-response imputation resulted in biased estimates, both underestimates and overestimates. In the example trial data, non-response imputation estimated a smaller difference in proportions than multiply imputed approaches. CONCLUSIONS: With moderate amounts of missing data, multiply imputing the continuous outcome variable prior to dichotomizing performed similar to multiply imputing the binary responder status. With higher rates of missingness, multiply imputing the continuous variable was less biased and had well-controlled coverage probabilities of the 95% confidence interval compared to imputing the dichotomous response. In general, multiple imputation using the longitudinally measured continuous outcome in the imputation model performed better than imputing missing observations as non-responders.

Feasibility and acceptability of a beverage intervention for Hispanic adults: results from a pilot randomized controlled trial.

OBJECTIVE: To assess the feasibility and acceptability of a beverage intervention in Hispanic adults. DESIGN: Eligible individuals identified as Hispanic, were 18-64 years old and had BMI 30·0-50·0 kg/m2. Participants were randomized 2:2:1 to one of three beverages: Mediterranean lemonade (ML), green tea (GT) or flavoured water control (FW). After a 2-week washout period, participants were asked to consume 32 oz (946 ml) of study beverage daily for 6 weeks and avoid other sources of tea, citrus, juice and sweetened beverages; water was permissible. Fasting blood samples were collected at baseline and 8 weeks to assess primary and secondary efficacy outcomes. SETTING: Tucson, AZ, USA.ParticipantsFifty-two participants were recruited over 6 months; fifty were randomized (twenty-one ML, nineteen GT, ten FW). Study population mean (sd) age 44·6 (sd 10·2) years, BMI 35·9 (4·6) kg/m2; 78 % female. RESULTS: Forty-four (88 %) completed the 8-week assessment. Self-reported adherence was high. No significant change (95 % CI) in total cholesterol (mg/dl) from baseline was shown -1·7 (-14·2, 10·9), -3·9 (-17·2, 9·4) and -13·2 (-30·2, 3·8) for ML, GT and FW, respectively. Mean change in HDL-cholesterol (mg/dl) -2·3 (-5·3, 0·7; ML), -1·0 (-4·2, 2·2; GT), -3·9 (-8·0, 0·2; FW) and LDL-cholesterol (mg/dl) 0·2 (-11·3, 11·8; ML), 0·5 (-11·4, 12·4; GT), -9·8 (-25·0, 5·4; FW) were also non-significant. Fasting glucose (mg/dl) increased significantly by 5·2 (2·6, 7·9; ML) and 3·3 (0·58, 6·4; GT). No significant change in HbA1c was demonstrated. Due to the small sample size, potential confounders and effect modifiers were not investigated. CONCLUSIONS: Recruitment and retention figures indicate that a larger-scale trial is feasible; however, favourable changes in cardiometabolic biomarkers were not demonstrated.

Self-reported hearing difficulty and its association with general, cognitive, and psychosocial health in the state of Arizona, 2015.

BACKGROUND: Hearing loss is among the leading causes of disability in persons 65 years and older worldwide and is known to have an impact on quality of life as well as social, cognitive, and physical functioning. Our objective was to assess statewide prevalence of self-reported hearing ability in Arizona adults and its association with general health, cognitive decline, diabetes and poor psychosocial health. METHODS: A self-report question on hearing was added to the 2015 Behavioral Risk Factor Surveillance System (BRFSS), a telephone-based survey among community-dwelling adults aged > 18 years (n = 6462). Logistic and linear regression were used to estimate the associations between self-reported hearing loss and health outcomes. RESULTS: Approximately 1 in 4 adults reported trouble hearing (23.2, 95% confidence interval: 21.8, 24.5%), with responses ranging from "a little trouble hearing" to being "deaf." Adults reporting any trouble hearing were at nearly four times higher odds of reporting increased confusion and memory loss (OR 3.92, 95% CI: 2.94, 5.24) and decreased odds of reporting good general health (OR = 0.50, 95% CI: 0.40, 0.64) as compared to participants reporting no hearing difficulty. Those reporting any trouble hearing also reported an average 2.5 more days of poor psychosocial health per month (ß = 2.52, 95% CI: 1.64, 3.41). After adjusting for sex, age, questionnaire language, race/ethnicity, and income category the association between diabetes and hearing loss was no longer significant. CONCLUSIONS: Self-reported hearing difficulty was associated with report of increased confusion and memory loss and poorer general and psychosocial health among Arizona adults. These findings support the feasibility and utility of assessing self-reported hearing ability on the BRFSS. Results highlight the need for greater inclusion of the full range of hearing disability in the planning process for public health surveillance, programs, and services at state and local levels.

Protocol for LINKS (linking individual needs to community and clinical services): a prospective matched observational study of a community health worker community clinical linkage intervention on the U.S.-Mexico border.

BACKGROUND: Latinos are currently the largest and fastest growing racial/ethnic group in the United States and have the lowest rates nationally of regular sources of primary care. The changing demographics of Latino populations have significant implications for the future health of the nation, particularly with respect to chronic disease. Community-based agencies and clinics alike have a long history of engaging community health workers (CHWs) to provide a broad range of tangible and emotional support strategies for Latinos with chronic diseases. In this paper, we present the protocol for a community intervention designed to evaluate the impact of CHWs in a Community-Clinical Linkage model to address chronic disease through innovative utilization of electronic health records (EHRs) and application of mixed methodologies. Linking Individual Needs to Community and Clinical Services (LINKS) is a 3-year, prospective matched observational study designed to examine the feasibility and impact of CHW-led Community-Clinical Linkages in reducing chronic disease risk and promoting emotional well-being among Latinos living in three U.S.-Mexico border communities. METHODS: The primary aim of LINKS is to create Community-Clinical Linkages between three community health centers and their respective county health departments in southern Arizona. Our primary analysis is to examine the impact of the intervention 6 to 12-months post program entry. We will assess chronic disease risk factors documented in the EHRs of participants versus matched non-participants. By using a prospective matched observational study design with EHRs, we have access to numerous potential comparators to evaluate the intervention effects. Secondary analyses include modeling within-group changes of extended research-collected measures. This approach enhances the overall evaluation with rich data on physical and emotional well-being and health behaviors of study participants that EHR systems do not collect in routine clinical practice. DISCUSSION: The LINKS intervention has practical implications for the development of Community-Clinical Linkage models. The collaborative and participatory approach in LINKS illustrates an innovative evaluation framework utilizing EHRs and mixed methods research-generated data collection. TRIAL REGISTRATION: This study protocol was retrospectively registered, approved, and made available on Clinicaltrials.gov by NCT03787485 as of December 20, 2018.