Implementation and Evaluation of a mHealth-Based Community Health Worker Feedback Loop for Hispanics with and at Risk for Diabetes.

BACKGROUND: Gaps in accessibility and communication hinder diabetes care in poor communities. Combining mobile health (mHealth) and community health workers (CHWs) into models to bridge these gaps has great potential but needs evaluation. OBJECTIVE: To evaluate a mHealth-based, Participant-CHW-Clinician feedback loop in a real-world setting. DESIGN: Quasi-experimental feasibility study with intervention and usual care (UC) groups. PARTICIPANTS: A total of 134 participants (n = 67/group) who were all low-income, uninsured Hispanics with or at-risk for type 2 diabetes. INTERVENTION: A 15-month study with a weekly to semimonthly mHealth Participant-CHW-Clinician feedback loop to identify participant issues and provide participants monthly diabetes education via YouTube. MAIN MEASURES: We used pre-defined feasibility measures to evaluate our intervention: (a) implementation, the execution of feedback loops to identify and resolve participant issues, and (b) efficacy, intended effects of the program on clinical outcomes (baseline to 15-month HbA1c, systolic blood pressure (SBP), diastolic blood pressure (DBP), and weight changes) for each group and their subgroups (at-risk; with diabetes, including uncontrolled (HbA1c ≥ 7%)). KEY RESULTS: CHWs identified 433 participant issues (mean = 6.5 ± 5.3) and resolved 91.9% of these. Most issues were related to supplies, 26.3% (n = 114); physical health, 23.1% (n = 100); and medication access, 20.8% (n = 90). Intervention participants significantly improved HbA1c (- 0.51%, p = 0.03); UC did not (- 0.10%, p = 0.76). UC DBP worsened (1.91 mmHg, p < 0.01). Subgroup analyses revealed HbA1c improvements for uncontrolled diabetes (intervention: - 1.59%, p < 0.01; controlled: - 0.72, p = 0.03). Several variables for UC at-risk participants worsened: HbA1c (0.25%, p < 0.01), SBP (4.05 mmHg, p < 0.01), DBP (3.21 mmHg, p = 0.01). There were no other significant changes for either group. CONCLUSIONS: A novel mHealth-based, Participant-CHW-Clinician feedback loop was associated with improved HbA1c levels and identification and resolution of participant issues. UC individuals had several areas of clinical deterioration, particularly those at-risk for diabetes, which is concerning for progression to diabetes and disease-related complications. CLINICAL TRIAL: NCT03394456, accessed at https://clinicaltrials.gov/ct2/show/NCT03394456.

A Dynamic Risk Model for Multitype Recurrent Events.

Recurrent events can occur more than once in the same individual; such events may be of different types, known as multitype recurrent events. They are very common in longitudinal studies. Often there is a terminating event, after which no further events can occur. The risk of any event, including terminating events such as death or cure, is typically affected by prior events. We propose a flexible joint multitype recurrent-events model that explicitly provides estimates of the change in risk for each event due to subject characteristics, including number and type of prior events and the absolute risk for every event type (terminating and nonterminating), and predicts event-free survival probability over a desired time period. The model is fully parametric, and therefore a standard likelihood function and robust standard errors can be constructed. We illustrate the model with applications to the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (1994-2002) and provide discussion of the results and model features.

Non-homogeneous continuous-time Markov chain with covariates: Applications to ambulatory hypertension monitoring.

Hypertension significantly increases the risk for many health conditions including heart disease and stroke. Hypertensive patients often have continuous measurements of their blood pressure to better understand how it fluctuates over the day. The continuous-time Markov chain (CTMC) is commonly used to study repeated measurements with categorical outcomes. However, the standard CTMC may be restrictive, because the rates of transitions between states are assumed to be constant through time, while the transition rates for describing the dynamics of hypertension are likely to be changing over time. In addition, the applications of CTMC rarely account for the effects of other covariates on state transitions. In this article, we considered a non-homogeneous continuous-time Markov chain with two states to analyze changes in hypertension while accounting for multiple covariates. The explicit formulas for the transition probability matrix as well as the corresponding likelihood function were derived. In addition, we proposed a maximum likelihood estimation algorithm for estimating the parameters in the time-dependent rate function. Lastly, the model performance was demonstrated through both a simulation study and application to ambulatory blood pressure data.

Estimation of non-monotonic transition rates in a semi-Markov process with covariates adjustments and application to caregivers' stress data.

With the large ongoing number of aged people and Alzheimer's disease (AD) patients worldwide, unpaid caregivers have become the primary sources of their daily caregiving. Alzheimer's family caregivers often suffer from physical and mental morbidities owing to various reasons. The aims of this paper were to develop alternate methods to understand the transition properties, the dynamic change, and the long-run behavior of AD caregivers' stress levels, by assuming their transition to the next level only depends on the duration of the current stress level. In this paper, we modeled the transition rates in the semi-Markov Process with log-logistic hazard functions. We assumed the transition rates were non-monotonic over time and the scale of transition rates depended on covariates. We also extended the uniform accelerated expansion to calculate the long-run probability distribution of stress levels while adjusting for multiple covariates. The proposed methods were evaluated through an empirical study. The application results showed that all the transition rates of caregivers' stress levels were right skewed. Care recipients' baseline age was significantly associated with the transitions. The long-run probability of severe state was slightly higher, implying a prolonged recovery time for severe stress patients.

Prediction of breast cancer-related lymphedema by dermal backflow detected with near-infrared fluorescence lymphatic imaging.

PURPOSE: Mild breast cancer-related lymphedema (BCRL) is clinically diagnosed as a 5%-10% increase in arm volume, typically measured no earlier than 3-6 months after locoregional treatment. Early BCRL treatment is associated with better outcomes, yet amid increasing evidence that lymphedema exists in a latent form, treatment is typically delayed until arm swelling is obvious. In this study, we investigated whether near-infrared fluorescence lymphatic imaging (NIRF-LI) surveillance could characterize early onset of peripheral lymphatic dysfunction as a predictor of BCRL. METHODS: In a prospective, longitudinal cohort/observational study (NCT02949726), subjects with locally advanced breast cancer who received axillary lymph node dissection and regional nodal radiotherapy (RT) were followed serially, between 2016 and 2021, before surgery, 4-8 weeks after surgery, and 6, 12, and 18 months after RT. Arm volume was measured by perometry, and lymphatic (dys) function was assessed by NIRF-LI. RESULTS: By 18 months after RT, 30 of 42 study subjects (71%) developed mild-moderate BCRL (i.e., ≥ 5% arm swelling relative to baseline), all manifested by "dermal backflow" of lymph into lymphatic capillaries or interstitial spaces. Dermal backflow had an 83% positive predictive value and 86% negative predictive value for BCRL, with a sensitivity of 97%, specificity of 50%, accuracy of 83%, positive likelihood ratio of 1.93, negative likelihood ratio of 0.07, and odds ratio of 29.00. Dermal backflow appeared on average 8.3 months, but up to 23 months, before the onset of mild BCRL. CONCLUSION: BCRL can be predicted by dermal backflow, which often appears months before arm swelling, enabling early treatment before the onset of edema and irreversible tissue changes.

Among Adolescents, BDNF and Pro-BDNF Lasting Changes with Alcohol Use Are Stage Specific.

Adolescent alcohol use demonstrates distinct developmental trajectories with dissimilar times of onset and trajectories. Given the importance of brain-derived neurotrophic factor (mature BDNF) in this development stage, the current study investigated its relationship with alcohol use. It also extends the literature by assessing the role of its precursor (pro-BDNF). Therefore, over the span of 5 years, we enrolled and followed participants to define age-related changes in BDNF levels in healthy adolescents. Then, the onset and frequency of alcohol use from ages 11 to 18 were collected to determine how the relationship between alcohol, pro-BDNF, and m-BDNF unfolds over time. With respect to development, analyses demonstrated that BDNF concentration slowly increases throughout adolescence. However, despite having similar basal BDNF levels, compared to controls, adolescents that started drinking before 15 years of age always exhibited lower BDNF levels. They also had a significant decrease in pro-BDNF levels. On the other hand, levels of mature BDNF steadily increased (974.896 ± 275 pg/ml) in those starting alcohol use after the age of 15. Similar to the younger users, a significant drop in pro-BDNF levels was observed over the course of the study. Our results suggested that both pathways may participate in the complex processes of alcohol dependence. The findings highlight the relevance of assessing alcohol-associated changes across the different phases of this vulnerable developmental period. This is the first study evidencing that m-BDNF changes associated with drinking behaviors differed between young and older adolescents. It is also the first article, documenting that drinking during adolescence leads to long-term decreases in pro-BDNF. These results have important implications for policies and programs targeting alcohol use disorders.

Time-Varying Exposure to Ozone and Risk of Stillbirth in a Nonattainment Urban Region.

In a racially and ethnically diverse urban area (Harris County, Texas) with historic nonattainment O3 levels, we obtained birth and fetal death records from 2008-2013 and estimated maternal residential O3 concentrations from conception until delivery using inverse-distance interpolation from the local air monitoring network. We examined multipollutant models (with fine particulate matter and nitrogen dioxide) and effect measure modification by race/ethnicity and length of gestation. We found a 9% (95% confidence interval (CI): 1, 18) increased stillbirth risk associated with a 3.6-parts-per-billion increase in O3 exposure. The risk was higher among women with pregnancies of <37 gestational weeks (hazard ratio (HR) = 1.13, 95% CI: 1.04, 1.23) compared with women with pregnancies of longer gestation (HR = 1.05, 95% CI: 0.87, 1.27) and among Hispanic women (HR = 1.14, 95% CI: 1.02, 1.27). We also conducted a case-crossover analysis and detected no associations with short-term exposure. To our knowledge, this study is the first to use time-to-event analyses to examine stillbirth risk associated with time-varying prenatal ozone (O3) exposure over pregnancy. Our findings indicate that maternal O3 exposure over pregnancy is associated with stillbirth risk and that Hispanic women and women with shorter pregnancies might be at particular risk.

Association of left atrial volume index and all-cause mortality in patients referred for routine cardiovascular magnetic resonance: a multicenter study.

BACKGROUND: Routine cine cardiovascular magnetic resonance (CMR) allows for the measurement of left atrial (LA) volumes. Normal reference values for LA volumes have been published based on a group of European individuals without known cardiovascular disease (CVD) but not on one of similar United States (US) based volunteers. Furthermore, the association between grades of LA dilatation by CMR and outcomes has not been established. We aimed to assess the relationship between grades of LA dilatation measured on CMR based on US volunteers without known CVD and all-cause mortality in a large, multicenter cohort of patients referred for a clinically indicated CMR scan. METHOD: We identified 85 healthy US subjects to determine normal reference LA volumes using the biplane area-length method and indexed for body surface area (LAVi). Clinical CMR reports of patients with LA volume measures (n = 11,613) were obtained. Data analysis was performed on a cloud-based system for consecutive CMR exams performed at three geographically distinct US medical centers from August 2008 through August 2017. We identified 10,890 eligible cases. We categorized patients into 4 groups based on LAVi partitions derived from US normal reference values: Normal (21-52 ml/m2), Mild (52-62 ml/m2), Moderate (63-73 ml/m2) and Severe (> 73 ml/m2). Mortality data were ascertained for the patient group using electronic health records and social security death index. Cox proportional hazard risk models were used to derive hazard ratios for measuring association of LA enlargement and all-cause mortality. RESULTS: The distribution of LAVi from healthy subjects without known CVD was 36.3 ± 7.8 mL/m2. In clinical patients, enlarged LA was associated with older age, atrial fibrillation, hypertension, heart failure, inpatient status and biventricular dilatation. The median follow-up duration was 48.9 (IQR 32.1-71.2) months. On univariate analyses, mild [Hazard Ratio (HR) 1.35 (95% Confidence Interval [CI] 1.11 to 1.65], moderate [HR 1.51 (95% CI 1.22 to 1.88)] and severe LA enlargement [HR 2.14 (95% CI 1.81 to 2.53)] were significant predictors of death. After adjustment for significant covariates, moderate [HR 1.45 (95% CI 1.1 to 1.89)] and severe LA enlargement [HR 1.64 (95% CI 1.29 to 2.08)] remained independent predictors of death. CONCLUSION: LAVi determined on routine cine-CMR is independently associated with all-cause mortality in patients undergoing a clinically indicated CMR.

Impacts of cold weather on emergency hospital admission in Texas, 2004-2013.

Cold weather has been identified as a major cause of weather-related deaths in the U.S. Although the effects of cold weather on mortality has been investigated extensively, studies on how cold weather affects hospital admissions are limited particularly in the Southern United States. This study aimed to examine impacts of cold weather on emergency hospital admissions (EHA) in 12 major Texas metropolitan statistical areas (MSAs) for the 10-year period, 2004-2013. A two-stage approach was employed to examine the associations between cold weather and EHA. First, the cold effects on each MSA were estimated using distributed lag non-linear models (DLNM). Then a random effects meta-analysis was applied to estimate pooled effects across all 12 MSAs. Percent increase in risk and corresponding 95% confidence intervals (CIs) were estimated as with a 1 °C (°C) decrease in temperature below a MSA-specific threshold for cold effects. Age-stratified and cause-specific EHA were modeled separately. The majority of the 12 Texas MSAs were associated with an increased risk in EHA ranging from 0.1% to 3.8% with a 1 °C decrease below cold thresholds. The pooled effect estimate was 1.6% (95% CI: 0.9%, 2.2%) increase in all-cause EHA risk with 1 °C decrease in temperature. Cold wave effects were also observed in most eastern and southern Texas MSAs. Effects of cold on all-cause EHA were highest in the very elderly (2.4%, 95% CI: 1.2%, 3.6%). Pooled estimates for cause-specific EHA association were strongest in pneumonia (3.3%, 95% CI: 2.8%, 3.9%), followed by chronic obstructive pulmonary disease (3.3%, 95% CI: 2.1%, 4.5%) and respiratory diseases (2.8%, 95% CI: 1.9%, 3.7%). Cold weather generally increases EHA risk significantly in Texas, especially in respiratory diseases, and cold effects estimates increased by elderly population (aged over 75 years). Our findings provide insight into better intervention strategy to reduce adverse health effects of cold weather among targeted vulnerable populations.

PM2.5 metal constituent exposure and stillbirth risk in Harris County, Texas.

There is limited evidence on the role of exposure to chemical constituents of fine particulate matter (PM2.5) in risk for stillbirth. Thus, we conducted a case-control study in Harris County, Texas between 2008 and 2013, utilizing a 6:1 ratio of controls to individually matched cases. We linked birth and fetal death records with PM2.5 data from a single air monitoring station and estimated maternal exposures to metal constituents of PM2.5 over the risk period (defined by the gestational length of each case). We applied conditional logistic regression and modeled air pollutant exposures as continuous variables. We observed null associations for most metal constituents (Al, Cr, Cu, Fe, Pb, Mn, Ni, Se and Ti). However, we observed a modest increase in risk for stillbirth (adjusted odds ratio (OR) = 1.11, 95% confidence interval (CI): 1.02, 1.20) associated with a 0.007 µg/m3 interquartile range (IQR) increase in exposure to zinc (Zn) PM2.5. This study adds to the scarce literature evaluating associations between PM2.5 metal constituents and stillbirth and points to the need for further research in this area.

Cervical, Vaginal, and Vulvar Cancer Costs Incurred by the Medicaid Program in Publicly Insured Patients in Texas.

OBJECTIVES: To determine from the perspective of the State of Texas, the direct medical care costs associated with cervical, vaginal, and vulvar cancers in Texas Medicaid enrollees. MATERIALS AND METHODS: We conducted a case-control study and searched Texas Medicaid databases between 2008 and 2012 for eligible cancer patients. A comparison group was selected for each cancer site using a 2-step 1:1 propensity score matching method. Patients were followed for 2 years after cancer diagnosis to estimate monthly and yearly direct medical costs. For each cancer site, the differential cost between patients and the matched comparison individuals was the estimated cost associated with cancer. RESULTS: The study included 583 cervical, 62 vaginal, and 137 vulvar cancer patients and equal numbers of cancer-free comparison individuals. Among the cases, 322 cervical cancer patients, 46 vaginal cancer patients, and 102 vulvar cancer patients were Medicaid-Medicare dual eligible enrollees. For Medicaid-only enrollees, the adjusted first- and second-year mean total differential costs were US $19,859 and $3,110 for cervical cancer, US $19,627 and $4,582 for vaginal cancer, and US $7,631 and $777 for vulvar cancer patients, respectively. For Medicaid-Medicare dual eligible enrollees, adjusted first- and second-year mean total differential costs incurred by Medicaid were US $2,565 and $792 for cervical cancer, US $1,293 and $181 for vaginal cancer, and US $1,774 and $1,049 for vulvar cancer patients, respectively. CONCLUSIONS: The direct medical costs associated with cervical, vaginal, and vulvar cancers in Texas Medicaid were substantial in the first 2 years after cancer diagnosis, but dual eligibility for Medicare coverage attenuated Medicaid costs.

Risk of adverse events associated with front-line anti-myeloma treatment in Medicare patients with multiple myeloma.

This study aims to examine the risks of adverse events associated with anti-multiple myeloma (MM) therapies in a large population-based cohort of elderly patients with MM. Patients diagnosed with advanced MM from 2005 through 2009 and receiving anti-MM therapy were identified from the Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked data. We compared safety outcomes between novel agents (proteasome inhibitor (PI) and immunomodulatory drugs (IMiD)) and other therapies and between PI- or IMiD-based regimens and PI plus IMiD combination regimens. Of 2587 patients with advanced MM, 2048 (79%) received novel agents and 539 (21%) received other therapies. Patients with preexisting anemia and thrombocytopenia were significantly more likely to receive novel agents (85.9 vs. 82.4%, P = 0.038; 13.8 vs. 10.4%, P = 0.036), while those with preexisting cardiovascular disease and hypertension were significantly less likely to receive novel agents (73.4 vs. 79.8%, P = 0.003; 81.3 vs. 85.2%, P = 0.035). The hazard ratios for anemia, peripheral neuropathy, and thromboembolic events for patients receiving novel agents compared with those receiving other therapies were 1.19 (95% CI, 1.06-1.32), 1.57 (95% CI, 1.15-2.15), and 1.31 (95% CI, 1.03-1.67). The hazard ratios for anemia, neutropenia, and thromboembolic events for patients receiving PI plus IMiD combination therapies compared with those receiving PI- or IMiD-based therapies were 1.31 (95% CI, 1.12-1.54), 1.66 (95% CI, 1.27-2.18, and 1.37 (95% CI, 1.02-1.86). Novel agents significantly increased the risk of anemia, peripheral neuropathy, and thromboembolic events. PI plus IMiD combination therapies were associated with significantly higher risk for anemia, neutropenia, and thromboembolic events.

Mean medical costs associated with vaginal and vulvar cancers for commercially insured patients in the United States and Texas.

OBJECTIVE: To estimate the average medical costs for vaginal and vulvar cancers in a commercially insured population in the U.S. and Texas. METHODS: 2011-2014U.S. MarketScan databases were used to estimate the average medical costs associated with vaginal and vulvar cancers. Women with newly diagnosed vaginal or vulvar cancer were matched to a comparison group without cancer using propensity score. Year 1 and year 2 costs after index diagnosis date were estimated. A generalized linear model was used to estimate the cost for censored months. The differential costs between groups were defined as the net costs associated with cancer diagnosis and treatment. RESULTS: The analysis included 355 women with vaginal cancer and 997 with vulvar cancer in the U.S. The year 1 and year 2 costs for vaginal cancer were $86,995 and $51,107, respectively. The year 1 and year 2 costs for vulvar cancer were $37,657 and $19,139, respectively. The major factors associated with higher monthly vaginal and vulvar cancer costs were higher Charlson Comorbidity Index score and higher medical costs prior to cancer diagnosis. Monthly costs for vaginal and vulvar cancers decreased rapidly from month 1 to month 6 after diagnosis and then remained stable. CONCLUSIONS: Seventy to 75% of all vaginal and vulvar cancers are due to HPV infections and mean medical costs associated with these cancers are substantial. These data will serve as key cost parameters in the economic evaluation of HPV vaccination dissemination and estimation of the long-term net economic benefit of promoting HPV vaccination.

Bayesian variable selection for multistate Markov models with interval-censored data in an ecological momentary assessment study of smoking cessation.

The application of sophisticated analytical methods to intensive longitudinal data, collected with ecological momentary assessments (EMA), has helped researchers better understand smoking behaviors after a quit attempt. Unfortunately, the wealth of information captured with EMAs is typically underutilized in practice. Thus, novel methods are needed to extract this information in exploratory research studies. One of the main objectives of intensive longitudinal data analysis is identifying relations between risk factors and outcomes of interest. Our goal is to develop and apply expectation maximization variable selection for Bayesian multistate Markov models with interval-censored data to generate new insights into the relation between potential risk factors and transitions between smoking states. Through simulation, we demonstrate the effectiveness of our method in identifying associated risk factors and its ability to outperform the LASSO in a special case. Additionally, we use the expectation conditional-maximization algorithm to simplify estimation, a deterministic annealing variant to reduce the algorithm's dependence on starting values, and Louis's method to estimate unknown parameter uncertainty. We then apply our method to intensive longitudinal data collected with EMA to identify risk factors associated with transitions between smoking states after a quit attempt in a cohort of socioeconomically disadvantaged smokers who were interested in quitting.

The Time-Varying Relations Between Risk Factors and Smoking Before and After a Quit Attempt.

Introduction: Intensive longitudinal data (ILD) collected with ecological momentary assessments (EMAs) can provide a rich resource for understanding the relations between risk factors and smoking in the time surrounding a cessation attempt. Methods: Participants (N = 142) were smokers seeking treatment at a safety-net hospital smoking cessation clinic who were randomly assigned to receive standard clinic care (ie, counseling and cessation medications) or standard care plus small financial incentives for biochemically confirmed smoking abstinence. Participants completed EMAs via study provided smartphones several times per day for 14 days (1 week prequit through 1 week postquit). EMAs assessed current contextual factors including environmental (eg, easy access to cigarettes, being around others smoking), cognitive (eg, urge to smoke, stress, coping expectancies, cessation motivation, cessation self-efficacy, restlessness), behavioral (ie, recent smoking and alcohol consumption), and affective variables. Temporal relations between risk factors and smoking were assessed using a logistic time-varying effect model. Results: Participants were primarily female (57.8%) and Black (71.8%), with an annual household income of <$20000 per year (71.8%), who smoked 17.6 cigarettes per day (SD = 8.8). Individuals assigned to the financial incentives group had decreased odds of smoking compared with those assigned to usual care beginning 3 days before the quit attempt and continuing throughout the first week postquit. Environmental, cognitive, affective, and behavioral variables had complex time-varying impacts on smoking before and after the scheduled quit attempt. Conclusions: Knowledge of time-varying effects may facilitate the development of interventions that target specific psychosocial and behavioral variables at critical moments in the weeks surrounding a quit attempt. Implications: Previous research has examined time-varying relations between smoking and negative affect, urge to smoke, smoking dependence, and certain smoking cessation therapies. We extend this work using ILD of unexplored variables in a socioeconomically disadvantaged sample of smokers seeking cessation treatment. These findings could be used to inform ecological momentary interventions that deliver treatment resources (eg, video- or text-based content) to individuals based upon critical variables surrounding their attempt.

m-Health Policy Readiness and Enabling Factors: Comparisons of Sub-Saharan Africa and Organization for Economic Cooperation and Development Countries.

BACKGROUND: As an innovative solution to poor access to care in low- and middle-income countries (LMICs), m-health has gained wide attention in the past decade. INTRODUCTION: Despite enthusiasm from the global health community, LMICs have not demonstrated high uptake of m-health promoting policies or public investment. MATERIALS AND METHODS: To benchmark the current status, this study compared m-health policy readiness scores between sub-Saharan Africa and high-income Organization for Economic Cooperation and Development (OECD) countries using an independent two-sample t test. In addition, the enabling factors associated with m-health policy readiness were investigated using an ordinal logistic regression model. The study was based on the m-health policy readiness scores of 112 countries obtained from the World Health Organization Third Global Survey on e-Health. RESULTS: The mean m-health policy readiness score for sub-Saharan Africa was statistically significantly lower than that for OECD countries (p = 0.02). The enabling factors significantly associated with m-health policy readiness included information and communication technology development index (odds ratio [OR] 1.57; 95% confidence interval [CI] 1.12-2.2), e-health education for health professionals (OR 4.43; 95% CI 1.60-12.27), and the location in sub-Saharan Africa (OR 3.47; 95% CI 1.06-11.34). DISCUSSION: The findings of our study suggest dual policy goals for m-health in sub-Saharan Africa. First, enhance technological and educational support for m-health. Second, pursue global collaboration for building m-health capacity led by sub-Saharan African countries with hands-on experience and knowledge. CONCLUSION: Globally, countries should take a systematic and collaborative approach in pursuing m-health policy with the focus on technological and educational support.

Molecular and clinical spectra of FBXL4 deficiency.

F-box and leucine-rich repeat protein 4 (FBXL4) is a mitochondrial protein whose exact function is not yet known. However, cellular studies have suggested that it plays significant roles in mitochondrial bioenergetics, mitochondrial DNA (mtDNA) maintenance, and mitochondrial dynamics. Biallelic pathogenic variants in FBXL4 are associated with an encephalopathic mtDNA maintenance defect syndrome that is a multisystem disease characterized by lactic acidemia, developmental delay, and hypotonia. Other features are feeding difficulties, growth failure, microcephaly, hyperammonemia, seizures, hypertrophic cardiomyopathy, elevated liver transaminases, recurrent infections, variable distinctive facial features, white matter abnormalities and cerebral atrophy found in neuroimaging, combined deficiencies of multiple electron transport complexes, and mtDNA depletion. Since its initial description in 2013, 36 different pathogenic variants in FBXL4 were reported in 50 affected individuals. In this report, we present 37 additional affected individuals and 11 previously unreported pathogenic variants. We summarize the clinical features of all 87 individuals with FBXL4-related mtDNA maintenance defect, review FBXL4 structure and function, map the 47 pathogenic variants onto the gene structure to assess the variants distribution, and investigate the genotype-phenotype correlation. Finally, we provide future directions to understand the disease mechanism and identify treatment strategies.

Mean direct medical care costs associated with cervical cancer for commercially insured patients in Texas.

OBJECTIVE: To determine the mean cervical cancer medical care costs for patients enrolled in commercial insurance in Texas. Cost is represented by insurer and patient payments for care. METHODS: We estimated the mean medical care costs during the first 2years after the index diagnosis date for patients with cervical cancer (cases). Cases were identified using claims-based International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9), diagnosis codes and matched to controls without a claims-based ICD-9 code for cancer using a 2-step propensity score matching method. Index dates for the cases were randomly assigned to potential controls, and cases and controls were matched by index date. Data for cancer cases and controls were obtained from the de-identified 2011-2014 U.S. MarketScan databases. A generalized linear model was employed to compute the cost for censored months during the 2-year follow-up period. Differential costs were assessed by subtracting the medical costs incurred by controls from those incurred by cases. RESULTS: During 2011-2014, 475 commercially insured Texas patients with newly diagnosed cervical cancer met the inclusion criteria. The first-year and second-year mean medical costs were $60,828 and $37,721 for cases and $9982 and $10,066 for controls, respectively. The differential costs of cervical cancer for the first and second years were $50,846 and $27,656, respectively. The major correlates of higher monthly cervical cancer costs were higher Charlson Comorbidity Index score during 6months period prior to diagnosis, higher healthcare costs between 6months and 3months prior to diagnosis, and residence in the western region of Texas. Costs for cervical cancer patients decreased steeply between month 1 and month 5 after diagnosis and then were stable, while costs for the control group were stable throughout the follow-up period. CONCLUSIONS: Mean direct medical costs associated with cervical cancer in Texas were substantial. These data will serve as key cost parameters in models of costs associated with human papillomavirus (HPV)-related cancers in Texas and the economic evaluation of HPV vaccination dissemination in Texas.

A joint logistic regression and covariate-adjusted continuous-time Markov chain model.

The use of longitudinal measurements to predict a categorical outcome is an increasingly common goal in research studies. Joint models are commonly used to describe two or more models simultaneously by considering the correlated nature of their outcomes and the random error present in the longitudinal measurements. However, there is limited research on joint models with longitudinal predictors and categorical cross-sectional outcomes. Perhaps the most challenging task is how to model the longitudinal predictor process such that it represents the true biological mechanism that dictates the association with the categorical response. We propose a joint logistic regression and Markov chain model to describe a binary cross-sectional response, where the unobserved transition rates of a two-state continuous-time Markov chain are included as covariates. We use the method of maximum likelihood to estimate the parameters of our model. In a simulation study, coverage probabilities of about 95%, standard deviations close to standard errors, and low biases for the parameter values show that our estimation method is adequate. We apply the proposed joint model to a dataset of patients with traumatic brain injury to describe and predict a 6-month outcome based on physiological data collected post-injury and admission characteristics. Our analysis indicates that the information provided by physiological changes over time may help improve prediction of long-term functional status of these severely ill subjects. Copyright © 2017 John Wiley & Sons, Ltd.

Role of maternal occupational physical activity and psychosocial stressors on adverse birth outcomes.

OBJECTIVES: We examined the association of an array of estimated maternal occupational physical activities and psychosocial stressors during pregnancy with odds for preterm birth (PTB) and small-for-gestational age (SGA). METHODS: Data for infants born without major birth defects delivered from 1997 to 2009 whose mothers reported working at least 1 month during pregnancy were obtained from the National Birth Defects Prevention Study. We linked occupational codes to the US Department of Labor's Occupational Information Network, which provides estimates of exposure for multiple domains of physical activity and psychosocial stressors by occupational categories. We conducted factor analysis using principal components extraction with 17 occupational activities and calculated factor scores. ORs for PTB and SGA across quartiles of factor scores in each trimester were computed using logistic regression. RESULTS: Factor analysis grouped occupational domains into 4 groups based on factor loadings. These groups were 'occupational physical activity', 'interpersonal stressor', 'automated work' and 'job responsibility'. High levels of 'occupational physical activity' were significantly associated with SGA (adjusted OR (AOR) for highest quartile compared with lowest quartile of factor score: 1.36; 95% CIs 1.02 to 1.82; p for trend=0.001) and were also positively associated with PTB (AOR: 1.24; 95% CI 0.93 to 1.64; p for trend=0.01). No clear results were observed across domains of psychosocial stressors. CONCLUSIONS: Our findings expand understanding of associations between occupational physical activity and psychosocial stressors and PTB and SGA and suggest that additional research is needed to further examine these relationships.