Team-based home blood pressure monitoring for blood pressure equity a protocol for a stepped wedge cluster randomized trial.

BACKGROUND: Home Blood Pressure Monitoring (HBPM) that includes a team with a clinical pharmacist is an evidence-based intervention that improves blood pressure (BP). Yet, strategies for promoting its adoption in primary care are lacking. We developed potentially feasible and sustainable implementation strategies to improve hypertension control and BP equity. METHODS: We assessed barriers and facilitators to HBPM and iteratively adapted implementation strategies through key informative interviews and guidance from a multistakeholder stakeholder team involving investigators, clinicians, and practice administration. RESULTS: Strategies include: 1) pro-active outreach to patients; 2) provision of BP devices; 3) deployment of automated bidirectional texting to support patients through education messages for patients to transmit their readings to the clinical team; 3) a hypertension visit note template; 4) monthly audit and feedback reports on progress to the team; and 5) training to the patients and teams. We will use a stepped wedge randomized trial to assess RE-AIM outcomes. These are defined as follows Reach: the proportion of eligible patients who agree to participate in the BP texting; Effectiveness: the proportion of eligible patients with their last BP reading <140/90 (six months); Adoption: the proportion of patients invited to the BP texting; Implementation: patients who text their BP reading ≥10 of days per month; and Maintenance: sustained BP control post-intervention (twelve months). We will also examine RE-AIM metrics stratified by race and ethnicity. CONCLUSIONS: Findings will inform the impact of strategies for the adoption of team-based HPBM and the impact of the intervention on hypertension control and equity. REGISTRATION DETAILS: www. CLINICALTRIALS: gov Identifier: NCT05488795.

Seemingly Unrelated Regression Analysis of the Cost and Health-Related Quality of Life Outcomes of the REVAMP Randomized Clinical Trial.

OBJECTIVE: This study aimed to evaluate the 9-month cost and health-related quality of life (HRQOL) outcomes of resistance versus viral load testing strategies to manage virological failure in low-middle income countries. METHODS: We analyzed secondary outcomes from the REVAMP clinical trial: a pragmatic, open label, parallel-arm randomized trial investigating resistance versus viral load testing for individuals failing first-line treatment in South Africa and Uganda. We collected resource data, valued according to local cost data and used the 3-level version of EQ-5D to measure HRQOL at baseline and 9 months. We applied seemingly unrelated regression equations to account for the correlation between cost and HRQOL. We conducted intention-to-treat analyses with multiple imputation using chained equations for missing data and performed sensitivity analyses using complete cases. RESULTS: For South Africa, resistance testing and opportunistic infections were associated with statistically significantly higher total costs, and virological suppression was associated with lower total cost. Higher baseline utility, higher cluster of differentiation 4 (CD4) count, and virological suppression were associated with better HRQOL. For Uganda, resistance testing and switching to second-line treatment were associated with higher total cost, and higher CD4 was associated with lower total cost. Higher baseline utility, higher CD4 count, and virological suppression were associated with better HRQOL. Sensitivity analyses of the complete-case analysis confirmed the overall results. CONCLUSION: Resistance testing showed no cost or HRQOL advantage in South Africa or Uganda over the 9-month REVAMP clinical trial.

Disease Burden in Children With Spinal Muscular Atrophy: Results From a Large Cross-Sectional Study.

Background:To facilitate advances in spinal muscular atrophy therapeutic research, it is important to determine the impact and prevalence of symptoms experienced by children with spinal muscular atrophy. Methods: We conducted qualitative interviews with caregivers of children with spinal muscular atrophy. From these interviews, we generated a survey inquiring about 260 symptoms of importance grouped into 17 symptomatic themes. Results: Sixteen caregivers of children with spinal muscular atrophy aged from 4 months to 12 years participated in initial interviews, and 77 caregivers completed the survey. Higher symptom prevalence was associated with spinal muscular atrophy type, SMN2 copy number, and functional status. Hip, thigh, or knee weakness had the greatest reported impact on the lives of children with spinal muscular atrophy. Conclusions: This research provides one of the largest data sets regarding disease burden in children with spinal muscular atrophy. The most prevalent symptoms are not identical to those with the greatest impact. This unique insight into the most impactful symptoms will help focus therapeutic development in spinal muscular atrophy.

Criteria-Based Assessment of a Teleophthalmology Diabetic Retinopathy Evaluation Program in a Primary Care Setting.

Background:Studies have shown that teleophthalmology programs using a nonmydriatic camera in primary care settings can improve rates of diabetic retinopathy (DR) screening. However, such programs are not yet widespread due to common challenges in sustainability.Purpose:To comprehensively evaluate clinical and operational measures of an urban primary care clinic's 1-year pilot teleophthalmology DR evaluation program.Materials and Methods:This retrospective analysis used five metrics to evaluate the program: clinical diabetic retinal exam (DRE) rate, visual acuity and pathology, camera utilization, billing and insurance reimbursements, and outcomes of follow-up referrals.Results:Two hundred eleven patients were screened over 14 months. The DRE rate had more than doubled (34-75%). Of the patients, 55.9% had vision better than 20/50 in each eye and 21% with at least 1 eye worse than or equal to 20/70. DR was noted in 11% of patients. The program's first few months saw greatest camera use. Government and Medicare Advantage insurers were significantly (p < 0.001) less likely to reimburse than commercial insurers. Twenty-seven percent of patients screened had documented follow-up with an eye care provider within 16 months of their screening. Patients diagnosed with DR or recommended follow-up within 1 month were significantly (p < 0.001) more likely to schedule an appointment.Discussion:Challenges to program sustainability include efficient utilization, reimbursement from governmental insurers, and adherence to follow-up recommendations.Conclusions:Assessing teleophthalmology programs with the aforementioned five metrics allows for a comprehensive evaluation of impact and sustainability. This may be utilized to standardize the implementation and evaluation of such programs across diverse settings.

Monte Carlo methods for nonparametric regression with heteroscedastic measurement error.

Nonparametric regression is a fundamental problem in statistics but challenging when the independent variable is measured with error. Among the first approaches was an extension of deconvoluting kernel density estimators for homescedastic measurement error. The main contribution of this article is to propose a new simulation-based nonparametric regression estimator for the heteroscedastic measurement error case. Similar to some earlier proposals, our estimator is built on principles underlying deconvoluting kernel density estimators. However, the proposed estimation procedure uses Monte Carlo methods for estimating nonlinear functions of a normal mean, which is different than any previous estimator. We show that the estimator has desirable operating characteristics in both large and small samples and apply the method to a study of benzene exposure in Chinese factory workers.

Impact of non-cardiovascular disease burden on thirty-day hospital readmission in heart failure patients.

BACKGROUND: Little is known about the impact of non-cardiovascular disease (CVD) burden on 30- -day readmission in heart failure (HF) patients. The aim of the study was to assess the role of non-CVD burden on 30-day readmission in HF patients. \ METHODS: We analyzed the effect of non-CVD burden by frequency of ICD-9 code categories on readmis-sions of patients discharged with a primary diagnosis of HF. We first modeled the probability of readmis-sion within 30 days as a function of demographic and clinical covariates in a randomly selected training dataset of the total cohort. Variable selection was carried out using a bootstrap LASSO procedure with 1000 bootstrap samples, the final model was tested on a validation dataset. Adjusted odds ratios and confidence intervals were reported in the validation dataset. RESULTS: There were a total of 6228 HF hospitalizations, 1523 (24%) with readmission within 30 days of discharge. The strongest predictor for 30-day readmissions was any hospital admission in the prior year (p < 0.001). Cardiovascular risk factors did not enter the final model. However, digestive system diseases increased the risk for readmission by 17% for each diagnosis (p = 0.046), while respiratory diseases and genitourinary diseases showed a trend toward a higher risk of readmission (p = 0.07 and p = 0.09, respectively). Non-CVDs out-competed cardiovascular covariates previously reported to predict readmission. CONCLUSIONS: In patients with HF hospitalization, prior admissions predicted 30-day readmission. Diseases of the digestive system also increase 30-day readmission rates. Assessment of non-CVD burden in HF patients could serve as an important risk marker for 30-day readmissions.

The REVAMP trial to evaluate HIV resistance testing in sub-Saharan Africa: a case study in clinical trial design in resource limited settings to optimize effectiveness and cost effectiveness estimates.

BACKGROUND: In sub-Saharan Africa, rates of sustained HIV virologic suppression remain below international goals. HIV resistance testing, while common in resource-rich settings, has not gained traction due to concerns about cost and sustainability. OBJECTIVE: We designed a randomized clinical trial to determine the feasibility, effectiveness, and cost-effectiveness of routine HIV resistance testing in sub-Saharan Africa. APPROACH: We describe challenges common to intervention studies in resource-limited settings, and strategies used to address them, including: (1) optimizing generalizability and cost-effectiveness estimates to promote transition from study results to policy; (2) minimizing bias due to patient attrition; and (3) addressing ethical issues related to enrollment of pregnant women. METHODS: The study randomizes people in Uganda and South Africa with virologic failure on first-line therapy to standard of care virologic monitoring or immediate resistance testing. To strengthen external validity, study procedures are conducted within publicly supported laboratory and clinical facilities using local staff. To optimize cost estimates, we collect primary data on quality of life and medical resource utilization. To minimize losses from observation, we collect locally relevant contact information, including Whatsapp account details, for field-based tracking of missing participants. Finally, pregnant women are followed with an adapted protocol which includes an increased visit frequency to minimize risk to them and their fetuses. CONCLUSIONS: REVAMP is a pragammatic randomized clinical trial designed to test the effectiveness and cost-effectiveness of HIV resistance testing versus standard of care in sub-Saharan Africa. We anticipate the results will directly inform HIV policy in sub-Saharan Africa to optimize care for HIV-infected patients.

Model selection and inference for censored lifetime medical expenditures.

Identifying factors associated with increased medical cost is important for many micro- and macro-institutions, including the national economy and public health, insurers and the insured. However, assembling comprehensive national databases that include both the cost and individual-level predictors can prove challenging. Alternatively, one can use data from smaller studies with the understanding that conclusions drawn from such analyses may be limited to the participant population. At the same time, smaller clinical studies have limited follow-up and lifetime medical cost may not be fully observed for all study participants. In this context, we develop new model selection methods and inference procedures for secondary analyses of clinical trial data when lifetime medical cost is subject to induced censoring. Our model selection methods extend a theory of penalized estimating function to a calibration regression estimator tailored for this data type. Next, we develop a novel inference procedure for the unpenalized regression estimator using perturbation and resampling theory. Then, we extend this resampling plan to accommodate regularized coefficient estimation of censored lifetime medical cost and develop postselection inference procedures for the final model. Our methods are motivated by data from Southwest Oncology Group Protocol 9509, a clinical trial of patients with advanced nonsmall cell lung cancer, and our models of lifetime medical cost are specific to this population. But the methods presented in this article are built on rather general techniques and could be applied to larger databases as those data become available.

On Huberized calibration regression for censored medical cost data.

Authors have observed that the distribution of medical expenditures has features that do not lend it to parametric modeling and can present significant challenges for least-squares-type estimators, even on a logarithmic scale. In this note, we discuss caveats and extensions of coefficient estimation in the bivariate accelerated lifetime model of medical cost and survival time on covariates. We consider the setting where medical cost is observed only when the event occurs and potential right-censoring of the event time induces a dependent censoring mechanism on cost. We adopt Huang's (2002) estimation framework using the weighted log-rank estimating equations and investigate his proposal for robust mark-scale coefficient estimation. Due to modeling restrictions on the joint distribution of survival time and cost, we conclude that his robust mark-scale coefficient estimator would benefit from a time-scale adjustment. We use basic principles from robust estimation to define a new weighted marked process that subsequently leads to a new time-corrected robust regression calibration estimator. Our simulation studies illustrate how the proposed estimator has desirable operating characteristics, including reduced sensitivity to extreme values in the cost distribution, smaller finite sample bias and variance than earlier proposals. We illustrate the method in an analysis of lifetime medical cost data from a lung cancer study conducted by the Southwest Oncology Group.

Variable selection in the presence of missing data: resampling and imputation.

In the presence of missing data, variable selection methods need to be tailored to missing data mechanisms and statistical approaches used for handling missing data. We focus on the mechanism of missing at random and variable selection methods that can be combined with imputation. We investigate a general resampling approach (BI-SS) that combines bootstrap imputation and stability selection, the latter of which was developed for fully observed data. The proposed approach is general and can be applied to a wide range of settings. Our extensive simulation studies demonstrate that the performance of BI-SS is the best or close to the best and is relatively insensitive to tuning parameter values in terms of variable selection, compared with several existing methods for both low-dimensional and high-dimensional problems. The proposed approach is further illustrated using two applications, one for a low-dimensional problem and the other for a high-dimensional problem.

Gender-specific risk factors for virologic failure in KwaZulu-Natal: automobile ownership and financial insecurity.

We sought to examine which socioeconomic indicators are risk factors for virologic failure among HIV-1 infected patients receiving antiretroviral therapy (ART) in KwaZulu-Natal, South Africa. A case-control study of virologic failure was conducted among patients recruited from the outpatient clinic at McCord Hospital in Durban, South Africa between October 1, 2010 and June 30, 2012. Cases were those failing first-line ART, defined as viral load >1,000 copies/mL. Univariate logistic regression was performed on sociodemographic data for the outcome of virologic failure. Variables found significant (p < 0.05) were used in multivariate models and all models were stratified by gender. Of 158 cases and 300 controls, 35 % were male and median age was 40 years. Gender stratification of models revealed automobile ownership was a risk factor among males, while variables of financial insecurity (unemployment, non-spouse family paying for care, staying with family) were risk factors for women. In this cohort, financial insecurity among women and automobile ownership among men were risk factors for virologic failure. Risk factor differences between genders demonstrate limitations of generalized risk factor analysis.

Early warning indicators for first-line virologic failure independent of adherence measures in a South African urban clinic.

We sought to develop individual-level Early Warning Indicators (EWI) of virologic failure (VF) for clinicians to use during routine care complementing WHO population-level EWI. A case-control study was conducted at a Durban clinic. Patients after ≥ 5 months of first-line antiretroviral therapy (ART) were defined as cases if they had VF [HIV-1 viral load (VL)>1000 copies/mL] and controls (2:1) if they had VL ≤ 1000 copies/mL. Pharmacy refills and pill counts were used as adherence measures. Participants responded to a questionnaire including validated psychosocial and symptom scales. Data were also collected from the medical record. Multivariable logistic regression models of VF included factors associated with VF (p<0.05) in univariable analyses. We enrolled 158 cases and 300 controls. In the final multivariable model, male gender, not having an active religious faith, practicing unsafe sex, having a family member with HIV, not being pleased with the clinic experience, symptoms of depression, fatigue, or rash, low CD4 counts, family recommending HIV care, and using a TV/radio as ART reminders (compared to mobile phones) were associated with VF independent of adherence measures. In this setting, we identified several key individual-level EWI associated with VF including novel psychosocial factors independent of adherence measures.

The influence of a Vascular Surgery Hospitalist program on physician and patient satisfaction, resident education, and resource utilization.

A number of surgery practice models have been developed to address general and trauma surgeon workforce shortages and on-call issues and to improve surgeon satisfaction. These include the creation of acute or urgent care surgery services and "surgical hospitalist" programs. To date, no practice models corresponding to those developed for general and trauma surgeons have been proposed to address these same issues among vascular surgeons or other surgical subspecialists. In 2003, our practice established a Vascular Surgery Hospitalist program. Since its inception nearly a decade ago, it has undergone several modifications. We reviewed hospital administrative databases and surveys of faculty, residents, and patients to evaluate the program's impact. Benefits of the Vascular Surgery Hospitalist program include improved surgeon satisfaction, resource utilization, timeliness of patient care, communication among referring physicians and ancillary staff, and resident teaching/supervision. Elements of this program may be applicable to a variety of surgical subspecialty settings.

The value of a carotid duplex surveillance program for stroke prevention.

BACKGROUND: Although duplex ultrasonography (DU) can readily identify progression of carotid stenosis, controversy regarding the natural history of asymptomatic carotid stenosis as well as the need and appropriate interval for carotid DU surveillance still exists. Furthermore, consensus has not yet been made in the surgical literature regarding the usefulness, cost-effectiveness, or timing of DU surveillance after carotid endarterectomy (CEA). The purpose of this study was to determine how often DU surveillance for asymptomatic carotid disease or postintervention stenosis resulted in any change in the patient's clinical management, how many strokes were prevented by DU surveillance, and the cost of such a DU surveillance program per stroke prevented. METHODS: We reviewed a 9-year vascular surgical database to identify all patients enrolled in a carotid DU surveillance program for asymptomatic carotid stenosis or following CEA between January 1, 2000, and December 31, 2008. The number of duplex scans and CEAs performed in those patients through March 2010 was also determined. The results of the Asymptomatic Carotid Atherosclerosis Study were then used to estimate the number of strokes prevented by CEA in the study population. Reimbursement data were assessed to calculate the average cost of each DU and the cost of the DU surveillance program for each stroke prevented. RESULTS: During the study period, there were 11,531 carotid duplex scans performed on 3,003 patients (mean: 3.84 scans per patient) who had been enrolled in the DU surveillance program. CEA for asymptomatic carotid stenosis was performed on 225 (7.5%) patients. The DU surveillance program prevented approximately 13 strokes (871 carotid duplex scans per stroke prevented). The mean cost of each duplex scan was $332 ± 170. The total cost of the DU surveillance program was approximately $3,830,000 or $290,000 per stroke prevented. CONCLUSIONS: Although a carotid DU surveillance program generates substantial revenue for a vascular surgery practice, it is costly and inefficient. A reappraisal of the "value" of carotid DU surveillance in stroke prevention is warranted. Consideration should be given to eliminating routine surveillance of postendarterectomy carotids in the absence of contralateral disease and limiting the number of DU surveillance studies for asymptomatic carotid disease.

Physician practice variation in the pediatric emergency department and its impact on resource use and quality of care.

OBJECTIVE: To evaluate variation in case-mix adjusted resource use among pediatric emergency department (ED) physicians and its correlation with ED length of stay (LOS) and return rates. METHODS: Resource use patterns at 2 EDs for 36 academic physicians (163,669 patients at ED1) and 45 private physicians (289,199 patients at ED2) from 2003 to 2006 were abstracted for common laboratory tests, imaging studies, intravenous therapy (fluids/antibiotics), LOS and 72-hour return rate for discharged patients, and hospital admissions for all patients. Case-mix adjustment was based on triage acuity, diagnostic category, demographics, and temporal measures. OUTCOME MEASURES: (1) adjusted overall resource use for ED1 and ED2 physicians and (2) observed-to-expected ratios for ED1 physicians. RESULTS: Case-mix adjusted hospital admission rates among physicians varied nearly 3-fold (6.3%-18%) for ED1 and 8-fold (2.5%-19.4%) for ED2. Intravenous therapy use varied 2-fold (4.9%-10.4%) at ED1 and 3-fold (3.6%-11.4%) at ED2. Emergency department 2 physicians had an almost 2-fold (10.9%-20.6%) variation in imaging use. Variation in head computed tomography use was 2-fold (1.1%-2.5%) at ED1 and 5-fold (0.9%-4.8%) at ED2. Physicians had longer than expected LOS if they had higher than expected use of laboratory tests (r, 0.41; 95% confidence interval [CI], 0.09-0.65; P < 0.05) and imaging (r, 0.48; 95% CI, 0.17-0.69; P < 0.01). Return rate was not significantly correlated with resource use in any category. Physicians with higher than expected use of laboratory tests had higher than expected use of imaging (r, 0.62; 95% CI, 0.36-0.78; P < 0.001), head computed tomography (r, 0.49; 95% CI, 0.19-0.70; P < 0.01), and intravenous therapy (r, 0.51; 95% CI, 0.20-0.71; P < 0.01). CONCLUSIONS: Significant variation exists in physician use of common ED resources. Higher resource use was associated with increased LOS but did not reduce return to ED. Practice variation such as this may represent an opportunity to improve health care quality and decrease costs.

Outcome of the use of stent grafts to salvage failed arteriovenous accesses.

BACKGROUND: Since elements of the Dialysis Outcome Quality Initiative (K/DOQI) were implemented a decade ago, there has been a reduction in mortality for patients on hemodialysis. As patient longevity has increased, AV access site preservation by salvaging failed arteriovenous (AV) accesses has become increasingly important. However, efforts to salvage an AV access must be balanced against futile and expensive procedures. The Viabahn Endoprosthesis is a self-expandable stent graft (SG) that can be used to treat vein rupture or fibrotic lesions with significant elastic recoil following balloon angioplasty. The literature comprising the outcome of the use of SGs in salvaging failed AV accesses is limited. The purpose of this study is to determine the outcome of failed AV accesses treated with SGs and to identify patient or graft factors predictive of success. METHODS: The vascular access database and office, hospital, and dialysis unit records were retrospectively reviewed to identify all patients who underwent placement of an SG for the treatment of a thrombosed AV access between September 2004 and December 2007. Mean patient follow-up was 6 months. The K/DOQI goal for patency following a surgical intervention (6 months or later) was used to determine procedure success or failure. Kaplan-Meier life-table analysis was used to determine patency. Patient demographics and graft factors (location, diameter, length) were analyzed to identify predictors of success. RESULTS: Fifty-five SGs were placed in 48 patients (males, 29%; mean age, 61 years; diabetes mellitus, 47%) with a failed AV access. The indications were to treat significant elastic recoil or vein rupture following balloon angioplasty (47 patients) and to treat an AV graft seroma (1 patient). Cost for the VE ranged from $2337 to $3367 per patient. The procedure was deemed successful (patent at 6 months) in 29 + or - 7% of cases. Procedure success was not influenced by AV access location, endoprosthesis size (diameter or length), or patient demographic factors (p > 0.05). CONCLUSION: Use of the SG to salvage AV accesses falls short of the current K/DOQI clinical outcome goals for successful surgical intervention in the majority of cases. Given these results and the cost of the SG, its use is indicated in cases where AV access salvage will have an impact on long-term survival such as for patients in whom there are few options for new access placement. Further studies are needed to compare the SG to less costly options, such as angioplasty alone or angioplasty with the use of bare metal stents.

Predictors of health resource use by disabled older female Medicare beneficiaries living in the community.

OBJECTIVES: To identify specific clinical factors that could best predict resource use by disabled older women. DESIGN: Cross-sectional. SETTING: Urban community in Baltimore, Maryland. PARTICIPANTS: One thousand two community-dwelling, moderately to severely disabled, female Medicare beneficiaries aged 65 and older, from the Women's Health and Aging Study I (WHAS). MEASUREMENTS: WHAS data were merged with participants' 1992-1994 Medicare claims data for the year after baseline evaluation, reflecting inpatient, outpatient, home-based, and skilled-nursing services. The independent contributions of factors hypothesized to predict health expenditures were assessed, using chi-square and regression analyses, with the logarithm of Medicare expenditures as the primary outcome. RESULTS: Demographic factors were not associated with Medicare expenditures. Factors associated with expenditures in bivariate analyses included heart disease (1.4x), chronic obstructive pulmonary disease (1.3x), diabetes mellitus (1.1x), smoking, comorbidity, and severity of disability, as well as low creatinine clearance, serum albumin, caloric expenditure, or skinfold thickness. Heart disease, diabetes mellitus, and low skinfold thickness remained significant after adjustment for other factors. CONCLUSION: Heart disease, diabetes mellitus, and low skinfold thickness are important independent predictors of 1-year Medicare expenditures by disabled older women. Many other variables that reflect disease, disability, nutrition, or personal habits have less predictive ability. Most demographic factors are not predictors of expenditures in this population. Focusing on the best predictors may facilitate more-effective risk adjustment and creation of related health policies.