A 680,000-person megastudy of nudges to encourage vaccination in pharmacies.

Encouraging vaccination is a pressing policy problem. To assess whether text-based reminders can encourage pharmacy vaccination and what kinds of messages work best, we conducted a megastudy. We randomly assigned 689,693 Walmart pharmacy patients to receive one of 22 different text reminders using a variety of different behavioral science principles to nudge flu vaccination or to a business-as-usual control condition that received no messages. We found that the reminder texts that we tested increased pharmacy vaccination rates by an average of 2.0 percentage points, or 6.8%, over a 3-mo follow-up period. The most-effective messages reminded patients that a flu shot was waiting for them and delivered reminders on multiple days. The top-performing intervention included two texts delivered 3 d apart and communicated to patients that a vaccine was "waiting for you." Neither experts nor lay people anticipated that this would be the best-performing treatment, underscoring the value of simultaneously testing many different nudges in a highly powered megastudy.

Comparison of Clinical Decision Support Tools to Improve Pediatric Lipid Screening.

OBJECTIVE: To test whether different clinical decision support tools increase clinician orders and patient completions relative to standard practice and each other. STUDY DESIGN: A pragmatic, patient-randomized clinical trial in the electronic health record was conducted between October 2019 and April 2020 at Geisinger Health System in Pennsylvania, with 4 arms: care gap-a passive listing recommending screening; alert-a panel promoting and enabling lipid screen orders; both; and a standard practice-no guideline-based notification-control arm. Data were analyzed for 13 346 9- to 11-year-old patients seen within Geisinger primary care, cardiology, urgent care, or nutrition clinics, or who had an endocrinology visit. Principal outcomes were lipid screening orders by clinicians and completions by patients within 1 week of orders. RESULTS: Active (care gap and/or alert) vs control arm patients were significantly more likely (P < .05) to have lipid screening tests ordered and completed, with ORs ranging from 1.67 (95% CI 1.28-2.19) to 5.73 (95% CI 4.46-7.36) for orders and 1.54 (95% CI 1.04-2.27) to 2.90 (95% CI 2.02-4.15) for completions. Alerts, with or without care gaps listed, outperformed care gaps alone on orders, with odds ratios ranging from 2.92 (95% CI 2.32-3.66) to 3.43 (95% CI 2.73-4.29). CONCLUSIONS: Electronic alerts can increase lipid screening orders and completions, suggesting clinical decision support can improve guideline-concordant screening. The study also highlights electronic record-based patient randomization as a way to determine relative effectiveness of support tools. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04118348.

A megastudy of text-based nudges encouraging patients to get vaccinated at an upcoming doctor's appointment.

Many Americans fail to get life-saving vaccines each year, and the availability of a vaccine for COVID-19 makes the challenge of encouraging vaccination more urgent than ever. We present a large field experiment (N = 47,306) testing 19 nudges delivered to patients via text message and designed to boost adoption of the influenza vaccine. Our findings suggest that text messages sent prior to a primary care visit can boost vaccination rates by an average of 5%. Overall, interventions performed better when they were 1) framed as reminders to get flu shots that were already reserved for the patient and 2) congruent with the sort of communications patients expected to receive from their healthcare provider (i.e., not surprising, casual, or interactive). The best-performing intervention in our study reminded patients twice to get their flu shot at their upcoming doctor's appointment and indicated it was reserved for them. This successful script could be used as a template for campaigns to encourage the adoption of life-saving vaccines, including against COVID-19.

National Health and Wellness Survey exploratory cluster analysis of males 40-70 years old focused on erectile dysfunction and associated risk factors across the USA, Italy, Brazil and China.

OBJECTIVES: Prior studies of erectile dysfunction (ED) tend to narrowly focus on relationships with specific comorbidities, rather than evaluating a more comprehensive array of risk factors and assessing naturalistic patterns among them. This study identifies natural clusters of male characteristics from a general population sample per country, quantifies ED dynamics in these profiles and compares profiles across the US, Italy, Brazil and China samples. METHODS: National Health and Wellness Survey 2015 and 2016 patient-reported data on men aged 40-70 years (USA n = 15,652; Italy n = 2,521; Brazil n = 2,822; China n = 5,553) were analysed. Hierarchical agglomerative clustering identified clusters where predictors included demographics, health characteristics/behaviours, ED risk factors and provider visits in the past 6 months. Multinomial logistic regression assessed the independent utility of variables in predicting cluster membership, compared with the healthiest control cluster per country. RESULTS: Different natural clusters were found across countries, with four clusters for the USA, Italy and China and three clusters for Brazil. Age, income, employment, health behaviours and ED risk factors predicted different cluster membership across countries. In the USA, Italy and Brazil, younger clusters were predicted by ED, unhealthy behaviours and ED risk factors. Unique cluster profiles were identified in China, with ED and ED risk factors (aside from hypertension) not predicting cluster membership, while socio-demographics and health behaviours were strongly predictive. CONCLUSIONS: Natural cluster profiles revealed notable ED rates among adult males of age 40-70 in four different countries. Clusters were mainly predicted by unhealthy behaviours, ED risk factors and ED, regardless of level or presence of positive health characteristics and behaviours. This analysis identified meaningful subgroups of men with heightened ED risk factors, which can help healthcare providers to better recognise specific populations with the greatest need for intervention.

The association of erectile dysfunction with productivity and absenteeism in eight countries globally.

AIM: To evaluate the association of erectile dysfunction (ED) with work productivity loss, activity impairment and health-related quality of life (HRQoL) across Brazil, China, France, Germany, Italy, Spain, the UK and the US. METHODS: This cross-sectional observational study used data from adult men (40-70 years old; N = 52 697) from the 2015 and 2016 National Health and Wellness Surveys. ED assessment was based on self-reported difficulty in achieving or maintaining an erection in the past 6 months. Impairment to work and non-work activities and HRQoL were assessed for each country and compared against the US. Multivariable models tested interactions between ED status and country for each outcome. RESULTS: Overall ED prevalence was reported as 49.7%, with Italy reporting the highest rate (54.7%). Men with ED reported significantly higher absenteeism (7.1% vs 3.2%), presenteeism (22.5% vs 10.1%), overall work productivity impairment (24.8% vs 11.2%), activity impairment (28.6% vs 14.5%) and significantly lower Mental Component Summary scores (MCS; 46.7 vs 51.2), Physical Component Summary scores (PCS; 48.3 vs 53.0), and health state utilities (SF-6D: 0.693 vs 0.778; all, P < 0.001) than men with no ED. After adjusting for covariates, compared with the US, the association of ED status with overall work productivity impairment was greatest in the UK (26% higher; P < 0.05), and with MCS, PCS and SF-6D scores was greatest in China (-2.67, -1.58, and -0.043 points, respectively; all, P < 0.001). Greater ED severity was significantly associated with higher impairment to work and non-work activities and lower HRQoL, with China reporting the highest burden, compared with the US (most P < 0.05). CONCLUSION: ED poses a significant burden with respect to work productivity and HRQoL, with greater severity associated with worse outcomes. Better management and earlier detection may help reduce this burden, especially in countries reporting a strong association between ED and poor economic and health outcomes.

An empirical tool for estimating the share of unmet need due to healthcare inefficiencies, suboptimal access, and lack of effective technologies.

BACKGROUND: Although there has been growing attention to the measurement of unmet need, which is the overall epidemiological burden of disease, current measures ignore the burden that could be eliminated from technological advances or more effective use of current technologies. METHODS: We developed a conceptual framework and empirical tool that separates unmet need from met need and subcategorizes the causes of unmet need into suboptimal access to and ineffective use of current technologies and lack of current technologies. Statistical models were used to model the relationship between health-related quality of life (HR-QOL) and treatment utilization using data from the National Health and Wellness Survey (NHWS). Predicted HR-QOL was combined with prevalence data from the Global Burden of Disease Study (GBD) to estimate met need and the causes of unmet need due to morbidity in the US and EU5 for five diseases: rheumatoid arthritis, breast cancer, Parkinson's disease, hepatitis C, and chronic obstructive pulmonary disease (COPD). RESULTS: HR-QOL was positively correlated with adherence to medication and patient-perceived quality and negatively correlated with financial barriers. Met need was substantial across all disease and regions, although significant unmet need remains. While the majority of unmet need was driven by lack of technologies rather than ineffective use of current technologies, there was considerable variation across diseases and regions. Overall unmet need was largest for COPD, which had the highest prevalence of all diseases in this study. CONCLUSION: We developed a methodology that can inform decisions about which diseases to invest in and whether those investments should focus on improving access to currently available technologies or inventing new technologies.

Alzheimer's disease severity and its association with patient and caregiver quality of life in Japan: results of a community-based survey.

BACKGROUND: Alzheimer's disease (AD) dementia, a progressive neurodegenerative disease, exerts significant burden upon patients, caregivers, and healthcare systems globally. The current study investigated the associations between AD dementia patient disease severity and health-related quality of life (HRQoL) of both patients (proxy report) and their caregivers living in Japan, as well as caregiving-related comorbidities such as depression. METHODS: This cross-sectional study used self-reported data from caregivers of people diagnosed with AD dementia by a healthcare provider in Japan. Caregivers were identified via online panels and invited to participate in an online survey between 2014 and 2015. Caregivers completed survey items for themselves, in addition to providing proxy measures for patients with AD dementia for whom they were caring. Patient and caregiver HRQoL was measured using the EuroQoL 5-Dimension (EQ-5D). Additional outcomes for caregivers of AD dementia patients included the Patient Health Questionnaire (PHQ-9) of depressive symptomology, as well as comorbidities experienced since initiating caregiving for their AD dementia patients. These outcomes were examined as a function of AD dementia severity, as measured by long-term care insurance (LTCI) categories. Bivariate analyses between LTCI and outcomes were conducted using independent t-tests and chi-square tests. Multivariable analyses, controlling for potential confounders, were conducted using generalized linear models (GLMs) specifying a normal distribution. RESULTS: Across 300 caregiver respondents, multivariable results revealed that increasing AD dementia severity was significantly associated with poorer patient and caregiver EQ-5D scores and a high proportion of caregivers (30.0%) reported PHQ-9 scores indicative of major depressive disorder (MDD). The most frequent comorbidities experienced after becoming caregivers of AD dementia patients included hypertension (12.7%) and insomnia (11.0%). Depression and other comorbidities did not differ significantly by patient severity. CONCLUSIONS: The current study provides unique insight into the specific degree of incremental burden associated with increasing AD dementia severity among patients and caregivers alike. Importantly, greater disease severity was associated with poorer quality of life among both patients and caregivers. These results suggest that earlier detection and treatment of AD dementia may provide an opportunity to reduce the burden of disease for patients, caregivers, and society at large.

Caregiving for patients with Alzheimer's disease or dementia and its association with psychiatric and clinical comorbidities and other health outcomes in Brazil.

OBJECTIVES: Individuals with dementia due to Alzheimer's disease often receive care from family members who experience associated burden. This study provides the first broad, population-based account of caregiving-related health outcome burden in Brazil. METHODS: Data were analyzed from the 2012 National Health and Wellness Survey in Brazil (n = 12,000), an Internet-based survey of adults (aged 18+ years), using stratified sampling by sex and age to ensure demographic representation of Brazil's adult population. Caregivers of individuals with Alzheimer's disease or dementia were compared with non-caregivers on comorbidities, productivity impairment, health-related quality of life, resource utilization, sociodemographic/health characteristics and behaviors, and Charlson comorbidity index scores. Regression models assessed outcomes associated with caregiving, adjusting for potential confounds. RESULTS: Among 10,853 respondents, caregivers' (n = 209) average age was 42.1 years, 53% were female, and 52% were married/living with a partner. Caregivers versus non-caregivers (n = 10,644) were more frequently obese, smokers, insured, employed, college-educated, and wealthier and had higher Charlson comorbidity index, all p < 0.05. Adjusting for covariates, caregiving was associated with significantly increased risk of depressive symptoms (odds ratio [OR] = 2.008), major depressive disorder (OR = 1.483), anxiety (OR = 1.714), insomnia (OR = 1.644), hypertension (OR = 1.584), pain (OR = 1.704), and diabetes (OR = 2.103), all p < 0.015. Caregiving was also associated with lower health utilities (-0.024 points) and mental health status (-1.70 points), higher rates of presenteeism-related impairment (32.7% greater) and overall work impairment (35.9% greater), and higher traditional provider visit rates (28.7% greater), all p < 0.035. CONCLUSIONS: Caregiver status was found to be a factor associated with worse health outcomes and psychiatric and clinical disorders.

Impact of caring for persons with Alzheimer's disease or dementia on caregivers' health outcomes: findings from a community based survey in Japan.

BACKGROUND: This study assessed how family caregivers for patients with Alzheimer's disease (AD) or dementia in Japan differed from non-caregivers in characteristics and health outcomes (i.e., comorbidities, health-related quality of life [HRQoL], productivity, and resource use). Caregivers were hypothesized to experience significantly poorer outcomes than non-caregivers. METHODS: Data were combined from the 2012 and 2013 National Health and Wellness Survey in Japan (n = 60000). Caregivers for adult relatives with AD or dementia were compared with non-caregivers on: comorbidities (including Patient Health Questionnaire (PHQ-9) cutoff scores suggesting presence/absence of major depressive disorder (MDD)), Work Productivity and Activity Impairment (WPAI), SF-36v2-based HRQoL, and healthcare resource utilization. Sociodemographic characteristics, health characteristics and behaviors, and Charlson comorbidity index (CCI) scores were compared across groups. Propensity matching, based on scores generated from a logistic regression predicting caregiving, was used to match caregivers with non-caregivers with similar likelihood of being caregivers. Bivariate comparisons across matched groups served to estimate outcomes differences due to caregiving. RESULTS: Among 55060 respondents, compared with non-caregivers (n = 53758), caregivers (n = 1302) were older (52.6 vs. 47.5 years), more frequently female (53 % vs. 49 %), married/partnered, frequent alcohol drinkers, current smokers, exercisers, and not employed, and they averaged higher CCI scores (0.37 vs. 0.14), all p < 0.05. Propensity scores incorporated sex, age, body mass index (BMI), exercise, alcohol, smoking, marital status, CCI, insured status, education, employment, income, and children in household. A greedy matching algorithm produced 1297 exact matches, excluding 5 non-matched caregivers. Health utilities scores were significantly lower among caregivers (0.724) vs. non-caregivers (0.764), as were SF-36v2 Physical and Mental Component Summary scores. Caregivers vs. non-caregivers had significantly higher absenteeism, presenteeism-related impairment, overall work impairment (25.8 % vs. 20.4 %, respectively), and activity impairment (25.4 % vs. 21.8 %), more emergency room and traditional provider visits (7.70 vs. 5.35) in the past six months, and more frequent MDD (14 % vs. 9 %), depression, insomnia, anxiety, and pain. CONCLUSIONS: Those providing care for patients with AD or dementia in Japan experienced significantly poorer HRQoL and greater comorbid risk, productivity impairment, and resource use. These findings inform the need for greater support for caregivers and their patients.

Patient characteristics and outcomes associated with nitrovasodilator use in the treatment of acute heart failure.

Nitrovasodilators (NVs) are commonly recommended for the treatment of acute heart failure (AHF); however, registries suggest their use is not common. The objectives of this study were to determine patient characteristics associated with NV use and to explore the association between NV use and outcomes [length of stay (LoS) and inpatient mortality] in patients with AHF. A survey of US physicians (n = 426) who treat at least 5 AHF patients per month with NV provided a patient sample (n = 812 treated with NV and n = 322 not-NV) derived from chart review. Factors associated with NV use as well as patient characteristics and outcomes associated with NV use were explored using bivariate analysis, logistic regression, and negative binomial regression as appropriate. NV-treated patients were more likely to be female, have a higher systolic blood pressure, higher B-type natriuretic peptide and troponin, and stay in the intensive care unit while hospitalized, but less likely to be hyponatremic or hospitalized once previously. Overall, average LoS was 5.10 days (SD = 4.52) with 5.21 days (SD = 0.15) for the NV group and 4.94 days (SD = 0.31) for the non-NV group. The overall inpatient mortality rate was 2.1%. Among physicians who frequently use NV to treat AHF patients, there are distinct patient characteristics between NV treated and nontreated patients, suggesting a phenotype-driven approach. However, no differences in LoS or mortality were observed.

Warfarin and Aspirin Use for Stroke Prevention Among Patients With Atrial Fibrillation: The US National Health and Wellness Survey.

Vitamin K antagonist (VKA) and aspirin (ASA) are recommended for stroke prevention in patients with atrial fibrillation (AF). This study examined VKA and ASA use and their clinical correlates, including CHADS2 stroke risk scores, among adult patients with AF in the general population. Participants included 1290 (1.72%) adults reporting diagnosis with AF (mean age, 64.9 years; 65% men) from the 2009 US National Health and Wellness Survey, an online, self-administered, nationwide, stratified random sample survey of 75,000 adults. Antithrombotic use patterns, including VKA, ASA, VKA+ASA, and non-VKA/ASA, and their correlates were examined using logistic regressions. Respondents with AF were treated with VKA (26.6%), ASA (34.5%), VKA+ASA (15.4%), or neither (23.5%). Among those with CHADS2 ≥1, 19.3% did not report use of VKA or ASA. Among those with CHADS2 ≥2, 35.7% were treated only with ASA. Adjusting for covariates in logistic regressions, CHADS2 ≥1 was associated with VKA and/or ASA (vs. non-VKA/ASA) use (P ≤ 0.02), but CHADS2 score did not differentiate VKA versus ASA use (P > 0.4). Comorbidities were associated with ASA versus VKA use (P ≤ 0.01). Older age, male gender, married status, and obesity were each associated with use of at least one of the treatments investigated (all P < 0.05). One-in-five AF patients with CHADS2 ≥1 were untreated and more than one-third with CHADS2 ≥2 treated with only ASA for stroke prevention. Our findings suggest that although patient characteristics including CHADS2 score were associated with either VKA or ASA use, CHADS2 score was unrelated to VKA versus ASA treatment.

Caring for relatives with lung cancer in Europe: an evaluation of caregivers' experience.

PURPOSE: Informal caregiving for cancer patients is associated with substantial costs and negative health impact. This study investigated the health, humanistic and economic consequences of caring for lung cancer patients in five European Union (EU) countries. METHODS: The study included respondents to the 2010/2011 EU National Health and Wellness Survey from France, Germany, Italy, Spain and the United Kingdom who self-reported being caregivers of a relative with lung cancer (n = 107) or non-caregivers (n = 103,868). Bivariate and multivariable analyses tested the association of caregiving with stress-related comorbidities; health-related quality of life (HRQoL), using the Short Form-12; healthcare resource use; and work productivity/activity impairment, using the Work Productivity and Activity Impairment (WPAI) questionnaire. Costs were based on absenteeism and presenteeism rates. RESULTS: Caregivers versus non-caregivers had significantly higher odds of depression, insomnia, headache and gastrointestinal symptoms, and worse HRQoL. Caregivers reported significantly higher rates of presenteeism-related, overall work and activity impairment; higher odds of impairment across WPAI measures; and higher annual indirect costs with presenteeism and overall work impairment. CONCLUSIONS: Caregiving for lung cancer patients is associated with significant health/work impairments and costs, highlighting a need for increased, personalized caregiver support.

Quantifying the burden of informal caregiving for patients with cancer in Europe.

PURPOSE: Informal caregivers for patients with cancer provide critical emotional and instrumental support, but this role can cause substantial burden. This study expands our understanding of cancer-related caregiving burden in Europe. METHODS: Caregivers (n = 1,713) for patients with cancer and non-caregivers (n = 103,868) were identified through the 2010 and 2011 European Union National Health and Wellness Survey, administered via the Internet to adult populations in France, Germany, Italy, Spain, and the United Kingdom. Respondents completed measures of sociodemographics and health behaviors, health-related quality of life (using SF-12v2), work productivity and activity impairment (using WPAI), healthcare resource use (emergency room visits, hospitalizations, and traditional provider visits), and reported diagnosis of stress-related comorbidities (depression, anxiety, insomnia, headache, migraine, and gastrointestinal problems). Two-sided tests of means or proportions compared caregivers against non-caregivers. Multivariable regression models, comparing caregivers for patients with any cancer vs. non-caregivers on all health outcomes, adjusted for covariates (age, sex, college, income, marital status, employment, body mass index, alcohol, smoking, and Charlson comorbidity index). RESULTS: Caregivers for patients with cancer vs. non-caregivers reported significant (P < 0.05) impairment across all health outcomes, even after adjusting for several confounds (e.g., 3.26-point lower mental health status, 0.043-point lower health utilities, 1.46 times as much work impairment, and 1.97 times the odds of anxiety). CONCLUSIONS: Caregivers for patients with cancer experienced significant impairments. These findings reinforce the need for enhancing our understanding of the caregiving experience and developing supportive and personalized multicomponent interventions for caregivers, given their pivotal role in providing support for patients.

Prevalence of pain reporting and associated health outcomes across emerging markets and developed countries.

OBJECTIVE: The current study represents the first broad, multi-country, population-based survey of pain, assessing the association between pain and health outcomes, plus comparing the burden of pain across emerging and developed countries. DESIGN: Data from the 2011/2012 National Health and Wellness Surveys were used. Respondents reporting pain (neuropathic pain, fibromyalgia, back pain, surgery pain, and/or arthritis pain) vs no pain in emerging (Brazil, China, Russia) vs developed (European Union, Japan, United States) countries were compared on sociodemographic characteristics and measures of quality of life (SF-12v2 and SF-36v2), work productivity and activity impairment, and health care resource use. SUBJECTS: Respondents included 128,821 without pain and 29,848 with pain in developed countries, and 37,244 without pain and 4,789 with pain in emerging countries. RESULTS: Pain reporting and treatment rates were lower in China (6.2% and 28.3%, respectively) and Japan (4.4% and 26.3%, respectively) than in other countries (≥ 14.3% and 35.8%, respectively). Significant impairments in quality of life, productivity, and resource use were associated with pain across all health outcomes in both developed and emerging countries, with some productivity and physical health status impairments greater with pain in developed countries, whereas mental health status impairment and resource use were greater with pain in emerging countries. CONCLUSIONS: Pain was associated with burden across all study outcomes in all regions. Yet, differences emerged in the degree of impairment, pain reporting, diagnosis, treatment rates, and characteristics of patients between emerging and developed nations, thus helping guide a broader understanding of this highly prevalent condition globally.

Chronic myeloid leukemia (CML): association of treatment satisfaction, negative medication experience and treatment restrictions with health outcomes, from the patient's perspective.

BACKGROUND: The availability of the tyrosine-kinase inhibitor (TKI), imatinib, and later introduction of second generation TKIs, dasatinib and nilotinib, have not only improved clinical outcomes of patients with chronic myeloid leukemia (CML), but also provide multiple therapeutic options for CML patients. Despite the widespread use of these oral therapies, little is known about the impact of different treatment regimens on patient-reported outcomes (PROs) among CML patients. The objective of this study was to assess the impact of patient-reported treatment restrictions and negative medication experiences (NMEs) on satisfaction and other health outcomes among patients with CML treated with oral TKIs. METHODS: Participants recruited from survey panels and patient networks in the United States (US) and Europe completed an online questionnaire. Respondents included adults (≥ 18 years) with chronic-phase CML currently on TKI treatment. Study variables included treatment difficulty (i.e., difficulty in following treatment regimens), CML dietary/dosing requirements, NMEs, and validated PROs assessing treatment satisfaction, health-related quality of life (HRQoL), activity impairment, and non-adherence. Structural equation models assessed associations among variables, controlling for covariates. RESULTS: 303 patients with CML (US n=152; Europe n=151; mean age 51.5 years; 46.2% male) completed the questionnaire. Approximately 30% of patients reported treatment difficulties; treatment difficulty was higher among nilotinib (63.3%) than among dasatinib (2.6%) or imatinib (19.2%) treated patients (p<0.0001). Non-adherence was generally low; however, patients on nilotinib vs. imatinib reported missing doses more often (p<0.05). Treatment satisfaction was associated with significantly increased HRQoL (p<0.05) and lower activity impairment (p<0.01). NMEs were associated with decreased treatment satisfaction (p<0.01) and HRQoL (p<0.05), and greater activity impairment (p<0.01). Higher overall treatment restrictions were associated with greater treatment difficulty (p<0.001), which correlated with non-adherence (p<0.01). CONCLUSIONS: Treatment satisfaction and NMEs are important factors associated with HRQoL among patients with CML. Increased treatment restrictions and associated difficulty may affect adherence with TKIs. Choosing a CML treatment regimen that is simple and conveniently adaptable in patients' normal routine can be an important determinant of HRQoL and adherence.

Anxiety and depression associated with caregiver burden in caregivers of stroke survivors with spasticity.

OBJECTIVE: To investigate the relationship between anxiety/depression and caregiver burden in informal caregivers of stroke survivors with spasticity. DESIGN: Data were collected via online surveys from informal caregivers 18 years or older who cared for stroke survivors. SETTING: Internet-based survey. PARTICIPANTS: 2007 through 2009 U.S. National Health and Wellness Survey database or Lightspeed Research general panel respondents (N=153). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Anxiety and depression were self-reported by the caregiver as a physician diagnosis. Depression severity was measured by the Patient Health Questionnaire-9 (PHQ-9). Caregiver burden was measured by the Oberst Caregiving Burden Scale (OCBS) and the Bakas Caregiving Outcomes Scale (BCOS). Logistic regression analyses were conducted with anxiety, depression, and the PHQ-9 depression severity categories as a result of each caregiver burden scale. RESULTS: Data were analyzed for 153 informal caregivers; they were mostly women (70.6%) and white (78.4%), with a mean age of 51.6 years. For every 1-point increase in the OCBS Difficulty Scale, the odds of anxiety or depression were 2.57 times as great (P<.001) and 1.88 times as great (P=.007), respectively. The odds of PHQ-9 severe depression versus all other categories combined were 2.48 times as great (P<.001). For every 1-point decrease in the BCOS, the odds of anxiety or depression were 2.43 times as great (P<.001) and 2.27 times as great (P=.002), respectively. The odds of PHQ-9 severe depression versus all other categories combined were 4.55 times as great (P<.001). CONCLUSIONS: As caregiver burden increases, caregivers are more likely to have anxiety and depression. Depression severity also increases. Providing treatment to stroke survivors with spasticity that lessens the time and more importantly, the difficulty of caregiving may lead to a reduction in caregiver anxiety and depression.

A Randomized Trial of Behavioral Nudges Delivered Through Text Messages to Increase Influenza Vaccination Among Patients With an Upcoming Primary Care Visit.

PURPOSE: To evaluate if nudges delivered by text message prior to an upcoming primary care visit can increase influenza vaccination rates. DESIGN: Randomized, controlled trial. SETTING: Two health systems in the Northeastern US between September 2020 and March 2021. SUBJECTS: 74,811 adults. INTERVENTIONS: Patients in the 19 intervention arms received 1-2 text messages in the 3 days preceding their appointment that varied in their format, interactivity, and content. MEASURES: Influenza vaccination. ANALYSIS: Intention-to-treat. RESULTS: Participants had a mean (SD) age of 50.7 (16.2) years; 55.8% (41,771) were female, 70.6% (52,826) were White, and 19.0% (14,222) were Black. Among the interventions, 5 of 19 (26.3%) had a significantly greater vaccination rate than control. On average, the 19 interventions increased vaccination relative to control by 1.8 percentage points or 6.1% (P = .005). The top performing text message described the vaccine to the patient as "reserved for you" and led to a 3.1 percentage point increase (95% CI, 1.3 to 4.9; P < .001) in vaccination relative to control. Three of the top five performing messages described the vaccine as "reserved for you." None of the interventions performed worse than control. CONCLUSIONS: Text messages encouraging vaccination and delivered prior to an upcoming appointment significantly increased influenza vaccination rates and could be a scalable approach to increase vaccination more broadly.

Tophi and frequent gout flares are associated with impairments to quality of life, productivity, and increased healthcare resource use: Results from a cross-sectional survey.

BACKGROUND: The prevalence of gout is increasing, and most research on the associated burden has focused on serum urate (sUA) levels. The present study quantifies the impact of the presence of tophi and frequency of acute gout attacks on health-related quality of life (HRQOL), productivity, and healthcare resource utilization. METHODS: Patients with self-reported gout (n=620; 338 in US and 282 across France, Germany, and UK) were contacted based on inclusion in the 2010 US and EU National Health and Wellness Surveys (Kantar Health) and the Lightspeed Research ailment panel. Respondents were categorized into mutually-exclusive groups based on number of gout flares experienced in the past 12 months (0/don't recall, 1-2, 3, 4-5, 6+), current presence of tophi (none, 1+, or not sure), and sUA level awareness (yes, no). HRQOL (SF-12v2), healthcare provider visits in the last 6 months, and work productivity and activity impairment (WPAI) were compared across groups. RESULTS: Most patients were males, mean age of 61 years, who reported experiencing at least one acute gout flare in the past 12 months, and 12.3% (n=76) reported presence of tophi. Among the 27.7% (n=172) of patients who were aware of their sUA levels, higher sUA was associated with more flares and tophi. Decreased HRQOL was associated with more frequent flares and presence of tophi. In multivariable models predicting outcomes based on presence of tophi and number of flares, both flares (≥4) and tophi (≥1) were associated with HRQOL decrements on physical and mental component summary scores and health utilities (all p<0.05), after adjustment for age, gender, and time since diagnosis. Flares were also associated with greater activity impairment. CONCLUSIONS: Impairments associated with gout flares and presence of tophi, across patients in the US and EU, underscore the importance of effective management of this potentially curable condition.

Overlapping splicing regulatory motifs--combinatorial effects on splicing.

Regulation of splicing in eukaryotes occurs through the coordinated action of multiple splicing factors. Exons and introns contain numerous putative binding sites for splicing regulatory proteins. Regulation of splicing is presumably achieved by the combinatorial output of the binding of splicing factors to the corresponding binding sites. Although putative regulatory sites often overlap, no extensive study has examined whether overlapping regulatory sequences provide yet another dimension to splicing regulation. Here we analyzed experimentally-identified splicing regulatory sequences using a computational method based on the natural distribution of nucleotides and splicing regulatory sequences. We uncovered positive and negative interplay between overlapping regulatory sequences. Examination of these overlapping motifs revealed a unique spatial distribution, especially near splice donor sites of exons with weak splice donor sites. The positively selected overlapping splicing regulatory motifs were highly conserved among different species, implying functionality. Overall, these results suggest that overlap of two splicing regulatory binding sites is an evolutionary conserved widespread mechanism of splicing regulation. Finally, over-abundant motif overlaps were experimentally tested in a reporting minigene revealing that overlaps may facilitate a mode of splicing that did not occur in the presence of only one of the two regulatory sequences that comprise it.

The Association of Oral Stimulant Medication Adherence with Work Productivity among Adults with ADHD.

OBJECTIVE: Examine associations between oral psychostimulant pharmacotherapy adherence, work productivity, and related indirect costs among US adults with ADHD. METHODS: Medication adherence (Medication Adherence Reasons Scale [MAR-Scale]), work productivity and activity impairment (Work Productivity and Activity Impairment-General Health questionnaire), and ADHD symptom level (Adult ADHD Self-Report Scale version 1.1 Symptom Checklist) were assessed in this noninterventional online survey of adults who self-reported having an ADHD diagnosis and were currently receiving oral psychostimulant treatment for ≥3 months. RESULTS: Of 602 respondents, 395 had low/medium adherence (LMA: MAR-Scale total score ≥1) and 207 had high adherence (HA: MAR-Scale total score 0). After adjusting for covariates, the LMA group had significantly greater levels of absenteeism, absenteeism-related indirect costs, and total indirect costs (all p < .01) than the HA group. CONCLUSION: In adults with ADHD using oral psychostimulants, lower medication adherence was associated with greater absenteeism and indirect costs.