Natural malaria infection elicits rare but potent neutralizing antibodies to the blood-stage antigen RH5.

Plasmodium falciparum reticulocyte-binding protein homolog 5 (RH5) is the most advanced blood-stage malaria vaccine candidate and is being evaluated for efficacy in endemic regions, emphasizing the need to study the underlying antibody response to RH5 during natural infection, which could augment or counteract responses to vaccination. Here, we found that RH5-reactive B cells were rare, and circulating immunoglobulin G (IgG) responses to RH5 were short-lived in malaria-exposed Malian individuals, despite repeated infections over multiple years. RH5-specific monoclonal antibodies isolated from eight malaria-exposed individuals mostly targeted non-neutralizing epitopes, in contrast to antibodies isolated from five RH5-vaccinated, malaria-naive UK individuals. However, MAD8-151 and MAD8-502, isolated from two malaria-exposed Malian individuals, were among the most potent neutralizers out of 186 antibodies from both cohorts and targeted the same epitopes as the most potent vaccine-induced antibodies. These results suggest that natural malaria infection may boost RH5-vaccine-induced responses and provide a clear strategy for the development of next-generation RH5 vaccines.

Analysis of the diverse antigenic landscape of the malaria protein RH5 identifies a potent vaccine-induced human public antibody clonotype.

The highly conserved and essential Plasmodium falciparum reticulocyte-binding protein homolog 5 (PfRH5) has emerged as the leading target for vaccines against the disease-causing blood stage of malaria. However, the features of the human vaccine-induced antibody response that confer highly potent inhibition of malaria parasite invasion into red blood cells are not well defined. Here, we characterize 236 human IgG monoclonal antibodies, derived from 15 donors, induced by the most advanced PfRH5 vaccine. We define the antigenic landscape of this molecule and establish that epitope specificity, antibody association rate, and intra-PfRH5 antibody interactions are key determinants of functional anti-parasitic potency. In addition, we identify a germline IgG gene combination that results in an exceptionally potent class of antibody and demonstrate its prophylactic potential to protect against P. falciparum parasite challenge in vivo. This comprehensive dataset provides a framework to guide rational design of next-generation vaccines and prophylactic antibodies to protect against blood-stage malaria.

Association Between ICD-10 Codes for Social Needs and Subsequent Emergency and Inpatient Use.

BACKGROUND: International Classification of Diseases, 10th revision Z codes capture social needs related to health care encounters and may identify elevated risk of acute care use. OBJECTIVES: To examine associations between Z code assignment and subsequent acute care use and explore associations between social need category and acute care use. RESEARCH DESIGN: Retrospective cohort study. SUBJECTS: Adults continuously enrolled in a commercial or Medicare Advantage plan for ≥15 months (12-month baseline, 3-48 month follow-up). OUTCOMES: All-cause emergency department (ED) visits and inpatient admissions during study follow-up. RESULTS: There were 352,280 patients with any assigned Z codes and 704,560 sampled controls with no Z codes. Among patients with commercial plans, Z code assignment was associated with a 26% higher rate of ED visits [adjusted incidence rate ratio (aIRR) 1.26, 95% CI: 1.25-1.27] and 42% higher rate of inpatient admissions (aIRR 1.42, 95% CI: 1.39-1.44) during follow-up. Among patients with Medicare Advantage plans, Z code assignment was associated with 42% (aIRR 1.42, 95% CI: 1.40-1.43) and 28% (aIRR 1.28, 95% CI: 1.26-1.30) higher rates of ED visits and inpatient admissions, respectively. Within the Z code group, relative to community/social codes, socioeconomic Z codes were associated with higher rates of inpatient admissions (commercial: aIRR 1.10, 95% CI: 1.06-1.14; Medicare Advantage: aIRR 1.24, 95% CI 1.20-1.27), and environmental Z codes were associated with lower rates of both primary outcomes. CONCLUSIONS: Z code assignment was independently associated with higher subsequent emergency and inpatient utilization. Findings suggest Z codes' potential utility for risk prediction and efforts targeting avoidable utilization.

Examining How Social Risk Factors Are Integrated Into Clinical Settings Using Existing Data: A Scoping Review.

PURPOSE: Integrating social care into clinical care requires substantial resources. Use of existing data through a geographic information system (GIS) has the potential to support efficient and effective integration of social care into clinical settings. We conducted a scoping literature review characterizing its use in primary care settings to identify and address social risk factors. METHODS: In December 2018, we searched 2 databases and extracted structured data for eligible articles that (1) described the use of GIS in clinical settings to identify and/or intervene on social risks, (2) were published between December 2013 and December 2018, and (3) were based in the United States. Additional studies were identified by examining references. RESULTS: Of the 5,574 articles included for review, 18 met study eligibility criteria: 14 (78%) were descriptive studies, 3 (17%) tested an intervention, and 1 (6%) was a theoretical report. All studies used GIS to identify social risks (increase awareness); 3 studies (17%) described interventions to address social risks, primarily by identifying relevant community resources and aligning clinical services to patients' needs. CONCLUSIONS: Most studies describe associations between GIS and population health outcomes; however, there is a paucity of literature regarding GIS use to identify and address social risk factors in clinical settings. GIS technology may assist health systems seeking to address population health outcomes through alignment and advocacy; its current application in clinical care delivery is infrequent and largely limited to referring patients to local community resources.

Association of primary care visit length with outpatient utilization, continuity, and care processes.

BACKGROUND: Little is known about how variation in the scheduled length of primary care visits can impact patients' patterns of health care utilization. OBJECTIVE: To evaluate how the scheduled length of in-person visits with primary care physicians (PCPs) was associated with PCP and patient characteristics, outpatient utilization, and preventive care receipt. METHODS: This retrospective cohort study examined data from a large American academic health system. PCP visit length template was defined as either 15- and 30-min scheduled appointments (i.e. 15/30), or 20- and 40-min scheduled appointments (i.e. 20/40). RESULTS: Of 222 included PCPs, 85 (38.3%) used the 15/30 template and 137 (61.7%) used the 20/40 template. The 15/30 group had higher proportions of male (49.4%, vs. 35.8% in the 20/40 group) and family medicine (37.6% vs. 21.2%) physicians. In adjusted patient-level analysis (N = 238,806), having a 15/30 PCP was associated with 9% more primary care visits (incidence rate ratio [IRR], 1.09; 95% confidence interval [CI], 1.03-1.14), and 8% fewer specialty care visits (IRR, 0.92; 95% CI, 0.86-0.98). PCP visit length template was not associated with significant differences in obstetrics/gynaecology visits, continuity of care, or preventive care receipt. In interaction analyses, having a 15/30 PCP was associated with additional primary care visits among non-Hispanic White patients (IRR, 1.10; 95% CI, 1.04-1.16) but not among non-Hispanic Black patients. CONCLUSION: PCPs' choices about the scheduled length of in-person visits may impact their patients' specialty care use, and have varying impacts across different racial/ethnic groups.

Randomized Trial Evaluating Health System Expenditures with Transitional Care Services for Adults with No Usual Source of Care at Discharge.

BACKGROUND: Multidisciplinary transitional care services reduce readmissions for high-risk patients, but it is unclear if health system costs to offer these intensive services are offset by avoidance of higher downstream expenditures. OBJECTIVE: To evaluate net costs for a health system offering transitional care services DESIGN: One-year pragmatic, randomized trial PARTICIPANTS: Adults aged ≥ 18 without a usual source of follow-up care at the time of hospital discharge were enrolled through a high-volume, urban academic medical center in Chicago, IL, USA, from September 2015 through February 2016. INTERVENTIONS: Eligible patients were silently randomized before discharge by an automated electronic health record algorithm allocating them in a 1:3 ratio to receive routine coordination of post-discharge care (RC) versus being offered intensive, multidisciplinary transitional care (TC) services. MAIN MEASUREMENTS: Health system costs were collected from facility administrative systems and transformed to standardized costs using Medicare reference files. Multivariable generalized linear models estimated proportional differences in net costs over one year. KEY RESULTS: Study patients (489 TC; 164 RC) had a mean age of 44 years; 34% were uninsured, 55% had public insurance, and 49% self-identified as Black or Latinx. Over 90 days, cost differences between groups were not statistically significant. Over 180 days, the TC group had 41% lower ED/observation costs (adjusted cost ratio [aCR], 0.59; 95% CI, 0.36-0.97), 50% lower inpatient costs (aCR, 0.50; 95% CI, 0.27-0.95), and 41% lower total healthcare costs (aCR, 0.59; 95% CI, 0.36-0.99) than the RC group. Over 365 days, total cost differences remained of similar magnitude but no longer were statistically significant. CONCLUSIONS: Offering TC services for vulnerable adults at discharge reduced net health system expenditures over 180 days. The promising economic case for multidisciplinary transitional care interventions warrants further research. TRIAL REGISTRATION: National Clinical Trials Registry (NCT03066492).

Activation of Human Vδ2+ γδ T Cells by Staphylococcus aureus Promotes Enhanced Anti-Staphylococcal Adaptive Immunity.

Murine studies have shown the potential for γδ T cells to mediate immunity to Staphylococcus aureus in multiple tissue settings by the secretion of diverse cytokines. However, the role played by γδ T cells in human immune responses to S. aureus is almost entirely unknown. In this study, we establish the capacity of human Vδ2+ γδ T cells for rapid activation in response to S. aureus In coculture with S. aureus-infected monocyte-derived dendritic cells (DCs), Vδ2+ cells derived from peripheral blood rapidly upregulate CD69 and secrete high levels of IFN-γ. DCs mediate this response through direct contact and IL-12 secretion. In turn, IFN-γ released by Vδ2+ cells upregulates IL-12 secretion by DCs in a positive feedback loop. Furthermore, coculture with γδ T cells results in heightened expression of the costimulatory molecule CD86 and the lymph node homing molecule CCR7 on S. aureus-infected DCs. In cocultures of CD4+ T cells with S. aureus-infected DCs, the addition of γδ T cells results in heightened CD4+ T cell activation. Our findings identify γδ T cells as potential key players in the early host response to S. aureus during bloodstream infection, promoting enhanced responses by both innate and adaptive immune cell populations, and support their consideration in the development of host-directed anti-S. aureus treatments.

Opioids and the Risk of Fracture: A Self-Controlled Case Series Study in the Clinical Practice Research Datalink.

Self-controlled study designs can be used to assess the association between exposures and acute outcomes while controlling for important confounders. Using routinely collected health data, a self-controlled case series design was used to investigate the association between opioid use and bone fractures in 2008-2017 among adults registered in the United Kingdom Clinical Practice Research Datalink. The relative incidence of fracture was estimated, comparing periods when these adults were exposed and unexposed to opioids, adjusted for time-varying confounders. Of 539,369 people prescribed opioids, 67,622 sustained fractures and were included in this study. The risk of fracture was significantly increased when the patient was exposed to opioids, with an adjusted incidence rate ratio of 3.93 (95% confidence interval (CI): 3.82, 4.04). Fracture risk was greatest in the first week of starting opioid use (adjusted incidence rate ratio: 7.81, 95% CI: 7.40, 8.25) and declined with increasing duration of use. Restarting opioid use after a gap in exposure significantly increased fracture risk (adjusted incidence rate ratio: 5.05, 95% CI: 4.83, 5.29) when compared with nonuse. These findings highlight the importance of raising awareness of fractures among patients at opioid initiation and demonstrate the utility of self-controlled methods for pharmacoepidemiologic research.

Identifying and addressing social determinants of health in outpatient practice: results of a program-wide survey of internal and family medicine residents.

BACKGROUND: Up to 60% of preventable mortality is attributable to social determinants of health (SDOH), yet training on SDOH competencies is not widely implemented in residency. The objective of this study was to assess internal and family medicine residents' competence at identifying and addressing SDOH. METHODS: Residents' perceived competence at identifying, discussing, and addressing SDOH in outpatient settings was assessed using a single questionnaire administered in March 2017. In this cross-sectional analysis, bivariate associations of resident characteristics with the following outcomes were examined: identifying, discussing, and addressing patients' challenges related to SDOH through referrals. RESULTS: The survey was completed by 129 (84%) residents. Twenty residents (16%) reported an annual income of less than $50,000 during childhood. Overall, 108 residents (84%) reported previous SDOH training. Two-thirds had outpatient practices in Veterans Affairs or safety-net clinics. Thirty-nine (30%) intended to pursue a career in primary care. The following numbers of residents reported high levels of competence for performing these outcomes: identifying patients' challenges related to SDOH: 37 (29%); discussing them with patients: 18 (14%); and addressing these challenges through referrals to internal and external resources: 13 (10%) and 11 (9%), respectively. Factors associated with higher competence included older age, lower childhood household income, prior education about SDOH, primary practice site and intention to practice primary care. CONCLUSIONS: Most residents had previous SDOH training, yet only a small proportion of residents reported being highly competent at identifying or addressing SDOH. Providing opportunities for practical training may be a key component in preparing medical residents to identify and address SDOH effectively in outpatient practice.

Personal social networks and organizational affiliation of South Asians in the United States.

BACKGROUND: Understanding the social lives of South Asian immigrants in the United States (U.S) and their influence on health can inform interpersonal and community-level health interventions for this growing community. This paper describe the rationale, survey design, measurement, and network properties of 700 South Asian individuals in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) social networks ancillary study. METHODS: MASALA is a community-based cohort, established in 2010, to understand risk factors for cardiovascular disease among South Asians living in the U.S. Survey data collection on personal social networks occurred between 2014 and 2017. Network measurements included size, composition, density, and organizational affiliations. Data on participants' self-rated health and social support functions and health-related discussions among network members were also collected. RESULTS: Participants' age ranged from 44 to 84 (average 59 years), and 57% were men. South Asians had large (size=5.6, SD=2.6), kin-centered (proportion kin=0.71, SD=0.28), and dense networks. Affiliation with religious and spiritual organizations was perceived as beneficial to health. Emotional closeness with network members was positively associated with participants' self-rated health (p-value <0.001), and networks with higher density and more kin were significantly associated with health-related discussions. DISCUSSION: The MASALA networks study advances research on the cultural patterning of social relationships and sources of social support in South Asians living in the U.S. Future analyses will examine how personal social networks and organizational affiliations influence South Asians' health behaviors and outcomes. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02268513.

Increased Emergency Department Use in Illinois After Implementation of the Patient Protection and Affordable Care Act.

STUDY OBJECTIVE: We examine emergency department (ED) use and hospitalizations through the ED after Patient Protection and Affordable Care Act (ACA) health insurance expansion in Illinois, a Medicaid expansion state. METHODS: Using statewide hospital administrative data from 2011 through 2015 from 201 nonfederal Illinois hospitals for patients aged 18 to 64 years, mean monthly ED visits were compared before and after ACA implementation by disposition from the ED and primary payer. Visit data were combined with 2010 to 2014 census insurance estimates to compute payer-specific ED visit rates. Interrupted time-series analyses tested changes in ED visit rates and ED hospitalization rates by insurance type after ACA implementation. RESULTS: Average monthly ED visit volume increased by 14,080 visits (95% confidence interval [CI] 4,670 to 23,489), a 5.7% increase, after ACA implementation. Changes by payer were as follows: uninsured decreased by 24,158 (95% CI -27,037 to -21,279), Medicaid increased by 28,746 (95% CI 23,945 to 33,546), and private insurance increased by 9,966 (95% 6,241 to 13,690). The total monthly ED visit rate increased by 1.8 visits per 1,000 residents (95% CI 0.6 to 3.0). The monthly ED visit rate decreased by 8.7 visit per 1,000 uninsured residents (95% CI -11.1 to -6.3) and increased by 10.2 visit per 1,000 Medicaid beneficiaries (95% CI 4.4 to 16.1) and 1.3 visits per 1,000 privately insured residents (95% CI 0.6 to 1.9). After adjusting for baseline trends and season, these changes remained statistically significant. The total number of hospitalizations through the ED was unchanged. CONCLUSION: ED visits by adults aged 18 to 64 years in Illinois increased after ACA health insurance expansion. The increase in total ED visits was driven by an increase in visits resulting in discharge from the ED. A large post-ACA increase in Medicaid visits and a modest increase in privately insured visits outpaced a large reduction in ED visits by uninsured patients. These changes are larger than can be explained by population changes alone and are significantly different from trends in ED use before ACA implementation.

Effect on cardiovascular disease risk factors of interventions to alter consultations between practitioners and patients with type 2 diabetes: A systematic review and meta-analysis of trials in primary care.

OBJECTIVE: To examine the effect on cardiovascular (CVD) risk factors of interventions to alter consultations between practitioners and patients with type 2 diabetes. SEARCH STRATEGY: Electronic and manual citation searching to identify relevant randomized controlled trials (RCTs). INCLUSION CRITERIA: RCTs that compared usual care to interventions to alter consultations between practitioners and patients. The population was adults aged over 18 years with type 2 diabetes. Trials were set in primary care. DATA EXTRACTION AND SYNTHESIS: We recorded if explicit theory-based interventions were used, how consultations were measured to determine whether interventions had an effect on these and calculated weighted mean differences for CVD risk factors including glycated haemoglobin (HbA1c ), systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), LDL cholesterol (LDL-C) and HDL cholesterol (HDL-C). RESULTS: We included seven RCTs with a total of 2277 patients with type 2 diabetes. A range of measures of the consultation was reported, and underlying theory to explain intervention processes was generally undeveloped and poorly applied. There were no overall effects on CVD risk factors; however, trials were heterogeneous. Subgroup analysis suggested some benefit among studies in which interventions demonstrated impact on consultations; statistically significant reductions in HbA1c levels (weighted mean difference, -0.53%; 95% CI: [-0.77, -0.28]; P<.0001; I2 =46%). CONCLUSIONS: Evidence of effect on CVD risk factors from interventions to alter consultations between practitioners and patients with type 2 diabetes was heterogeneous and inconclusive. This could be explained by variable impact of interventions on consultations. More research is required that includes robust measures of the consultations and better development of theory to elucidate mechanisms.

Prospective associations between sedentary time, physical activity, fitness and cardiometabolic risk factors in people with type 2 diabetes.

AIMS/HYPOTHESIS: The aim of this study was to examine the prospective associations between objectively measured physical activity energy expenditure (PAEE), sedentary time, moderate-to-vigorous-intensity physical activity (MVPA), cardiorespiratory fitness (CRF) and cardiometabolic risk factors over 4 years in individuals with recently diagnosed diabetes. METHODS: Among 308 adults (mean age 61.0 [SD 7.2] years; 34% female) with type 2 diabetes from the Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen Detected Diabetes in Primary Care (ADDITION)-Plus study, we measured physical activity using individually calibrated combined heart rate and movement sensing. Multivariable linear regression models were constructed to examine the associations between baseline PAEE, sedentary time, MVPA, CRF and cardiometabolic risk factors and clustered cardiometabolic risk (CCMR) at follow-up, and change in these exposures and change in CCMR and its components over 4 years of follow-up. RESULTS: Individuals who increased their PAEE between baseline and follow-up had a greater reduction in waist circumference (-2.84 cm, 95% CI -4.84, -0.85) and CCMR (-0.17, 95% CI -0.29, -0.04) compared with those who decreased their PAEE. Compared with individuals who decreased their sedentary time, those who increased their sedentary time had a greater increase in waist circumference (3.20 cm, 95% CI 0.84, 5.56). Increases in MVPA were associated with reductions in systolic blood pressure (-6.30 mmHg, 95% CI -11.58, -1.03), while increases in CRF were associated with reductions in CCMR (-0.23, 95% CI -0.40,-0.05) and waist circumference (-3.79 cm, 95% CI -6.62, -0.96). Baseline measures were generally not predictive of cardiometabolic risk at follow-up. CONCLUSIONS/INTERPRETATION: Encouraging people with recently diagnosed diabetes to increase their physical activity and decrease their sedentary time may have beneficial effects on their waist circumference, blood pressure and CCMR.

Residential neighbourhood greenspace is associated with reduced risk of incident diabetes in older people: a prospective cohort study.

BACKGROUND: Three cross sectional studies suggest that neighbourhood greenspace may protect against incident diabetes. This study uses data from a longitudinal study with a large sample size to investigate the association between greenspace and the occurrence of incident diabetes over time. METHODS: Data was from the European Prospective Investigation of Cancer Norfolk, UK, cohort, recruitment 1993-2007 (N = 23,865). Neighbourhoods were defined as 800 m circular buffers around participants' home locations, according to their home postcode (zip code). Greenspace exposure was defined as the percentage of the home neighbourhood that was woodland, grassland, arable land, mountain, heath and bog, according to the UK Land Cover Map. Cox proportional hazards regression examined the association between neighbourhood greenspace exposure and incident diabetes. The population attributable fraction assessed the proportion of diabetes cases attributable to exposure to least green neighbourhoods. Mediation analysis assessed if physical activity explained associations between greenspace and diabetes. Interaction analysis was used to test for the modifying effect of rurality and socio-economic status on the relationship between greenspace and diabetes. Models were adjusted for known and hypothesised confounders. RESULTS: The mean age of participants was 59 years at baseline and 55.1% were female. The mean follow-up time was 11.3 years. Individuals living in the greenest neighbourhood quartile had a 19% lower relative hazard of developing diabetes (HR 0.81; 95% CI 0.67, 0.99; p = 0.035; linear trend p = 0.010). The hazard ratio remained similar (HR 0.81; 95% CI 0.65, 0.99; p = 0.042) after adjusting for age, sex, BMI, whether a parent had been diagnosed with diabetes and socio-economic status at the individual and neighbourhood level. A HR of 0.97 was attributed to the pathway through physical activity in a fully adjusted model, although this was non-significant (95% CI 0.88, 1.08; p = 0.603). The incidence of diabetes in the least green neighbourhoods (with 20% greenspace on average) would fall by 10.7% (95% CI -2.1%, 25.2%; p = 0.106) if they were as green as the average neighbourhood observed across the whole cohort (59% greenspace on average). There were no significant interactions between rurality or socio-economic status and level of greenspace. CONCLUSIONS: Greener home neighbourhoods may protect against risk of diabetes in older adults, although this study does not support a mediation role for physical activity. Causal mechanisms underlying the associations require further investigation.

Protocol for Get Moving: a randomised controlled trial to assess the effectiveness of three minimal contact interventions to promote fitness and physical activity in working adults.

BACKGROUND: Web-based interventions for physical activity offer several advantages over face-to-face, print-and telephone-based interventions and are scalable and potentially cost-effective. Recent reviews of web-based interventions in adults show that they have positive but small effects on physical activity but identify a number of limitations including a reliance on self-report measures of outcome. This trial used an objective measure of physical activity to assess the effectiveness of three minimal contact interventions: 1) A multi-component web-based intervention incorporating objective monitoring and graphical feedback of physical activity; 2) A version of the first intervention that consisted only of objective monitoring plus web-based graphical feedback; and 3) Self-monitoring of physical activity using a paper diary. METHODS/DESIGN: Get Moving is an individually randomised controlled trial with allocation of 488 participants to one of three interventions or to a no-intervention control group. Participants are physically inactive working adults aged 18-65 years. They attended a baseline assessment session at which anthropometric, biological and questionnaire measures were taken and they completed a treadmill exercise test. They then wore a combined movement and heart rate monitor for six days and nights before being randomised to one of the four trial arms. The baseline measures were repeated at the follow-up assessment which took place approximately 12 weeks post-randomisation, conducted by staff blind to group allocation. Participants wore the movement and heart rate monitor for six days and nights before this. The co-primary outcomes are: physical activity energy expenditure measured using individually calibrated combined heart-rate and movement data; and cardiorespiratory fitness measured using a sub-maximal treadmill exercise test. DISCUSSION: Strengths of the trial include the use of an objective measure of physical activity, a measure of cardiorespiratory fitness, relatively large sample size and the use of robust methods of randomisation, allocation concealment and blinding to outcome assessment. Get Moving will contribute to the evidence base on minimal contact interventions for increasing physical activity. The interventions could be implemented in other settings such as primary care. TRIAL REGISTRATION: ISRCTN31844443. Registered 18 June 2010.

Factor structure and construct validity of the temporal experience of pleasure scales.

Feelings of pleasure felt in the moment of goal attainment (consummatory pleasure) are thought to be dissociable from feelings of desire connected with the motivated approach of goals (anticipatory pleasure). The Temporal Experience of Pleasure Scales (TEPS; Gard, Gard, Kring, & John, 2006) was developed to assess individual differences in these distinct processes. Recently, an independent evaluation of the psychometric characteristics of a Chinese-translated TEPS suggested a more complex factor structure (Chan et al., 2012). This study aimed to reexamine the factor structure and convergent and divergent validity of the TEPS in two previously unexamined multiethnic samples. University students in the United Kingdom (N = 294) completed the TEPS and university students in Australia (N = 295) completed the TEPS as well as a battery of conceptually related questionnaires. A confirmatory factor analysis of Gard et al.'s (2006) 2-factor model produced inadequate fit, which model-modification indexes suggested might be due to item cross-loadings. This issue was examined further using an exploratory factor analysis, which revealed a clear 2-factor solution despite cross-loadings among some items. Finally, mixed evidence for convergent-divergent validity was obtained, in terms of relationships between the TEPS and measures of anhedonia, approach-motivation, and positive emotion.

Association between objectively assessed sedentary time and physical activity with metabolic risk factors among people with recently diagnosed type 2 diabetes.

AIMS/HYPOTHESIS: The aim of our study was to examine the associations between sedentary time (SED-time), time spent in moderate-to-vigorous-intensity physical activity (MVPA), total physical activity energy expenditure (PAEE) and cardiorespiratory fitness with metabolic risk among individuals with recently diagnosed type 2 diabetes. METHODS: Individuals participating in the Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen Detected Diabetes in Primary Care (ADDITION)-Plus trial underwent measurement of SED-time, MVPA and PAEE using a combined activity and movement sensor (n = 394), and evaluation of cardiorespiratory fitness (n = 291) and anthropometric and metabolic status. Clustered metabolic risk was calculated by summing standardised values for waist circumference, triacylglycerol, HbA1c, systolic blood pressure and the inverse of HDL-cholesterol. Multivariate linear regression analyses were used to quantify the associations between SED-time, MVPA, PAEE and cardiorespiratory fitness with individual metabolic risk factors and clustered metabolic risk. RESULTS: Each additional 1 h of SED-time was positively associated with clustered metabolic risk, independently of sleep duration and MVPA (ß = 0.16 [95% CI 0.03, 0.29]). After accounting for SED-time, MVPA was associated with systolic blood pressure (ß = -2.07 [-4.03, -0.11]) but not with clustered metabolic risk (ß = 0.01 [-0.28, 0.30]). PAEE and cardiorespiratory fitness were significantly and independently inversely associated with clustered metabolic risk (ß = -0.03 [-0.05, -0.02] and ß = -0.06 [-0.10, -0.03], respectively). Associations between SED-time and metabolic risk were generally stronger in the low compared with the high fitness group. CONCLUSIONS/INTERPRETATION: PAEE was inversely associated with metabolic risk, whereas SED-time was positively associated with metabolic risk. MVPA was not associated with clustered metabolic risk after accounting for SED-time. Encouraging this high-risk group to decrease SED-time, particularly those with low cardiorespiratory fitness, and increase their overall physical activity may have beneficial effects on disease progression and reduction of cardiovascular risk. TRIAL REGISTRATION: ISRCTN99175498.

Electronic health record-based patient identification and individualized mailed outreach for primary cardiovascular disease prevention: a cluster randomized trial.

BACKGROUND: Many individuals at higher risk for cardiovascular disease (CVD) do not receive recommended treatments. Prior interventions using personalized risk information to promote prevention did not test clinic-wide effectiveness. OBJECTIVE AND DESIGN: To perform a 9-month cluster-randomized trial, comparing a strategy of electronic health record-based identification of patients with increased CVD risk and individualized mailed outreach to usual care. PARTICIPANTS: Patients of participating physicians with a Framingham Risk Score of at least 5 %, low-density lipoprotein (LDL)-cholesterol level above guideline threshold for drug treatment, and not prescribed a lipid-lowering medication were included in the intention-to-treat analysis. INTERVENTION: Patients of physicians randomized to the intervention group were mailed individualized CVD risk messages that described benefits of using a statin (and controlling hypertension or quitting smoking when relevant). MAIN MEASURES: The primary outcome was occurrence of a LDL-cholesterol level, repeated in routine practice, that was at least 30 mg/dl lower than prior. A secondary outcome was lipid-lowering drug prescribing. Clinicaltrials.gov identifier: NCT01286311. KEY RESULTS: Fourteen physicians with 218 patients were randomized to intervention, and 15 physicians with 217 patients to control. The mean patient age was 60.7 years and 77% were male. There was no difference in the primary outcome (11.0 % vs. 11.1 %, OR 0.99, 95 % CI 0.56-1.74, P = 0.96), but intervention group patients were twice as likely to receive a prescription for lipid-lowering medication (11.9 %, vs. 6.0 %, OR 2.13, 95 % CI 1.05-4.32, p = 0.038). In post hoc analysis with extended follow-up to 18 months, the primary outcome occurred more often in the intervention group (22.5 % vs. 16.1 %, OR 1.59, 95 % CI 1.05-2.41, P = 0.029). CONCLUSIONS: In this effectiveness trial, individualized mailed CVD risk messages increased the frequency of new lipid-lowering drug prescriptions, but we observed no difference in proportions lowering LDL-cholesterol after 9 months. With longer follow-up, the intervention's effect on LDL-cholesterol levels was apparent.

Primary care delivery of behavioral weight loss services for adults with cardiovascular risk factors: development of pragmatic practice components and results of a randomized feasibility trial.

Background: Intensive lifestyle interventions (ILI) improve weight loss and cardiovascular risk factors, but health systems face challenges implementing them. We engaged stakeholders to cocreate and evaluate feasibility of primary care implementation strategies and of a pragmatic randomization procedure to be used for a future effectiveness trial. Methods: The study setting was a single, urban primary care office. Patients with BMI ≥ 27 and ≥ 1 cardiovascular risk factor were sent a single electronic health record (EHR) message between December 2019 and January 2020 offering services to support an initial weight loss goal of about 10 pounds in 10 weeks. All patients who affirmed weight loss interest were pragmatically enrolled in the trial and offered "Basic Lifestyle Services" (BLS), including a scale that transmits weight data to the EHR using cellular networks, a coupon to enroll in lifestyle coaching resources through a partnering fitness organization, and periodic EHR messages encouraging use of these resources. About half (n = 42) of participants were randomized by an automated EHR algorithm to also receive "Customized Lifestyle Services" (CLS), including weekly email messages adapted to individual weight loss progress and telephonic coaching by a nurse for those facing challenges. Interventions and assessments spanned January to July 2020, with interference by the coronavirus pandemic. Weight measures were collected from administrative sources. Qualitative analysis of stakeholder recommendations and patient interviews assessed acceptability, appropriateness, and sustainability of intervention components. Results: Over 6 weeks, 426 patients were sent the EHR invitation message and 80 (18.8%) affirmed interest in the weight loss goal and were included for analysis. EHR data were available to ascertain a 6-month weight value for 77 (96%) patients. Overall, 62% of participants lost weight; 15.0% exhibited weight loss ≥ 5%, with no statistically significant difference between CLS or BLS arms (p = 0.85). CLS assignment increased participation in daily self-weighing (43% versus 21% of patients through 12 weeks) and enrollment in referral-based lifestyle support resources (52% versus 37%). Conclusions: This preliminary study demonstrates feasibility of implementation strategies for primary care offices to offer and coordinate ILI core components, as well as a pragmatic randomization procedure for use in a future randomized comparative trial.

Treatment modification after initiating second-line medication for type 2 diabetes.

OBJECTIVES: To describe changes in antidiabetic medication (ADM) use and characteristics associated with changes in ADM use after initiation of noninsulin second-line therapy. STUDY DESIGN: Retrospective cohort study. METHODS: This study analyzed private health plan claims for adults with type 2 diabetes who initiated 1 of 5 index ADM classes: sulfonylureas, dipeptidyl peptidase 4 inhibitors (DPP4is), sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), or thiazolidinediones. Analyses evaluated 3 treatment modification outcomes-discontinuation, switching, and intensification-over 12-month follow-up. RESULTS: Of 82,624 included adults, nearly two-thirds (63.6%) experienced any treatment modification. Discontinuation was the most common modification (38.6%), especially among patients prescribed GLP-1 RAs (50.3%). Switching occurred in 5.2% of patients and intensification in 19.8%. In adjusted analysis, compared with patients prescribed sulfonylureas, discontinuation risk was 7% higher (HR, 1.07; 95% CI, 1.04-1.10) among patients prescribed DPP4is and 28% higher (HR, 1.28; 95% CI, 1.23-1.33) among patients prescribed GLP-1 RAs. Compared with sulfonylureas, all other index ADM classes had higher risks of switching and lower risks of intensification. Younger age group and female sex were both associated with higher risks of all modifications. Compared with index ADM prescription by a family medicine or internal medicine physician, index prescription by an endocrinologist was associated with both lower discontinuation risk and higher intensification risk. CONCLUSIONS: Most patients experienced a treatment modification within 1 year. Results highlight the need for new prescribing approaches and patient supports that can maximize medication adherence and reduce health system waste.