Social Risks and Health Care Use in Medically Complex Patients.

Importance: Integrated health care systems have initiated major investments to identify and address social risks, particularly for patients with multiple medical conditions. Objective: To evaluate the association of social risks with health care use among patients with complex multimorbidity. Design, Setting, and Participants: This longitudinal cohort study assessed Kaiser Permanente Northern California (KPNC) patients with (1) moderate medical complexity (defined by high comorbidity score, high risk of hospitalization, and/or prior emergency department [ED] admissions) and (2) high medical complexity (eg, meeting additional criteria, such as ≥7 medications and laboratory evidence of poor disease control). Exposure: Social risks (eg, requiring medical financial assistance and self-reported social barriers to care). Main Outcomes and Measures: Inpatient and outpatient health care use during 12 months of follow-up (January 15, 2023, to January 14, 2024). Results: The sample included 97 252 KPNC patients (mean [SD] age, 69.5 [16] years; 52.1% female; 10.6% Asian, 11.1% Black, 18.3% Hispanic, 54.6% White, and 5.5% other race or ethnicity [eg, American Indian or Alaskan Native, Native Hawaiian or Pacific Islander, multiracial, or unknown race]; and 8.8% insured by Medicaid), including 27 827 with moderate medical complexity (5074 [18.2%] with social risks) and 69 425 with high medical complexity (17 343 [25.0%] with social risks). In fully adjusted models, for moderate medical complexity, social risks were associated with higher odds of inpatient admissions (odds ratio [OR], 1.2; 95% CI, 1.1-1.4), ED visits (OR, 1.2; 95% CI, 1.1-1.3), and mental health visits (OR, 1.2; 95% CI, 1.1-1.3) vs individuals without social risks. Among individuals with high medical complexity, social risks were associated with higher odds of inpatient admissions (OR, 1.2; 95% CI, 1.1-1.2), ED visits (OR, 1.2; 95% CI, 1.1-1.2), and 30-day readmissions (OR, 1.2; 95% CI, 1.1-1.3) and higher odds of mental health visits (OR, 1.3; 95% CI, 1.2-1.3) vs individuals without social risks. Conclusions and relevance: In this cohort study of individuals with medical complexity, coexisting social risks were associated with substantial downstream health care use. Efforts to reduce use in individuals with complex medical comorbidity could include concurrent efforts to identify and reduce social risks.

The Percentage of Patients Experiencing Financial Strain Depends on the Screening Measure: Evidence From a Cross-Sectional Survey of Adult Members of an Integrated Healthcare Delivery System.

OBJECTIVES: Financial strain has important consequences for patients, providers, and health care systems. However, there is currently no gold standard measure to screen for financial strain. This study compared the performance of 3 single-item screeners using a composite measure of financial strain as a "gold standard." METHODS: We conducted a secondary analysis of unweighted data from a 2021 survey of Kaiser Permanente Northern California health plan members comparing the percentages of adults who experienced financial strain based on 3 general single-item screeners, a screener specific to medical and dental health care use, and a composite financial strain measure. The study sample was comprised of 2734 non-Medicaid insured adults who answered all financial strain questions. Kappa statistics evaluating agreement of the 3 general screeners with the composite measure were calculated for the sample overall, by age group, and within age group, by 4 levels of income and 4 racial/ethnic subgroups. RESULTS: Among 947 adults aged 35 to 65, 30.7% had just enough money or not enough money to make ends meet, 23.3% had a somewhat hard or hard time paying for basics, 18.8% had trouble paying for ≥1 type of expense, 20.5% had delayed/used less medical/dental care, and 41.5% had experienced financial strain based on the composite measure. Among 1787 adults aged 66 to 85, the percentages who screened positive on these measures were 22.7%, 19.4%, 12.9%, 19.8%, and 34.4%, respectively. Across the sample, by income categories and racial/ethnic groups, the making ends meet screener identified higher percentages of adults experiencing financial strain and performed better when compared with the composite measure than the hard to pay for the very basics and trouble paying for expenses screeners. Overall, substantial decreases in the percentages of adults who screened positive on the financial strain measures were seen as level of income increased. Within income categories, middle-aged adults were more likely than older adults to have experienced financial strain based on the composite and general single-item screeners. CONCLUSIONS: As social risk screening becomes part of the standard of care, it will be important to assess how well different brief screeners for financial strain perform with diverse patient populations.

Pharmacokinetics and pharmacodynamics of PTC518, an oral huntingtin lowering splicing modifier: A first-in-human study.

AIMS: PTC518 is an orally administered, centrally and peripherally distributed huntingtin (HTT) pre-mRNA splicing modifier being developed for the treatment of Huntington's disease (HD) for which there is a high unmet medical need as there are currently no approved disease-modifying treatments. This first-in-human study investigated the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of PTC518 in healthy volunteers. METHODS: This phase 1, single-centre, randomized study in 77 healthy male and female volunteers evaluated the safety and tolerability and PK of PTC518 following single ascending doses and multiple ascending doses, PD as assessed by HTT mRNA and HTT protein levels after single and multiple doses, and food effects. RESULTS: PTC518 demonstrated a favourable safety profile. The majority of treatment-emergent adverse events were mild and transient. PTC518 Tmax was reached at 6-7 h and the terminal T1/2 was 54.0-75.3 h following a single oral dose. Exposure increased with dose though less than dose proportionally. The PTC518 concentrations in cerebrospinal fluid were approximately 2.6-fold higher than the unbound free-drug concentrations in plasma. A significant dose-dependent reduction of up to approximately 60% in HTT mRNA and a significant dose-dependent, time-dependent and sustained reduction in HTT protein levels of up to 35% were observed after PTC518 treatment. CONCLUSIONS: PTC518 was well tolerated, and proof of mechanism of this novel splicing modifier was demonstrated by the dose-dependent decrease in systemic HTT mRNA and HTT protein levels. Results from this first-in-human study support further studies in patients with HD and demonstrate the potential for PTC518 as a breakthrough treatment for HD.

Association between frailty and overall survival among older adults with hepatocellular carcinoma.

INTRODUCTION: Older adults undergoing cancer treatment often experience more treatment-related toxicities and increased risk of mortality compared to younger patients. The role of frailty among older individuals as a predictor of outcomes has gained growing significance. We evaluated the association between frailty and overall survival (OS) in patients with hepatocellular carcinoma (HCC) ≥60 years. MATERIALS AND METHODS: Older adults ≥60 years with HCC enrolled in a prospective single-institution registry underwent a patient-reported geriatric assessment (GA) covering multiple health domains related to prior to their initial medical oncology appointment. Frailty was measured using a 44-item deficit accumulation frailty index. We categorized patients as robust, pre-frail, and frail using standard cutpoints. The primary outcome was overall survival (OS). Univariable and multivariable models were built to evaluate the association between frailty and OS after adjusting for potential confounders. RESULTS: Total of 116 older adults with HCC with a median age of 67 years were enrolled; 82% male, 27% Black, and 78% with stage III/IV disease. Overall, 19 (16.3%) were robust, 39 (33.6%) pre-frail, and 58 (50.1%) frail. There were 76 patients receiving liver directed therapy. Of these, 13 (17%) were robust, 26 (34%) were pre-frail, and 37 (49%) were frail. Over a median follow up of 0.9 years, 53 patients died. After adjusting for age, stage, etiology, and Child-Pugh class, being frail (vs. robust) was associated with worse OS (hazard ratio (HR) 2.6 [95% CI 1.03-6.56]; p = 0.04). DISCUSSION: Half of the participants in this study were frail, which was independently associated with worse survival in adults ≥60 years of age with HCC. Identification of pre-treatment frailty may allow opportunities to guide treatment decisions and prognostication.

Rationale and design of the KP ENRICH trial: A food is medicine intervention in low-income high-risk adults with diabetes within Kaiser Permanente.

BACKGROUND: Food insecurity is associated with poor glycemic control and increased risk for diabetes-related complications. The clinical benefit of addressing these challenges through a medically supportive grocery prescription (GRx) program in patients with type 2 diabetes mellitus (T2D) remains unclear. We report the aims and design of a randomized clinical trial to evaluate the effectiveness of a 6-month GRx intervention on hemoglobin A1c (HbA1c) levels among low-income adults with T2D. METHODS: The Kaiser Permanente Evaluating Nutritional Interventions in Food-Insecure High-Risk Adults (KP ENRICH) Study is a pragmatic randomized trial enrolling 1100 participants within Kaiser Permanente Northern California and Southern California, two integrated health care delivery systems serving >9 million members. Medicaid-insured adults with T2D and baseline HbA1c ≥7.5% will be randomized at a 1:1 ratio to either GRx, delivered as $100 per month for select items from among a curated list of healthful food groups in an online grocery ordering and home-delivery platform along with biweekly digital nutrition educational materials, or control, consisting of free membership and deliveries from the online grocery platform but without curated food groups or purchasing dollars. The primary outcome is 6-month change in HbA1c. Secondary outcomes include 12-month change in HbA1c, and 6- and 12-month change in medical resource utilization, food security, nutrition security, dietary habits, diabetes-related quality of life, and dietary self-efficacy. CONCLUSIONS: The results of this large randomized clinical trial of GRx will help inform future policy and health system-based initiatives to improve food and nutrition security, disease management, and health equity among patients with T2D.

Predicting Self-Reported Social Risk in Medically Complex Adults Using Electronic Health Data.

BACKGROUND: Social barriers to health care, such as food insecurity, financial distress, and housing instability, may impede effective clinical management for individuals with chronic illness. Systematic strategies are needed to more efficiently identify at-risk individuals who may benefit from proactive outreach by health care systems for screening and referral to available social resources. OBJECTIVE: To create a predictive model to identify a higher likelihood of food insecurity, financial distress, and/or housing instability among adults with multiple chronic medical conditions. RESEARCH DESIGN AND SUBJECTS: We developed and validated a predictive model in adults with 2 or more chronic conditions who were receiving care within Kaiser Permanente Northern California (KPNC) between January 2017 and February 2020. The model was developed to predict the likelihood of a "yes" response to any of 3 validated self-reported survey questions related to current concerns about food insecurity, financial distress, and/or housing instability. External model validation was conducted in a separate cohort of adult non-Medicaid KPNC members aged 35-85 who completed a survey administered to a random sample of health plan members between April and June 2021 (n = 2820). MEASURES: We examined the performance of multiple model iterations by comparing areas under the receiver operating characteristic curves (AUCs). We also assessed algorithmic bias related to race/ethnicity and calculated model performance at defined risk thresholds for screening implementation. RESULTS: Patients in the primary modeling cohort (n = 11,999) had a mean age of 53.8 (±19.3) years, 64.7% were women, and 63.9% were of non-White race/ethnicity. The final, simplified model with 30 predictors (including utilization, diagnosis, behavior, insurance, neighborhood, and pharmacy-based variables) had an AUC of 0.68. The model remained robust within different race/ethnic strata. CONCLUSIONS: Our results demonstrated that a predictive model developed using information gleaned from the medical record and from public census tract data can be used to identify patients who may benefit from proactive social needs assessment. Depending on the prevalence of social needs in the target population, different risk output thresholds could be set to optimize positive predictive value for successful outreach. This predictive model-based strategy provides a pathway for prioritizing more intensive social risk outreach and screening efforts to the patients who may be in greatest need.

Effectiveness of supervised versus self-directed rehabilitation for adults aged 50 years and over with ankle fractures: protocol for the AFTER trial.

Aims: Ankle fractures are common, mainly affecting adults aged 50 years and over. To aid recovery, some patients are referred to physiotherapy, but referral patterns vary, likely due to uncertainty about the effectiveness of this supervised rehabilitation approach. To inform clinical practice, this study will evaluate the effectiveness of supervised versus self-directed rehabilitation in improving ankle function for older adults with ankle fractures. Methods: This will be a multicentre, parallel-group, individually randomized controlled superiority trial. We aim to recruit 344 participants aged 50 years and older with an ankle fracture treated surgically or non-surgically from at least 20 NHS hospitals. Participants will be randomized 1:1 using a web-based service to supervised rehabilitation (four to six one-to-one physiotherapy sessions of tailored advice and prescribed home exercise over three months), or self-directed rehabilitation (provision of advice and exercise materials that participants will use to manage their recovery independently). The primary outcome is participant-reported ankle-related symptoms and function six months after randomization, measured by the Olerud and Molander Ankle Score. Secondary outcomes at two, four, and six months measure health-related quality of life, pain, physical function, self-efficacy, exercise adherence, complications, and resource use. Due to the nature of the interventions, participants and intervention providers will be unblinded to treatment allocation. Conclusion: This study will assess whether supervised rehabilitation is more effective than self-directed rehabilitation for adults aged 50 years and older after ankle fracture. The results will provide evidence to guide clinical practice. At the time of submission, the trial is currently completing recruitment, and follow-up will be completed in 2024.

Food Insecurity and Hypoglycemia among Older Patients with Type 2 Diabetes Treated with Insulin or Sulfonylureas: The Diabetes & Aging Study.

BACKGROUND: Severe hypoglycemia is a serious adverse drug event associated with hypoglycemia-prone medications; older patients with diabetes are particularly at high risk. Economic food insecurity (food insecurity due to financial limitations) is a known risk factor for hypoglycemia; however, less is known about physical food insecurity (due to difficulty cooking or shopping for food), which may increase with age, and its association with hypoglycemia. OBJECTIVE: Study associations between food insecurity and severe hypoglycemia. DESIGN: Survey based cross-sectional study. PARTICIPANTS: Survey responses were collected in 2019 from 1,164 older (≥ 65 years) patients with type 2 diabetes treated with insulin or sulfonylureas. MAIN MEASURES: Risk ratios (RR) for economic and physical food insecurity associated with self-reported severe hypoglycemia (low blood glucose requiring assistance) adjusted for age, financial strain, HbA1c, Charlson comorbidity score and frailty. Self-reported reasons for hypoglycemia endorsed by respondents. KEY RESULTS: Food insecurity was reported by 12.3% of the respondents; of whom 38.4% reported economic food insecurity only, 21.1% physical food insecurity only and 40.5% both. Economic food insecurity and physical food insecurity were strongly associated with severe hypoglycemia (RR = 4.3; p = 0.02 and RR = 4.4; p = 0.002, respectively). Missed meals ("skipped meals, not eating enough or waiting too long to eat") was the dominant reason (77.5%) given for hypoglycemia. CONCLUSIONS: Hypoglycemia prevention efforts among older patients with diabetes using hypoglycemia-prone medications should address food insecurity. Standard food insecurity questions, which are used to identify economic food insecurity, will fail to identify patients who have physical food insecurity only.

Managing Multiple Chronic Conditions during COVID-19 Among Patients with Social Health Risks.

BACKGROUND: Optimal care for persons with multiple chronic conditions (MCC) requires primary and specialty care continuity, access to multiple providers, social risk assessment, and self-management support. The COVID-19 pandemic abruptly changed primary care delivery to increase reliance on telehealth and virtual care. We report on the experiences of individuals with MCC and their family caregivers on managing their health and receiving health care during the initial pandemic. METHODS: Semistructured qualitative interviews with 30 patients (19 English speaking, 11 Spanish speaking) plus 9 accompanying care partners, who had 2+ primary care encounters between March 1, 2020, and November 30, 2020, 2+ chronic conditions, and 1 or more self-reported social risks. Questions focused on access to and experiences with care, roles for care partners, and self-management during the first 6 months of the pandemic. RESULTS: Participants experienced substantial changes in care delivery. The most commonly reported changes were a shift to more virtual relative to in-person care and shifting roles for care partners. Changes fostered new perspectives on self-management and an appreciation of personal resilience and self-reliance. Virtual care was an acceptable complement to in-person care, though not a substitute for periodic in-person visits. It was more acceptable for English speakers and with a usual provider. CONCLUSION: New models of care delivery that recognize patient and family resilience and resourcefulness, emphasize provider continuity, and combine virtual and in-person care may support self-management for individuals with MCC and social needs.

Willingness to take less medication for type 2 diabetes among older patients: The Diabetes & Aging Study.

BACKGROUND: To examine the willingness of older patients to take less diabetes medication (de-intensify) and to identify characteristics associated with willingness to de-intensify treatment. METHODS: Survey conducted in 2019 in an age-stratified, random sample of older (65-100 years) adults with diabetes on glucose-lowering medications in the Kaiser Permanente Northern California Diabetes Registry. We classified survey responses to the question: "I would be willing to take less medication for my diabetes" as willing, neutral, or unwilling to de-intensify. Willingness to de-intensify treatment was examined by several clinical characteristics, including American Diabetes Association (ADA) health status categories used for individualizing glycemic targets. Analyses were weighted to account for over-sampling of older individuals. RESULTS: A total of 1337 older adults on glucose-lowering medication(s) were included (age 74.2 ± 6.0 years, 44% female, 54.4% non-Hispanic white). The proportions of participants willing, neutral, or unwilling to take less medication were 51.2%, 27.3%, and 21.5%, respectively. Proportions of willing to take less medication varied by age (65-74 years: 54.2% vs. 85+ years: 38.5%) and duration of diabetes (0-4 years: 61.0% vs. 15+ years: 44.2%), both p < 0.001. Patients on 1-2 medications were more willing to take less medication(s) compared with patients on 10+ medications (62.1% vs. 46.6%, p = 0.03). Similar proportions of willingness to take less medications were seen across ADA health status, and HbA1c. Willingness to take less medication(s) was similar across survey responses to questions about patient-clinician relationships. CONCLUSIONS: Clinical guidelines suggest considering treatment de-intensification in older patients with longer duration of diabetes, yet patients with these characteristics are less likely to be willing to take less medication(s).

Training the next generation of delivery science researchers: 10-year experience of a post-doctoral research fellowship program within an integrated care system.

Introduction: Learning health systems require a workforce of researchers trained in the methods of identifying and overcoming barriers to effective, evidence-based care. Most existing postdoctoral training programs, such as NIH-funded postdoctoral T32 awards, support basic and epidemiological science with very limited focus on rigorous delivery science methods for improving care. In this report, we present the 10-year experience of developing and implementing a Delivery Science postdoctoral fellowship embedded within an integrated health care delivery system. Methods: In 2012, the Kaiser Permanente Northern California Division of Research designed and implemented a 2-year postdoctoral Delivery Science Fellowship research training program to foster research expertise in identifying and addressing barriers to evidence-based care within health care delivery systems. Results: Since 2014, 20 fellows have completed the program. Ten fellows had PhD-level scientific training, and 10 fellows had clinical doctorates (eg, MD, RN/PhD, PharmD). Fellowship alumni have graduated to faculty research positions at academic institutions (9), and research or clinical organizations (4). Seven alumni now hold positions in Kaiser Permanente's clinical operations or medical group (7). Conclusions: This delivery science fellowship program has succeeded in training graduates to address delivery science problems from both research and operational perspectives. In the next 10 years, additional goals of the program will be to expand its reach (eg, by developing joint research training models in collaboration with clinical fellowships) and strengthen mechanisms to support transition from fellowship to the workforce, especially for researchers from underrepresented groups.

Severe hypoglycemia and falls in older adults with diabetes: The Diabetes & Aging Study.

Objective: To estimate rates of severe hypoglycemia and falls among older adults with diabetes and evaluate their association. Research Design and Methods: Survey in an age-stratified, random sample adults with diabetes age 65-100 years; respondents were asked about severe hypoglycemia (requiring assistance) and falls in the past 12 months. Prevalence ratios (adjusted for age, sex, race/ethnicity) estimated the increased risk of falls associated with severe hypoglycemia. Results: Among 2,158 survey respondents, 79 (3.7%) reported severe hypoglycemia, of whom 68 (86.1%) had no ED visit or hospitalization for hypoglycemia. Falls were reported by 847 (39.2%), of whom 745 (88.0%) had no fall documented in outpatient or inpatient records. Severe hypoglycemia was associated with a 70% greater prevalence of falls (adjusted prevalence ratio = 1.7 (95% CI, 1.3-2.2)). Conclusion: While clinical documentation of events likely reflects severity or care-seeking behavior, severe hypoglycemia and falls are common, under-reported life-threatening events.

Telephone-based social health screening by pharmacists in the nonadherent Medicare population.

BACKGROUND: Unmet social health needs are associated with medication nonadherence. Although pharmacists are well positioned to address medication nonadherence, there is limited experience with screening for and addressing social health needs. OBJECTIVES: To compare the prevalence of social health needs among Medicare patients with higher vs lower social health risk using a predictive model. To also evaluate pre-post changes in medication adherence and health care use following a pharmacist-initiated social health screening. METHODS: A social health screening workflow was implemented into a routine pharmacist adherence program at an integrated health care delivery system. The social health screening was conducted during medication adherence outreach phone calls with Medicare members who were overdue for statin, blood pressure, or diabetes medications. We developed a social health need predictive algorithm to flag higher-risk patients and tested this algorithm against a random subset of lower-risk patients. Screening conversations were guided by a focus group that developed open-ended questions to identify social health needs. Comparisons in social health needs were made between higher- and lower-risk patients. Use and adherence outcomes were compared pre and post for patients who accepted a referral to social health resources and patients who declined a referral. RESULTS: 1,217 patients were contacted and screened for social health needs by pharmacists. Patients flagged by the social risk algorithm were more likely to report social health needs (28.7% vs 12.7% in the unflagged group; P < 0.01). Commonly reported needs included transportation (43%), finances (34%), caregiving (22%), mental health (11%), and food access (10%). 221 patients accepted a referral to a central resource website and call center that connected patients to local services. One year after screening dates, patients who did not accept a referral spent more time in the hospital (mean change +0.7 days, SD = 7.3, P < 0.01), had fewer primary care visits (mean change -0.5 visits, SD = 6.5, P < 0.01), and had a shorter length of membership (mean change -0.4 months, SD = 1.9, P < 0.01). Patients who accepted a referral had increased statin adherence (62.3% adherent pre vs 74.7% post, P = 0.02). CONCLUSIONS: We implemented a workflow for pharmacists to screen for social health needs. The social health need prediction model doubled the identification rate of patients who have needs. Intervening on social health needs during these calls may improve statin adherence and may have no adverse effect on health care utilization or health plan membership. DISCLOSURES: Social health risk predictive model development and validation was funded by the Agency for Healthcare Research and Quality (AHRQ R18HS027343).

Development of a rapid lateral flow assay for detection of anti-coccidioidal antibodies.

Coccidioides spp. are dimorphic fungi that are capable of infecting human and non-human mammals and can cause diverse manifestations of coccidioidomycosis or Valley fever (VF). In combination with clinical symptoms and radiographic findings, antibody-based diagnostic tests are often used to diagnose and monitor patients with VF. Chitinase 1 (CTS1) has previously been identified as the seroreactive antigen used in these diagnostic assays to detect anticoccidial IgG. Here, an indirect enzyme-linked immunosorbent assay to detect IgG to CTS1 demonstrated 165 of 178 (92.7%) patients with a positive result by immunodiffusion (ID) and/or complement fixation (CF) had antibodies to the single antigen CTS1. We then developed a rapid antibody lateral flow assay (LFA) to detect anti-CTS1 antibodies. Out of 143 samples tested, the LFA showed 92.9% positive percent agreement [95% confidence interval (CI), 84.3%-96.9%] and 97.7% negative percent agreement (95% CI, 87.9%-99.6%) with ID and CF assays. Serum or plasma from canines, macaques, and dolphins was also tested by the CTS1 LFA. Test line densities of the CTS1 LFA correlated in a linear manner with the reported CF and ID titers for human and non-human samples, respectively. This 10-min point-of-care test for the rapid detection of anti-coccidioidal antibodies could help to inform healthcare providers in real-time, potentially improving the efficiency of healthcare delivery.

Glycemic control and diabetes complications across health status categories in older adults treated with insulin or insulin secretagogues: The Diabetes & Aging Study.

BACKGROUND: For older adults with type 2 diabetes (T2D) treated with insulin or sulfonylureas, Endocrine Society guideline recommends HbA1c between 7% to <7.5% for those in good health, 7.5% to <8% for those in intermediate health, and 8% to <8.5% for those in poor health. Our aim was to examine associations between attained HbA1c below, within (reference), or above recommended target range and risk of complication or mortality. METHODS: Retrospective cohort study of adults ≥65 years old with T2D treated with insulin or sulfonylureas from an integrated healthcare delivery system. Cox proportional hazards models of complications during 2019 were adjusted for sociodemographic and clinical variables. Primary outcome was a combined outcome of any microvascular or macrovascular event, severe hypoglycemia, or mortality during 12-month follow-up. RESULTS: Among 63,429 patients (mean age: 74.2 years, 46.8% women), 8773 (13.8%) experienced a complication. Complication risk was significantly elevated for patients in good health (n = 16,895) whose HbA1c was above (HR 1.97, 95% CI 1.62-2.41) or below (HR 1.29, 95% CI 1.02-1.63) compared to within recommended range. Among those in intermediate health (n = 30,129), complication risk was increased for those whose HbA1c was above (HR 1.45, 95% CI 1.30-1.60) but not those below the recommended range (HR 0.99, 95% CI 0.89-1.09). Among those in poor health (n = 16,405), complication risk was not significantly different for those whose HbA1c was below (HR 0.98, 95% CI 0.89-1.09) or above (HR 0.96, 95% CI 0.88-1.06) recommended range. CONCLUSIONS: For older adults with T2D in good health, HbA1c below or above the recommended range was associated with significantly elevated complication risk. However, for those in poor health, achieving specific HbA1c levels may not be helpful in reducing the risk of complications.

Evaluation of the immunogenicity and efficacy of an rVSV vaccine against Zika virus infection in macaca nemestrina.

Zika virus (ZIKV) is a mosquito-borne flavivirus that causes an acute febrile illness. ZIKV can be transmitted between sexual partners and from mother to fetus. Infection is strongly associated with neurologic complications in adults, including Guillain-Barré syndrome and myelitis, and congenital ZIKV infection can result in fetal injury and congenital Zika syndrome (CZS). Development of an effective vaccine is imperative to protect against ZIKV vertical transmission and CZS. Recombinant Vesicular Stomatitis virus (rVSV) is a highly effective and safe vector for the delivery of foreign immunogens for vaccine purposes. Here, we evaluate an rVSV vaccine expressing the full length pre-membrane (prM) and ZIKV envelope (E) proteins (VSV-ZprME), shown to be immunogenic in murine models of ZIKV infection, for its capacity to induce immune responses in nonhuman primates. Moreover, we assess the efficacy of the rVSVΔM-ZprME vaccine in the protection of pigtail macaques against ZIKV infection. Administration of the rVSVΔM-ZprME vaccine was safe, but it did not induce robust anti-ZIKV T-cell responses, IgM or IgG antibodies, or neutralizing antibodies in most animals. Post ZIKV challenge, animals that received the rVSVΔM control vaccine lacking ZIKV antigen had higher levels of plasma viremia compared to animals that received the rVSVΔM-ZprME vaccine. Anti-ZIKV neutralizing Ab titers were detected in a single animal that received the rVSVΔM-ZprME vaccine that was associated with reduced plasma viremia. The overall suboptimal ZIKV-specific cellular and humoral responses post-immunization indicates the rVSVΔM-ZprME vaccine did not elicit an immune response in this pilot study. However, recall antibody response to the rVSVΔM-ZprME vaccine indicates it may be immunogenic and further developments to the vaccine construct could enhance its potential as a vaccine candidate in a nonhuman primate pre-clinical model.

Development and Validation of the Life Expectancy Estimator for Older Adults with Diabetes (LEAD): the Diabetes and Aging Study.

BACKGROUND: Estimated life expectancy for older patients with diabetes informs decisions about treatment goals, cancer screening, long-term and advanced care, and inclusion in clinical trials. Easily implementable, evidence-based, diabetes-specific approaches for identifying patients with limited life expectancy are needed. OBJECTIVE: Develop and validate an electronic health record (EHR)-based tool to identify older adults with diabetes who have limited life expectancy. DESIGN: Predictive modeling based on survival analysis using Cox-Gompertz models in a retrospective cohort. PARTICIPANTS: Adults with diabetes aged ≥ 65 years from Kaiser Permanente Northern California: a 2015 cohort (N = 121,396) with follow-up through 12/31/2019, randomly split into training (N = 97,085) and test (N = 24,311) sets. Validation was conducted in the test set and two temporally distinct cohorts: a 2010 cohort (n = 89,563; 10-year follow-up through 2019) and a 2019 cohort (n = 152,357; 2-year follow-up through 2020). MAIN MEASURES: Demographics, diagnoses, utilization and procedures, medications, behaviors and vital signs; mortality. KEY RESULTS: In the training set (mean age 75 years; 49% women; 48% racial and ethnic minorities), 23% died during 5 years follow-up. A mortality prediction model was developed using 94 candidate variables, distilled into a life expectancy model with 11 input variables, and transformed into a risk-scoring tool, the Life Expectancy Estimator for Older Adults with Diabetes (LEAD). LEAD discriminated well in the test set (C-statistic = 0.78), 2010 cohort (C-statistic = 0.74), and 2019 cohort (C-statistic = 0.81); comparisons of observed and predicted survival curves indicated good calibration. CONCLUSIONS: LEAD estimates life expectancy in older adults with diabetes based on only 11 patient characteristics widely available in most EHRs and claims data. LEAD is simple and has potential application for shared decision-making, clinical trial inclusion, and resource allocation.

Social Risks, Social Needs, and Attitudes Toward Social Health Screening 1 Year Into the COVID-19 Pandemic: Survey of Adults in an Integrated Health Care Delivery System.

Introduction Information about demographic differences in social risks, needs, and attitudes toward social health screening in non-highly vulnerable adult populations is lacking. Methods The authors analyzed data for 2869 Kaiser Permanente Northern California non-Medicaid-covered members aged 35 to 85 who responded to a 2021 English-only mailed/online survey. The survey covered 7 social risk and 11 social needs domains and attitudes toward social health screening. The authors used data weighted to the Kaiser Permanente Northern California membership to estimate prevalence of risks, needs, and screening receptivity in the overall population, by race/ethnicity (White, Black, Latinx, Asian American/Pacific Islander) and age (35-65 years old, 66-85 years old). Multivariable regression was used to evaluate differences between groups. Results Overall, 26% of adults were financially strained, 12% food insecure, 12% housing insecure, and 5% transportation insecure. Additionally, 7%, 8%, and 17% had difficulty paying for utilities, medical expenses, and dental care, respectively. Over 40% of adults wanted help with ≥ 1 social need. Dental care, vision/hearing care, paying for medical expenses and utilities, and managing debt/credit card repayment surpassed food, housing, and transportation needs. Prevalence of social risks and needs was generally higher among middle-aged versus older and Black and Latinx versus White adults. Among the 70% of adults receptive to screening, 85% were willing to complete a questionnaire and 40% were willing to have staff ask questions; 18% did not want to be screened. Conclusion When implementing social health screening in diverse patient populations, the prevalence of social risks and needs, as well as the acceptability of social health screening and screening modalities, will vary among demographic subgroups.

Understanding patient experience of distal tibia or ankle fracture: a qualitative systematic review.

To systematically review qualitative studies of patients with distal tibia or ankle fracture, and explore their experience of injury and recovery. We undertook a systematic review of qualitative studies. Five databases were searched from inception to 1 February 2022. All titles and abstracts were screened, and a subset were independently assessed. Methodological quality was appraised using the Critical Appraisal Skills Programme (CASP) checklist. The GRADE-CERQual checklist was used to assign confidence ratings. Thematic synthesis was used to analyze data with the identification of codes which were drawn together to form subthemes and then themes. From 2,682 records, 15 studies were reviewed in full and four included in the review. A total of 72 patients were included across the four studies (47 female; mean age 50 years (17 to 80)). Methodological quality was high for all studies, and the GRADE-CERQual checklist provided confidence that the findings were an adequate representation of patient experience of distal tibia or ankle fracture. A central concept of 'being the same but different' conveyed the substantial disruption to patients' self-identity caused by their injury. Patient experience of 'being the same but different' was expressed through three interrelated themes, with seven subthemes: i) being proactive where persistence, doing things differently and keeping busy prevailed; ii) living with change including symptoms, and living differently due to challenges at work and leisure; and iii) striving for normality, adapting while lacking in confidence, and feeling fearful and concerned about the future. Ankle injuries were disruptive, draining, and impacted on patients' wellbeing. Substantial short- and longer-term challenges were experienced during recovery. Rehabilitation and psychosocial treatment strategies may help to ameliorate these challenges. Patients may benefit from clinicians being cognisant of patient experience when assessing, treating, and discussing expectations and outcomes with patients.