Pragmatic trial evaluating the impact of simulation training on high-risk prescribing to older adults by junior physicians.

BACKGROUND: High-risk medications like benzodiazepines, sedative hypnotics, and antipsychotics are commonly prescribed for hospitalized older adults, despite guidelines recommending avoidance. Prior interventions have not fully addressed how physicians make such prescribing decisions, particularly when experiencing stress or cognitive overload. Simulation training may help improve prescribing decision-making but has not been evaluated for overprescribing. METHODS: In this two-arm pragmatic trial, we randomized 40 first-year medical resident physicians (i.e., interns) on inpatient general medicine services at an academic medical center to either intervention (a 40-minute immersive simulation training) or control (online educational training) groups. The primary outcome was the number of new benzodiazepine, sedative hypnotic, or antipsychotic orders for treatment-naïve older adults during hospitalization. Secondary outcomes included the same outcome by all providers, being discharged on one of the medications, and orders for related or control medications. Outcomes were measured using electronic health record data over each intern's service period (~2 weeks). Outcomes were evaluated using generalized estimating equations, adjusting for clustering. RESULTS: In total, 522 treatment-naïve older adult patients were included in analyses. Over follow-up, interns prescribed ≥1 high-risk medication for 13 (4.9%) intervention patients and 13 (5.0%) control patients. The intervention led to no difference in the number of new prescriptions (Rate Ratio [RR]: 0.85, 95%CI: 0.31-2.35) versus control and no difference in secondary outcomes. In secondary analyses, intervention interns wrote significantly fewer "as-needed" ("PRN") order types for the high-risk medications (RR: 0.29, 95%CI: 0.08-0.99), and instead tended to write more "one-time" orders than control interns, though this difference was not statistically significant (RR: 2.20, 95%CI: 0.60-7.99). CONCLUSIONS: Although this simulation intervention did not impact total high-risk prescribing for hospitalized older adults, it did influence how the interns prescribed, resulting in fewer PRN orders, suggesting possibly greater ownership of care. Future interventions should consider this insight and implementation lessons raised. TRIAL REGISTRATION: Clinicaltrials.gov(NCT04668248).

The impact of using reinforcement learning to personalize communication on medication adherence: findings from the REINFORCE trial.

Text messaging can promote healthy behaviors, like adherence to medication, yet its effectiveness remains modest, in part because message content is rarely personalized. Reinforcement learning has been used in consumer technology to personalize content but with limited application in healthcare. We tested a reinforcement learning program that identifies individual responsiveness ("adherence") to text message content and personalizes messaging accordingly. We randomized 60 individuals with diabetes and glycated hemoglobin A1c [HbA1c] ≥ 7.5% to reinforcement learning intervention or control (no messages). Both arms received electronic pill bottles to measure adherence. The intervention improved absolute adjusted adherence by 13.6% (95%CI: 1.7%-27.1%) versus control and was more effective in patients with HbA1c 7.5- < 9.0% (36.6%, 95%CI: 25.1%-48.2%, interaction p < 0.001). We also explored whether individual patient characteristics were associated with differential response to tested behavioral factors and unique clusters of responsiveness. Reinforcement learning may be a promising approach to improve adherence and personalize communication at scale.

Disentangling drug contributions: anticholinergic burden in older adults linked to individual medications: a cross-sectional population-based study.

BACKGROUND: Medications with potent anticholinergic properties have well-documented adverse effects. A high cumulative anticholinergic burden may arise from the concurrent use of multiple medications with weaker anticholinergic effects. We sought to identify patterns of high anticholinergic burden and associated patient characteristics. METHODS: We identified patients aged ≥ 65 who filled ≥ 1 medication with anticholinergic adverse effects in 2019 and had a cumulative Anticholinergic Burden score (ACB) ≥ 4 (i.e., high anticholinergic burden) in a large US health insurer. We classified patients based on how they attained high burden, as follows: 1) only filling strong or moderate anticholinergic medications (i.e., ACB = 2 or 3, "moderate/strong"), 2) only filling lightly anticholinergic medications (i.e., ACB = 1, "light/possible"), and 3) filling any combination ("mix"). We used multinomial logistic regression to assess the association between measured patient characteristics and membership in the three anticholinergic burden classifications, using the moderate/strong group as the referent. RESULTS: In total, 83,286 eligible patients with high anticholinergic burden were identified (mean age: 74.3 years (SD:7.1), 72.9% female). Of these, 4.5% filled only strong/moderate anticholinergics, 4.3% filled only light/possible anticholinergics, and the rest filled a mix (91.2%). Within patients in the mixed group, 64.3% of medication fills were for light/possible anticholinergics, while 35.7% were for moderate/strong anticholinergics. Compared with patients in the moderate/strong anticholinergics group, patients filling only light/possible anticholinergics were more likely to be older (adjusted Odds Ratio [aOR] per 1-unit of age: 1.06, 95%CI: 1.05-1.07), less likely to be female (aOR: 0.56, 95%CI: 0.50-0.62 vs. male), more likely to have comorbidities (e.g., heart failure aOR: 3.18, 95%CI: 2.70-3.74 or depression aOR: 1.20, 95%CI: 1.09-1.33 vs. no comorbidity), and visited fewer physicians (aOR per 1-unit of change: 0.98, 95%CI: 0.97-0.98). Patients in the mixed group were older (aOR per 1-unit of age: 1.02, 95%CI: 1.02-1.03) and less likely to be female (aOR: 0.89, 95%CI: 0.82-0.97 vs. male) compared with those filling moderate/strong anticholinergics. CONCLUSION: Most older adults accumulated high anticholinergic burden through a combination of light/possible and moderate/strong anticholinergics rather than moderate/strong anticholinergics, with light/possible anticholinergics being the major drivers of overall anticholinergic burden. These insights may inform interventions to improve prescribing in older adults.

"How" Versus "Why" Messaging to Increase Uptake of Booster Vaccination Against COVID-19: Results of a Pragmatic Randomized Trial.

BACKGROUND: Messages aimed at increasing uptake of vaccines have been modestly successful, perhaps in part because they often focus on why individuals should receive a vaccine. Construal Level Theory posits that messages emphasizing "how" to get a vaccine may be more effective at encouraging vaccination than emphasizing "why." This message framing may be particularly important for COVID-19 booster acceptance. OBJECTIVE: To determine if pre-visit patient portal messages designed using Construal Level Theory increase rates of COVID-19 booster vaccination. DESIGN AND INTERVENTIONS: This 3-arm randomized trial was conducted across three large, diverse primary care clinics in Massachusetts between February and May 2022, testing the impact of "how" versus "why" framed pre-visit messages versus no messages ("usual care"). Messages were sent by patient portal two business days before a visit. PARTICIPANTS: Adults with upcoming primary care visits who had electronic health record evidence of receiving their initial COVID-19 vaccination series but not a booster dose. MAIN MEASURES: Receipt of a COVID-19 booster vaccination after the message was sent through the visit date (primary outcome) or 6 weeks (secondary outcome). KEY RESULTS: A total of 3665 patients were randomized (mean age: 53.5 years (SD: 17.3), 59% female, 65.2% White, 26.6% Hispanic), with 1249 to "how" 1199 to "why," and 1217 to usual care arms. Except for clinic and preferred language, characteristics were well balanced across arms. Rates of COVID-19 booster were 13.6% (usual care), 11.7% ("how") (odds ratio (OR) "how" vs usual care: 0.87, 95%CI: 0.67-1.14), and 13.7% ("why") ("why" vs usual care: OR: 1.01, 95%CI: 0.81-1.28). At 6 weeks, "why" outperformed "how" for vaccination (OR: 1.26, 95%CI: 1.06-1.49), with no difference versus usual care. CONCLUSIONS: We found no differences on visit booster receipt after single pre-visit portal messages designed using Construal Level Theory. Further studies to identify effective messaging interventions are needed, especially as additional doses are recommended. CLINICAL TRIAL REGISTRATION: This trial is registered at clinicaltrials.gov, ID: NCT04871776 . Initial release occurred 04/30/2021.

Disagreement between pharmacy claims and direct interview to identify patients with non-adherence to chronic cardiometabolic medications.

BACKGROUND: Accurate methods of identifying patients with suboptimal adherence to cardiometabolic medications are needed, and each approach has benefits and tradeoffs. METHODS: We used data from a large trial of patients with poorly controlled cardiometabolic disease and evidence of medication non-adherence measured using pharmacy claims data whose adherence was subsequently assessed during a telephone consultation with a clinical pharmacist. We then evaluated if the pharmacist assessment agreed with the non-adherence measured using claims. When pharmacist and claims assessments disagreed, we identified reasons why claims were insufficient and used multivariable modified Poisson regression to identify patient characteristics associated with disagreement. RESULTS: Of 1,069 patients identified as non-adherent using claims (proportion of days covered [PDC] <80%), 646 (60.4%) were confirmed as non-adherent on pharmacist interview. For the 423 patients (39.6%) where the interview disagreed with the claims, the most common reasons were paying cash or using an alternate insurance (36.6%), medication discontinuation or regimen change (32.8%), and recently becoming adherent (26.7%). Compared to patients whose claims and interview both showed non-adherence, patients whose interview disagreed with claims were less likely to miss outpatient office visits (RR:0.91, 95%CI:0.85-0.97) and more likely to have a baseline PDC above the median (RR:1.35, 95%CI:1.10-1.64). CONCLUSIONS: Among patients identified as non-adherent by claims, 39.6% were observed to be adherent when assessed during pharmacist consultation. This discrepancy was largely driven by paying out-of-pocket, using alternative insurance, or medication discontinuation or change. These findings have important implications for using pharmacy claims to identify and intervene upon medication non-adherence.

Reducing ethnic and racial disparities by improving undertreatment, control, and engagement in blood pressure management with health information technology (REDUCE-BP) hybrid effectiveness-implementation pragmatic trial: Rationale and design.

BACKGROUND: While racial/ethnic disparities in blood pressure control are documented, few interventions have successfully reduced these gaps. Under-prescribing, lack of treatment intensification, and suboptimal follow-up care are thought to be central contributors. Electronic health record (EHR) tools may help address these barriers and may be enhanced with behavioral science techniques. OBJECTIVE: To evaluate the impact of a multicomponent behaviorally-informed EHR-based intervention on blood pressure control. TRIAL DESIGN: Reducing Ethnic and racial Disparities by improving Undertreatment, Control, and Engagement in Blood Pressure management with health information technology (REDUCE-BP) (NCT05030467) is a two-arm cluster-randomized hybrid type 1 pragmatic trial in a large multi-ethnic health care system. Twenty-four clinics (>350 primary care providers [PCPs] and >10,000 eligible patients) are assigned to either multi-component EHR-based intervention or usual care. Intervention clinic PCPs will receive several EHR tools designed to reduce disparities delivered at different points, including a: (1) dashboard of all patients visible upon logging on to the EHR displaying blood pressure control by race/ethnicity compared to their PCP peers and (2) set of tools in an individual patient's chart containing decision support to encourage treatment intensification, ordering home blood pressure measurement, interventions to address health-related social needs, default text for note documentation, and enhanced patient education materials. The primary outcome is patient-level change in systolic blood pressure over 12 months between arms; secondary outcomes include changes in disparities and other clinical outcomes. CONCLUSION: REDUCE-BP will provide important insights into whether an EHR-based intervention designed using behavioral science can improve hypertension control and reduce disparities.

Effect of a Biopsychosocial Intervention or Postural Therapy on Disability and Health Care Spending Among Patients With Acute and Subacute Spine Pain: The SPINE CARE Randomized Clinical Trial.

Importance: Low back and neck pain are often self-limited, but health care spending remains high. Objective: To evaluate the effects of 2 interventions that emphasize noninvasive care for spine pain. Design, Setting, and Participants: Pragmatic, cluster, randomized clinical trial conducted at 33 centers in the US that enrolled 2971 participants with neck or back pain of 3 months' duration or less (enrollment, June 2017 to March 2020; final follow-up, March 2021). Interventions: Participants were randomized at the clinic-level to (1) usual care (n = 992); (2) a risk-stratified, multidisciplinary intervention (the identify, coordinate, and enhance [ICE] care model that combines physical therapy, health coach counseling, and consultation from a specialist in pain medicine or rehabilitation) (n = 829); or (3) individualized postural therapy (IPT), a postural therapy approach that combines physical therapy with building self-efficacy and self-management (n = 1150). Main Outcomes and Measures: The primary outcomes were change in Oswestry Disability Index (ODI) score at 3 months (range, 0 [best] to 100 [worst]; minimal clinically important difference, 6) and spine-related health care spending at 1 year. A 2-sided significance threshold of .025 was used to define statistical significance. Results: Among 2971 participants randomized (mean age, 51.7 years; 1792 women [60.3%]), 2733 (92%) finished the trial. Between baseline and 3-month follow-up, mean ODI scores changed from 31.2 to 15.4 for ICE, from 29.3 to 15.4 for IPT, and from 28.9 to 19.5 for usual care. At 3-month follow-up, absolute differences compared with usual care were -5.8 (95% CI, -7.7 to -3.9; P < .001) for ICE and -4.3 (95% CI, -5.9 to -2.6; P < .001) for IPT. Mean 12-month spending was $1448, $2528, and $1587 in the ICE, IPT, and usual care groups, respectively. Differences in spending compared with usual care were -$139 (risk ratio, 0.93 [95% CI, 0.87 to 0.997]; P = .04) for ICE and $941 (risk ratio, 1.40 [95% CI, 1.35 to 1.45]; P < .001) for IPT. Conclusions and Relevance: Among patients with acute or subacute spine pain, a multidisciplinary biopsychosocial intervention or an individualized postural therapy intervention, each compared with usual care, resulted in small but statistically significant reductions in pain-related disability at 3 months. However, compared with usual care, the biopsychosocial intervention resulted in no significant difference in spine-related health care spending and the postural therapy intervention resulted in significantly greater spine-related health care spending at 1 year. Trial Registration: ClinicalTrials.gov Identifier: NCT03083886.

Patient and Provider Web-Based Decision Support for Breast Cancer Chemoprevention: A Randomized Controlled Trial.

Significant underutilization of breast cancer chemoprevention remains, despite guidelines stating that physicians should recommend chemoprevention with antiestrogen therapy to high-risk women. We randomized women, ages 35 to 75 years, who met high-risk criteria for breast cancer, without a personal history of breast cancer or prior chemoprevention use, to standard educational materials alone or combined with a web-based decision aid. All healthcare providers, including primary care providers and breast specialists, were given access to a web-based decision support tool. The primary endpoint was chemoprevention uptake at 6 months. Secondary outcomes included decision antecedents (perceived breast cancer risk/worry, chemoprevention knowledge, self-efficacy) and decision quality (decision conflict, chemoprevention informed choice) based upon patient surveys administered at baseline, 1 and 6 months after randomization. Among 282 evaluable high-risk women enrolled from November 2016 to March 2020, mean age was 57 years (SD, 9.9) and mean 5-year invasive breast cancer risk was 2.98% (SD, 1.42). There was no significant difference in chemoprevention uptake at 6 months between the intervention and control groups (2.1% vs. 3.5%). Comparing the intervention and control arms at 1 month, there were significant differences among high-risk women in accurate breast cancer risk perceptions (56% vs. 39%, P = 0.017), adequate chemoprevention knowledge (49% vs. 27%, P < 0.001), mean decision conflict (34.0 vs. 47.0, P < 0.001), and informed choice (41% vs. 23%, P = 0.003). These differences were no longer significant at 6 months. Although our decision support tools did not result in a significant increase in chemoprevention uptake, we did observe improvements in decision antecedents and decision quality measures. PREVENTION RELEVANCE: In this randomized controlled trial of decision support for 300 high-risk women and 50 healthcare providers, we did not observe a significant increase in chemoprevention uptake, which remained low at under 5%. However, these decision support tools may increase knowledge and informed choice about breast cancer chemoprevention.

Strategies to Identify and Recruit Women at High Risk for Breast Cancer to a Randomized Controlled Trial of Web-based Decision Support Tools.

We evaluated strategies to identify and recruit a racially/ethnically diverse cohort of women at high-risk for breast cancer to a randomized controlled trial (RCT). We enrolled 300 high-risk women and 50 healthcare providers to a RCT of standard educational materials alone or in combination with web-based decision support tools. We implemented five strategies to identify high-risk women: (i) recruitment among patients previously enrolled in a study evaluating breast cancer risk; (ii) automated breast cancer risk calculation using information extracted from the electronic health record (EHR); (iii) identification of women with atypical hyperplasia or lobular carcinoma in situ (LCIS) using International Classification of Diseases (ICD)-9/10 diagnostic codes; (iv) clinical encounters with enrolled healthcare providers; (v) recruitment flyers/online resources. Breast cancer risk was calculated using either the Gail or Breast Cancer Surveillance Consortium (BCSC) models. We identified 6,229 high-risk women and contacted 3,459 (56%), of whom 17.2% were identified from prior study cohort, 37.5% through EHR risk information, 14.8% with atypical hyperplasia/LCIS, 29.0% by clinical encounters, and 1.5% through recruitment flyers. Women from the different recruitment sources varied by age and 5-year invasive breast cancer risk. Of 300 enrolled high-risk women, 44.7% came from clinical encounters and 27.3% from prior study cohort. Comparing enrolled with not-enrolled participants, there were significant differences in mean age (57.2 vs. 59.1 years), proportion of non-Whites (41.5% vs. 54.8%), and mean 5-year breast cancer risk (3.0% vs. 2.3%). We identified and successfully recruited diverse high-risk women from multiple sources. These strategies may be implemented in future breast cancer chemoprevention trials. PREVENTION RELEVANCE: We describe five strategies to identify and successfully recruit a large cohort of racially/ethnically diverse high-risk women from multiple sources to a randomized controlled trial evaluating interventions to increase chemoprevention uptake. Findings could inform recruitment efforts for future breast cancer prevention trials to increase recruitment yield of high-risk women.

The Impact of HIV on Non-AIDS defining gastrointestinal malignancies: A review.

BACKGROUND: Cancer is the leading cause of morbidity and mortality among people living with HIV (PLWH). Although gastrointestinal (GI) cancers are not associated with HIV, their incidence is rising among PLWH, and yet little is known about how HIV affects their presentation, treatment and outcomes. METHODS: We searched PubMed using "HIV" and "cancer", "esophageal cancer", "gastric cancer", "stomach cancer", "gastroesophageal cancer", "colorectal cancer", "colon cancer", or "rectal cancer". We included studies comparing an HIV-positive group (n ≥ 4) to an HIV-negative group, with respect to clinical presentation, treatment, or mortality of GI cancers. RESULTS: Of 18 articles that met inclusion criteria, 17 were retrospective, and 13 described patients in the United States. At diagnosis with colorectal, but not pancreatic, gastric, or esophageal cancer, PLWH were younger than patients who were HIV-negative. PLWH did not present with more advanced stage GI cancers than patients who were HIV-negative. Compared to HIV-negative controls, PLWH with colorectal cancer had a higher proportion of right-sided versus left-sided colon cancers and a higher proportion of rectal versus colon cancers. Among patients diagnosed with colorectal or pancreatic cancer, PLWH were less likely to receive cancer treatment than other patients; no studies examined the association of HIV status with treatment for esophageal or gastric cancer. PLWH with GI malignancies had higher all-cause mortality compared to patients who were HIV-negative, but evidence for cancer-specific mortality was limited and mixed. CONCLUSION: PLWH with GI malignancies were less likely to receive cancer treatment and had higher all-cause mortality than patients who were HIV-negative. Most of the studies focused on colorectal cancer; more studies are needed in pancreatic, gastric and esophageal cancer. Future studies should investigate the effects of HIV on cancer-specific mortality, especially among patients in low- and middle-income countries, including those with high HIV prevalence.