Adoption of Extended-Interval Dosing of Single-Agent Pembrolizumab and Comparative Effectiveness vs Standard Dosing in Time-to-Treatment Discontinuation.

Importance: Extended-interval dosing of pembrolizumab (400 mg every 6 weeks) was approved by US Food and Drug Administration (FDA) in April 2020 as an alternative to standard-interval dosing (200 mg every 3 weeks). Extended-interval dosing may enhance access, alleviate patient and health system financial toxicity, and improve patient quality of life, particularly during the COVID-19 pandemic. Neither adoption nor effectiveness of extended interval in the US has been adequately described.

Planning and Reporting Effective Web-Based RAND/UCLA Appropriateness Method Panels: Literature Review and Preliminary Recommendations.

Background: The RAND/UCLA Appropriateness Method (RAM), a variant of the Delphi Method, was developed to synthesize existing evidence and elicit the clinical judgement of medical experts on the appropriate treatment of specific clinical presentations. Technological advances now allow researchers to conduct expert panels on the internet, offering a cost-effective and convenient alternative to the traditional RAM. For example, the Department of Veterans Affairs recently used a web-based RAM to validate clinical recommendations for de-intensifying routine primary care services.

Focus and features of prescribing indications spanning multiple chronic conditions in older adults: A narrative review.

Background: Inappropriate prescribing is frequent in older adults and associated with adverse outcomes. Prescribing indications aim to optimize prescribing, but little is known about the focus and features of prescribing indications for the most common chronic conditions in older adults. Understanding the conditions, medications, and issues addressed (e.

Rising use of surveillance colonoscopy and potential impacts.

Objectives: To quantify temporal changes in colonoscopy indication and assess appropriateness of surveillance use in older adults.

Study Design: Retrospective longitudinal study of national Veterans Health Administration (VHA) data of all patients who underwent outpatient colonoscopy in 2005-2014.

Methods: After validating an electronic algorithm for classifying colonoscopy indication in VHA, we examined trends in colonoscopy indication over time and across patient characteristics.

Type 2 Diabetes Management, Control and Outcomes During the COVID-19 Pandemic in Older US Veterans: an Observational Study.

Background: The COVID-19 pandemic required a change in outpatient care delivery models, including shifting from in-person to virtual visits, which may have impacted care of vulnerable patients.

Objective: To describe the changes in management, control, and outcomes in older people with type 2 diabetes (T2D) associated with the shift from in-person to virtual visits.

Design And Participants: In veterans aged ≥ 65 years with T2D, we assessed the rates of visits (in person, virtual), A1c measurements, antidiabetic deintensification/intensification, ER visits and hospitalizations (for hypoglycemia, hyperglycemia, other causes), and A1c level, in March 2020 and April-November 2020 (pandemic period).

Agreement among measures examining low-value imaging for low back pain.

Objectives: To quantify the extent of patient-level agreement among 3 published measures of low-value imaging for acute low back pain (LBP).

Study Design: In this retrospective cohort study using commercial insurance claims from MarketScan, we assessed 3 published measures of low-value imaging for agreement in identifying LBP diagnoses (denominator), red-flag diagnoses (denominator exclusions), and imaging procedures (numerator).

Methods: Using a cohort of patients, aged 18 to 64 years, with a diagnosis of LBP in 2014, we assessed agreement surrounding both the overuse event (imaging procedures) and inclusion in the reference population (LBP definition and exclusion diagnoses) using percent agreement and Fleiss κ among 3 overuse measures.

Applying User-Centered Design to Develop Practical Strategies that Address Overuse in Primary Care.

Introduction: Engaging patients and frontline clinicians in re-designing clinical care is essential for improving care delivery in a complex clinical environment. This study sought to assess an innovative user-centered design approach to improving clinical care quality, focusing on the use cases of de-intensifying non-beneficial care within the following areas: (1) de-intensifying diabetes treatment in high-risk patients; (2) stopping screening for carotid artery stenosis in asymptomatic patients; and (3) stopping colorectal cancer screening in average-risk, older adults.

Methods: The user-centered design approach, consisting of patient and patient-clinician charrettes (defined as intensive workshops where key stakeholders collaborate to develop creative solutions to a specific problem) and participant surveys, has been described previously.

Identifying Recommendations for Stopping or Scaling Back Unnecessary Routine Services in Primary Care.

Importance: Much of health care involves established, routine use of medical services for chronic conditions or prevention. Stopping these services when the evidence changes or if the benefits no longer outweigh the risks is essential. Yet, most guidelines focus on escalating care and provide few explicit recommendations to stop or scale back (ie, deintensify) treatment and testing.

Comparison of Payment Changes and Choosing Wisely Recommendations for Use of Low-Value Laboratory Tests in the United States and Canada.

Importance: Evidence comparing the consequences of Choosing Wisely recommendations across health systems or with the consequences of recommendations plus policy change is lacking.

Objectives: To compare changes in the use of 2 low-value laboratory tests after the release of Choosing Wisely recommendations across 3 health care jurisdictions and changes associated with a related policy change.

Design, Setting, And Participants: This cross-sectional study was a population-based interrupted time series of adult patients (aged 18-64 years) who had primary care visits between January 1, 2010, and June 30, 2015, or established hypothyroidism between January 1, 2012, and June 30, 2015, across 3 health care delivery jurisdictions: Ontario, Canada; the US Veterans Health Administration; and the US employer-sponsored insurance market.

Developing Strategies to Reduce Unnecessary Services in Primary Care: Protocol for User-Centered Design Charrettes.

Background: Overtreatment and overtesting expose patients to unnecessary, wasteful, and potentially harmful care. Reducing overtreatment or overtesting that has become ingrained in current clinical practices and is being delivered on a routine basis will require solutions that incorporate a deep understanding of multiple perspectives, particularly those on the front lines of clinical care: patients and their clinicians. Design approaches are a promising and innovative way to incorporate stakeholder needs, desires, and challenges to develop solutions to complex problems.

Effects of Guideline and Formulary Changes on Statin Prescribing in the Veterans Affairs.

Objective: To compare the effects of two sequential policy changes-the addition of a high-potency statin to the Department of Veterans Affairs (VA) formulary and the release of the American College of Cardiology/American Heart Association (ACC/AHA) cholesterol guidelines-on VA provider prescribing.

Data Sources/study Setting: Retrospective analysis of 1,100,682 VA patients, 2011-2016.

Study Design: Interrupted time-series analysis of changes in prescribing of moderate-to-high-intensity statins among high-risk patients and across high-risk subgroups.

Perceived Barriers to Implementing Individual Choosing Wisely Recommendations in Two National Surveys of Primary Care Providers.

Background: While some research has examined general attitudes about efforts to reduce overutilization of services, such as the Choosing Wisely (CW) initiative, little data exists regarding primary care providers' attitudes regarding individual recommendations.

Objective: We sought to identify whether particular CW recommendations were perceived by primary care providers as difficult to follow, difficult for patients to accept, or both.

Design: Two national surveys, one by mail to a random sample of 2000 U.

Rates of Deintensification of Blood Pressure and Glycemic Medication Treatment Based on Levels of Control and Life Expectancy in Older Patients With Diabetes Mellitus.

Importance: Older patients with diabetes mellitus receiving medical treatment whose blood pressure (BP) or blood glucose level are potentially dangerously low are rarely deintensified. Given the established risks of low blood pressure and blood glucose, this is a major opportunity to decrease medication harm.

Objective: To examine the rate of BP- and blood glucose-lowering medicine deintensification among older patients with type 1 or 2 diabetes mellitus who potentially receive overtreatment.

Endothelin-1 gene polymorphisms influence cerebrospinal fluid endothelin-1 levels following aneurysmal subarachnoid hemorrhage.

Aneurysmal subarachnoid hemorrhage is a type of stroke with high morbidity and mortality. Increased endothelin-1 (ET-1) levels have been associated with increased risk of cerebral vasospasm, which is associated with increased morbidity. The purpose of this study was to investigate the relationships between ET-1 genotypes and ET-1 protein levels in cerebrospinal fluid (CSF) measured 72 hr before angiographic vasospasm measurement in subjects at high risk of cerebral vasospasm.

Factors associated with persistent poorly controlled diabetes mellitus: clues to improving management in patients with resistant poor control.

Objectives: Patients with persistent poorly controlled diabetes mellitus (PPDM), defined as an uninterrupted hemoglobin A1c >8.0% for ≥1 year despite standard care, are at high risk for complications. Additional research to define patient factors associated with PPDM could suggest barriers to improvement in this group and inform the development of targeted strategies to address these patients' resistant diabetes.

Characteristics of diabetic patients associated with achieving and maintaining blood pressure targets in the Adherence and Intensification of Medications program.

Objectives: To determine patient characteristics associated with achieving and sustaining blood pressure (BP) targets in the Adherence and Intensification of Medications program, a program led by pharmacists trained in motivational interviewing and authorized to make BP medication changes.

Methods: We conducted a retrospective cohort study of patients with diabetes and persistent hypertension in Kaiser Permanente and the Department of Veterans Affairs. Using two-level logistic regression, baseline survey data from 458 program participants were examined to determine patient characteristics associated with (1) discharge from the program with a target BP (short-term success) and (2) maintenance of the target BP over a nine-month period (long-term success).

Accounting for clinical action reduces estimates of gender disparities in lipid management for diabetic veterans.

Background: Women with diabetes have higher low-density lipoprotein (LDL) levels than men, resulting in apparent disparities between genders on quality indicators tied to LDL thresholds.

Objective: To investigate whether gender disparities persist when accounting for clinical action with statins or cardiovascular risk.

Design: Retrospective cohort study.

Hypothermia decreases cerebrospinal fluid asymmetric dimethylarginine levels in children with traumatic brain injury.

Objectives: Pathological increases in asymmetric dimethylarginine, an endogenous nitric oxide synthase inhibitor, have been implicated in endothelial dysfunction and vascular diseases. Reduced nitric oxide early after traumatic brain injury may contribute to hypoperfusion. Currently, methods to quantify asymmetric dimethylarginine in the cerebrospinal fluid have not been fully explored.

Assessing appropriateness of lipid management among patients with diabetes mellitus: moving from target to treatment.

Background: Performance measures that emphasize only a treat-to-target approach may motivate overtreatment with high-dose statins, potentially leading to adverse events and unnecessary costs. We developed a clinical action performance measure for lipid management in patients with diabetes mellitus that is designed to encourage appropriate treatment with moderate-dose statins while minimizing overtreatment.

Methods And Results: We examined data from July 2010 to June 2011 for 964 818 active Veterans Affairs primary care patients ≥18 years of age with diabetes mellitus.

Monitoring performance for blood pressure management among patients with diabetes mellitus: too much of a good thing?

Background: Performance measures that reward achieving blood pressure (BP) thresholds may contribute to overtreatment. We developed a tightly linked clinical action measure designed to encourage appropriate medical management and a marker of potential overtreatment, designed to monitor overly aggressive treatment of hypertension in the face of low diastolic BP.

Methods: We conducted a retrospective cohort study in 879 Department of Veterans Affairs (VA) medical centers and smaller community-based outpatient clinics.

Improving blood pressure control through a clinical pharmacist outreach program in patients with diabetes mellitus in 2 high-performing health systems: the adherence and intensification of medications cluster randomized, controlled pragmatic trial.

Background: Even in high-performing health systems, some patients with diabetes mellitus have poor blood pressure (BP) control because of poor medication adherence and lack of medication intensification. We examined whether the Adherence and Intensification of Medications intervention, a pharmacist-led intervention combining elements found in efficacy studies to lower BP, improved BP among patients with diabetes mellitus with persistent hypertension and poor refill adherence or insufficient medication intensification in 2 high-performing health systems.

Methods And Results: We conducted a prospective, multisite cluster randomized pragmatic trial with randomization of 16 primary care teams at 5 medical centers (3 Veterans Affairs and 2 Kaiser Permanente) to the Adherence and Intensification of Medications intervention or usual care.

Role of endothelin-1 in human aneurysmal subarachnoid hemorrhage: associations with vasospasm and delayed cerebral ischemia.

Background: Endothelin-1 (ET-1) is a potent vasoconstrictor implicated in the pathogenesis of vasospasm and delayed cerebral ischemia (DCI) in aneurysmal subarachnoid hemorrhage (aSAH) patients. The aim of this study was to investigate the relationship between cerebrospinal fluid (CSF) ET-1 levels and angiographic vasospasm and DCI.

Methods: Patients with aSAH were consented (n = 106).