Projected environmental and public health benefits of extended-interval dosing: an analysis of pembrolizumab use in a US national health system.

BACKGROUND: Health care is a major source of greenhouse gas emissions, leading to climate change and public health harms. Changes are needed to improve the environmental sustainability of health-care practices, but such changes should not sacrifice patient outcomes or financial sustainability. Alternative dosing strategies that reduce the frequency with which specialty drugs are administered, without sacrificing patient outcomes, are an attractive possibility for improving environmental sustainability. We sought to inform environmentally sustainable cancer care by estimating and comparing the environmental and financial effects of alternative, clinically equivalent strategies for pembrolizumab administration. METHODS: We conducted a retrospective analysis using a cohort of patients from the Veterans Health Administration (VHA) in the USA who received one or more pembrolizumab doses between May 1, 2020, and Sept 30, 2022. Using baseline, real-world administration of pembrolizumab, we generated simulated pembrolizumab use data under three near-equivalent counterfactual pembrolizumab administration strategies defined by combinations of weight-based dosing, pharmacy-level vial sharing and dose rounding, and extended-interval dosing (ie, every 6 weeks). For each counterfactual dosing strategy, we estimated greenhouse gas emissions related to pembrolizumab use across the VHA cohort using a deterministic environmental impact model that estimated greenhouse gas emissions due to patient travel, drug manufacture, and medical waste as the primary outcome measure. FINDINGS: We identified 7813 veterans who received at least one dose of pembrolizumab-containing therapy in the VHA during the study period. 59 140 pembrolizumab administrations occurred in the study period, of which 46 255 (78·2%) were dosed at 200 mg every 3 weeks, 12 885 (21·8%) at 400 mg every 6 weeks, and 14 955 (25·3%) were coadministered with infusional chemotherapies. Adoption of weight-based, extended-interval pembrolizumab dosing (4 mg/kg every 6 weeks) and pharmacy-level stewardship strategies (ie, dose rounding and vial sharing) for all pembrolizumab infusions would have resulted in 24·7% fewer administration events than baseline dosing (44 533 events vs 59 140 events) and an estimated 200 metric tons less CO2 emitted per year as a result of pembrolizumab use within the VHA (650 tons vs 850 tons of CO2, a relative reduction of 24%), largely due to reductions in distance travelled by patients to receive treatment. Similar results were observed when weight-based and extended-interval dosing were applied only to pembrolizumab monotherapy and pembrolizumab in combination with oral therapies. INTERPRETATION: Alternative pembrolizumab administration strategies might have environmental advantages over the current dosing and compounding paradigms. Specialty medication dosing can be optimised for health-care spending and environmental sustainability without sacrificing clinical outcomes. FUNDING: None.

Inappropriate Diagnosis of Pneumonia Among Hospitalized Adults.

Importance: Little is known about incidence of, risk factors for, and harms associated with inappropriate diagnosis of community-acquired pneumonia (CAP). Objective: To characterize inappropriate diagnosis of CAP in hospitalized patients. Design, Setting, and Participants: This prospective cohort study, including medical record review and patient telephone calls, took place across 48 Michigan hospitals. Trained abstractors retrospectively assessed hospitalized patients treated for CAP between July 1, 2017, and March 31, 2020. Patients were eligible for inclusion if they were adults admitted to general care with a discharge diagnostic code of pneumonia who received antibiotics on day 1 or 2 of hospitalization. Data were analyzed from February to December 2023. Main Outcomes and Measures: Inappropriate diagnosis of CAP was defined using a National Quality Forum-endorsed metric as CAP-directed antibiotic therapy in patients with fewer than 2 signs or symptoms of CAP or negative chest imaging. Risk factors for inappropriate diagnosis were assessed and, for those inappropriately diagnosed, 30-day composite outcomes (mortality, readmission, emergency department visit, Clostridioides difficile infection, and antibiotic-associated adverse events) were documented and stratified by full course (>3 days) vs brief (≤3 days) antibiotic treatment using generalized estimating equation models adjusting for confounders and propensity for treatment. Results: Of the 17 290 hospitalized patients treated for CAP, 2079 (12.0%) met criteria for inappropriate diagnosis (median [IQR] age, 71.8 [60.1-82.8] years; 1045 [50.3%] female), of whom 1821 (87.6%) received full antibiotic courses. Compared with patients with CAP, patients inappropriately diagnosed were older (adjusted odds ratio [AOR], 1.08; 95% CI, 1.05-1.11 per decade) and more likely to have dementia (AOR, 1.79; 95% CI, 1.55-2.08) or altered mental status on presentation (AOR, 1.75; 95% CI, 1.39-2.19). Among those inappropriately diagnosed, 30-day composite outcomes for full vs brief treatment did not differ (25.8% vs 25.6%; AOR, 0.98; 95% CI, 0.79-1.23). Full vs brief duration of antibiotic treatment among patients was associated with antibiotic-associated adverse events (31 of 1821 [2.1%] vs 1 of 258 [0.4%]; P = .03). Conclusions and Relevance: In this cohort study, inappropriate diagnosis of CAP among hospitalized adults was common, particularly among older adults, those with dementia, and those presenting with altered mental status. Full-course antibiotic treatment of those inappropriately diagnosed with CAP may be harmful.

Development of Patient Safety Measures to Identify Inappropriate Diagnosis of Common Infections.

BACKGROUND: Inappropriate diagnosis of infections results in antibiotic overuse and may delay diagnosis of underlying conditions. Here we describe the development and characteristics of 2 safety measures of inappropriate diagnosis of urinary tract infection (UTI) and community-acquired pneumonia (CAP), the most common inpatient infections on general medicine services. METHODS: Measures were developed from guidelines and literature and adapted based on data from patients hospitalized with UTI and CAP in 49 Michigan hospitals and feedback from end-users, a technical expert panel (TEP), and a patient focus group. Each measure was assessed for reliability, validity, feasibility, and usability. RESULTS: Two measures, now endorsed by the National Quality Forum (NQF), were developed. Measure reliability (derived from 24 483 patients) was excellent (0.90 for UTI; 0.91 for CAP). Both measures had strong validity demonstrated through (a) face validity by hospital users, the TEPs, and patient focus group, (b) implicit case review (ĸ 0.72 for UTI; ĸ 0.72 for CAP), and (c) rare case misclassification (4% for UTI; 0% for CAP) due to data errors (<2% for UTI; 6.3% for CAP). Measure implementation through hospital peer comparison in Michigan hospitals (2017 to 2020) demonstrated significant decreases in inappropriate diagnosis of UTI and CAP (37% and 32%, respectively, P < .001), supporting usability. CONCLUSIONS: We developed highly reliable, valid, and usable measures of inappropriate diagnosis of UTI and CAP for hospitalized patients. Hospitals seeking to improve diagnostic safety, antibiotic use, and patient care should consider using these measures to reduce inappropriate diagnosis of CAP and UTI.

Adopting Weight-Based Dosing With Pharmacy-Level Stewardship Strategies Could Reduce Cancer Drug Spending By Millions.

Immune checkpoint inhibitors, a class of drugs used in approximately forty unique cancer indications, are a sizable component of the economic burden of cancer care in the US. Instead of personalized weight-based dosing, immune checkpoint inhibitors are most commonly administered at "one-size-fits-all" flat doses that are higher than necessary for the vast majority of patients. We hypothesized that personalized weight-based dosing along with common stewardship efforts at the pharmacy level, such as dose rounding and vial sharing, would lead to reductions in immune checkpoint inhibitor use and lower spending. Using data from the Veterans Health Administration (VHA) and Medicare drug prices, we estimated reductions in immune checkpoint inhibitor use and spending that would be associated with pharmacy-level stewardship strategies, in a case-control simulation study of individual patient-level immune checkpoint inhibitor administration events. We identified baseline annual VHA spending for these drugs of approximately $537 million. Combining weight-based dosing, dose rounding, and pharmacy-level vial sharing would generate expected annual VHA health system savings of $74 million (13.7 percent). We conclude that adoption of pharmacologically justified immune checkpoint inhibitor stewardship measures would generate sizable reductions in spending for these drugs. Combining these operational innovations with value-based drug price negotiation enabled by recent policy changes may improve the long-term financial viability of cancer care in the US.

Germline Genetic Testing After Cancer Diagnosis.

Importance: Germline genetic testing is recommended by practice guidelines for patients diagnosed with cancer to enable genetically targeted treatment and identify relatives who may benefit from personalized cancer screening and prevention. Objective: To describe the prevalence of germline genetic testing among patients diagnosed with cancer in California and Georgia between 2013 and 2019. Design, Setting, and Participants: Observational study including patients aged 20 years or older who had been diagnosed with any type of cancer between January 1, 2013, and March 31, 2019, that was reported to statewide Surveillance, Epidemiology, and End Results registries in California and Georgia. These patients were linked to genetic testing results from 4 laboratories that performed most germline testing for California and Georgia. Main Outcomes and Measures: The primary outcome was germline genetic testing within 2 years of a cancer diagnosis. Testing trends were analyzed with logistic regression modeling. The results of sequencing each gene, including variants associated with increased cancer risk (pathogenic results) and variants whose cancer risk association was unknown (uncertain results), were evaluated. The genes were categorized according to their primary cancer association, including breast or ovarian, gastrointestinal, and other, and whether practice guidelines recommended germline testing. Results: Among 1 369 602 patients diagnosed with cancer between 2013 and 2019 in California and Georgia, 93 052 (6.8%) underwent germline testing through March 31, 2021. The proportion of patients tested varied by cancer type: male breast (50%), ovarian (38.6%), female breast (26%), multiple (7.5%), endometrial (6.4%), pancreatic (5.6%), colorectal (5.6%), prostate (1.1%), and lung (0.3%). In a logistic regression model, compared with the 31% (95% CI, 30%-31%) of non-Hispanic White patients with male breast cancer, female breast cancer, or ovarian cancer who underwent testing, patients of other races and ethnicities underwent testing less often: 22% (95% CI, 21%-22%) of Asian patients, 25% (95% CI, 24%-25%) of Black patients, and 23% (95% CI, 23%-23%) of Hispanic patients (P < .001 using the χ2 test). Of all pathogenic results, 67.5% to 94.9% of variants were identified in genes for which practice guidelines recommend testing and 68.3% to 83.8% of variants were identified in genes associated with the diagnosed cancer type. Conclusions and Relevance: Among patients diagnosed with cancer in California and Georgia between 2013 and 2019, only 6.8% underwent germline genetic testing. Compared with non-Hispanic White patients, rates of testing were lower among Asian, Black, and Hispanic patients.

Distinct health care use patterns of patients with chronic gastrointestinal diseases.

OBJECTIVES: Patients with complex chronic conditions have varying multidisciplinary care needs and utilization patterns, which limit the effectiveness of initiatives designed to improve continuity of care (COC) and reduce utilization. Our objective was to categorize patients with complex chronic conditions into distinct groups by pattern of outpatient care use and COC to tailor interventions. STUDY DESIGN: Observational cohort study from 2014 to 2015. METHODS: We identified patients whose 1-year hospitalization risk was in at least the 90th percentile in 2014 who had a chronic gastrointestinal disease (cirrhosis, inflammatory bowel disease, chronic pancreatitis) as case examples of complex chronic disease. We described frequency of office visits, number of outpatient providers, and 2 COC measures (usual provider of care, Bice-Boxerman COC indices) over 12 months. We used latent profile analysis, a statistical method for identifying distinct subgroups, to categorize patients based on overall, primary care, gastroenterology, and mental health continuity patterns. RESULTS: The 26,751 veterans in the cohort had a mean (SD) of 13.3 (8.6) office visits and 7.2 (3.8) providers in 2014. Patients were classified into 5 subgroups: (1) high gastroenterology-specific COC with mental health use; (2) high gastroenterology-specific COC without mental health use; (3) high overall utilization with mental health use; (4) low overall COC with mental health use; and (5) low overall COC without mental health use. These groups varied in their sociodemographic characteristics and risk for hospitalization, emergency department use, and mortality. CONCLUSIONS: Patients at high risk for health care utilization with specialty care needs can be grouped by varying propensity for health care continuity patterns.

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. Objective: To describe adoption of extended-interval dosing of pembrolizumab since its FDA approval and to measure its preliminary real-world effectiveness compared with standard-interval dosing. Design, Setting, and Participants: This was a retrospective cohort study that used data from the Veterans Health Administration (VHA), a US-based, nationwide single-payer health system. Participants were veterans who were prescribed single-agent pembrolizumab within the VHA between April 1, 2020, and July 1, 2021. Patients receiving combinations of pembrolizumab and cytotoxic chemotherapy or tyrosine kinase inhibitors were excluded. A subcohort of veterans with non-small cell lung cancer (NSCLC) was also identified using claims-based codes. Exposures: Single-agent pembrolizumab at extended or standard intervals. Main Outcomes and Measures: The number and proportion of single-agent pembrolizumab prescriptions that were extended compared with standard interval. Effectiveness was described in terms of time-to-treatment discontinuation (TTD) and extended- to standard-interval pembrolizumab prescriptions were compared using Cox proportional hazards regression. Results: A total of 835 veterans (mean age [SD], 70.9 [8.7] years; 809 [96.9%] men) began single-agent pembrolizumab during the study period (all-diseases cohort), and of these, 234 (mean [SD] age, 71.6 [7.3] years; 225 [96.2%] men) had NSCLC (NSCLC cohort). Extended-interval adoption reached its steady state plateau of approximately 35% by January 2021; 65% of participants who began standard-interval single-agent pembrolizumab received only standard-interval dosing during the treatment course. In analysis consistent with the intention-to-treat principle, no differences in TTD were observed between standard- and extended-interval dosing in either the all-diseases cohort (HR, 1.00; 95% CI, 1.00-1.00) or the NSCLC cohort (HR, 1.00; 95% CI, 1.00-1.00). Conclusions and Relevance: This retrospective cohort study found that extended-interval dosing comprised a minority of single-agent pembrolizumab prescriptions despite the FDA approval and its potential health system and public health benefits. The findings support the TTD equivalence of standard- and extended-interval pembrolizumab across indications, complementing clinical pharmacology and single-arm clinical trial data in melanoma. This study provides further support for extended-interval pembrolizumab dosing.

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. A substantial literature describes and tests various aspects of the traditional RAM in health research; yet we know comparatively less about how researchers implement web-based expert panels. OBJECTIVE: The objectives of this study are twofold: (1) to understand how the web-based RAM process is currently used and reported in health research and (2) to provide preliminary reporting guidance for researchers to improve the transparency and reproducibility of reporting practices. METHODS: The PubMed database was searched to identify studies published between 2009 and 2019 that used a web-based RAM to measure the appropriateness of medical care. Methodological data from each article were abstracted. The following categories were assessed: composition and characteristics of the web-based expert panels, characteristics of panel procedures, results, and panel satisfaction and engagement. RESULTS: Of the 12 studies meeting the eligibility criteria and reviewed, only 42% (5/12) implemented the full RAM process with the remaining studies opting for a partial approach. Among those studies reporting, the median number of participants at first rating was 42. While 92% (11/12) of studies involved clinicians, 50% (6/12) involved multiple stakeholder types. Our review revealed that the studies failed to report on critical aspects of the RAM process. For example, no studies reported response rates with the denominator of previous rounds, 42% (5/12) did not provide panelists with feedback between rating periods, 50% (6/12) either did not have or did not report on the panel discussion period, and 25% (3/12) did not report on quality measures to assess aspects of the panel process (eg, satisfaction with the process). CONCLUSIONS: Conducting web-based RAM panels will continue to be an appealing option for researchers seeking a safe, efficient, and democratic process of expert agreement. Our literature review uncovered inconsistent reporting frameworks and insufficient detail to evaluate study outcomes. We provide preliminary recommendations for reporting that are both timely and important for producing replicable, high-quality findings. The need for reporting standards is especially critical given that more people may prefer to participate in web-based rather than in-person panels due to the ongoing COVID-19 pandemic.

Interpretability, credibility, and usability of hospital-specific template matching versus regression-based hospital performance assessments; a multiple methods study.

BACKGROUND: Hospital-specific template matching (HS-TM) is a newer method of hospital performance assessment. OBJECTIVE: To assess the interpretability, credibility, and usability of HS-TM-based vs. regression-based performance assessments. RESEARCH DESIGN: We surveyed hospital leaders (January-May 2021) and completed follow-up semi-structured interviews. Surveys included four hypothetical performance assessment vignettes, with method (HS-TM, regression) and hospital mortality randomized. SUBJECTS: Nationwide Veterans Affairs Chiefs of Staff, Medicine, and Hospital Medicine. MEASURES: Correct interpretation; self-rated confidence in interpretation; and self-rated trust in assessment (via survey). Concerns about credibility and main uses (via thematic analysis of interview transcripts). RESULTS: In total, 84 participants completed 295 survey vignettes. Respondents correctly interpreted 81.8% HS-TM vs. 56.5% regression assessments, p < 0.001. Respondents "trusted the results" for 70.9% HS-TM vs. 58.2% regression assessments, p = 0.03. Nine concerns about credibility were identified: inadequate capture of case-mix and/or illness severity; inability to account for specialized programs (e.g., transplant center); comparison to geographically disparate hospitals; equating mortality with quality; lack of criterion standards; low power; comparison to dissimilar hospitals; generation of rankings; and lack of transparency. Five concerns were equally relevant to both methods, one more pertinent to HS-TM, and three more pertinent to regression. Assessments were mainly used to trigger further quality evaluation (a "check oil light") and motivate behavior change. CONCLUSIONS: HS-TM-based performance assessments were more interpretable and more credible to VA hospital leaders than regression-based assessments. However, leaders had a similar set of concerns related to credibility for both methods and felt both were best used as a screen for further evaluation.

Evaluating alternative methods of comparing antihypertensive treatment intensity.

OBJECTIVES: To change blood pressure treatment, clinicians can modify medication count or dose. However, existing studies have measured count modification, which may miss clinically important dose change in the absence of count change. This research demonstrates how dose modification captures more information about management than medication count alone. STUDY DESIGN: Retrospective cohort study. METHODS: We included patients 65 years and older with established primary care at the Veterans Health Administration (July 2011-June 2013). We captured medication count and standardized dose change over 90 to 120 days using a validated pharmacy fill algorithm. We determined frequency of dose change without count change (and vice versa), no change in either, change in same direction ("concordant"), and change in opposite direction ("discordant"). We compared change according to systolic blood pressure (SBP) and compared concordance using a minimum threshold definition of dose change of at least 50% (instead of any change) of baseline dose modification. RESULTS: Among 440,801 patients, 64.2% had dose change; 22.0%, count change; 35.6%, no change in either; 42.4%, dose change without count modification; and 0.2%, count change without dose modification. Discordance occurred in 2.1% of observations. Using the minimum threshold definition of change, 68.7% had no change in either dose or count. Treatment was more frequently changed at SBP greater than 140 mm Hg. CONCLUSIONS: Measuring change in antihypertensive treatment using medication count frequently missed an isolated dose change in treatment modification and less often misclassified regimen modifications where there was no modification in total dose. In future research, measuring dose modification using our new algorithm would capture change in hypertension treatment intensity more precisely than current methods.

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). We used negative binomial regression to assess change over time (reference: pre-pandemic period, July 2018 to February 2020), by baseline Charlson Comorbidity Index (CCI; > 2 vs. <= 2) and A1c level. KEY RESULTS: Among 740,602 veterans (mean age 74.2 [SD 6.6] years), there were 55% (95% CI 52-58%) fewer in-person visits, 821% (95% CI 793-856%) more virtual visits, 6% (95% CI 1-11%) fewer A1c measurements, and 14% (95% CI 10-17%) more treatment intensification during the pandemic, relative to baseline. Patients with CCI > 2 had a 14% (95% CI 12-16%) smaller relative increase in virtual visits than those with CCI <= 2. We observed a seasonality of A1c level and treatment modification, but no association of either with the pandemic. After a decrease at the beginning of the pandemic, there was a rebound in other-cause (but not hypo- and hyperglycemia-related) ER visits and hospitalizations from June to November 2020. CONCLUSION: Despite a shift to virtual visits and a decrease in A1c measurement during the pandemic, we observed no association with A1c level or short-term T2D-related outcomes, providing some reassurance about the adequacy of virtual visits. Further studies should assess the longer-term effects of shifting to virtual visits in different populations to help individualize care, improve efficiency, and maintain appropriate care while reducing overuse.

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. Following the charrettes, we used inductive coding to identify and categorize themes emerging from the de-intensification ideas prioritized by participants as well as facilitator notes and audio recordings from the charrettes. RESULTS: Thirty-five patients participated in the patient design charrettes, generating 134 unique de-intensification ideas and prioritizing 32, which were then distilled into six patient-generated principles of de-intensification by the study team. These principles provided a starting point for a subsequent patient-clinician charrette. In this follow-up charrette, 9 patients who had participated in an earlier patient design charrette collaborated with 7 clinicians to generate 63 potential de-intensification solutions. Six of these potential solutions were developed into multi-faceted, fully operationalized de-intensification strategies. DISCUSSION: The de-intensification strategies that patients and clinicians prioritized and operationalized during the co-design charrette process were detailed and multi-faceted. Each component of a strategy had a rationale based on feasibility, practical considerations, and ways of overcoming barriers. The charrette-based process may be a useful way to engage clinicians and patients in developing the complex and multi-faceted strategies needed to improve care delivery.

Association of Genetic Testing Results With Mortality Among Women With Breast Cancer or Ovarian Cancer.

BACKGROUND: Breast cancer and ovarian cancer patients increasingly undergo germline genetic testing. However, little is known about cancer-specific mortality among carriers of a pathogenic variant (PV) in BRCA1/2 or other genes in a population-based setting. METHODS: Georgia and California Surveillance Epidemiology and End Results (SEER) registry records were linked to clinical genetic testing results. Women were included who had stages I-IV breast cancer or ovarian cancer diagnosed in 2013-2017, received chemotherapy, and were linked to genetic testing results. Multivariable Cox proportional hazard models were used to examine the association of genetic results with cancer-specific mortality. RESULTS: 22 495 breast cancer and 4320 ovarian cancer patients were analyzed, with a median follow-up of 41 months. PVs were present in 12.7% of breast cancer patients with estrogen and/or progesterone receptor-positive, HER2-negative cancer, 9.8% with HER2-positive cancer, 16.8% with triple-negative breast cancer, and 17.2% with ovarian cancer. Among triple-negative breast cancer patients, cancer-specific mortality was lower with BRCA1 (hazard ratio [HR] = 0.49, 95% confidence interval [CI] = 0.35 to 0.69) and BRCA2 PVs (HR = 0.60, 95% CI = 0.41 to 0.89), and equivalent with PVs in other genes (HR = 0.65, 95% CI = 0.37 to 1.13), vs noncarriers. Among ovarian cancer patients, cancer-specific mortality was lower with PVs in BRCA2 (HR = 0.35, 95% CI = 0.25 to 0.49) and genes other than BRCA1/2 (HR = 0.47, 95% CI = 0.32 to 0.69). No PV was associated with higher cancer-specific mortality. CONCLUSIONS: Among breast cancer and ovarian cancer patients treated with chemotherapy in the community, BRCA1/2 and other gene PV carriers had equivalent or lower short-term cancer-specific mortality than noncarriers. These results may reassure newly diagnosed patients, and longer follow-up is ongoing.

A Statewide Collaborative Quality Initiative to Improve Antibiotic Duration and Outcomes in Patients Hospitalized With Uncomplicated Community-Acquired Pneumonia.

BACKGROUND: Community-acquired pneumonia (CAP) is a common cause for hospitalization and antibiotic overuse. We aimed to improve antibiotic duration for CAP across 41 hospitals participating in the Michigan Hospital Medicine Safety Consortium (HMS). METHODS: This prospective collaborative quality initiative included patients hospitalized with uncomplicated CAP who qualified for a 5-day antibiotic duration. Between 23 February 2017 and 5 February 2020, HMS targeted appropriate 5-day antibiotic treatment through benchmarking, sharing best practices, and pay-for-performance incentives. Changes in outcomes, including appropriate receipt of 5 ± 1-day antibiotic treatment and 30-day postdischarge composite adverse events (ie, deaths, readmissions, urgent visits, and antibiotic-associated adverse events), were assessed over time (per 3-month quarter), using logistic regression and controlling for hospital clustering. RESULTS: A total of 41 hospitals and 6553 patients were included. The percentage of patients treated with an appropriate 5 ±â€…1-day duration increased from 22.1% (predicted probability, 20.9% [95% confidence interval: 17.2%-25.0%]) to 45.9% (predicted probability, 43.9% [36.8%-51.2%]; adjusted odds ratio [aOR] per quarter, 1.10 [1.07-1.14]). Thirty-day composite adverse events occurred in 18.5% of patients (1166 of 6319) and decreased over time (aOR per quarter, 0.98 [95% confidence interval: .96-.99]) owing to a decrease in antibiotic-associated adverse events (aOR per quarter, 0.91 [.87-.95]). CONCLUSIONS: Across diverse hospitals, HMS participation was associated with more appropriate use of short-course therapy and fewer adverse events in hospitalized patients with uncomplicated CAP. Establishment of national or regional collaborative quality initiatives with data collection and benchmarking, sharing of best practices, and pay-for-performance incentives may improve antibiotic use and outcomes for patients hospitalized with uncomplicated CAP.

Hospital-specific Template Matching for Benchmarking Performance in a Diverse Multihospital System.

BACKGROUND: Hospital-specific template matching is a newer method of hospital performance measurement that may be fairer than regression-based benchmarking. However, it has been tested in only limited research settings. OBJECTIVE: The objective of this study was to test the feasibility of hospital-specific template matching assessments in the Veterans Affairs (VA) health care system and determine power to detect greater-than-expected 30-day mortality. RESEARCH DESIGN: Observational cohort study with hospital-specific template matching assessment. For each VA hospital, the 30-day mortality of a representative subset of hospitalizations was compared with the pooled mortality from matched hospitalizations at a set of comparison VA hospitals treating sufficiently similar patients. The simulation was used to determine power to detect greater-than-expected mortality. SUBJECTS: A total of 556,266 hospitalizations at 122 VA hospitals in 2017. MEASURES: A number of comparison hospitals identified per hospital; 30-day mortality. RESULTS: Each hospital had a median of 38 comparison hospitals (interquartile range: 33, 44) identified, and 116 (95.1%) had at least 20 comparison hospitals. In total, 8 hospitals (6.6%) had a significantly lower 30-day mortality than their benchmark, 5 hospitals (4.1%) had a significantly higher 30-day mortality, and the remaining 109 hospitals (89.3%) were similar to their benchmark. Power to detect a standardized mortality ratio of 2.0 ranged from 72.5% to 79.4% for a hospital with the fewest (6) versus most (64) comparison hospitals. CONCLUSIONS: Hospital-specific template matching may be feasible for assessing hospital performance in the diverse VA health care system, but further refinements are needed to optimize the approach before operational use. Our findings are likely applicable to other large and diverse multihospital systems.

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. RESULTS: In our cohort of 1,835,620 patients with acute LBP, the 3 measures agreed 100% on the presence of acute LBP and also had excellent agreement (99%; κ = 0.98) in identifying imaging for LBP. However, there was substantial disagreement on whom to exclude for red-flag diagnoses, leading to lower agreement (75%; κ = 0.61) on whom to include in the reference population of acute LBP without red flags, among whom imaging for LBP is considered of low value. CONCLUSIONS: Our findings demonstrate the need for further consensus surrounding how to translate guideline recommendations to administrative measures that assess overuse of imaging for acute LBP, particularly with respect to defining which patients should be excluded from the measures. This finding is also important for other overuse measures that rely on exclusions.

Adding a New Medication Versus Maximizing Dose to Intensify Hypertension Treatment in Older Adults : A Retrospective Observational Study.

BACKGROUND: There are 2 approaches to intensifying antihypertensive treatment when target blood pressure is not reached, adding a new medication and maximizing dose. Which strategy is better is unknown. OBJECTIVE: To assess the frequency of intensification by adding a new medication versus maximizing dose, as well as the association of each method with intensification sustainability and follow-up systolic blood pressure (SBP). DESIGN: Large-scale, population-based, retrospective cohort study. Observational data were used to emulate a target trial with 2 groups, new medication and maximizing dose, who underwent intensification of their drug regimen. SETTING: Veterans Health Administration (2011 to 2013). PATIENTS: Veterans aged 65 years or older with hypertension, an SBP of 130 mm Hg or higher, and at least 1 antihypertensive medication at less than the maximum dose. MEASUREMENTS: The following 2 intensification approaches were emulated: adding a new medication, defined as a total dose increase with new medication, and maximizing dose, defined as a total dose increase without new medication. Inverse probability weighting was used to assess the observational effectiveness of the intensification approach on sustainability of intensified treatment and follow-up SBP at 3 and 12 months. RESULTS: Among 178 562 patients, 45 575 (25.5%) had intensification by adding a new medication and 132 987 (74.5%) by maximizing dose. Compared with maximizing dose, adding a new medication was associated with less intensification sustainability (average treatment effect, -15.2% [95% CI, -15.7% to -14.6%] at 3 months and -15.1% [CI, -15.6% to -14.5%] at 12 months) but a slightly larger reduction in mean SBP (-0.8 mm Hg [CI, -1.2 to -0.4 mm Hg] at 3 months and -1.1 mm Hg [CI, -1.6 to -0.6 mm Hg] at 12 months). LIMITATION: Observational data; largely male population. CONCLUSION: Adding a new antihypertensive medication was less frequent and was associated with less intensification sustainability but slightly larger reductions in SBP. Trials would provide the most definitive support for our findings. PRIMARY FUNDING SOURCE: National Institute on Aging and Veterans Health Administration.

Factors associated with antihypertensive treatment intensification and deintensification in older outpatients.

BACKGROUND: New hypertension performance measures encourage more intensive treatment in older adults. Treatment intensification includes starting new medications and increasing the dose of old ones. Medication dose is particularly important to older adults, given their vulnerability to dose-related side effects. We previously validated a standardized measure of beneficial doses tested in hypertension trials, Hypertension Daily Dose (HDD). AIM OF THE STUDY: To test whether changes in treatment intensity using HDD was associated with systolic blood pressure (SBP) and patient characteristics. METHODS: Longitudinal study of all Veterans aged ≥65 years with a diagnosis of hypertension. We defined 3 groups of risk: 1) cardiovascular risk; 2) geriatric/frail; 3) low-risk (comparator). Using multinomial regression, we assessed the probability of deintensification, intensification, vs. stable treatment, according to SBP and group. RESULTS: Among 1,331,111 Veterans, 19.9% had deintensification, and 29.6% intensification. Deintensification decreased, while intensification increased, with SBP. Compared to low-risk patients, cardiovascular risk patients had 1.11 (95% CI 1.10-1.13) times the odds of intensifying, and geriatric/frail patients 1.45 (95%CI 1.43-1.47) times the odds of deintensifying. DISCUSSION: Patient-level HDD change was consistent with an expected association with cardiovascular risk and geriatric/frail conditions, suggesting that HDD can be used longitudinally to assess hypertension treatment modification in large health systems.

Clinical outcomes of modifying hypertension treatment intensity in older adults treated to low blood pressure.

BACKGROUND/OBJECTIVES: Hypertension treatment reduces cardiovascular events. However, uncertainty remains about benefits and harms of deintensification or further intensification of antihypertensive medication when systolic blood pressure (SBP) is tightly controlled in older multimorbid patients, because of their frequent exclusion in trials. We assessed the association of hypertension treatment deintensification or intensification with clinical outcomes in older adults with tightly controlled SBP. DESIGN: Longitudinal cohort study (2011-2013) with 9-month follow-up. SETTING: U.S.-nationwide primary care Veterans Health Administration healthcare system. PARTICIPANTS: Veterans aged 65 and older with baseline SBP <130 mmHg and ≥1 antihypertensive medication during ≥2 consecutive visits (N = 228,753). EXPOSURE: Deintensification or intensification, compared with stable treatment. MAIN OUTCOMES AND MEASURES: Cardiovascular events, syncope, or fall injury, as composite and distinct outcomes, within 9 months after exposure. Adjusted logistic regression and inverse probability of treatment weighting (IPTW, sensitivity analysis). RESULTS: Among 228,753 patients (mean age 75 [SD 7.5] years), the composite outcome occurred in 11,982/93,793 (12.8%) patients with stable treatment, 14,768/72,672 (20.3%) with deintensification, and 11,821/62,288 (19.0%) with intensification. Adjusted absolute outcome risk (95% confidence interval) was higher for deintensification (18.3% [18.1%-18.6%]) and intensification (18.7% [18.4%-19.0%]), compared with stable treatment (14.8% [14.6%-15.0%]), p < 0.001 for both effects in the multivariable model). Deintensification was associated with fewer cardiovascular events than intensification. At baseline SBP <95 mmHg, cardiovascular event risk was similar for deintensification and stable treatment, and fall risk lower for deintensification than intensification. IPTW yielded similar results. Mean follow-up SBP was 124.1 mmHg for stable treatment, 125.1 mmHg after deintensification (p < 0.001), and 124.0 mmHg after intensification (p < 0.001). CONCLUSION: Antihypertensive treatment deintensification in older patients with tightly controlled SBP was associated with worse outcomes than continuing same treatment intensity. Given higher mortality among patients with treatment modification, confounding by indication may not have been fully corrected by advanced statistical methods for observational data analysis.