Predictors of stool deoxyribonucleic acid test use in the United States: Implications for outreach to under-resourced populations.

OBJECTIVE: Although colorectal cancer screening (CRCS) is a public health priority, uptake is suboptimal in under-resourced groups. Noninvasive modalities, including stool deoxyribonucleic acid (sDNA) testing, may mitigate economic, geographic, cultural, or impairment-related barriers to CRCS. We assessed use of sDNA testing and other CRCS modalities in U.S. residents, comparing subgroups defined by several social determinants of health (SDOH). METHODS: A nationally representative sample of community-dwelling respondents aged 50-75 years self-reported use of CRCS modalities in the 2020 Behavioral Risk Factor Surveillance System Survey. Statistical analyses assessed up-to-date screening status and choice of modality in the recommended screening interval. RESULTS: Of 179,833 sampled respondents, 60.8% reported colonoscopy, 5.7% sDNA testing, 5.5% another modality. The rate of up-to-date screening was 72.0% overall and negatively associated with Hispanic ethnicity (63.6%), lower educational and annual income levels (e.g.,

Association of Antibiotic Treatment Duration With Recurrence of Uncomplicated Urinary Tract Infection in Pediatric Patients.

Background: Gaps and inconsistencies in published information about optimal antibiotic treatment duration for uncomplicated urinary tract infection (UTI) in pediatric patients pose a dilemma for antibiotic stewardship. Objective: Evaluate the association of antibiotic treatment duration with recurrence rates in children with new-onset cystitis or pyelonephritis. Methods: Retrospective cohort analysis of patients aged 2 to 17 years with new-onset cystitis or pyelonephritis and without renal/anatomical abnormality was conducted using Truven Health MarketScan Database for 2013-2015. Results: Of 7698 patients, 85.5% had cystitis, 14.3% pyelonephritis. Duration of antibiotic treatment was as follows: 3 to 5 days for cystitis (20.4%) or 7 (33.6%), 10 (44.2%), or 14 (1.8%) days for any UTI. Recurrence occurred in 5.5% of patients. Covariates associated with increased recurrence risk included pretreatment antibiotic exposure (odds ratio [OR] = 1.29; 95% CI = 1.06-1.57), pyelonephritis on diagnosis date (OR = 1.44; 95% CI = 1.03-2.00), follow-up visit during antibiotic treatment (OR = 3.21; 95% CI = 2.20-4.68), parenteral antibiotic (OR = 1.89; 95% CI = 1.33-2.69), and interaction of pyelonephritis diagnosis with nitrofurantoin monotherapy (OR = 3.68; 95% CI = 1.20-11.29). After adjustment for covariates, the association between duration of antibiotic treatment and recurrence was not significant (compared with 7 days: 10 days: OR = 1.07, 95% CI = 0.85-1.33; 14 days: OR = 0.89, 95% CI = 0.45-1.78). Conclusions and Relevance: Antibiotic treatment duration was not significantly associated with recurrence of uncomplicated UTI in a national pediatric cohort. Results provide support for shorter-course treatment, consistent with antimicrobial stewardship efforts.

Beneficial Agents for Patients With Type 2 Diabetes and Cardiovascular Disease or Obesity: Utilization in an Era of Accumulating Evidence.

This study was an analysis of a national sample of U.S. medical office visits from 2014 to 2016, a period when evidence of effectiveness was emerging for a variety of beneficial type 2 diabetes agents with regard to potential reduction in diabetes comorbidities. Ideal therapy was defined as an American Diabetes Association-identified beneficial agent plus metformin. The associations between atherosclerotic cardiovascular disease or obesity and use of these agents were explored.

Joint effects of advancing age and number of potentially inappropriate medication classes on risk of falls in Medicare enrollees.

BACKGROUND: Injurious falls among older adults are both common and costly. The prevalence of falls is known to increase with age and with use of fall-risk drugs/potentially inappropriate medications (FRD/PIM). Little is known about the joint effects of these two risk factors. METHODS: Data for 2013-2015 were obtained from the Truven Health MarketScan® Medicare database comprising utilization and eligibility (enrollment) data for approximately 4 million enrollees annually. A case-control design was used to compare enrollees aged 65-99 years diagnosed with > 1 fall event (n = 110,625) with enrollees without falls (n = 1,567,412). An exploratory analysis of joint age-FRD/PIM effects on fall risks was based on number needed to harm (NNH) calculations for each FRD/PIM therapy class count (compared with 0 FRD/PIMs), stratified by age group. Logistic regression analyses adjusted for demographics, comorbidities, and fracture history, measured in the 1 year prior to the fall date (cases) or a randomly assigned date (controls). RESULTS: For each FRD/PIM class count, NNH values decreased with older age (e.g., for 1 FRD/PIM class: from NNH = 333 for ages 65-74 years to NNH = 83 for ages 90-99 years; for 2 FRD/PIM classes: from NNH = 91 for ages 65-74 years to NNH = 38 for ages 90-99 years). NNH decreased to < 15 patients at > 6 classes for age 65-74 years, > 5 classes for age 75-84 years, and > 4 classes for age 85-99 years. Adjusted odds of falling were increased for age-FRD/PIM combinations with smaller NNH values: adjusted odds ratio (AOR) = 1.127 (95% confidence interval [CI] = 1.098-1.156) for NNH = 83-91; AOR = 1.427 (95% CI = 1.398-1.456) for NNH = 17-48; AOR = 1.983 (1.9034-2.032) for NNH < 15. CONCLUSION: FRD/PIM use and age appear to have joint effects on fall risk. Older adults at high risk, indicated by small NNH, may be appropriate for fall prevention initiatives, and clinicians may wish to consider decreasing the number of FRD/PIMs utilized by these patients.

Adverse Events Associated With Antibiotics and Intravenous Therapies for Post-Lyme Disease Syndrome in a Commercially Insured Sample.

Background: Non-guideline-endorsed posttreatment courses of antibiotics for post-Lyme disease syndrome (PLDS) have been linked to adverse patient outcomes, but these findings have yet to be validated in large systematic evaluations. Methods: A retrospective cohort analysis of medical and pharmacy claims derived from the Truven Health Market Scan Commercial Claims and Encounters Database assessed 90-day incidence rates of adverse events (AEs) associated with PLDS treatment (PLDS-Tx). Patients were diagnosed with PLDS ≥6 months after initial diagnosis and standard antibiotic treatment for Lyme disease. Comparison cohorts included intravenous (IV) PLDS-Tx with or without oral antibiotics; oral antibiotic-only PLDS-Tx; or neither. Results: Composite AE incidence rates were higher for patients treated with IV or oral PLDS-Tx than for patients not receiving either treatment (18.7%, 16.8%, and 13.4%, respectively; P = .019). Significant between-group differences in AE incidence rates were noted for electrolyte imbalance (4.0%, 1.5%, and 0.7%, respectively; P = .001) and infection (14.0%, 12.7%, and 9.3%; P = .006). Infection prevalence increased by 22.0% in the IV treatment group and 17.7% in the oral group. Incidence rates for all-cause and AE-related hospital stays and emergency department visits were higher for treated than nontreated patients, particularly when treatment was IV (all P < .01). Of IV-treated patients, 7.3% experienced an incident all-cause inpatient stay and 11.3% an incident all-cause emergency department visit, compared with, respectively, 2.2% and 3.4% of those treated with oral antibiotics and 0.9% and 1.9% of nontreated patients. Conclusions: Use of IV therapies or oral antibiotics for PLDS was associated with increased patient morbidity within 90 days.

Updated cost-of-care estimates for commercially insured patients with multiple sclerosis: retrospective observational analysis of medical and pharmacy claims data.

BACKGROUND: For patients with multiple sclerosis (MS), previous research identified key disease sequelae as important cost drivers and suggested that among users of disease-modifying drugs (DMDs) in 2004, DMDs represented 73% of the total cost of care. More recent studies were limited to incident disease/treatment and/or excluded DMDs from cost estimates. To support contemporary pharmacoeconomic analyses, the present study was conducted to provide updated information about MS-related costs and cost drivers including DMDs. METHODS: For each of 2 years, 2006 and 2011, commercially insured, continuously eligible patients with ≥ 1 medical claim diagnosis of MS were sampled. MS-related charges were based on medical claims with MS diagnosis plus medical/pharmacy claims for DMDs. 2006 charges were adjusted to 2011 $ using the medical care component of the consumer price index (CPI). Subgroups of patients using DMDs (interferon [IFN] beta-1a intramuscular or subcutaneous, IFN beta-1b, glatiramer, natalizumab) in 2011 were identified. By-group differences were tested with bivariate statistics. RESULTS: Mean (standard deviation [SD]) age of 15,902 sample patients in 2011 was 47.6 (11.8) years, 76% female. Mean [SD] MS charges ($26,520 [$38,478] overall) were significantly (P < 0.001) higher for patients with common disease sequelae: malaise/fatigue (n = 2,235; $39,948 [$48,435]), paresthesia (n = 1,566; $33,648 [$45,273]), depression (n = 1,255; $42,831 [$51,693]), and abnormality of gait (n = 1,196; $48,361 [$55,472]). From 2006 to 2011, CPI-adjusted MS charges increased by 60%. Among patients treated with a single DMD in 2011, inpatient care was 6% of charges (range = 4%-8%; P = 0.155); outpatient care was 19% (range = 14%-20% except for natalizumab [29%]; P < 0.001); and DMDs were 75% (range = 67%-81%; P < 0.001). CONCLUSIONS: Common MS sequelae remain important cost drivers. Although MS treatment costs are increasing, the proportion of MS charges due to DMDs in 2011 is similar to that reported in 2004.

Finding our Voice: Evaluation of Goal Setting Using the Habits of Preceptors Rubric in Terms of Focus, "SMARTness," and Impact.

INTRODUCTION: Effective leadership propels teams from effectiveness to greatness and is accomplished when everyone achieves and contributes their full potential, or "voice." The Clinician Educators Program Teaching and Learning Curriculum fosters preceptor development using the Habits of Preceptors Rubric (HOP-R) to guide participants in finding their precepting "voice." After the HOP-R self-assessment, participants select a habit of focus (HOF) and craft a SMART (specific/measurable/achievable/relevant/time-bound) goal. This report describes a pilot rubric, SMART-EP (emotional intelligence(EI)/professionalism), exploring goal "SMARTness" alongside change (impact) in participants' perceived precepting capabilities. METHODS: HOP-R self-ratings (2018-2020) and HOF/SMART goals (2019-2020) were retrospectively reviewed by two raters. Perceived preceptor capabilities were measured by analyzing the change in self-assessed habit level ratings between the first/fourth-quarter surveys. SMART goals were categorized by HOF and inclusion of SMART-EP components. Participants were guided in the inclusion of SMART, but not -EP, components. RESULTS: In aggregate, 120 participants completed HOP-R surveys (2018-2020). Within-subject changes across all 11 habits were significant (P < .001). For the SMART-EP rubric analysis (2019-2020), 71 participants had an average "SMARTness" score of 3.92 (of 5) with corresponding interrater reliability of 0.91. Goals included 2.77 (of 4) EI traits and 1.72 (of 3) professionalism components. DISCUSSION: The SMART-EP rubric provided insights into preceptor development opportunities among participants. Beyond SMART components, participants often included elements of EI and professionalism. Ratings confirm and support the consistency of the HOP-R as a tool to assess precepting habits.

Pandemics, policy, and the power of paradigm: will COVID-19 lead to a new scientific revolution?

Critical historical analysis of the 19th-century cholera and 21st-century coronavirus-19 (COVID-19) pandemics suggests that in conflicts over pandemic-mitigation policies, the professional backgrounds of principal opponents reveal dominant and minority scientific paradigms, presaging possible epistemological shifts. Epistemic conflict over cholera helped spur biomedical expertise as the dominant paradigm for U.S. public health science and policy beginning in the 20th century. This paradigm was reflected in federal government reliance on infectious disease physicians as the primary scientific decision makers in the COVID-19 pandemic. Similarly, epistemic conflict over challenges to behavioral and social well-being in 2020 may highlight discordance between the dominant biomedical paradigm used in making federal policy and the inherently holistic impact of that policy on population health, suggesting need for a new paradigm of multidisciplinary scientific engagement. Because population-wide public health initiatives affect many aspects of health-physiological, psychological, behavioral, and social-that are best measured and interpreted by experts in these respective fields, multidisciplinary scientific engagement would facilitate optimal, holistic evaluation of policy benefits and harms. This multidisciplinary approach, analogous to that currently recommended in medical management of chronic disease, would advance epidemiological research to inform evidence-based policy for public health crises in which U.S. population-wide interventions are contemplated.

Association of Potential for Deaths of Despair With Age and Military Service Era.

INTRODUCTION: Predictors of deaths of despair, including substance use disorder, psychological distress, and suicidality, are known to be elevated among young adults and recent military veterans. Limited information is available to distinguish age effects from service-era effects. We assessed these effects on indicators of potential for deaths of despair in a large national sample of U.S. adults aged ≥19 years. MATERIALS AND METHODS: The study was a retrospective, cross-sectional analysis of publicly available data for 2015-2019 from 201,846 respondents to the National Survey on Drug Use and Health (NSDUH), which measures psychological symptoms and substance use behaviors using standardized scales and diagnostic definitions. Indicators of potential for a death of despair included liver cirrhosis, past-year serious suicidal ideation, serious psychological distress per the Kessler-6 scale, and active substance use disorder (e.g., binge drinking on ≥5 occasions in the past month, nonmedical use of prescribed controlled substances, and illicit drug use). Bivariate, age-stratified bivariate, and multivariate logistic regression analyses were performed using statistical software and tests appropriate for the NSDUH complex sampling design. Covariates included demographic characteristics, chronic conditions, and religious service attendance. RESULTS: Indicators were strongly and consistently age-associated, with ≥1 indicator experienced by 45.5% of respondents aged 19-25 years and 10.7% of those aged ≥65 years (P < .01). After age stratification, service-era effects were modest and occurred only among adults aged ≥35 years. The largest service-associated increase was among adults aged 35-49 years; service beginning or after 1975 was associated (P < .01), with increased prevalence of ≥1 indicator (30.2%-34.2% for veterans and 25.2% for nonveterans) or ≥2 indicators (6.4%-8.2% for veterans and 5.4% for nonveterans). Covariate-adjusted results were similar, with adjusted probabilities of ≥1 indicator declining steadily with increasing age: among those 19-34 years, 39.9% of nonveterans and 42.2% of Persian Gulf/Afghanistan veterans; among those aged ≥65 years, 10.3% of nonveterans, 9.2% of World War II/Korea veterans, and 14.4% of Vietnam veterans. CONCLUSIONS: After accounting for age, military service-era effects on potential for a death of despair were modest but discernible. Because underlying causes of deaths of despair may vary by service era (e.g., hostility to Vietnam service experienced by older adults versus environmental exposures in the Persian Gulf and Afghanistan), providers treating veterans of different ages should be sensitive to era-related effects. Findings suggest the importance of querying for symptoms of mental distress and actively engaging affected individuals, veteran or nonveteran, in appropriate treatment to prevent deaths of despair.

Association of Asthma Exacerbation Risk and Physician Time Expenditure With Provision of Asthma Action Plans and Education for Pediatric Patients.

OBJECTIVE: To provide information about factors underlying provision of asthma action plans (AAPs) to a minority of pediatric patients with asthma, assess whether risk of exacerbation acts on provision of AAP and asthma education directly, suggesting targeting to highest-risk patients, or indirectly by influencing physician-patient interaction time. METHODS: This study was a retrospective cross-sectional analysis of a nationally representative sample of physician office visits that consisted of patients aged 2 to 18 years with asthma. Exacerbation risk comprised proxy indicators of control and severity. Direct and time-mediated effects of exacerbation risk on provision of AAP and education were calculated from logistic regression models. RESULTS: Asthma action plans were provided in 14.3% of visits, education in 23.9%. Total direct effects of exacerbation risk (ORs = 3.88-4.69) far exceeded indirect, time-mediated effects (both ORs = 1.03) on AAPs. Direct effects on education were similar but smaller. After adjusting for risk, physician time expenditure of ≥30 minutes was associated with nearly doubled odds of providing AAP or education (ORs = 1.90-1.99). Visits that included allied health professionals alongside physician care were significantly associated with all 4 outcomes in multivariate analyses (ORs = 3.06-5.28). CONCLUSIONS: Exacerbation risk has a strong, direct association with AAP provision in pediatric asthma, even controlling for physician time expenditure. Provision of AAP and education to pediatric patients with asthma may be facilitated by increasing available time for office visits and involving allied health professionals.

A "Virtual Pharmacy Shelf" to Enhance the Rigor and Efficiency of Standardized-Patient OSCEs for Over-the-Counter Medication Advice.

BACKGROUND: Realistic simulation in health professional education can be costly or cumbersome. ACTIVITY: A low-cost, tablet-based simulated "virtual shelf" of over-the-counter (OTC) medications, hyperlinked to Drug Facts labels, eliminated use of physical product boxes or printed drug lists in objective structured clinical examinations (OSCE) for Doctor of Pharmacy students learning to provide OTC advice. RESULTS AND DISCUSSION: The application reduced instructor preparation and OSCE administration time by allowing students to tap product options instead of thumbing through medication lists. The shelf is realistic, easily updated, and transferable to other OSCEs when visual recognition is important or treatment options change frequently.

Association of Cardiovascular Disease and Military Veteran Status With Impairments in Physical and Psychological Functioning: Retrospective Cross-Sectional Analysis of US National Survey Data.

INTRODUCTION: The Veterans Health Administration (VHA) provides multidisciplinary team-based care with peer-to-peer support for diabetes and obesity, but not for most heart diseases. OBJECTIVE: To inform disease-care models, assess physical and psychological functioning in veterans with, or at high risk of, heart disease. METHODS: Retrospective, cross-sectional cohort analysis of data from the National Survey on Drug Use and Health, 2015-2019, based on standard measures of functioning: self-rated health, serious psychological distress, and high-risk substance use. Cohorts were veterans with respondent-reported heart disease, or at high risk of cardiovascular disease based on age/comorbidity combinations (HD/risk); nonveterans with HD/risk; and veterans without HD/risk. Ordinal logistic regression models adjusted for demographics, social determinants of health, and chronic conditions. A priori alpha was set to 0.01 because of large sample size (N = 28,314). RESULTS: Among those with HD/risk, veterans (n = 3,483) and nonveterans (n = 16,438) had similar physical impairments, but distress trended higher among veterans (adjusted odds ratio = 1.36, 99% confidence interval [CI] = 0.99-1.86). Among those with comorbid HD/risk and behavioral health problems, regression-adjusted treatment rates were similar for veterans and nonveterans with psychological symptoms (55.9% vs. 55.2%, respectively, P = 0.531) or high-risk substance use (18.7% vs. 19.4%, P = .547); veterans were more likely to receive outpatient mental health treatment (36.1% [CI = 34.4%-37.8%] vs. 28.9% [CI = 28.2%-29.6%]). CONCLUSION: An upward trend in distress among veterans compared with nonveterans with HD/risk was not explained by differences in behavioral health treatment utilization. Further research should test multidisciplinary team-based care for veterans with HD/risk, similar to that used for other chronic diseases.

Outcomes of Pharmacist-Conducted Admission Medication-Regimen Reviews in Long-term Care Facilities.

Objective To assess the outcomes of pharmacist-completed aMRRs. The 2018 installation of the Improving Medicare Post-Acute Care Transformation (IMPACT) Act requires medication regimen reviews (aMRR) upon admission to long-term care (LTC) hospitals, nursing facilities, and inpatient-rehabilitation facilities. While the legislation does not require that pharmacists perform the reviews, pharmacists are aptly suited to add value to this practice. Design Retrospective analysis of residents admitted to LTC facilities. Setting Twenty-four LTC facilities located in Arizona served by one pharmacist-consult service. Patients, Participants Cohort of 603 LTC residents whose medical records were reviewed by consultant pharmacists during March 2020. Results For 603 residents, 1092 aMRRs were completed and 921 interventions were made. The most prevalent interventions were medication monitoring (N = 276), medications without appropriate indication (N = 130), and overdosage (N = 116). Of 921 interventions, 41 were classified as ECA Level 6, avoided hospital admission, and 30 as Level 7, avoided life-threatening event. Of 165 recommendations rated by both pharmacy student assessors and a supervising postgraduate year 2 resident, agreement occurred in 161 (97.6% agreement, kappa reliability = 0.934). Conclusion Pharmacist-conducted aMRRs identified clinically important threats to patient safety. Study results demonstrate potential for positive economic and resident care outcomes from pharmacist-performed aMRR interventions.

Modest Association of Long-Term ACE Inhibitor Treatment With Lung Cancer: The Promise and Pitfalls of Epidemiological Drug-Safety Analyses.

Results of the carefully executed Evaluation of Treatment with Angiotensin Converting Enzyme Inhibitors and the Risk of Lung Cancer (ERACER) study, reported in this issue, echo those of several previous observational analyses of the association of long-term angiotensin-converting enzyme (ACE) inhibitor use with incident lung cancer. These epidemiological drug-safety analyses merit cautious interpretation. First, the number needed to harm (NNH) of 6667 reported in ERACER for ACE inhibitors compared with angiotensin-2 receptor blockers (ARBs) after approximately 12 years of follow-up should be balanced against therapeutic benefits. Previously reported meta-analyses of randomized controlled trials (RCTs) over a mean 4.3-year follow-up suggested number needed to treat (NNT) of 67 for all-cause mortality, 116 for cardiovascular mortality, and 86 for a composite of myocardial infarction (MI) and stroke for ACE inhibitors, compared with nonsignificant benefits for ARBs on the mortality outcomes and NNT of 157 for ARBs on the MI/stroke composite. Second, confounding by indication is possible because until 2013, ACE inhibitors, not ARBs, were first-line medications for heart failure, which is associated with incident lung cancer. Third, findings may be compromised by detection bias due to investigation of ACE inhibitor-induced cough, or by residual confounding due to influential factors not measurable in the available data, such as socioeconomic status (SES) or smoking history. The important questions raised by ERACER and similar drug-safety analyses should be addressed in long-term RCTs or in enhanced large-database pharmacoepidemiological analyses, measuring both NNH and NNT and controlling for SES, indication, medication, and dosage.

Physical and psychological functioning in veterans with diabetes: Disease-related versus service-related effects.

OBJECTIVE: Research on veterans with diabetes (VWD) suggested elevated rates of mental illness and substance use disorder but used samples studied 14-21 years ago without comparator groups. To inform translational research and care-delivery models for diabetes, the purpose of this study was to compare VWD, nonveterans with diabetes (NVWD), and veterans without diabetes (VWOD) on physical and psychological functioning. METHOD: The study was a retrospective analysis of cross-sectional data from the National Survey on Drug Use and Health, a population-based household-interview survey, 2015 to 2018. Psychological disorders and high-risk substance use were identified with validated scales and standard diagnostic definitions. RESULTS: Regardless of veteran status, diabetes was associated with impaired health: self-rated poor health 9.3% VWD (n = 1,320), 9.0% NVWD (n = 10,246), 3.5% VWOD (n = 8,314); past-year hospitalization 20.4-23.9% for those with diabetes, 12.9% for VWOD (p < .001); obesity 49.0-54.8% for those with diabetes, 31.8% for VWOD. Mental illness was more prevalent in those with diabetes (17.0-21.8%) than in VWOD (14.8%); high-risk substance use was less prevalent (9.7-9.8% vs. 14.0%, p < .001). Post hoc analysis by active-duty service era identified high rates of psychological problems, including mental illness (29.7%), among VWD with recent service. CONCLUSIONS: Diabetes is associated with similar impairments in veterans and nonveterans. Among VWD, recent service may increase psychological risk. Findings support guideline-recommended patient-centered care for VWD and NVWD. Translational research should assess expansion of Veterans Health Administration (VHA) multidisciplinary disease- and self-management models to non-VHA settings. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Unexplained mortality during the US COVID-19 pandemic: retrospective analysis of death certificate data and critical assessment of excess death calculations.

OBJECTIVES: Cause-of-death discrepancies are common in respiratory illness-related mortality. A standard epidemiological metric, excess all-cause death, is unaffected by these discrepancies but provides no actionable policy information when increased all-cause mortality is unexplained by reported specific causes. To assess the contribution of unexplained mortality to the excess death metric, we parsed excess deaths in the COVID-19 pandemic into changes in explained versus unexplained (unreported or unspecified) causes. DESIGN: Retrospective repeated cross-sectional analysis, US death certificate data for six influenza seasons beginning October 2014, comparing population-adjusted historical benchmarks from the previous two, three and five seasons with 2019-2020. SETTING: 48 of 50 states with complete data. PARTICIPANTS: 16.3 million deaths in 312 weeks, reported in categories-all causes, top eight natural causes and respiratory causes including COVID-19. OUTCOME MEASURES: Change in population-adjusted counts of deaths from seasonal benchmarks to 2019-2020, from all causes (ie, total excess deaths) and from explained versus unexplained causes, reported for the season overall and for time periods defined a priori: pandemic awareness (19 January through 28 March); initial pandemic peak (29 March through 30 May) and pandemic post-peak (31 May through 26 September). RESULTS: Depending on seasonal benchmark, 287 957-306 267 excess deaths occurred through September 2020: 179 903 (58.7%-62.5%) attributed to COVID-19; 44 022-49 311 (15.2%-16.1%) to other reported causes; 64 032-77 054 (22.2%-25.2%) unexplained (unspecified or unreported cause). Unexplained deaths constituted 65.2%-72.5% of excess deaths from 19 January to 28 March and 14.1%-16.1% from 29 March through 30 May. CONCLUSIONS: Unexplained mortality contributed substantially to US pandemic period excess deaths. Onset of unexplained mortality in February 2020 coincided with previously reported increases in psychotropic use, suggesting possible psychiatric or injurious causes. Because underlying causes of unexplained deaths may vary by group or region, results suggest excess death calculations provide limited actionable information, supporting previous calls for improved cause-of-death data to support evidence-based policy.

What is the price benchmark to replace average wholesale price (AWP)?

An article on the front page of the Wall Street Journal on October 6, 2006, thrust into the public media the otherwise esoteric controversy concerning the use of average wholesale price (AWP) as the primary basis for reimbursements to pharmacies for pharmaceuticals in the United States. Although used widely for nearly 40 years, AWP had been criticized prior to this investigative report as unreliable, subject to manipulation, and not representative of the actual purchase price for pharmaceuticals. The Wall Street Journal article, based on a tentative settlement of litigation in which First DataBank (San Francisco, CA) and the McKesson Corporation (San Francisco, CA) were accused of unilaterally increasing AWPs, included the findings that (a) at least since 2003, AWP was not based on calculation of an "average" wholesale price but instead reflected the pricing of McKesson Corporation, a single drug wholesaler; and (b) AWP had undergone a systematic change beginning in 2001 when First DataBank had converted its markups of wholesale acquisition cost (WAC) to a common multiplier of 1.25,1 effectively increasing the AWP by 4% for AWPs that were previously calculated using a multiplier of 1.20. In March 2009, the future of AWP became uncertain as a result of circumstances surrounding the court settlement of the litigation that had begun in 2005 against First DataBank. On March 17, 2009, U.S. District Court Judge Patti B. Saris approved the proposed settlement of 2 civil action lawsuits filed by private health plan payers of pharmaceuticals against the 2 largest publishers of AWP, First DataBank (along with wholesaler McKesson) and Medi-Span (Indianapolis, IN, subsidiary of Wolters Kluwer Health). On March 30, 2009, Judge Saris signed a final order and judgment certifying the class (of "Private Payor" purchasers) which settled 2 national class action lawsuits against the 2 largest publishers of AWP. As part of the formal settlement, Medi-Span and First DataBank agreed to adjust the markup factor used to calculate AWP downward to 1.20 times WAC "for any prescription pharmaceutical" that had "a mark up factor basis from WAC to AWP in excess of 1.20" for the 1,442 specific national drug code (NDC) numbers that were listed in the court complaint. The "rollback" of AWP as a result of reducing the WAC/DP (direct price) multiplier to no more than 1.20 was implemented by First DataBank and Medi-Span on September 26, 2009, 180 days from the date of the judgment, as ordered. At the same time, these AWP publishers voluntarily implemented price modifications to all products that had a WAC markup greater than 1.20. This decision expanded the list of NDC numbers from the 1,442 specified in the lawsuit to well over 50,000 items. The expanded list included both prescription and nonprescription (over-the-counter [OTC]) items, both active and inactive NDC numbers on the drug database, as well as a variety of markup factors. The adjusted AWPs had markup factors that ranged from 1.20 to 1.33. About two-thirds to three-fourths of the NDC numbers with adjusted AWPs had a pre-settlement WAC markup of 1.25. This U.S. District Court decision on March 30, 2009, was also accompanied by separate announcements from the defendants Medi-Span and First DataBank that they would voluntarily discontinue publication of AWP.

Changes in PBM Business Practices in 2019: True Innovation or More of the Same?

In 2019, pharmacy benefit managers (PBMs) responded to intense public criticism with business model changes described as movements toward full transparency and innovation to reduce costs for benefit plan sponsors. We critically analyze these changes in light of key challenges in specialty drug management: pharmaceutical manufacturer practices (price increases driven by coverage mandates and lack of price control, intensive and sometimes misleading advertising, patent extensions), FDA changes (increased reliance on manufacturer funding, weakened evidentiary base for drug approvals), and provider prescribing patterns (lag from evidence to routine practice, manufacturer influences on the knowledge base, direct manufacturer payments to frequent prescribers). The persistence of controversial PBM practices suggests that business model changes were mostly cosmetic, without altering key marketplace dysfunctions. Examples include "spread" pricing, in which PBMs pay pharmacies less than employer-paid amounts; rebate-influenced formulary development; and shifting of prescription volume to PBM-owned pharmacies. Spread in Medicaid was estimated at $224.8 million in Ohio and $123.5 million in Kentucky in 1-year periods and is the subject of an ongoing federal investigation. Rebate influence on formulary development is suggested by slow biosimilar adoption and a study documenting little association between brand exclusions and clinical or cost-effectiveness. Even in 100% passthrough arrangements, the price differential between rebated products and lower-cost alternatives may far exceed revenues returned to the payer. Shifting of business to PBM-owned pharmacies was identified in Florida managed Medicaid in 2018, where the state's 5 largest specialty pharmacies, all owned by managed care organizations or PBMs, collected 28% of prescription drug profit despite dispensing only 0.4% of claims. Finally, contract provisions and terms typically limit the ability of plan sponsors to monitor PBM performance. These include "offsetting," changes in definitions (e.g., "single-source generic") during the contract term, restrictions on audit rights, and exclusion of some pharmaceutical manufacturer revenues from "100%" passthroughs. We conclude that ostensibly positive changes in PBM practices have been offset by undisclosed business arrangements, shifts to alternative revenue sources, and opaque contractual terms. Establishing and maintaining a sustainable benefit will require fundamental alterations to this dysfunctional market DISCLOSURES: This work was funded solely by Archimedes, with no external funding. Motheral is the CEO of Archimedes, a specialty drug management company, and EpiphanyRx, a PBM that provides alternatives to the business models described in this article. Fairman is a consultant to Archimedes.

Treatment Needs and Service Utilization in Older U.S. Adults Evidencing High-Risk Substance Use.

Objectives: Because substance misuse by older adults poses clinical risks and has not been recently assessed, we examined substance use patterns, treatment needs, and service utilization in those evidencing high-risk use. Methods: We identified National Survey on Drug Use and Health respondents (2015-2018) aged ≥50 years reporting multiple-occasion binge drinking, illicit drug use, prescription drug misuse, or substance dependence. Past-year psychological symptoms were assessed using validated scales. Results: The sample, representing 10.2% of community-dwelling older U.S. adults, evidenced clinically important risks: 65.2% past-month binge drinking, 27.3% mental illness, 14.3% psychological distress, 10.6% combined alcohol/drug use, and 6.5% suicidality. Treatment receipt was uncommon (27.7%), positively associated with distress, and negatively associated with binge drinking. Of those not receiving treatment, 3.8% perceived treatment need. Discussion: Findings highlight the value of substance misuse screening and brief interventions, suggesting potential treatment referral opportunities for those evidencing psychological distress.