Genomic signatures of exceptional longevity and negligible aging in the long-lived red sea urchin.

The red sea urchin (Mesocentrotus franciscanus) is one of the Earth's longest-living animals, reported to live more than 100 years with indeterminate growth, life-long reproduction, and no increase in mortality rate with age. To understand the genetic underpinnings of longevity and negligible aging, we constructed a chromosome-level assembly of the red sea urchin genome and compared it to that of short-lived sea urchin species. Genome-wide syntenic alignments identified chromosome rearrangements that distinguish short- and long-lived species. Expanded gene families in long-lived species play a role in innate immunity, sensory nervous system, and genome stability. An integrated network of genes under positive selection in the red sea urchin was involved in genomic regulation, mRNA fidelity, protein homeostasis, and mitochondrial function. Our results implicated known longevity genes in sea urchin longevity but also revealed distinct molecular signatures that may promote long-term maintenance of tissue homeostasis, disease resistance, and negligible aging.

Impact of Season and Other Factors on Initiation, Discontinuation, and Switching of Systemic Drug Therapy in Patients with Psoriasis: A Retrospective Study.

This study investigated whether systemic drug prescribing for psoriasis varies by season and other exacerbating factors. Eligible patients with psoriasis were assessed for each season for initiation, discontinuation, and switching of systemic drugs. A total of 360,787 patients were at risk of initiating any systemic drugs in 2016‒2019; 39,572 patients and 35,388 patients were at risk of drug discontinuation or switching to a biologic and a nonbiologic systemic drug, respectively. The initiation of biologic therapy in 2016‒2019 peaked in spring (1.28%), followed by summer (1.11%), fall (1.08%), and winter (1.01%). Nonbiologic systemic drugs followed a similar pattern. Those aged 30‒39 years, male, those with psoriatic arthritis, those who live in the South region, those who live in areas with lower altitudes, and those who live in areas with lower humidity had higher initiation with the same seasonality pattern. Discontinuation of biologic drugs peaked in summer, and switching of biologics was highest in spring. Season is associated with initiation, discontinuation, and switching, although seasonality pattern is less clear for nonbiologic systemic drugs. Approximately 14,280 more patients with psoriasis in the United States are estimated to initiate a biologic in spring than in other seasons, and over 840 more biologic users switched in spring than in winter. The findings may provide evidence for healthcare resource planning in psoriasis management.

Evaluation of VTE, MACE, and Serious Infections Among Patients with RA Treated with Baricitinib Compared to TNFi: A Multi-Database Study of Patients in Routine Care Using Disease Registries and Claims Databases.

INTRODUCTION: The aim of this work is to evaluate baricitinib safety with respect to venous thromboembolism (VTE), major adverse cardiovascular events (MACE), and serious infection relative to tumor necrosis factor inhibitors (TNFi) in patients with rheumatoid arthritis (RA). METHODS: Patients with RA from 14 real-world data sources (three disease registries, eight commercial and three government health insurance claims databases) in the United States (n = 9), Europe (n = 3), and Japan (n = 2) were analyzed using a new user active comparator design. Propensity score matching (1:1) controlled for potential confounding. Meta-analysis of incidence rate ratios (IRR) and incidence rate differences (IRD) for each outcome, from each data source was executed using modified Poisson regression and Cochran-Mantel-Haenszel analysis. RESULTS: Of 9013 eligible baricitinib-treated patients, 7606 were propensity score-matched with TNFi-treated patients, contributing 5879 and 6512 person-years of baricitinib and TNFi exposure, respectively. Across data sources, 97 patients (56 baricitinib) experienced VTE during follow-up, 93 experienced MACE (54 baricitinib), and 321 experienced serious infection (176 baricitinib). Overall IRRs comparing baricitinib with TNFi treatment were 1.51 (95% CI 1.10, 2.08) for VTE, 1.54 (95% CI 0.93, 2.54) for MACE, and 1.36 (95% CI 0.86, 2.13) for serious infection. IRDs for VTE, MACE, and serious infection, respectively, were 0.26 (95% CI -0.04, 0.57), 0.22 (95% CI -0.07, 0.52), and 0.57 (95% CI -0.07, 1.21) per 100 person-years greater for baricitinib than TNFi. CONCLUSIONS: Overall results suggest increased risk of VTE with baricitinib versus TNFi, with consistent point estimates from the two largest data sources. A numerically greater risk was observed for MACE and serious infection when comparing baricitinib versus TNFi, with different point estimates from the two largest data sources. Findings from this study and their impact on clinical practice should be considered in context of limitations and other evidence regarding the safety and efficacy of baricitinib and other Janus kinase inhibitors. TRIAL REGISTRATION: EU PAS Register ( http://encepp.eu ), identifier #32271.

Durability of the Single-Dose Ad26.COV2.S Vaccine in the Prevention of COVID-19 Infections and Hospitalizations in the US Before and During the Delta Variant Surge.

Importance: Vaccination against the SARS-CoV-2 virus is critical to control the pandemic. Randomized clinical trials demonstrated efficacy of the single-dose Ad26.COV2.S COVID-19 vaccine, but data on longer-term protection in clinical practice and effectiveness against variants are needed. Objective: To assess the association between receiving the Ad26.COV2.S vaccine and COVID-19-related infections and hospitalizations before and during the Delta variant surge. Design, Setting, and Participants: This cohort study included adults aged 18 years and older who were newly Ad26.COV2.S-vaccinated matched to as many as 10 unvaccinated individuals by date, location, age, sex, and comorbidity index. This was followed by 1:4 propensity score matching on COVID-19 risk factors. Data were collected from US insurance claims data from March 1, 2020, through August 31, 2021. Exposures: Vaccination with Ad26.COV2.S vs no vaccination. Main Outcomes and Measures: Vaccine effectiveness (VE) was estimated for recorded COVID-19 infection and COVID-19-related hospitalization, nationwide and in subgroups by age, high-risk factors, calendar time, and states with high incidences of the Delta variant. VE estimates were corrected for underrecording of vaccinations in insurance data. Results: Among 422 034 vaccinated individuals (mean [SD] age, 54.7 [17.4] years; 236 437 [56.0%] women) and 1 645 397 matched unvaccinated individuals (mean [SD] age, 54.5 [17.5] years; 922 937 [56.1%] women), VE was 76% (95% CI, 75%-77%) for COVID-19 infections and 81% (95% CI, 78%-82%) for COVID-19-related hospitalizations. VE was stable for at least 180 days after vaccination and over calendar time. Among states with high Delta variant incidence, VE during June to August 2021 was 74% (95% CI, 71%-77%) for infections and 81% (95% CI, 75%-86%) for hospitalizations. VE for COVID-19 was higher in individuals younger than 65 years (78%; 95% CI, 77%-79%) and lower in immunocompromised patients (64%; 95% CI, 59%-68%). All estimates were corrected for vaccination underrecording; uncorrected VE, which served as a lower bound, was 66% (95% CI, 64%-67%) for any recorded COVID-19 infection and 72% (95% CI, 69%-74%) for COVID-19-related hospitalization. Conclusions and Relevance: This cohort study in US clinical practice showed stable VE of Ad26.COV2.S for at least 6 months before as well as during the time the Delta variant emerged and became dominant.

The American lobster genome reveals insights on longevity, neural, and immune adaptations.

The American lobster, Homarus americanus, is integral to marine ecosystems and supports an important commercial fishery. This iconic species also serves as a valuable model for deciphering neural networks controlling rhythmic motor patterns and olfaction. Here, we report a high-quality draft assembly of the H. americanus genome with 25,284 predicted gene models. Analysis of the neural gene complement revealed extraordinary development of the chemosensory machinery, including a profound diversification of ligand-gated ion channels and secretory molecules. The discovery of a novel class of chimeric receptors coupling pattern recognition and neurotransmitter binding suggests a deep integration between the neural and immune systems. A robust repertoire of genes involved in innate immunity, genome stability, cell survival, chemical defense, and cuticle formation represents a diversity of defense mechanisms essential to thrive in the benthic marine environment. Together, these unique evolutionary adaptations contribute to the longevity and ecological success of this long-lived benthic predator.

Unique age-related transcriptional signature in the nervous system of the long-lived red sea urchin Mesocentrotus franciscanus.

The red sea urchin, Mesocentrotus franciscanus, is one the earth's longest-lived animals, reported to live more than 100 years with indeterminate growth, life-long reproduction and no increase in mortality rate with age. To gain insight into mechanisms associated with longevity and negligible senescence, age-related transcriptional profiles were examined in tissues of the red sea urchin. Genome-wide transcriptional profiling using RNA-Seq revealed few age-related changes in gene expression in muscle and esophagus tissue. In contrast, radial nerve showed an unexpected level of complexity with the expression of 3,370 genes significantly altered more than two-fold with age, including genes involved in nerve function, signaling, metabolism, transcriptional regulation and chromatin modification. There was an age-related upregulation in expression of genes involved in synaptogenesis, axonogenesis and neuroprotection suggesting preservation of neuronal processes with age. There was also an upregulation in expression of positive regulators and key components of the AMPK pathway, autophagy, proteasome function, and the unfolded protein response. This unique age-related gene expression profile in the red sea urchin nervous system may play a role in mitigating the detrimental effects of aging in this long-lived animal.

Metabarcoding assessment of prokaryotic and eukaryotic taxa in sediments from Stellwagen Bank National Marine Sanctuary.

Stellwagen Bank National Marine Sanctuary (SBNMS) in the Gulf of Maine is a historic fishing ground renowned for remarkable productivity. Biodiversity conservation is a key management priority for SBNMS and yet data on the diversity of microorganisms, both prokaryotic and eukaryotic, is lacking. This study utilized next generation sequencing to characterize sedimentary communities within SBNMS at three sites over two seasons. Targeting 16S and 18S small subunit (SSU) rRNA genes and fungal Internal Transcribed Spacer (ITS) rDNA sequences, samples contained high diversity at all taxonomic levels and identified 127 phyla, including 115 not previously represented in the SBNMS Management Plan and Environmental Assessment. A majority of the diversity was bacterial, with 59 phyla, but also represented were nine Archaea, 18 Animalia, 14 Chromista, eight Protozoa, two Plantae, and 17 Fungi phyla. Samples from different sites and seasons were dominated by the same high abundance organisms but displayed considerable variation in rare taxa. The levels of biodiversity seen on this small spatial scale suggest that benthic communities of this area support a diverse array of micro- and macro-organisms, and provide a baseline for future studies to assess changes in community structure in response to rapid warming in the Gulf of Maine.

Two-Way Clinical Messaging in a CML Specialty Pharmacy Service Model.

BACKGROUND: Adherence to treatment is correlated with treatment success in chronic myeloid leukemia (CML). CVS Specialty explored novel methods to improve adherence in this population to ensure optimal adherence and lower the risk of unsuccessful treatment. One novel program explored involved an interactive 2-way clinical messaging technology that coaches patients with adherence and knowledge about taking their treatment and managing their conditions. Clinical secure messaging is a 2-way messaging program distinct from the 1-way refill reminders and order status messages that patients were receiving if opted into the messaging program. OBJECTIVE: To assess the effect on adherence of 2-way clinical messaging in a CML population treated with tyrosine kinase inhibitors (TKIs) compared with patients enrolled in 1-way refill reminders. METHODS: A retrospective cohort study was conducted using prescription claims data. Patients new to TKI therapy and enrolled in at least 1-way messaging were identified and divided into control and study cohorts based on clinical messaging enrollment status. Participants were followed for 365 days after their first fill. Adherence outcomes were defined by medication possession ratio (MPR), length of therapy, first fill drop-off rate, and gap days between refills. Optimal adherence was defined as an MPR ≥ 85%. RESULTS: Patients receiving clinical messaging had on average a 7.64% higher MPR score (MPR: 73.94% vs. 66.30%) compared with the control arm (P = 0.0063). This translates to 22% more patients being optimally adherent while exposed to clinical messaging (P = 0.022). Patients in the exposed group had a mean 32-day increase in average length of therapy compared with the control group (243 days vs. 275 days, P = 0.0043), potentially driving an increase in adherence. Additional drivers included a 5.4 percentage point reduction in first fill drop-off rates (4.66% vs. 10.04%, P = 0.0149). Persistency after 12 months was similar between the study arms (41%). CONCLUSIONS: Two-way clinical messaging positively affected adherence outcomes in a CML population. This effect was in addition to 1-way refill reminders and order status messages. The nature of the clinical content encourages further investigation into this novel execution of adherence coaching and counseling through a digital platform. DISCLOSURES: Funding for this research was provided by CVS Health. The sponsor was involved at all stages of the study's conduct and reporting. Sawicki and Friend are employed by CVS Health. The other authors were employed by CVS at the time of this study. The authors have nothing more to disclose. Posters based on this work were presented at the AMCP Managed Care & Specialty Pharmacy Annual Meeting 2016; April 19-22, 2016; San Francisco, CA, and AMCP Nexus 2016; October 3-6, 2016; National Harbor, MD.

Correction to: Outcomes Associated with Generic Drugs Approved Using Product-Specific Determinations of Therapeutic Equivalence.

Page 432, Fig. 2 Plots of model-based outcome incidence rates (per 100 person-years of exposure) before and after introduction of first generic versions of study and control drugs.

Impact of a patient engagement tool on preventive service uptake.

BACKGROUND: We studied whether integrating the US Department of Health and Human Services' myHealthfinder tool, an interactive tool that recommends preventive services, into CVS Health's digital platforms could increase preventive service uptake at its retail clinic, MinuteClinic. METHODS: We used a quasi-experimental, pre-post, difference-in-differences design. In a web-based campaign, consumers in "exposed" states visiting CVS pharmacy and MinuteClinic websites could view and use the myHealthfinder tool. Consumers in "unexposed" states could not. A September 26, 2015 email campaign to registered MinuteClinic patients in exposed states described and included links to the myhealthfinder tool. We assessed consumer engagement with the myHealthfinder tool via number of website visits, myHealthfinder sessions, and myHealthfinder recommendations delivered. Using the difference-in-differences approach, we assessed mean changes in influenza, pneumococcal, and/or hepatitis A vaccine uptake, as well as other preventive services, per clinic, per month at MinuteClinics. RESULTS: In exposed states, 39,225 (1.6%) website visits included myhealthfinder use, and 13,688 personalized recommendations for preventive services were delivered. The web-based campaign was associated with an increase in mean pneumococcal vaccines (1.19 vaccines per clinic per month; 95% CI, 0.11-2.28). The email campaign resulted in a 5% increase in influenza vaccines (74.83 vaccines per clinic per month; 1.65-148.02). The myhealthfinder campaigns did not significantly change preventive service uptake for any of the other services at MinuteClinics. CONCLUSIONS: Our findings highlight the potential role of personalized patient education tools and public-private partnerships to communicate about preventive care. Getting patients to act on these recommendations was more difficult.

"Impact of drug-reimbursement policies on prescribing: A case-study of a newly marketed long-acting injectable antipsychotic among relapsed schizophrenia patients".

OBJECTIVE: To quantify and explain variation in use of long-acting injectable antipsychotics (LAIs) in the United States, and understand the relationship between patient characteristics, drug reimbursement policies, and LAI prescribing after relapse. METHODS: A cohort of recently relapsed patients with schizophrenia ages 18 to 64, were identified immediately after discharge from a related inpatient hospitalization, partial hospitalization, or emergency room visit, drawn from 2004 to 2006 Medicaid claims, and followed for 90 days until LAI initiation. Data on state-level Medicaid prior authorization (PA) policies for LAIs were collected. Sequential longitudinal Poisson regression models were developed to understand the relationship between patient and PA policy variables and LAI prescribing, including prior adherence to oral antipsychotics, demographics, clinical variables, and presence of PA policy for LAI. RESULTS: Among 36 282 patients, 3.1% received risperidone LAI, and 3.8% received a first-generation (FGA) LAI with wide variation across states. Prior adherence ranged from 29% to 89% but was marginally associated with initiation and did not explain variation for LAI prescribing. FGA initiation was associated with geography and race/ethnicity but not PA policy. For risperidone LAI initiation, demographics and clinical factors explained, respectively, 5.0% and 3.0% of the variation; PA policy had a large negative association with initiation (RR = 0.41; 95%CI 0.20-0.87) and explained 8.4% of the variation. CONCLUSIONS: PA policies may represent a major treatment barrier for risperidone LAI among relapsed patients. Non-adherence plays a little role in predicting which patients receive LAIs. Policy makers and health insurers will need to consider these findings when guiding the use of LAIs. KEY POINTS Among a nationwide cohort of relapsed schizophrenia patients enrolled in US Medicaid, 3.1% received Risperdal Consta, a long-acting injectable antipsychotic (LAI), and 3.8% initiated a first-generation first-generation LAI within 90 days after discharge. During 2004 to 2006, there was marked variation in 90 day post-relapse initiation of Risperdal-Consta-a newly marketed medication during this period-and also marked variation in 90 day post-relapse initiation of any first-generation LAI, which appeared to be associated with race/ethnicity and geography. Prior authorization policies were associated with substantially lower initiation of Risperdal Consta in this cohort of relapsed patients even after accounting for clinical indication (non-adherence), relapse history, demographics, adjunctive medication, and mental health service use.

Automatable algorithms to identify nonmedical opioid use using electronic data: a systematic review.

OBJECTIVE: Improved methods to identify nonmedical opioid use can help direct health care resources to individuals who need them. Automated algorithms that use large databases of electronic health care claims or records for surveillance are a potential means to achieve this goal. In this systematic review, we reviewed the utility, attempts at validation, and application of such algorithms to detect nonmedical opioid use. MATERIALS AND METHODS: We searched PubMed and Embase for articles describing automatable algorithms that used electronic health care claims or records to identify patients or prescribers with likely nonmedical opioid use. We assessed algorithm development, validation, and performance characteristics and the settings where they were applied. Study variability precluded a meta-analysis. RESULTS: Of 15 included algorithms, 10 targeted patients, 2 targeted providers, 2 targeted both, and 1 identified medications with high abuse potential. Most patient-focused algorithms (67%) used prescription drug claims and/or medical claims, with diagnosis codes of substance abuse and/or dependence as the reference standard. Eleven algorithms were developed via regression modeling. Four used natural language processing, data mining, audit analysis, or factor analysis. DISCUSSION: Automated algorithms can facilitate population-level surveillance. However, there is no true gold standard for determining nonmedical opioid use. Users must recognize the implications of identifying false positives and, conversely, false negatives. Few algorithms have been applied in real-world settings. CONCLUSION: Automated algorithms may facilitate identification of patients and/or providers most likely to need more intensive screening and/or intervention for nonmedical opioid use. Additional implementation research in real-world settings would clarify their utility.

The impact of a retail prescription synchronization program on medication adherence.

OBJECTIVES: To understand the impact of prescription synchronization, offered through the ScriptSync® program at CVS pharmacies nationwide, on adherence and reducing visits to the pharmacy. DESIGN: Cohort study, conducted between March 26, 2015, and December 18, 2015. Program enrollment occurred in August 2015, with a 120-day baseline period preceding enrollment and a 120-day follow-up period. SETTING AND PARTICIPANTS: CVS retail community pharmacies across the United States. CVS Pharmacy patients voluntarily enrolling in the prescription synchronization program at CVS retail community pharmacies across the United States who filled 3 or more eligible prescriptions before program enrollment. The study included 126,597 patients who enrolled in the program and 81,355 patients who enrolled after the study enrollment period. OUTCOME MEASURES: Adherence was defined as the medication possession ratio. The average number of pharmacy visits per month was a second outcome measure. RESULTS: Exposed patients had a 7.5 percentage point adherence improvement (from 79.6% to 87.1%), compared with a 2.8 percentage point improvement among the unexposed (from 78.1% to 80.9%) for a benefit of 4.7 percentage points (P < 0.0001). Among patients with adherence opportunities, the net impact on adherence was 10.6% (P < 0.0001). The program resulted in 0.17 fewer visits per month (P < 0.0001). CONCLUSION: Offering prescription refill synchronization at a large national retail pharmacy chain resulted in improved adherence and fewer visits to the pharmacy in the 4 months following ScriptSync enrollment. Prescription refill synchronization programs should be considered in the care of patients with multiple comorbidities.

Antibiotic stewardship in the retail clinic setting: Implementation in 1100 clinics nationwide.

In light of increasing antibiotic resistance and a slowed antibiotic development pipeline, stewardship is more urgent than ever. To date, most stewardship guidelines and best practice recommendations for implementation focus on local or regional health care organizations. CVS MinuteClinic has implemented a consistent, evidence-based stewardship approach in its >1100 clinics in 33 states. The approach is associated with higher quality antibiotic use than that in primary care practices and emergency departments. Given MinuteClinic's scale, sharing this approach and lessons learned may assist other organizations in implementing large-scale stewardship programs that foster judicious use of antibiotics for the public's health.

Association of Changes in Medication Use and Adherence With Accountable Care Organization Exposure in Patients With Cardiovascular Disease or Diabetes.

Importance: Many of the quality measures used to assess accountable care organization (ACO) performance in the Medicare Shared Savings Program (MSSP) focus on disease control and medication use among patients with cardiovascular disease and diabetes. To date, the association between participation in the MSSP by provider organizations and medication use or adherence among their patients with cardiovascular disease or diabetes has not been described. Objective: To assess the association between exposure to the MSSP and changes in the use of and adherence to common antihypertensive, lipid-lowering, and hypoglycemic medications. Design, Setting, and Participants: Fee-for-service Medicare claims from January 1, 2009, to December 31, 2014, were used to conduct difference-in-differences comparisons of changes for ACO-attributed beneficiaries from before the start of ACO contracts to 2014 with concurrent changes for beneficiaries attributed to local non-ACO providers (control group). A random 20% sample of Medicare beneficiaries contributing 4 482 168 to 10 849 224 beneficiary-years for analysis from 2009 to 2014, depending on the drug class, was examined. Differential changes were estimated separately for cohorts of ACOs entering the MSSP in 2012, 2013, and 2014. Data analysis was conducted from November 1, 2016, to April 5, 2017. Exposures: Patient attribution to an ACO after entry into the MSSP. Main Outcomes and Measures: Any use (at least 1 prescription fill) and proportion of days covered (PDC), a standard claims-based measure of adherence, assessed for each of 6 drug classes: statins, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers, ß-blockers, thiazide diuretics, calcium channel blockers, and metformin. Results: Differences in patient characteristics between the MSSP and control group were generally small after geographic adjustment and changed minimally from the precontract period to 2014. There were no significant differential changes in medication use from the precontract period to 2014 for any cohort of MSSP ACOs in any drug class, except for a slight differential increase in the use of thiazides among beneficiaries with hypertension in the 2013 entry cohort (adjusted differential change, 0.5 percentage point; 95% CI, 0.1-0.8 percentage points; or 1.5% of the overall percentage using thiazides [33.4%], P = .01). Similarly, there were no significant differential changes in PDC among beneficiaries with at least 1 prescription fill, except for slight differential increases in the PDC for ß-blockers in the 2012 entry cohort (adjusted differential change, 0.3 percentage point; 95% CI, 0.1-0.5 percentage points; or 0.4% of the mean PDC [82.3%], P = .003) and for metformin in the 2012 and 2013 cohorts (adjusted differential change, 0.5 percentage point; 95% CI, 0.1-0.9 percentage points; or 0.6% of the mean PDC [78.2%], P = .01 for both). Conclusions and Relevance: Exposure to the MSSP has not been associated with meaningful changes in medication use or adherence among patients with cardiovascular disease and diabetes.

Home infusion: Safe, clinically effective, patient preferred, and cost saving.

BACKGROUND: As the U.S. healthcare payment system shifts from volume to value, identifying care approaches that improve outcomes while lowering costs are essential. We sought to understand the utility of home infusion versus medical-setting infusion as a mechanism to affect the three-part aim: better care, better health outcomes, and lower costs. STUDY DESIGN: Systematic review. METHODS: We searched MEDLINE, EMBASE, and Science Citation Index for articles related to the safety, clinical effectiveness, quality of life and satisfaction, and/or costs of home infusion as compared with infusion in an outpatient medical facility or hospital. RESULTS: Of 253 potentially relevant articles, 13 met all inclusion criteria. Study design, disease state, and outcomes varied considerably. As compared to medical setting infusion patients, home infusion patients were no more likely to experience adverse drug events or side effects (all p>0.05). Clinical outcomes were as good or better, e.g., for patients with hemophilia, a 40% (0.50-0.70) reduced likelihood of hospitalization for bleeding complications. Patients overwhelmingly preferred home infusion, reporting significantly better physical and mental well being and less disruption of family and personal responsibilities. Home infusion costs were significantly lower than medical setting infusion costs, with savings between $1928 and $2974 per treatment course. CONCLUSIONS: Home infusion care can provide safe, clinically effective care improve patients' quality of life and reduce healthcare costs. As the overhaul of the healthcare payment system gains momentum, the home infusion care delivery model offers strong promise as one in a set of approaches that can improve care and lower costs.

Impact of CVS Pharmacy's Discontinuance of Tobacco Sales on Cigarette Purchasing (2012-2014).

OBJECTIVES: To assess the impact of CVS Health's discontinuation of tobacco sales on cigarette purchasing. METHODS: We used households' purchasing data to assess rates at which households stopped cigarette purchasing for at least 6 months during September 2014 to August 2015 among 3 baseline groups: CVS-exclusive cigarette purchasers, CVS+ (CVS and other retailers), and other-exclusive (only non-CVS retailers). In state-level analyses using retailers' point-of-sale purchase data, an interrupted time series compared cigarette purchasing before (January 2012 to August 2014) and after (September 2014 to April 2015) tobacco removal in 13 intervention states with CVS market share of at least 15% versus 3 control states with no CVS stores. RESULTS: Compared with other-exclusive purchasers, CVS-exclusive purchasers were 38% likelier (95% confidence interval = 1.06, 1.81) to stop cigarette purchasing after tobacco removal. Compared with control states, intervention states had a significant mean decrease of 0.14 (95% confidence interval = 0.06, 0.22) in packs per smoker per month. CONCLUSIONS: After CVS's tobacco removal, household- and population-level cigarette purchasing declined significantly. Private retailers can play a meaningful role in restricting access to tobacco. This highlights one approach to reducing tobacco use and improving public health.

Outcomes Associated with Generic Drugs Approved Using Product-Specific Determinations of Therapeutic Equivalence.

OBJECTIVE: We sought to examine rates of clinical outcomes among patients before and after market introduction of generic versions of five drugs approved using product-specific equivalence determinations. METHODS: We used data from a large national insurer to identify patients who initiated a study (acarbose tablets, salmon calcitonin nasal spray, enoxaparin injection, vancomycin capsules, venlafaxine extended-release tablets) or control drug (nateglinide, glimepiride, alendronate, fondaparinux, metronidazole, sertraline, paroxetine) in each calendar month between 2003 and 2012 and to determine rates of claims-based proxies for lack of effectiveness outcomes following initiation. We used segmented time-series analyses to evaluate level (short-term) and slope (longer-term) changes in outcomes upon introduction of a generic study or control drug. RESULTS: Among study drugs, we observed three increases (one with p < 0.05) and three decreases (two with p < 0.05) in the level of outcome rates. All changes in slope indicated decreases in outcomes from the brand-only to the generic period; four had p < 0.05. For control drugs, we observed positive level changes for eight of nine drug-outcome pairs; two had p < 0.05. We observed negative slope changes for eight out of nine pairs; six had p < 0.05. We observed a significant increase in level change following the introduction of generic bupropion versions that were later found to be not bioequivalent (p < 0.01). CONCLUSIONS: We did not find evidence that introduction of generic drugs approved using product-specific therapeutic equivalence determinations was associated with worse clinical outcomes than those among initiators of the brand-name versions of the same products. We observed similar patterns for control drugs.

The international generalisability of evidence for health policy: A cross country comparison of medication adherence following policy change.

Copayments for prescriptions may increase morbidity and mortality via reductions in adherence to medications. Relevant data can inform policy to minimise such unintended effects. We explored the generalisability of evidence for copayments by comparing two international copayment polices, one in Massachusetts and one in Ireland, to assess whether effects on medication adherence were comparable. We used national prescription data for public health insurance programmes in Ireland and Medicaid data in the U.S. New users of oral anti-hypertensive, anti-hyperlipidaemic and diabetic drugs were included (total n=14,259 in U.S. and n=43,843 in Ireland). We examined changes in adherence in intervention and comparator groups in each setting using segmented linear regression with generalised estimating equations. In Massachusetts, a gradual decrease in adherence to anti-hypertensive medications of -1% per month following the policy occurred. In contrast, the response in Ireland was confined to a -2.9% decrease in adherence immediately following the policy, with no further decrease over the 8 month follow-up. Reductions in adherence to oral diabetes drugs were larger in the U.S. group in comparison to the Irish group. No difference in adherence changes between the two settings for anti-hyperlipidaemic drugs occurred. Evidence on cost-sharing for prescription medicines is not 'one size fits all'. Time since policy implementation and structural differences between health systems may influence the differential impact of copayment policies in international settings.

An Insurer's Care Transition Program Emphasizes Medication Reconciliation, Reduces Readmissions And Costs.

Adverse drug events and the challenges of clarifying and adhering to complex medication regimens are central drivers of hospital readmissions. Medication reconciliation programs can reduce the incidence of adverse drug events after discharge, but evidence regarding the impact of medication reconciliation on readmission rates and health care costs is less clear. We studied an insurer-initiated care transition program based on medication reconciliation delivered by pharmacists via home visits and telephone and explored its effects on high-risk patients. We examined whether voluntary program participation was associated with improved medication use, reduced readmissions, and savings net of program costs. Program participants had a 50 percent reduced relative risk of readmission within thirty days of discharge and an absolute risk reduction of 11.1 percent. The program saved $2 for every $1 spent. These results represent real-world evidence that insurer-initiated, pharmacist-led care transition programs, focused on but not limited to medication reconciliation, have the potential to both improve clinical outcomes and reduce total costs of care.