Project description:ImportanceList prices set by manufacturers for brand-name prescription drugs in the US have been increasing faster than inflation, although confidential manufacturer rebates offset some of these increases. Most commercially insured patients pay at least some out-of-pocket costs for prescription drugs, and higher patient spending is associated with lower adherence and worse health outcomes.ObjectiveTo examine whether price changes for brand-name drugs are correlated with changes in patient out-of-pocket spending and whether this association varies by insurance benefit design.Design, setting, and participantsA cohort study of 79 brand-name drugs with available pricing data from January 2015 to December 2017 was conducted, with data obtained from a national commercial insurance claims database.ExposuresChange in the list prices set by manufacturers and estimated net prices after rebates among non-Medicaid payers.Main outcomes and measuresChange in median out-of-pocket spending among all patients and stratified by insurance pharmacy benefit design, including high-deductible insurance plans and plans with any amount of deductibles or coinsurance.ResultsAmong 79 drugs, median increases were 16.7% (interquartile range [IQR], 13.6%-21.1%) for list prices, 5.4% (IQR, -3.9% to 11.7%) for net prices, and 3.5% (IQR, 1.4%-9.1%) for out-of-pocket spending from 2015 to 2017. Changes in list prices were correlated with changes in net prices (r = 0.34; P = .002). Overall, changes in out-of-pocket spending were not correlated with changes in list prices (r = 0.14; P = .22) or net prices (r = 0.04; P = .71). Among 53.7% of patients who paid any drug deductible or coinsurance, median out-of-pocket spending increased by 15.0%, and changes were moderately correlated with changes in list prices (r = 0.38; P = .001) but not net prices (r = 0.06; P = .62).Conclusions and relevanceSome commercially insured patients who pay only prescription drug copayments appear to be insulated from increases in drug prices. However, more than half of patients pay deductibles or coinsurance and may experience substantial increases in out-of-pocket spending when drug prices increase. Among these patients, there was no evidence that manufacturer rebates to insurers are associated with patients' out-of-pocket spending. Policies to rein in unregulated annual increases in list prices for brand-name drugs may have important consequences for patient out-of-pocket spending.
Project description:We report X-ray crystallographic structures of three inhibitors bound to dehydrosqualene synthase from Staphylococcus aureus: 1 (BPH-651), 2 (WC-9), and 3 (SQ-109). Compound 2 binds to the S2 site with its -SCN group surrounded by four hydrogen bond donors. With 1, we report two structures: in both, the quinuclidine headgroup binds in the allylic (S1) site with the side chain in S2, but in the presence of PPi and Mg(2+), the quinuclidine's cationic center interacts with PPi and three Mg(2+), mimicking a transition state involved in diphosphate ionization. With 3, there are again two structures. In one, the geranyl side chain binds to either S1 or S2 and the adamantane headgroup binds to S1. In the second, the side chain binds to S2 while the headgroup binds to S1. These results provide structural clues for the mechanism and inhibition of the head-to-head prenyl transferases and should aid future drug design.
Project description:ObjectiveThis study aimed to estimate global inpatient, outpatient, prescribing and care home costs for patients with atrial fibrillation using population-based, individual-level linked data.DesignA two-part model was employed to estimate the probability of resource utilisation and costs conditional on positive utilisation using individual-level linked data.SettingsScotland, 5 years following first hospitalisation for AF between 1997 and 2015.ParticipantsPatients hospitalised with a known diagnosis of AF or atrial flutter.Primary and secondary outcome measuresInpatient, outpatient, prescribing and care home costs.ResultsThe mean annual cost for a patient with AF was estimated at £3785 (95% CI £3767 to £3804). Inpatient admissions and outpatient visits accounted for 79% and 8% of total costs, respectively; prescriptions and care home stay accounted for 7% and 6% of total costs. Inpatient cost was the main driver across all age groups. While inpatient cost contributions (~80%) were constant between 0 and 84 years, they decreased for patients over 85 years. This is offset by increasing care home cost contributions. Mean annual costs associated with AF increased significantly with increasing number of comorbidities.ConclusionThis study used a contemporary and representative cohort, and a comprehensive approach to estimate global costs associated with AF, taking into account resource utilisation beyond hospital care. While overall costs, considerably affected by comorbidity, did not increase with increasing age, care home costs increased proportionally with age. Inpatient admission was the main contributor to the overall financial burden of AF, highlighting the need for improved mechanisms of early diagnosis to prevent hospitalisations.
Project description:BackgroundIn 2007, the American Heart Association recommended that antibiotic prophylaxis (AP) be restricted to those at high risk of developing complications due to infective endocarditis (IE) undergoing invasive dental procedures. The authors aimed to estimate the appropriateness of AP prescribing according to type of dental procedure performed in patients at high risk, moderate risk, or low or unknown risk of developing IE complications.MethodsEighty patients at high risk, 40 patients at moderate risk, and 40 patients at low or unknown risk of developing IE complications were randomly selected from patients with linked dental care, health care, and prescription benefits data in the IBM MarketScan Databases, one of the largest US health care convenience data samples. Two clinicians independently analyzed prescription and dental procedure data to determine whether AP prescribing was likely, possible, or unlikely for each dental visit.ResultsIn patients at high risk of developing IE complications, 64% were unlikely to have received AP for invasive dental procedures, and in 32 of 80 high-risk patients (40%) there was no evidence of AP for any dental visit. When AP was prescribed, several different strategies were used to provide coverage for multiple dental visits, including multiday courses, multidose prescriptions, and refills, which sometimes led to an oversupply of antibiotics.ConclusionsAP prescribing practices were inconsistent, did not always meet the highest antibiotic stewardship standards, and made retrospective evaluation difficult. For those at high risk of developing IE complications, there appears to be a concerning level of underprescribing of AP for invasive dental procedures.Practical implicationsSome dentists might be failing to fully comply with American Heart Association recommendations to provide AP cover for all invasive dental procedures in those at high risk of developing IE complications.
Project description:Coronavirus Disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus -2 (SARS-CoV-2) has been widely spread in the world with a high mortality. Cytokine storm syndrome (CSS) and acute lung injury caused by SARS-CoV-2 infection severely threaten the patients. With the purpose to find effective and low-toxic drugs to mitigate CSS, entecavir and imipenem were identified to reduce TNF-? using a LPS-induced macrophage model from the anti-infective drug library. Entecavir and imipenem efficiently suppressed the release of inflammatory cytokines by partly intervention of NF-?B activity. The acute lung injury was also alleviated and the survival time was prolonged in mice. In addition, entecavir and imipenem inhibited the release of TNF-? and IL-10 in human peripheral blood mononuclear cells (hPBMCs). Collectively, we proposed that entecavir and imipenem might be candidates for the treatment of CSS.
Project description:Background:The objectives of this study were to develop methods to measure population-based outpatient antibiotic prescribing in Massachusetts and to describe the findings as a first step toward institution of ongoing surveillance. Methods:We analyzed outpatient prescription claims from the Massachusetts All-Payers Claims Database from 2011 to 2015. We grouped claims for antibiotics according to the World Health Organization's Anatomical Therapeutic Chemical Classification System using the National Library of Medicine's RXNorm database. We grouped prescribers into 17 specialties. Antibiotic use rates were calculated, and simple frequencies were used to describe patterns. Results:The overall annual rate of outpatient antibiotic use for individuals aged 0-64 years was 696 prescriptions per 1000 people. During 2015, 68% of people in Massachusetts had no antibiotic prescription, and 17% had only 1 prescription. There was dramatic variability in antibiotic use rates by census tract within the state (rates of penicillin use ranged from 31 to 265 prescriptions per 1000 people, macrolides from 28 to 333, cephalosporins from 8 to 89, quinolones from 13 to 118). Antibiotic use rates were generally lower in urban census tracts. From 2011 to 2015, there was a 17% decline in antibiotic prescribing, with the greatest decline for macrolides (28%). Conclusions:There was variability in antibiotic prescribing within Massachusetts by age, sex, and antibiotic class. Variation in antibiotic use across census tracts within the state was similar to the variation in use across US states. Continued measurement and detailed local population rates of antibiotic use in Massachusetts will provide feedback for local prescribers.
Project description:ObjectiveTo report the frequency, types, and causes of errors associated with outpatient computer-generated prescriptions, and to develop a framework to classify these errors to determine which strategies have greatest potential for preventing them.Materials and methodsThis is a retrospective cohort study of 3850 computer-generated prescriptions received by a commercial outpatient pharmacy chain across three states over 4 weeks in 2008. A clinician panel reviewed the prescriptions using a previously described method to identify and classify medication errors. Primary outcomes were the incidence of medication errors; potential adverse drug events, defined as errors with potential for harm; and rate of prescribing errors by error type and by prescribing system.ResultsOf 3850 prescriptions, 452 (11.7%) contained 466 total errors, of which 163 (35.0%) were considered potential adverse drug events. Error rates varied by computerized prescribing system, from 5.1% to 37.5%. The most common error was omitted information (60.7% of all errors).DiscussionAbout one in 10 computer-generated prescriptions included at least one error, of which a third had potential for harm. This is consistent with the literature on manual handwritten prescription error rates. The number, type, and severity of errors varied by computerized prescribing system, suggesting that some systems may be better at preventing errors than others.ConclusionsImplementing a computerized prescribing system without comprehensive functionality and processes in place to ensure meaningful system use does not decrease medication errors. The authors offer targeted recommendations on improving computerized prescribing systems to prevent errors.
Project description:BackgroundThe opioid crisis in the United States has led to increasing hospitalizations for drug use-associated infective endocarditis (DUA-IE). Outpatient parenteral antimicrobial therapy (OPAT), the preferred modality for intravenous antibiotics for infective endocarditis, has demonstrated similar outcomes among patients with DUA-IE versus non-DUA-IE, but current studies suffer selection bias. The utilization of OPAT for DUA-IE more generally is not well studied.MethodsThis retrospective cohort study compared OPAT use for DUA-IE versus non-DUA-IE in adults hospitalized between January 1, 2015 and September 1, 2019 at 3 urban hospitals. We used multivariable regression analysis to assess the association between DUA-IE and discharge with OPAT, adjusting for clinically significant covariables.ResultsThe cohort included 518 patients (126 DUA-IE, 392 non-DUA-IE). Compared to those with non-DUA-IE, DUA-IE patients were younger (53.0 vs 68.2 years, P < .001) and more commonly undomiciled (9.5% vs 0.3%, P < .01). Patients with DUA-IE had a significantly lower odds of discharge with OPAT than non-DUA-IE patients (adjusted odds ratio [aOR] = 0.20; 95% confidence interval [CI], 0.10-0.39). Odds of discharge with OPAT remained lower for patients with DUA-IE after excluding undomiciled patients (aOR = 0.22; 95% CI, 0.11-0.43) and those with patient-directed discharges (aOR = 0.27; 95% CI, 0.14-0.52).ConclusionsSignificantly fewer patients with DUA-IE were discharged with OPAT compared to those with non-DUA-IE, and undomiciled patients or patient-directed discharges did not fully account for this difference. Efforts to increase OPAT utilization among patients with DUA-IE could have important benefits for patients and the healthcare system.
Project description:To determine whether retail prices for prescription drugs are higher in poorer areas.The MyFloridarx.com website, which provides retail prescription prices at Florida pharmacies, and median ZIP code income from the 2000 Census.We compared mean pharmacy prices for each of the four study drugs across ZIP code income groups. Pharmacies were classified as either chain pharmacies or independent pharmacies.Prices were downloaded in November 2006.Across the four study drugs, mean prices were highest in the poorest ZIP codes: 9 percent above the statewide average. Independent pharmacies in the poorest ZIP codes charged the highest mean prices.Retail prescription prices appear to be higher in poorer ZIP codes of Florida.