Cost-effectiveness of ceftolozane/tazobactam compared with piperacillin/tazobactam as empiric therapy based on the in-vitro surveillance of bacterial isolates in the United States for the treatment of complicated urinary tract infections.

BACKGROUND: A challenge in the empiric treatment of complicated urinary tract infection (cUTI) is identifying the initial appropriate antibiotic therapy (IAAT), which is associated with reduced length of stay and mortality compared with initial inappropriate antibiotic therapy (IIAT). We evaluated the cost-effectiveness of ceftolozane/tazobactam compared with piperacillin/tazobactam (one of the standard of care antibiotics), for the treatment of hospitalized patients with cUTI. METHODS: A decision-analytic Monte Carlo simulation model was developed to compare the costs and effectiveness of empiric treatment with either ceftolozane/tazobactam or piperacillin/tazobactam in hospitalized adult patients with cUTI infected with Gram-negative pathogens in the US. The model applies the baseline prevalence of resistance as reported by national in-vitro surveillance data. RESULTS: In a cohort of 1000 patients, treatment with ceftolozane/tazobactam resulted in higher total costs compared with piperacillin/tazobactam ($36,413 /patient vs. $36,028/patient, respectively), greater quality-adjusted life years (QALYs) (9.19/patient vs. 9.13/patient, respectively) and an incremental cost-effectiveness ratio (ICER) of $6128/QALY. Ceftolozane/tazobactam remained cost-effective at a willingness to pay of $100,000 per QALY compared to piperacillin/tazobactam over a range of input parameter values during one-way and probabilistic sensitivity analysis. CONCLUSIONS: Model results show that ceftolozane/tazobactam is likely to be cost-effective compared with piperacillin/tazobactam for the empiric treatment of hospitalized cUTI patients in the United States.

Comparing the outcomes and costs of cardiac monitoring with implantable loop recorders and mobile cardiac outpatient telemetry following stroke using real-world evidence.

Aim: Patients with ischemic stroke (IS) commonly undergo monitoring to identify atrial fibrillation with mobile cardiac outpatient telemetry (MCOT) or implantable loop recorders (ILRs). The authors compared readmission, healthcare cost and survival in patients monitored post-stroke with either MCOT or ILR. Materials & methods: The authors used claims data from Optum's de-identified Clinformatics® Data Mart Database to identify patients with IS hospitalized from January 2017 to December 2020 who were prescribed ambulatory cardiac monitoring via MCOT or ILR. They compared the costs associated with the initial inpatient visit as well as the rate and causes of readmission, survival and healthcare costs over the following 18 months. Datasets were balanced using patient baseline and hospitalization characteristics. Multivariable generalized linear gamma regression was used for cost comparisons. Cox proportional hazard regression was used for survival and readmission analysis. Sub-cohorts were analyzed based on the severity of the index IS. Results: In 2244 patients, readmissions were significantly lower in the MCOT monitored group (30.2%) compared with the ILR group (35.4%) (hazard ratio [HR] 1.23; 95% CI: 1.04-1.46). Average cost over 18 months starting with the index IS was $27,429 (USD) lower in the MCOT group (95% CI: $22,353-$32,633). Survival difference bordered on statistical significance and trended to lower mortality in MCOT (8.9%) versus ILR (11.3%) (HR 1.30; 95% CI: 1:00-1.69), led by significance in patients with complications or comorbidities with the index event (MCOT 7.5%, ILR 11.5%; HR 1.62; 95% CI: 1.11-2.36). Conclusion: The use of MCOT versus ILR as the primary monitor following IS was associated with significant decreases in readmission, lower costs for the initial IS and total care over the next 18 months, significantly lower mortality for patients with complications and comorbidities at the index stroke, and a trend toward improved survival across all patients.

Impact of surgical complications on hospital costs and revenues: retrospective database study of Medicare claims.

Aim: To compare the length of stay, hospital costs and hospital revenues for Medicare patients with and without a subset of potentially preventable postoperative complications after major noncardiac surgery. Materials & methods: Retrospective data analysis using the Medicare Standard Analytical Files, Limited Data Set, 5% inpatient claims files for years 2016-2020. Results: In 74,103 claims selected for analysis, 71,467 claims had no complications and 2636 had one or more complications of interest. Claims with complications had significantly longer length of hospital stay (12.41 vs 3.95 days, p < 0.01), increased payments to the provider ($34,664 vs $16,641, p < 0.01) and substantially higher estimates of provider cost ($39,357 vs $16,158, p < 0.01) compared with claims without complications. This results on average in a negative difference between payments and costs for patients with complications compared with a positive difference for claims without complications (-$4693 vs $483, p < 0.01). Results were consistent across three different cost estimation methods used in the study. Conclusion: Compared with patients without postoperative complications, patients developing complications stay longer in the hospital and incur increased costs that outpace the increase in received payments. Complications are therefore costly to providers and payers, may negatively impact hospital profitability, and decrease the quality of life of patients. Quality initiatives aimed at reducing complications can be immensely valuable for both improving patient outcomes and hospital finances.

Continuous vital sign monitoring in patients after elective abdominal surgery: a retrospective study on clinical outcomes and costs.

Aim: To assess changes in outcomes and costs upon implementation of continuous vital sign monitoring in postsurgical patients. Materials & methods: Retrospective analysis of clinical outcomes and in-hospital costs compared with a control period. Results: During the intervention period patients were less frequently admitted to the intensive care unit (ICU) (p = 0.004), had shorter length of stay (p < 0.001) and lower costs (p < 0.001). The intervention was associated with a lower odds of ICU admission (odds ratio: 0.422; p = 0.007) and ICU related costs (odds ratio: -662.4; p = 0.083). Conclusion: Continuous vital sign monitoring may have contributed to fewer ICU admissions and lower ICU costs in postsurgical patients.

Costs and outcomes of mobile cardiac outpatient telemetry monitoring post-transcatheter aortic valve replacement.

Aim: To estimate the costs and outcomes of transcatheter aortic valve replacement (TAVR) recipients based on the use of mobile cardiac outpatient telemetry (MCOT) monitoring. Materials & methods: A retrospective database study was conducted to estimate costs, contribution margins (CMs), pacemaker insertions and other outcomes for patients undergoing TAVR procedures with MCOT monitoring post-procedure versus non-MCOT monitoring. Results: A total of 4164 patients were identified (283 MCOT monitoring and 3881 non-MCOT monitoring). The rate of pacemaker insertion following hospital discharge was higher in the MCOT cohort (6.6 MCOT vs 2.1% non-MCOT; p = 0.007). MCOT use was associated with lower costs and improved CMs of the index TAVR admission (costs: US$40,569 MCOT vs $43,289 non-MCOT; p = 0.003; CMs: US$7087 MCOT vs $5177 non-MCOT; p = 0.047) with no difference through the subsequent 60-day period following discharge. Conclusion: MCOT for ambulatory cardiac monitoring post-TAVR discharge is associated with higher rates of pacemaker insertion, at no overall greater costs.

Economics of implementing an early deterioration detection solution for general care patients at a US hospital.

Aim: This study estimates the costs and outcomes pre- versus post-implementation of an early deterioration detection solution (EDDS), which assists in identifying patients at risk of clinical decline. Materials & methods: A retrospective database analysis was conducted to assess average costs per discharge, length of stay (LOS), complications, in-hospital mortality and 30-day all-cause re-admissions pre- versus post-implementation of an EDDS. Results: Average costs per discharge were significantly reduced by 18% (US$16,201 vs $13,304; p = 0.007). Average LOS was also significantly reduced (6 vs 5 days; p = 0.033), driven by a reduction in general care LOS of 1 day (p = 0.042). Complications, in-hospital mortality and 30-day all-cause re-admissions were similar. Conclusion: Costs and LOS were lower after implementation of an EDDS for general care patients.

Early deterioration detection solutions (EDDS) assist in identifying patients at risk of clinical decline to enable a timely response. This study estimates the costs and outcomes before and after implementation of an EDDS at a US hospital for general care patients. Results show average costs per discharge and average length of stay were significantly reduced after implementation. Complications, in-hospital mortality and 30-day all-cause re-admissions were similar in the two time periods.

Mobile Cardiac Outpatient Telemetry Patch vs Implantable Loop Recorder in Cryptogenic Stroke Patients in the US - Cost-Minimization Model.

PURPOSE: The aim of this study was to compare costs and outcomes of mobile cardiac outpatient telemetry (MCOT) patch followed by implantable loop recorder (ILR) compared to ILR alone in cryptogenic stroke patients from the US health-care payors' perspective. PATIENTS AND METHODS: A quantitative decision tree cost-minimization simulation model was developed. Eligible patients were 18 years of age or older and were diagnosed with having a cryptogenic stroke, without previously documented atrial fibrillation (AF). All patients were assigned first to one then to the alternative monitoring strategies. Following AF detection, patients were initiated on oral anticoagulants (OAC). The model assessed direct costs for one year attributed to MCOT patch followed by ILR or ILR alone using a monitoring duration of 30 days post-cryptogenic stroke. RESULTS: In the base case modeling, the MCOT patch arm detected 4.6 more patients with AFs compared to the ILR alone arm in a cohort of 1000 patients (209 vs 45 patients with detected AFs, respectively). Using MCOT patch followed by ILR in half of the patients initially undiagnosed with AF leads to significant cost savings of US$4,083,214 compared to ILR alone in a cohort of 1000 patients. Cost per patient with detected AF was significantly lower in the MCOT patch arm $29,598 vs $228,507 in the ILR only arm. CONCLUSION: An initial strategy of 30-day electrocardiogram (ECG) monitoring with MCOT patch in diagnosis of AF in cryptogenic stroke patients realizes significant cost-savings compared to proceeding directly to ILR only. Almost 8 times lower costs were achieved with improved detection rates and reduction of secondary stroke risk due to new anticoagulant use in subjects with MCOT patch detected AF. These results strengthen emerging recommendations for prolonged ECG monitoring in secondary stroke prevention.

Evidence-based Clinical Decision Support Systems for the prediction and detection of three disease states in critical care: A systematic literature review.

Background: Clinical decision support (CDS) systems have emerged as tools providing intelligent decision making to address challenges of critical care. CDS systems can be based on existing guidelines or best practices; and can also utilize machine learning to provide a diagnosis, recommendation, or therapy course. Methods: This research aimed to identify evidence-based study designs and outcome measures to determine the clinical effectiveness of clinical decision support systems in the detection and prediction of hemodynamic instability, respiratory distress, and infection within critical care settings. PubMed, ClinicalTrials.gov and Cochrane Database of Systematic Reviews were systematically searched to identify primary research published in English between 2013 and 2018. Studies conducted in the USA, Canada, UK, Germany and France with more than 10 participants per arm were included. Results: In studies on hemodynamic instability, the prediction and management of septic shock were the most researched topics followed by the early prediction of heart failure. For respiratory distress, the most popular topics were pneumonia detection and prediction followed by pulmonary embolisms. Given the importance of imaging and clinical notes, this area combined Machine Learning with image analysis and natural language processing. In studies on infection, the most researched areas were the detection, prediction, and management of sepsis, surgical site infections, as well as acute kidney injury. Overall, a variety of Machine Learning algorithms were utilized frequently, particularly support vector machines, boosting techniques, random forest classifiers and neural networks. Sensitivity, specificity, and ROC AUC were the most frequently reported performance measures. Conclusion: This review showed an increasing use of Machine Learning for CDS in all three areas. Large datasets are required for training these algorithms; making it imperative to appropriately address, challenges such as class imbalance, correct labelling of data and missing data. Recommendations are formulated for the development and successful adoption of CDS systems.

Short- and long-term health consequences of sleep disruption.

Sleep plays a vital role in brain function and systemic physiology across many body systems. Problems with sleep are widely prevalent and include deficits in quantity and quality of sleep; sleep problems that impact the continuity of sleep are collectively referred to as sleep disruptions. Numerous factors contribute to sleep disruption, ranging from lifestyle and environmental factors to sleep disorders and other medical conditions. Sleep disruptions have substantial adverse short- and long-term health consequences. A literature search was conducted to provide a nonsystematic review of these health consequences (this review was designed to be nonsystematic to better focus on the topics of interest due to the myriad parameters affected by sleep). Sleep disruption is associated with increased activity of the sympathetic nervous system and hypothalamic-pituitary-adrenal axis, metabolic effects, changes in circadian rhythms, and proinflammatory responses. In otherwise healthy adults, short-term consequences of sleep disruption include increased stress responsivity, somatic pain, reduced quality of life, emotional distress and mood disorders, and cognitive, memory, and performance deficits. For adolescents, psychosocial health, school performance, and risk-taking behaviors are impacted by sleep disruption. Behavioral problems and cognitive functioning are associated with sleep disruption in children. Long-term consequences of sleep disruption in otherwise healthy individuals include hypertension, dyslipidemia, cardiovascular disease, weight-related issues, metabolic syndrome, type 2 diabetes mellitus, and colorectal cancer. All-cause mortality is also increased in men with sleep disturbances. For those with underlying medical conditions, sleep disruption may diminish the health-related quality of life of children and adolescents and may worsen the severity of common gastrointestinal disorders. As a result of the potential consequences of sleep disruption, health care professionals should be cognizant of how managing underlying medical conditions may help to optimize sleep continuity and consider prescribing interventions that minimize sleep disruption.

A systematic literature review of cysteamine bitartrate in the treatment of nephropathic cystinosis.

OBJECTIVES: To summarize available clinical evidence for cysteamine bitartrate preparations in the treatment of nephropathic cystinosis as identified through a systematic literature review (SLR). METHODS: We searched MEDLINE, MEDLINE In-Process and Embase using Ovid with a predefined search strategy through 19 January 2016. All publicly available clinical reports on the use of delayed-release (DR) cysteamine bitartrate (Procysbi 1 ) or immediate-release (IR) cysteamine bitartrate (Cystagon 2 ) in patients with cystinosis were included. RESULTS: We identified a total of 103 publications and 10 trial records. Of these, 9 studies describe DR cysteamine bitartrate (n = 267 patients), 42 describe IR cysteamine bitartrate (n = 1,427 patients) and in 53 studies the exact preparation was not specified (n = 906 patients). The vast majority of the studies used a non-randomized study design, with randomized clinical trials (RCTs) being scarce (1 study comparing DR and IR formulation) and case reports (n = 49) being the most common study design representing 47% of the total. CONCLUSION: A substantial evidence base for cysteamine bitartrate in the treatment of nephropathic cystinosis was identified. However, the majority of the evidence was of relatively low quality, with evidence levels of 3 or 4.

Do payers value rarity? An analysis of the relationship between disease rarity and orphan drug prices in Europe.

Background and Objective: Orphan drugs have been a highlight of discussions due to their higher prices than non-orphan drugs. There is currently no European consensus on the method of value assessment for orphan drugs. This study assessed the relationship between the prevalence of rare diseases and the annual treatment cost of orphan drugs in France, Germany, Italy, Norway, Spain, Sweden, and UK. Methods: Approved orphan drugs and prevalence data were extracted from the European Medicines Agency website. Annual treatment costs were calculated using ex-factory price. Simple regression was used to analyse the relationship between costs and prevalence. A specific bivariate analysis was performed for the rarest diseases (≤1 per 10,000). Results: 120 drugs were analysed. Prevalence ranged from 0.001 to 5 per 10,000 (mean 1.24, median 1). Annual treatment costs per patient ranged from €755 to €1,051,956 (mean €100,000, median €39,303). Results show a statistically significant inverse correlation between annual treatment cost and disease prevalence in all countries (France: r = -0.370, p = 0.002; Germany: r = -0.365, p = 0.002; Italy: r = -0.340, p = 0.002; Spain: r = -0.316, p = 0.041; UK: r = -0.358, p = 0.0004; Sweden: r = -0.414, p = 0.014; Norway: r = -0.367, p = 0.002). When analysis was focused on the rarest diseases, a stronger correlation exists in all countries (France: r = -0.525, Germany: r = -0.482, Italy: r = -0.497, Spain: r = -0.531, UK: r = -0.436, Sweden: r = -0.455, Norway: r = -0.466; all p < 0.05 except Sweden p = 0.077). Conclusions: This study shows an inverse correlation between annual treatment cost and prevalence with high statistical significance in the studied countries. Although pricing is a complex process where different attributes are assessed, this study supports the idea that payers value rarity in pricing decisions.

Cost-effectiveness of ceftolozane/tazobactam plus metronidazole versus piperacillin/tazobactam as initial empiric therapy for the treatment of complicated intra-abdominal infections based on pathogen distributions drawn from national surveillance data in the United States.

BACKGROUND: The prevalence of antimicrobial resistance among gram-negative pathogens in complicated intra-abdominal infections (cIAIs) has increased. In the absence of timely information on the infecting pathogens and their susceptibilities, local or regional epidemiology may guide initial empirical therapy and reduce treatment failure, length of stay and mortality. The objective of this study was to assess the cost-effectiveness of ceftolozane/tazobactam + metronidazole compared with piperacillin/tazobactam in the treatment of hospitalized US patients with cIAI at risk of infection with resistant pathogens. METHODS: We used a decision-analytic Monte Carlo simulation model to compare the costs and quality-adjusted life years (QALYs) of persons infected with nosocomial gram-negative cIAI treated empirically with either ceftolozane/tazobactam + metronidazole or piperacillin/tazobactam. Pathogen isolates were randomly drawn from the Program to Assess Ceftolozane/Tazobactam Susceptibility (PACTS) database, a surveillance database of non-duplicate bacterial isolates collected from patients with cIAIs in medical centers in the USA from 2011 to 2013. Susceptibility to initial therapy was based on the measured susceptibilities reported in the PACTS database determined using standard broth micro-dilution methods as described by the Clinical and Laboratory Standards Institute (CLSI). RESULTS: Our model results, with baseline resistance levels from the PACTS database, indicated that ceftolozane/tazobactam + metronidazole dominated piperacillin/tazobactam, with lower costs ($44,226/patient vs. $44,811/patient respectively) and higher QALYs (12.85/patient vs. 12.70/patient, respectively). Ceftolozane/tazobactam + metronidazole remained the dominant choice in one-way and probabilistic sensitivity analyses. CONCLUSIONS: Based on surveillance data, ceftolozane/tazobactam is more likely to be an appropriate empiric therapy for cIAI in the US. Results from a decision-analytic simulation model indicate that use of ceftolozane/tazobactam + metronidazole would result in cost savings and improves QALYs, compared with piperacillin/tazobactam.

Efficacy and Safety of Aclidinium/Formoterol versus Tiotropium in COPD: Results of an Indirect Treatment Comparison.

INTRODUCTION: The objective of this study was to estimate the relative efficacy and safety of fixed-dose combination aclidinium/formoterol 400/12 µg twice daily compared to tiotropium 18 µg once daily in adult patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). METHODS: A systematic literature review performed in March 2014, using a predefined search strategy in MEDLINE, EMBASE and Cochrane Library, identified 17 randomized placebo-controlled trials, (tiotropium n = 15; aclidinium/formoterol n = 2). Outcomes of interest were: bronchodilation (peak and trough forced expiratory volume in 1 s (FEV1)), COPD symptoms [Transition Dyspnea Index (TDI) focal score and % of responders (>1 unit improvement)] and Health Related Quality of Life (HRQoL) [St. George's Respiratory Questionnaire (SGRQ) total score and % responders (>4 unit improvement)], % of patients with ≥1 exacerbations, adverse events (AE), serious adverse events (SAE), hospitalization and mortality, all at 24 weeks. In the absence of head-to-head trials between aclidinium/formoterol and tiotropium, a Bayesian indirect treatment comparison (ITC) was used with placebo as common control. RESULTS: Regarding bronchodilation, aclidinium/formoterol was found to be more efficacious than tiotropium at peak FEV1, with mean difference in change from baseline (DCFB) 143 mL [95% credible interval (CrI): 112, 174] and at trough FEV1 [DCFB 26 mL (95% CrI -2, 55)]. Aclidinium/formoterol is expected to be more efficacious than tiotropium in improving dyspnea symptoms measured by TDI [DCFB 0.54 points (95% CrI 0.09, 0.99); odds ratio (OR) of responders 1.51 (95% CrI 1.11, 2.06)]. SGRQ results are comparable for aclidinium/formoterol versus tiotropium [DCFB -0.52 (95% CrI -2.21, 1.17); OR of responders 1.16 (95% CrI 0.47, 2.87)]. The ITC results suggest similar safety profiles regarding AEs, SAEs and hospitalization. CONCLUSION: Based on the ITC, aclidinium/formoterol is expected to be more efficacious than tiotropium in terms of lung function and symptom control while providing comparable HRQoL results and safety profile. FUNDING: AstraZeneca.

Comparison of Inhaled Antibiotics for the Treatment of Chronic Pseudomonas aeruginosa Lung Infection in Patients With Cystic Fibrosis: Systematic Literature Review and Network Meta-analysis.

PURPOSE: In Europe, 4 inhaled antibiotics (tobramycin, colistimethate sodium, aztreonam, and levofloxacin) are currently approved for the treatment of chronic Pseudomonas aeruginosa lung infection in patients with cystic fibrosis (CF). Levofloxacin inhalation solution (LIS) is the most recently approved inhaled antibiotic for adult patients with CF. A systematic literature review and Bayesian network meta-analysis (NMA) was conducted to compare the relative short-term (4 weeks) and long-term (24 weeks) outcomes of these inhaled antibiotics versus LIS. METHODS: A systematic literature search was conducted on February 16, 2016, using EMBASE and Medline via OvidSP. All randomized controlled trials comparing any of the aforementioned inhaled antibiotics with 4 or 24 weeks of follow-up were evaluated. NMA was performed for the following outcomes: relative and absolute percent changes from baseline in forced expiratory volume in 1 second (FEV1%) predicted, change in P aeruginosa sputum density, respiratory symptoms score from the CF questionnaire-revised, hospitalization, additional antibiotics use, and study withdrawal rates. RESULTS: Of the 685 articles identified, 7 unique studies were included in the 4 weeks' NMA and 9 unique studies were included in the 24 weeks' NMA. Aztreonam was predicted to result in the greatest numerically increase in FEV1% predicted at 4 weeks, whereas LIS were predicted to be numerically greater than colistimethate sodium, tobramycin inhaled solution (TIS), and tobramycin inhaled powder (TIP). However, all of the 95% credibility intervals (CrIs) of these comparisons included zero. At 24 weeks, none of the treatments was significantly more effective than LIS. The estimates for the mean change from baseline to 24 weeks in relative FEV1% versus LIS was -0.55 (95% CrI, -3.91 to 2.80) for TIS, -2.36 (95% CrI, -7.32 to 2.63) for aztreonam, -2.95 (95% CrI, -10.44 to 4.51) for TIP, and -9.66 (95% CrI, -15.01 to -4.33) for placebo. Compared with LIS, the odds ratio for hospitalization at 24 weeks was 1.92 (95% CrI, 1.01-3.30) for TIS, 2.25 (95% CrI, 1.01-4.34) for TIP, and 3.16 (95% CrI, 1.53-5.78) for placebo, all statistically worse than LIS. P aeruginosa sputum density scores, additional use of antipseudomonal antibiotics, and study withdrawal rates were comparable among all inhaled antibiotics at all times. IMPLICATIONS: Based on this NMA, the analyses for many of the outcomes did not provide significant evidence to indicate that the other approved inhaled antibiotics were more effective than LIS for the treatment of chronic P aeruginosa lung infection in patients with CF. Study withdrawal rates seemed to be comparable among these inhaled antibiotics.

Dosing frequency and adherence in chronic psychiatric disease: systematic review and meta-analysis.

BACKGROUND: The purpose of this study was to investigate the impact of dosing frequency on adherence in severe chronic psychiatric and neurological diseases. METHODS: A systematic literature review was conducted for articles in English from medical databases. Diseases were schizophrenia, psychosis, epilepsy, bipolar disorder, and major depressive disorder. RESULTS: Of 1420 abstracts screened, 12 studies were included. Adherence measures included Medication Event Monitoring System (MEMS(®)), medication possession ratio, medication persistence, and refill adherence. Three schizophrenia and one epilepsy study used MEMS, and all showed a trend towards higher adherence rates with less frequent dosing regimens. Three depression and one schizophrenia study used the medication possession ratio; the pooled odds ratio of being adherent was 89% higher (ie, 1.89, 95% credibility limits 1.71-2.09) on once-daily versus twice-daily dosing. Two studies in depression and one in all bupropion patients assessed medication persistence and refill adherence. The pooled odds ratio for the two depression studies using medication persistence was 2.10 (95% credibility limits 1.86-2.37) for once-daily versus twice-daily dosing. For refill adherence after 9 months, 65%-75% of patients on once-daily versus 56% on twice-daily dosing had at least one refill. In all but one of the studies using other measures of adherence, adherence rates were higher with once-daily dosing compared with more frequent dosing regimens. No relevant studies were identified for bipolar disorder or psychosis. CONCLUSION: Differences in study design and adherence measures used across the studies were too large to allow pooling of all results. Despite these differences, there was a consistent trend of better adherence with less frequent dosing.

Medication adherence in schizophrenia: factors influencing adherence and consequences of nonadherence, a systematic literature review.

BACKGROUND: Nonadherence to medication is a recognized problem and may be the most challenging aspect of treatment. METHODS: We performed a systematic review of factors that influence adherence and the consequences of nonadherence to the patient, healthcare system and society, in patients with schizophrenia. Particular attention was given to the effect of nonadherence on hospitalization rates, as a key driver of increased costs of care. A qualitative systematic literature review was conducted using a broad search strategy using disease and adherence terms. Due to the large number of abstracts identified, article selection was based on studies with larger sample sizes published after 2001. Thirty-seven full papers were included: 15 studies on drivers and 22 on consequences, of which 12 assessed the link between nonadherence and hospitalization. RESULTS: Key drivers of nonadherence included lack of insight, medication beliefs and substance abuse. Key consequences of nonadherence included greater risk of relapse, hospitalization and suicide. Factors positively related to adherence were a good therapeutic relationship with physician and perception of benefits of medication. The most frequently reported driver and consequence were lack of insight and greater risk of hospitalization respectively. CONCLUSIONS: Improving adherence in schizophrenia may have a considerable positive impact on patients and society. This can be achieved by focusing on the identified multitude of factors driving nonadherence.

Relative efficacy of bivalirudin versus heparin monotherapy in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention: a network meta-analysis.

In the absence of head-to-head clinical data, the objective of this study was to indirectly compare the efficacy and safety of a bivalirudin-based anticoagulation strategy with that of heparin monotherapy in patients with ST-elevation myocardial infarction (STEMI) intended for primary percutaneous coronary intervention. A systematic literature review was performed to identify randomized controlled trials to build a network of bivalirudin and heparin monotherapy strategies in STEMI patients using heparin, with glycoprotein IIb/IIIa inhibitor as a common reference strategy. At 30 days, the bivalirudin-based strategy was expected to result in lower mortality rates than heparin monotherapy (odds ratio [OR], 0.55; credible limit [CrL], 0.32-0.95). This relationship was sustained at 1 year. At 30 days, the risk for stroke (OR, 0.88; CrL, 0.37-2.13), myocardial infarction (OR, 0.79; CrL, 0.40-1.55), and thrombolysis in myocardial infarction major and minor bleedings (OR, 0.66; CrL, 0.45-0.98) tended to be numerically reduced with bivalirudin in comparison with heparin monotherapy. For patients with STEMI intended for primary percutaneous coronary intervention, bivalirudin is associated with lower mortality rates in comparison with heparin monotherapy. This study suggests that bivalirudin is more effective and safer than heparin monotherapy and should therefore be preferred over heparin monotherapy.