Impact of Pre-existing Type 2 Diabetes Mellitus and Cardiovascular Disease on Healthcare Resource Utilization and Costs in Patients With COVID-19.

Background: The economic burden associated with type 2 diabetes mellitus (T2DM) and concurrent cardiovascular disease (CVD) among patients with COVID-19 is unclear. Objective: We compared healthcare resource utilization (HCRU) and costs in patients with COVID-19 and T2DM and CVD (T2DM + CVD), T2DM only, or neither T2DM nor CVD (T2DM/CVD). Methods: A retrospective observational study in COVID-19 patients using data from the Healthcare Integrated Research Database (HIRD®) was conducted. Patients with COVID-19 were identified between March 1, 2020, and May 31, 2021, and followed from first diagnosis or positive lab test to the end of health plan enrollment, end of study period, or death. Patients were assigned one of 3 cohorts: pre-existing T2DM+CVD, T2DM only, or neither T2DM/CVD. Propensity score matching and multivariable analyses were performed to control for differences in baseline characteristics. Study outcomes included all-cause and COVID-19-related HCRU and costs. Results: In all, 321 232 COVID-19 patients were identified (21 651 with T2DM + CVD, 28 184 with T2DM only, and 271 397 with neither T2DM/CVD). After matching, 6967 patients were in each group. Before matching, 46.0% of patients in the T2DM + CVD cohort were hospitalized for any cause, compared with 18.0% in the T2DM-only cohort and 6.3% in the neither T2DM/CVD cohort; the corresponding values after matching were 34.2%, 26.0%, and 21.2%. The proportion of patients with emergency department visits, telehealth visits, or use of skilled nursing facilities was higher in patients with COVID-19 and T2DM + CVD compared with the other cohorts. Average all-cause costs during follow-up were 12 324,7882, and $7277 per-patient-per-month after matching for patients with T2DM + CVD, T2DM-only, and neither T2DM/CVD, respectively. COVID-19-related costs contributed to 78%, 75%, and 64% of the overall costs, respectively. The multivariable model showed that per-patient-per-month all-cause costs for T2DM + CVD and T2DM-only were 54% and 21% higher, respectively, than those with neither T2DM/CVD after adjusting for residual confounding. Conclusion: HCRU and costs in patients were incrementally higher with COVID-19 and pre-existing T2DM + CVD compared with those with T2DM-only and neither T2DM/CVD, even after accounting for baseline differences between groups, confirming that pre-existing T2DM + CVD is associated with increased HCRU and costs in COVID-19 patients, highlighting the importance of proactive management.

Cost-Effectiveness Analysis of Empagliflozin for Treatment of Patients With Heart Failure With Reduced Ejection Fraction in the United States.

BACKGROUND: In the EMPEROR-Reduced trial (Empagliflozin Outcome Trial in Patients with Chronic Heart Failure and a Reduced Ejection Fraction), empagliflozin plus standard of care reduced the composite of cardiovascular death or hospitalization for heart failure versus standard of care in adults with heart failure with reduced ejection fraction. This analysis investigated the cost-effectiveness of the 2 regimens from the perspective of US payors. METHODS AND RESULTS: A Markov cohort model was developed based on Kansas City Cardiomyopathy Questionnaire Clinical Summary Score quartiles and death. Transition probabilities between health states, risk of cardiovascular/all-cause death, hospitalization for heart failure and adverse events, treatment discontinuation, and health utilities were estimated from trial data. Medicare and commercial payment rates were combined for treatment acquisition, acute event management, and disease management. An annual discount rate of 3% was used. Empagliflozin plus standard of care yielded 18% fewer hospitalizations for heart failure and 6% fewer deaths versus standard of care over a lifetime, providing cost-offsets while adding 0.19 life years and 0.19 quality-adjusted life years at an incremental cost of $16 815/patient. The incremental cost-effectiveness ratio was $87 725/quality-adjusted life years gained. Results were consistent across payors, subpopulations, and in deterministic sensitivity analyses. In probabilistic sensitivity analyses, empagliflozin plus standard of care was cost-effective in 3%, 62%, and 80% of iterations at thresholds of $50 000, $100 000, and $150 000/quality-adjusted life years. CONCLUSIONS: Empagliflozin plus standard of care may prevent hospitalizations for heart failure, extend life, and increase quality-adjusted life years for patients with heart failure with reduced ejection fraction at an acceptable cost for US payors.

Impact of Caring for Individuals With Heart Failure in the United States: A Systematic Literature Review.

BACKGROUND: Given the functional impairments and complex care routines associated with heart failure (HF), patients often rely on the support of informal caregivers. Although the importance of caregivers' roles is widely recognized, the intensity and time required for care duties may negatively impact caregiver health and well-being, potentially precipitating their own need for care. OBJECTIVE: The aim of this study was to synthesize estimates of economic, clinical, burden, and health-related quality-of-life impact among caregivers of those with HF in the United States. METHODS: A systematic review was conducted to identify studies reporting estimates of caregiver impact. Abstract and full-text review as well as data extraction were performed according to established guidelines. Patient and caregiver characteristics were summarized, as well as estimates of impact of caring for those with HF. RESULTS: From 3680 abstracts, 44 studies reporting caregiver burden estimates were included. Mean caregiver age ranged from 41.4 to 71.4 years; caregivers were primarily female (range, 49%-100%) and the patient's spouse/partner (21%-100%). Time spent caregiving (6 studies) ranged from 2 to 52 h/wk, and depression was identified in up to 40% of caregivers (9 studies). Numerous instruments were used to measure burden, which consistently documented the high impact of caregiving. CONCLUSIONS: This review demonstrates the multifaceted impact of caregiving for patients with HF. Despite limited data, notable findings included the considerable burden to caregivers, variability in time spent caregiving, and frequent experience of depression among caregivers, possibly leading to increased healthcare resource use. Future research is needed to better characterize the caregiving impact in HF, including evaluating the drivers of burden.

Impact of pre-existing type 2 diabetes with and without cardiovascular disease on patients with COVID-19.

AIM: To compare adverse outcomes among COVID-19 patients with pre-existing type 2 diabetes (T2D) only, T2D and cardiovascular disease (CVD), or neither. METHODS: This retrospective cohort study used administrative claims, laboratory and mortality data from the HealthCore Integrated Research Database. Patients with COVID-19 were identified from 3 January 2020 to 31 May 2021 and stratified by the presence of T2D and CVD. Outcomes included hospitalization, intensive care unit (ICU) admission, mortality and complications following COVID-19 infection. Propensity score matching and multivariable analyses were performed. RESULTS: A total of 321 232 COVID-19 patients were identified (21 651 T2D + CVD, 28 184 T2D only, and 271 397 neither) with a mean (SD) follow-up of 5.4 (3.0) months. After matching, 6 967 patients were identified for each group, and residual baseline differences remained. Adjusted analyses showed that COVID-19 patients with T2D + CVD were 59% more probable to be hospitalized, 74% more probable to be admitted to the ICU, and had a 26% higher mortality risk than those with neither. COVID-19 patients with T2D only were 28% and 32% more probable to be admitted to the hospital and ICU than those with neither, respectively. Among all T2D + CVD patients, acute respiratory distress syndrome (31%) and acute kidney disease (24%) were observed. CONCLUSION: Our study highlights the incrementally poorer outcomes associated with pre-existing T2D + CVD in COVID-19 patients compared with those without T2D/CVD and suggests consideration of a more optimal management approach in these patients.

Evaluation of emerging NASH therapies: the impact of treatment efficacy profiles on long-term health outcomes.

Aim: Evaluations of nonalcoholic steatohepatitis (NASH) treatments require predicting lifetime outcomes from short-term clinical trials. Materials & methods: A Markov model with NASH fibrosis stages F0-F3, NASH resolution, compensated cirrhosis (F4/CC), and liver-related complication (LRC) states was developed using literature-based standard of care (SoC) data. Hypothetical efficacy profiles were defined affecting resolution (100%-increase), fibrosis improvement (100% increase), or fibrosis worsening (50% decrease). Results: For the SoC, 10-year LRC rates increased with baseline fibrosis stage (F1: 3.0%; F2: 9.8%; F3: 27.2%; F4/CC: 64.9%). The fibrosis worsening profile reduced predicted 10-year LRC rates (F1: 1.9%; F2: 6.5%; F3: 19.1%; F4/CC: 55.0%) more than the resolution and fibrosis improvement profiles (F1: 2.6%/2.6%; F2: 8.5%/8.3%; F3: 23.3%/23.0%; F4/CC: NA/59.0%). Scenario analyses considered alternative SoC progression, treatment efficacy and treatment-stopping rules. Conclusion: Potential NASH efficacy profiles have differing impacts on predicted long-term outcomes, providing insights for future stakeholders.

Many new treatments are being investigated for nonalcoholic steatohepatitis (NASH), a progressive and life-threatening disease often resulting in liver fibrosis (scarring) and advanced liver disease. The clinical value of these treatments and whether they are good value for money will depend on their ability to reduce the risk of advanced liver disease and subsequent liver transplantation. We developed a disease progression model which tracks survival and quality of life for two identical groups of NASH patients over their lifetimes. One group received a new hypothetical treatment for NASH while the other received current standard care. We used the model to estimate the potential health benefits of different hypothetical treatments for NASH. Our results suggest that treatments slowing fibrosis worsening may lead to greater long-term health benefits than treatments that improve NASH or improve existing fibrosis. These findings may provide insights to researchers involved in the development of new treatments for NASH.

Burden of hospitalization for heart failure in the United States: a systematic literature review.

BACKGROUND: Heart failure (HF) affects approximately 6 million Americans, with prevalence projected to increase by 46% and direct medical costs to reach $53 billion by 2030. Hospitalizations are the largest component of direct costs for HF; however, recent syntheses of the economic and clinical burden of hospitalization for heart failure (HHF) are lacking. OBJECTIVE: To synthesize contemporary estimates of cost and clinical outcomes of HHF in the United States. METHODS: A systematic literature review was conducted using MEDLINE and Embase to identify articles reporting cost or charge per HHF in the United States published between January 2014 and May 2019. Subgroups of interest were those with both HF and renal disease or diabetes, as well as HF with reduced or preserved ejection fraction (HFrEF or HFpEF). RESULTS: 23 studies reporting cost and/or charge per HHF were included. Sample sizes ranged from 989 to approximately 11 million (weighted), mean age from 65 to 83 years, and 39% to 74% were male. Cost per HHF ranged from $7,094 to $9,769 (median) and $10,737 to $17,830 (mean). Charge per HHF ranged from $22,162 to $40,121 (median), and $50,569 to $50,952 (mean). Among patients with renal disease, HHF mean cost ranged from $9,922 to $41,538. For those with HFrEF or HFpEF, mean cost ranged from $11,600 to $17,779 and $7,860 to $10,551, respectively. No eligible studies were identified that reported HHF costs or charges among patients with HF and diabetes. Cost and charge per HHF increased with length of stay, which ranged from 3 to 5 days (median) and 4 to 7 days (mean). CONCLUSIONS: This synthesis demonstrates the substantial economic burden of HHF and the variability in estimates of this burden. Factors contributing to variability in estimates include length of stay, age and sex of the sample, HF severity, and frequencies of comorbidities. Further research into cost drivers of HHF is warranted to understand potential mechanisms to reduce associated costs. DISCLOSURES: This study was funded by Boehringer Ingelheim Pharmaceuticals. Osenenko, Deighton, and Szabo are employees of Broadstreet HEOR, which received funds from Boehringer Ingelheim Pharmaceuticals for this work. Kuti and Pimple are employees of Boehringer Ingelheim Pharmaceuticals. This study was presented in abstract form at the 2020 American Heart Association (AHA) Quality of Care and Outcomes Research (QCOR) 2020 Scientific Sessions (May 15-16, Virtual Meeting).

Cost-Effectiveness of Empagliflozin in Patients With Diabetic Kidney Disease in the United States: Findings Based on the EMPA-REG OUTCOME Trial.

RATIONALE & OBJECTIVE: Benefits of sodium-glucose cotransporter 2 inhibitors on kidney outcomes have been demonstrated in clinical trials. Among patients with type 2 diabetes and established cardiovascular (CV) disease enrolled in the EMPA-REG OUTCOME study (ClinicalTrials.gov identifier NCT01131676), empagliflozin added to standard of care (SOC) reduced the risk of incident or worsening nephropathy compared with SOC alone. This analysis evaluated the cost-effectiveness of empagliflozin versus SOC alone in the subpopulation with diabetic kidney disease (DKD) from the perspective of US commercial insurers and Medicare. STUDY DESIGN: Discrete event simulation model. SETTING & POPULATION: Patients with DKD in a US health care system. INTERVENTIONS: Empagliflozin 10 or 25mg with SOC versus SOC alone. SOC included glucose-lowering therapies and medications to treat CV risk factors. OUTCOMES: Incremental cost-effectiveness ratios (2020 US dollars per quality-adjusted life-year [QALY] gained). Costs and QALYs were discounted 3.0% per year. MODEL, PERSPECTIVE, & TIME FRAME: Cost-effectiveness analysis, commercial insurers and Medicare perspective, lifetime horizon. RESULTS: The incremental cost-effectiveness ratio of empagliflozin with SOC versus SOC alone was $25,974 per QALY. Empagliflozin added 0.67 QALYs and $17,322 per patient over a lifetime horizon. Results were driven by fewer clinical events (including CV death, heart failure hospitalization, albuminuria progression, and a composite kidney outcome) experienced by patients receiving empagliflozin with SOC versus SOC alone. Results were sensitive to rates of CV death, nonfatal myocardial infarction, and heart failure hospitalization, as well as to drug costs and time horizon. Probabilistic sensitivity analyses indicated 91% of simulations at <$50,000 per QALY. LIMITATIONS: The EMPA-REG OUTCOME study was not powered to assess treatment benefits in a subgroup and excluded patients with estimated glomerular filtration rate<30mL/min/1.73m2. CONCLUSIONS: Based on the EMPA-REG OUTCOME study, this cost-effectiveness analysis suggests that, for commercial insurers and Medicare, adding empagliflozin to SOC may be a cost-effective treatment option for patients with DKD.

Assessing risk of future cardiovascular events, healthcare resource utilization and costs in patients with type 2 diabetes, prior cardiovascular disease and both.

BACKGROUND: Description of risk of cardiovascular (CV) events associated with diabetes is evolving. This US-based real-world study estimated risk of future CV events and heart failure (HF) from type 2 diabetes (T2DM) only, prior CV events only or T2DM plus prior CV events, versus controls, and evaluated healthcare resource utilization (HCRU) and costs. METHODS AND MATERIALS: This retrospective cohort study queried claims and mortality data for 638,301 patients: T2DM only (377,205); prior CV events only (130,964); both T2DM and prior CV events (130,132); and matched (1:1) controls, during 1 January 2012-31 December 2012. Cardiovascular diagnoses/events and death were assessed individually, and as composite endpoint (myocardial infarction [MI], stroke, transient ischemic attack [TIA], peripheral artery disease [PAD]), during follow-up, ending 31 July 2018. RESULTS: Adjusting for age and gender, patients with T2DM only were 1.6, prior CV events only 2.5 and T2DM plus prior CV events 3.8 times likelier to have primary composite CV events relative to controls, p < .001. HF development was elevated across all three cohorts. Adjusted results showed inpatient admissions for T2DM only, CV events only and T2DM plus prior CV events were 1.37, 2.76 and 3.63 times greater than controls, respectively. All-cause healthcare costs were highest in the T2DM plus prior CV events cohort ($2783 per patient per month [PPPM]) followed by the prior CV events only ($1910 PPPM) and T2DM only cohorts ($1343 PPPM), and controls ($825 PPPM). Adjusted all-cause total costs were 1.48 for T2DM only, 1.49 for prior CV events only and 1.93 for T2DM plus prior CV events times higher compared to controls. CONCLUSION: In this large and geographically broad US based cohort, CV risk for T2DM patients was elevated, as was the risk for patients with prior CV events, while patients with T2DM plus prior CV events had the highest risk of future CV events. The substantial clinical and economic burden of CV events and HF in patients with both T2DM and prior CV events suggest a need for an integrated treatment and targeted intervention across both conditions.

Differences in All-Cause Health Care Utilization and Costs in a Type 2 Diabetes Mellitus Population with and Without a History of Cardiovascular Disease.

BACKGROUND: Multiple studies have reported that type 2 diabetes mellitus (T2DM) is a major risk factor for cardiovascular diseases (CVD), and presence of T2DM and CVD increases risk of death. There is growing interest in examining the effects of antidiabetic treatments on the reduction of cardiovascular events in T2DM adults with a history of CVD and thus at higher risk of cardiovascular events. OBJECTIVE: To estimate the incremental all-cause health care utilization and costs among adults with T2DM and a history of CVD compared with adults without a history of CVD, using a national linked electronic medical records (EMR) and claims database. METHODS: Adults aged ≥ 18 years with evidence of at least 1 T2DM-related diagnosis code or antidiabetic medication (date of earliest occurrence was defined as the index date) in calendar year 2012 were identified. The population was divided into 2 cohorts (with and without a history of CVD) and followed until the end of their enrollment coverage, death, or 12 months, whichever came first. Multivariable generalized linear models were used to assess differences in health care utilization and per patient per month (PPPM) total costs (plan- and patient-paid amount for health care services) between the 2 groups during the post-index year, while adjusting for an a priori list of demographic and clinical characteristics. RESULTS: A total of 138,018 adults with T2DM was identified, of which 16,547 (12%) had a history of CVD. The unadjusted resource utilization (outpatient: 27.5 vs. 17.8; emergency room [ER]: 0.8 vs. 0.4; inpatient: 0.4 vs. 0.2 days; and total unique drug prescriptions: 10.1 vs. 8.3) and PPPM total health care costs ($2,655.1 vs. $1,435.0) were significantly higher in T2DM adults with a history of CVD versus T2DM adults without a history of CVD. The adjusted models revealed that T2DM adults with a history of CVD had a 31% higher number of ER visits (rate ratio [RR] = 1.31, 95% CI = 1.25-1.37); 27% more inpatient visits (RR = 1.27, 95% CI = 1.21-1.34); 15% longer mean inpatient length of stay (RR = 1.15, 95% CI = 1.06-1.25); and 11% more outpatient visits (RR = 1.11, 95% CI = 1.09-1.13) compared with T2DM adults without a history of CVD. Furthermore, the difference in total PPPM health care cost was found to be 16% ($200) higher in adults with a history of CVD (RR = 1.16, 95% CI = 1.13-1.19). PPPM costs associated with outpatient and ER visits were approximately 21% and 19% higher among adults with a history of CVD, respectively (P < 0.0001), while costs for inpatient visits were similar between the 2 groups. In addition, a subgroup analysis revealed that adjusted differences in PPPM total cost was larger in the younger age group (56% higher cost in those aged < 45 years) and diminished in the older age group (only 2% higher in those aged ≥ 65 years). CONCLUSIONS: Study findings showed that resource utilization and costs remains significantly higher in T2DM patients with a history of CVD compared with patients without a history of CVD even after controlling for significant patient comorbid and demographic characteristics. Also, younger age groups had higher differences in outcomes compared with older age groups. This study underscores the importance of cost-effective interventions that may reduce economic burden in this T2DM population with a history of CVD. DISCLOSURES: This study was funded by Boehringer Ingelheim. At the time of this study, Mehta and Mountford were employed by IQVIA, which received funding from Boehringer Ingelheim to conduct this study. Mountford is employed by Allergan, which has no connection with this study. Ghosh, Sander, and Kuti are employed by Boehringer Ingelheim. Study concept and design were contributed by Mountford, Mehta, and Ghosh, along with Sander and Kuti. Mountford and Mehta collected the data, and data interpretation was performed by all the authors. The manuscript was written by Sander and Kuti, along with the other authors, and revised by Mehta and Gosh, along with the other authors.

Cardiovascular event incidence and cost in type 2 diabetes mellitus: a Medicare claims-based actuarial analysis.

OBJECTIVE: To assess the economic burden of cardiovascular events in Medicare beneficiaries with type 2 diabetes mellitus (T2DM). METHODS: This claims-based actuarial analysis queried 2013 and 2014 Medicare 5% samples, defining a denominator of fee-for-service beneficiaries. Average per patient per month allowed cost ($PPPM) was calculated for T2DM, demographically adjusted non-T2DM, and denominator. Per member per month allowed cost ($PMPM) was calculated by dividing total population cost by member months in the denominator. Costs of five pre-specified cardiovascular events were calculated as a contribution to denominator $PMPM, as contribution to $PPPM in T2DM, and as incremental cost. RESULTS: During the study period, 22.1% of Medicare fee-for-service beneficiaries had T2DM; of these, 9.68% experienced a cardiovascular event or cardiovascular-related death. T2DM cost represented 37.9% of total allowed $PMPM for the denominator. Average total allowed $PPPM for a T2DM beneficiary was $1,834, compared with $850 for a non-T2DM beneficiary (2.2-times higher). Annual rates of myocardial infarction, stroke, unstable angina admission, heart failure admission, and coronary revascularization in T2DM were 3.3-, 2.4-, 3.2-, 4.0-, and 2.8-times higher than in non-T2DM, and utilization of health services was also greater in T2DM. Cardiovascular events in T2DM accounted for 50% of denominator cardiovascular event cost; 3.6% of denominator population $PMPM was attributable to cardiovascular events in T2DM. Risk-adjusted incremental cardiovascular event cost represented 18.1% of $PPPM in T2DM or 6.9% of $PMPM in the denominator population. CONCLUSIONS: Cardiovascular events in Medicare fee-for-service beneficiaries with T2DM contribute substantially to Medicare cardiovascular events, resource utilization, and cost.

Pharmacokinetics, antifungal activity and clinical efficacy of anidulafungin in the treatment of fungal infections.

IMPORTANCE OF THE FIELD: Anidulafungin is one of three available intravenous echinocandins that plays an important role in the treatment of serious fungal infections. Currently, anidulafungin is approved for the treatment of esophageal candidiasis, candidemia and other invasive Candida infections including intra-abdominal abscesses and peritonitis. AREAS COVERED IN THIS REVIEW: This paper covers a comprehensive review of anidulafungin. WHAT THE READER WILL GAIN: The reader will be provided the most recent data available regarding the pharmacology, pharmacokinetics, in vitro activity and clinical utility of anidulafungin for the treatment of serious fungal infections. TAKE HOME MESSAGE: Echinocandin antifungals, such as anidulafungin, are now considered first line for the treatment of candidemia and invasive candidiasis, particularly in critically ill patients or those who have previously received azole therapy. Anidulafungin has potent in vitro activity against Candida and Aspergillus species, predictable pharmacokinetics that does not require dosage adjustment, few drug interactions and is well tolerated. Because of these favorable characteristics, anidulafungin is an important addition to our antifungal armamentarium.

Student measurement of blood pressure using a simulator arm compared with a live subject's arm.

OBJECTIVE: To compare accuracy of blood pressure measurements using a live subject and a simulator arm, and to determine students' preferences regarding measurement. METHODS: This was a crossover study comparing blood pressure measurements from a live subject and a simulator arm. Students completed an anonymous survey instrument defining opinions on ease of measurement. RESULTS: Fifty-seven students completed blood pressure measurements on live subjects while 72 students completed blood pressure measurements using the simulator arm. There were no significant systematic differences between the 2 measurement techniques. Systolic blood pressure measurements from a live subject arm were less likely to be within 4 mm Hg compared with measurements of a simulator arm. Diastolic blood pressure measurements were not significantly different between the 2 techniques. CONCLUSIONS: Accuracy of student measurement of blood pressure using a simulator arm was similar to the accuracy with a live subject. There was no difference in students' preferences regarding measurement techniques.

Length of stay and hospital costs associated with a pharmacodynamic-based clinical pathway for empiric antibiotic choice for ventilator-associated pneumonia.

STUDY OBJECTIVE: To determine hospital costs associated with the use of a clinical pathway implemented in our intensive care units (ICUs) to optimize antibiotic regimen selection for patients with ventilator-associated pneumonia (VAP) compared with costs in a historical control group treated according to prescriber preference. DESIGN: Retrospective cost analysis from the hospital perspective. SETTING: Single, tertiary-care medical center. PATIENTS: One hundred sixty-six adults with VAP from the medical, surgical, and neurotrauma ICUs (73 historical control patients [2004-2005] and 93 patients given an empiric antibiotic clinical pathway for VAP [2006-2007]). MEASUREMENTS AND MAIN RESULTS: The VAP clinical pathway consisted of an ICU-specific three-drug regimen that considered local minimum inhibitory concentration distributions and a pharmacodynamically optimized dosing strategy. Hospital cost data were collected and inflated to 2007 according to the consumer price index. The VAP-related length of treatment, hospitalization costs, and antibiotic costs were compared between groups. The median VAP length of treatment was 24 days (interquartile range [IQR] 13-35 days] and 11 days (IQR 7-17 days) for historical and clinical pathway groups, respectively (p<0.001). Daily hospital costs were similar for both cohorts over the first 7 days, after which costs declined significantly for patients treated with the clinical pathway (p<0.001). When controlling for baseline differences between groups and length of stay before development of VAP, patients treated with the clinical pathway had shorter lengths of ICU stay after VAP, shorter total hospital lengths of stay after VAP, and lower hospital costs after the treatment of VAP. Median total antibiotic costs for individual patients were similar between groups ($535 [IQR $261-998] vs $482 [IQR $222-985] clinical pathway vs control, p=0.45), and the proportion of VAP hospital resources consumed by antibiotics for both groups was low. CONCLUSION: Although aggressive dosing of more costly antibiotics was empirically prescribed using the clinical pathway, patients in this group exhibited a shorter duration of treatment, reduced hospital length of stay after VAP, and lower hospital costs without any significant increase in antibiotic expenditures.

Impact of inappropriate antibiotic therapy on mortality in patients with ventilator-associated pneumonia and blood stream infection: a meta-analysis.

OBJECTIVES: Studies have found that initial treatment of ventilator-associated pneumonia (VAP) and blood stream infections (BSI) with inappropriate antimicrobial therapy is associated with higher rates of mortality, but additional studies have failed to confirm this. METHODS: Databases were searched to identify studies that met the following criteria: observational trials, patients with VAP or BSI receiving appropriate and inappropriate antimicrobial therapy, and mortality data. We conducted random-effects model meta-analyses, both with and without adjustment. RESULTS: Meta-analyses of VAP studies using unadjusted and adjusted data indicated that inappropriate therapy significantly increased patients' odds of mortality (odds ratio [OR], 2.34; 95% confidence interval [CI], 1.51-3.63; P = .0001, I 2 = 28.5% and OR, 3.03; 95% CI, 1.12-8.19; P = .0292, I 2 = 89.2%, respectively). Meta-analyses of BSI studies using unadjusted and adjusted data showed that inappropriate therapy significantly increased patients' odds of mortality (OR, 2.33; 95% CI, 1.96-2.76; P < .0001, I 2 = 48.7% and OR, 2.28; 95% CI, 1.43-3.65; P = .0006, I 2 = 88.2%, respectively). CONCLUSIONS: There appears to be an association between initial inappropriate antimicrobial therapy and increased mortality in patients with VAP and BSI.

The development of new-onset type 2 diabetes associated with choosing a calcium channel blocker compared to a diuretic or beta-blocker.

OBJECTIVE: It has been acknowledged that patients who receive a beta-blocker or diuretic based regimen are at increased risk of developing new-onset diabetes. Recently, angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have been shown to decrease patients' odds of developing new-onset type 2 diabetes. A number of large placebo-controlled multi-center trials in post-myocardial infarction and heart failure patients have shown the ability of renin-angiotensin-aldosterone system medications to reduce the onset of type 2 diabetes. Pharmacologic data has shown improved insulin sensitivity with ACEIs and ARBs. Controversy persists regarding the influence of calcium channel blockers on the development of new-onset diabetes. RESEARCH DESIGN AND METHODS: Two reviewers conducted a systematic literature search of Medline, EMBASE, CINAHL, and the Cochrane Library (1966 to December 2006) to extract a consensus of trial data involving calcium channel blockers versus diuretics or beta-blockers with an endpoint of new-onset type 2 diabetes. Studies were included if they were randomized controlled trials versus routine treatment, not observational studies of clinical practice. A random-effects model was utilized. Subgroup and sensitivity analyses were conducted. RESULTS: Out of 1721 trials, six meeting inclusion criteria were identified, including 99 006 patients. Calcium channel blockers were associated with a reduced incidence of new-onset type 2 diabetes (odds ratio 0.81; 95% confidence interval [CI] 0.73-0.90; p = 0.0001) compared with diuretic or beta-blocker therapy. The reduction in new-onset type 2 diabetes was maintained when a calcium channel blocker was compared to only thiazide diuretics (OR 0.86; 95% CI 0.75-0.99; p = 0.0346). The meta-analysis was limited by the varying definition of new-onset type 2 diabetes mellitus, as well as the potential for publication bias, which is a limit of any meta-analysis. CONCLUSIONS: Calcium channel blockers may be associated with reduced odds of developing new-onset type 2 diabetes compared to diuretics and beta-blockers.