Trends in inpatient antiparkinson drug use in the USA, 2001-2012.

PURPOSE: Although therapeutic options and clinical guidelines for Parkinson's disease (PD) have changed significantly in the past 15 years, prescribing trends in the USA remain unknown. The purpose of this population-based cohort study was to examine patterns of inpatient antiparkinson drug use between January 2001 and December 2012 in relation to clinical guideline publication, drug introduction/withdrawal, and emerging safety concerns. METHODS: A total of 16,785 inpatients receiving pharmacological treatment for PD were identified in the Cerner Health Facts database. Our primary outcome was standardized (age, sex, race, and census region) annual prevalence of antiparkinson drug use. We also examined antiparkinson medication trends and polypharmacy by age and sex. RESULTS: The most frequently prescribed antiparkinson drugs between 2001 and 2012 were levodopa (85%) and dopamine agonists (28%). Dopamine agonist use began declining in 2007, from 34 to 27% in 2012. The decline followed publication of the American Academy of Neurology's practice parameter refuting levodopa toxicity, pergolide withdrawal, and pramipexole label revisions. Despite safety concerns for cognitive impairment and falls, individuals ≥80 years of age demonstrated stable rates of dopamine agonist use from 2001 to 2012. Polypharmacy was most common in younger patients. CONCLUSIONS: Dopamine agonist use declined from 2007 to 2012, suggesting that increased awareness of safety issues and practice guidelines influenced prescribing. These events appear to have minimally influenced treatment provided to older PD patients. Antiparkinson prescribing trends indicate that safety and best practice information may be communicated effectively.

Relationship of fluconazole prophylaxis with fungal microbiology in hospitalized intra-abdominal surgery patients: a descriptive cohort study.

INTRODUCTION: Historically, Candida albicans has represented the most common cause of candidemia. However, the proportion of bloodstream infections due to non-albicans Candida species has increased. Because of the risk for candidemia in intra-abdominal surgical patients, some experts advocate the use of fluconazole prophylaxis. The impact of this practice on the distribution of Candida species isolated in breakthrough fungal infections in this population is unknown. We examined the association of fluconazole prophylaxis with the distribution of Candida species in intra-abdominal surgery patients. METHODS: We retrospectively identified cases with a positive blood culture (BCx) for Candida among hospitalized adult intra-abdominal surgery patients between July 2005 and October 2012. Distribution of Candida species isolated represented our primary endpoint. Qualifying surgical cases were determined based on a review of discharge International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. Patients receiving low-dose fluconazole prior to the positive BCx with a known indication for prophylaxis including neutropenia, ICU exposure or history of organ transplantation were classified as prophylaxis. Appropriateness of fungal treatment was determined by the timing and selection of antifungal agent based on fungal isolate. RESULTS: Among 10,839 intra-abdominal surgery patients, 227 had candidemia. The most common Candida species isolated was C. albicans (n = 90, 39.6%) followed by C. glabrata (n = 81, 35.7%) and C. parapsilosis (n = 38, 16.7%). Non-albicans Candida accounted for 57.7% of isolates among the 194 non-prophylaxis patients and 75.8% among the 33 prophylaxis patients (P = 0.001). C. glabrata, the most common non-C. albicans species, was more prevalent than C. albicans in persons given prophylaxis, but not in those without prophylaxis. A total of 63% of those with candidemia were treated inappropriately based on the timing and selection of antifungal administration. CONCLUSIONS: Selection pressure from fluconazole prophylaxis in at-risk surgical patients may be associated with a drift toward fluconazole-resistant species in subsequent candidemia. Tools are needed to guide appropriate treatment through the prompt recognition and characterization of candidemia.

A risk score for identifying methicillin-resistant Staphylococcus aureus in patients presenting to the hospital with pneumonia.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) represents an important pathogen in healthcare-associated pneumonia (HCAP). The concept of HCAP, though, may not perform well as a screening test for MRSA and can lead to overuse of antibiotics. We developed a risk score to identify patients presenting to the hospital with pneumonia unlikely to have MRSA. METHODS: We identified patients admitted with pneumonia (Apr 2005-Mar 2009) at 62 hospitals in the US. We only included patients with lab evidence of bacterial infection (e.g., positive respiratory secretions, blood, or pleural cultures or urinary antigen testing). We determined variables independently associated with the presence of MRSA based on logistic regression (two-thirds of cohort) and developed a risk prediction model based on these factors. We validated the model in the remaining population. RESULTS: The cohort included 5975 patients and MRSA was identified in 14%. The final risk score consisted of eight variables and a potential total score of 10. Points were assigned as follows: two for recent hospitalization or ICU admission; one each for age < 30 or > 79 years, prior IV antibiotic exposure, dementia, cerebrovascular disease, female with diabetes, or recent exposure to a nursing home/long term acute care facility/skilled nursing facility. This study shows how the prevalence of MRSA rose with increasing score after stratifying the scores into Low (0 to 1 points), Medium (2 to 5 points) and High (6 or more points) risk. When the score was 0 or 1, the prevalence of MRSA was < 10% while the prevalence of MRSA climbed to > 30% when the score was 6 or greater. CONCLUSIONS: MRSA represents a cause of pneumonia presenting to the hospital. This simple risk score identifies patients at low risk for MRSA and in whom anti-MRSA therapy might be withheld.

Development and validation of a bedside risk score for MRSA among patients hospitalized with complicated skin and skin structure infections.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a frequent cause of complicated skin and skin structure infections (cSSSI). Patients with MRSA require different empiric treatment than those with non-MRSA infections, yet no accurate tools exist to aid in stratifying the risk for a MRSA cSSSI. We sought to develop a simple bedside decision rule to tailor empiric coverage more accurately. METHODS: We conducted a large multicenter (N=62 hospitals) retrospective cohort study in a US-based database between April 2005 and March 2009. All adult initial admissions with ICD-9-CM codes specific to cSSSI were included. Patients admitted with MRSA vs. non-MRSA were compared with regard to baseline demographic, clinical and hospital characteristics. We developed and validated a model to predict the risk of MRSA, and compared its performance via sensitivity, specificity and other classification statistics to the healthcare-associated (HCA) infection risk factors. RESULTS: Of the 7,183 patients with cSSSI, 2,387 (33.2%) had MRSA. Factors discriminating MRSA from non-MRSA were age, African-American race, no evidence of diabetes mellitus, cancer or renal dysfunction, and prior history of cardiac dysrhythmia. The score ranging from 0 to 8 points exhibited a consistent dose-response relationship. A MRSA score of 5 or higher was superior to the HCA classification in all characteristics, while that of 4 or higher was superior on all metrics except specificity. CONCLUSIONS: MRSA is present in 1/3 of all hospitalized cSSSI. A simple bedside risk score can help discriminate the risk for MRSA vs. other pathogens with improved accuracy compared to the HCA definition.

Current trends in pharmacy benefit designs: a threat to disease management in chronic complex diseases.

With a focus on those patients who are candidates for treatment with biologic agents, we review the impact that current pharmacy benefit trends have on patients with chronic complex diseases and how they affect opportunities for disease management in this unique patient population. Dramatic increases in health care costs have led to a variety of strategies to manage cost. Many of these strategies either limit access to care or increase the patient's responsibility for choosing and paying for care, especially for medications. These strategies have a disproportionate impact on patients with chronic complex diseases, particularly those who require the use of biologic medications. A fundamental prerequisite of disease management has been coverage of disease-modifying therapies. If current pharmacy benefit trends continue, unintended consequences will likely occur including lost opportunities for disease management. Current pharmacy benefit trends could adversely impact disease management, particularly for patients requiring the use of biologic agents. Health plans should consider innovative benefit designs that reflect an appropriate level of cost sharing across all key stake-holders, ensuring appropriate access to needed therapies. Additional research is needed to clarify the value of newer approaches to therapies or benefit design changes.

Associations Between Cardiovascular Events and Nonergot Dopamine Agonists in Parkinson's Disease.

BACKGROUND: Knowledge of possible cardiovascular risks from Parkinson's disease (PD) medications is critical to informing safe and effective treatment decisions. The objective of our study was to determine whether PD patients treated with nonergot dopamine agonists (DAs) are at increased risk of adverse cardiovascular or cerebrovascular outcomes, relative to PD patients receiving other treatments. METHODS: Matched case-control studies were conducted within a cohort of 14,122 inpatients receiving treatment for PD who were identified in the Cerner Health Facts database. Primary outcomes were associations between nonergot DA use and diagnosis of adverse cardiovascular events (acute myocardial infarction, heart failure [HF], hypotension, and valvulopathy). Secondary outcomes included associations between nonergot DA use and diagnosis of adverse cerebrovascular events (cerebrovascular accident and ischemic stroke) and odds of significant exposure-outcome relationships by patient factors. RESULTS: HF was the only adverse event that demonstrated a significant association with nonergot DA use. Individuals treated with pramipexole were more likely to be diagnosed with HF, relative to no use (adjusted odds ratio [AOR]: 1.28; 95% confidence interval [CI]: 1.07-1.53). The association between pramipexole and HF was greater among individuals treated with pramipexole monotherapy (relative to levodopa monotherapy) (AOR, 1.50; 95% CI: 1.09-2.06). Compared to nonusers, men and older individuals treated with pramipexole were more likely to be diagnosed with HF. CONCLUSIONS: Results from our study suggest an association between pramipexole use and HF. Findings warrant replication; however, individuals with PD and independent risk factors for, or a history of, HF may benefit from limited use of this drug.

Adverse Clinical Outcomes and Resource Utilization Associated with Methicillin-Resistant and Methicillin-Sensitive Staphylococcus aureus Infections after Elective Surgery.

BACKGROUND: Current studies of post-operative Staphylococcus aureus disease focus primarily on surgical site infections and are often limited to infections caused by methicillin-resistant Staphylococcus aureus (MRSA). The objective of this retrospective cohort analysis was to describe the occurrence of and outcomes associated with post-operative MRSA and methicillin-sensitive S. aureus (MSSA) infections in patients undergoing elective surgical procedures. METHODS: Data were extracted from Health Facts for inpatients aged 18 years or older with pre-defined International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) procedure codes, meeting additional criteria indicating that the procedure was elective. Post-operative S. aureus infection was identified by one or more qualifying culture positive for MRSA or MSSA. Multivariable regression models compared patients with MRSA, MSSA, and no S. aureus infection. RESULTS: Among 34,866 qualifying patients, the incidence of S. aureus infections was 0.9% during the index admission and 1.7% within 90 d after elective surgery, of which 36.6% and 38.4% were MRSA, respectively. The highest rates were observed among patients undergoing general surgery (2.2% during index admission, 3.2% within 90 d) and plastic surgery (1.8% during index admission, 3.1% within 90 d). Patients with MRSA and MSSA experienced poorer outcomes than uninfected patients, based on index admission length of stay (LOS; mean, 30.2, 22.7, and 5.7 d, respectively), hospital charges ($165,651, $134,313, and $52,077), and hospital mortality (odds ratios, 6.4 for MRSA, 4.8 for MSSA versus uninfected patients). Relative to MSSA infection, MRSA infection was associated with greater total hospital LOS and hospital charges but not with increased re-admission or mortality. CONCLUSIONS: The burden of post-operative S. aureus infection is shared among elective surgical procedures, however, rates and types of infections vary. Whereas MRSA infection results in substantially greater health care cost and LOS, mortality and re-admission rates are similar among patients with MRSA and MSSA. In elective surgery, infection control and surveillance for both MRSA and MSSA are warranted.

Effects of generic-only drug coverage in a Medicare HMO.

Rising pharmacy costs and demand for prescription drug coverage for broader populations of seniors have resulted in the implementation of generic-only pharmacy benefits in Medicare health maintenance organizations (HMOs). The impact on cost and quality of care is unknown. We examined data for members of a California Medicare HMO whose coverage changed to a generic-only benefit and found that the change was associated with reduced health plan pharmacy cost, increased out-of-pocket pharmacy costs for members, increased overall hospital admissions, changed drug-use patterns, and a negative impact on quality metrics for certain conditions. These findings have important implications for future research and health policy decisions.

Risks of cardiovascular disease in patients receiving antiretroviral therapy for HIV infection: implications for treatment.

As mortality rates decrease in the HIV/AIDS population because of antiretroviral therapies, modifiable risk factors for cardiovascular disease take on increased significance. There is compelling evidence that the patient population treated for HIV infection is at an increased risk for atherosclerotic cardiovascular disease. While a portion of this risk appears to be related to traditional cardiac risk factors, there is also evidence that iatrogenic factors play a role. Antiretroviral therapy has been associated with hypertriglyceridemia, hypercholesterolemia, and low high-density lipoprotein cholesterol levels. Insulin resistance and hyperglycemia are among the side effects reported with protease inhibitor (PI) use. Although a few studies report conflicting results, significant data suggest that antiretroviral therapy, particularly PI use, may be associated with a higher incidence of cardiovascular events. The management of cardiac risk will play an increasing role in the treatment of HIV/AIDS.

Applying the PAIN indicators in a managed care setting to improve pain management.

The PAIN indicators create an excellent platform for identifying appropriate patients for whom pain management should be improved within a health plan. The PAIN indicators can be applied efficiently to standard health plan integrated claims data from which a health plan can implement a flexible, phased approach to improving pain management. The program also can be expanded beyond OA and persistent LBP to affect a broader high-risk group with evidence of poorly controlled pain. Pain management has traditionally been an area that has been difficult to target; therefore, pain-specific quality-management initiatives have not been implemented in most health plans. The PAIN indicators can serve as a valuable health plan tool that can be readily implemented and will allow a health plan to advance its overall quality of care in the important area of pain management.

Association of blood glucose levels with in-hospital mortality and 30-day readmission in patients undergoing invasive cardiovascular surgery.

OBJECTIVE: This study aimed to evaluate the association of mean and maximum blood glucose (BG) levels with in-hospital mortality and 30-day hospital readmission among patients in the intensive care unit (ICU) undergoing invasive cardiovascular (CV) surgery. RESEARCH DESIGN AND METHODS: The retrospective database analysis consisted of data from 3132 patients from 17 hospitals who underwent an invasive CV surgery during 1/2000-12/2006. Patients with hyperglycemia were identified based on serum BG levels recorded from 12 hours prior to and 24 hours after ICU admission. Separate logistic regression models were used to examine the association of mean and maximum BG levels to in-hospital mortality and 30-day readmission, adjusting for patient demographics, comorbidities and laboratory values. RESULTS: The adjusted odds ratio (OR) for in-hospital mortality was 1.07 (95% CI: 1.01-1.12; p < .001) for every 0.56-mmol/L increase in mean BG, and OR = 1.06 (95% CI: 1.03-1.08, p < .001) for every 0.56-mmol/L increase in maximum BG. Mean BG was not associated with 30-day readmission while maximum BG had a borderline association: OR = 1.02 (95% CI: 1.00-1.03, p = .06). LIMITATION: The results are not generalizable to all cardiovascular surgical patients since only those undergoing invasive procedures were included in the study. CONCLUSIONS: Higher mean and maximum BG levels were associated with increased risk of in-hospital mortality but not with 30-day readmission. Further research is needed to identify optimal BG targets and the effects of avoiding extreme hyperglycemia on patient outcomes.

Are atrial fibrillation patients receiving warfarin in accordance with stroke risk?

BACKGROUND: Clinical guidelines for the management of atrial fibrillation and atrial flutter provide recommendations for anticoagulation based on patients' overall risk of stroke. To determine the real-world compliance of physicians with these recommendations, we conducted a retrospective cohort study examining the utilization of warfarin in atrial fibrillation/flutter patients by stroke risk level. METHODS: Patients with a qualifying atrial fibrillation/flutter diagnosis during > or =18 months' continuous enrollment between January 2003 and September 2007, and with > or =6 months' eligibility after the first atrial fibrillation/flutter diagnosis, were identified from the US MarketScan database (Thomson Reuters, New York, NY). Warfarin use within 30 days of the first diagnosis was assessed according to stroke risk, estimated using the Congestive heart failure, Hypertension, Age >75 years, Diabetes, Stroke (CHADS(2)) score. RESULTS: Of 171,393 patients included in the analysis, 20.0% had a CHADS(2) score of 0 (low risk), 61.6% a score of 1-2 (moderate risk), and 18.4% a score of 3-6 (high risk). Warfarin, recommended for high stroke-risk patients, was given to only 42.1% of those with a CHADS(2) score of 3-6. A similar percentage of patients with moderate (43.5%) or low stroke risk (40.1%) received warfarin. Only 29.6% of high-risk, 33.3% of moderate-risk, and 34.1% of low-risk patients who were started on warfarin received uninterrupted therapy for 6 months following their initial prescription. CONCLUSIONS: These data suggest that guideline recommendations that anticoagulation should be provided in accordance with stroke risk in atrial fibrillation patients are not routinely followed in clinical practice. The causes and clinical implications of under-utilization of anticoagulation in atrial fibrillation patients with high stroke risk warrant further study.

Pattern of clopidogrel use in hospitalized patients receiving percutaneous coronary interventions.

PURPOSE: The pattern of clopidogrel loading in patients who had undergone percutaneous coronary intervention (PCI) was studied in a retrospective analysis of clinical records. METHODS: A database of deidentified electronic medical records from hospitals and hospital-affiliated outpatient facilities throughout the United States was analyzed for PCI patients with or without a diagnosis of acute coronary syndrome (ACS) who received clopidogrel loading doses of > or =300 mg between 48 hours before and 6 hours after PCI. A high dose was defined as > or =600 mg, and pretreatment was defined as more than 6 hours before PCI for 300-599 mg and 2 or more hours before PCI for > or =600 mg. RESULTS: Among 6253 PCI patients who met the criteria, there were 2331 with a diagnosis of ACS (ACS-PCI) and 3922 without an ACS diagnosis (elective PCI). Of the ACS-PCI patients, 1359 had ST-segment elevation myocardial infarction (STEMI) and 972 had unstable angina (UA) or non-ST-segment elevation myocardial infarction (NSTEMI). A majority of ACS-PCI patients (57%) received a > or =600-mg loading dose, 34% received a 300-mg loading dose, and the rest received a loading dose between 300 and 600 mg. Loading consisted of a single bolus in 75% of patients, two doses in 21.5%, and three or more doses in 3.1%. The first dose was during or after PCI in 56% of the UA/NSTEMI group and in 71% of both the elective PCI and STEMI groups. Among the UA/NSTEMI group, only 33% met criteria for pretreatment. CONCLUSION: Reported practice patterns of clopidogrel administration before PCI for UA/NSTEMI were not consistent with evidence generated from published clinical trials and guidelines. Recommended pre-treatment with clopidogrel was frequently not practiced.