Jayashri Sankaranarayanan

Clinical outcomes and nephrotoxicity associated with vancomycin trough concentrations during treatment of deep-seated infections

Objective: Higher vancomycin concentrations are thought necessary for treatment of deep-seated methicillin-resistant Staphylococcus aureus (MRSA) infection, yet this may result in greater risk of nephrotoxicity. We evaluated the relationship of serum vancomycin trough concentration with clinical outcomes and nephrotoxicity for patients with deep-seated MRSA infection. Methods: A retrospective cohort study evaluated adults with MRSA pneumonia, endocarditis or osteomyelitis who received vancomycin for ≥ 5 days from June 2005 to June 2007. Patients were stratified by mean vancomycin trough level [low (< 15 mg/l), high (≥ 15 mg/l)]. Outcomes were clinical response, mortality, length of stay (LOS) and nephrotoxicity. Three definitions of nephrotoxicity were used: i) rise in serum creatinine (SCr) ≥ 0.5 mg/dl; ii) 50% increase in SCr; and iii) 25% decrease in estimated creatinine clearance. Results: Fifty-five patients experiencing MRSA pneumonia (n = 28), endocarditis (n = 9), osteomyelitis (n = 20) and multiple infections (n = 2) were stratified into low (n = 39) and high (n = 16) groups. High group patients were more likely to be septic (p = 0.01) and have a higher APACHE II score (p = 0.01). After adjustment for APACHE II score, clinical response rates among survivors did not differ significantly. Risk of death was not significantly different between the high (19%) and low (5%) group patients (p = 0.1). LOS did not differ significantly between groups (p = 0.7). Nephrotoxicity occurred in the low and high groups, respectively, for 10 and 31% (p = 0.04) with definition 1, 10 and 31% (p = 0.04) with definition 2, and 13 and 25% (p = 0.1) with definition 3. After adjustment for APACHE II score, odds of nephrotoxicity based on definitions 1 or 2 were increased among the high versus low groups (OR = 3.27, 95% CI: 0.7 – 15.25, p = 0.1), although not statistically significant. Conclusions: Clinical outcomes did not differ significantly between high and low trough groups for deep-seated MRSA infections. Nephrotoxicity was consistently higher in the high trough group, regardless of the definition used.

Clinical practice patterns of managing low-risk adult febrile neutropenia during cancer chemotherapy in the USA

PurposeThe purpose of the study was to determine oncologists’ current practice patterns for antibiotic management of low-risk fever and neutropenia (FN) after chemotherapy.Materials and methodsA self-administered survey was developed to query management practices for low-risk FN patients and sent to 3,600 randomly selected American Society of Clinical Oncology physician members; hypothetical case scenarios were included to assess factors influencing decisions about outpatient treatment.ResultsOf 3,560 actively practicing oncologists, 1,207 replied (34%). Outpatient antibiotics are used by 82% for selected low-risk FN patients (27% used in them >65% of their patients). Oral levofloxacin (50%), ciprofloxacin (36%), and ciprofloxacin plus amoxicillin/clavulanate (35%) are common outpatient regimens. Fluoroquinolone prophylaxis is used by 45% of oncologists, in a subset of afebrile patients at low risk for FN; growth factors are used adjunctively by 48% for treating low-risk FN. Factors associated with choosing outpatient treatment were: frequency of use in oncologists’ own practices, absence of hematologic malignancy, lower patient age, no infiltrate on X-ray, no prior serious infection, shorter expected FN duration, lower creatinine levels, and shorter distance of patient’s residence from the hospital.ConclusionsUS oncologists, who responded are willing to prescribe outpatient oral antibiotic treatment for low-risk FN, although practices vary considerably and are based on favorable clinical factors. However, practices are often employed that are not recommended for low-risk patients by current guidelines, including fluoroquinolone prophylaxis, adjunctive and/or prophylactic growth factors, and use of levofloxacin for empiric therapy. Educational efforts are needed to better guide cost-effective and supportive care.

A Multicenter Evaluation of Prolonged Empiric Antibiotic Therapy in Adult ICUs in the United States.

Objective:The purpose of this study is to determine the rate of prolonged empiric antibiotic therapy in adult ICUs in the United States. Our secondary objective is to examine the relationship between the prolonged empiric antibiotic therapy rate and certain ICU characteristics. Design:Multicenter, prospective, observational, 72-hour snapshot study. Setting:Sixty-seven ICUs from 32 hospitals in the United States. Patients:Nine hundred ninety-eight patients admitted to the ICU between midnight on June 20, 2011, and June 21, 2011, were included in the study. Intervention:None. Measurements and Main Results:Antibiotic orders were categorized as prophylactic, definitive, empiric, or prolonged empiric antibiotic therapy. Prolonged empiric antibiotic therapy was defined as empiric antibiotics that continued for at least 72 hours in the absence of adjudicated infection. Standard definitions from the Centers for Disease Control and Prevention were used to determine infection. Prolonged empiric antibiotic therapy rate was determined as the ratio of the total number of empiric antibiotics continued for at least 72 hours divided by the total number of empiric antibiotics. Univariate analysis of factors associated with the ICU prolonged empiric antibiotic therapy rate was conducted using Student t test. A total of 660 unique antibiotics were prescribed as empiric therapy to 364 patients. Of the empiric antibiotics, 333 of 660 (50%) were continued for at least 72 hours in instances where Centers for Disease Control and Prevention infection criteria were not met. Suspected pneumonia accounted for approximately 60% of empiric antibiotic use. The most frequently prescribed empiric antibiotics were vancomycin and piperacillin/tazobactam. ICUs that utilized invasive techniques for the diagnosis of ventilator-associated pneumonia had lower rates of prolonged empiric antibiotic therapy than those that did not, 45.1% versus 59.5% (p = 0.03). No other institutional factor was significantly associated with prolonged empiric antibiotic therapy rate. Conclusions:Half of all empiric antibiotics ordered in critically ill patients are continued for at least 72 hours in absence of adjudicated infection. Additional studies are needed to confirm these findings and determine the risks and benefits of prolonged empiric therapy in the critically ill.

Good Research Practices for Measuring Drug Costs in Cost-Effectiveness Analyses: Medicare, Medicaid and Other US Government Payers Perspectives: The ISPOR Drug Cost Task Force Report—Part IV

OBJECTIVES Public programs finance a large share of the US pharmaceutical expenditures. To date, there are not guidelines for estimating the cost of drugs financed by US public programs. The objective of this study was to provide standards for estimating the cost of drugs financed by US public programs for utilization in pharmacoeconomic evaluations. METHODS This report was prepared by the ISPOR Task Force on Good Research Practices-Use of Drug Costs for Cost-Effectiveness Analysis Medicare, Medicaid, and other US Government Payers Subgroup. The Subgroup was convened to assess the methodological and practical issues confronted by researchers when estimating the cost of drugs financed by US public programs, and to propose standards for more transparent, accurate and consistent costing methods. RESULTS The Subgroup proposed these recommendations: 1) researchers must consider regulation requirements that affect the drug cost paid by public programs; 2) drug cost must represent the actual acquisition cost, incorporating any rebates or discounts; 3) transparency with respect to cost inputs must be ensured; 4) inclusion of the public programs perspective is recommended; 5) high cost drugs require special attention, particularly when drugs represent a significant proportion of health-care expenditures for a specific disease; and 6) because of variations across public programs, sensitivity analyses for actual acquisition cost, real-world adherence, and generics availability are warranted. Specific recommendations also were proposed for the Medicare and Medicaid programs. CONCLUSIONS As pharmacoeconomic evaluations for coverage decisions made by US public programs grows, the need for precise and consistent estimation of drug costs is warranted. Application of the proposed recommendations will allow researchers to include accurate and unbiased cost estimates in pharmacoeconomic evaluations.

Rurality and Other Determinants of Early Colorectal Cancer Diagnosis in Nebraska: A 6-Year Cancer Registry Study, 1998-2003

BACKGROUND There are no studies of rurality, and other determinants of colorectal cancer (CRC) stage at diagnosis with population-based data from the Midwest. METHODS This retrospective study identified, incident CRC patients, aged 19 years and older, from 1998-2003 Nebraska Cancer Registry (NCR) data. Using federal Office of Management and Budget classifications, we grouped patients by residence in metropolitan, micropolitan nonmetropolitan, or rural nonmetropolitan counties (non-core based statistical areas). In univariate and multivariate logistic regression analyses, we examined the association of the county classification and of other determinants with early (in situ/local) versus late (regional/distant) stage at CRC diagnosis. RESULTS Of the 6,561 CRC patients identified, 45% were from metropolitan counties, 24% from micropolitan nonmetropolitan counties and 31% from rural nonmetropolitan counties, with 32%, 38%, and 33%, respectively, being diagnosed at an early stage. Multivariate analysis showed micropolitan nonmetropolitan residents were significantly more likely than rural nonmetropolitan residents to be diagnosed at an early stage (adjusted OR, 1.22; 95% CI: 1.05-1.42, P < .05). However, rural nonmetropolitan and metropolitan residents did not significantly differ in the likelihood of early diagnosis. Residents with Medicare rather than those with private insurance (P < .0001), married rather than unmarried residents (P < .01), and residents with rectal cancer rather than those with colon cancer (P < .0001) were more likely to be diagnosed at an early stage. CONCLUSIONS Early CRC diagnosis needs to be increased in rural (non-core) non-metropolitan residents, unmarried residents, and those with private insurance.

Diagnosis and treatment of adult attention-deficit/hyperactivity disorder at US ambulatory care visits from 1996 to 2003

ABSTRACT Objective: To determine national-estimates and characteristics of United States (US) ambulatory care visits made by adults, aged 18 years or older, with attention-deficit hyperactivity disorder (ADHD) diagnosis, treatment patterns, and significant factors associated with adult-ADHD treatment. Methods: Retrospective analyses were conducted of the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey over a combined 8‐year period (1996–2003). Mental-health disorder (including ADHD) visits were identified using International Classification of Diseases, 9th revision, Clinical Modification (ICD‐9‐CM) diagnostic codes. Significant factors of adult-ADHD treatment were determined in multivariable logistic regression analyses. Results: An estimated total 10.5 million ambulatory-ADHD visits accounted for 3.5% of 301 million adult mental-health disorder visits. The census-adjusted visit rate was 0.3–0.4%. Increasing in numbers from the year 2000, ADHD visits were most often to psychiatrists, by Caucasian men, aged 18 to 40 years. Significantly fewer ADHD visits without, versus with, psychiatric comorbidity (mainly depression) received various treat-ments – behavioral (46% vs. 83%), antidepressant (18% vs. 66%), or combined behavioral and ADHD-specific (stimulant or atomoxetine) pharmacotherapy (36% vs. 57%) respectively. However, more ADHD visits without than with psychiatric comorbidity received ADHD-specific pharmacotherapy alone (76% vs. 68%) or no treatment (14% vs. 6.5%). At ADHD visits, adjusting for gender, age, and US census geographic-region, psychiatric comorbidity (odds ratio [OR], 6.5, 95% confidence interval [Cl], 3.5–12.4, p < 0.05) and self-pay reimbursement-source (OR, 2.7, 95% Cl, 1.3–5.7, p < 0.05) significantly increased the likelihood of behavioral treatment. Insurance reimbursement-sources other than private and self-pay significantly decreased the likelihood of an ADHD-specific pharmacotherapy (OR, 0.4, 95% Cl, 0.2–0.7, p < 0.05) or any ADHD-treatment (OR, 0.2, 95% Cl, 0.1–0.5, p < 0.05). Conclusions: Adult-ADHD visits have increased in recent years, with a census-adjusted visit rate of 0.3–0.4%. Psychiatric comorbidity and reimbursement-source were associated with ADHD-treatment. Limited treatment may be a significant problem in US-ambulatory care. It is important to continue validation studies, educate providers, examine the efficacy of multimodal-treatments, and study insurance-related barriers to adult ADHD-treatment.

Epidemiology and characteristics of emergency departments visits by US adults with psychiatric disorder and antipsychotic mention from 2000 to 2004

ABSTRACT Background and objective: There is limited research to acquaint clinicians and payers about antipsychotic use in psychiatric patients visiting United States (US) emergency departments (EDs). The study objective is to describe the epidemiology and compare characteristics of ED visits by adults ≥ 18 years with psychiatric diagnoses and different types of antipsychotic. Methods: Data for 2000–2004 adult ED visits were obtained from the National Hospital Ambulatory Medical Care Survey. Sample-weighted national estimates of (1) typical, (2) atypical, or (3) typical–atypical combination antipsychotic-associated psychiatric ED visits with 95% confidence intervals (CIs) were produced. Characteristics of the three psychiatric ED visit groups with antipsychotic mention, (prescribed, supplied, administered, ordered or continued) were analyzed retrospectively. Significant characteristics for atypical versus typical antipsychotic mention at visits were determined using multivariate logistic regression. Results: Adults made an estimated 26 million ED visits over the 5-year study period that resulted in a psychiatric diagnosis. Of 2 million (or 8%) of these psychiatric ED visits, 38, 55, and 8% mentioned typical, atypical, and combination antipsychotics respectively. From 2000 to 2004 there was an 8-, 3.5-, and 1.5-fold increase in ED visits with combination, atypical, and typical antipsychotics, respectively. The majority of antipsychotic-associated psychiatric ED visits were made by young adults less than 40 years old, Caucasians, needing urgent treatment, and reimbursed by public insurance. More combination-, and typical versus atypical antipsychotic-associated ED visits included a mention of medications for extrapyramidal symptoms (40%, 14% vs. 4%; p < 0.0001) and antianxiety medications (50%, 48% vs. 27%; p < 0.0001). More combination and atypical than typical antipsychotic-related ED visits had anticonvulsant (42%, 35% vs. 12%; p < 0.0001) and antidepressant mentions (31%, 42% vs. 11%; p < 0.0001). A diagnosis of depression (OR 3.2, 95% CI: 1.9–5.3; p < 0.001) or bipolar-disorder (OR 2.5, 95% CI: 1.3–5.0; p = 0.008), and the number of medications received (OR 1.4, 95% CI: 1.0–1.8; p = 0.034) significantly increased the likelihood of atypical versus typical antipsychotic mention at psychiatric ED visits. Conclusions: Despite limitations of analyses with cross-sectional visit data, an increasing number of combination- and atypical antipsychotic-associated US adult ED visits depict the burden on the healthcare system. The associated characteristics of these visits deserve the attention of providers, and payers for cost-effective patient management.

Rurality and other factors associated with adherence to immunosuppressant medications in community-dwelling solid-organ transplant recipients

BACKGROUND Data on immunosuppressant adherence of community-dwelling adult solid-organ transplant recipients (SOTRs) from rural populations in the United States are limited. Therefore, understanding the association of rurality and other factors of immunosuppressant adherence will help providers design and deliver patient-centered adherence enhancing interventions. OBJECTIVES The objective was to examine factors associated with a previously validated 4-item Immunosuppressant Therapy Adherence Scale (ITAS) score in community-dwelling adult SOTRs who received a transplant from an academic center in the Midwestern United States. METHODS For this observational study, cross-sectional survey data (patient demographic, medical condition, immunosuppressant therapy, and self-reported ITAS) received from adult SOTRs aged 19 years or older with other data from an academic transplant centers database were merged. Using multivariate logistic regression, significant SOTR characteristics associated with being adherent (ITAS score=12) versus nonadherent (ITAS score <12) were examined. RESULTS The survey response rate was 30% (n=556/1827). Those SOTRs responding (n=556) had a kidney (48%), liver (47%), or other (4.5%) transplant. They were more likely to be 50- to 64-year olds (52%), men (55%), white (90%), metroresident (59%), with an annual income less than

Correlates and economic outcomes of proton pump inhibitor use by routes in intensive care unit patients

55,000. The SOTRs were living with a transplant for 6.3 years (median), reported excellent-to-good health status (77%), and received different immunosuppressant regimens. More than half of the SOTRs (58%) were adherent. In multivariate analyses, compared with patients aged 65 years or older, younger patients, nonmetro rural- versus metroresident, and those having more (≥6) versus less (<6) comorbidities were significantly less likely to report adherence. SOTRs receiving tacrolimus-based combination immunosuppressant versus tacrolimus alone were more likely to report adherence. CONCLUSIONS When designing and delivering patient care-centered interventions including those that use technology to increase immunosuppressant adherence, providers need to consider rural residence besides other well-established patient factors (younger age, immunosuppressant drug, and comorbidities) of nonadherence.

Evaluation of outcomes of intravenous to oral antimicrobial conversion initiatives: a literature review.

Objectives were to evaluate correlates, and economic outcomes of proton pump inhibitor (PPI) use by route in the intensive care unit from an institutional-payer perspective. A 13-month retrospective study of electronic medical records was conducted of 534 adult (≥19 year-old) intensive care unit patients receiving a PPI (39% enteral-only, 34% parenteral-only, 27% both-route) in a Midwest USA academic medical center. Possible cost-savings with sensitivity analysis were estimated as differences in drug costs (US dollars) between switch eligible parenteral and alternate enteral-PPI medication doses. In multivariate logistic-regression of switch criteria (any oral-medication, orogastric-tube, nothing by oral route), significant correlate for enteral versus parenteral PPI-use was any oral-medication use but not orogastric-tube. Using enteral esomeprazole/lansoprazole instead of parenteral (esomeprazole/pantoprazole) PPI (in 37% i.e. 696 of 1895 switch-eligible doses) would have saved US