Initiating immunoglobulin replacement therapy helps reduce severe infections and shifts healthcare resource utilization to outpatient services among US patients with inborn errors of immunity.

AIMS: Patients with inborn errors of immunity (IEI) are predisposed to severe recurrent/chronic infections, and often require hospitalization, resulting in substantial burden to patients/healthcare systems. While immunoglobulin replacement therapies (IgRTs) are the standard first-line treatment for most forms of IEI, limited real-world data exist regarding clinical characteristics and treatment costs for patients with IEI initiating such treatment. This retrospective analysis examined infection and treatment characteristics in US patients with IEI initiating IgRT with immune globulin infusion (human), 10% (IG10%). Healthcare resource utilization (HCRU) and associated costs before and after treatment initiation were compared. Additionally, the impact of COVID-19 on infection diagnoses was evaluated. METHODS: Patients with IEI initiating IG10% between July 2012 and August 2019 were selected from Merative MarketScan Databases using diagnosis/prescription codes. Patients were followed 6 months before and after first IG10% claim date. Demographic and clinical characteristics were described. Treatment characteristics and HCRU before and after IG10% initiation were compared. Infection diagnoses during 2020 and 2019 (March-December) were compared. RESULTS: The study included 1,497 patients with IEI diagnoses (mean age = 43.4 years) initiating IG10%, with frequently reported comorbidities like asthma (32.1%). Following IG10% initiation, fewer severe infection diagnoses (11.6% vs 19.9%), fewer infection-related inpatient (10.8% vs 19.5%) and outpatient services (71.6% vs 79.9%), and lower infection-related total healthcare costs ($7,849 vs $13,995; p < 0.001)-driven by lower inpatient costs ($2,746 vs $9,900)-were observed than before. Fewer patients had infection diagnoses during COVID-19 (22.8%) than the prior year (31.2%). CONCLUSION: Patients with IEI are susceptible to severe infections leading to high disease burden and treatment costs. Following IG10% initiation, we observed fewer infections, lower infection-related treatment costs, and shift in care (inpatient to outpatient) leading to significant cost savings. Among patients with IEI, 27% fewer infection diagnoses were observed during the early COVID-19 lockdown period than the prior year.

Some people are born with inborn errors of immunity, or IEI. This study included 1,497 people with IEI who recently started taking a drug called immunoglobulin therapy. Before taking this drug, the participants got infections easily, were hospitalized often, and had to take other costly medicines. After starting this drug, they had fewer infections and could be treated at the doctor's office. They had fewer infections during the COVID-19 pandemic than before the pandemic.

Effects of Supplementation with Dried Neem Leaf Extract on Lipid Peroxidation and Antioxidant Enzyme mRNA Expression in the Pectoralis Major Muscle of Broiler Chickens.

This study was conducted to evaluate the effects of dietary supplementation of dried neem (Azadirachta indica) leaf extract (DNE) on lipid peroxidation and the expression of genes encoding mRNAs in antioxidant enzymes in the pectoralis major muscle of chickens. A total of 24 male broiler chickens (ROSS308) were divided into three groups (n=8) at 21 days of age. The control group of chickens was fed a basal diet, and the remaining two groups of chickens were fed a basal diet supplemented with DNE at a concentration of 0.5% or 2.0% until 35 days of age. Growth performance (body weight, weight gain, feed intake, and feed conversion ratio) and tissue weights did not differ among the three groups. The 2.0% DNE-supplemented diet decreased the muscle malondialdehyde content, a marker of lipid peroxidation, and drip loss compared to the control chickens. In addition, the expression of genes encoding mRNAs of antioxidant enzymes (i.e., Cu/Zn-superoxide dismutase, Mn-superoxide dismutase, glutathione peroxidase 7, and catalase) were higher in the pectoralis major muscle of chickens fed the 2.0% DNE-supplemented diet than in the control chickens. Therefore, DNE supplementation increased the expression of genes encoding mRNAs in antioxidant enzymes and reduced lipid peroxidation and drip loss in the pectoralis major muscle of broiler chickens.

Real World Analysis of Small Cell Lung Cancer Patients: Prognostic Factors and Treatment Outcomes.

In this observational study, we assessed treatment patterns and prognostic factors in patients with small cell lung cancer (SCLC) in a large state-mandated healthcare organization in Israel. Methods: All incident cases with histologically confirmed SCLC who initiated systemic anti-cancer treatment between 2011 and 2017 were identified. Treatment patterns and overall survival (OS) were evaluated for each line of therapy. Results: A total of 235 patients were identified (61% male, median age 64 years, 95% ever smokers, 64% had extensive stage). The first-line treatment was platinum-etoposide regimen for 98.7% of the cohort. The second and third-line regimen were given to 43% and 12% of patients, respectively. Mean OS for extensive and limited stage patients was 9.1 and 23.5 months respectively. In a multivariable model, increased risk for mortality was observed among patients with an ECOG performance status (PS) of 2 compared to a PS of 0-1 for the extensive stage patients (Hazard ratio (HR) = 1.63, 95% confidence ratios (CI): 1.00-2.65); and for males compared to females for the limited stage patients (HR = 2.17; 95% CI: 1.12-4.20). Regarding all 2nd line patients in a multivariable model incorporating relevant confounding factors, demonstrated a significantly better outcome with platinum-based regimens compared to topotecan. Median survival after initiation of 2nd line in platinum-sensitive patients was longer (p = 0.056) for those re-challenged with platinum-based regimen (n = 7): 6.8mo (6.1-not reported (NR)), compared with those switched to a different treatment (n = 27): 4.5 mo (2.6-6.6) for extensive stage patients, and a non-significant difference was also observed for limited stage patients. Conclusion: To our knowledge, this is one of the largest real-world studies of SCLC patients. OS for SCLC patients was similar to that reported in clinical trials. PS for extensive stage patients and sex for limited stage patients were significant correlates of prognosis. Re-challenge of the platinum-based doublet was associated with longer OS compared to switching treatment in extensive stage patients.

Veliparib with carboplatin and paclitaxel in BRCA-mutated advanced breast cancer (BROCADE3): a randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: BRCA1 or BRCA2-mutated breast cancers are sensitive to poly(ADP-ribose) polymerase (PARP) inhibitors and platinum agents owing to deficiency in homologous recombination repair of DNA damage. In this trial, we compared veliparib versus placebo in combination with carboplatin and paclitaxel, and continued as monotherapy if carboplatin and paclitaxel were discontinued before progression, in patients with HER2-negative advanced breast cancer and a germline BRCA1 or BRCA2 mutation. METHODS: BROCADE3 was a randomised, double-blind, placebo-controlled, phase 3 trial done at 147 hospitals in 36 countries. Eligible patients (aged ≥18 years) had deleterious germline BRCA1 or BRCA2 mutation-associated, histologically or cytologically confirmed advanced HER2-negative breast cancer, an Eastern Cooperative Oncology Group performance status of 0-2, and had received up to two previous lines of chemotherapy for metastatic disease. Patients were randomly assigned (2:1) by interactive response technology by means of permuted blocks within strata (block size of 3 or 6) to carboplatin (area under the concentration curve 6 mg/mL per min intravenously) on day 1 and paclitaxel (80 mg/m2 intravenously) on days 1, 8, and 15 of 21-day cycles combined with either veliparib (120 mg orally twice daily, on days -2 to 5) or matching placebo. If patients discontinued carboplatin and paclitaxel before progression, they could continue veliparib or placebo at an intensified dose (300 mg twice daily continuously, escalating to 400 mg twice daily if tolerated) until disease progression. Patients in the control group could receive open-label veliparib monotherapy after disease progression. Randomisation was stratified by previous platinum use, history of CNS metastases, and oestrogen and progesterone receptor status. The primary endpoint was investigator-assessed progression-free survival per Response Evaluation Criteria in Solid Tumors version 1.1. Efficacy analyses were done by intention to treat, which included all randomly assigned patients with a centrally confirmed BRCA mutation, and safety analyses included all patients who received at least one dose of velilparib or placebo. This study is ongoing and is registered with ClinicalTrials.gov, NCT02163694. FINDINGS: Between July 30, 2014, and Jan 17, 2018, 2202 patients were screened, of whom 513 eligible patients were enrolled and randomly assigned. In the intention-to-treat population (n=509), 337 patients were assigned to receive veliparib plus carboplatin-paclitaxel (veliparib group) and 172 were assigned to receive placebo plus carboplatin-paclitaxel (control group). Median follow-up at data cutoff (April 5, 2019) was 35·7 months (IQR 24·9-43·6) in the veliparib group and 35·5 months (23·1-45·9) in the control group. Median progression-free survival was 14·5 months (95% CI 12·5-17·7) in the veliparib group versus 12·6 months (10·6-14·4) in the control group (hazard ratio 0·71 [95% CI 0·57-0·88], p=0·0016). The most common grade 3 or worse adverse events were neutropenia (272 [81%] of 336 patients in the veliparib group vs 143 [84%] of 171 patients in the control group), anaemia (142 [42%] vs 68 [40%]), and thrombocytopenia (134 [40%] vs 48 [28%]). Serious adverse events occurred in 115 (34%) patients in the veliparib group versus 49 (29%) patients in the control group. There were no study drug-related deaths. INTERPRETATION: The addition of veliparib to a highly active platinum doublet, with continuation as monotherapy if the doublet were discontinued, resulted in significant and durable improvement in progression-free survival in patients with germline BRCA mutation-associated advanced breast cancer. These data indicate the utility of combining platinum and PARP inhibitors in this patient population. FUNDING: AbbVie.

Comparison of antegrade percutaneous versus retrograde ureteroscopic lithotripsy for upper ureteric calculus for stone clearance, morbidity, and complications.

INTRODUCTION: The optimal management of upper ureteric calculus remains controversial. We compare the outcomes of antegrade percutaneous ureterolithotripsy (APCUL) with retrograde ureteroscopic lithotripsy (URSL) for upper ureteric calculus with respect to stone clearance, morbidity, and complication rates. MATERIALS AND METHODS: This prospective study was carried out from December 2014 to June 2016. A total of 117 patients with upper ureteric calculus sized (10-20) mm who underwent APCUL or URSL were included in the study. RESULTS: APCUL and URSL were performed in 64 and 53 patients, respectively. The mean age and stone size were comparable between the two groups. The stone clearance rate at 1-month follow-up was 93.75% in the antegrade group and 81.13% in the retrograde group (P = 0.036). Mean anaesthesia time was significantly longer for the APCUL group while the actual mean operative time was significantly longer for the URSL group (P < 0.001). The overall complication rate was higher in antegrade group (P = 0.804), whereas most of the major complications (Clavien Grade III or more) occurred only in the URSL group (P = 0.007). Blood transfusion was required only in the APCUL group (7.8% versus 0%; P = 0.50). In the URSL group, stone retropulsion occurred in four patients, of which three subsequently required shock wave lithotripsy and one required percutaneous nephrolithotomy in a second sitting. CONCLUSION: APCUL has better stone-free rates as compared to URSL for an upper ureteric calculus of size 10-20 mm. Although the postoperative minor complications are higher in the antegrade group, severe complications occurred only in the retrograde group. Hence, antegrade approach can be considered as the preferred option to achieve better stone clearance in a single sitting with acceptable morbidity and complication rates.

Applying Machine Learning Techniques to Identify Undiagnosed Patients with Exocrine Pancreatic Insufficiency.

BACKGROUND: Exocrine pancreatic insufficiency (EPI) is a serious condition characterized by a lack of functional exocrine pancreatic enzymes and the resultant inability to properly digest nutrients. EPI can be caused by a variety of disorders, including chronic pancreatitis, pancreatic cancer, and celiac disease. EPI remains underdiagnosed because of the nonspecific nature of clinical symptoms, lack of an ideal diagnostic test, and the inability to easily identify affected patients using administrative claims data. OBJECTIVES: To develop a machine learning model that identifies patients in a commercial medical claims database who likely have EPI but are undiagnosed. METHODS: A machine learning algorithm was developed in Scikit-learn, a Python module. The study population, selected from the 2014 Truven MarketScan® Commercial Claims Database, consisted of patients with EPI-prone conditions. Patients were labeled with 290 condition category flags and split into actual positive EPI cases, actual negative EPI cases, and unlabeled cases. The study population was then randomly divided into a training subset and a testing subset. The training subset was used to determine the performance metrics of 27 models and to select the highest performing model, and the testing subset was used to evaluate performance of the best machine learning model. RESULTS: The study population consisted of 2088 actual positive EPI cases, 1077 actual negative EPI cases, and 437 530 unlabeled cases. In the best performing model, the precision, recall, and accuracy were 0.91, 0.80, and 0.86, respectively. The best-performing model estimated that the number of patients likely to have EPI was about 12 times the number of patients directly identified as EPI-positive through a claims analysis in the study population. The most important features in assigning EPI probability were the presence or absence of diagnosis codes related to pancreatic and digestive conditions. CONCLUSIONS: Machine learning techniques demonstrated high predictive power in identifying patients with EPI and could facilitate an enhanced understanding of its etiology and help to identify patients for possible diagnosis and treatment.

The economic impact of switching from Synthroid for the treatment of hypothyroidism.

AIMS: To compare hypothyroidism-related costs for patients who continuously used Synthroid and patients who switched from Synthroid to alternative therapies. MATERIALS AND METHODS: Truven's Health Analytics MarketScan Commercial Claims and Encounters database from January 1, 2007 to June 30, 2014 was queried for US adults diagnosed with hypothyroidism who initiated Synthroid and adhered to such therapy for at least 6 months. Propensity score matching matched continuous users of Synthroid to patients who switched from Synthroid to alternative levothyroxine agents. Kruskal-Wallis tests assessed differences between the matched cohorts in several categories of costs, including disease-related drug costs, non-drug medical costs, and total direct medical costs. RESULTS: There were 10,159 individuals included in the study, with 7,991 continuous users of Synthroid and 2,168 switchers. After matching (n = 2,052 for each cohort), continuous use of Synthroid was associated with significantly lower hypothyroidism-related non-drug medical costs ($595 vs $1,023; p = .003) and reduced hypothyroidism-related total medical costs ($757 vs $1,132; p = .010), despite being associated with significantly higher drug costs ($161 vs $109; p < .001). Hypothyroidism-related total medical costs rose as the number of switches of hypothyroidism treatment increased, with continuous users having significantly lower hypothyroidism-related total medical costs ($757) compared with patients who switched twice ($1,179; p = .001) or three or more times ($1,268; p = .004). LIMITATIONS: The analyses focused on continuously insured patients who were adherent to Synthroid for at least 6 months and results may not be generalizable. The reliance on claims data does not allow for clinical examination of hypothyroidism or inclusion of some factors that may be associated with outcomes. The analyses assume that all prescriptions filled are taken as prescribed. CONCLUSIONS: Results indicate that there are significant direct economic healthcare costs associated with switching from Synthroid to alternative levothyroxine therapies, and that these costs increase as patients switch therapies more frequently.

Psychometric Evaluation of the Hypogonadism Impact of Symptoms Questionnaire Short Form (HIS-Q-SF).

BACKGROUND: The Hypogonadism Impact of Symptoms Questionnaire Short Form (HIS-Q-SF) is a patient-reported outcome measurement designed to evaluate the symptoms of hypogonadism. The HIS-Q-SF is an abbreviated version including17 items from the original 28-item HIS-Q. AIM: To conduct item analyses and reduction, evaluate the psychometric properties of the HIS-Q-SF, and provide guidance on score interpretation. METHODS: A 12-week observational longitudinal study of hypogonadal men was conducted as part of the original HIS-Q psychometric evaluation. Participants completed the original HIS-Q every 2 weeks. Blood samples were collected to evaluate testosterone levels. Participants completed the Aging Male's Symptoms Scale, the International Index of Erectile Function, the Short Form-12, and the PROMIS Sexual Activity, Satisfaction with Sex Life, Sleep Disturbance, and Applied Cognition Scales (baseline and weeks 6 and 12). Clinicians completed the Clinical Global Impression of Severity and Change scales and a clinical form. MAIN OUTCOME MEASURES: Item performance was evaluated using descriptive statistics and Rasch analyses. Reliability (internal consistency and test-retest), validity (concurrent and know groups), and responsiveness were assessed. RESULTS: One hundred seventy-seven men participated (mean age = 54.1 years, range = 23-83). Similar to the full HIS-Q, the final abbreviated HIS-Q-SF instrument includes five domains (sexual, energy, sleep, cognition, and mood) with two sexual subdomains (libido and sexual function). For key domains, test-retest reliability was very good, and construct validity was good for all domains. Known-groups validity was demonstrated for all domain scores, subdomain scores, and total score based on the Clinical Global Impression-Severity. All domains and subdomains were responsive to change based on patient-rated anchor questions. CLINICAL IMPLICATIONS: The HIS-Q-SF could be a useful tool in clinical practice, epidemiologic studies, and other academic research settings. STRENGTHS AND LIMITATIONS: Careful consideration was given to the selection of the final HIS-Q-SF items based on quantitative data and clinical expert feedback. Overall, the reduced set of items demonstrated strong psychometric properties. Testosterone levels for the participating men were not as low as anticipated, which could have limited the ability to examine the relations between the HIS-Q-SF and testosterone levels. Further, the analyses used data collected through administration of the full HIS-Q, and future studies should administer the standalone HIS-Q-SF to replicate the psychometric analyses reported in the present study. CONCLUSION: Similar to the original HIS-Q, the HIS-Q-SF has evidence supporting reliability, validity, and responsiveness. The short form includes a smaller set of items that might be more suitable for use in clinical practice or academic research settings. Gelhorn HL, Roberts LJ, Khandelwal N, et al. Psychometric Evaluation of the Hypogonadism Impact of Symptoms Questionnaire Short Form (HIS-Q-SF). J Sex Med 2017;14:1046-1058.

Clinical Characteristics, Health Care Utilization and Costs Among Men with Primary or Secondary Hypogonadism in a US Commercially Insured Population.

INTRODUCTION: Hypogonadism is broadly associated with increases in chronic comorbid conditions and health care costs. Little is known about the specific impact of primary and secondary hypogonadism on health care costs. AIM: To characterize the health care cost and utilization burden of primary and secondary hypogonadism in a population of US men with commercial insurance. METHODS: Newly diagnosed patients with International Classification of Diseases, Ninth Revision, Clinical Modification codes associated with specific medical conditions known to have a high prevalence of testosterone deficiency (ie, relating to primary or secondary hypogonadism) or who had fills for testosterone replacement therapy from January 1, 2007 through April 30, 2013 were identified in administrative claims data from the HealthCore Integrated Research Database. A cohort of patients without hypogonadism was matched on demographics and comorbidities. The matched hypogonadism and non-hypogonadism cohorts (n = 5,777 in each cohort) were compared during a 12-month follow-up period. MAIN OUTCOME MEASURES: Direct health care expenditures and utilization were assessed for all causes and for hypogonadism-related claims. Costs included out-of-pocket patient expenditures and those paid by the insurer. RESULTS: Hypogonadism and matched non-hypogonadism cohorts were similar in demographics (mean age = 50 years) and diagnosed comorbid conditions in the 12 months preceding the index date. In the year after the index date, mean all-cause expenditures for patients with hypogonadism increased by 62% (from $5,425 to $8,813) compared with 25% for the matched controls (from $4,786 to $5,992; P < .01 for follow-up difference between groups). Approximately 16% of total mean costs ($1,377), primarily outpatient and pharmacy costs, were identifiable as related to hypogonadism. CONCLUSION: These data from a population of US men with commercial insurance coverage showed a greater resource use burden for patients with primary and secondary hypogonadism compared with similar patients without hypogonadism. Additional management might be required to address unmet need and decrease the cost burden for patients with hypogonadism.

Hospital resource use of patients receiving isavuconazole vs voriconazole for invasive mold infections in the phase III SECURE trial.

OBJECTIVE: In the phase III SECURE trial, isavuconazole was non-inferior to voriconazole for all-cause mortality for the primary treatment of invasive mold disease (IMD) caused by Aspergillus spp. and other filamentous fungi. This analysis assessed whether hospital resource utilization was different between patients treated with isavuconazole vs voriconazole in SECURE. METHODS: The analysis population comprised adults with proven/probable/possible IMD enrolled in SECURE. The primary endpoint was hospital length of stay (LOS) in the overall trial population. Patients were also stratified by estimated glomerular filtration rate-modification of diet in renal disease category (< 60 mL/min/1.73 m(2) [moderate-to-severe impairment] and ≥60 mL/min/1.73 m(2) [mild or no impairment]), body mass index (BMI; <25, ≥25-<30, and ≥30 kg/m(2)), and age (≤45, >45-≤65, and >65 years). RESULTS: Data from 516 patients (258 per arm) were evaluated. Overall, median LOS was not statistically significantly different between the isavuconazole (15.0 days) and voriconazole (16.0 days; p = 0.607) arms. Median LOS was statistically significantly shorter in patients with moderate-to-severe renal impairment treated with isavuconazole (9.0 days) vs voriconazole (19.0 days; hazard ratio [HR]: 3.44; 95% confidence interval [CI] = 1.51-7.83). Median LOS was shorter, but not significantly, in patients with a BMI ≥30 kg/m(2) (isavuconazole 13.5 days vs voriconazole 22 days; HR = 1.57; 95% CI = 0.70-3.52) or aged >65 years (isavuconazole 15.0 days vs voriconazole 20.0 days; HR = 1.37; 95% CI = 0.87-2.16). LIMITATIONS: As the patient subgroups analyzed were small, sub-group findings should be interpreted with caution in light of the lack of statistical significance for each sub-group-by-treatment interaction. CONCLUSIONS: Isavuconazole may reduce hospital LOS in certain subgroups of patients with IMD, especially those with moderate-to-severe renal impairment.

Drug-Drug Interaction Associated with Mold-Active Triazoles among Hospitalized Patients.

The majority of hospitalized patients receiving mold-active triazoles are at risk of drug-drug interactions (DDIs). Efforts are needed to increase awareness of DDIs that pose a serious risk of adverse events. Triazoles remain the most commonly utilized antifungals. Recent developments have included the mold-active triazoles (MATs) itraconazole, voriconazole, and posaconazole, which are first-line agents for the treatment of filamentous fungal infections but have the potential for DDIs. This objective of this study was to evaluate the prevalence of triazole DDIs. Hospitalized U.S. adults with MAT use were identified in the Cerner HealthFacts database, which contained data from over 150 hospitals (2005 to 2013). The severities of DDIs with MATs were categorized, using drug labels and the drug information from the Drugdex system (Thompson Micromedex), into four groups (contraindicated, major, moderate, and minor severity). DDIs of minor severity were not counted. A DDI event was considered to have occurred if the following two conditions were met: (i) the patient used at least one drug with a classification of at least a moderate interaction with the MAT during the hospitalization and (ii) there was a period of overlap between the administration of the MAT and that of the interacting drug of at least 1 day. A total of 6,962 hospitalizations with MAT use were identified. Among them, 88% of hospitalizations with voriconazole use, 86% of hospitalizations with itraconazole use, and 93% of hospitalizations with posaconazole use included the use of a concomitant interacting drug. A total of 68% of hospitalizations with posaconazole use, 34% of hospitalizations with itraconazole use, and 20% of hospitalizations with voriconazole use included the use of at least one drug with a DDI of contraindicated severity. A total of 83% of hospitalizations with posaconazole use, 61% of hospitalizations with itraconazole use, and 82% of hospitalizations with voriconazole use included the use of at least one drug that resulted in a severe DDI. The findings of this study demonstrate that a majority of hospitalized patients receiving MAT are at risk for severe drug-drug interactions and highlight the need for antifungal stewardship.

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.

Oral chemotherapy program improves adherence and reduces medication wastage and hospital admissions.

Adherence, medication wastage, and reduction in hospital admissions were investigated in a retrospective test-control study design for patients enrolled in the oral chemotherapy cycle management program (CMP), a program that offers clinical support, dose monitoring, and early identification of side effects for patients on select oral chemotherapy. Patients who initiated oral chemotherapy with sorafenib, sunitinib, or erlotinib during June 2008 through December 2009 and who were enrolled in the CMP were included as a test group. Patients who initiated oral chemotherapy with these drugs using Walgreens Specialty Pharmacy during January 2007 through May 2008 and were not part of the CMP were included as control group 1, and patients from a national payor database who initiated therapy with sorafenib, sunitinib, or erlotinib during June 2008 through August 2010 were included as control group 2. Compared with control group 1, patients in the CMP group showed no significant differences with regard to their possession ratios (P > .05), but demonstrated significantly higher persistency rates (P < .05) at the end of 6 months follow-up. For patients in the CMP group who discontinued therapy, approximately 34% could have experienced reduced wastage had they been on a split medication plan. Patients who are monitored closely and able to identify serious side effects early can avoid complications leading to hospitalizations. The study showed potential savings on drug costs because of a split-fill medication plan, and savings from reduced hospitalization associated with timely identification and management of severe side effects. A clinical program, such as CMP, effectively improves adherence and reduces wastage and hospitalizations for oral chemotherapeutic agents, realizing potential cost savings to both payors and patients.

Community pharmacy and mail order cost and utilization for 90-day maintenance medication prescriptions.

BACKGROUND: Pharmacy benefit management (PBM) companies promote mail order programs that typically dispense 90-day quantities of maintenance medications, marketing this feature as a key cost containment strategy to address plan sponsors' rising prescription drug expenditures. In recent years, community pharmacies have introduced 90-day programs that provide similar cost advantages, while allowing these prescriptions to be dispensed at the same pharmacies that patients frequent for 30-day quantities. OBJECTIVE: To compare utilization rates and corresponding costs associated with obtaining 90-day prescriptions at community and mail order pharmacies for payers that offer equivalent benefits in different 90-day dispensing channels. METHODS: We performed a retrospective, cross-sectional investigation using pharmacy claims and eligibility data from employer group clients of a large PBM between January 2008 and September 2010. We excluded the following client types: government, third-party administrators, schools, hospitals, 340B (federal drug pricing), employers in Puerto Rico, and miscellaneous clients for which the PBM provided billing services (e.g., the pharmacy's loyalty card program members). All employer groups in the sample offered 90-day community pharmacy and mail order dispensing and received benefits management services, such as formulary management and mail order pharmacy, from the PBM. We further limited the sample to employer groups that offered equivalent benefits for community pharmacy and mail order, defined as groups in which the mean and median copayments per claim for community and mail order pharmacy, by tier, differed by no more than 5%. Enrollees in the sample were required to have a minimum of 6 months of eligibility in each calendar year but were not required to have filled a prescription in any year. We evaluated pharmacy costs and utilization for a market basket of 14 frequently dispensed therapeutic classes of maintenance medications. The proportional share of claims for each therapeutic class in the mail order channel was used to weight the results for the community pharmacy channel. Using ordinary least squares regression models, we controlled for differences between channel users with respect to the following confounding factors: age, gender, presence or absence of each of the top 11 drug-inferred conditions (e.g., asthma/chronic obstructive pulmonary disease, cardiovascular disease), drug mix, and calendar year. We calculated estimated predicted means holding all covariates at their mean values. For both 90-day dispensing channels, we calculated number of 90-day claims per member per year (PMPY) and cost per pharmacy claim, with all claims counts adjusted to 30-day equivalents (i.e., number of 90-day claims × 3). Differences were compared using t-tests for statistical significance. RESULTS: Of 355 PBM clients prior to exclusions, 72 unique employers covering 644,071 unique members (range of approximately 100 to more than 100,000 members per employer) were included in the analysis. On an unadjusted basis, community pharmacies represented 80.8% of 90-day market basket claims (in 30-day equivalents: 3.97 claims PMPY vs. 0.95 in mail order) and 77.2% of total allowed charges. After adjustments for therapeutic group mix and patient characteristics, predicted mean pharmacy claim counts PMPY were 4.09 for community pharmacy compared with 0.85 for mail order (P less than 0.001). Predicted mean allowed charges per claim for community and mail order pharmacies did not significantly differ ($49.03 vs. $50.04, respectively, P = 0.202). CONCLUSIONS: When offered maintenance medications through community and mail order pharmacies on a benefit-equivalent basis, commercially insured employees and their dependents utilized the community pharmacy channel more frequently by a margin of more than 4 to 1 in terms of claims PMPY. Overall allowed charges per claim for community and mail order pharmacy did not significantly differ.

Impact of an online prescription management account on medication adherence.

OBJECTIVES: To assess medication adherence rates of patients utilizing an online prescription management account compared with nonusers. STUDY DESIGN: A retrospective analysis was conducted using de-identified pharmacy claims data from a pharmacy benefit manager covering the period from April 1, 2009, to March 31, 2011. Patients who were continuously eligible throughout the study period and that had at least 1 prescription fill for any of the 8 therapeutic groups examined in the study were selected for inclusion. METHODS: Adherence was assessed by measuring the proportion of days covered (PDC). Propensity score matching was utilized to minimize differences in age, gender, chronic condition score, copay, household income, and urban locality between the users and nonusers groups. Results were reported for all therapeutic groups combined, as well as by individual therapeutic group. RESULTS: Overall, patients utilizing the online account had a significantly higher weighted average PDC (73.19% vs 61.64%, P <.0001). Users also had a higher average PDC for each individual therapeutic group, although the beta-blocker group was not statistically significant. The percentage of patients achieving an average PDC of >80% was also found to be greater in the users group across each therapeutic group and overall. CONCLUSIONS: Patients who utilized an online prescription management account had higher rates of medication adherence as compared with nonusers. Additional studies are needed to assess which specific components of the prescription management account have the biggest impact on adherence.

Medication adherence for 90-day quantities of medication dispensed through retail and mail order pharmacies.

OBJECTIVES: To examine relative medication adherence of patients filling 90-day supplies of maintenance medications using retail and mail order channels. It was hypothesized that adherence rates would not differ across the 2 channels. STUDY DESIGN: A cross-sectional retrospective analysis was conducted using de-identified pharmacy claims data from a large pharmacy benefit manager (PBM) database over a 2-year period (January 2008 to August 2010). Patients who were continuously eligible for at least 12 months during this time frame, with benefit plan designs that allowed filling of 90-day supplies either at retail or by mail order pharmacy, were selected. METHODS: Adherence was measured by medication possession ratio (MPR) within a 1-year period. Propensity score matching was employed to minimize differences between the Retail-90 group and Mail Order-90 group. RESULTS: Overall, patients filling 90-day prescriptions for 9 therapeutic groups (antiasthmatics and bronchodilators, antidepressants, antidiabetics, antihyperlipidemics, antihypertensives, beta blockers, calcium channel blockers, diuretics, and thyroid agents) at retail pharmacies demonstrated a propensity score­matched average MPR that was statistically higher than for patients filling prescriptions via mail order (77.0% vs 76.0%). There were no significant differences in MPR (post-matching) between 90-day retail and mail order channels for individual therapeutic groups, except for antidiabetics (80.2% vs 83.1%). CONCLUSIONS: On a propensity-matched basis, patients who fill maintenance prescriptions at retail have a slightly, but statistically significantly, higher MPR than patients who fill their prescriptions by mail

The impact of 90-day prescriptions on adherence at workplace pharmacies compared to traditional mail order.

This study evaluated adherence to medications used to treat chronic conditions for patients with 90-day prescriptions, comparing patients with access to workplace pharmacy services versus patients using mail order services. De-identified pharmacy claims data were used to compute medication possession ratio and gaps in therapy. Results were compared for patients who filled 90-day prescriptions at workplace pharmacies versus patients who filled 90-day prescriptions using mail order pharmacy services in a 1-year period. Statistical tests to assess between group differences were performed controlling for differences because of age, sex, number of select chronic conditions, number of unique medication therapeutic classes, and patient out-of-pocket cost per therapy day. Statistically significant differences were found between patients who filled their maintenance medications at the worksite compared to those who used mail-order pharmacy services. Patients filling prescriptions at a workplace pharmacy were 22% less likely to have a gap in therapy of over 30 days compared to similar patients using mail order services. Workplace pharmacy utilizers also had overall adherence rates 3.68% higher than patients who utilized mail order pharmacy services. Our analysis suggests that it may not be just the quantity of medication dispensed that impacts patients' adherence to their prescription medication, but a variety of other factors including pharmacist-patient interaction. Having a pharmacist on-site and available to patients with chronic considerations could provide added value. These results can aid employers and other stakeholders to decide which prescription benefits to offer their employees and members.

Impact of clinical oral chemotherapy program on wastage and hospitalizations.

PURPOSE: The oral chemotherapy cycle management program (CMP) provides clinical management support to patients receiving certain oral chemotherapies. The CMP includes a dose-monitoring (ie, split-fill) plan for early identification and management of adverse effects. If serious adverse effects are identified mid cycle, the remainder of the monthly supply is withheld, thus avoiding potential waste associated with early therapy discontinuation. This study investigated medication wastage and estimated potential cost savings for patients who were enrolled in the CMP, as compared with those who were not enrolled in the program. STUDY DESIGN: Retrospective test-control study. PATIENTS AND METHODS: Patients whose oral chemotherapy was initiated between June 2008 and February 2010 and who were enrolled in the CMP were included as the test group. Patient whose oral chemotherapy was initiated between June 2007 and May 2008 and who were not part of the CMP were included as the control group. RESULTS: Medication wastage associated with early therapy discontinuation was found to be lower in the CMP group. Approximately 34% of patients in the CMP group could have avoided medication wastage if split-fill plans had been available, potentially realizing savings of approximately $934.20 per patient. Linear probability regression models showed that the CMP group had a 2.9% probability for reduction in hospital admissions (P < .05), resulting in additional savings of approximately $440.0 per patient. Combined savings resulting from reduced wastage and hospital admissions was approximately $1,374 per patient. CONCLUSION: Dose-monitoring programs such as the CMP effectively reduce wastage and serious adverse effects associated with oral chemotherapeutic agents, realizing potential cost savings for both payers and patients.

Impact of clinical oral chemotherapy program on wastage and hospitalizations.

OBJECTIVE: The oral chemotherapy cycle management program (CMP) provides clinical management support to patients receiving certain oral chemotherapies. The CMP includes a dose-monitoring (ie, split-fill) plan for early identification and management of adverse effects. If serious adverse effects are identified mid cycle, the remainder of the monthly supply is withheld, thus avoiding potential waste associated with early therapy discontinuation. This study investigated medication wastage and estimated potential cost savings for patients who were enrolled in the CMP, as compared with those who were not enrolled in the program. STUDY DESIGN: Retrospective test-control study. PATIENTS AND METHODS: Patients whose oral chemotherapy was initiated between June 2008 and February 2010 and who were enrolled in the CMP were included as the test group. Patients whose oral chemotherapy was initiated between June 2007 and May 2008 and who were not part of the CMP were included as the control group. RESULTS: Medication wastage associated with early therapy discontinuation was found to be lower in the CMP group. Approximately 34% of patients in the CMP group could have avoided medication wastage if split-fill plans had been available, potentially realizing savings of approximately $934.20 per patient. Linear probability regression models showed that the CMP group had a 2.9% probability for reduction in hospital admissions (P <.05), resulting in additional savings of approximately $440.00 per patient. Combined savings resulting from reduced wastage and hospital admissions was approximately $1374 per patient. CONCLUSION: Dose-monitoring programs such as the CMP effectively reduce wastage and serious adverse effects associated with oral chemotherapeutic agents, realizing potential cost savings for both payers and patients.

Technology Update: An Overview of PDA-Based Software Applications for Practicing Pharmacists.

When it comes to the adoption of portable information technology devices called personal digital assistants and the selection of new application software to be used on the personal digital assistant, most healthcare professionals in general, including pharmacists, are in a dilemma as to which hardware and software applications are best suited for them. Having made a personal digital assistant device selection, an even more difficult task is deciding which of the hundreds of clinical applications should be installed on their personal digital assistant for everyday practice. This article provides an overview of the personal digital assistant-based clinical software applications that are most important and relevant for use by practicing pharmacists in any community setting.