Patient Experiences with Clostridioides difficile Infection and Its Treatment: A Systematic Literature Review.

INTRODUCTION: Clostridioides difficile infection (CDI) is a globally recognized cause of morbidity and mortality with devastating effects on health-related quality of life (HRQoL). The objective of this study was to conduct the first systematic literature review (SLR) to assess the humanistic burden of CDI on patient experiences, including HRQoL and related constructs, and attitudes towards treatment alternatives. METHODS: An SLR was conducted to identify peer-reviewed articles that assessed CDI, including recurrent CDI (rCDI), and patient-reported outcomes or HRQoL. PubMed, Embase, and the Cochrane Collaboration abstracting services were used to conduct literature searches from 2010 to 2021 in the English language. This SLR was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) criteria. RESULTS: Of 511 identified articles, 21 met study inclusion criteria. The SLR showed CDI has a devastating impact on patients' overall HRQoL that continues well beyond infection clearance. The impact of CDI on physical, emotional, social, and professional well-being rivaled abdominal symptoms of uncontrollable diarrhea, being worse for patients with rCDI. Patients with CDI feel isolated, depressed, lonely, and continue to be frightened of recurrences as well as being contagious to others. Most believe that they will never be free of CDI. CONCLUSION: CDI and rCDI are debilitating conditions affecting physical, psychological, social, and professional functioning of patients' HRQoL, even long after the event has occurred. The results of this SLR suggest that CDI is a devastating condition in need of better prevention strategies, improved psychological support, and treatments that address the microbiome disruption to break the cycle of recurrence. Additional safe and effective therapies are needed to address this unmet medical need.

Clostridioides difficile infection is a gut bacterial infection that can happen after a person has taken antibiotics to treat another infection. C. difficile infection can lead to other medical problems and death. This review of the literature aimed to understand how C. difficile infection (first, previous, and repeat occurrences), the severe diarrhea it causes, and available treatments (both old and new) for C. difficile infection can impact a person's quality of life, daily self-care activities, and attitudes toward treatment. Results from this review of 21 studies showed that C. difficile infection has a negative impact on the quality of life of patients, affecting their physical, mental, and social health. C. difficile infection also disrupted the professional lives of patients and their ability to perform work activities. This negative effect continued over time, long after the infection had cleared because patients feared it would come back again. Treating C. difficile infection improved quality of life. Findings suggest that C. difficile infection is a devastating condition that needs better prevention strategies, improved psychological support, and treatments that stop the cycle of repeated gut infections by restoring good gut flora.

A systematic review of real-world healthcare resource use and costs of Clostridioides difficile infections.

Objective: To conduct a systematic review of published real-world evidence describing the cost and healthcare resource use for Clostridiodes difficile infection (CDI) in the United States. Methods: A systematic literature review was conducted searching for terms for CDI and healthcare costs. Titles of articles and abstracts were reviewed to identify those that met study criteria. Studies were evaluated to examine overall design and comparison groups in terms of healthcare resource use and cost for CDI. Results: In total, 28 articles met the inclusion criteria. Moreover, 20 studies evaluated primary CDI or did not specify, and 8 studies1-8 evaluated both primary CDI and recurrent (rCDI). Data from Medicare were used in 6 studies. Nearly all studies used a comparison group, either controls without CDI (N = 20) or comparison between primary CDI and rCDI (N = 7). Two studies examined costs of rCDI by the number of recurrences. Overall, the burden of CDI is significant, with higher aggregate costs for patients with rCDI. Compared with non-CDI controls, hospital length of stay increased in patients with both primary and rCDI compared to patients without CDI. Patients with primary CDI cost healthcare systems $24,000 more than patients without CDI. Additionally, 2 studies that evaluated the impact of recurrence among those patients with an index case of CDI demonstrated significantly higher direct all-cause medical costs among those with rCDI compared to those without. Conclusion: CDI, and particularly rCDI, is a costly condition with hospitalizations being the main cost driver.

Cost-effectiveness of herpes zoster vaccines in the U.S.: A systematic review.

The purpose of this study was to conduct a systematic review to evaluate the cost-effectiveness evidence of herpes zoster vaccines in the U.S. A systematic literature review was undertaken for U.S. studies focused on the cost-effectiveness of herpes zoster vaccines. Eligibility criteria included studies that evaluated the cost-effectiveness of the recombinant zoster vaccine (RZV) and zoster vaccine live (ZVL) and were published between 2015 and 2021. Article titles and abstracts were reviewed to identify relevant publications. The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) criteria for economic evaluations were used to evaluate the studies. Eleven published studies met inclusion and exclusion criteria. Seven studies compared RZV and ZVL. Four studies compared ZVL dosing regimens with or without a no vaccine option. All studies incorporated health system costs. Ten out of eleven (90.9%) studies conducted their analyses from a societal perspective and included indirect costs. For measurements of effectiveness, ten of eleven (90.9%) studies estimated quality-adjusted life years, four (36.4%) used shingles cases averted, two (18.2%) employed deaths prevented, and one (9.1%) measured life years saved. All studies that compared RZV with no vaccine found RZV to be a cost-effective strategy to prevent both shingles and post-herpetic neuralgia. Additionally, these analyses showed that RZV consistently dominated ZVL. Compliance with the second RZV dose was important for full benefit of the vaccine. The studies identified in this systematic review identified well-constructed cost-effectiveness analyses of herpes zoster vaccines in the U.S. RZV was more cost-effective than no vaccine or ZVL. This systematic review supports removal of ZVL from the U.S. market.

Botulinum Toxin Type A Overdoses: Analysis of the FDA Adverse Event Reporting System Database.

INTRODUCTION: Published literature on overdoses related to botulinum toxin A (BtxA) agents is scarce. OBJECTIVE: The aim of this study was to assess the BtxA drug class' respective agents for associations with overdose. METHODS: United States Food and Drug Administration (FDA) adverse event reporting system (FAERS) database was utilized to search for overdoses. The analysis was conducted on data between second quarter 2014 and third quarter 2017. BtxA cases were included when they were considered the "Primary Suspect" drug. Overdose was defined as presence of 'overdose' being reported as an adverse event. Primary outcome was incidence of 'overdose' compared within the respective agents. Additionally, a disproportionality analysis was conducted utilizing reporting odds ratio (ROR) versus onabotulinumtoxinA as a referent while controlling for confounding variables. RESULTS: A total of 3,837,406 unique adverse events were reported during the study period for all drugs in the FAERS database. Of which, 13,078 were BtxA cases. The rate of adverse events involving overdose for abobotulinumtoxinA (20.2%; 215/1065) was significantly higher than both onabotulinumtoxinA (0.4%; 48/11,323; p < 0.0001) and incobotulinumtoxinA (0.1%; 1/690; p < 0.0001). In the regression analysis, abobotulinumtoxinA (ROR 73.26; 95% CI 51.17-104.90) had a significant association with overdose, whereas incobotulinumtoxinA (ROR 0.73; 95% CI 0.10-5.36) did not, versus the referent onabotulinumtoxinA. CONCLUSION: The present analysis showed adverse events of abobotulinumtoxinA were significantly associated with overdose versus the other two BtxA agents. Overdose can be difficult to research, particularly for in-clinic administered drugs. Future studies should venture to confirm these results in new and novel ways.

Evaluation of a guided continuous quality improvement program in community pharmacies.

BACKGROUND: The importance of creating and sustaining a strong culture of patient safety has been recognized as a critical component of safe medication use. This study aims to assess changes in attitudes toward patient safety culture and frequency of quality-related event (QRE) reporting after guided implementation of a continuous quality improvement (CQI) program in a panel of community pharmacies in the United States (U.S.). METHODS: Twenty-one community pharmacies volunteered to participate in the project and were randomly assigned to intervention or control groups. Pharmacy staff in the intervention group received guided training to ensure full implementation of a CQI program while those in the control group partially implemented the program. Pharmacy staff in both groups completed retrospective pre-post safety culture questionnaires and reported medication errors and near misses that occurred in their practices. Rasch analysis was applied to assess questionnaire validity and reliability and to confirm if the ordinal level data approximated interval level measures. Paired t-tests and repeated measure analysis of covariance tests were subsequently used to compare observed changes in the attitudes of subjects and frequency of QREs reporting in intervention and control groups. RESULTS: Sixty-nine employees completed the questionnaire, a 43.9% response rate. Improvement in attitudes toward patient safety was statistically significant in the intervention group in six domains: staff, training, and skill (p = 0.017); patient counseling (p = 0.043); communication about mistakes (p < 0.001); response to mistakes (p < 0.001); organizational learning - continuous improvement (p < 0.001); and overall patient safety perceptions (p = 0.033). No significant differences were observed in QRE reporting rates between intervention and control groups. However, differences were observed in the types of QREs reported (e.g., incorrect safety cap) and the point in the prescription processing workflow where a QRE was detected (e.g., partner check station, and drug utilization review station) in the intervention group (p < 0.001). CONCLUSION: Guided CQI program implementation increased the self-reported patient safety culture attitudes among staff.

The economic burden of spinal muscular atrophy.

AIM: To evaluate the economic burden of spinal muscular atrophy (SMA). MATERIALS AND METHODS: This study used Department of Defense Military Healthcare System (MHS) data from 2003-2012. Healthcare costs were determined for patients with at least one inpatient or three outpatient claims with a diagnosis of SMA before 18 years of age and who had ≥ 6 months of data after first SMA diagnosis or expired within 6 months of initial diagnosis. A comparator cohort was selected using a 3:1 match based on age and gender. RESULTS: A total of 239 individuals with SMA diagnosis met the inclusion criteria along with 717 matched comparator patients. More patients with SMA had hospitalizations (69.5%) compared to the comparator cohort (17.2%, p < 0.001). Median total expenditures across all years of data for patients with SMA were $83 652 (25-75th percentile = $29 620-228 754) vs the comparator group of $4329 (25-75(th) percentile = $1229-10 062 (p < 0.001)) over an average (SD) of 6.9 ± 3.6 years. The annualized mean costs of total healthcare expenditures were significantly higher for the SMA cases than the comparison cohort, $47 862 ± 88 607 compared to $1861 ± 6374, respectively (p < 0.001). The sub-group of patients with early diagnosis (n = 45) had 4.3 ± 2.9 years of observation with a median cost of $167 921 ($53 349-678 412). Mean age (SD) at first observed SMA diagnosis was 7.5 ± 6.4 years. Mean (SD) duration of follow-up after initial SMA diagnosis was 4.8 ± 3.3 years, with a median post-diagnosis cost of $60 213 ($18 229-192 559). The major costs for all patients were outpatient visits [median = $53 152 ($23 902-136 150)], followed by inpatient costs [median = $11 258 ($0-51 987)] and total prescription costs [median = $3167 ($943-13 283)]. LIMITATIONS: The analysis is limited to the data available and may under-estimate the total cost of SMA. CONCLUSIONS: Individuals with SMA have a high degree of morbidity, particularly those diagnosed during infancy. SMA patients have significant medical expenditures and high utilization of healthcare services.

Health Resource Utilization and Cost for Patients with Incontinent Overactive Bladder Treated with Anticholinergics.

BACKGROUND: Overactive bladder (OAB) is a common medical condition with significant economic and humanistic burden. Inadequately managed OAB may exacerbate or result in comorbidities such as depression, falls, and urinary tract infections, which can further increase the burden to the health care system. Anticholinergics are often prescribed for management of OAB with urinary incontinence ("wet" OAB). However, research has shown that patient adherence and persistence to anticholinergic therapy is poor, with approximately 80% of patients ultimately failing their first prescribed anticholinergic medication within the first year. While there has been a fair amount of research on the economic burden of OAB, the real-world impact of initiating anticholinergic therapy in patients with wet OAB has not been well studied. OBJECTIVE: To compare falls/fractures, anxiety/depression, health care resource utilization, and health care costs between a cohort of patients with wet OAB who initiated anticholinergic therapy and a matched cohort of patients without OAB. METHODS: This study was a retrospective medical and pharmacy claims analysis. Cases were members of a primary care-based, multispecialty physician medical group located in California. Cases were eligible for inclusion if they were prescribed anticholinergic therapy between January 2008 and May 2012 based on pharmacy claims, had a diagnosis of OAB, and reported having ≥ 1 urinary incontinence episode per day. Wet OAB cases were matched to non-OAB controls in a 1:3 ratio based on sex, age, and observation time. Medical and pharmacy claims data were used to analyze patient comorbidities, as well as track health care resource utilization (HRU) and direct payer costs. RESULTS: After initiating anticholinergic therapy, wet OAB patients had a 46% higher adjusted risk of experiencing falls/fractures (P < 0.001) and a 33% higher adjusted risk of experiencing depression/anxiety (P = 0.022) than non-OAB patients. Wet OAB was significantly associated with increased HRU rates of hospital admissions, outpatient visits, prescriptions filled, and diagnostic tests performed. After adjustment for covariates, total health care cost was 33% higher for wet OAB patients than non-OAB patients, resulting in an increased cost of $1,746 per member per year. CONCLUSIONS: The findings of this research suggest OAB patients who initiate anticholinergic therapy and still experience incontinence are at a greater risk for comorbidities such as falls/fractures and depression/anxiety, and use significantly more health care resources, than patients without OAB. Programs to improve patient monitoring and referrals, the appropriate use of alternative treatments within guidelines, and adherence to evidence-based practice parameters may improve clinical outcomes and decrease HRU for these patients. DISCLOSURES: This study was sponsored by Allergan, Irvine, California, which reviewed and approved the final manuscript. At the time of the study, Yehoshua had received a fellowship at the University of Arizona, which was funded by Allergan. Yehoshua, Joshi, and Campbell are employees of Allergan. Vasaveda has received consulting fees from Allergan, Medtronic, and Boston Scientific. Chancelor has received consulting fees from Allergan and Medtronic. All authors met the ICMJE authorship criteria. Neither honoraria nor payments were made for authorship. Study design was created by Yehoshua, Pulicharam, Malone, and Armstrong. Pulicharam took the lead in data collection, along with Chancellor and Campbell, and data interpretation was performed by Chancellor, Vasavada, Malone, and Armstrong. The manuscript was written by Yehoshua and revised by Joshi and Yehoshua, with assistance from the other authors.

The impact of lower urinary tract symptoms on health-related quality of life among patients with multiple sclerosis.

AIMS: Lower urinary tract symptoms are commonly experienced among patients with multiple sclerosis (MS), however, their impact on health-related quality of life (HRQOL) has not been well characterized. Herein the incremental impact of lower urinary tract symptoms on HRQOL among patients with MS has been evaluated. METHODS: A cross-sectional online survey was administered to US residents with a self-reported MS diagnosis. Data pertaining to demographics, disease history, urinary symptoms, and HRQOL, including the Short Form 36, version 2 (SF-36v2), were collected. Patients were stratified into four urinary symptom groups: no/minimal urinary symptoms, urinary urgency (UU), urinary urgency incontinence (UUI), and other lower urinary tract symptoms. Multiple linear regression models evaluated the impact of these symptoms. RESULTS: Out of the 1,052 respondents, mean age was 47.8 ± 10.6 years; mean time since MS diagnosis was 8.5 ± 7.8 years. UUI and UU subgroups showed the greatest adjusted HRQOL decrement compared with the no/minimal urinary symptoms group, scoring 2.8 (SE ± 0.7, UUI) and 3.5 (SE ± 0.8, UU) points lower on SF-36v2 Physical Component Summary, respectively, and 3.7 (SE ± 1.0, UUI) and 5.0 (SE ± 1.2, UU) points lower on SF-36v2 Mental Component Summary (P < 0.001 for all), respectively. CONCLUSIONS: Both UU and UUI symptoms contribute to a decrement in HRQOL among patients with MS.

Prevalence and Incidence of Epilepsy in an Elderly and Low-Income Population in the United States.

BACKGROUND AND PURPOSE: The purpose of this study was to estimate the incidence and prevalence of epilepsy among an elderly and poor population in the United States. METHODS: Arizona Medicaid claims data from January 1, 2008 to December 31, 2010 were used for this analysis. Subjects who were aged ≥65 years and were continuously enrolled in any Arizona Medicaid health plans (eligible to patients with low income) for ≥12 months between January 1, 2008 and December 31, 2009 were considered eligible for inclusion in the study cohort. In addition to meeting the aforementioned criteria, incident and prevalent cases must have had epilepsy-related healthcare claims. Furthermore, incident cases were required to have a 1-year "clean" period immediately preceding the index date. Negative binomial and logistic regression models were used to assess the factors associated with epilepsy incidence and prevalence. RESULTS: The estimated epilepsy incidence and prevalence for this population in 2009 were 7.9 and 19.3 per 1,000 person-years, respectively. The incidence and prevalence rates were significantly higher for patients with comorbid conditions that were potential risk factors for epilepsy and were of younger age than for their non-comorbid and older counterparts (p<0.05). The prevalence rates were significantly higher for non-Hispanic Blacks and male beneficiaries than for non-Hispanic Whites and female beneficiaries, respectively (p<0.05). CONCLUSIONS: This patient population had higher epilepsy incidence and prevalence compared with the general US population. These differences may be at least in part attributable to their low socioeconomic status.

Cost-effectiveness of comprehensive medication reviews versus noncomprehensive medication review interventions and subsequent successful medication changes in a Medicare Part D population.

BACKGROUND: An estimated 1.5 million preventable medication-related adverse events occur annually, with some resulting in serious injury and even death. To help address this issue, the Centers for Medicare Medicaid Services (CMS) now require medication therapy management (MTM) programs to offer comprehensive medication reviews (CMRs) to all Medicare Part D beneficiaries at least once a year. During a CMR, patients receive an extensive amount of medication and educational information. In contrast, noncomprehensive medication reviews (non-CMRs) are more targeted and focus on resolving a particular medication-related problem (MRP) via short patient consultations, patient letters, and direct provider interventions.   OBJECTIVE: To conduct a cost-effectiveness analysis comparing CMRs with non-CMR interventions on successful medication regimen changes and reductions in adverse drug events (ADEs). METHODS: This decision analytic model compared the cost-effectiveness of CMRs with other intervention methods (non-CMRs) from a payer's perspective. For this model, a successful outcome was defined as a beneficiary case devoid of an ADE due to MRPs. The model was extensively tested and subjected to a thorough one-way sensitivity analysis and a second-order probabilistic sensitivity analysis with 10,000 iterations from the variable distributions.  RESULTS: Non-CMR interventions were less costly and more effective than CMRs. The point estimate for direct medical costs was $193 for CMRs and $157 for non-CMRs, and the estimated probability of avoiding an ADE was 0.93 and 0.94 for CMRs and non-CMRs, respectively. The 10,000 iteration-Monte Carlo simulation scatterplot and cost-effectiveness acceptability curve (CEAC) revealed a dominance by non-CMRs in preventing harmful ADEs from cost and effectiveness perspectives; however, there was an overlap in the 95% CIs for both cost and ADEs prevented. Despite this, a non-CMR intervention saved estimated $5,377.08 per ADE prevented. One-way sensitivity analysis indicated the results were sensitive to the cost of treating a preventable ADE. In 100% of cases, the CEAC demonstrated that non-CMRs were likely the most cost-effective intervention regardless of the health plan's willingness to pay.  CONCLUSIONS: The cost-effectiveness acceptability curve suggests that non-CMR interventions were less costly and more effective than CMRs; however, there was overlap in the 95% CIs for costs and ADEs prevented. In all cases, the CEAC demonstrated that non-CMRs were the most economical intervention with regard to time and cost. Non-CMRs show promise as a viable method to address MRPs, reduce ADEs, and improve patient-related health outcomes.

Lower urinary tract symptom prevalence and management among patients with multiple sclerosis.

BACKGROUND: This study was conducted to assess self-reported prevalence and management of lower urinary tract symptoms (LUTS), along with drivers of treatment seeking, among patients with multiple sclerosis (MS). METHODS: An online, cross-sectional survey was administered to US-residing participants with self-reported MS to assess presence of LUTS, including urinary incontinence (UI). Participants experiencing LUTS were asked additional questions related to management and current therapies. Multivariate logistic regression identified drivers of treatment-seeking behavior. RESULTS: A total of 1052 participants completed the survey; 1047 were included in the analysis. Nine hundred sixty-six participants (92%) reported at least one LUTS, the most common being post-micturition dribble (64.9%), urinary urgency (61.7%), and a feeling of incomplete emptying (60.7%). Eight hundred twenty-six (79%) reported having some type of UI. Of those with any type of LUTS, 70% (n = 680) had previously discussed urinary symptoms with a health-care provider (HCP), while only 32% (n = 311) had seen an HCP in the past year. Logistic regression found urgency (odds ratio [OR] 1.20 [95% confidence interval (CI), 1.00-1.44]), intermittent urine stream (OR 1.40 [95% CI, 1.15-1.69]), and urgency UI (OR 1.78 [95% CI, 1.22-2.60]) to be significant predictors of seeking treatment. Of those who had discussed LUTS with an HCP, 480 (70.6%) were currently receiving at least one LUTS treatment; the most common treatments were reducing fluid intake, pelvic exercises, oral anticholinergic medications, and avoiding certain foods/alcohol. CONCLUSIONS: LUTS are commonly experienced among people with MS but are largely untreated. Proper LUTS assessment and work-up is warranted in MS patients.

Adherence to clotting factors among persons with hemophilia A or B.

OBJECTIVE: Evaluate adherence to clotting factor treatment and associated outcomes for patients with hemophilia using an integrated delivery database. METHODS: This was a retrospective, observational study tracking patients between 2006 and 2011. Patients with diagnosis codes for hemophilia were identified. Bleeding and complication rates were annualized over the study period. Medication adherence was assessed using prescription claims for clotting factors by examining sequential time periods of 180 days for each patient's continuous enrollment. Adherence within the time period was calculated using the 'days supply' field divided by 180 days. Under the assumption that severe patients should be treated prophylactically, patients were considered adherent within the time period if the ratio of 'days supply' to observed days was 60% or greater. RESULTS: A total of 207 patients (74.9 and 25.1% hemophilia A and B, respectively) met the inclusion/exclusion criteria. There were 101 (48.8%) mild, 32 (15.5%) moderate, and 74 (35.7%) severe patients with hemophilia. The percentage of time periods where adherence to clotting factors was 60% or greater was 14% (SD = 28%) for mild disease, 21% (SD = 32%) for moderate disease, and 51% (SD = 36%) for severe disease. Among patients with severe disease, 27 (36.5%) were adherent ≤ 30% of time periods, 22 (29.7%) adherent 31-70% of the time periods, and 25 (33.8%) were adherent ≥ 71% of time periods. Joint bleeding episodes and hospitalizations were uncommon events among the three groups. CONCLUSIONS: Among patients with severe disease, the majority (66.2%) were adherent <70% of the time.

Health outcomes and cost-effectiveness of certolizumab pegol in the treatment of Crohn's disease.

Crohn's disease (CD) causes chronic inflammation of the gastrointestinal tract and leads to fluctuations between active disease and remission. Certolizumab pegol is one of the newer biological treatments for patients with moderate-to-severe CD. Certolizumab pegol was shown to be effective in CD patients achieving response and remission in both randomized and non-randomized studies, and is an alternative biological treatment for CD. The available data show that certolizumab pegol achieves similar therapeutic efficacy and health-related quality of life scores in CD patients as the other biological agents, but at a higher cost, if dose escalation of other biologics is not considered. Considering subcutaneous self-administration, and lower number and frequency of injections, patients may prefer certolizumab pegol over the other biological treatments.

Costs and utilization of hemophilia A and B patients with and without inhibitors.

OBJECTIVE: To evaluate the health system costs among patients with hemophilia A and B with and without inhibitors over 5 years. METHODS: This was a retrospective, observational study utilizing medical and pharmacy electronic medical records and administrative encounters/claims data tracking US patients between 2006-2011. Patients with diagnosis codes for hemophilia A and B were identified. Patients with inhibitors were characterized by utilization of bypassing agents activated prothrombin complex concentrate or factor VIIa on two or more distinct dates. Severity was classified as mild, moderate, or severe based on laboratory tests of clotting factor. RESULTS: There were 160 hemophilia A patients and 54 hemophilia B patients identified. From this group, seven were designated as patients with inhibitors (five with hemophilia A and two with hemophilia B). Hemophilia A patients without inhibitors reported 65 (41.9%) as being severe, 19 (12.3%) as moderate, and 71 (45.8%) as mild. Hemophilia B patients without inhibitors reported nine (17.3%) had severe, 13 (25.0%) had moderate, and 30 (57.7%) had mild hemophilia. All patients with inhibitors had been hospitalized in the previous 5 years compared to 64 (41.3%) with hemophilia A without inhibitors and 22 (42.3%) with hemophilia B without inhibitors. The median aggregate cost per year (including factor and health resource use) was $325,780 for patients with inhibitors compared to $98,334 for hemophilia A patients without inhibitors and $23,265 for hemophilia B patients without inhibitors. CONCLUSIONS: The results suggest that, while the frequency of inhibitors within the hemophilia cohort was low, there was a higher frequency of hospitalizations, and the associated median aggregate costs per year were 3-fold higher than those patients without inhibitors. In contrast, hemophilia B patients experience less severe disease and account for lower aggregate yearly costs compared to either patients with hemophilia A or patients with inhibitors.

Prescriber perceptions of a near real-time fax alert program for potential drug-drug interactions.

BACKGROUND: Health systems have developed interventions to reduce harm associated with drug-drug interactions. Pharmacy benefit managers are in an important position to identify the coprescribing of medications known to interact, since they process data on a large portion of prescription claims in the United States. Electronic health records and electronic prescribing also include alerts through their systems' clinical decision support. However, limited data are available that assess prescribers' perceptions of processes that screen for potential drug-drug interactions (PDDIs). OBJECTIVE: To determine prescribers' perceptions of near real-time fax alerts for PDDIs. METHODS: This was a 6-month prospective study where a pharmacy benefit manager distributed evidence-based summaries of 18 different PDDIs that included references and suggested management strategies. Fax alerts were individualized letters sent to the prescriber of the second drug of a PDDI pair for an individual patient. A 16-item questionnaire to assess prescribers' perceptions of the intervention accompanied each individualized PDDI evidence-based summary. RESULTS: A total of 8,075 fax alerts were distributed with 977 returning questionnaires, yielding a 12.1% response rate. There were 848 (86.8%) responses completed by physicians, and 71 (7.3%) completed by nurse practitioners. The most common PDDI fax alerts sent were for warfarin-statin (3,511, 43.5%) and warfarin-thyroid (2,111, 26.1%) interactions. 42.6% of respondents agreed or strongly agreed that fax alerts were a good way to communicate with them. However, 37.5% of respondents either agreed or strongly agreed that the fax alert was a "waste of my time." In contrast, respondents thought notification of carbamazepine-macrolide (mean 1.5 ± 0.71), ciprofloxacin-tizanidine (mean 2.3 ± 1.0), and statin-macrolide (mean 2.3 ± 1.1) was not a waste of time. Also, 59.1% of respondents either disagreed or strongly disagreed that they would prefer to receive a telephone call when interactions like this occur. Half (50.5%) of the respondents indicated their computer systems provided drug interaction alerts. Prescribers who had previously received alerts and specialists were less likely to respond to the questionnaire (OR = 0.685, P ≤ 0.0001 and OR = 0.851, P = 0.0205, respectively). CONCLUSIONS: The positive response to fax alerts by physicians varies by the component drugs of the PDDI alerts.

Cost-effectiveness of biological agents used in ulcerative colitis.

Ulcerative colitis (UC) produces bloody diarrhoea, severe abdominal pain, and need for clinic visits, hospitalizations, and surgeries. UC results in reduced health-related quality of life for patients and large direct medical and indirect costs for health systems and employers. Patients with the most severe disease require the most medical services, and these patients have larger costs than patients with mild or moderate disease. Despite biological therapies being quite expensive, they are indicated for patients unresponsive to initial standard therapies. Future hospitalizations may be reduced by starting a biological treatment. Cost-effectiveness results vary between countries, health systems, and model designs. Since restorative proctocolectomy can be curative, this surgery dominates biological therapy by being both less costly and more effective when measuring health system costs and patient quality-adjusted life years for 20 years. However the dose, duration, and effectiveness of biological treatments significantly impact estimates of their cost-effectiveness.

Is scorpion antivenom cost-effective as marketed in the United States?

PURPOSE: The purpose of this study was to analyze the cost-effectiveness of scorpion antivenom compared to no antivenom, in the United States, using a decision analysis framework. METHODS: A decision analytic model was created to assess patient course with and without antivenom. Costs were determined from the perspective of a health care payer. Cost data used in the model were extracted from Arizona Medicaid. The probability of clinical events occurring with and without antivenom was obtained from the published literature, medical claims obtained from Arizona Medicaid, and results of recent clinical trials. Patients that became so ill that mechanical ventilator support was necessary were considered treatment failures. A Monte Carlo simulation was run 1000 times and sampled simultaneously across all variable distributions in the model. RESULTS: The mean success rate was 99.87% (95% CI 99.64%-99.98%) with scorpion antivenom and 94.31% (95% CI 91.10%-96.61%) without scorpion antivenom. The mean cost using scorpion antivenom was $10,708 (95% CI $10,556 - $11,010) and the mean cost without scorpion antivenom was $3178 (95% CI $1627 - $5184). Since the 95% CIs do not overlap for either the success or cost, use of the scorpion antivenom was significantly more effective and significantly more expensive than no antivenom. Cost-effectiveness analysis found that the scorpion antivenom was not cost-effective at its current price as marketed in the United States. CONCLUSION: The scorpion antivenom marketed in the United States is extremely effective, but too costly to justify its use in most clinical situations. Formulary committees should restrict the use of this antivenom to only the most severe scorpion envenomations.

A systematic review of economic studies on biological agents used to treat Crohn's disease.

BACKGROUND: Identifying clinical scenarios that maximize the cost-effectiveness of biological treatments can lead to optimized health care cost-saving and clinical effectiveness from a society's perspective. METHODS: Published articles between January 1995 and June 2012 were searched in PubMed, EMBASE, ABI/INFORM, Tuft's Cost-Effectiveness Analysis Registry Database, Cochrane National Health Service Economic Evaluation Database, International Pharmaceutical Abstracts, Web of Science, and Google Scholar. Studies of interest included the following: (1) cost studies, (2) economic evaluations, or (3) narrative or systematic reviews related to economic evaluations of biological treatments for moderate-to-severe Crohn's disease (CD). The primary outcomes of interest included costs associated with biological treatments and cost-effectiveness measures, including incremental cost-effectiveness ratios. A threshold of $100,000/quality-adjusted life year (£60,000/quality-adjusted life year) gained was used for treatment cost-effectiveness. RESULTS: Thirty-eight studies were identified, including 15 economic evaluations and 23 cost studies or reviews of economic evaluations. Economic evaluations found that infliximab and adalimumab were more cost-effective than standard therapy for luminal CD when provided as an induction therapy followed by episodic therapy over 5 or more years. The cost-effectiveness of infliximab and adalimumab versus standard therapy for luminal CD was less certain when used as 1-year maintenance treatment with or without previous induction therapy. Cost studies revealed that infliximab therapy reduced health care resource utilization and cost. Older reviews were inconclusive about the cost-effectiveness of biological treatments used for CD. CONCLUSIONS: Current evidence suggests that biological treatments may be cost-effective for CD under certain clinical scenarios. Future studies evaluating all biological treatments are needed to compare their respective benefits and costs.