Effect of etranacogene dezaparvovec on quality of life for severe and moderately severe haemophilia B participants: Results from the phase III HOPE-B trial 2 years after gene therapy.

INTRODUCTION: For people with haemophilia B (PwHB), bleeding may occur despite prophylaxis, negatively affecting health-related quality of life (HRQoL). The pivotal phase 3 HOPE-B trial investigating the adeno-associated virus gene transfer product, etranacogene dezaparvovec (EDZ), demonstrated sustained factor IX (FIX) activity and bleed protection in PwHB with baseline FIX levels ≤2%. AIM: Assess how EDZ affects HRQoL in HOPE-B trial participants. METHODS: HRQoL was evaluated using generic and disease-specific patient reported outcomes (PROs) including the EQ-5D-5L and the Hem-A-QoL questionnaires. Mean domain and total scores were compared 6 months pre- and the first 2 years post-EDZ administration using repeated measures linear mixed models. The percentage of participants with minimal clinically important improvements in HRQoL was also evaluated. RESULTS: Two years post-EDZ, there were nominally significant increases in the least squares (LS) mean score for the EQ-5D-5L Index Value (.04; p = .0129), reflecting better HRQoL. Nominally significant decreases in the LS mean scores, reflecting better HRQoL, were also found for the Hem-A-QoL total score (-6.0; p < .0001) and the Treatment (-13.94; p < .0001), Feelings (-9.01; p < .0001), Future (-6.45; p = .0004) and Work/School (-5.21; p = .0098) domains. The percentage of participants with ≥15-point improvement ranged from 45.83% (95% CI: 31.37%, 60.83%) for Treatment to 13.89% (95% CI: 4.67%, 29.50%) for Family Planning. Results were similar for Year 1. CONCLUSION: In conclusion, gene therapy with EDZ improved HRQoL in the first and second years in several Hem-A-QoL domains, including Treatment, Feelings, Work/School and Future domains, whereas improvement in other aspects of HRQoL were not demonstrated.

Incidence, risk factors, and long-term outcomes associated with antibody-mediated rejection - The long-term Deterioration of Kidney Allograft Function (DeKAF) prospective cohort study.

Major gaps remain in our understanding of antibody-mediated rejection (AMR) after kidney transplant. We examined the incidence, risk factors, response to treatment, and effects on outcomes of AMR at seven transplant programs in the long-term Deterioration of Kidney Allograft Function prospective study cohort. Among 3131 kidney recipients, there were 194 observed AMR cases (6.2%) during (mean ± SD) 4.85 ± 1.86 years of follow-up. Time to AMR was 0.97 ± 1.17 (median, 0.48) years. Risk factors for AMR included younger recipient age, human leukocyte antigen DR mismatches, panel-reactive antibody >0%, positive T- or B-cell cross-match, and delayed graft function. Compared with no AMR, the adjusted time-dependent hazard ratio for death-censored graft failure is 10.1 (95% confidence interval, 6.5-15.7) for all AMR patients, 4.0 (2.5, 9.1) for early AMR (<90 days after transplant), and 24.0 (14.0-41.1) for late AMR (≥90 days after transplant). Patients were treated with different therapeutic combinations. Of 194 kidney transplant recipients with AMR, 50 (25.8%) did not respond to treatment, defined as second AMR within 100 days or no improvement in estimated glomerular filtration rate by 42 days. Long-term outcomes after AMR are poor, regardless of the initial response to treatment. Better prevention and new therapeutic strategies are needed to improve long-term allograft survival.

Healthcare utilization and cost of cancer-related care prior to allogeneic hematopoietic cell transplantation for hematologic malignancies in the US: a retrospective real-world analysis.

BACKGROUND: Hematopoietic cell transplantation (HCT) is a potentially curative therapy as well as a costly procedure. Published studies have examined the cost of HCT in the US and the complications that follow but little is known about the cancer-related healthcare costs and resource utilization prior to the procedure and none of the studies have examined the variability in cost based on the type of hematologic malignancy involved. The aim of this study was to estimate mean cancer-related costs and resources incurred before the HCT is performed from the time the hematologic malignancy first develops. METHODS: The IBM® MarketScan® Research Databases were used to identify adult patients ≥18 years of age with commercial or Medicare supplemental insurance who had undergone allogeneic HCT for hematologic malignancies from January 1, 2008 to December 31, 2017. Healthcare utilization and costs were assessed during the 6 months prior to diagnosis (pre-diagnostic period) and the follow-up period from diagnosis just prior to the HCT (pre-HCT period). Multivariable regression models were constructed to estimate total all-cause costs and cancer-related costs as well as healthcare utilization by type in each time period. RESULTS: A total of 2663 commercially insured patients and 266 with Medicare supplemental insurance were included in the study population. The mean-adjusted incremental cancer-related costs for commercially insured patients was $399,011 in the overall observation period including the pre-diagnostic and pre-HCT periods combined, 9% of which was incurred in the pre-diagnostic period. The corresponding mean-adjusted incremental cancer-related costs for Medicare supplemental patients was $195,575 for the same time period but the patterns of healthcare utilization were similar to the commercially insured population. Inpatient care accounted for approximately one-half the cost in both patient populations. By type of hematologic malignancy, costs were lowest for myeloproliferative disorders ($211,561) and highest for acute lymphocytic leukemia ($462,072) in the commercially insured population. CONCLUSION: This study demonstrates that overall patients with hematologic malignancies requiring HCT have considerable cancer-related healthcare resource utilization and costs leading up to HCT compared to the period of time prior to developing cancer.

An international survey assessing the effects of the duration of attack-free period on health-related quality of life for patients with hereditary angioedema.

BACKGROUND: Hereditary angioedema (HAE) is characterized by unpredictable and often severe cutaneous and mucosal swelling that affects the extremities, face, larynx, gastrointestinal tract, or genitourinary area. Introduction of novel long-term prophylactic treatment options (lanadelumab, berotralstat, and C1-esterase inhibitor SC [human]) into the treatment armamentarium has substantially reduced HAE attacks, allowing patients to be attack free for longer with improvements to their quality of life. Using data drawn from a wide-ranging survey of patients with HAE, we examined the relationship between duration of time attack free and health-related quality of life (HRQoL), exploring the possibility that there is an association between observed improvement in HRQoL and attack-free duration. METHODS: A survey among patients with HAE on long-term prophylaxis (LTP) in six countries (the US, Australia, Canada, UK, Germany, and Japan) assessed the relationship between attack-free duration and mean Angioedema Quality of Life (AE-QoL) scores, quality of life benefits, and rescue medication used. Analysis of covariance (ANCOVA) was used to assess the roles of LTP and attack-free period (< 1 month, 1- < 6 months, ≥ 6 months) on total AE-QoL scores. Results include descriptive p-values for strength of association, without control for multiplicity. Descriptive statistics were used to show the relationship between time attack free and quality of life benefits. RESULTS: Longer durations of time for which participants reported being attack free at the time of the survey correlated with better AE-QoL scores and less use of rescue medication. The mean total AE-QoL scores were 51.8, 33.2, and 19.9 for those who reported having been attack free for < 1 month, 1- < 6 months, and ≥ 6 months, respectively, with higher scores reflecting more impairment. The ANCOVA results showed a strong association between attack-free duration and AE-QoL total score. CONCLUSION: This study shows that longer attack-free duration has an influential role for better HRQoL in patients receiving LTP. Prolonging the attack-free period is an important goal of therapy and recent advances in LTP have increased attack-free duration. However, opportunities exist for new treatments to further increase attack-free duration and improve HRQoL for all patients with HAE.

Burden of rotavirus hospitalisations in young children in three paediatric hospitals in the United States determined by active surveillance compared to standard indirect methods.

AIM: The number of rotavirus hospitalisations is usually estimated from assigned diagnosis codes for gastroenteritis despite lack of validation for these indirect methods. Reliable estimates before and after introduction of vaccines are needed to quantify the absolute impact of new immunisation programs. METHODS: This 2-year study conducted at three hospitals prior to the licensure of the rotavirus vaccines in the USA compared two indirect methods for estimating hospitalisations for rotavirus gastroenteritis with estimates derived from prospective recruitment of children presenting with diarrhoea, vomiting or fever. For active surveillance, rotavirus gastroenteritis was confirmed by demonstration of stool antigen. The indirect residual and proportional methods assumed rotavirus to have caused a proportion of hospitalisations coded as acute gastroenteritis identified from computerised records. RESULTS: There were 447 rotavirus hospitalisations among inpatients 31 days through 4 years of age admitted with vomiting and/or diarrhoea, compared with 306 and 228 hospitalisations identified by the two indirect methods. Only 52% of children hospitalised with gastroenteritis received a qualifying diagnosis code at discharge. Relative to active surveillance, the sensitivity and specificity (95% confidence interval (CI)) in identifying rotavirus-attributable hospitalisations was 45% (95% CI: 43-48%) and 89% (88-90%) for the residual method and 34% (30-39%) and 92% (90-94%) for the proportional method. CONCLUSIONS: Many children admitted to the hospital with diarrhoea, vomiting or fever were not assigned discharge codes for acute gastroenteritis. Consequently, standard indirect methods missed a substantial number of rotavirus-associated hospitalisations, thereby underestimating the absolute number of children who could potentially benefit from vaccination.

The symptom experience of hereditary angioedema (HAE) patients beyond HAE attacks: literature review and clinician interviews.

BACKGROUND: Hereditary angioedema (HAE) is a genetic disorder characterized by re-occurring swelling episodes called "attacks," usually in the limbs, face, airways, and intestinal tract. New prophylactic therapies have reduced the frequency of these attacks. This study describes results from a literature review and clinician interviews assessing patient HAE symptom experiences and timing, and then evaluates whether existing patient-reported outcome (PRO) tools adequately reflect this experience. METHODS: A targeted literature review as well as interviews with key opinion leaders (KOLs), were conducted to capture information about the patient experience and their symptoms. An assessment of various PROs was then conducted to determine how well they each covered HAE symptoms and impacts. RESULTS: Nineteen HAE symptoms were identified. KOLs reported that patients on prophylactic therapy experienced some symptoms indicating an attack was imminent, but then never experienced an attack. The comparison of the different PROs found that the Hereditary Angioedema Patient-Reported Outcome was the instrument that most thoroughly examined the symptoms of patients with HAE. CONCLUSIONS: Given the introduction of new prophylactic therapies, further research is needed to determine the effect of being attack-free for longer periods of time on health-related quality of life.

Interpreting indirect treatment comparisons and network meta-analysis for health-care decision making: report of the ISPOR Task Force on Indirect Treatment Comparisons Good Research Practices: part 1.

Evidence-based health-care decision making requires comparisons of all relevant competing interventions. In the absence of randomized, controlled trials involving a direct comparison of all treatments of interest, indirect treatment comparisons and network meta-analysis provide useful evidence for judiciously selecting the best choice(s) of treatment. Mixed treatment comparisons, a special case of network meta-analysis, combine direct and indirect evidence for particular pairwise comparisons, thereby synthesizing a greater share of the available evidence than a traditional meta-analysis. This report from the ISPOR Indirect Treatment Comparisons Good Research Practices Task Force provides guidance on the interpretation of indirect treatment comparisons and network meta-analysis to assist policymakers and health-care professionals in using its findings for decision making. We start with an overview of how networks of randomized, controlled trials allow multiple treatment comparisons of competing interventions. Next, an introduction to the synthesis of the available evidence with a focus on terminology, assumptions, validity, and statistical methods is provided, followed by advice on critically reviewing and interpreting an indirect treatment comparison or network meta-analysis to inform decision making. We finish with a discussion of what to do if there are no direct or indirect treatment comparisons of randomized, controlled trials possible and a health-care decision still needs to be made.

Conducting indirect-treatment-comparison and network-meta-analysis studies: report of the ISPOR Task Force on Indirect Treatment Comparisons Good Research Practices: part 2.

Evidence-based health care decision making requires comparison of all relevant competing interventions. In the absence of randomized controlled trials involving a direct comparison of all treatments of interest, indirect treatment comparisons and network meta-analysis provide useful evidence for judiciously selecting the best treatment(s). Mixed treatment comparisons, a special case of network meta-analysis, combine direct evidence and indirect evidence for particular pairwise comparisons, thereby synthesizing a greater share of the available evidence than traditional meta-analysis. This report from the International Society for Pharmacoeconomics and Outcomes Research Indirect Treatment Comparisons Good Research Practices Task Force provides guidance on technical aspects of conducting network meta-analyses (our use of this term includes most methods that involve meta-analysis in the context of a network of evidence). We start with a discussion of strategies for developing networks of evidence. Next we briefly review assumptions of network meta-analysis. Then we focus on the statistical analysis of the data: objectives, models (fixed-effects and random-effects), frequentist versus Bayesian approaches, and model validation. A checklist highlights key components of network meta-analysis, and substantial examples illustrate indirect treatment comparisons (both frequentist and Bayesian approaches) and network meta-analysis. A further section discusses eight key areas for future research.

Efficacy of the pentavalent rotavirus vaccine, RotaTeq® (RV5), between doses of a 3-dose series and with less than 3 doses (incomplete regimen).

Post-hoc analyses of the Rotavirus Efficacy and Safety Trial (REST) were conducted to determine whether the pentavalent rotavirus vaccine (RV5) confers early protection against rotavirus gastroenteritis (RVGE) before completion of the 3-dose regimen. To evaluate the efficacy of RV5 between doses in reducing the rates of RVGE-related hospitalizations and emergency department (ED) visits in infants who ultimately received all 3 doses of RV5/placebo, events occurring from 2 weeks after the first and second doses to receipt of the subsequent dose (Analysis A) and events occurring from 2 weeks after the first and second doses to 2 weeks after the subsequent dose (Analysis B) were analyzed. In Analysis A, RV5 reduced the rates of combined hospitalizations and ED visits for G1-G4 RVGE or RVGE regardless of serotype between doses 1 and 2 by 100% (95% confidence interval [CI]: 72-100%) or 82% (95% CI: 39-97%), respectively, and between doses 2 and 3, RV5 reduced the rates of combined hospitalizations and ED visits for G1-G4 RVGE or RVGE regardless of serotype by 91% (95% CI: 63-99%) or 84% (95% CI: 54-96%), respectively. Similar rate reductions were observed in Analysis B. These data suggest that RV5 provides a high level of protection between doses against hospitalizations and ED visits for RVGE starting as early as 14 days after the first dose.

Cost, healthcare utilization, and outcomes of antibody-mediated rejection in kidney transplant recipients in the US.

BACKGROUND: Antibody-mediated rejection (AMR) is one of the leading causes of graft loss in kidney transplant recipients but little is known about the associated cost and healthcare burden of AMR. METHODS: We developed an algorithm to detect AMR using the 2006-2011 Centers for Medicare & Medicaid Services (CMS) using ICD-10 and billing codes as there is no specific ICD-10 or procedure code for AMR. We then compared healthcare utilization, cost, and risk of graft failure or death in AMR. patients versus matched controls. RESULTS: The algorithm had a 39.4% true-positive rate (69/175) and a 4.1% false-positive rate (110/2,655). We identified 5,679/101,554 (5.6%) with AMR, who had a nearly 3-fold higher risk of graft failure (hazard ratio [HR], 2.75, 95% confidence interval [CI], 2.50 to 3.03; p < .0001) and death (HR, 2.59; 95% CI, 2.35 to 2.86; p < .0001) at 2 years, nearly 5 times the hospitalizations in the 60 d before AMR diagnosis, and increased nephrology and emergency department visits. Mean AMR attributable healthcare costs were 4 times higher than matched controls, at $13,066 more per patient in the 60 d before AMR diagnosis and $35,740 per patient per year higher in the 2 years after AMR diagnosis. CONCLUSIONS: US kidney transplant recipients with AMR have substantially greater healthcare utilization and higher costs and risk of graft loss and mortality.

Severity of Acute Graft-versus-Host Disease and Associated Healthcare Resource Utilization, Cost, and Outcomes.

Acute graft-versus-host disease (aGVHD) contributes to poor outcomes and increased healthcare resource utilization (HRU) after allogeneic hematopoietic stem cell transplantation (HCT). However, HRU and the economic burden of aGVHD based on severity of the disease is not well characterized. Our study cohort comprised 290 adults who underwent allogeneic HCT between 2010 and 2018. Costs, HRU, and all-cause mortality in the 100-day and 365-day periods after HCT were compared between patients with aGVHD and those without aGVHD. The impact of aGVHD severity and gastrointestinal (GI) involvement on mortality, HRU, and economic burden was also evaluated. Medical costs and total hospital length of stay (LOS) were retrieved from administrative data that allocate costs to services based on departmental input for resource use and were adjusted to 2018 dollars. The Wilcoxon rank-sum test was used to compare the number of inpatient days and total costs. Multivariable linear regression was fitted on log-transformed costs. Compared with patients without aGVHD, those with aGVHD had a significantly greater median hospital LOS (28 days versus 22 days) and higher rates of intensive care unit (ICU) admission (13% versus 6%) and rehospitalization (59% versus 38%) during the first 100 days post-HCT. The presence of grade I-II aGVHD significantly prolonged the hospital LOS by a median of 3 days and increased the readmission rate by 18%, whereas grade III-IV aGVHD was associated with a nearly 30% increase in the readmission rate and a doubling of inpatient LOS, ICU admission rate, and mortality in the first 100 days post-HCT. Compared with the absence of aGVHD, lower GI involvement in aGVHD was also associated with increased risk of readmission (30%) and twice as many inpatient days, doubling the likelihood of ICU admission and mortality over the first 100 days. Similar findings were observed over days 101 to 365 post-HCT. The mean cost attributable to aGVHD regardless of grade was $60,923 in the first 100 days post-HCT. This cost varied by grade. The mean aGVHD- attributable costs were $18,071 for grade I, $36,115 for grade II and $120,929 for grade III/IV aGVHD and $114,668 for aGVHD involving the lower GI tract. In the 101- to 365-day period, the mean attributable aGVHD cost regardless of grade was $17,527. This cost also varied by grade. There were no additional aGVHD-attributable costs for grade I, but the mean aGVHD-attributable costs were $9743 for grade II, $62,220 for grade III/IV, and $55,724 for aGVHD with lower GI involvement compared with the controls without aGVHD. High-grade aGVHD and GI involvement in aGVHD, especially lower GI aGVHD, is associated with a considerably increased mortality and healthcare economic burden. Therefore, it is imperative that new therapeutic strategies be developed for this patient population.

Robustness of the healthcare utilization results from the Rotavirus Efficacy and Safety Trial (REST) evaluating the human-bovine (WC3) reassortant pentavalent rotavirus vaccine (RV5).

BACKGROUND: The Rotavirus Efficacy and Safety Trial was a placebo-controlled Phase III study that evaluated the safety and efficacy of a three-dose pentavalent rotavirus vaccine (RV5) including its effect on healthcare utilization for rotavirus gastroenteritis (RVGE). The per-protocol (PP) analyses, which counted events occurring 14 days after dose 3 among infants without protocol violations, have already been published. This paper evaluates the consistency of the healthcare utilization results based on the modified intention to treat (MITT) analyses with the PP analyses. The MITT analyses include all infants receiving at least one dose of vaccine or placebo and follow-up begins after dose 1. The paper also explores the consistency of the results for different subgroups of the study population with different types of surveillance. METHODS: Data on healthcare utilization for acute gastroenteritis were collected via telephone interviews after administration of the first dose. Parents were either contacted every 6 weeks or every 2 weeks depending on the substudy in which they were enrolled. Those contacted every 2 weeks were also asked to complete symptom diaries. Poisson regression was used to evaluate the effect of RV5 on the rates of RVGE-associated healthcare encounters in all of the analyses. RESULTS: In the first 2 years after vaccination, RV5 reduced the combined rate of hospitalizations and emergency department (ED) visits 88.9% (95% CI: 84.9, 91.9) for all RVGE regardless of serotype in the MITT analysis compared with a 94.5% (95% CI: 91.2, 96.6) reduction based on the G1-G4 PP analysis. By type of surveillance, the rate reductions for the G1-G4 PP analysis were 91.0% (95% CI: 81.7, 95.5) and 95.9% (95% CI: 92.2, 97.8) among parents contacted every 2 weeks (number evaluable = 4,451) and every 6 weeks (number evaluable = 52,683) respectively. CONCLUSIONS: Our analyses demonstrated that the effect of RV5 on reducing the rate of hospitalizations and ED visits based on the MITT analyses were generally consistent with the PP analyses. The rate of events for subgroups with different intensities of surveillance differed but the effect of RV5 on the relative rate reductions were consistent with the results that have already been published. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT00090233.

Safety and efficacy of a pentavalent human-bovine (WC3) reassortant rotavirus vaccine.

BACKGROUND: Rotavirus is a leading cause of childhood gastroenteritis and death worldwide. METHODS: We studied healthy infants approximately 6 to 12 weeks old who were randomly assigned to receive three oral doses of live pentavalent human-bovine (WC3 strain) reassortant rotavirus vaccine containing human serotypes G1, G2, G3, G4, and P[8] or placebo at 4-to-10-week intervals in a blinded fashion. Active surveillance was used to identify subjects with serious adverse and other events. RESULTS: The 34,035 infants in the vaccine group and 34,003 in the placebo group were monitored for serious adverse events. Intussusception occurred in 12 vaccine recipients and 15 placebo recipients within one year after the first dose including six vaccine recipients and five placebo recipients within 42 days after any dose (relative risk, 1.6; 95 percent confidence interval, 0.4 to 6.4). The vaccine reduced hospitalizations and emergency department visits related to G1-G4 rotavirus gastroenteritis occurring 14 or more days after the third dose by 94.5 percent (95 percent confidence interval, 91.2 to 96.6 percent). In a nested substudy, efficacy against any G1-G4 rotavirus gastroenteritis through the first full rotavirus season after vaccination was 74.0 percent (95 percent confidence interval, 66.8 to 79.9 percent); efficacy against severe gastroenteritis was 98.0 percent (95 percent confidence interval, 88.3 to 100 percent). The vaccine reduced clinic visits for G1-G4 rotavirus gastroenteritis by 86.0 percent (95 percent confidence interval, 73.9 to 92.5 percent). CONCLUSIONS: This vaccine was efficacious in preventing rotavirus gastroenteritis, decreasing severe disease and health care contacts. The risk of intussusception was similar in vaccine and placebo recipients. (ClinicalTrials.gov number, NCT00090233.)

The burden of rotavirus hospitalizations among Medicaid and non-Medicaid children younger than 5 years old.

OBJECTIVES: We sought to compare the burden of hospitalizations associated with rotavirus gastroenteritis (RGE) in children younger than 5 years in US Medicaid and non-Medicaid populations in 2000 and 2003. METHODS: We used the Kids' Inpatient Database (KID) to examine the burden of RGE-associated hospitalizations in terms of numbers and rates of hospitalizations, lengths of stay, and hospital charges. Two indirect methods were also used to estimate RGE-associated hospitalizations, because rotavirus testing is not routinely performed. RESULTS: Approximately 40% of children younger than 5 years were enrolled in Medicaid in 2003, but this population accounted for nearly 50% of all RGE-associated hospitalizations and 60% of total charges. Children enrolled in Medicaid had significantly greater hospitalization rates, average lengths of stay, and average charges per stay than did those not enrolled. CONCLUSIONS: Although RGE affects all socioeconomic groups, the Medicaid population accounted for a disproportionate number of the hospitalizations. With the inclusion of rotavirus vaccines in the pediatric immunization schedule, it is important that US children, especially those enrolled in Medicaid programs, are vaccinated to reduce the burden of RGE.

Incremental 1-year medical resource utilization and costs for patients with herpes zoster from a set of US health plans.

BACKGROUND: Nearly 1 million new episodes of herpes zoster (HZ) occur annually in the US, yet little is known about the medical resource utilization (RU) and costs associated with HZ and its complications. OBJECTIVES: To describe the medical RU and cost burden of HZ in the first 90 days and the first year after diagnosis from the health insurer perspective and to stratify this burden for patients diagnosed with post-herpetic neuralgia (PHN) and those who are immunocompromised. In addition, this study explores costs from the societal perspective as a result of work loss in the first year after diagnosis. METHODS: The medical RU and cost data were obtained from the MarketScan Research Database for the years 1998-2003. This database contains inpatient, outpatient and prescription drug data for approximately 14 million individuals of all ages, covered under a variety of fee-for-service and capitated provider reimbursement arrangements, including those with Medicare and private insurance. The work loss estimates were based on the MarketScan Health and Productivity Management Database. Claims for services incurred between 1 January 1998 and 31 December 2003 were screened to identify a cohort of HZ patients based on the presence of at least one International Classification of Diseases, 9th Revision (ICD-9) diagnosis code 053.xx. Each patient was assigned an index date based on the earliest observed occurrence of an HZ diagnosis. A cohort of PHN patients was identified as a subset of the HZ cohort with ICD-9 codes 053.12, 053.13, 053.19 or 729.2x in the period of 90 days to 12 months after the index date. Multivariable regression was used to compare HZ cases with matched controls after adjusting for demographic characteristics, insurance status, co-morbidities and medical expenditure in the 6 months prior to diagnosis for each of the endpoints. Separate regression models were developed, in which age and immune status were stratified. All costs were adjusted to March 2008 values using the medical care component of the Consumer Price Index. The average per patient cost of all HZ cases was $US605 in the first 90 days after diagnosis and $US1052 at 1 year. For the subset with PHN, the average per patient cost of HZ at 1 year was $US3815. For the subset with an immunocompromising condition, the average HZ cost at 1 year was $US1745. The majority of the costs were the result of outpatient visits and prescription drugs. The subset of HZ cases that had both absence hour and short-term disability (STD) records available had 26.5 absence hours and 2.9 STD days. Healthcare utilization, medical care costs and work loss all increased with age for all HZ cases. Based on the results from the present study, the direct medical cost burden of HZ in the US is high, exceeding $US1000 per HZ patient. This direct medical cost may be nearly twice as high in immunocompromised patients and four times as high in the subset of HZ cases with PHN. The direct medical cost burden of HZ may exceed $US1 billion annually in the US. The majority of medical RU and cost burden is incurred by the elderly. Although many people with HZ may no longer be in the workforce, HZ does contribute to lost work time.

Cost-effectiveness of introducing a rotavirus vaccine in developing countries: the case of Mexico.

BACKGROUND: In developing countries rotavirus is the leading cause of severe diarrhoea and diarrhoeal deaths in children under 5. Vaccination could greatly alleviate that burden, but in Mexico as in most low- and middle-income countries the decision to add rotavirus vaccine to the national immunisation program will depend heavily on its cost-effectiveness and affordability. The objective of this study was to assess the cost-effectiveness of including the pentavalent rotavirus vaccine in Mexico's national immunisation program. METHODS: A cost-effectiveness model was developed from the perspective of the health system, modelling the vaccination of a hypothetical birth cohort of 2 million children monitored from birth through 60 months of age. It compares the cost and disease burden of rotavirus in an unvaccinated cohort of children with one vaccinated as recommended at 2, 4, and 6 months. RESULTS: Including the pentavalent vaccine in the national immunisation program could prevent 71,464 medical visits (59%), 5,040 hospital admissions (66%), and 612 deaths from rotavirus gastroenteritis (70%). At US$10 per dose and a cost of administration of US$13.70 per 3-dose regimen, vaccination would cost US$122,058 per death prevented, US$4,383 per discounted life-year saved, at a total net cost of US$74.7 million dollars to the health care system. Key variables influencing the results were, in order of importance, case fatality, vaccine price, vaccine efficacy, serotype prevalence, and annual loss of efficacy. The results are also very sensitive to the discount rate assumed when calculated per life-year saved. CONCLUSION: At prices below US $15 per dose, the cost per life-year saved is estimated to be lower than one GNP per capita and hence highly cost effective by the WHO Commission on Macroeconomics and Health criteria. The cost-effectiveness estimates are highly dependent upon the mortality in the absence of the vaccine, which suggests that the vaccine is likely to be significantly more cost-effective among poorer populations and among those with less access to prompt medical care - such that poverty reduction programs would be expected to reduce the future cost-effectiveness of the vaccine.

Safety and efficacy of the pentavalent human-bovine (WC3) reassortant rotavirus vaccine in healthy premature infants.

BACKGROUND: Premature infants seem to be at greater risk of hospitalization from rotavirus gastroenteritis than term infants. Safety and efficacy of the pentavalent human-bovine (WC3) reassortant rotavirus vaccine were assessed in premature infants enrolled in the large-scale, blinded, placebo-controlled rotavirus efficacy and safety trial (REST). METHODS: Healthy infants 6-12 weeks of chronologic age at study entry were randomized to receive 3 oral doses of pentavalent rotavirus vaccine or placebo at 4- to 10-week intervals. Infants born at < or =36 weeks of gestational age were eligible if thriving at the time of enrollment. Safety and efficacy were retrospectively assessed in these premature infants comparing vaccine with placebo recipients. Cases of rotavirus gastroenteritis were defined as forceful vomiting and/or > or =3 watery or looser-than-normal stools within a 24-hour period, accompanied by detection of rotavirus antigen in the stool. RESULTS: A total of 2070 infants between 25 and 36 gestational weeks received at least 1 dose of vaccine or placebo; 1005 vaccine recipients and 1061 placebo recipients were evaluable for safety. Serious adverse events occurred in 55 vaccine recipients (5.5%) and 62 placebo recipients (5.8%). In a nested substudy of 308 premature infants evaluable for detailed safety (154 in each group), the frequencies of fever, diarrhea, vomiting, and irritability were comparable between vaccine and placebo recipients. Overall, 3 doses of the pentavalent vaccine reduced the rate of hospitalizations and emergency department visits in premature infants due to rotavirus gastroenteritis by 100% (95% CI: 82.2-100) compared with placebo. The vaccine also prevented 73.0% (95% CI: -2.2-95.2) of rotavirus gastroenteritis cases of any severity. CONCLUSIONS: In this post hoc analysis of healthy premature infants, the pentavalent rotavirus vaccine was generally well-tolerated and substantially reduced rotavirus-attributable hospitalizations and emergency department visits compared with placebo. Overall, vaccine safety and efficacy seemed to be generally comparable to the results in the REST study population as a whole. These results support vaccinating healthy premature infants on the same schedule as term infants.

Acute/subacute herpes zoster: healthcare resource utilisation and costs in a group of US health plans.

BACKGROUND: Although there are estimated to be nearly 1 million cases of herpes zoster diagnosed in the US each year, the economic costs associated with herpes zoster in the US have not been well described. OBJECTIVE: To describe the healthcare resource utilisation and costs associated with physician-diagnosed acute/subacute herpes zoster, from a payer perspective, using a large US healthcare claims database. METHODS: Data for the period 2000-1 were obtained from the Medstat Marketscan healthcare claims database. The duration of acute/subacute herpes zoster was considered to include the 21 days preceding, and 90 days following, the initial herpes zoster diagnosis. Resource utilisation was examined for individuals with newly diagnosed acute/subacute herpes zoster (n = 8741) and compared, through regression analyses, with that observed for control individuals from the same population (n = 50,000). Similar analyses were conducted for costs; the costs included reflected healthcare payments from patients, insurers and other sources. Regression analyses controlled for demographics (age, gender), conditions that have been observed with greater frequency among patients with acute/subacute herpes zoster in prior studies (cancer, HIV infection, organ transplantation, other immunosuppressive conditions and therapies) and the number of billed services within each of seven categories of care that were potentially related to acute/subacute herpes zoster and that were utilised within the 30-180 days prior to the diagnosis for affected patients, and over an analogous period for controls. RESULTS: The acute/subacute phase of herpes zoster was estimated to result in an average of 1.7 (standard error [SE] 0.02) additional physician and hospital outpatient visits, 0.05 (SE 0.003) additional emergency room visits, 0.03 (SE 0.003) additional inpatient hospital admissions, 2.1 (SE 0.03) additional prescriptions filled and $US431 (SE 17.60) in additional healthcare costs per patient. Among patients with acute/subacute herpes zoster, 21.1% had a diagnosis code with a designation for a herpes zoster-related complication, and 9.4% had three or more outpatient visits with a diagnosis code for herpes zoster. The average estimated incremental costs per patient with acute/subacute disease increased with age, ranging from $US258 (SE 37.70) among patients aged < or =19 years to $US805 (SE 106.30) among those aged > or =80 years. The numbers of additional outpatient visits, inpatient admissions, prescriptions filled for pain medications and coded complications were also substantially higher among older than younger patients with acute/subacute herpes zoster. CONCLUSIONS: The management of acute/subacute herpes zoster was found to result in substantial healthcare costs, with outpatient care and prescription drugs comprising the majority of the cost burden. To more fully understand the overall cost of herpes zoster disease to society, future studies should examine the healthcare costs associated with post-herpetic neuralgia and productivity losses due to herpes zoster and post-herpetic neuralgia.

Efficacy of a pentavalent rotavirus vaccine in reducing rotavirus-associated health care utilization across three regions (11 countries).

OBJECTIVE: To evaluate the effect of a human-bovine reassortant pentavalent rotavirus vaccine (PRV) on health care encounters in nearly 70 000 subjects randomized in three regions - Europe, the United States, and Latin America/the Caribbean - in the Rotavirus Efficacy and Safety Trial (REST). METHODS: Healthy 6- to 12-week-old infants received 3 doses of PRV or placebo at 4- to 10-week intervals. The exact binomial method for ratios of Poisson counts was used to evaluate the effect of PRV on the rate of rotavirus-related hospitalizations and emergency department (ED) visits involving rotavirus G-types 1-4 occurring > or =14 days after the third dose of vaccine for up to 2 years. RESULTS: In fully vaccinated infants, reductions in rotavirus-associated hospitalizations and ED visits were 94.7% (95% CI: 90.9, 96.9) in Europe, 94.9% (95% CI: 84.0, 98.9) in the United States, and 90.0% (95% CI: 29.4, 99.8) in the Latin American/Caribbean regions. CONCLUSIONS: PRV reduced hospitalizations and ED visits within each region in REST. Results were consistent across regions and across the overall study cohort.

The incidence of herpes zoster in a United States administrative database.

BACKGROUND: Few recent studies have reported data on the incidence of herpes zoster (HZ) in U.S. general clinical practice. OBJECTIVE: To estimate the age- and sex-specific incidence of HZ among U.S. health plan enrollees. DESIGN: Data for the years 2000 to 2001 were obtained from the Medstat MarketScan database, containing health insurance enrollment and claims data from over 4 million U.S. individuals. Incident HZ cases were identified through HZ diagnosis codes on health care claims. The burden of HZ among high-risk individuals with recent care for cancer, HIV, or transplantation was examined in sub-analyses. Overall incidence rates were age- and sex-adjusted to the 2000 U.S. population. PARTICIPANTS: MarketScan U.S. health plan enrollees of all ages. MEASUREMENTS AND MAIN RESULTS: We identified 9,152 incident cases of HZ (3.2 per 1,000 person-years) (95% confidence interval [CI], 3.1 to 3.2 per 1,000). Annual HZ rates per 1,000 person-years were higher among females (3.8) than males (2.6) (P<.0001). HZ rates rose sharply with age, and were highest among individuals over age 80 (10.9 per 1,000 person-years) (95% CI, 10.2 to 11.6). The incidence of HZ per 1,000 person-years among patients with evidence of recent care for transplantation, HIV infection, or cancer (10.3) was greater than for individuals without recent care for these conditions (3.0) (P<.0001). CONCLUSIONS: The overall incidence of HZ reported in the present study was found to be similar to rates observed in U.S. analyses conducted 10 to 20 years earlier, after age- and sex-standardizing estimates from all studies to the 2000 U.S. population. The higher rate of HZ in females compared with males contrasts with prior U.S. studies.