Temporal changes in treatment patterns by age group and functional status before and after PD-1/L1 inhibitor approvals in advanced urothelial carcinoma.

Introduction: Metastatic urothelial carcinoma (mUC) has poor prognosis. A high unmet need exists for novel treatment for those who are unfit for platinum-based chemotherapy. Methods: We aimed to describe real-world temporal changes in patient characteristics and 1L treatment selection for mUC patients in the United States following the approval of anti-PD-1/L1 treatments. This study was a retrospective, observational study using anonymized and structured oncology electronic medical record (EMR) data from IQVIA and the US Oncology Network iKnowMed (USON). Results: After approval of 1L anti-PD-1/L1 treatment for mUC, there is a marked increase in the use of 1L anti-PD-1/L1 monotherapies, accompanied by a proportional decrease in 1L platinum-based treatments and non-guideline-based therapy; particularly among the elderly (> 75 years) and those with poor ECOG performance status (ECOG PS 2+). Discussion: Anti-PD-1/L1 monotherapies fulfill the prior unmet need of frail mUC patients who are ineligible for platinum-based therapies.

Real-world clinical outcomes of patients with metastatic renal cell carcinoma receiving pembrolizumab + axitinib vs. ipilimumab + nivolumab.

BACKGROUND: Immune-Oncology (IO) therapies have changed first-line (1L) treatment paradigm for metastatic renal cell carcinoma (mRCC) in last few years with robust clinical trial data. We examined clinical outcomes among clear cell mRCC (mccRCC) patients who received pembrolizumab + axitinib (pembro-axi) or ipilimumab + nivolumab (ipi-nivo) in the US community oncology setting. METHODS: This retrospective cohort study utilized data from electronic health records and chart review within The US Oncology Network to identify adult patients with mccRCC initiating 1L pembro-axi or ipi-nivo from January 01, 2019 to December 31, 2020 and followed through March 31, 2021. Physician-recorded response (real-world overall response rate [rwORR] and real-world disease control rate [rwDCR]) was assessed descriptively. Real-world progression-free survival (rwPFS), real-world time to next treatment (rwTTNT) and time on treatment (rwToT) were estimated using Kaplan-Meier analysis. Association of 1L systemic treatment with time-to-event outcomes was examined using multivariable cox proportional hazards models. RESULTS: Study included 331 mccRCC patients (pembro-axi:44%, ipi-nivo:56%). Median age was 65 years, 75.5% were male, and 82.5% had intermediate/poor (I/P) IMDC risk score. RwORR and rwDCR were 71.0% and 80.0% for pembro-axi and 45.2% and 58.6% for ipi-nivo. In multivariable analysis, pembro-axi was associated with longer rwToT (aHR, 0.53 [95% CI, 0.40, 0.71]), rwTTNT (aHR, 0.60 [95% CI, 0.42, 0.87]), and rwPFS (aHR, 0.70 [95% CI, 0.49, 0.99]) compared to ipi-nivo (P < 0.01). CONCLUSIONS: Our study provides insight into newer mccRCC treatment tolerability and effectiveness in the real-world US community setting. Our real-world results were comparable to data from clinical trials, which is encouraging for mccRCC patients.

Real-world Treatment Patterns and Clinical Outcomes for Metastatic Renal Cell Carcinoma in the Current Treatment Era.

Background: Immuno-oncology (IO) agents and tyrosine kinase inhibitors (TKIs) have revolutionized the treatment paradigm for metastatic renal cell carcinoma (mRCC). Data on real-world usage and outcomes are limited. Objective: To examine real-world treatment patterns and clinical outcomes for mRCC. Design setting and participants: This retrospective cohort study included 1538 patients with mRCC who received first-line treatment with pembrolizumab + axitinib (P + A; n = 279, 18%), ipilimumab + nivolumab (I + N; n = 618, 40%), or TKI monotherapy (TKIm; cabozantinib, sunitinib, pazopanib, or axitinib; n = 641, 42%) between January 1, 2018 and September 30, 2020 in US Oncology Network/non-network practices. Outcome measurements and statistical analysis: The relationship with outcomes, time on treatment (ToT), time to next treatment (TTNT), and overall survival (OS) was analyzed using multivariable Cox proportional-hazards models. Results and limitations: The median age of the cohort was 67 yr (interquartile range 59.5-74.4), 70% were male, 79% had clear cell RCC, and 87% had an intermediate or poor International mRCC Database Consortium risk score. The median ToT was 13.6 for P + A versus 5.8 for I + N versus 3.4 mo for TKIm (p < 0.001) and the median TTNT was 16.4 for P + A versus 8.3 for I + N versus 8.4 mo for TKIm (p < 0.001) . Median OS was not reached for P + A, 27.6 mo for I + N, and 26.9 mo for TKIm (p = 0.237). On adjusted multivariable analysis, treatment with P + A was associated with better ToT (adjusted hazard ratio [aHR] 0.59, 95% confidence interval [CI] 0.47-0.72 vs I + N; 0.37, 95% CI, 0.30-0.45 vs TKIm; p < 0.0001) and better TTNT (aHR 0.61, 95% CI 0.49-0.77 vs I + N; 0.53, 95% CI 0.42-0.67 vs TKIm; p < 0.0001). Limitations include the retrospective design and the limited follow-up for characterization of survival. Conclusions: We noted substantial uptake of IO-based therapies in the first-line community oncology setting since their approval. In addition, the study provides insights into clinical effectiveness, tolerability, and/or compliance of IO-based therapies. Patient summary: We examined the use of immunotherapy for patients with metastatic kidney cancer. The findings suggest rapid implementation of these new treatments by oncologists working in the community setting, which is reassuring for patients with this disease.

A Real-World Evidence Study of CDK4/6 Inhibitor Treatment Patterns and Outcomes in Metastatic Breast Cancer by Germline BRCA Mutation Status.

INTRODUCTION: Limited data exist on real-world treatment patterns and the effectiveness of cyclin-dependent kinase (CDK) 4/6 inhibitors in germline BRCA (gBRCA)-mutated breast cancer. METHODS: Adults with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC) treated with CDK4/6 inhibitor therapy between 2013 and 2018 were retrospectively selected from the Flatiron Health database. Patients with known gBRCA status were classified as mutated (gBRCAm) or wild type (gBRCAwt). Time-to-first subsequent therapy or death (TFST) and overall survival (OS) were calculated from the earliest line of therapy with a CDK4/6 inhibitor. RESULTS: Of 2968 patients with HR+/HER2- mBC receiving a CDK4/6 inhibitor, 859 (28.9%) had known gBRCA status, of whom 9.9% were gBRCAm and 90.1% gBRCAwt. Median (95% confidence interval [CI]) TFST was 10 (7-11) months in the gBRCAm group, 10 (9-11) months in the gBRCAwt group, and 11 (10-12) months in the combined gBRCAwt and unknown gBRCA group; median (95% CI) OS was 26 (21-not estimated), 37 (31-51), and 33 (31-35) months, respectively. Cox models indicated the gBRCAm group had shorter TFST (stratified hazard ratio [sHR] 1.24; 95% CI 0.96-1.59) and OS (sHR 1.50; 95% CI 1.06-2.14) than the gBRCAwt group. The gBRCAm group had shorter TFST (sHR 1.38; 95% CI 1.08-1.75) and OS (sHR 1.22; 95% CI 0.88-1.71) than the combined group. CONCLUSION: The results of this real-world study suggest that treatment outcomes with CDK4/6 inhibitors may be worse in patients with gBRCAm mBC than in their counterparts with gBRCAwt and unknown gBRCA status, suggesting potential differences in tumor biology. This result highlights the unmet need in patients with gBRCAm requiring optimized treatment selection and sequencing. Future exploration in larger samples of patients who have had biomarker testing is warranted.

Cross-sectional study estimating the psychosocial impact of genital warts and other anogenital diseases in South Korea.

OBJECTIVES: To estimate self-reported human papillomavirus (HPV) disease-related psychosocial impact among male and female patients in South Korea. DESIGN: In this multicentre cross-sectional study, psychosocial impacts were estimated using a one-time survey capturing HPV Impact Profile (HIP) results, CuestionarioEspecifico en Condilomas Acuminados (CECA; in Spanish)-'Specific questionnaire for Condylomata Acuminata' and the EuroQol-5 Dimension (EQ-5D) surveys. Student's t-tests or Mann-Whitney U tests were used for continuous comparisons; χ2 or Fisher's exact tests were applied for categorical comparisons. SETTING: 5098 clinics throughout Seoul, Busan, Daegu, Kwangju and Daejeon (South Korea). PARTICIPANTS: Patients with and without genital warts (GW) (males) and selected HPV diseases (females) visiting primary care physicians, obstetricians/gynaecologists, urologists and dermatologists with 2-30 years experience. RESULTS: Of 150 male and 250 female patients, HIP scores showed 85.3% of male patients with GW and 32.0% without reported moderate psychological impact (p<0.0001). In categorised total scores, 88.5% of female patients with and 66.0% without selected HPV-related diseases reported moderate or high psychological impacts (p=0.0004). In the CECA questionnaire, male patients had mean (SD) scores of 10.51 (3.79) in 'emotional health' and 15.90 (6.13) in 'sexual activity'. Female patients with GW reported lower scores in both dimensions with mean scores of 7.18 (4.17) in 'emotional health' and 10.97 (5.80) in 'sexual activity' (p<0.0001), indicating worse health-related quality of life (HRQoL). For the EQ-5D, male patients with GW reported lower mean Visual Analogue Scale (VAS) scores than those without (75.1 vs 81.13, p<0.0135). Mean VAS score and utility values were lower for females with HPV-related diseases than those without (72.18 vs 76.86 and 0.90 vs 0.94, respectively). CONCLUSION: In South Korea, GW in men and HPV-related diseases in women negatively impact patient well-being and HRQoL scores. Among women, those with GW suffered a greater psychosocial impact than those with other selected HPV-related diseases.

Prevalence and Burden Related to Genital Warts in India.

The prevalence of genital warts (GW) and self-reported human papillomavirus (HPV) as well as disease-related psychosocial impact among male and female patients aged 18-60 years in India were assessed. GW prevalence was estimated using a 2-week daily log of patients examined from June 7-September 22, 2011 by 200 participating physicians in 6 regions of India. Psychosocial impact was estimated using one-time, self-administered surveys, including HPV Impact Profile (HIP), Cuestionario Específico para Condiloma Acuminado ([Spanish] CECA; "Specific questionnaire for Condylomata Acuminata") and EuroQol-5 Dimension survey. T-tests or Mann-Whitney U-tests were used for continuous comparisons and Chi-square or Fisher exact tests were applied for categorical comparisons. Overall GW prevalence in India was estimated at 1.07% (95% confidence interval = 0.97-1.17) and was higher among men than women. Regional prevalence ranged from high in Delhi (2.17%) to low in Bangalore (0.40%). Patients aged 25-29 years had the highest GW prevalence (1.42%). GW patients were most often newly diagnosed (74.07%). Among those with existing GW, 56.24% were recurrent, and 43.76% were resistant. According to total HIP scores, 55.4% of male GW patients and 20.0% of those without GW reported moderate psychological impact (p < 0.0001). HIP scores among women revealed that patients with abnormal Papanicolaou (Pap) test results (34.3%), precancerous lesions (46.2%), external GW (48.0%), and those without HPV-related disease (18.5%) reported moderate psychological impact (p = 0.0089) (Psychosocial impact results are reported in the Supplementary Data ). Estimated national GW prevalence, diagnosis, and treatment costs in India were higher for men than for women. GW in men and HPV infection in women had a negative psychosocial impact on well-being and health-related quality of life (HRQoL) scores, especially among women diagnosed with GW and precancerous lesions compared to those with other selected HPV-related diseases. Despite its limitations, this study provides an estimation of GW data in India not previously available.

A cross-sectional study estimating the burden of illness related to genital warts in South Korea.

OBJECTIVES: Estimate the prevalence of genital warts (GW) and GW-related healthcare resource use and costs among male and female patients seeking treatment in South Korea. DESIGN: To estimate GW prevalence, physicians in five major South Korean regions recorded daily logs of patients (n=71 655) seeking care between July 26 and September 27, 2011. Overall prevalence estimates (and 95% CIs) were weighted by the estimated number of physicians in each specialty and the estimated proportion of total patients visiting each specialist type. Healthcare resource use was compared among different specialties. Corresponding p values were calculated using Mann-Whitney U tests. SETTING: The database covers 5098 clinics and hospitals for five major regions in South Korea: Seoul, Busan, Daegu, Gwangju and Daejeon. PARTICIPANTS: Primary care physicians (general practice/family medicine), obstetricians/gynaecologists, urologists and dermatologists with 2-30 years' experience. RESULTS: The estimated overall GW prevalence was 0.7% (95% CI 0.7% to 0.8%). Among women, GW prevalence was 0.6% (95% CI 0.6% to 0.7%); among men prevalence was 1.0% (95% CI 0.9% to 1.0%), peaking among patients aged 18-24 years. Median costs for GW diagnosis and treatment for male patients were US$58.2 (South Korean Won (KRW) ₩66 857) and US$66.3 (KRW₩76 113) for female patients. CONCLUSIONS: The estimated overall GW prevalence in South Korea was 0.7% and was higher for male patients. The overall median costs associated with a GW episode were higher for female patients than for male patients.

Geographic variation and risk factors for systemic and limb ischemic events in patients with symptomatic peripheral artery disease: Insights from the REACH Registry.

BACKGROUND: Patients with symptomatic peripheral artery disease (PAD) are at high risk of ischemic events. However, data about predictors of this risk are limited. HYPOTHESIS: We analyzed baseline characteristics and 4-year follow-up of patients enrolled in the international REduction of Atherothrombosis for Continued Health (REACH) Registry with symptomatic PAD and no history of stroke/transient ischemic attack to describe annual rates of recurrent ischemic events globally and geographically. METHODS: The primary outcome was systemic ischemic events (composite of cardiovascular death, myocardial infarction, or stroke) at 4 years. The secondary outcome was limb ischemic events (composite of lower limb amputation, peripheral bypass graft, and percutaneous intervention for PAD) at 2 years. Multivariate analysis identified risk factors associated with recurrent ischemic events. RESULTS: The primary endpoint rate reached 4.7% during the first year and increased continuously (by 4%-5% each year) to 17.6% by year 4, driven mainly by cardiovascular mortality (11.1% at year 4). Japan experienced lower adjusted ischemic rates (P < 0.01) vs North America. Renal impairment (P < 0.01), congestive heart failure (P < 0.01), history of diabetes (P < 0.01), history of myocardial infarction (P = 0.01), vascular disease (single or poly, P < 0.01), and older age (P < 0.01) were associated with increased risk of systemic ischemic events, whereas statin use was associated with lower risk (P = 0.03). The limb ischemic event rate was 5.7% at 2 years. CONCLUSIONS: Four-year systemic ischemic risk in patients with PAD and no history of stroke or transient ischemic attack remains high, and was mainly driven by cardiovascular mortality.

Residual Ischemic Risk and Its Determinants in Patients With Previous Myocardial Infarction and Without Prior Stroke or TIA: Insights From the REACH Registry.

BACKGROUND: Although the rate of in-hospital ischemic events after myocardial infarction (MI) has dramatically decreased, long-term residual risk may remain substantial. However, most of the information on current residual risk is derived from highly selected randomized trials. HYPOTHESIS: In patients with previous MI and no prior ischemic stroke/transient ischemic attack (TIA), residual ischemic risk increases over time. METHODS: Using the international Reduction of Atherothrombosis for Continued Health (REACH) registry, we analyzed baseline characteristics and 4-year follow-up of patients with previous MI and no history of stroke/TIA to describe annual rates of recurrent ischemic events globally and by geography. The primary outcome was the composite of cardiovascular death, MI, or stroke. Multivariate analysis identified risk factors associated with recurrent ischemic events. RESULTS: Data from 16 770 patients enrolled at 5587 sites in 44 countries were analyzed. The rate of the primary outcome increased annually from 4.7% during year 1 to reach a 4-year rate of 15.1%. Compared with North America, Japan experienced lower ischemic event rates (P < 0.01), whereas Eastern Europe (P < 0.01) and the Middle East (P = 0.01) experienced higher ischemic event rates. The presence of congestive heart failure, polyvascular disease, diabetes, atrial fibrillation or flutter, and older age were associated with increased residual risk (all P < 0.01). Statin use was associated with lower ischemic risk (P < 0.01). CONCLUSIONS: In this study, residual ischemic risk after MI accrued progressively up to 4 years of follow-up, emphasizing the value of intensive secondary prevention strategies to minimize residual risk.

In Vitro Activity of Oral Antimicrobial Agents against Pathogens Associated with Community-Acquired Upper Respiratory Tract and Urinary Tract Infections: A Five Country Surveillance Study.

INTRODUCTION: Bacterial infections that cause community-acquired urinary tract infections (CA-UTI) and upper respiratory tract infections (CA-URTI) are most frequently treated empirically. However, an increase in antimicrobial resistance has become a problem when treating outpatients. METHODS: This study determined the in vitro activities of oral antibiotics among 1501 pathogens from outpatients with CA-UTI and CA-URTI in medical centers during 2012 and 2013 from Argentina, Mexico, Venezuela, Russia, and the Philippines. Minimal inhibitory concentrations (MICs) were determined using broth microdilution and susceptibility defined by Clinical Laboratory Standards Institute (CLSI) and European Committee for Antimicrobial Susceptibility Testing (EUCAST) criteria. RESULTS: Ceftibuten (MIC50, ≤0.25 mg/L) was more potent in vitro compared to other ß-lactams against Enterobacteriaceae from CA-UTI. Susceptibility to fluoroquinolones using CLSI criteria varied: Argentina and Mexico (50%), the Philippines (60%), Venezuela (70%), and Russia (80%). Fosfomycin susceptibility was >90% against Enterobacteriaceae in each country. Susceptibility among Enterobacteriaceae to trimethoprim-sulfamethoxazole was 30.6-75.6% and nitrofurantoin susceptibility also varied among the countries and was higher when EUCAST breakpoints were applied (65->90%) compared to CLSI (52-84%). All Haemophilus influenzae isolates from CA-URTI were susceptible to ceftibuten, cefixime, cefpodoxime, and cefuroxime using CLSI breakpoint criteria. EUCAST criteria produced intermediate and resistant MIC values for these oral cephalosporins. Country-specific susceptibility variation for fluoroquinolones, macrolides, and trimethoprim-sulfamethoxazole was observed among Streptococcus pneumoniae and Streptococcus pyogenes from CA-URTI. CONCLUSION: This study demonstrated that antimicrobial susceptibility patterns varied in the five countries investigated among pathogens from CA-UTI and CA-URTI. FUNDING: Merck & Co. Inc., Kenilworth, New Jersey, USA.

Costs of adult vaccination in medical settings and pharmacies: an observational study.

BACKGROUND: Community pharmacies are a convenient setting for vaccinating adults against infectious diseases in the United States. Whether the costs paid for vaccination in pharmacies differ from those in medical settings is unclear. OBJECTIVE: To examine whether the direct medical costs paid for adult vaccination differ by vaccination setting. METHODS: This was an observational retrospective study using 2010 MarketScan Commercial Claims and Encounters and Medicare Supplemental and Coordination of Benefits databases. Adults receiving herpes zoster or shingles vaccine, pneumococcal vaccine 23-valent, or influenza vaccines were identified using Current Procedural Terminology codes and National Drug Code numbers from medical and pharmacy claims files, respectively, between January 1 and December 31, 2010, in 1 of the following 3 settings: physician offices; other medical settings (e.g., inpatient/outpatient hospitals, emergency rooms); and pharmacies. Patients were adults aged ≥60 years on the date of zoster vaccination and aged ≥19 years on the date of pneumococcal or influenza vaccinations. The final study samples meeting inclusion/exclusion criteria were 54,042 for zoster vaccine, 154,994 for pneumococcal vaccine, and 1,657,264 for influenza vaccine. The vaccination costs included the health plan and enrollee paid amounts for the product; vaccine administration; dispensing fee; and, where applicable, the visit. The mean (SD) vaccination costs paid per vaccine administration were estimated by vaccine and type of setting, overall, and by geographic region and type of health plan. The costs paid for the same vaccine across vaccination settings were compared using analysis of variance with post hoc tests (Tukey). RESULTS: Of those receiving zoster, pneumococcal, and influenza vaccines, 25%, 1%, and 7%, respectively, received the vaccines at a pharmacy. Compared with other U.S. regions, pharmacy-based vaccination for these 3 vaccines was generally more frequent in the West and the South. Overall, the mean (SD) costs paid per enrollee per vaccine administration at physician offices, other medical settings, and pharmacies were as follows: for zoster vaccine, $208.72 (42.10), $209.51 (50.83), and $168.50 (15.66), respectively (P <0.05); for pneumococcal vaccine, $65.69 (27.54), $72.11 (49.95), and $54.98 (9.72), respectively (P <0.05); and for influenza vaccine, $29.29 (15.29), $24.20 (13.12), and $21.57 (6.63), respectively (P <0.05). The mean amounts paid also differed by geographic region and type of health plan, with costs usually lower for the vaccinations given at pharmacies. CONCLUSIONS: The average direct costs paid per adult vaccination were lower in pharmacies compared with physician offices and other medical settings by 16%-26% and 11%-20%, respectively. These results were mostly consistent across geographic regions and types of health plans. These data may help payers and policymakers understand the economic value of adult vaccination in different settings, especially in pharmacies.

Systematic review of the incidence and prevalence of genital warts.

BACKGROUND: Anogenital warts (AGWs) are a common, highly infectious disease caused by the human papillomavirus (HPV), whose high recurrence rates contribute to direct medical costs, productivity loss and increased psychosocial impact. Because of the lack of a systematic review of the epidemiology of AGWs in the literature, this study reviewed the published medical literature on the incidence and prevalence of AGWs. METHODS: A comprehensive literature search was performed on the worldwide incidence and prevalence of AGWs between 2001 and 2012 using the PubMed and EMBASE databases. An additional screening of abstracts from relevant sexual health and infectious disease conferences from 2009 to 2011 was also conducted. Only original studies with general adult populations (i.e., at least including ages 20 through 40 years) were included. RESULTS: The overall (females and males combined) reported annual incidence of any AGWs (including new and recurrent) ranged from 160 to 289 per 100,000, with a median of 194.5 per 100,000. New AGW incidence rates among males ranged from 103 to 168 per 100,000, with a median of 137 per 100,000 and among females from 76 to 191 per 100,000, with a median of 120.5 per 100,000 per annum. The reported incidence of recurrent AGWs was as high as 110 per 100,000 among females and 163 per 100,000 among males. Incidence peaked before 24 years of age in females and between 25 and 29 years of age among males. The overall prevalence of AGWs based on retrospective administrative databases or medical chart reviews or prospectively collected physician reports ranged from 0.13% to 0.56%, whereas it ranged from 0.2% to 5.1% based on genital examinations. CONCLUSIONS: The literature suggests that AGWs are widespread and the prevalence depends on study methodology as suggested by higher rates reported from routine genital examinations versus those from treatment records. However, there remains a need for more population-based studies from certain regions including Africa, Latin America and Southern Asia to further elucidate the global epidemiology of this disease.

The Cost-Effectiveness Analysis of a Quadrivalent Human Papillomavirus Vaccine (6/11/16/18) for Females in Japan.

OBJECTIVE: We assessed the epidemiological and economic impact of a quadrivalent human papillomavirus (HPV) (6/11/16/18) vaccine for females in preventing cervical cancer, cervical intraepithelial neoplasia grades 2 and 3 (CIN 2/3), cervical intraepithelial neoplasia grade 1 (CIN 1), and genital warts in Japan by using a transmission dynamic model. METHODS: A published mathematical model of the transmission dynamics of HPV infection and disease was adapted for Japan. Model inputs were used from Japan or the Asia/Pacific region when available; otherwise, the default values in the original model were used. The transmission dynamic model was used to assess the epidemiological and economic impact of a quadrivalent HPV (6/11/16/18) vaccine for females in preventing cervical cancer, CIN 2/3, CIN 1, and genital warts in Japan.Maintaining current cervical cancer screening practices, we evaluated two strategies: routine vaccination of females by age 12 years (S1), and S1 combined with a temporary (5 years) female catch-up program for age 12 to 24 years (S2). The vaccine coverage rate was 80% for the routine and 50% for the catch-up vaccination programs. RESULTS: Compared with no vaccination, both vaccination strategies significantly reduced the incidence of HPV 6/11/16/18-related disease. The most effective strategy was S2. By using this strategy over 100 years in the Japanese population, the estimated cumulative percentage reduction in incident HPV 6/11/16/18-related genital warts-female, genital warts-male, cervical CIN 1, CIN 2/3, and cervical cancer cases was 90% (2,113,723 cases), 86% (2,082,637 cases), 72% (263,406 cases), 71% (1,328,366 cases), and 58% (323,145 cases), respectively. The cost-effectiveness ratios were JPY 1,244,000, and JPY 1,205,800 per quality-adjusted life-year gained for S1 and S2 compared with no vaccination, respectively, over a time horizon of 100 years. CONCLUSION: We conclude that a quadrivalent HPV vaccination program for females can reduce the incidence of cervical cancer, CIN, and genital warts in Japan at a cost-per-quality-adjusted life-year ratio within the range defined as cost-effective.

Estimated health and economic impact of quadrivalent HPV (types 6/11/16/18) vaccination in Brazil using a transmission dynamic model.

BACKGROUND: Cervical cancer is the second most common cancer among women in Brazil. We examined the health and economic impacts of quadrivalent HPV vaccination in Brazil. METHODS: We adapted a previously developed transmission dynamic model to estimate the effectiveness of HPV vaccination on cervical cancer, cervical intraepithelial neoplasia grades 2 and 3 (CIN2/3), CIN1, and genital warts. We evaluated following vaccination strategies: routine vaccination of 12-year-old girls and routine vaccination in combination with a catch-up vaccination of 12 to 26-year-old women. RESULTS: The model projected that the vaccination would reduce the incidence rates of HPV 6/11/16/18-related cervical cancer, CIN2/3, CIN1, and female genital warts by 94% to 98% at year 100. Routine vaccination in combination with a catch-up vaccination could prevent approximately 163,000 cases of cervical cancer, 48,000 deaths from cervical cancer, 2.3 million cases of CIN2/3, and 11.4 million genital warts in the next 50 years. The incremental cost-effectiveness ratios for female vaccination strategies ranged from R$350 to R$720 (US$219 to US$450) per quality-adjusted life year (QALY) gained. CONCLUSIONS: Our study demonstrates that quadrivalent HPV female vaccination can be a cost-effective public health intervention that can substantially reduce the burden of cervical diseases and genital warts in Brazil.

Health and economic burden of HPV-related diseases in Singapore.

OBJECTIVE: To assess the health and economic burden of human papillomavirus (HPV)-related diseases (cervical cancer, cervical intraepithelial neoplasia (CIN) 1/2/3, and genital warts) in Singapore over a period of 25 years beginning in 2008. METHODS: Incidence-based modeling was used to estimate the incidence cases and associated economic burden, with the assumption that age-stratified incidence rates will remain the same throughout the period of 25 years. The incidence rates in 2008 were projected based on data obtained from the National Cancer Registry for cervical cancer, and from a combination of published data and hospital registry review for CIN1/2/3 and genital warts. The population growth rate was factored into the projection of incidence cases over time. Direct cost data per cervical cancer and per CIN1/2/3 case were obtained from the financial database of large local hospitals while cost data for genital warts were obtained from the National Skin Center; these costs were multiplied by the number of incidence cases to produce an aggregate estimate of the economic burden over the 25-year period (in 2008 Singapore dollars) using a 3% discount rate. RESULTS: The total number of incidence cases of HPV-disease over 25 years beginning in 2008 was estimated to be 60,183, including 8,078 for cervical cancer, 11,685 for CIN 2/3, 8,849 for CIN1, and 31,572 for genital warts. The estimated total direct cost was 83.2 million Singapore Dollars over 25 years: 57.6 million attributable to cervical cancer, 13.0 million to CIN2/3, 6.83 million to CIN1, and 5.70 million to genital warts. CONCLUSION: HPV-related diseases are expected to impose significant health and economic burden on the Singapore healthcare resources in the next 25 years.

Work and productivity loss related to herpes zoster.

OBJECTIVE: To estimate absenteeism and presenteeism-related work loss due to herpes zoster (HZ) among working individuals of 50-64 years of age. METHODS: This telephone survey included individuals with ≥1 insurance claim for HZ in the past year in administrative claims data from five US commercial health plans. Demographic information, characteristics of the HZ episode; impact of HZ on activities of daily living (ADL), and work days loss and productivity were surveyed. RESULTS: Responses were obtained from 153 of 1654 individuals who were contacted and were eligible for the survey (9.3%). Most had moderate or severe HZ (72.6%). Close to two-thirds reported some impact of HZ on ADL such as shopping, housework/chores, and social engagement. About half (51%) reported missing work due to HZ, and about an equal percentage reported little or much worse productivity than usual due to HZ while at work. On average, age-adjusted absenteeism- and presenteeism-related work loss was estimated at 31.6 hours, and 84.4 hours, respectively, with a combined work loss of 116.0 hours per HZ episode in a working person of 50-64 years of age. Work loss tended to increase with age and the duration and severity of the HZ episode. CONCLUSIONS: The study documents a substantial societal burden of HZ-related work and productivity loss. This is important information to take into consideration, in addition to the direct medical burden, when making policy decisions around vaccine prevention of HZ. LIMITATIONS: The study may potentially be subject to selection bias due to low survey response rate and since only those cases who sought care for a HZ episode were captured. The study may also be subject to respondent recall bias. Finally, since some respondents could still be having the HZ episode at the time of survey, the study may potentially have under-estimated the work and productivity loss.

Incidence and costs of cervical intraepithelial neoplasia in a US commercially insured population.

OBJECTIVE: This study aimed to estimate incidence, cost per episode of care, and US population burden of cervical intraepithelial neoplasia (CIN). MATERIALS AND METHODS: For women continuously enrolled in a US health plan from January 1, 1999 to December 31, 2004, medical claims were used to identify potential CIN diagnosis. Presence and grade of CIN (CIN 1, CIN 2,3, or no CIN) were verified in medical records for a randomly selected subset (n = 254). Incidence, costs, and population burden were calculated. RESULTS: Annual incidence for CIN 1 and CIN 2,3 was 1.6 and 1.2 per 1,000 women, respectively. Incidence was highest among women aged 21 to 30 years (3.3 and 3.6 per 1,000) and women aged 31 to 40 years (2.9 and 2.7 per 1,000). Costs per episode of care were higher for CIN 2,3 ($1,634 vs $1,084). Estimated annual burden per 1,000 US women was $1,059 for CIN 1 and $1,803 for CIN 2,3. CONCLUSIONS: We estimate that 412,000 women in the United States are diagnosed with CIN annually, with an associated cost of approximately $570 million.

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.

Assessing incidence and economic burden of genital warts with data from a US commercially insured population.

OBJECTIVE: This study examined the incidence of and healthcare costs attributable to genital warts within a large US commercially insured, geographically dispersed population. RESEARCH DESIGN AND METHODS: Using a retrospective cohort study design, this longitudinal analysis assessed administrative claims of integrated medical and pharmacy encounters from five Blue Cross Blue Shield health plans. Genital warts cases were identified using a methodology previously described by Insinga et al. MAIN OUTCOME MEASURES: Age- and gender-specific incidence of genital warts per 1000 person-years in 2004, and duration-of-episode attributable direct medical costs (2004 US dollars) and healthcare resource utilization of cases diagnosed in 2002. Overall outcome measures were age- and gender-adjusted to the 2004 US civilian population. RESULTS: Genital warts incidence in 2004 was 1.2/1000 females and 1.1/1000 males. Incidence was highest among females aged 20-24 (4.6/1000) and males aged 25-29 (2.7/1000). Projected overall incidence was over 340,000 cases in 2004. Mean duration-of-episode per incident case in 2002 was 95.4 days (males 116.3 days; females 69.7 days). Mean ambulatory visits per episode were 1.5 for females and 1.9 for males, with <1 drug prescription/episode. Mean costs were $647/episode ($745 males; $528 females). The 2004 estimated economic burden was $760 per 1000 individuals in the general population with the total exceeding $220 million. LIMITATIONS: Only those genital warts cases that sought evaluation or for which the treating provider was covered by the health plan were captured in the study. CONCLUSIONS: Genital warts represent a significant health and cost burden in the US. Adoption of novel healthcare technologies such as vaccines along with traditional interventions such as physician education of signs and symptoms, condom use and abstinence or limiting number of sexual partners may significantly help reduce the burden of genital warts.