Knowledge, attitude, and practice toward herpes zoster (HZ) and HZ vaccination: Concept elicitation findings from a multi-country study in the Asia Pacific.

Herpes zoster (HZ) is a prevalent disease characterized by a painful rash. A multi­country study was conducted to elicit public and physician knowledge, attitude, and practice (KAP) toward HZ disease and vaccination for the assessment of local factors influencing HZ vaccine perceptions in four Asian-Pacific countries/territories One-to-one qualitative interviews were conducted in 2022, among the public (people aged ≥ 50 years, adults with parents aged ≥ 50 years, zoster vaccine live-vaccinated individuals aged ≥ 50 years in Republic of Korea, and HZ patients; n = 78) and physicians (general practitioners and specialists; n = 24). Themes surrounding KAP toward HZ and HZ vaccination were summarized using a thematic analysis. A substantial knowledge gap related to HZ was observed among the public, including its causes, long-term impacts, and the at-risk population. There was a low perceived risk of HZ and low general awareness of HZ vaccine availability, although country/territory-specific differences existed. Fear of HZ-associated pain contributed toward vaccination intent among HZ patients and adults with parents aged ≥ 50 years. HZ-naïve adults who were encouraged to receive the vaccine by others were not motivated to do so due to optimism bias. Physicians were perceived to be a reliable source of information. However, physicians did not always proactively discuss HZ vaccination due to time constraints and a perceived need to prioritize other vaccinations including influenza and pneumococcal vaccines. Initiatives are needed to improve public awareness of HZ and its complications, in terms of overall impact on individuals and society, and highlight the important role of physicians in recommending vaccination.

Population-Based Study of Pertussis Incidence and Risk Factors among Persons >50 Years of Age, Australia.

Despite vaccination programs, pertussis has been poorly controlled, especially among older adults in Australia. This longitudinal, retrospective, observational study aimed to estimate the incidence and risk factors of pertussis among persons ≥50 years of age in Australia in the primary care setting, including those with underlying chronic obstructive pulmonary disease (COPD) or asthma. We used the IQVIA general practitioner electronic medical record database to identify patients ≥50 years of age with a clinical diagnosis of pertussis during 2015-2019. Pertussis incidence rates ranged from 57.6 to 91.4 per 100,000 persons and were higher among women and highest in those 50-64 years of age. Patients with COPD or asthma had higher incidence rates and an increased risk for pertussis compared with the overall population ≥50 years of age. Our findings suggest that persons ≥50 years of age in Australia with COPD or asthma have a higher incidence of and risk for pertussis diagnosis.

Burden of Herpes Zoster in Individuals with Immunocompromised Conditions and Autoimmune Diseases in the Republic of Korea: A Nationwide Population-Based Database Study.

INTRODUCTION: To estimate herpes zoster (HZ) incidence rate (IR) and economic burden in individuals with immunocompromised conditions and autoimmune diseases (IC/AID) in the Republic of Korea (ROK). METHODS: The nationwide Health Insurance Review and Assessment Service database was used to identify HZ cases from 2016 to 2020 in ROK. HZ and non-HZ IC/AID cases were matched 1:3 using age, sex, institution, Charlson comorbidity index, IC/AID, and index date. Annual HZ IRs/1000 persons and 1-year HZ-associated all-cause direct medical costs for IC/AID cases were calculated. RESULTS: Among 65,976 individuals with IC/AID (mean age 57.14 years [standard deviation 14.1]; 64.94% female), annual HZ IR (95% confidence interval) fluctuated from 2016 to 2020, averaging 23.41/1000 persons (22.21-24.62) and was higher in women (26.85 [25.40-28.31]) than men (18.96 [18.03-19.89]). IRs were highest in individuals aged ≥ 50 years, and in those with transplants (including solid organ and hematopoietic stem cell transplants; 37.12 [35.45-38.79]) and hemato-oncology conditions (35.5 [31.6-39.3]). Mean 12-month all-cause direct medical costs were higher in individuals with IC/AID and HZ (4,759,671 Korean Republic won [KRW]; approximately 4046 United States dollar [USD; according to the 2020 conversion rate from UNCTAD; 1 KRW = 0.00085 USD]) than those without HZ (3,786,658 KRW; 3219 USD). CONCLUSION: Individuals with IC/AID have a substantial disease and economic burden from HZ in ROK, highlighting the need for appropriate HZ prevention measures in the IC/AID population.

Incidence and Healthcare Burden of Pertussis among Older Adults with and without Pre-Existing Chronic Obstructive Pulmonary Disease or Asthma in South Korea.

A retrospective cohort study was conducted to examine trends in the incidence and burden of pertussis among adults ≥50 years in South Korea, with/without pre-existing chronic obstructive pulmonary disease (COPD) or asthma. The nationwide Health Insurance Review and Assessment Service (HIRA) database was used to identify patients ≥50 years diagnosed with pertussis (2009-2018). Mean annual incidence of pertussis per 100 000 persons and overall mean incidence rate ratios (IRR) were calculated for patients with pre-existing COPD or asthma versus those with neither. Incremental healthcare costs (all-cause and pertussis-related) and healthcare utilisation (number of outpatient visits, emergency room visits, and number and length of hospitalisations) up to 12 months after, compared to 3 months before pertussis diagnosis, were also measured for each group (matched on sex, age, and Charlson Comorbidity Index). Of 1011 pertussis cases, 175 had asthma, 96 had COPD (not mutually exclusive), and 796 had neither. Overall mean pertussis incidence was 2.5, 3.4, and 0.5 for adults with pre-existing COPD, asthma, and those with neither. IRR (95% confidence interval) of pertussis for adults with pre-existing COPD and asthma was 4.9 (4.0-|6.1) and 6.7 (5.7-7.9). Both COPD-pertussis and asthma-pertussis groups had higher mean incremental all-cause costs and length of hospitalisations than the general-pertussis group 3 months following pertussis diagnosis. In conclusion, individuals ≥50 years in South Korea with pre-existing COPD or asthma were at an increased risk of being diagnosed with pertussis and had higher healthcare resource utilisation than those without these conditions.

Risk Factors of Pertussis Among Older Adults in South Korea: A Nationwide Health Data-Based Case-Control Study.

INTRODUCTION: To better understand the conditions associated with pertussis diagnosis among older adults in South Korea, a matched case-control study was conducted of individuals ≥ 50 years diagnosed with pertussis between 2009 and 2018. METHODS: Pertussis cases were identified using the nationwide Health Insurance Review and Assessment service (HIRA) database. Each case was then matched to up to 10 controls identified using the National Health Insurance Service-National Sample Cohort (NHIS-NSC) by age, sex, and geographic region at index date. In the 12 months and 30 days prior to index date, the presence of clinical characteristics previously reported to be related to pertussis and pertussis-like conditions were assessed, respectively. A conditional multivariate logistic regression model was then used to calculate odds ratios (ORs) of pertussis diagnosis, adjusted for each of the characteristics. RESULTS: Pertussis cases (n = 1004) generally demonstrated a higher prevalence of comorbidities compared to controls (n = 9710). Pre-existing asthma and chronic obstructive pulmonary disease (COPD) within 12 months of index date were associated with a two-fold increased risk of pertussis with adjusted ORs (95% confidence interval) of 2.08 (1.68-2.58) and 2.32 (1.59-3.39), respectively. Gastroesophageal reflux disease [GERD; 2.67 (2.23-3.19)], cancer [1.68 (1.23-2.31)], cardiovascular disease [1.62 (1.31-2.00)], renal disease [1.56 (1.12-2.16)], autoimmune disease [1.50 (1.25-1.79)], and hyperlipidemia [1.43 (1.16-1.77)] were also associated with pertussis diagnosis. Finally, acute respiratory events within 30 days prior to index date, such as pneumonia, acute bronchitis, and upper respiratory tract infection (URTI), were highly associated with increased odds of pertussis diagnosis [adjusted ORs of 8.28 (5.10-13.44), 4.86 (3.84-6.14), and 2.90 (2.30-3.67), respectively]. CONCLUSIONS: This study's findings complement and expand upon previous studies on the adult pertussis population, generating real-world data to describe underlying clinical characteristics of those diagnosed with pertussis in South Korea.

Development of a real-world database for asthma and COPD: The SingHealth-Duke-NUS-GSK COPD and Asthma Real-World Evidence (SDG-CARE) collaboration.

PURPOSE: The SingHealth-Duke-GlaxoSmithKline COPD and Asthma Real-world Evidence (SDG-CARE) collaboration was formed to accelerate the use of Singaporean real-world evidence in research and clinical care. A centerpiece of the collaboration was to develop a near real-time database from clinical and operational data sources to inform healthcare decision making and research studies on asthma and chronic obstructive pulmonary disease (COPD). METHODS: Our multidisciplinary team, including clinicians, epidemiologists, data scientists, medical informaticians and IT engineers, adopted the hybrid waterfall-agile project management methodology to develop the SingHealth COPD and Asthma Data Mart (SCDM). The SCDM was developed within the organizational data warehouse. It pulls and maps data from various information systems using extract, transform and load (ETL) pipelines. Robust user testing and data verification was also performed to ensure that the business requirements were met and that the ETL pipelines were valid. RESULTS: The SCDM includes 199 data elements relevant to asthma and COPD. Data verification was performed and found the SCDM to be reliable. As of December 31, 2019, the SCDM contained 36,407 unique patients with asthma and COPD across the spectrum from primary to tertiary care in our healthcare system. The database updates weekly to add new data of existing patients and to include new patients who fulfil the inclusion criteria. CONCLUSIONS: The SCDM was systematically developed and tested to support the use RWD for clinical and health services research in asthma and COPD. This can serve as a platform to provide research and operational insights to improve the care delivered to our patients.

Epidemiological, clinical and economic burden of severe eosinophilic asthma in Taiwan: Results from a large tertiary care hospital.

BACKGROUND: Burden of severe eosinophilic asthma (SEA) data in Asia are limited. OBJECTIVE: This retrospective, observational study characterized SEA epidemiology, healthcare resource use (HCRU) and costs for adult patients in Taiwan. METHODS: Data from Taichung Veterans General Hospital electronic medical record database, between 2013 to 2016, were extracted. Eligible general asthma patients were ≥ 18 years at index date, with ≥ 1 medical claim with an asthma diagnosis after the index date. Patients with SEA (meeting additional criteria: Global Initiative for Asthma Step 4/5 treatment guidelines [within 3 months preceding index date], ≥ 2 clinically significant exacerbations, and eosinophil counts ≥ 300 cells/µL [within 12 months preceding index date] or ≥ 150 cells/µL [on index date]) and SEA patients using high-dose inhaled corticosteroids (HD ICS) were also identified. Twelve months' pre-index data were used to evaluate exacerbation frequency, treatment patterns, HCRU, and costs (2016 US Dollars). RESULTS: Of 2,601 eligible general asthmatic patients, 162 (6.2%) met predefined criteria for SEA; of SEA patients, 72/162 (44.4%) had used HD ICS. SEA and HD ICS SEA patients experienced more clinically significant exacerbations than general asthma patients (1.6 ± 3.3 and 1.5 ± 2.6 vs 0.6 ± 2.0, p < 0.01). HD ICS SEA and SEA patients incurred at least 2-2.5-fold higher total asthma-related and all-cause costs than general asthma patients and had significantly greater HCRU. CONCLUSIONS: Of eligible Taiwanese general asthma patients, 6.2% met predefined SEA criteria. Compared with general asthma patients, SEA and HD ICS SEA patients used more respiratory medications, experienced more exacerbations, and incurred greater HCRU and higher costs.

Long-Term Effectiveness and Safety of Dutasteride versus Finasteride in Patients with Male Androgenic Alopecia in South Korea: A Multicentre Chart Review Study.

BACKGROUND: Dutasteride improves hair growth compared with finasteride in male androgenic alopecia (AGA) and is well tolerated. However, real-world evidence for long-term dutasteride use in AGA is lacking. OBJECTIVE: To describe baseline characteristics, treatment patterns and long-term safety and effectiveness of dutasteride versus finasteride. METHODS: This was a multicentre, retrospective medical chart review study conducted in South Korea. The index date was the first prescription of dutasteride or finasteride. Baseline characteristics were assessed 6 months prior to index. Safety and effectiveness (improvements in basic and specific [BASP] classification) data were collected from index throughout the observation period. RESULTS: Overall, 600 male adult patients were included (dutasteride, n=295; finasteride, n=305). Dutasteride-treated patients were older (p<0.001) and more likely to have moderate/severe BASP classification at baseline (p=0.010) compared with finasteride-treated patients. Among patients treated with recommended, on-label dosing exclusively (n=535: dutasteride, n=250; finasteride, n=285), dutasteride-treated patients showed greater improvement in hair growth than finasteride-treated patients, as measured by the BASP basic M classification (adjusted incidence rate ratio [95% confidence interval]: 2.06 [1.08, 3.95]; p=0.029). Among this same subset, overall occurrence of adverse events (AEs) during the observation period were not statistically equivalent between groups (dutasteride 7.6%, finasteride 10.5%; p=0.201), although reports of AEs of special interest were equivalent (p<0.001). CONCLUSION: Dutasteride showed greater effectiveness than finasteride in improving BASP classification in treating male AGA and had a similar or possibly lower occurrence of overall AEs. Dutasteride may provide an effective and safe treatment option for male patients with AGA.

Treatment patterns and cost of exacerbations in patients with chronic obstructive pulmonary disease using multiple inhaler triple therapy in South Korea.

BACKGROUND: Multiple inhaler triple therapy (MITT), comprising inhaled corticosteroids (ICS), long-acting beta-agonists (LABA), and long-acting muscarinic antagonists (LAMA), has been used as an escalation treatment for patients with chronic obstructive pulmonary disease (COPD). However, real-world use of MITT has not been investigated in Asia, including South Korea. This study reports baseline characteristics of patients with COPD initiated on MITT in South Korea, and their treatment patterns. Healthcare resource utilization (HRU) and costs associated with COPD exacerbations following MITT initiation were also assessed. METHODS: This was a retrospective cohort study using the South Korea National Health Insurance database (2014-2018). Included patients were ≥ 40 years, had a COPD diagnosis, were newly initiated on MITT and had ≥ 12 months' data both before (baseline) and after index date (the first day with overlapping supply of all MITT components). Treatment immediately before initiation and immediately following discontinuation of MITT were identified, and proportion of days covered (PDC) by MITT was calculated. HRU and costs (per person per year [PPPY]) associated with exacerbations were identified following MITT initiation; costs were calculated using the average 2020 exchange rate (0.0008 USD/KRW). RESULTS: Among 37,400 patients, the mean age was 69 (SD 10) years and 73% were males; 56% had ≥ 1 COPD exacerbation during the baseline period, with a mean of 2 (SD 5) events/year. ICS/LABA was the most frequent regimen prescribed immediately before initiation (37%) and immediately following discontinuation (41% of 34,264 patients) of MITT. At 3, 6, and 12 months from treatment initiation, mean PDC was 81%, 63% and 49%, respectively; median treatment duration was 102 days. The mean (95% confidence interval [CI]) number of total visits for severe COPD exacerbations was 0.77 PPPY (0.75-0.78); mean PPPY total healthcare costs were 2093 USD. CONCLUSIONS: Patients with COPD in South Korea experienced frequent exacerbations prior to MITT, and PDC by MITT was low. Patients may benefit from early optimization of COPD therapy, and greater emphasis on adherence to inhaled COPD therapy. Severe exacerbations were found to incur substantial costs; treatment alternatives that can reduce the rate of severe exacerbations are likely to minimize healthcare costs.

Real-world Treatment Patterns, Outcomes, and Healthcare Resource Utilization in Newly Treated Korean Patients With Asthma: A Retrospective Cohort Study.

PURPOSE: Although asthma treatment guidelines recommend regular inhaled medication, real-world treatment patterns and outcomes in South Korea have not been examined. We examined real-world treatment patterns and outcomes among patients treated for asthma in South Korea. METHODS: This retrospective cohort study utilized data from the South Korean National Health Insurance database (2013-2016). Newly treated patients with asthma aged ≥18 years without history of chronic obstructive pulmonary disease were included. Initial and maintenance medication prescriptions were examined. Treatment discontinuation and switch were described. Asthma exacerbation rates, poor asthma control, and healthcare resource utilization (HRU) were compared between maintenance treatment groups (inhaled versus oral) using adjusted incidence rate ratios (aIRR) and hazard ratios (aHR). RESULTS: Overall, 1,054,707 patients initiated any asthma medication; 37,868 patients initiated inhaled (n = 9,983, 26.4%) or oral (n = 27,885, 73.6%) maintenance medication. More patients initiating inhaled versus oral asthma medication discontinued treatment within 12 months (94.4% vs. 86.3%; P < 0.0001). Patients treated with inhaled and oral medication switched treatment (2.5% and 2.3%; P = 0.4160, respectively). Patients initiating inhaled medication had significantly lower rates of asthma exacerbation (aIRR, 0.52; 95% CI, 0.39-0.69), lack of asthma control (aHR, 0.55; 95% CI, 0.48-0.62; P < 0.0001), all-cause and asthma-related HRU versus oral medication. CONCLUSIONS: Despite current asthma guidelines, more patients in South Korea were prescribed oral than inhaled medications, resulting in suboptimal asthma management and increased HRU. This study highlights the need to reduce oral corticosteroid prescriptions for optimized treatment in asthma management.

Burden of illness in blood eosinophilic phenotype COPD patients in New Zealand.

BACKGROUND: Real-world data on eosinophilic chronic obstructive pulmonary disease (COPD)'s clinical burden, in exacerbating/stable states, and the stability of blood eosinophil count (BEC) measurements are limited. We described measured BEC distributions among general practice COPD patients in New Zealand (NZ). METHODS: This retrospective cohort study utilized the NZ-HealthStat primary care database. Participants were aged ≥40 years, with ≥1 BEC 6 months following a COPD diagnosis code during 2011-2012. Descriptive analyses included examinations of BEC stability and association with COPD exacerbations/treatments/comorbidities. RESULTS: The most frequent COPD comorbidity was asthma (n = 1180/2909, 40.56%). Among COPD patients: 65% had BECs >150 cells/µL; 35% had BECs >300 cells/µL (non-mutually exclusive threshold categories). Treatment patterns were similar, except for more frequent inhaled corticosteroid (ICS)/long-acting beta2-agonist use in COPD patients with asthma history (51%) than those without (31%). Factors associated with BECs >150 cells/µL in participants without ICS treatment included Maori/Pacific ethnicity, obesity, oral corticosteroid (OCS) use, and exacerbation history. When stratified by asthma history, ICS treatment, and neutrophil count above/below 5000 cells/µL, geometric mean BECs ranged from 136.70 to 398.52 cells/µL. Exploratory analyses showed a fair-good COPD/BEC measurement stability over 12 months. CONCLUSIONS: Asthma was a common COPD comorbidity in NZ, particularly in Maori/Pacific patients. No overall relationship was observed between BEC/COPD exacerbations, which may reflect background ICS confounding. However, analyses in non-ICS treated participants suggested that Maori/Pacific patients with obesity and COPD, OCS treatment, exacerbation history, and/or elevated BECs are at the highest risk of COPD exacerbations. One BEC measurement appears a good indicator of a patient's BECs over time.

Long-Acting Bronchodilator Use in Chronic Obstructive Pulmonary Disease in Primary Care in New Zealand: A Retrospective Study of Treatment Patterns and Evolution Using the HealthStat Database.

PURPOSE: Long-acting bronchodilator (LABD) use is the mainstay of pharmacologic treatment for chronic obstructive pulmonary disease (COPD). Few studies describe evolving patterns of LABD use in the setting of changing inhaler availability and updated clinical guidelines. METHODS: A retrospective cohort study in New Zealand using the HealthStat general practice database (01/2014 to 04/2018). Eligible patients (aged ≥40 years) had COPD and ≥1 LABD prescription (long-acting muscarinic antagonist [LAMA] and/or long-acting ß2-agonist [LABA]) during the index period (05/2015 to 04/2016). Demographics and clinical characteristics of all LABD users (overall/by treatment) were described at baseline. Patients starting LABD treatment during the index period, termed "new" users, were also described, as was their treatment evolution over 24 months of follow-up. Yearly LABD initiation rates were assessed from 2015 to 2017, covering changes to Pharmaceutical Management Agency criteria and clinical guidelines. RESULTS: Across 2140 eligible patients, the most common index treatments were inhaled corticosteroid (ICS)/LABA (59.0%) and open triple therapy (LAMA+LABA+ICS; 26.7%). ICS/LABA therapy was highest in younger patients, with open triple therapy highest in older patients. Prior yearly exacerbation rates were lowest in those receiving monotherapy (LABA: 0.9/year; LAMA: 1.1/year) versus dual therapy (all 1.4/year) and open triple therapy (2.2/year). Of 312 new LABD users, ICS/LABA was the most common index treatment (69.6%), followed by LAMA monotherapy (16.0%). Continuous use with index treatment was 31.1% at 12 months and 13.5% at 24 months; mean time to treatment change was 175.5 and 244.1 days, respectively. Among patients modifying treatment at 24 months, 23.0% augmented, 7.0% switched, 45.6% re-started, and 24.4% discontinued/stepped down. Among patients initiating LABD each year from 2015 to 2017, LAMA prescription increased (17% to 46%) while ICS prescription remained stable (approximately 20%). CONCLUSION: Predominant use of ICS/LABA (05/2015 to 04/2016) reflects available LABDs and previous restrictions on LAMA use in New Zealand.

Characterization and burden of severe eosinophilic asthma in New Zealand: Results from the HealthStat Database.

BACKGROUND: This retrospective cohort study aimed to characterize epidemiology, medication use and healthcare resource utilization (HCRU) of patients diagnosed with severe eosinophilic asthma (SEA) compared to other patients with asthma in New Zealand. METHODS: Adult patients with asthma with no concurrent diagnosis of Chronic Obstructive Lung Disease (COPD) were identified from the HealthStat primary care database and the National Minimum Dataset using asthma diagnosis, hospital codes and prescriptions. Patients with SEA were identified using a 1-year baseline period (2011) and were those with: inhaled corticosteroid prescription above medium dose (including high dose) plus controller medication, ≥2 exacerbations, and eosinophils ≥300 cells/µl (or ≥150 in 6 weeks prior to index date); patients were followed for 1 year (2012). RESULTS: 160/3,276 (4.9%) asthmatics with available eosinophil counts met SEA criteria. Patients with SEA were more likely to be Maori, former smokers, have more comorbidities, higher mean BMI and higher neutrophil counts compared with other patients with asthma. In the follow up period, SEA patients had over 4 times as many exacerbations; incidence of exacerbations of the same frequency was highest in Maori patients. CONCLUSIONS: Compared with other patients with asthma, SEA patients had over 1.5 times as many respiratory treatment prescriptions and higher all-cause HCRU and total healthcare costs; asthma-related healthcare costs were 3.6 times greater.

Menopausal hormone therapy use and long-term all-cause and cause-specific mortality in the Long Island Breast Cancer Study Project.

Previous studies have observed a reduced mortality risk associated with menopausal hormone therapy (MHT) use among breast cancer survivors. We sought to clarify whether such association could be explained by tumor heterogeneity, specific causes of death, confounding from comorbidities or health behaviors, and a comparison group of women without breast cancer. We interviewed 1508 women newly diagnosed with first primary breast cancer in 1996 to 1997 (~3 months after diagnosis), and 1556 age-matched women without breast cancer, about MHT use history. The National Death Index was used to ascertain vital status after a median of 17.6 years of follow-up (N = 597 deaths for breast cancer subjects). Multivariable-adjusted Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (95%CIs) for all-cause mortality, and cause-specific HR (cHR) for breast cancer and cardiovascular disease (CVD). The Fine-Gray model was used to account for competing causes of death. Among women with breast cancer, ever vs never MHT use was inversely associated with all-cause (HR = 0.77, 95%CI = 0.62-0.95), breast cancer-specific (cHR = 0.69, 95%CI = 0.48-0.98), and CVD-specific mortality (cHR = 0.57, 95%CI = 0.38-0.85). Difference of the association was observed in breast cancer-specific mortality according to hormone receptor status (negative tumors: cHR = 0.44, 95%CI = 0.19-1.01; positive tumors: cHR = 0.96, 95%CI = 0.60-1.53). Among the comparison group, we observed similar, but more modest inverse associations for all-cause and CVD-specific mortality. MHT use was inversely associated with mortality after breast cancer, even after accounting for competing causes of death and multiple confounders, and was evident among women without breast cancer. Potential heterogeneity by hormone receptor status requires more study.

Reproductive characteristics are associated with gene-specific promoter methylation status in breast cancer.

BACKGROUND: Reproductive characteristics are well-established risk factors for breast cancer, but the underlying mechanisms are not fully resolved. We hypothesized that altered DNA methylation, measured in tumor tissue, could act in concert with reproductive factors to impact breast carcinogenesis. METHODS: Among a population-based sample of women newly diagnosed with first primary breast cancer, reproductive history was assessed using a life-course calendar approach in an interviewer-administered questionnaire. Methylation-specific polymerase chain reaction and Methyl Light assays were used to assess gene promotor methylation status (methylated vs. unmethylated) for 13 breast cancer-related genes in archived breast tumor tissue. We used case-case unconditional logistic regression to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for associations with age at menarche and parity (among 855 women), and age at first birth and lactation (among a subset of 736 parous women) in association with methylation status. RESULTS: Age at first birth > 27 years, compared with < 23 years, was associated with lower odds of methylation of CDH1 (OR = 0.44, 95% CI = 0.20-0.99) and TWIST1 (OR = 0.48, 95% CI = 0.28-0.82), and higher odds of methylation of BRCA1 (OR = 1.63, 95% CI = 1.14-2.35). Any vs. no lactation was associated with higher odds of methylation of the PGR gene promoter (OR = 1.59, 95% CI = 1.01-2.49). No associations were noted for parity and methylation in any of the genes assayed. CONCLUSIONS: Our findings indicate that age at first birth, lactation and, perhaps age at menarche, are associated with gene promoter methylation in breast cancer, and should be confirmed in larger studies with robust gene coverage.

A survey of management practices in coexistent allergic rhinitis and asthma (Asia-pacific Survey of Physicians on Asthma and allergic Rhinitis): results from Thailand.

BACKGROUND: Underdiagnosis and undertreatment of allergic rhinitis (AR) in patients with asthma can worsen treatment outcomes. There is limited evidence of clinical practices for management of coexistent AR-asthma in Thailand. METHODS: A multicountry, cross-sectional study (Asia-pacific Survey of Physicians on Asthma and allergic Rhinitis) to evaluate physician perceptions and management practices related to AR-asthma overlap in 6 Asian countries was conducted. For Thailand specifically, AR-asthma linkage questionnaires were developed and translated to Thailaland. General physicians (GPs) or pediatricians, randomly selected from hospitals in urban cities, routinely treating >10 asthma patients/month were interviewed. Here we present the results for Thailand. RESULTS: Two hundred physicians (100 GPs and 100 pediatricians), of whom 70% worked in government hospitals, were interviewed. In their experience, 50% of asthma patients had AR and 28% of AR patients had asthma. Among diagnosed asthma patients, 65% of physicians routinely asked for any AR symptoms at every visit. Among diagnosed AR patients, 63% of physicians routinely asked for any asthma symptoms at every visit. In patients with coexisting AR-asthma, 91% of physicians treated both diseases simultaneously, while 6% of physicians treated asthma as a chronic disease but managed AR symptomatically. The most preferred treatment options for patients with AR-asthma were inhaled corticosteroids with intranasal steroids (46% in GPs, 71% in pediatricians). CONCLUSION: The physicians interviewed in Thailand are aware about coexistent asthma-AR. There is a need to increase the awareness further for coexistent AR-asthma and to educate nonspecialist physicians in the proper management of AR-asthma patients.

Asia Pacific survey of physicians on asthma and allergic rhinitis (ASPAIR): data from China.

BACKGROUND: In China, the prevalence of allergic rhinitis (AR) and asthma has increased in the past decade. As these two diseases frequently coexist, the Asia-Pacific Survey of Physicians on Asthma and Allergic Rhinitis (ASPAIR) study aimed to assess physicians' beliefs and treatment patterns of coexistent asthma-AR across six Asian countries. This analysis presents the results from China. METHODS: The 200 hospital-based general physicians and pediatricians were interviewed from five cities in China. Physicians were questioned in-person about their knowledge, beliefs and management practices for patients with coexistent asthma-AR. RESULTS: Approximately 70% of the physicians interviewed routinely evaluated their patients with asthma or AR for signs of coexistent disease. While the majority of physicians (>90% of physicians) recognized the increased burden of coexistent asthma-AR vs. one condition alone and that coexistent disease requires additional treatment, most physicians (96%) also believed that patients with coexistent asthma-AR were well managed if either condition alone improved. Similarly, although 71% of physicians selected a combination of intranasal and inhaled corticosteroids as their preferred treatment for coexistent asthma-AR, in line with treatment guidelines, two fifths of physicians indicated that treatment for coexistent disease requires too much medication and that their patients prefer oral medications and a third of physicians believed that corticosteroids should be delayed in children. CONCLUSIONS: This survey demonstrates that physicians interviewed in China have a broad understanding of coexistent asthma-AR and its impact on patients. A holistic approach to patient management with informed decisions regarding patients' overall treatment will benefit patients who suffer from coexistent disease.

Reproductive characteristics modify the association between global DNA methylation and breast cancer risk in a population-based sample of women.

DNA methylation has been implicated in breast cancer aetiology, but little is known about whether reproductive history and DNA methylation interact to influence carcinogenesis. This study examined modification of the association between global DNA methylation and breast cancer risk by reproductive characteristics. A population-based case-control study assessed reproductive history in an interviewer-administered questionnaire. Global DNA methylation was measured from white blood cell DNA using luminometric methylation assay (LUMA) and pyrosequencing assay (long interspersed elements-1 (LINE-1). We estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) among 1 070 breast cancer cases and 1 110 population-based controls. Effect modification was assessed on additive and multiplicative scales. LUMA methylation was associated with elevated breast cancer risk across all strata (comparing the highest to the lowest quartile), but estimates were higher among women with age at menarche ≤12 years (OR = 2.87, 95%CI = 1.96-4.21) compared to >12 years (OR = 1.66, 95%CI = 1.20-2.29). We observed a 2-fold increase in the LUMA methylation-breast cancer association among women with age at first birth >23 years (OR = 2.62, 95%CI = 1.90-3.62) versus ≤23 years (OR = 1.32, 95% CI = 0.84-2.05). No modification was evident for parity or lactation. Age at menarche and age at first birth may be modifiers of the association between global DNA methylation and breast cancer risk.

Prescriber Compliance With Liver Monitoring Guidelines for Pazopanib in the Postapproval Setting: Results From a Distributed Research Network.

OBJECTIVES: Pazopanib received US Food and Drug Administration approval in 2009 for advanced renal cell carcinoma. During clinical development, liver chemistry abnormalities and adverse hepatic events were observed, leading to a boxed warning for hepatotoxicity and detailed label prescriber guidelines for liver monitoring. As part of postapproval regulatory commitments, a cohort study was conducted to assess prescriber compliance with liver monitoring guidelines. METHODS: Over a 4-year period, a distributed network approach was used across 3 databases: US Veterans Affairs Healthcare System, a US outpatient oncology community practice database, and the Dutch PHARMO Database Network. Measures of prescriber compliance were designed using the original pazopanib label guidelines for liver monitoring. RESULTS: Results from the VA (n = 288) and oncology databases (n = 283) indicate that prescriber liver chemistry monitoring was less than 100%: 73% to 74% compliance with baseline testing and 37% to 39% compliance with testing every 4 weeks. Compliance was highest near drug initiation and decreased over time. Among patients who should have had weekly testing, the compliance was 56% in both databases. The more serious elevations examined, including combinations of liver enzyme elevations meeting the laboratory definition of Hy's law were infrequent but always led to appropriate discontinuation of pazopanib. Only 4 patients were identified for analysis in the Dutch database; none had recorded baseline testing. CONCLUSIONS: In this population-based study, prescriber compliance was reasonable near pazopanib initiation but low during subsequent weeks of treatment. This study provides information from real-world community practice settings and offers feedback to regulators on the effectiveness of label monitoring guidelines.

Asia-Pacific Survey of Physicians on Asthma and Allergic Rhinitis (ASPAIR): physician beliefs and practices about diagnosis, assessment, and treatment of coexistent disease.

BACKGROUND: Asthma and allergic rhinitis (AR) frequently coexist, and having both asthma and AR is associated with uncontrolled asthma and a heavier disease burden. The Asia-Pacific Survey of Physicians on Asthma and Allergic Rhinitis (ASPAIR) aimed to assess physicians' perceptions and their management practices for patients with coexistent disease. MATERIALS AND METHODS: A total of 1,204 general physicians and pediatricians from six countries in Asia, who routinely treat asthma patients, were interviewed in-person. Physicians were questioned about their attitudes and beliefs of coexistent asthma-AR, how they diagnose and treat patients, and their knowledge of international guideline recommendations. RESULTS: Physicians reported that 45% of their patients with asthma have coexistent AR and 37% of their patients with AR have coexistent asthma. Most physicians (77%) agreed that coexistent asthma-AR is a genuine condition and that patients suffer worse symptoms with both the conditions vs one alone (86%). Although nearly all agreed that both asthma and AR should be treated (91%) and that intranasal (INS) and inhaled corticosteroids (ICS) could be given concurrently to these patients, 40% also thought that treating both conditions effectively at the same time is difficult, and approximately a quarter believed that corticosteroid therapy should be delayed in children for both asthma and AR. While there was universal recognition and acceptance that guidelines provide sufficient information for treating uncontrolled coexistent disease (≥80% physicians in all countries), physicians revealed that 41% of their asthma patients are treated with short-acting rescue medications alone, and only 47% responded that treatment with concurrent INS and ICS, as recommended in the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines, was their preferred treatment for coexistent disease. CONCLUSION: The ASPAIR survey demonstrates a widespread acceptance of coexistent asthma-AR, and the associated burden, but highlights the need for increased healthcare practitioner communication and awareness to improve appropriate treatment and management of these coexistent conditions.