Prevalence and impact of vasomotor symptoms due to menopause among women in Brazil, Canada, Mexico, and Nordic Europe: a cross-sectional survey.

OBJECTIVE: This study investigated the prevalence and impact of moderate to severe vasomotor symptoms (VMS), related treatment patterns, and experiences in women. METHODS: The primary objective was to assess the prevalence of moderate to severe menopause-related VMS among postmenopausal women aged 40 to 65 years in Brazil, Canada, Mexico, and four Nordic European countries (Denmark, Finland, Norway, and Sweden) using an online survey. Secondary objectives assessed impact of VMS among perimenopausal and postmenopausal women with moderate to severe VMS using the Menopause-Specific Quality of Life questionnaire, Work Productivity and Activity Impairment questionnaire, Patient-Reported Outcomes Measurement Information System sleep disturbances assessment, and questions regarding treatment patterns and attitudes toward symptoms and available treatments. RESULTS: Among 12,268 postmenopausal women, the prevalence of moderate to severe VMS was about 15.6% and was highest in Brazil (36.2%) and lowest in Nordic Europe (11.6%). Secondary analyses, conducted among 2,176 perimenopausal and postmenopausal women, showed that VMS affected quality of life across all domains measured and impaired work activities by as much as 30%. Greater symptom severity negatively affected sleep. Many women sought medical advice, but most (1,238 [56.9%]) were not receiving treatment for their VMS. The majority (>70%) considered menopause to be a natural part of aging. Those treated with prescription hormone therapy and nonhormone medications reported some safety/efficacy concerns. CONCLUSIONS: Among women from seven countries, moderate to severe menopause-related VMS were widespread, varied by region, and largely impaired quality of life, productivity, and/or sleep.

Incidence, prevalence, and treatment of anemia of non-dialysis-dependent chronic kidney disease: A retrospective database study in France.

BACKGROUND: Minimal data are available regarding the prevalence and incidence of anemia among patients with non-dialysis-dependent chronic kidney disease (NDD-CKD) in France. METHODS: This was a retrospective non-interventional study of patients with a record of NDD-CKD in the Echantillon Généraliste des Bénéficiaires (EGB) database between January 01, 2012, and December 31, 2017. The primary objective was to estimate the annual incidence and prevalence of anemia of NDD-CKD. Secondary objectives included description of the demographics and clinical characteristics of patients with NDD-CKD-related anemia. An exploratory objective was to use machine learning to identify patients from the general population that might have NDD-CKD but without a recorded ICD-10 diagnosis of CKD. RESULTS: During 2012-2017, 9865 adult patients in the EGB database had confirmed NDD-CKD; of these, 49.1% (4848/9865) had anemia. From 2015 to 2017, estimates of incidence (108.7-114.7 per 1000 population) and prevalence (435.7-449.5 per 1000 population) of NDD-CKD-related anemia were stable. Less than half of patients with anemia of NDD-CKD were treated with oral iron, and approximately 15% were treated with erythropoiesis-stimulating agents. Based on adult French population projections in 2020 and an estimated prevalence rate in 2017 of 42.2 per 1000 population for confirmed plus possible NDD-CKD (as a proportion of the general French population), the estimated number of patients with possible NDD-CKD in France was 2,256,274, approximately five-fold greater than the number identified by diagnostic codes and hospitalizations. CONCLUSIONS: Anemia of NDD-CKD was shown to be a constant long-term burden in France, and its apparent prevalence may still be significantly underestimated. Given the potential treatment gap, additional initiatives to better identify and treat NDD-CKD anemia may improve patient management and treatment outcomes.

Prevalence and quality-of-life burden of vasomotor symptoms associated with menopause: A European cross-sectional survey.

OBJECTIVES: To determine, in a European cohort, the prevalence and health-related quality-of-life (QOL) burden of moderate-to-severe vasomotor symptoms (VMS) in postmenopausal women, and among subgroups of women not taking hormone therapy (HT). STUDY DESIGN: Screening surveys were sent to a random sample of women aged 40-65 years; those meeting the inclusion criteria completed the full questionnaire. Women with successfully treated VMS or breast cancer or who were receiving HT for medical conditions were excluded. MAIN OUTCOME MEASURES: Frequency and duration of VMS, perceptions of menopause, seeking advice from a healthcare professional, treatment for VMS symptoms, perceptions of HT use, out-of-pocket costs, and other approaches to coping with menopause. The Menopause-Specific QOL (MENQOL) questionnaire and Work Productivity and Activity Impairment (WPAI) questionnaire were included. RESULTS: Of 11,452 women who completed the screening survey, 5178 were postmenopausal and 2035 completed the full questionnaire. Prevalence of moderate-to-severe VMS ranged from 31 % in France to 52 % in Italy. The majority were in the HT-caution or HT-averse group, despite being eligible for HT. Most common menopausal symptoms reported in the MENQOL were "feeling tired or worn out," with aching in muscles and joints reported as the most common symptom in Spain. Weight gain was the most bothersome symptom in all countries, except for Spain, where low backache was more bothersome. Hot flashes and night sweats had a greater impact on daily than on working activities, as measured by the WPAI. CONCLUSIONS: A high proportion of European women reported experiencing moderate-to-severe VMS, with associated symptoms influencing QOL.

Prevalence, incidence, and treatment of anaemia in patients with non-dialysis-dependent chronic kidney disease: findings from a retrospective real-world study in Italy.

BACKGROUND: Limited data are available on the epidemiology and clinical management of anaemia in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD). METHODS: This retrospective observational study was based on records from databases of five Local Health Units across Italy. Adults with reported NDD-CKD stage 3a-5 between 1 January 2014 and 31 December 2016 were identified. Annual prevalence and incidence of anaemia (age- and sex-standardised) and clinical management (erythropoiesis-stimulating agents [ESAs], intravenous [IV] iron, and blood transfusions) were evaluated. Eligibility for ESAs was defined by ≥ 2 records of Hb < 10 g/dL, or < 11 g/dL over 6 months. RESULTS: Overall, 101,143 individuals with NDD-CKD (3a-5) recorded between 2014 and 2016 were identified, of whom 40,020 (39.6%) were anaemic. Prevalence of anaemia was 33.8% in 2016 and incidence of anaemia was stable (11.4-12.4%) from 2014 to 2016. Prevalence and incidence of anaemia increased with CKD stage. Among eligible patients, 12.8% with Hb < 11 g/dL and 15.5% with Hb < 10 g/dL received ESAs, and the proportion treated increased with CKD stage. Among ESA-treated patients with at least 2 years of follow up, 18.4% and 19.3% received IV iron in the Hb < 11 and < 10 g/dL groups, respectively, and 16.5% and 19.4% received blood transfusions. Corresponding proportions for the overall anaemic cohort were 9.0% and 11.3%, respectively. CONCLUSIONS: Anaemia is a significant issue in patients with NDD-CKD. Low rates of ESA treatment indicate a potential treatment gap and suggest that anaemia may not be adequately controlled in many patients.

Epidemiology and treatment patterns of UK women diagnosed with vasomotor symptoms: Findings from the Clinical Practice Research Datalink GOLD database.

OBJECTIVES: To describe the epidemiology and treatment of vasomotor symptoms (VMS) in the UK. STUDY DESIGN: Retrospective study that used electronic medical records from UK primary care centers. MAIN OUTCOME MEASURES: The prevalence and incidence of moderate-to-severe VMS, the proportion treated, persistence with initial treatment, treatment patterns, and menopausal hormone therapy (HT) experience were investigated over the study period (Jan. 2009-Dec. 2018). The study population comprised women aged 40-65 years registered at general practitioner clinics. For incident cases, the uptake of pharmacological non-hormonal or hormonal treatment was recorded, which included experience of HT. RESULTS: Over the 10-year study period, 1,481,646 women were included from the database, among whom there were 313,031 prevalent and 90,434 incident cases of VMS. Annual prevalence and incidence rates were stable over time, with a weighted average of 21.1 % and 15.3 per 1000 person-years, respectively (results varied across age groups). Among women who were incident VMS cases, 32.4 % (29,275) were initially prescribed non-hormonal treatments for a median of 3.9 months, 49.4 % (44,700) were prescribed hormonal treatments for 4.0 months, and 18.2 % (16,459) had no treatment. Approximately one-third of treated women switched between non-hormonal and hormonal treatments. The HT experience results showed that 52.7 % (47,639) of women were HT-eligible, 13.1 % (11,872) were HT-contraindicated (they may or may not have received HT), and 34.2 % (30,923) did not receive HT. CONCLUSIONS: Variations in prescribed treatment patterns suggest that education may be needed for clinicians and women regarding the potential pharmacological options for treating VMS in the UK.

Systematic review of progressive familial intrahepatic cholestasis.

BACKGROUND AND AIMS: Progressive familial intrahepatic cholestasis (PFIC) is a heterogeneous group of rare genetic disorders associated with bile acid secretion or transport defects. This is the first systematic review of the epidemiology, natural history and burden of PFIC. METHODS: MEDLINE and Embase were searched for publications on PFIC prevalence, incidence or natural history, and the economic burden or health-related quality of life (HRQoL) of patients with PFIC. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. RESULTS: Of 1269 records screened, 20 were eligible (epidemiology, 17; humanistic burden, 5; both, 2). Incidence of intrahepatic cholestasis, including but not limited to PFIC, was 1/18 000 live births in one study that did not use genetic testing. In two studies of infants and children (2-18 years) with cholestasis, 12-13% had genetically diagnosed PFIC. Of the three main PFIC subtypes, PFIC2 was the most common (21-91% of patients). Common symptoms (e.g. pruritus, jaundice, hepatomegaly, splenomegaly) generally appeared at about 3 months of age and tended to emerge earliest in patients with PFIC2. Patients reported that pruritus was often severe and led to dermal damage and reduced HRQoL. Disease progression led to complications including liver failure and hepatocellular carcinoma, with 20-83% of patients requiring liver transplantation. Mortality was 0-87% across 10 studies (treatment varied among studies), with a median age at death of ~4 years in one study. CONCLUSIONS: Patients with PFIC face debilitating symptoms and poor prognosis. Further research is needed to inform patient management and clinical trial design. Published data on the epidemiology and socioeconomic burden of PFIC is limited.

Systematic Review: The Epidemiology, Natural History, and Burden of Alagille Syndrome.

BACKGROUND AND AIM: Alagille syndrome (ALGS) is an inherited multisystem disorder typically manifesting as cholestasis, and potentially leading to end-stage liver disease and death. The aim of the study was to perform the first systematic review of the epidemiology, natural history, and burden of ALGS with a focus on the liver component. METHODS: Electronic databases and proceedings from key congresses were searched in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2009 guidelines. This analysis included publications reporting epidemiology, natural history, economic burden or health-related quality of life (HRQoL) outcomes in patients with ALGS. RESULTS: Of 525 screened publications, 20 met the inclusion criteria. Liver-related features included cholestasis (87%-100% of patients), jaundice (66%-85%), and cirrhosis (44%-95%). Between 15% and 47% of patients underwent liver transplantation and 4% to 14% received partial biliary diversion. Pruritus affected the majority of patients (59%-88%, of whom up to 45% had severe pruritus) and manifested during the first 10 years of life. Children with ALGS had significantly impaired HRQoL compared with healthy controls and those with other diseases. Itching was the symptom that most affected children with ALGS. No study assessed the economic burden of ALGS. CONCLUSIONS: Our findings consolidate information on the clinical course of ALGS, and highlight gaps in knowledge, most notably the absence of any research on the economic consequences of the disease. Further research is needed to establish the incidence of genetically confirmed ALGS. Disease-specific tools are also needed to improve the measurement of symptoms, such as itching, and better understand the impact of ALGS on HRQoL.

Health-Related Quality of Life and Costs Associated With Eosinophilic Esophagitis: A Systematic Review.

BACKGROUND & AIMS: Eosinophilic esophagitis (EoE) is a chronic immune-mediated disease characterized by esophageal inflammation and dysfunction. Little is known about the humanistic and economic burden of the disease on patients, their caregivers, and the health care system. A systematic review was conducted to evaluate the existing literature on the disease burden of EoE for patients and their caregivers. METHODS: The MEDLINE, Embase, and Evidence-Based Medicine Reviews databases and recent congresses were searched on March 23, 2017, for English-language publications describing the impact of EoE on health-related quality of life (HRQoL) in children and adults, and the economic burden associated with the disease. RESULTS: Of 676 articles identified, 22 met the inclusion criteria and were included in this analysis (HRQoL, 13; economic burden, 7; cost effectiveness, 2). The included studies showed that EoE is associated with a significant impact on HRQoL, resulting in disruption to and restrictions on daily life for patients, their caregivers, and, in some instances, their families. Treatment with topical corticosteroids, the 6-food elimination diet, or the cow's milk elimination diet significantly improved the HRQoL of patients with EoE. Symptom severity was associated strongly with the impact of EoE on HRQoL. Medical resource utilization costs for patients with EoE were significantly higher than those for healthy controls. CONCLUSIONS: EoE negatively impacts the HRQoL of patients and their families, and is a burden to the health care system. Although data are sparse, currently available treatments appear to improve HRQoL.

Development of a Novel Tool to Assess the Impact of Itching in Pediatric Cholestasis.

OBJECTIVES: The aim was to develop a clinical outcome assessment (COA) for itching in children with cholestatic pruritus. METHODS: This prospective study aimed to enroll patients aged 4-30 years with Alagille syndrome (ALGS) or progressive familial intrahepatic cholestasis type 1 and caregivers of patients aged 5 months to 14 years. Eligible patients experienced itching during ≥3 of the 7 days before enrollment and had not undergone liver transplant or surgical interruption of the enterohepatic circulation. Open-ended qualitative interviews confirmed that itching was a primary concern for patients and caregivers. Diaries were modified and then evaluated by participants during cognitive debriefing. Interview results were reviewed by clinical, COA and statistical experts. Diary questions were revised following an interim analysis before finalizing the Itch Reported Outcome (ItchRO). RESULTS: Thirty-six interviews were analyzed, representing 25 families of patients with ALGS. Itching was reported spontaneously (without prompting by the interviewer) by ten of 12 patients with ALGS and 19 of 20 caregivers. Consequences of itching included skin damage (78%), mood changes (59%), and difficulties staying asleep (59%) or falling asleep (53%). Two versions of the ItchRO were developed: ItchRO(Patient) for self-completion by patients and ItchRO(Observer) for caregivers. The ItchRO diaries comprise a single scorable item to assess itch and are to be completed twice daily (morning and evening). CONCLUSIONS: Itching was the most bothersome ALGS symptom reported by study participants. We have developed the ItchRO(Patient) and ItchRO(Observer) to assess itching in children with ALGS and other cholestatic liver diseases. These diaries are being validated for use in clinical trials.

Researching health-related quality of life at a community level: results from a population survey conducted in Burgas, Bulgaria.

Researching health-related quality of life (HrQoL) at a community health promotion level is an approach to understand the health inequalities. The objective of this study is to measure the health of a representative sample by conducting a population survey in Burgas by using the EuroQoL EQ-5D-3L questionnaire, and further to assess the influence of socio-economic, demographic and behavioural factors on HrQoL. The relationship between HrQoL and social capital is analysed through a network-based approach. The achieved ambition was to build the public health capacity of the key stakeholders in order to support decision making. A cross-sectional study was conducted in 2011 using a representative sample of the citizens of Burgas (n = 1050, >18 years old). Respondents were selected through the method of two-stage random selection. HrQoL was assessed by the standardized EQ-5D-3L questionnaire. People without any problem in all five dimensions represent only 26.5% (n = 278) of the respondents, whereas 52.2% (n = 548) reported a moderate problem in at least one dimension; any extreme problem reported 11.6% (n = 122) of the respondents. The mean state of health recorded on the Visual Analogue Scale was 70 (SD ±23). There were differences in self-reported health based on the respondent's age, occupation, education, income, smoking behaviour and membership in community groups. People who have hobby and practice sports assessed their health status higher. The results were communicated in a following Delphi-study; a consensus has been reached that the combination of routine measures of health with measurement of self-rated health could provide better understandings of the community health needs.

Efficacy of liraglutide in a real-life cohort.

INTRODUCTION: In the Liraglutide Effect and Action in Diabetes (LEAD) randomized clinical trials (RCTs) assessing liraglutide in type 2 diabetes mellitus (T2DM), glycated hemoglobin (A1c) was reduced by 7-16 mmol/mol and weight by up to 3.4 kg. As real-life efficacy data on liraglutide is limited, the authors assessed clinical effects in a real-life cohort. METHODS: In this retrospective analysis from the Israeli Health Maintenance Organization Maccabi, of patients with T2DM, treated with liraglutide ≥6 months during 2011-2012, evaluations were performed at baseline and 6 months. RESULTS: Insulin-naïve patients (n = 1,101) treated with liraglutide with at least one A1c or weight measurement were identified. In 933 patients with an additional A1c value after 6 months, A1c decreased by 9 mmol/mol (p < 0.0001, 95% CI 7-11) from 72 mmol/mol. In patients receiving >2 oral antidiabetic drugs (OADs) prior to liraglutide treatment (80.7% patients), A1c decreased by 7 mmol/mol, and in those receiving ≤2 OADs, by 12 mmol/mol. In 453 patients with baseline data available, weight decreased by 2.55 kg (p < 0.0001); 173 patients (38.18%) achieved ≥1% A1c reduction. Furthermore, 91 patients (20.1%) achieved National Institute for Health and Care Excellence (NICE) criteria (decreased A1c ≥1%; weight ≥3%). Weight reduction was marginally correlated with A1c reduction. CONCLUSIONS: Evidence from real-life use of liraglutide demonstrated clinical effects similar to those demonstrated in RCTs.

Mapping of health technology assessment in selected countries.

OBJECTIVES: The aim of this study was to develop and apply an instrument to map the level of health technology assessment (HTA) development at country level in selected countries. We examined middle-income countries (Argentina, Brazil, India, Indonesia, Malaysia, Mexico, and Russia) and countries well-known for their comprehensive HTA programs (Australia, Canada, and United Kingdom). METHODS: A review of relevant key documents regarding the HTA process was performed to develop the instrument which was then reviewed by selected HTAi members and revised. We identified and collected relevant information to map the level of HTA in the selected countries. This was supplemented by information from a structured survey among HTA experts in the selected countries (response rate: 65/385). RESULTS: Mapping of HTA in a country can be done by focusing on the level of institutionalization and the HTA process (identification, priority setting, assessment, appraisal, reporting, dissemination, and implementation in policy and practice). Although HTA is most advanced in industrialized countries, there is a growing community in middle-income countries that uses HTA. For example, Brazil is rapidly developing effective HTA programs. India and Russia are at the very beginning of introducing HTA. The other middle-income countries show intermediate levels of HTA development compared with the reference countries. CONCLUSIONS: This study presents a set of indicators for documenting the current level and trends in HTA at country level. The findings can be used as a baseline measurement for future monitoring and evaluation. This will allow a variety of stakeholders to assess the development of HTA in their country, help inform strategies, and justify expenditure for HTA.

Budget impact analysis of ixabepilone used according to FDA approved labeling in treatment-resistant metastatic breast cancer.

BACKGROUND: Breast cancer is one of the most common forms of cancer in the United States, with approximately 10% of newly diagnosed patients presenting with metastatic disease. Limited therapy options make the successful treatment of metastatic breast cancer (MBC) difficult. Current treatment options include drugs belonging to the classes of anthracyclines and taxanes as well as the drug capecitabine. Resistance to these classes of drugs is often acquired, thus highlighting the need for newer agents capable of managing treatment resistant disease. Ixabepilone is an antineoplastic agent from the epothilone class that was FDA-approved in October 2007 for the treatment of metastatic or locally advanced breast cancer. The FDA-approved indications for ixabepilone specify (a) use of ixabepilone in combination with capecitabine for the treatment of patients with metastatic or locally advanced breast cancer after (resistance to) treatment with an anthracycline and a taxane, or whose cancer is taxane resistant and for whom further anthracycline therapy is contraindicated; and (b) ixabepilone as a monotherapy for the treatment of metastatic or locally advanced breast cancer in patients whose tumors are resistant or refractory to an anthracycline, a taxane, and capecitabine. OBJECTIVES: To estimate the 3-year projected impact on the annual pharmacy budget for a hypothetical 1 million-member commercial plan that introduces and reimburses ixabepilone therapy for its FDA-approved indications: either as a monotherapy for patients pretreated with combined anthracyclines, taxanes, and capecitabine (ATC-p) or in combination with capecitabine for patients pretreated with anthracyclines and taxanes (AT-p). METHODS: U.S. prevalence and treatment data for MBC patients were obtained from published and nonpublished sources. The MBC population was stratified into AT-p and ATC-p populations. These 2 groups comprised the assumed study population. The model considered 2 scenarios-without (pre) and with (post) ixabepilone, either as monotherapy for ATC-p or combination therapy with capecitabine for AT-p patients. Market share data for chemotherapeutic treatment options for MBC pre-ixabepilone and in the first year post-ixabepilone were obtained from nonpublished, proprietary, real-world drug utilization data collected by IntrinsiQ LLC (Waltham, MA), for 2007 and 2008, respectively. Market shares for the second and third years post-ixabepilone were forecasted by the study authors based on IntrinsiQ data collected from January 2008 to January 2009 and the observed switching patterns in the 2007 and 2008 IntrinsiQ data. Drug costs were based on First DataBank Inc. Wholesale Acquisition Cost (accessed March 2009). The results for each indication were analyzed individually and summed to reflect the total impact of ixabepilone. Results were also considered on a per member per month (PMPM) basis to examine the relative impact on the plan. Sensitivity of the results to model assumptions was tested using univariate sensitivity analyses on the prevalence of AT-p and ATC-p, the price of ixabepilone, the price of comparator medications, and the ixabepilone market uptake. A key assumption was that ixabepilone would be used only in accordance with its current labeled indications. RESULTS: In a health plan population of 1 million members, the estimated number of female patients aged 20 years or older with recurrent MBC and previous treatment with either AT or ATC was 15 over the 3-year time horizon used in this budget impact model. For AT-p patients, the estimated incremental cost PMPM was $0.002 for each of the 3 years. The estimated incremental cost PMPM for the ATC-p population was $0.003 for year 1 and $0.004 for both year 2 and year 3. In sensitivity analyses, the PMPM impact varied between -$0.01 and $0.02 over the 3-year period. The model was most sensitive to the cost of ixabepilone. CONCLUSION: Given the poor prognosis and limited number of treatment options for patients with MBC, the need for widespread coverage of ixabepilone in accordance with FDA-approved indications can clearly be established. Assuming that ixabepilone is used only for its currently labeled indications, both the number of patients eligible for ixabepilone treatment and the expected budget impact of covering ixabepilone for this group of patients are relatively small.