Metabolic syndrome as a late effect of childhood hematopoietic stem cell transplantation - A thorough statistical evaluation of putative risk factors.

BACKGROUND: Metabolic syndrome (MetS) is frequent among survivors of childhood hematopoietic stem-cell transplantation (HSCT), but assessment of risk factors is challenged by survivor and participation bias in long-term follow-up studies. METHODS: A cohort of 395 pediatric patients transplanted between 1980 and 2018 was investigated. MetS was assessed at follow-up between December 2018 and March 2020. Two composite outcomes ((a) combining MetS and death, (b) combining MetS, death, and nonparticipation) were considered to address the risk of selection bias. RESULTS: Among 234 survivors invited to the follow-up, 96 individuals (median age 27 years) participated. MetS prevalence was 30% among participants. The only significant HSCT risk factor was a variable combining HSCT indication and conditioning with total-body irradiation (TBI) (p = .0011). Compared to acute leukemias (AL) treated with high-grade TBI (8-12 Gy), a lower MetS prevalence was seen for nonmalignant diseases treated with no/low-grade TBI (0-4.5 Gy) (OR = 0.04, 95% confidence interval (CI): 0.00-0.23). Analyses of the composite outcomes indicated overestimation of the effect of high-grade TBI due to selection bias. Scrutiny showed strong residual confounding between HSCT indication and high-grade TBI within AL-patients. The HSCT effect on MetS reflected HSCT effects on high-density-lipoprotein (HDL) and triglycerides. Compared to AL treated with high-grade TBI, nonmalignant diagnoses treated with no/low-grade TBI had higher HDL (+40%, 95% CI: +21% to +62%) and lower triglyceride (-59%, 95% CI: -71% to -42%). CONCLUSION: The TBI effect on MetS may be overestimated in follow-up studies due to selection bias and confounding. The TBI effect was confined to the potentially modifiable MetS criteria  HDL and triglyceride.

Socioeconomic inequality in hip replacement in four European countries from 2002 to 2009--area-level analysis of hospital data.

BACKGROUND: Cross-country comparisons of socioeconomic equity in health care typically use sample survey data on general services such as physician visits. This study uses comprehensive administrative data on a specific service: hip replacement. METHODS: We analyse 651 652 publicly funded hip replacements, excluding fractures and accidents, in adults over 35 in Denmark, England, Portugal and Spain from 2002 to 2009. Sub-national administrative areas are split into socioeconomic quintile groups comprising approximately one-fifth of the national population. Area-level Poisson regression with Huber-White standard errors is used to calculate age-sex standardised hip replacement rates by quintile group, together with gaps and ratios between richest and poorest groups (Q5 and Q1) and the middle group (Q3). RESULTS: We find pro-rich-area inequality in England (2009 Q5/Q1 ratio 1.35 [CI 1.25-1.45]) and Spain (2009 Q5/Q1 ratio 1.43 [CI 1.17-1.70]), pro-poor-area inequality in Portugal (2009 Q5/Q1 ratio 0.67 [CI 0.50-0.83]) and no significant inequality in Denmark. Pro-rich-area inequality increased over time in England and Spain but not significantly. Within-country differences between socioeconomic quintile groups are smaller than between-country differences in general population averages: hip replacement rates are substantially lower in Portugal and Spain (8.6 and 7.4 per 10 000 in 2009) than England and Denmark (20.2 and 27.8 per 10 000 in 2009). CONCLUSION: Despite limitations regarding individual-level inequality and area heterogeneity, analysis of area-level data on publicly funded hospital activity can provide useful cross-country comparisons and longitudinal monitoring of socioeconomic inequality in specific health services. Although this kind of analysis cannot provide definitive answers, it can raise important questions for decision makers.

Potentially avoidable hospitalizations in five European countries in 2009 and time trends from 2002 to 2009 based on administrative data.

INTRODUCTION: Potentially avoidable hospitalizations in chronic conditions are used to evaluate health-care performance. However, evidence comparing different countries at small geographical areas is still scarce. The aim of the present study is to describe and discuss differences in rates and time-trends across health-care areas from five European countries. METHODS: Observational, ecological study, on virtually all discharges produced in five European countries between 2002 and 2009. Potentially avoidable hospitalizations were operationally defined as a joint indicator composed of six chronic conditions. Episodes flagged as potentially avoidable were allocated to 913 geographical health-care areas. Age-sex standardized rates and standardized hospitalization ratios, as well as several statistics of variation, were estimated. RESULTS: Four hundred sixty-two thousand seven hundred and ninety-two episodes were flagged as potentially avoidable. Variation in rates across countries was notable, from 93.7 cases per 10,000 inhabitants in Denmark to 34.8 cases per 10,000 inhabitants in Portugal. Within-country variation was also noteworthy, from 3.12 times among extreme areas in Spain to a 1.46-fold difference in Denmark. The highest systematic variation was found in Denmark (empirical Bayes 0.45) and the lowest in England (empirical Bayes 0.08). Rates and systematic variation remained fairly stable over time, with Denmark and England experiencing a statistically significant decrease (20% and 10%, respectively). Income and educational level, hospital utilization propensity, and region of residence were found to be associated with avoidable admissions. CONCLUSION: The dramatic variation across countries, beyond age and sex differences, and its consistency over time, implies systemic, although differential, behaviour of the five health-care systems with regard to chronic care.

Costs of medically assisted reproduction treatment at specialized fertility clinics in the Danish public health care system: results from a 5-year follow-up cohort study.

OBJECTIVE: To examine the costs to the public health care system of couples in medically assisted reproduction. DESIGN: Longitudinal cohort study of infertile couples initiating medically assisted reproduction treatment. SETTING: Specialized public fertility clinics in Denmark. SAMPLE: Seven hundred and thirty-nine couples having no child at study entry and with data on kind of treatment and live birth (yes/no) for each treatment attempt at the specialized public fertility clinic. METHODS: Treatment data for medically assisted reproduction attempts conducted at the public fertility clinics were abstracted from medical records. Flow diagrams were drawn for different standard treatment cycles and direct costs at each stage in the flow charts were measured and valued by a bottom-up procedure. Indirect costs were distributed to each treatment cycle on the basis of number of visits as basis. Costs were adjusted to 2012 prices using a constructed medical price index. MAIN OUTCOME MEASURES: Live birth, costs. RESULTS: Total costs per live birth in 2012 prices were estimated to 10,755€. Costs per treated couple - irrespective of whether the treatment was terminated by a live birth or not - were estimated at 6607€. Costs per live birth of women <35 years at treatment initiation were 9338€ and 15,040€ for women ≥35 years. CONCLUSION: The public costs for live births after conception with medically assisted reproduction treatment are relatively modest. The results can be generalized to public fertility treatment in Denmark and to other public treatment settings with similar limitations in numbers of public treatment cycles offered.

Register-based studies of healthcare costs.

INTRODUCTION: The aim of this paper is to provide an overview and a few examples of how national registers are used in analyses of healthcare costs in Denmark. RESEARCH TOPICS: The paper focuses on health economic analyses based on register data. For the sake of simplicity, the studies are divided into three main categories: economic evaluations of healthcare interventions, cost-of-illness analyses, and other analyses such as assessments of healthcare productivity. CONCLUSION: We examined a number of studies using register-based data on healthcare costs. Use of register-based data renders a comprehensive data material, often in the form of time series, which is very useful in health economic analyses. The disadvantage of register-based data is the use of tariffs, charges, or market prices as proxies for costs in the computation of healthcare costs.

Economic evaluation of home blood pressure telemonitoring: a randomized controlled trial.

AIMS: The purpose of the present study was to compare the costs of home blood pressure (BP) telemonitoring (HBPM) with the costs of conventional office BP monitoring. In a randomized controlled trial, 105 hypertensive patients performed HBPM and 118 patients received usual care with conventional office BP monitoring during 6 months. Costs were quantified from the healthcare perspective. Non-parametric simulations were performed to quantify the uncertainty around the mean estimates and cost-effectiveness acceptability curves were made. MAJOR FINDINGS: Systolic and diastolic daytime and night-time ambulatory BP (ABP) were reduced in both groups. The uncertainty around the incremental cost effectiveness ratio point estimates was considerable for both systolic and diastolic ABP. For systolic ABP, the difference in cost effectiveness ratio between the two groups was 256 Danish kroner (DKK)/mmHg [95% uncertainty interval, UI -860 to 4544]. For diastolic ABP, the difference in cost effectiveness ratio between the two groups was 655 DKK/mmHg [95% UI -674 to 69315]. Medication and consultation costs were lowest in the intervention group, but were offset by the cost of the telemonitoring equipment. CONCLUSIONS: Cost-effectiveness analysis showed that telemonitoring of home BP was more costly compared with usual monitoring of office BP. The cost-effectiveness result is surrounded with considerable uncertainty.

Interchangeability of the EQ-5D and the SF-6D in long-lasting low back pain.

OBJECTIVES: The objective of this study was to investigate the interchangeability of the EuroQol 5D (EQ-5D) and the Short Form 6D (SF-6D) in individuals with long-lasting low back pain to guide the optimal choice of instrument and to inform decision-makers about any between-measure discrepancy, which require careful interpretation of the results of cost-utility evaluations. METHODS: A cross-sectional study was conducted across 275 individuals who had spinal surgery on indication of chronic low back pain. EQ-5D and SF-6D were mailed to respondents for self-completion. Statistical analysis of between-measure agreement (using English weights) was based on Bland and Altman's limits of agreement and a series of linear regressions. RESULTS: A moderate mean difference of 0.085 (SD 0.241) was found, but because it masked more severe bidirectional variation, the expected variation between observations of EQ-5D and SF-6D in future studies was estimated at 0.546. The EQ-5D's N3 term alone explained a factor of 0.79 of the variation in between-measure differences, while the explanatory value of adding variables of age, sex, diagnosis, previous surgery, and occupational status was basically zero. A final model including only dummy variables for the N3 term and five identified framing effects explained a factor of 0.86 of the variation in between-measure differences. CONCLUSIONS: Although the EQ-5D and the SF-6D are both psychometrically valid for generic outcome assessment in long-lasting low back pain, it appears that they cannot generally be used interchangeably for measurement of preference values. Sensitivity analysis examining the impact of between-measure discrepancy thus remains a necessary condition for the interpretation of the results of cost-utility evaluations.

The influence of economic incentives and regulatory factors on the adoption of treatment technologies: a case study of technologies used to treat heart attacks.

The Technological Change in Health Care Research Network collected unique patient-level data on three procedures for treatment of heart attack patients (catheterization, coronary artery bypass grafts and percutaneous transluminal coronary angioplasty) for 17 countries over a 15-year period to examine the impact of economic and institutional factors on technology adoption. Specific institutional factors are shown to be important to the uptake of these technologies. Health-care systems characterized as public contract systems and reimbursement systems have higher adoption rates than public-integrated health-care systems. Central control of funding of investments is negatively associated with adoption rates and the impact is of the same magnitude as the overall health-care system classification. GDP per capita also has a strong role in initial adoption. The impact of income and institutional characteristics on the utilization rates of the three procedures diminishes over time.

Drugs, sex, money and power: an HPV vaccine case study.

In this paper we compare the experiences of seven industrialized countries in considering approval and introduction of the world's first cervical cancer-preventing vaccine. Based on case studies, articles from public agencies, professional journals and newspapers we analyse the public debate about the vaccine, examine positions of stakeholder groups and their influence on the course and outcome of this policy process. The analysis shows that the countries considered here approved the vaccine and established related immunization programs exceptionally quickly even though there still exist many uncertainties as to the vaccine's long-term effectiveness, cost-effectiveness and safety. Some countries even bypassed established decision-making processes. The voice of special interest groups has been prominent in all countries, drawing on societal values and fears of the public. Even though positions differed among countries, all seven decided to publicly fund the vaccine, illustrating a widespread convergence of interests. It is important that decision-makers adhere to transparent and robust guidelines in making funding decisions in the future to avoid capture by vested interests and potentially negative effects on access and equity.

Hospital centralization and performance in Denmark-Ten years on.

Denmark implemented a major reform of the administrative and political structure in 2007 when the previous 13 counties were merged into five new regions and the number of municipalities was reduced from 271 to 98. A main objective was to create administrative units that were large enough to support a hospital structure with few acute hospitals in each region and to centralize specialized care in fewer hospitals. This paper analyses the reorganization of the somatic hospital sector in Denmark since 2007, discusses the mechanisms behind the changes and analyses hospital performance after the reform. The reform focused on improving acute services and quality of care. The number of acute hospitals was reduced from about 40-21 hospitals with new joint acute facilities, which include emergency care wards. The restructuring and geographical placement of acute hospitals took place in a democratic process subject to central guidelines and requirements. Since the reform, hospital productivity has increased by more than 2 per cent per year and costs have been stable. Overall, indicators point to a successful reform. However, it has also been criticized that some people in remote areas feel "left behind" in the economic development and that hospital staff are under increased workload pressure. Concurrent with the centralization of hospitals municipalities strengthened their health service with an emphasis on prevention and health promotion.

The impact of population ageing on future Danish drug expenditure.

Population ageing is likely to place an increasing burden on future health care budgets. Several studies, however, have demonstrated that the impact of ageing on future hospital expenditures will be overestimated when not accounting for proximity to death. This is because the greater health care expenditures among the elderly are not only due to age per se but due to the high "costs of dying". Similar studies for pharmaceutical expenditures are scarce. The aim of this study was first to estimate the impact of the ageing Danish population on future total expenditures (public outlays as well as private co-payment) on out-of-hospital prescription drugs, holding everything but demographic changes constant. Second, it was to describe the association between age and drug expenditure among survivors compared to that of decedents, and to evaluate the extent to which drug expenditure is increasing with proximity to death in the last 2 years of life. Taking expenditure during the last year of life and the changes in mortality rates into account, future expenditure of prescription drugs was projected by multiplying the estimated mean annual drug expenditure according to age, gender and survival status by the predicted future number of Danes in each stratum, and subsequently, summing up across all strata. A generalized method was developed to account for expenditure several years prior to death. The projection was based on current drug utilisation from a representative prescription database covering the county of Funen, Denmark, and the most recent Danish population forecast for the period 2003-2030. The total population was projected to increase by 0.8% during the period 2003-2030, while the increase was 58% for people aged 75 years and over. The total drug expenditure was projected to increase by 16.9% during the same period when accounting for proximity to death, while it was 17.9% when this was not done. The projected growth in drug expenditure was not merely due to the drug consumption of the elderly. Moreover, the drug expenditure of elderly decedents was only increasing slightly with proximity to death. We conclude that the ageing of the population per se is likely to increase future expenditure on prescription drugs. This predicted increase, however, is small compared to recently observed increases in drug expenditures. The results of the study indicate that Danish policies aimed at limiting the increase in public drug expenditure should focus on rational pharmacotherapy and on the promotion of prescription of cost-effective pharmaceuticals-rather than targeting the drug use of the elderly or reducing the reimbursement generally.

Handling value added tax (VAT) in economic evaluations: should prices include VAT?

In health economic evaluations, value added tax is commonly treated as a transfer payment. Following this argument, resources are valued equal to their net-of-tax prices in economic evaluations applying a societal perspective. In this article we argue that if there is the possibility that a new healthcare intervention may expand the healthcare budget, the social cost of input factors should be the gross-of-tax prices and not the net-of-tax prices. The rising interest in cost-benefit analysis and the use of absolute thresholds, net benefit estimates and acceptability curves in cost-effectiveness analysis makes this argument highly relevant for an appropriate use of these tools in prioritisation.

A SWOT analysis of the organization and financing of the Danish health care system.

The organization and financing of the Danish health care system was evaluated within a framework of a SWOT analysis (analysis of Strengths, Weaknesses, Opportunities and Threats) by a panel of five members with a background in health economics. The present paper describes the methods and materials used for the evaluation: selection of panel members, structure of the evaluation task according to the health care triangle model, selection of background material consisting of documents and literature on the Danish health care system, and a 1-week study visit.

Organization and financing of the Danish health care system.

The present paper aims at giving a short overview of the organization and financing of the Danish health care system as of 1997-1998 when the SWOT panel evaluated the system. The overview follows the triangular model of a health care system. The Danish system is characterized by being decentralized and single-funded. The hospital sector is public, and hospitals are financed and run by the counties (with only a very small private hospital sector alongside). General practitioners are private entrepreneurs but work under contract for the counties. Hospitals are financed by global budgets, while general practitioners are paid by a mixed remuneration system of capitation fees and fee-for-service. During the past 20 years, the government has repeatedly imposed budget ceilings on the counties which has limited growth in the health care sector.

Summary of the SWOT panel's evaluation of the organisation and financing of the Danish health care system.

The organisation and financing of the Danish health care system was evaluated within a framework of a SWOT analysis (analysis of strengths, weaknesses, opportunities and threats) by a panel of five members with a background in health economics. This paper systematically summarises the panel's assessments, within the framework of the triangular model of health care. The members of the panel are in agreement on a number of aspects, while their views on other aspects differ. In general they find many strength in the way the system is organised and financed more so in the primary sector than in the hospital sector.

[Mammographic screening in the municipality of Copenhagen 1991-1997. Evaluation of the preoperative assessment]. / Mammografiscreening i Københavns Kommune 1991-1997. Evaluering af det praeoperative udredningsforløb.

INTRODUCTION: A biennial mammography screening programme started for all women aged 50-69 in the municipality of Copenhagen, Denmark, in April 1991. The aim of the present study was to evaluate the quality of the preoperative diagnostic assessment for women recalled for further examination. Quality indicators were: validity of the fine-needle aspiration cytology, rate of malignant to benign surgery, and frequency of one-step surgery for malignant lesions. MATERIAL AND METHOD: Database registries during the first three screening rounds from April 1991 to March 1997 were studied retrospectively, for fine-needle aspiration cytology tests where surgical biopsy was also performed. RESULTS: In the period 1991-1997, 4,111 women were recalled for clinical mammography and subsequently 1,086 women underwent surgery. The use of the triple test in the preoperative assessment increased from 50% in the first screening round to 72% in the third. Throughout the period of evaluation, the number of inadequate fine-needle aspiration cytology (FNAC) was reduced from 32% to 6%. Inadequate FNAC from malignant lesions declined from 27% to 6%. The sensitivity of FNAC increased from 67% to 90% and the accuracy from 60% to 81%. The malignant/benign ratio of surgery rose from 1.4 in the first screening round to 2.8 in the third. One-step surgery as definitive treatment was performed in 67% of malignant instances. DISCUSSION: The preoperative diagnostic assessment improved during the evaluation period. The triple test was used more often over time, the validity of FNAC and the malignant/benign ratio of surgery increased.

Ten years of structural reforms in Danish healthcare.

A major structural reform of the Danish public sector took place in 2007 when the number of administrative units at the regional and municipal levels was reduced. The larger administrative units allowed for a new hospital structure with a reduced number of acute hospitals covering a population of between 200,000 and 400,000 inhabitants. The restructuring involves creation of acute hospitals with a 24-h acute service by a range of specialists. The idea was to weight quality higher than geographical closeness to the nearest hospital. Concurrently, the pre-hospital service will be expanded. The National Board of Health was given authority to approve regional plans for specialties rather than provide guidelines. The use of private hospitals was increased as a means to fulfil a waiting time guarantee of between 2 and 1 month. Increased use of private insurance also increased use of private hospitals. A new way of financing health care was intended to give municipalities incentives to invest in health prevention and health promotion. Concurrent reforms included economic incentives to increase hospital production as measured by DRGs; quality programmes to secure high quality and patient safety; and electronic patient records and increased use of IT systems.

Ageing and health care expenditure in EU-15.

The purpose of this paper is to investigate the relationship between ageing and the evolution of health care expenditure per capita in the EU-15 countries. A secondary purpose is to produce estimates that can be used in projections of future health care costs. Explanatory variables include economic, social, demographic and institutional variables as well as variables related to capacity and production technology in the health care sector. The study applies a co-integrated panel data regression approach to derive short-run relationships and furthermore reports long-run relationships between health care expenditure and the explanatory variables. Our findings suggest that there is a positive short-run effect of ageing on health care expenditure, but that the long-run effect of ageing is approximately zero. We find life expectancy to be a more important driver. Although the short-run effect of life expectancy on expenditure is approximately zero, we find that the long-run effect is positive, so that increasing life expectancy leads to a more than proportional, i.e. exponential, increase in health care expenditure.

[Lack of equity in access to health care]. / Ulighed i adgangen til sundhedsydelser.

Equity in access is seen when needs determine access irrespective of population characteristics such as socioeconomic status and ethnicity. Equity in access is often investigated using indirect measures like utilisation as an equity proxy; however, disease stage and survival constitute alternative measures. Despite that equity in access to health care is a local and global political objective, inequities in access are still widespread even e.g. in Danish health care where equal and easy access are express political goals.