Cost-effectiveness analysis of resorbable biosynthetic mesh in contaminated ventral hernia repair.

BACKGROUND: The aim of this study was to compare, in terms of cost and serious complications, the use of biosynthetic resorbable parietal mesh with biologic mesh in patients undergoing contaminated ventral hernia repair (modified Ventral Hernia Working Group grade 3). Poly-4-hydroxy-butyrate (P4HB) biosynthetic mesh has rarely been the subject of comparative studies in the context of contamination. Data are required to confirm the effects of a transition from biological mesh to biosynthetic resorbable mesh. PATIENTS AND METHODS: A cost-effectiveness analysis was conducted. It was based on a decision analysis model built with clinical and economic data issued from a before-after study that included 94 patients hospitalized for ventral hernia repair at the University Hospital of Strasbourg (France) from June 2011 to February 2018. The effectiveness endpoint was the number of patients presenting with a serious specific complication or a general complication at 6 months. Data for surgical hospitalization stays, home hospitalizations and ambulatory care costs were included. RESULTS: We found fewer serious complications with biosynthetic mesh: 21% versus 33% with biologic mesh. A cost savings of US $5146 was determined. Deterministic sensitivity analyses and a probabilistic analysis confirmed our findings and the robustness of the model. CONCLUSION: P4HB biosynthetic resorbable mesh appeared to be the most effective and the least costly option. Additional data will be needed to confirm the superiority of biosynthetic mesh in terms of the recurrence risk reduction over a longer period.

Who meets national early childhood sleep guidelines in Aotearoa New Zealand? A cross-sectional and longitudinal analysis.

Study Objectives: To investigate the proportion of children in Aotearoa New Zealand (NZ) who do or do not meet sleep duration and sleep quality guidelines at 24 and 45 months of age and associated sociodemographic factors. Methods: Participants were children (n = 6490) from the Growing Up in New Zealand longitudinal study of child development with sleep data available at 24 and/or 45 months of age (48.2% girls, 51.8% boys; 22.4% Maori [the Indigenous people of NZ], 12.9% Pacific, 13.4% Asian, 45.2% European/Other). Relationships between sociodemographic factors and maternally reported child sleep duration (across 24 hours) and night wakings were investigated cross-sectionally and longitudinally. Estimates of children in NZ meeting sleep guidelines were calculated using a range of analytical techniques including Bayesian linear regression, negative binomial multiple regression, and growth curve models. Results: In NZ, 29.8% and 19.5% of children were estimated to have a high probability of not meeting sleep duration guidelines and 15.4% and 8.3% were estimated to have a high probability of not meeting night waking guidelines at 24 and 45 months respectively, after controlling for multiple sociodemographic variables. Factors associated cross-sectionally with children's sleep included ethnicity, socioeconomic deprivation, material standard of living, rurality, and heavy traffic, and longitudinal sleep trajectories differed by gender, ethnicity, and socioeconomic deprivation. Conclusions: A considerable proportion of young children in NZ have a high probability of not meeting sleep guidelines but this declines across the ages of 24 and 45 months. Sleep health inequities exist as early as 24 months of age in NZ.

The comprehensive complication index (CCI): proposal of a new reporting standard for complications in major urological surgery.

PURPOSE: The comprehensive complication index (CCI) is a new tool for reporting the cumulative burden of postoperative complications on a continuous scale. This study validates the CCI for urological surgery and its benefits over the Clavien-Dindo-Classification (Clavien). MATERIAL AND METHODS: Data from a prospectively maintained data base of all consecutive patients at a university care-center was analyzed. Complications after radical cystectomy (RC), radical prostatectomy (RP), and partial nephrectomy (PN) were classified using the CCI and Clavien system. Differences in complications between the CCI and the Clavien were assessed and correlation analyses performed. Sample size calculations for hypothetical clinical trials were compared between CCI and Clavien to evaluate whether the CCI would reduce the number of required patients in a clinical trial. RESULTS: 682 patients (172 RC, 297 RP, 213 PN) were analyzed. Overall, 9.4-46.6% of patients had > 1 complication cumulatively assessed with the CCI resulting in an upgrading in the Clavien classification for 2.4-32.4% of patients. Therefore, scores between the systems differed for RC: CCI (mean ± standard deviation) 26.3 ± 20.8 vs. Clavien 20.4 ± 16.7, p < 0.001; PN: CCI 8.4 ± 14.7 vs. Clavien 7.0 ± 11.8, p < 0.001 and RP: CCI 5.8 ± 11.7 vs. Clavien 5.3 ± 10.6, p = 0.102. The CCI was more accurate in predicting LOS after RC than Clavien (p < 0.001). Sample size calculations based in the CCI (for future hypothetical trials) resulted in a reduction of required patients for all procedures (- 25% RC, - 74% PN, - 80% RP). CONCLUSION: The CCI is more accurate to assess surgical complications and reduces required sample sizes that will facilitate the conduction of clinical trials.

Economic burden of clinical trials in lung cancer in a German Comprehensive Cancer Center.

OBJECTIVES: The recent success of individualized lung cancer therapy has triggered fundamental changes in clinical research strategies. To date there is a strong focus on early proof of concept trials in genetically preselected small patient subgroups. This analysis focuses on the economic burden caused by such trials for advanced lung cancer patients in a German Comprehensive Cancer Center (CCC). METHODS: The profit margins between recruiting groups with ≤3 and >3 patients were compared. Clinical and economic data from clinical trials for advanced lung cancer (LC), pharma-sponsored trials (PhST) as well as investigator initiated trials (IIT), conducted between 2011 and 2015 at the Center for Integrated Oncology (CIO) Cologne, were analyzed using a profit-center calculation model. RESULTS: 161 patients were enrolled in 27 clinical trials. The key economic parameter determining costs and payments was the 'trial visits'. In comparison of the two groups (A≤3; B>3 patients enrolled) we found negative profit margins for the low recruiting group (€ -1444). Concerning the number of visits significant differences were found between PhST and IIT (p=0.009). Additionally, sub-analysis show structural differences in cost composition by conducting PhST and IIT. CONCLUSION: Trials with low patient numbers and IIT, do not cover the cost. To ensure adequate, cost-covering compensation by pharmaceutical companies CCCs have to thoroughly calculate the cost of early proof of concept trials. The findings of this study also underline the need for novel structures in public funding for investigator-initiated clinical trials in precision medicine.

[Assessment of ability to drive in patients with MCI and dementia]. / Beurteilung der Fahrtauglichkeit bei Patienten mit MCI und demenziellen Syndromen.

People with mild cognitive impairment and dementia are a frequent and continuously increasing patient group in practically all fields of medicine. The associated challenges involve nearly all areas of life in addition to the direct medical treatment. Assessment of the ability to drive in patients with cognitive deficits is becoming increasingly more important. What are the options available to physicians in order to make a valid assessment? Which legal aspects must be taken into consideration? Which rights and obligations arise from the framework conditions? These questions nowadays give rise to great uncertainty for many medical personnel; however, the increasing importance of these problems necessitates a clear procedure, which allows difficult decisions to be made with utmost sovereignty and legal certainty and to be able to give patients and relatives a plausible explanation. Because age is a substantial risk factor for the development of cognitive disorders, the question of the ability to drive is affected not only by neuropsychiatric diseases, such as mild cognitive disorders or dementia but also the frequently occurring somatic comorbidities. Estimation of the ability to drive is therefore a complex approach, which should be standardized in order to appreciate all relevant aspects. It would be desirable to have a practice-oriented algorithm, the formulation of which is the aim of this article. Additionally, we would like to make a contribution to road safety and make medical personnel fully aware of this topic.

Cost-effectiveness of hip protector use on a geriatric ward in Germany: a Markov model.

UNLABELLED: In this study, we determined the cost-effectiveness of hip protector use compared with no hip protector on a geriatric ward in Germany. From both the societal and the statutory health insurance (SHI) perspectives, the cost-effectiveness ratios for the provision of hip protectors were below 12,000/quality-adjusted life year (QALY) even if unrelated costs in added life years were included. INTRODUCTION: The aim of this study is to determine the cost-effectiveness of the provision of hip protectors compared with no hip protectors on a geriatric ward in Germany. METHODS: A lifetime decision-analytic Markov model was developed. Costs were measured from the societal and from the statutory health insurance (SHI) perspectives and comprised direct medical, non-medical and unrelated costs in additional life years gained. Health outcomes were measured in terms of quality-adjusted life years (QALYs). To reflect several levels of uncertainty, first- and second-order Monte Carlo simulation (MCS) approaches were applied. RESULTS: Hip protector use compared with no hip protector results in savings (costs, -5.1/QALYs, 0.003) for the societal perspective. For the SHI perspective, the incremental cost-effectiveness ratio was 4416 /QALY (costs, +13.4). If unrelated costs in life years gained were included, the cost-effectiveness ratio increases to 9794/QALY for the societal perspective and to 11,426/QALY for the SHI perspective. In the MCS, for the societal perspective without unrelated costs, 47 % of simulations indicated hip protectors to be cost saving (i.e. lower costs and higher effects). CONCLUSION: Although the gain in QALYs due to the provision of providing hip protectors to patients on geriatric wards is small, all scenarios showed acceptable cost-effectiveness ratios or even savings.

[Development of an instrument for the assessment of demand and monitoring of the health management in a health insurance]. / Entwicklung eines Instruments zur Bedarfsermittlung und zum Monitoring im Betrieblichen Gesundheitsmanagement (BGM) eines Versicherungskonzerns.

To identify and follow up the health relevant effects of change-management-projects and to determine improvements in activities following this change a specific health-controlling instrument with benchmarking options has been developed. This instrument applies scientific quality standards and shows the organisational value in form of an index (BGM-Systemindex). It shows the correlation between the four indices management system, health-related actions, health and absence rate and allows a qualitative view of corporate health promotion on and its long term effects. The initiator for the project was an employee survey, which showed a need for action to improve job satisfaction. The survey was the reason that management initiated an integral change-management-project. The project showed many interfaces with the corporate health promotion (BGM), thus enabling consequent changes to be made and their effects to be evaluated. The aim of the project was to clearly increase employee satisfaction up to the next employee survey. Overall the project can be considered a success as the main aim of the project to increase the employees job satisfaction in the given period of time was clearly accomplished. The BGM-Systemindex also stood the test for comprehensive monitoring of the employees health. The project was able to prove that the health relevant parameters could be optimised and that the quality, acceptance and efficiency of the intervention methods had improved. It also showed a positive development of the early and long term health indicators. This is a positive contrast to available literature, which shows that an insufficient or incorrectly used change management results in a lower employee satisfaction. As a result it was decided to use the tool in future.

Clinical Pharmacogenetics Implementation Consortium guidelines for HLA-B genotype and carbamazepine dosing.

Human leukocyte antigen B (HLA-B) is a gene that encodes a cell surface protein involved in presenting antigens to the immune system. The variant allele HLA-B*15:02 is associated with an increased risk of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in response to carbamazepine treatment. We summarize evidence from the published literature supporting this association and provide recommendations for the use of carbamazepine based on HLA-B genotype (also available on PharmGKB: http://www.pharmgkb.org). The purpose of this article is to provide information to allow the interpretation of clinical HLA-B*15:02 genotype tests so that the results can be used to guide the use of carbamazepine. The guideline provides recommendations for the use of carbamazepine when HLA-B*15:02 genotype results are available. Detailed guidelines regarding the selection of alternative therapies, the use of phenotypic tests, when to conduct genotype testing, and cost-effectiveness analyses are beyond the scope of this document. Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines are published and updated periodically on the PharmGKB website at (http://www.pharmgkb.org).

[Cost of illness of age-related macular degeneration. Systematic review on the development of a costs diary]. / Krankheitskosten der altersbedingten Makuladegeneration. Systematischer Review zur Entwicklung eines Kostentagebuchs.

Due to demographic changes in the German population a significant rise in incident cases of age-related macular degeneration (AMD) is to be expected in the coming years. Also the corresponding increase in costs of the illness requires appropriate survey instruments to allow accurate estimations of costs. The cost diary for patients with AMD developed in this study is based on a previously established systematic review. The seven studies that were included were evaluated regarding their quality in order to then extract the listed cost items. The result is a prospective survey instrument with six different cost sectors of AMD.

Life prolonging of disease management programs in patients with type 2 diabetes is cost-effective.

AIM: Our objective was to examine the cost-effectiveness of disease management programs (DMPs) for type 2 diabetes mellitus (T2DM) taking into account their life prolonging effect. METHODS: We compared real life costs in 19,888 propensity score matched pairs of T2DM DMP participants and T2DM patients in routine care (RC) according to sickness funds data. We estimated mean annual costs for survivors, last year of life costs for decedents, the influence of ageing on costs, incremental cost-effectiveness ratio and effects on hospitalization. RESULTS: Annual costs for survivors were 3,318€ (DMP) and 3,570€ (RC). The mean costs in the last year of life were 16,911€ (DMP) and 15,763€ (RC). Ageing had a cost triggering effect for survivors (30€/36€ per year in DMP-/RC-group; p<0.001) and a cost decreasing effect in the last year of life (546€/483€ per year in DMP-/RC-group; p<0.001). The incremental cost-effectiveness ratio of the DMP vs. RC was -1396€ per life-year gained. Hospitalizations increased with age in case of survival and decreased with age in case of death but were always lower in the DMP-group. CONCLUSION: Despite increase in costs due to longer life DMPs are cost-effective.

[When is the optimal time for hip ultrasound screening?]. / Wann ist der optimale Zeitpunkt für ein sonographisches Hüftscreening?

The perfect time for hip screening is when every pathologically deformed hip can be diagnosed by sonography and after spontaneous resolution of immature, dysplastic hips. In addition, the beginning of therapy should be early enough to provide the best possible outcome concerning the anatomically correct healing of the patient's hip. Even though every child should be screened by sonography in the first few days of life, a reasonable way could be ultrasound screening in the first week for clinically unstable hips or newborns with risk factors such as breech position combined with ultrasound screening of every newborn between the fourth and sixth week.

Risk assessment of substances that are both genotoxic and carcinogenic report of an International Conference organized by EFSA and WHO with support of ILSI Europe.

The European Food Safety Authority (EFSA) and the World Health Organization (WHO), with the support of the International Life Sciences Institute, European Branch (ILSI Europe), organized an international conference on 16-18 November 2005 to discuss how regulatory and advisory bodies evaluate the potential risks of the presence in food of substances that are both genotoxic and carcinogenic. The objectives of the conference were to discuss the possible approaches for risk assessment of such substances, how the approaches may be interpreted and whether they meet the needs of risk managers. ALARA (as low as reasonably achievable) provides advice based solely on hazard identification and does not take into account either potency or human exposure. The use of quantitative low-dose extrapolation of dose-response data from an animal bioassay raises numerous scientific uncertainties related to the selection of mathematical models and extrapolation down to levels of human exposure. There was consensus that the margin of exposure (MOE) was the preferred approach because it is based on the available animal dose-response data, without extrapolation, and on human exposures. The MOE can be used for prioritisation of risk management actions but the conference recognised that it is difficult to interpret it in terms of health risk.

Approaches to the risk assessment of genotoxic carcinogens in food: a critical appraisal.

The present paper examines the particular difficulties presented by low levels of food-borne DNA-reactive genotoxic carcinogens, some of which may be difficult to eliminate completely from the diet, and proposes a structured approach for the evaluation of such compounds. While the ALARA approach is widely applicable to all substances in food that are both carcinogenic and genotoxic, it does not take carcinogenic potency into account and, therefore, does not permit prioritisation based on potential risk or concern. In the absence of carcinogenicity dose-response data, an assessment based on comparison with an appropriate threshold of toxicological concern may be possible. When carcinogenicity data from animal bioassays are available, a useful analysis is achieved by the calculation of margins of exposure (MOEs), which can be used to compare animal potency data with human exposure scenarios. Two reference points on the dose-response relationship that can be used for MOE calculation were examined; the T25 value, which is derived from linear extrapolation, and the BMDL10, which is derived from mathematical modelling of the dose-response data. The above approaches were applied to selected food-borne genotoxic carcinogens. The proposed approach is applicable to all substances in food that are DNA-reactive genotoxic carcinogens and enables the formulation of appropriate semi-quantitative advice to risk managers.

[Established and current procedures in wound healing]. / Bewährte und aktuelle Verfahren in der Wundheilung.

Most chronic wounds are caused by arterial or venous vascular disease. Wound care is an interdisciplinary task and economic challenge. Numerous new wound dressings and treatment methods have been introduced recently. Basic research has enhanced our understanding of stimulation and inhibition of wound healing. Well-constructed clinical studies have shown some traditional approaches to be effective and others, less so. Successful wound healing requires treatment of the underlying disease as well as correction of local factors that may delay healing. The choice of dressings must be based on continuous re-assessment of the wound. Modern approaches for the most common types of chronic wounds, as well as options such as vacuum treatment and tissue-engineered skin are presented along with information on latest rules for reimbursement for wound care in Germany.

[Cost of miniplate osteosynthesis for treatment of mandibular fractures: a prospective evaluation]. / Kosten der Unterkieferfrakturversorgung: Eine prospektive Untersuchung.

PURPOSE: Up to now in maxillofacial surgery almost all inpatient treatments were reimbursed at the hospital's per diem rate. The real treatment cost is unknown and there is a lack of publications in this sphere. This study calculates the cost of surgical treatment of mandibular fractures. METHOD: The prospective study includes 104 patients whose mandibular fractures were treated using miniplate osteosynthesis. For each patient we took into account the time input by physicians and specialised nurses and calculated labour cost using the relevant wage rates. We added the cost for materials and drugs as well as for laboratory and radiographic examinations. Finally, we incorporated charges for the hotel and nursing components of inpatient treatment. RESULTS: The cost for the surgical treatment of mandibular fractures varied between 642 euro; for single and 1,070 euro; for triple fractures. The share of labour cost is about 1/3. Treatment cost varies with the length of hospital stay: 1,132 euro; for four days and 1,628 euro; for seven days on average. CONCLUSION: This prospective study can be compared with the recently published corresponding G-DRG rates. Moreover, the reported cost figures allow comparison with corresponding cost studies from other public health systems.

Assessment of intake from the diet.

Exposure assessment is one of the key parts of the risk assessment process. Only intake of toxicologically significant amounts can lead to adverse health effects even for a relatively toxic substance. In the case of chemicals in foods this is based on three major aspects: (i) how to determine quantitatively the presence of a chemical in individual foods and diets, including its fate during the processes within the food production chain; (ii) how to determine the consumption patterns of the individual foods containing the relevant chemicals; (iii) how to integrate both the likelihood of consumers eating large amounts of the given foods and of the relevant chemical being present in these foods at high levels. The techniques used for the evaluation of these three aspects have been critically reviewed in this paper to determine those areas where the current approaches provide a solid basis for assessments and those areas where improvements are needed or desirable. For those latter areas, options for improvements are being suggested, including, for example, the development of a pan-European food composition database, activities to understand better effects of processing on individual food chemicals, harmonisation of food consumption survey methods with the option of a regular pan-European survey, evaluation of probabilistic models and the development of models to assess exposure to food allergens. In all three areas, the limitations of the approaches currently used lead to uncertainties which can either cause an over- or underestimation of real intakes and thus risks. Given these imprecisions, risk assessors tend to build in additional uncertainty factors to avoid health-relevant underestimates. This is partly done by using screening methods designed to look for "worst case" situations. Such worse case assumptions lead to intake estimates that are higher than reality. These screening methods are used to screen all those chemicals with a safe intake distribution. For chemicals with a potential risk, more information is needed to allow more refined screening or even the most accurate estimation. More information and more refined methods however, require more resources. The ultimate aims are: (1) to obtain appropriate estimations for the presence and quantity of a given chemical in a food and in the diet in general; (2) to assess the consumption patterns for the foods containing these substances, including especially those parts of the population with high consumption and thus potentially high intakes; and (3) to develop and apply tools to predict reliably the likelihood of high end consumption with the presence of high levels of the relevant substances. It has thus been demonstrated that a tiered approach at all three steps can be helpful to optimise the use of the available resources: if relatively crude tools - designed to provide a "worst case" estimate - do not suggest a toxicologically significant exposure (or a relevant deficit of a particular nutrient) it may not be necessary to use more sophisticated tools. These will be needed if initially high intakes are indicated for at least parts of the population. Existing pragmatic approaches are a first crude step to model food chemical intake. It is recommended to extend, refine and validate this approach in the near future. This has to result in a cost-effective exposure assessment system to be used for existing and potential categories of chemicals. This system of knowledge (with information on sensitivities, accuracy, etc.) will guide future data collection.

The effect of anthropometric and socioeconomic factors on the racial difference in lung function.

African-Americans have lower lung function than whites. However, the relative contributions of body habitus and socioeconomic factors are unknown. To address this question, we analyzed data from 1242 white (806 women, 436 men) and 1084 African-American (696 women, 388 men) asymptomatic, nonsmoking adult participants of the third National Health and Nutrition Examination Survey (NHANES III). African-Americans were poorer, had larger FEV(1)/FVC and body mass index (BMI), but lower sitting height, FEV(1) and FVC than whites. Cross-sectional regression analyses using spirometric, anthropometric, and socioeconomic data were performed separately by sex to investigate racial differences in lung function. Sitting height accounted for 35-39% of the race difference in both sexes. Poverty index accounted for about 7.5% and 2.5% of the racial difference in women and men, respectively, whereas the effect of education accounted for about 2% in women and 4.7% in men. With further adjustment for BMI, we could account for only about half of the racial difference in FEV(1) and FVC. We conclude that the racial difference in lung function is only partially explained by a shorter upper body segment in African-Americans. Although low socioeconomic indicators are related to lower lung function, they explain only a small proportion of this racial difference.