Assessment of sex- and age-dependency of risk factors for intimal hyperplasia in heart transplant patients using the high resolution of optical coherence tomography.

BACKGROUND: Intimal hyperplasia in cardiac allograft vasculopathy (CAVIH) is limiting survival in pediatric and adult patients after heart transplantation (HTx). Analysis of risk factors for CAVIH using the high resolution of intracoronary optical coherence tomography (OCT) is scarce, particularly in children, and recommendations for CAV prevention are largely based on data obtained in adults. Whether the predictive value of risk factors is age- or sex-dependent is unknown. METHODS AND RESULTS: We used OCT to test the age- and sex-dependency of established risk factors regarding pathological CAVIH in a cohort of 102 pediatric and adult HTx patients (35% <18 years, 69% male). Modifiable parameters such as lipid values, and the diagnoses of dyslipidemia and diabetes showed age- and sex-dependent differences. Regarding CAVIH, receiver-operating characteristic analysis showed that LDL-c was relevant only in female patients (area under the curve [AUC] 0.79, p = 0.007), and total cholesterol in female (AUC 0.81; p = 0.004) and pediatric patients (AUC 0.73, p < 0.05). The association of dyslipidemia with CAVIH was stronger in adult (odds ratio [OR] 6.33) than in pediatric patients (OR 5.00) and in women (OR 6.00) than in men (OR 4.57). Diabetes was associated with CAVIH only in women (OR 11.25). CONCLUSION: In our cohort, modifiable risk factors, particularly total cholesterol and dyslipidemia, had a different impact depending on age and sex. Targeting risk factors in selected patients might improve individual CAVIH prevention.

The risk of infective endocarditis following interventional pulmonary valve implantation: A meta-analysis.

BACKGROUND: Interventional percutaneous pulmonary valve implantation (PPVI) was first reported in 2000. Today, two different valves are certified for this procedure [i.e. Medtronic Melody® valve (Medtronic, Dublin, Ireland) and Edwards Sapien™ valve (Edwards Lifesciences, Irvine, CA, USA)]. For a decade, studies have reported an increasing risk of infective endocarditis (IE) after PPVI; as patients for PPVI are usually younger, even a low annual incidence of IE is important. However, the overall incidence and potential differences between the valves remain unclear. METHODS: A systematic literature search was performed in the databases Medline, Cochrane Library, and Embase including the clinical trials register. The aim was to summarize and compare the cumulative incidence of IE after PPVI. Using a sensitivity analysis we set the incidence rates of the two valve types in ratio with a normal population. RESULTS: A total of 967 publications were identified searching for "pulmonary valve implantation," "PPVI," and 47 publications were used for final analysis. A total 3616 patients with Melody® valves and 501 with Sapien™ valves were included. IE after PPVI occurred in 214 patients with Melody® valves and in 5 patients only with Sapien™ valves. The pooled incidence for Melody® and Sapien™ valves was 4.9% (95% CI: 3.6-6.2) and 1.3% (95% CI: 0.3-2.3), respectively. Chi-square test was significant. The sensitivity analysis showed that the incidence rate ratio was 252.1 (95% CI: 187.6-338.6) for Melody® valves and for Sapien™ valves 2.7 (95% CI: 0.8-9.2). CONCLUSIONS: At present, there is an important difference for the risk of IE after PPVI. To reduce the risk of post PPVI endocarditis, a careful valve selection in favor of the Sapien™ valves seems to be beneficial.

The risk of bacterial endocarditis after percutaneous and surgical biological pulmonary valve implantation.

OBJECTIVE: This single center study compared the risk of bacterial endocarditis (BE) after surgical and percutaneous pulmonary valve implantation. METHODS: Between Jan 1st 2010 and Dec 31st 2015 all patients who received a biological pulmonary valve (surgical/interventional) were identified. The clinical follow-up was analyzed with regard to BE applying the modified Duke criteria and echocardiographic findings. RESULTS: We identified 246 patients who underwent a biological pulmonary valve implantation. The mean age was 15.9 years, (SD 12.7, Median 13.1). There were 166 surgical patients (67.5%), with 55 homografts (22.4%, mean diameter 27.4 mm), 106 Contegra® grafts (43.1%, mean diameter 17.4) and 5 Hancock® valves (2.0, mean diameter 25.6 mm) and 80 percutaneous pulmonary valve implantations (PPVI) (32.5%) with 51 Edwards Sapien® valves (20.7%, mean diameter 25.2 mm) and 29 Melody® valves (11.8%, mean diameter 21.9 mm). Patients with a bovione jugular conduit as the biologiocal substrate had an increased risk for BE and patients with Melody® valves had the highest risk for BE that was 5-8 times higher as compared to other valves. BE episodes were detected in 5/106 Contegras® (4,7%, 1.5 per 100 person-years), and in 6/29 of the Melody® valves (20.7%, 4.8 per 100 person-years). There were no cases of BE in patients treated with Edwards Sapien®, homografts or Hankock® valves. CONCLUSION: Whereas homografts and Edwards Sapien® valves seem to have a very low risk of BE, this risk is increased in Contegra® conduits and in Melody® valves.

Cost-effectiveness of childhood rotavirus vaccination in Germany.

BACKGROUND: Rotavirus (RV) causes a highly contagious gastroenteritis especially in children under five years of age. Since 2006 two RV-vaccines are available in Europe (Rotarix(®) and RotaTeq(®)). To support informed decision-making within the German Standing Committee on Vaccination (STIKO) the cost-effectiveness of these two vaccines was evaluated for the German healthcare setting. METHODS: A Markov model was developed to evaluate the cost-effectiveness from the statutory health insurance (SHI) and from the societal perspective. RV-cases prevented, RV-associated hospitalizations avoided, and quality-adjusted life years (QALY) gained were considered as health outcomes. RV-incidences were calculated based on data from the national mandatory disease reporting system. RV-vaccine efficacy was determined as pooled estimates based on data from randomized controlled trials. Vaccine list prices and price catalogues were used for cost-assessment. Effects and costs were discounted with an annual discount rate of 3%. RESULTS: The base-case analysis (SHI-perspective) resulted in an incremental cost-effectiveness and cost-utility ratio for Rotarix(®) of € 184 per RV-case prevented, € 2457 per RV-associated hospitalization avoided, and € 116,973 per QALY gained. For RotaTeq(®), the results were € 234 per RV-case prevented, € 2622 per RV-associated hospitalization avoided, and € 142,732 per QALY gained. Variation of various parameters in sensitivity analyses showed effects on the ICERs without changing the overall trend of base-case results. When applying base-case results to the 2012 birthcohort in Germany with 80% vaccination coverage, an estimated 206,000-242,000 RV-cases and 18,000 RV-associated hospitalizations can be prevented in this birthcohort over five years for an incremental cost of 44.5-48.2 million €. CONCLUSION: Our analyses demonstrate that routine RV-vaccination could prevent a substantial number of RV-cases and hospitalizations in the German healthcare system, but the saved treatment costs are counteracted by costs for vaccination. However, with vaccine prices reduced by ∼62-66%, RV-vaccination could even become a cost-saving preventive measure.

Over-, under- and misuse of pain treatment in Germany.

BACKGROUND: The HTA-report (Health Technology Assessment) deals with over- and undertreatment of pain therapy. Especially in Germany chronic pain is a common reason for the loss of working hours and early retirement. In addition to a reduction in quality of life for the affected persons, chronic pain is therefore also an enormous economic burden for society. OBJECTIVES: Which diseases are in particular relevant regarding pain therapy?What is the social-medical care situation regarding pain facilities in Germany?What is the social-medical care situation in pain therapy when comparing on international level?Which effects, costs or cost-effects can be seen on the micro-, meso- and macro level with regard to pain therapy?Among which social-medical services in pain therapy is there is an over- or undertreatment with regard to the micro-, meso- and macro level?Which medical and organisational aspects that have an effect on the costs and/or cost-effectiveness have to be particularly taken into account with regard to pain treatment/chronic pain?What is the influence of the individual patient's needs (micro level) in different situations of pain (e. g. palliative situation) on the meso- and macro level?Which social-medical and ethical aspects for an adequate treatment of chronic pain on each level have to be specially taken into account?Is the consideration of these aspects appropriate to avoid over- or undertreatment?Are juridical questions included in every day care of chronic pain patients, mainly in palliative care?On which level can appropriate interventions prevent over- or undertreatment? METHODS: A systematic literature research is done in 35 databases. In the HTA, reviews, epidemiological and clinical studies and economic evaluations are included which report about pain therapy and in particular palliative care in the years 2005 till 2010. RESULTS: 47 studies meet the inclusion criteria. An undertreatment of acupuncture, over- and misuse with regard to opiate prescription and an overuse regarding unspecific chest pain and chronic low back pain (LBP) can be observed. The results show the benefit and the cost-effectiveness of interdisciplinary as well as multi-professional approaches, multimodal pain therapy and cross-sectoral integrated medical care. Only rough values can be determined about the care situation regarding the supply of pain therapeutic and palliative medical facilities as the data are completely insufficient. DISCUSSION: Due to the broad research question the HTA-report contains inevitably different outcomes and study designs which partially differ qualitatively very strong from each other. In the field of palliative care hospices for in-patients and palliative wards as well as hospices for out-patients are becoming more and more important. Palliative care is a basic right of all terminally ill persons. CONCLUSION: Despite the relatively high number of studies in Germany the HTA-report shows a massive lack in health care research. Based on the studies a further expansion of out-patient pain and palliative care is recommended. Further training for all involved professional groups must be improved. An independent empirical analysis is necessary to determine over or undertreatment in pain care.

Effectiveness of programmes as part of primary prevention demonstrated on the example of cardiovascular diseases and the metabolic syndrome.

BACKGROUND: The HTA-report (HTA = Health Technology Assessment) deals with the primary prevention of cardiovascular diseases and diabetes mellitus type 2. In 2009 approximately 356,000 people died in Germany due to cardiovascular diseases. According to estimations about 6.3 million people are suffering from diabetes mellitus type 2. The interventions that are subsidized by the public health insurance are mainly focused on sufficient physical activities, healthy nutrition, stress management and the reduction of the consumption of addictive drugs and luxury food. OBJECTIVES: Which lifestyle-related measures and/or programmes for primary prevention of cardiovascular diseases and of the metabolic syndrome are effective? To what extent will the health status be improved by these offers? To what extent will existing health resources and skills be strengthened by these offers? Are there any differences regarding the effectiveness among the interventions with respect to different settings or subgroups? Which lifestyle-related interventions and/or programmes for primary prevention of cardiovascular diseases and of the metabolic syndrome are sustainable and cost-effective? Which outcome parameters are in the view of the contributors decisive for the evaluation of the effectiveness? In the view of the contributor are there different values between the outcome parameters? In the view of the payers and other actors are there different values between the outcome parameters? Which ethical and juridical factors have to be considered? Which social and/or socio-economic parameters influence the use of the services and effectiveness? METHODS: A systematic literature research is done in 35 databases. For the period 2005 to 2010, reviews, epidemiological and clinical studies as well as economical evaluations which deal with primary prevention programmes regarding cardiovascular diseases or the metabolic syndrome are included. RESULTS: 44 publications meet the inclusion criteria. These studies confirm the effectiveness of the primary prevention programmes. Physical activity programs seem to have a stronger effect than nutrition programmes. Psychological programmes prove as well effectiveness, if they include cognitive behaviour therapy. The identified economical studies indicate that programmes for cardiovascular prevention can be conducted cost-effectively. Interventions that focus on the general population turn out to be particularly cost-effective and sustainable. DISCUSSION: There is a wide range of primary preventive effective lifestyle-related interventions with high evidence. The outcomes and results are consistent with the recommendations of the two identified evidence-based guidelines regarding the recommendations on lifestyle and healthy nutrition. Furthermore, the cost-effectiveness of primary prevention services is proven. With regard to the economical studies it is however worth noting that this result is based on very few publications. The transferability has to be critically assessed as the studies mainly originate from the American health system. CONCLUSION: On the whole a comprehensive setting approach with educative, somatic, psychosocial and activity therapeutic components is recommended. The sustainability of a prevention intervention must be ensured from programme to programme. Long-term studies are necessary to make valid statements regarding the sustainable effectiveness: There is an essential deficit in the current practiced evaluation of the use of primary prevention services provided by the health insurance - mainly regarding the comprehensive setting approach - regarding the evidence-based evaluation of the prescribed preventive interventions. With regard to the ethical, social and economical evaluation the research situation is deficient. The situation has to be particularly analyzed for the socially deprived and one has to respond to their specific needs for prevention.

Prevention of alcohol misuse among children, youths and young adults.

BACKGROUND: Despite many activities to prevent risky alcohol consumption among adolescents and young adults there is an increase of alcohol intoxications in the group of ten to twenty year old juveniles. OBJECTIVES: This report gives an overview about the recent literature as well as the German federal prevention system regarding activities concerning behavioral and policy prevention of risky alcohol consumption among children, adolescents and young adults. Furthermore, effective components of prevention activities are identified and the efficiency and efficacy of ongoing prevention programs is evaluated. METHODS: A systematic literature review is done in 34 databases using Bool'sche combinations of the key words alcohol, prevention, treatment, children, adolescents and young adults. RESULTS: 401 studies were found and 59 studies were selected for the health technology assessment (HTA). Most of the studies are done in USA, nine in Germany. A family strengthening program, personalized computer based intervention at schools, colleges and universities, brief motivational interventions and policy elements like increase of prices and taxes proved effective. DISCUSSION: Among the 59 studies there are three meta-analyses, 15 reviews, 17 randomized controlled trials (RCT) and 18 cohort studies. Despite the overall high quality of the study design, many of them have methodological weaknesses (missing randomization, missing or too short follow-ups, not clearly defined measurement parameters). The transferability of US-results to the German context is problematic. Only a few prevention activities reach a sustainable reduction of frequency and/or amount of alcohol consumption. CONCLUSION: The HTA-report shows the need to develop specific and target group focused prevention activities for the German situation. Essential for that is the definition of target goals (reduction of consumption, change of behaviour) as well as the definition and empirical validation of risky alcohol consumption. The efficacy of prevention activities should be proven before they are launched. At present activities for the reduction or prevention of risky alcohol consumption are not sufficiently evaluated in Germany concerning their sustainable efficacy.

Outpatient pulmonary rehabilitation - rehabilitation models and shortcomings in outpatient aftercare.

BACKGROUND: The chronic obstructive pulmonary disease (COPD) and the bronchial asthma are widespread diseases. They need long-lasting and sustainable rehabilitation. OBJECTIVES: The goal of this HTA is to describe the present supply and the economic relevance of out-patient pulmonary rehabilitation in conjunction with its social aspects. A further target is to derivate options for actions in the health-care system and possible research necessities. METHODS: Relevant publications are identified by means of a structured search in 37 database accessed through the German Institute of Medical Documentation and Information (DIMDI). In addition a manual search of identified reference lists has been done. The present report includes German and English literature published from 2004 to 2009. The methodological quality was assessed by two independent researchers according to pre-defined quality criteria of evidence based medicine. RESULTS: Among 860 publications 31 medical studies, four economic studies and 13 ethical studies meet the inclusion criteria. The studies cover rehabilitation programmes in 19 countries. The majority of them has a high level of evidence (1A to 2C). The pulmonary rehabilitation programmes differ by the setting (in-patient, out-patient, in-home, community-based), by the length of intervention (from two weeks to 36 months), by the way and the frequency of intervention and by the duration of the follow-up treatment. Overall out-patient rehabilitation programmes achieve the same positive effects for COPD patients as in-patient programmes do. This is especially true for physical performance and health related quality of life. There are only a few studies dealing with asthma. Therefore, valid statements cannot be given. The results for cost-effectiveness are not distinct enough. DISCUSSION: Goals of pulmonary rehabilitation like prevention and adequate treatment of acute exacerbations, the minimisation of hospitalisation and the reduction of mortality are attained in out-patient as well as in in-patient pulmonary rehabilitation. Regarding the best frequency of training units per week or the duration and the content of a unit further research is needed. Final results for the ideal length of an in-patient rehabilitation are still missing. None of the studies deals with the analysis of the different treatment forms of a COPD which are frequently defined by an alteration of in-patient and out-patient treatments and participation in sports clubs or self-help groups. There are some other limitations of the studies. The results concerning self-management programmes are not distinct. (Self-) Selection leads to high drop-out rates. Many studies have only small sample sizes. Confounder and long-time effects are seldom researched, relevant economic evaluations do not exist The improvement of health related quality of life is primarily obtained by an improved disease management than by an improvement of a medical parameter. CONCLUSION: Out-patient pulmonary rehabilitation is as effective as in-patient pulmonary rehabilitation. But there is a critical shortage of out-patient pulmonary rehabilitation supply in Germany. Domains for further research are the evaluation of models for integrated care, the length, frequency and content of training programmes, psychiatric assessments and the cost-effectiveness of out-patient pulmonary rehabilitation.