Patient-reported outcomes using a wearable cardioverter-defibrillator: results from a systematic review.

OBJECTIVES: The aim of this study was to assess the effect of the wearable cardioverter-defibrillator (WCD) on patient-reported outcomes (PRO) in adult patients with high risk for sudden cardiac arrest. METHODS: We performed a systematic literature search in Medline (via PubMed) and Cochrane Library in February 2022 and included studies with a study population ≥18 years and prescribed WCD. PRO include health-related quality of life (QoL), symptoms, utilities, or satisfaction ratings. Study selection was done by two reviewers independently using predefined inclusion and exclusion criteria. Quality assessment of studies as well as data extraction was performed by one author and approved by a second author. Results of the included studies are presented quantitatively. RESULTS: One randomized controlled trial (RCT), one comparative non-randomized trial, and three single-arm trials were included. QoL was assessed in four studies, but with different assessment tools. One study additionally evaluated the change in depressive symptoms and anxiety and one study focused on acceptability of WCD but evaluated items that are closely related to QoL. Results of the RCT show no statistically significant difference in QoL assessed by SF-36 and EQ-5D comparing WCD and Guideline-Directed Medical Therapy (GDMT) versus GDMT alone. One comparative study reports an improvement in depressive symptoms and anxiety within groups but no significant difference between groups. Further, one single-arm study reported improvement in QoL between baseline and day 90 and day 180. CONCLUSIONS: The available evidence demonstrates that the usage of WCD is not affecting PRO, like QoL, depressive symptoms or anxiety negatively.

Effectiveness, efficacy, and safety of wearable cardioverter-defibrillators in the treatment of sudden cardiac arrest - Results from a health technology assessment.

OBJECTIVES: To assess the effectiveness, efficacy, and safety of a wearable cardioverter-defibrillator (WCD) in adult persons with high risk for sudden cardiac arrest and for which an implantable cardioverter is currently not applicable. METHODS: We performed a systematic literature search in Medline, Embase, Cochrane Library, and CRD-databases. Study selection was performed by two reviewers independently. Data were presented quantitatively; due to heterogeneity of studies no meta-analysis was performed. RESULTS: One randomized-controlled trial (RCT), one non-randomized comparative trial, and forty-four non-comparative trials were included. The RCT reported an overall mortality of 3.1 percent in the WCD group versus 4.9 percent in controls (relative risk [RR]: .64; 95 percent confidence interval [CI], .43-.98, p = .04), but no significant effect on arrhythmia-related mortality. The RR for arrhythmia-related mortality amounted to .67 (95 percent CI, .37-1.21, p = .18) as assessed in the RCT. Appropriate shocks were observed in 1.3 percent of patients in both comparative studies, and inappropriate shocks in .6 percent of patients in the RCT. Termination of ventricular tachycardia (VT) or ventricular fibrillation (VF) was successful in 75 to 100 percent of appropriate shocks in all studies. Adverse events assessed in the RCT showed a lower incidence of shortness of breath (38.8 percent vs. 45.3 percent; p = .004), higher incidence of rash at any location (15.3 percent vs. 7.1 percent; p < .001), and higher incidence of itching at any location (17.2 percent vs. 6.4 percent; p < .001) for WCD. CONCLUSIONS: Available evidence demonstrates that the WCD detects and terminates VT/VF events reliably and shows a high rate of appropriate shocks in mixed patient populations. Data of large registries confirm that the WCD is a safe intervention.

Budget impact analysis on the introduction of a guideline based hepatitis B and C screening into a routine check-up in the German primary care setting.

OBJECTIVES: Systematic screening for chronic hepatitis B and C does not yet exist in Germany. Therefore, the implementation of a screening approach within a preventive medical examination performed by primary care physicians ('Check-Up 35+') was evaluated in a recent prospective multicenter study. The present analysis estimates the financial consequences for the statutory health insurance by budget impact analysis. MATERIALS AND METHODS: A Markov cohort model was developed consisting of 21 health states. Four different screening scenarios derived from the previous multicenter study were compared to usual care, a strategy without screening for hepatitis. Actual cost data for Germany were calculated and systematic literature searches for all input parameters were performed. RESULTS: The base case results in incremental costs for the screening strategies compared to no hepatitis screening of 165-227 € per patient in a 20-year horizon. Two main parameters influence the financial consequences: (A) detection and treatment increase the costs in the beginning. (B) Screening avoids hepatitis induced end-stage liver disease. The initial higher costs exceed the later savings. Sensitivity analyses demonstrate a strong impact of medication costs for the treatment of additionally detected hepatitis infections on the outcome. This finding is robust to sensitivity analysis. CONCLUSIONS: The screening strategy proposed here implies additional costs for the statutory health insurance, however, a decision regarding its usefulness must consider criteria other than cost. For example, the high burden of disease due to liver cirrhosis and liver carcinoma should be considered. Therefore, an additional cost-effectiveness-analysis should be conducted.

Common misunderstandings of evidence-based medicine.

Currently, most evidence assessments in guidelines or health technology assessments (HTAs) rely on the assumption that a randomized controlled trial (RCT) is always the best source of evidence. However, if the outcome in a control group is certain, e.g. death within a short time with an almost 100% chance, or if an event can only occur in the treatment group, there is no need for a randomized control group; the evidence cannot be improved by a control group, nor by an RCT design. If a cause-effect relationship is certain ("primary or direct evidence"), a therapeutic effect can be diluted in the population of an RCT by cross-over, etc. This can lead to serious misinterpretations of the effect. While experts such as the GRADE group or Cochrane institutes recommend using all available evidence, the leading approach in many guidelines and HTAs is assessing "the best available trials", i.e. RCTs. But since RCTs only deliver probabilities of cause-effect relationships, it is not appropriate to demand RCTs for certain effects. A control group can only diminish the net value of a treatment since the outcome in the control group is subtracted from the outcome in the treatment group. Therefore, under identical circumstances, an RCT will always show lower effect rates compared to a single arm study of the same quality, for desired as well as for adverse effects. Considering these inconsistencies in evidence-based medicine interpretation, the evidence pyramid with RCTs at the top is not always a reliable indicator for the best quality of evidence.

Clinical effectiveness and cost effectiveness of tailoring chronic hepatitis C treatment with peginterferon alpha-2b plus ribavirin to HCV genotype and early viral response: a decision analysis based on German guidelines.

BACKGROUND: Recently developed German guidelines for antiviral treatment in patients with chronic hepatitis C recommend basing drug dosage, intended treatment duration and early stopping rules on the genotype of the hepatitis C virus and early viral responses to treatment. OBJECTIVES: To evaluate effectiveness and cost effectiveness of different antiviral treatment strategies including the German guidelines, for chronic hepatitis C. METHODS: A validated lifetime Markov model was used to project life expectancy, QALYs and lifetime costs for the following strategies: (i) no antiviral therapy (NoAVT); (ii) interferon-alpha-2b plus ribavirin for 48 weeks (IFN + R); (iii) peginterferon-alpha-2b plus weight-based ribavirin for 48 weeks (PEG + R); (iv) peginterferon-alpha-2b plus ribavirin according to German guidelines with genotype-dependent treatment duration, dosage and 12-week viral response evaluation (GUIDE). Clinical and resource utilization data were derived from a clinical trial, the published literature and a survey of German hepatologists. Incremental cost-effectiveness ratios (ICERs) were calculated adopting the German societal perspective. Costs (in euro, year 2005 values) and health outcomes were discounted at 3% annually. Uncertainty was assessed using deterministic and probabilistic sensitivity analyses. RESULTS: Compared with NoAVT, PEG + R increased undiscounted life expectancy by 5.0 life-years (5.2 QALYs) and GUIDE increased undiscounted life expectancy by 4.9 years (5.1 QALYs). Compared with PEG + R, GUIDE saved 13% of hepatitis C virus-related lifetime costs per patient. GUIDE dominated IFN + R. Compared with NoAVT, discounted ICERs were euro1500 per QALY for GUIDE and euro3200 per QALY for PEG + R. CONCLUSION: Administering GUIDE should allow tailoring treatment efficiently to genotype, bodyweight and early viral response in patients with chronic hepatitis C, and appears cost effective compared with other well accepted medical interventions.

Impact of 4 different definitions used for the assessment of the prevalence of the Metabolic Syndrome in primary healthcare: The German Metabolic and Cardiovascular Risk Project (GEMCAS).

BACKGROUND: The metabolic syndrome (MetSyn) places individuals at increased risk for type 2 diabetes and cardiovascular disease. Prevalence rates of the population of the MetSyn are still scarce. Moreover, the impact of different definitions of the MetSyn on the prevalence is unclear. Aim here is to assess the prevalence of the MetSyn in primary health care and to investigate the impact of four different definitions of the MetSyn on the determined prevalence with regard to age, gender and socio-economic status. METHODS: The German-wide cross-sectional study was conducted during two weeks in October 2005 in 1.511 randomly selected general practices. Blood samples were analyzed, blood pressure and waist circumference assessed, data on lifestyle, medication, chronic disorders, and socio-demographic characteristics collected. MetSyn prevalence was estimated according to the definitions of NCEP ATP III (2001), AHA/NHLBI (2004, 2005), and IDF (2005). Descriptive statistics and prevalence rate ratios using the PROG GENMOD procedure, were calculated. Cohen's kappa was used as measure for interreliability between the different prevalence estimates. RESULTS: Data of 35,869 patients (age range: 18-99, women 61.1%) were included. The prevalence was lowest using the NCEP ATP III- (all: 19.8%, men 22.7%, women: 18.0%), highest according to the IDF-definition (32.7%, 40.3%, 28.0%). The increase in prevalence with recent definitions was more pronounced for men than for women, and was particularly high for men and women aged 60-79 years. The IDF-definition resulted in a higher prevalence especially in those with the highest educational status. Agreement (kappa) between the NCEP ATP III- and IDF-definition was 0.68 (men 0.61, women 0.74), between the updated the AHA/NHLBI- (2005) and IDF-definition 0.85 (men 0.79, women 0.89). CONCLUSION: The prevalence of metabolic syndrome is associated with age, gender, and educational status and increases considerably with each newly published definition. Our data highlight the need for a better evidence regarding thresholds of the components of the metabolic syndrome, especially with regard to the IDF-definition - according to which in some populations a majority of subjects are diagnosed with the metabolic syndrome.

Using competence network collaboration and decision-analytic modeling to assess the cost-effectiveness of interferon alpha-2b plus ribavirin as initial treatment of chronic hepatitis C in Germany.

The objective of this study was to translate and apply a decision-analytic model for chronic hepatitis C (CHC) to the German health care context using competence network collaboration. The German Hepatitis C Model (GEHMO) competence network used a systematic multistep approach to identify and transfer a high quality Markov model for CHC to the German health care context. GEHMO was used to project lifetime clinical and economic outcomes and to determine the cost-effectiveness of initial antiviral therapy with interferon a-2b plus ribavirin from a societal perspective. In 40-year-old patients combination therapy for 24 and 48 weeks increased life expectancy by 1.6 and 2.3 years, respectively, compared with interferon alone for 48 weeks. The discounted incremental cost-utility ratios (ICUR) for combination therapy were euro 5,500 per quality-adjusted life-year gained (QALY) for 24 weeks and euro 6,800/QALY for 48 weeks of treatment. ICUR was euro 9,800/QALY for moving from 24 to 48 weeks of treatment. Combination therapy remained cost-effective in sensitivity analyses. In conclusion, combination therapy with interferon alpha-2b and ribavirin is effective and cost-effective compared with other well-accepted medical treatments. Competence network collaboration and decision modeling provide a useful and efficient approach to combine evidence from international studies with country-specific parameters.

Cost-effectiveness analysis of a vaccination program for the prevention of herpes zoster and post-herpetic neuralgia in adults aged 50 and over in Germany.

Herpes zoster (HZ; shingles) is a common viral disease that affects the nerves and surrounding skin causing a painful dermatomal rash and leading to debilitating complications such as, mainly, post-herpetic neuralgia (PHN). Currently, there is no effective treatment for HZ and PHN. The objective of this study was to assess the cost-effectiveness of a HZ vaccination program in Germany. An existing Markov Model was adapted to the German healthcare setting to compare a vaccination policy to no vaccination on a lifetime time-horizon, considering 2 scenarios: vaccinating people starting at the age of 50 or at the age of 60 years, from the perspective of the statutory health insurance (SHI) and the societal perspective. According to the perspective, vaccinating 20% of the 60+ German population resulted in 162,713 to 186,732 HZ and 31,657 to 35,793 PHN cases avoided. Corresponding incremental cost-effectiveness ratios (ICER) were 39,306 €/QALY from the SHI perspective and 37,417 €/QALY from a societal perspective. Results for the 50+ German population ranged from 336,468 to 394,575 HZ and from 48,637 to 56,087 PHN cases avoided from the societal perspective. Corresponding ICER were 39,782 €/QALY from a SHI perspective and 32,848 €/QALY from a societal perspective. Sensitivity analyses showed that results are mainly impacted by discount rates, utility values and use of alternative epidemiological data.The model indicated that a HZ vaccination policy in Germany leads to significant public health benefits and could be a cost-effective intervention. The results were robust and consistent with local and international existing literature.

[Traditional Chinese Pharmacotherapy in Patients with Chronic Rhinosinusitis - an Observational Trial Considering the Origin of Medicinal Drugs]. / Traditionelle chinesische Arzneitherapie bei Patienten mit chronischer Rhinosinusitis − eine Therapiebeobachtung mit Berücksichtigung der Arzneimittelherkunft.

BACKGROUND: The use of Chinese medicinal drugs is becoming more common in Germany. However, the import from China results in aggravated quality controls and potentially jeopardized therapeutic safety. Therefore, in 1999 the Bavarian Department for Agriculture has initiated an interdisciplinary research project to cultivate and analyze important Chinese herbal plants. Currently 16 Bavarian-produced Chinese drugs are in use and distributed to patients by pharmacies. Despite a comparable quality of Bavarian pharmaceutical products, there are concerns remaining as the Bavarian medical drugs have been used for treatment purposes on patients since 2006, without their effect having been compared to the Chinese products. Therefore we performed an observational trial using a parallel group design on patients with chronic rhinosinusitis. METHODS: The duration of the trial was 4 weeks. After a 4-week follow-up, the patients were interviewed via telephone. During the trial the patients were given 2 × 50 ml of a decoction of Chinese medicinal herbs, either (a) from Bavarian controlled cultivation (Bavaria group) or (b) from Chinese production (China group). The therapeutic success was evaluated using numerical rating scales. RESULTS: In total, 64 patients completed the observational trial (31 Bavaria group, 33 China group). Both groups showed significant improvements in the main symptom scores of chronic rhinosinusitis as well as in secondary symptoms, such as the overall state of health or the tendency to catch a cold. There were no significant differences between the groups concerning the main symptoms scores. Overall the herbal decoctions had no severe side effects. CONCLUSION: This observational trial shows that Chinese herbal drugs from Bavarian cultivation are as effective as medicinal herbs imported from China, but the effects of concomitant therapies must be considered as well. The symptom score improvements during the treatment period were obvious and should stimulate further investigation on the efficacy of this herbal formula in the treatment of chronic rhinosinusitis.

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.

Alternative methods for the treatment of post-menopausal troubles.

BACKGROUND: Menopause is described as the transition from the reproductive phase of a women to the non reproductive. Changes in hormone levels might lead to complaints and health consequences especially during peri- and postmenopause. Hormone therapy has a potential damaging health risk profile and is recommended for temporal limited therapy for acute vasomotor symptoms only. OBJECTIVE: The present HTA-report aims to assess the effectiveness and the cost-effectiveness of alternative treatment methods for women with postmenopausal symptoms in Germany regarding patient relevant endpoints (reduction of symptoms and frequency of adverse events and improvement of quality of life). METHODS: A systematic literature search was carried out in 33 relevant databases in September 2010. Citations were selected according to pre-defined criteria and were extracted and evaluated. RESULTS: In the systematic research 22 studies are identified for the effectiveness evaluation, 22 primary studies and one review. High doses of isolated genistein reduce the frequency/intensity of hot flashes while low doses of genistein show no significant effect. Intake of isoflavone extract such as genistein, daidzein, glycitein in various combinations does not have an effect on improvement of cognitive function or vaginal dryness. The effect of black cohosh and hop extract for menopausal complaints cannot be determined since results are heterogenous. The combination of isoflavone, black cohosh, monk's pepper, valerian and vitamin E has a positive effect on menopause symptoms. Ginkgo biloba shows no significant effect on menopause symptoms and cognitive improvement beside mental flexibility. Acupuncture has a significant influence on hot flashes especially in severe cases. DISCUSSION/CONCLUSION: No final statement can be drawn regarding the effectiveness of alternative treatment methods due to qualitative shortcomings of included studies and a general limited availability of studies in this field. Furthermore, the generalization of the present HTA is limited due to the inclusion of only postmenopausal women.

Effectiveness of pharmaceutical therapy of ADHD (Attention-Deficit/Hyperactivity Disorder) in adults - health technology assessment.

BACKGROUND: Attention-Deficit/Hyperactivity Disorder (ADHD) is a mental disorder. Symptoms include hyperactivity, lack of attentiveness, and frivolousness. This disorder always begins in childhood, but can remain through adulthood. ADHD affects all areas of life and limits the quality of life due to its symptoms and the high rate of associated disorders that can develop. An established form of therapy is using stimulant medications, most commonly, containing Methylphenidate as the active ingredient. However, in Germany this ingredient is not approved for adults suffering from ADHD. Therefore, many adults cannot obtain appropriate medication to treat this disorder. OBJECTIVE: The following report (Health Technology Assessment [HTA]) examines the effectiveness and cost-effectiveness of the medical treatment of ADHD in adults as well as the ethical, social and legal aspects thereof. METHODS: In August 2009, a systematic literature search is performed in all relevant scientific databases. The selected citations fulfill predetermined inclusion criteria. The data in the publications is then systematically extracted, reviewed and assessed. A manual search of citations is conducted as well. RESULTS: NINETEEN STUDIES FULFILL THE INCLUSION CRITERIA: nine randomised controlled studies (RCT), five meta-analyses, three economic studies and two studies relevant to the legal aspects of the HTA. All RCT reveal that adult patients who receive medication containing a stimulant (Methylphenidate and Amphetamine) and Atomoxetine, see a reduction of ADHD symptoms compared to the placebo-treated patients. The drug response rate among the control group ranges from 7 to 42%; in the treatment group from 17 to 59.6%. The meta-analyses confirm the findings of the RCT. In light of the control group, it can be ascertained that there are higher annual costs (both direct and indirect) for patients with ADHD. The average annual medical expenses for an adult with ADHD were 1,262 $ in 1998 and 1,673 $ in 2001 (the converted and inflation-adjusted rate for 2009: between 1,270 and 1,619 Euro). The use of stimulants use may impair the patient's ability to drive, travel or do sports. No relevant studies can be identified concerning the ethical, social and/or legal aspects of stimulant medication for ADHD patients. DISCUSSION/CONCLUSION: Medical treatment, particularly including Methylphenidate and Atomoxetine, proves to have a positive effect. In order to attain an optimal drug response, dosing must be determined on an individual basis. There is a need of high-quality studies that directly compare various agents - an aspect which is relevant to medical effectiveness of a therapy. No definite statement can be made about the cost-effectiveness of the medical treatment of ADHD in adults. More health economic studies are therefore required. Apart from the unquestionable mental indication, it is already recommended by health economic reasons to establish the conditions for an adequate treatment with these medicaments also for adults.

Decision-analytic modeling to evaluate the long-term effectiveness and cost-effectiveness of HPV-DNA testing in primary cervical cancer screening in Germany.

BACKGROUND: Persistent infections with high-risk types of human papillomavirus (HPV) are associated with the development of cervical neoplasia. Compared to cytology HPV testing is more sensitive in detecting high-grade cervical cancer precursors, but with lower specificity. HPV based primary screening for cervical cancer is currently discussed in Germany. Decisions should be based on a systematic evaluation of the long-term effectiveness and cost-effectiveness of HPV based primary screening. RESEARCH QUESTIONS: What is the long-term clinical effectiveness (reduction in lifetime risk of cervical cancer and death due to cervical cancer, life years gained) of HPV testing and what is the cost-effectiveness in Euro per life year gained (LYG) of including HPV testing in primary cervical cancer screening in the German health care context? How can the screening program be improved with respect to test combination, age at start and end of screening and screening interval and which recommendations should be made for the German health care context? METHODS: A previously published and validated decision-analytic model for the German health care context was extended and adapted to the natural history of HPV infection and cervical cancer in order to evaluate different screening strategies that differ by screening interval, and tests, including cytology alone, HPV testing alone or in combination with cytology, and HPV testing with cytology triage for HPV-positive women. German clinical, epidemiological and economic data were used. In the absence of individual data, screening adherence was modelled independently from screening history. Test accuracy data were retrieved from international meta-analyses. Predicted outcomes included reduction in lifetime-risk for cervical cancer cases and deaths, life expectancy, lifetime costs, and discounted incremental cost-effectiveness ratios (ICER). The perspective of the third party payer and 3% annual discount rate were adopted. Extensive sensitivity analyses were performed in order to evaluate the robustness of results and identify areas of future research. RESULTS: In the base case analysis screening resulted in a 53% to 97% risk reduction for cervical cancer with a discounted ICER between 2,600 Euro/LYG (cytology alone every five years) and 155,500 Euro/LYG (Annual cytology age 20 to 29 years, and annual HPV age 30 years and older). Annual cytology, the current recommended screening strategy in Germany, was dominated. In sensitivity analyses variation in the relative increase in the sensitivity of HPV testing as compared to cytology, HPV test costs, screening adherence, HPV incidence, and annual discount rate influenced the ICER results. Variation in the screening start age also influenced the ICER. All cytology strategies were dominated by HPV screening strategies, when relative sensitivity increase by HPV testing compared to cytology was higher (scenario analysis with data for test accuracy from German studies). HPV testing every one, two or three years was more effective than annual cytology. With increased screening adherence a longer screening interval and with low screening adherence a shorter interval would be more cost-effective. With a reduction in HPV incidence of more than 70% triennial HPV screening in women aged 30 years and older (and biennial Pap screening in women aged 20 to 29 years) is cost-effective. The discounted ICER increases with increasing annual discount rate. Increasing screening start age to 25 years had no relevant loss in effectiveness but resulted in lower costs. An optimal strategy may be biennial HPV testing age 30 years and older with biennial cytology at age 25 to 29 years (ICER of 23,400 Euro/LYG). CONCLUSIONS: Based on these results, HPV-based cervical cancer screening is more effective than cytology and could be cost-effective if performed at intervals of two years or greater. Increasing the age at screening start to 25 years causes no relevant loss in effectiveness but saves resources. In the German context an optimal screening strategy could be biennial HPV testing at age 30 years and older with biennial cytology at the age of 25 to 29 years. An extension to a three-yearly screening interval requires substantially improved screening adherence or a higher relative increase in the sensitivity of HPV testing as compared to cytology. The implementation of an organised screening program for quality-controlled introduction of HPV-screening and -vaccination with continued systematic outcome evaluation is recommended.

Cost-effectiveness of cardiac resynchronization therapy in combination with an implantable cardioverter defibrillator (CRT-D) for the treatment of chronic heart failure from a German health care system perspective.

AIM: The aim of the study was to assess the incremental cost-effectiveness ratio (ICER) of Cardiac Resynchronization Therapy in combination with an Implantable Cardioverter Defibrillator (CRT-D) plus Optimal Pharmacological Therapy (OPT) compared to OPT alone in patients with chronic heart failure. METHODS AND RESULTS: A decision analytic model was used to estimate the ICER from a German Health Care System perspective. Effectiveness data were used as reported in the COMPANION study. Direct medical costs were considered for inpatient and outpatient treatments. Resource utilization was valued by the prices charged in 2005. Costs and effects were discounted by a discount rate of 3% per year. One-way and two-way sensitivity analyses were performed. The base-case analysis resulted in accumulated discounted QALYs of 0.958 for OPT, respectively 1.261 for CRT-D + OPT. Accumulated discounted costs were 4618 Euro for OPT, and 31 292 Euro for CRT-D + OPT, respectively, thus resulting in incremental costs per QALY gained of 88 143 Euro after two years. Considering a device longevity of seven years, this resulted in incremental costs per QALY of 24 650 Euro. CONCLUSION: CRT-D plus OPT may be a cost-effective alternative for the treatment of patients with CHF in NYHA functional class III and IV depending on device longevity.

Behaviour therapy for obesity treatment considering approved drug therapy.

INTRODUCTION: Obesity is a worldwide health problem whose prevalence is on the increase. Many obesity-associated diseases require intensive medical treatment and are the cause of a large proportion of health-related expenditures in Germany. Treatment of obesity includes nutritional, exercise and behaviour therapy, usually in combination. The goal of behaviour therapy for obesity is to bring about a long-term alteration in the eating and exercise habits of overweight and obese individuals. Under certain circumstances, drug treatment may be indicated. OBJECTIVES: What is the effectiveness of behaviour therapy for obesity considering approved drugs reduce weight under medical, economic, ethical-social and legal aspects? METHODS: A systematic review was conducted using relevant electronic literature databases. Publications chosen according to predefined criteria are evaluated by approved methodical standards of the evidence-based medicine systematically and qualitatively. RESULTS: In total 18 studies, included one HTA and one meta-analysis could be identified according to the predefined inclusion criteria. Three studies compare behaviour therapy to other therapy forms (advice or instruction on nutritional changes, physical activity or a combination of the two), six studies evaluate different forms of behaviour therapy, four studies and four studies compare behaviour therapies mediated by Internet or telephone. Three studies could be identified examining the effect of the combination of behaviour and drug therapy. Furthermore one HTA and one meta-analysis could be included in the evaluation. The behaviour therapy in comparison with other therapy forms reveals a higher effectiveness. In comparison of the different therapeutic approaches of the behaviour therapy intensive behaviour therapy forms and group therapy show a higher effectiveness. Studies related to behaviour therapy based on media support demonstrate a weight reduction both through the interventions of media alone as well as through the intervention of media in conjunction with personal support within the groups. However, analyses of the inter-group comparisons offer no statistically significant difference. However, analyses of the inter-group comparisons offer no statistically significant difference. Comparative analyses confirm the effectiveness of behaviour therapy in combination with additional drug treatment when compared to behaviour therapy alone. In all the studies presented here, relevant changes in weight of -5% to -10% are only partially achieved. High weight losses of less than -10% were found among the intervention group in two of the studies. One study reported a weight loss of -11.4% with the "group therapy" intervention method, while another study reported a weight loss of -11.2% with the "behaviour therapy plus drug treatment" intervention method. Studies with a subsequent follow-up period indicate a clear weight loss at the end of the intervention followed by a renewed weight gain towards the end of the follow-up period. For the evaluation of economic, social-ethical or legal aspects we could not identify any studies. DISCUSSION: A comparative assessment among the studies proved difficult due to their heterogeneous nature. Little conformity can be detected in either the contents of the behaviour therapy or in the treatment plans. The length of the follow-up periods also varies from study to study. Many studies only analyze weight changes within one group or for the entire study population. However, the results of these analyses all indicate a significant weight loss at the end of the intervention. CONCLUSION: Some effects of behaviour therapy on a reduction in weight can be shown. However, relevant weight changes of -5% to -10% are only achieved to a certain extent. The extremely heterogeneous nature of the interventions makes a comparison of the study results very difficult. A trend can be detected indicates that those treatments which offer drug treatment in addition to behaviour therapy are more effective than behaviour therapy alone. For the verification of long-term successes of a behaviour therapy too few data are available.

Elastic robust intramedullary nailing for forearm fracture in children.

BACKGROUND: Forearm fractures are the most common fractures in children (23% of all fractures). Basically there are two treatment options available for diaphyseal forearm fractures in children: closed reduction with cast immobilisation (conservative therapy) and the elastic stable intramedullary nailing (ESIN). Treatment decision is influenced by the doctor's estimation of fracture instability. Stable fractures can be treated conservatively whereas instable forearm shaft fractures can be treated according the following three treatment strategies: conservative therapy in an outpatient settingconservative therapy in the operating room in attendance to change to ESIN in case that no stabilisation can be achieved with cast immobilisationimmediate treatment with ESIN in the operating room. OBJECTIVES: Aim of this Health Technology Assessment (HTA) report is to assess and report the published evidence concerning effectiveness and cost-effectiveness of ESIN as a treatment option for diaphyseal forearm fractures in children and to identify future research need. Important parameters for the assessment of effectiveness are objective parameters (axis deviation, losses of motion, and numbers of reductions in case of redislocations) and subjective parameters (pain or impairment in quality of life). Furthermore, a health economic evaluation shall be done which refers to the costs of the different therapy strategies. METHODS: An extensive, systematic literature search in medical, economic, and HTA literature databases was performed. Relevant data were extracted and synthesised. RESULTS: Three cohort studies and seven case series have been identified. Controlled clinical studies, systematic reviews and/or HTA reports that gave evidence to answer the own study question have not been found. The identified studies partly differed in respect of defined indication for ESIN, study population and treatment strategies. For that reason comparability of results was limited. In the majority of cases the publications reported a successful consolidation of fractures treated with ESIN. The cohort studies reported no differences in mobility after treatment with ESIN compared to patients who were treated conservatively. No publications that argue health economic aspects of the ESIN in children could be identified in the literature search. A cost data assessment conducted by the authors of this report showed that ESIN is associated with higher costs compared to the other treatment strategies (without considering long term costs due to reduction in case of redisplacement). CONCLUSIONS: Little evidence for a dominance of ESIN in treating forearm shaft fractures of children compared to conservative therapy could be found. Accomplishment of ESIN without complications causes more costs than conservative therapy both in outpatient and in inpatient setting. However, if fracture stabilisation cannot be achieved by conservative therapy, further interventions will be necessary. They will result in a burden for the patients and higher costs.

Assessing the prevalence of the Metabolic Syndrome according to NCEP ATP III in Germany: feasibility and quality aspects of a two step approach in 1550 randomly selected primary health care practices.

OBJECTIVE: Metabolic Syndrome (MetSyn) describes a cluster of metabolic disorders and is considered a risk factor for development of cardiovascular disease. Although a high prevalence is commonly assumed in Germany data about the degree of its occurrence in the population and in subgroups are still missing. The aim of this study was to assess the prevalence of the MetSyn according to the NCEP ATP-III (National Cholesterol Education Program Adult Treatment Panel III) criteria in persons aged >or=18 years attending a general practitioner in Germany. Here we describe in detail the methods used and the feasibility of determining the MetSyn in a primary health care setting. RESEARCH DESIGN AND METHODS: The German-wide cross-sectional study was performed during two weeks in October 2005. Blood samples were analyzed in a central laboratory. Waist circumference and blood pressure were assessed, data on smoking, life style, fasting status, socio-demographic characteristics and core information from non-participants collected. Quality control procedures included telephone-monitoring and random on-site visits. In order to achieve a maximal number of fasting blood samples with a minimal need for follow-up appointments a stepwise approach was developed. Basic descriptive statistics were calculated, the Taylor expansion method used to estimate standard errors needed for calculation of confidence intervals for clustered observations. RESULTS: In total, 1511 randomly selected general practices from 397 out of 438 German cities and administrative districts enrolled 35,869 patients (age range: 18-99, women 61.1%). More than 50,000 blood samples were taken. Fasting blood samples were available for 49% of the participants. Of the participating patients 99.3% returned questionnaires to the GP, only 12% were not filled out completely. The overall prevalence of the MetSyn (NCEP/ATP III 2001) was found to be 19.8%, with men showing higher prevalence rates than women (22.7% respective 18.0%). CONCLUSIONS: This study was designed to provide data as robust as possible within the confines of an epidemiological study. Judging by the low degree of missing data and the high data quality, the feasibility for this kind of a research setting (short evaluation period, practitioners as data assessment sites) was found to be very good. The results will help to gain a more comprehensive insight into the prevalence of MetSyn for patients in primary health care in Germany.

Cost-effectiveness of quantitative ultrasound as a technique for screening of osteoporotic fracture risk: report on a health technology assessment conducted in 2001.

AIM: On behalf of the German Agency for Health Technology Assessment (DAHTA@DIMDI) a rapid economic HTA was conducted. Aim of the HTA was to evaluate the cost-effectiveness of quantitative ultrasound (QUS) for screening of osteoporotic fracture risk. Study population was formed by postmenopausal women. QUS was compared to the dual X-ray absorptiometry (DXA) as the most frequently used method of measurement. METHODS: According to the recommendations for rapid economic HTA a comprehensive literature search was conducted. Data of identified and relevant publications have been extracted in form of a qualitative and quantitative information synthesis. The authors calculated incremental cost-effectiveness ratios for different screening procedures: (1) one-step proceeding comparing QUS with DXA, (2) two-step proceeding starting with QUS followed by DXA in pathologic cases. RESULTS: An additional case diagnosed by DXA in a one-step proceeding rises additional costs of about 1,000 EURO. A two-step proceeding with QUS is cost-effective as long as the costs of one QUS examination are lower than 31%-51% of the costs of one DXA examination. DISCUSSION: All considered studies showed methodological limitations. None of them included long term effects like avoided bone fractures. Considering long-term effects probably would change the results. Due to the weakness of data no concluding judgement about the cost-effectiveness of QUS can be given.