Reduction of common cold symptoms by encapsulated juice powder concentrate of fruits and vegetables: a randomised, double-blind, placebo-controlled trial

Dietary supplements have been suggested in the prevention of the common cold, but previous investigations have been inconsistent. The present study was designed to determine the preventive effect of a dietary supplement from fruits and vegetables on common cold symptoms. In a randomised, double-blind, placebo-controlled trial, healthcare professionals (mainly nursing staff aged 18–65 years) from a university hospital in Berlin, Germany, were randomised to four capsules of dietary supplement (Juice Plus+®) or matching placebo daily for 8 months, including a 2-month run-in period. The number of days with moderate or severe common cold symptoms within 6 months (primary outcome) was assessed by diary self-reports. We determined means and 95 % CI, and differences between the two groups were analysed by ANOVA. A total of 529 subjects were included into the primary analysis (Juice Plus+®: 263, placebo: 266). The mean age of the participants was 39·9 (sd 10·3) years, and 80 % of the participants were female. The mean number of days with moderate or severe common cold symptoms was 7·6 (95 % CI 6·5, 8·8) in the Juice Plus+® group and 9·5 (8·4, 10·6) in the placebo group (P = 0·023). The mean number of total days with any common cold symptoms was similar in the Juice Plus+® and in the placebo groups (29·4 (25·8, 33·0) v. 30·7 (27·1, 34·3), P = 0·616). Intake of a dietary supplement from fruits and vegetables was associated with a 20 % reduction of moderate or severe common cold symptom days in healthcare professionals particularly exposed to patient contact

Why Is It So Difficult to Evaluate Nursing Interventions in Dementia?

Two recent health technology assessment (HTA) reports published in Germany focused on non-pharmacological interventions for patients with dementia. One of the major results was the poor methodological quality of the studies in this field. This paper concisely presents the main quantitative and qualitative findings of the HTA report published by the German Agency for HTA at the Institute of Medical Information and Documentation (dahta@DIMDI), followed by a detailed discussion of the major methodological problems observed for the inclusion criteria, interventions, the setting, number of patients included, duration of observation, comparators, clinical endpoints, health economics, and, most obvious, the impossibility of blinding and eliminating placebo effects for future clinical studies. We conclude with several suggestions addressing these challenges for future research in this field

Human papillomavirus (HPV) vaccination for the prevention of HPV 16/18 induced cervical cancer and its precursors

Introduction: Essential precondition for the development of cervical cancer is a persistent human papillomavirus (HPV) infection. The majority - approximately 70% - of cervical carcinomas is caused by two high-risk HPV types (16 and 18). Recently, two vaccines have been approved to the German market with the potential to induce protection against HPV 16 and HPV 18 among additional low-risk virus types. Objectives: To analyse whether HPV vaccination is effective with regard to the reduction of cervical cancer and precursors of cervical carcinoma (CIN), respectively? Does HPV vaccination represent a cost-effective alternative or supplement to present screening practice? Are there any differences concerning cost-effectiveness between the two available vaccines? Should HPV vaccination be recommended from a health economic point of view? If so, which recommendations can be conveyed with respect to a (re)organization of the German vaccination strategy? Which ethical, social and legal implications have to be considered? Methods: Based on a systematic literature review, randomized controlled trials (RCT) looking at the effectiveness of HPV vaccination for the prevention of cervical carcinoma and its precursors - cervical intraepithelial neoplasia - have been identified. In addition, health economic models were identified to address the health economic research questions. Quality assessment of medical and economic literature was assured by application of general assessment standards for the systematic and critical appraisal of scientific studies. Results: Vaccine efficacy in prevention of CIN 2 or higher lesions in HPV 16 or HPV 18 negative women, who received all vaccination doses, ranges between 98% and 100%. Side effects of the vaccination are mainly associated with injection site reactions (redness, turgor, pain). No significant differences concerning serious complications between the vaccination- and the placebo-groups were reported. Results of base case scenarios in the identified health economic modeling analyses range from approximately 3,000 Euro to 40,000 Euro per additional QALY (QALY = Quality-adjusted life year) and approximately 9,000 Euro to 65,000 Euro per additional life year (LYG), respectively. Discussion: The included studies show that both available HPV vaccines are effective in preventing HPV 16 and HPV 18 infections and probable resulting premalignant lesions of the cervix. However, the duration of protection is currently unclear. With regard to side effects, the vaccination can be considered as secure. Nevertheless, the number of cases within the clinical studies is not sufficient to determine the occurrence of rarely occurring (severe) adverse events in a reliable way. A reduction in the incidence and induced mortality through cervical cancer in Germany is not only depending on the vaccine’s clinical efficacy. Effects of the new technology on the overall participation rate in screening programs and the resulting vaccination rate and immunization status are also important factors. The results of identified health economic models vary substantially due to the heterogeneity of methodological approaches as well as chosen input parameters. However, almost all model-based analyses reached the conclusion that the implementation of a vaccination with lifelong protection can be considered as cost-effective, if the present screening practice continues. A comparison of the two vaccines shows, that the cost effectiveness ratios are more favorable with the quadrivalent vaccine than with the bivalent alternative when considering QALY as primary outcome parameter. The reason for this finding might be that in the case of the quadrivalent vaccine the prevention of genital warts can also be incorporated into the analysis. Variations of the duration of protection as well as the discounting rate were identified as the primary influencing factors of cost-effectiveness results. Conclusion: Implementation of HPV vaccination might lead to a reduction of cervical cancer in immunized women. However, uptake of immunization should be accompanied by further studies in order to assess long-term effectiveness and safety aiming at an optimization of possible implementation processes. High numbers of participants are of particular importance regarding immunization. This has to be backed up by programs to optimize early detection – as this affects even those women who already underwent immunization. Since cost-effectiveness evidence might be significantly affected by the unclear duration of protective benefits, a final verdict on the vaccination’s cost-effectiveness in the German setting is not possible. Hence, risk-sharing-agreements between third-party payers and manufacturers would pose an option to balance the consequences of uncertainty towards the duration of protection on cost-effectiveness

Efficacy and cost-effectiveness of the 13C-urea breath test as the primary diagnostic investigation for the detection of Helicobacter pylori infection compared to invasive and non-invasive diagnostic tests

Background: Helicobacter pylori (H. pylori) is one of the most common bacterial infections in humans. There is a risk factor for gastric or duodenal ulcers, gastric cancer and MALT (Mucosa Associated Lymphoid Tissue)-Lymphomas. There are several invasive and non-invasive methods available for the diagnosis of H. pylori. The 13C-urea breath test is a non-invasive method recommended for monitoring H. pylori eradication therapy. However, this test is not yet used for primary assessment of H. pylori in Germany. Objectives: What are the clinical and health economic benefits of the 13C-urea breath test in the primary assessment of H. pylori compared to other invasive and non-invasive methods? Methods: A systematic literature search including a hand search was performed for studies investigating test criteria and cost-effectiveness of the 13C-urea breath test in comparison to other methods used in the primary assessment of H. pylori. Only studies that directly compared the 13C-urea breath test to other H. pylori-tests were included. For the medical part, biopsy-based tests were used as the gold standard. Results: 30 medical studies are included. Compared to the immunoglobulin G (IgG) test, the sensitivity of the 13C-urea breath test is higher in twelve studies, lower in six studies and one study reports no differences. The specificity is higher in 13 studies, lower in three studies and two studies report no differences. Compared to the stool antigen test, the sensitivity of the 13C-urea breath test is higher in nine studies, lower in three studies and one study reports no difference. The specificity is higher in nine studies, lower in two studies and two studies report no differences. Compared to the urease test, the sensitivity of the 13C-urea breath test is higher in four studies, lower in three studies and four studies report no differences. The specificity is higher in five studies, lower in five studies and one study reports no difference. Compared to histology, the sensitivity of the 13C-urea breath test is higher in one study and lower in two studies. The specificity is higher in two studies and lower in one study. One study each compares the 13C-urea breath test to the 14C-urea breath test and the polymerase chain reaction (PCR) test, respectively, and reports no difference in sensitivity and specificity with the 14C-urea breath test, and lower sensitivity and higher specificity compared to PCR. The statistical significance of these differences is described for six of the 30 studies. Nine health economic evaluations are included in the Health Technology Assessment (HTA) report. Among these studies, the test-and-treat strategy using the 13C-urea breath test is compared to test-and-treat using serology in six analyses and to test and treat using the stool antigen test in three analyses. Thereby, test-and-treat using the breath test is shown to be cost-effective over the serology based strategy in three models and is dominated by a test-and-treat strategy using the stool antigen test in one model. A cost-effectiveness comparison between the urea breath test approach and the empirical antisecretory therapy is carried out in four studies. Of these, two studies report that the strategy using the urea breath test is cost-effective over the empirical antisecretory therapy. In two studies, test-and-treat using the 13C-urea breath test is compared to the empirical eradication therapy and in five studies to endoscopy-based strategies. The breath test approach dominates endoscopy in two studies and is dominated by this strategy in one study. Discussion: All included medical and economic studies are limited to a greater or lesser extent. Additionally, the results of the studies are heterogeneous regarding medical and economic outcomes respectively. Thus, the majority of the medical studies do not report the statistical significance of the differences in sensitivity and specificity. In direct comparisons the 13C- urea breath test shows higher sensitivity and specificity than the IgG and stool antigen tests. In comparison to the urease test, results for sensitivity are inconsistent, and the specificity is slightly higher for the 13C-urea breath test. There are not enough results for comparisons between the 13C-urea breath test and the 14C-urea breath test, histology and PCR to describe tendencies. The included economic studies suggest that the test-and-treat strategy using the 13C-urea breath test is cost-effective compared to test-and-treat using serology as well as empirical antisecretory therapies. Due to a lack of valid studies, it is not possible to assess the breath test approach in comparison to test-and-treat using the stool antigen test and the empirical eradication therapy respectively, regarding the cost-effectiveness. The results of economic analyses comparing test-and-treat using the breath test to endoscopy strategies are too heterogeneous to draw any conclusions. Overall, none of the included economic models is able to completely capture the complexity of managing patients with dyspeptic complaints. Conclusions/Recommendations: Based on available medical and economic studies, there is no sufficient evidence to recommend test and-treat using 13C-urea breath testing for the detection of H. pylori infection as the standard procedure for the management of uninvestigated dyspepsia in the German health care system. In addition, it must be considered that the DVGS guidelines of the Deutsche Gesellschaft für Verdauungs- und Stoffwechselkrankheiten (DVGS) recommend endoscopy based methods for the management of patients with dyspeptic complaints

Review on the medical and health economic evidence for an inclusion of colposcopy in primary screening programs for cervical cancer

Introduction: With 3.2% of all cancer cases in 2002, cervical carcinoma is the tenth most common cancer in Germany and causes 1.8% of all cancer deaths in women in Germany. To date diagnosis in Germany solely has been based on cervical cytology which has been criticised due to its low sensitivity and consequently high rate of false negative results. Objectives: How does colposcopy compare to cytological tests in terms of sensitivity and specificity, and what may be the effects of changes in screening for cervical carcinoma in Germany? Is there health economic evidence that may foster an inclusion of colposcopy into national screening programms? Methods: A systematic literature review was performed, including studies that compared colposcopy to cervical cytology in terms of sensitivity and specificity. In addition, a systematic review of the relevant health economic literature was performed to analyse cost-effectiveness issues relevant to the German setting. Results: A total of four studies fulfilled the inclusion criteria, of which only two were of high methodologic quality. In all studies, the sensitivity of colposcopy was lower than that of cytology. In three studies the specificity of colposcopy was lower than that of cytology, in one study specificity of colposcopy and cytology was similar. No health economic data suggesting positive effects of adding colposcopy in primary screening could be identified. Discussion: Only few studies have compared the test criteria of colposcopy with those of cytology for screening in cervical cancer. In all studies, sensitivity of colposcopy was even lower than the sensitivity of cytology, which has been critisized because of its low sensitivity. Conclusion: Based on the present data, an inclusion of colposcopy in primary cervical cancer screening programmes can not be recommended

Promotion of Physical Activity Using Point-of-Decision Prompts in Berlin Underground Stations

To evaluate point-of-decision prompts in the promotion of stair use in Germany, motivational posters were placed at three underground stations in Berlin. The proportion of passengers using stairs or stairways was counted before, during installation, and two weeks after removal of posters. In total, 5,467 passersby were counted. Stair use increased significantly in women, but not in men. The present pilot study thereby shows that the use of point-of-decision prompts is also feasible in Germany and it provides some evidence of effectiveness. Methodologically rigorous studies are warranted to confirm these findings

Concepts of care for people with dementia

Introduction: Today there are approximately one million people with dementia in Germany. If current demographic trends continue, this number is likely to rise substantially in the coming years. In the older population, dementia is the most frequent reason for long-term care. Because most forms of dementia cannot be cured, the aim of treatment is to delay disease progression and to maintain functioning and quality of life. Research questions: What is the evidence on different approaches to the long-term usual care of patients with dementia in terms of common endpoints such as quality of life, and social behaviour? How is the cost-effectiveness of these concepts to be evaluated? Which ethical, social, or legal issues are discussed in this context? Methods: Based on a systematic literature review, we include randomized, controlled studies that had at least 30 participants and investigated one or more of the following approaches of dementia care: validation therapy/emotion-oriented usual care, ergotherapy, sensory stimulation, relaxation techniques, reality orientation therapy, and reminiscence therapy. Studies had to be published after 1996 (after 1990 for the economic part) in English or German. Results: A total of 20 studies meet the inclusion criteria. Of these, three focus on validation therapy/emotion-oriented usual care, five on ergotherapy, seven on different kinds of sensory stimulation, two on reality orientation, two on reminiscence therapy, and one on a type of relaxation technique. There are no significant differences between the intervention and control groups in two of the three studies on validation therapy or emotion-oriented usual care, in two of the five studies on ergotherapy, in three of the seven studies on sensory stimulation, in both of the two studies on reminiscence therapy, and in the one study on relaxation. In the remaining ten studies, seven report some positive results in favour of the respective interventions, and three studies (ergotherapy, aroma therapy, and music/massage) report positive effects with respect to all of the endpoints measured. Six publications present economic results for usual-care-concepts. One study reports additional costs of 16 GBP (24.03 Euro (2006)) per patient per week for occupational therapie. Two publications declare incremental cost of 24.30 USD (25.62 Euro (2006)) per mini-mental-state-examination-(MMSE)-point gained per month respectively 1,380,000 ITL (506.21 Euro (2006)) per MMSE-point gained. Two publications focus on mixed interventions. One study reports the additional costs of an activity program (1.13 USD (1.39 Euro (2006)) per day per patient) and the other additional time for the usual care for mobile demented patients (average of 45 minutes per day per patient). With respect to ethical and social aspects the discussion focusses on the problem of autonomy: dementia does not necessarily mean inability to decide over the participtation in studies. Legal questions address the financial situation of patients, the organisation of their care and the legal representation of dementia patients. Discussion: Only a few studies on the nursing interventions considered in this report are methodologically robust. Most of the studies have a small number of participants and show substantial differences in terms of their inclusion criteria, implementation, and endpoints. This heterogeneity is reflected in the results: in half of the studies, the interventions have no positive effects compared to the control group. The other half of the studies reports some positive effects with regard to specific endpoints. All of the economic studies are, from a methodologial and a thematic standpoint, not suitable to answer the questions raised. Ethical, social and legal aspects are discussed but not systematically analysed. Conclusion: The studies conducted to date do not provide sufficient evidence of neither efficacy nor cost-effectiveness for any of the nursing interventions considered in the present HTA. However, lack of evidence does not mean lack of efficacy. Instead, more methodologically sound studies are needed. Particullary desireable are studies reflecting the framework of dementia care in Germany. This holds also for the healtheconomic evaluations of the chosen interventions

Assessment of effectiveness and cost-effectiveness of HPV testing in primary screening for cervical

Introduction: The introduction of a screening programme for cervical carcinoma in Germany has led to a significant reduction in incidence of the disease. To date, however, diagnosis in Germany has been based solely on cervical cytology, which has been criticised because of a low sensitivity and consequently high rate of false negative results. Because an infection with the human papillomavirus (HPV) previously was found to be a necessary aetiological factor in the development of cervical cancer, there has been some discussion that HPV testing should be included in cervical cancer screening. Objectives: How do HPV tests compare to cytological tests in terms of sensitivity and specificity, and what are the effects of screening for cervical carcinoma in Germany? Is there health economic evidence that may foster an inclusion of HPV testing into national screening programms? Methods: A systematic literature review was performed, including studies that compared the HPV test to cervical cytology in terms of sensitivity and specificity in the diagnosis of CIN 2+ (CIN=Cervical Intraepithelial Neoplasia). In addition, a systematic review of the relevant health economic literature was performed to analyze cost-effectiveness in the German setting. Results: A total of 24 studies fulfilled the inclusion criteria. One study consisted of three substudies. Hence, results of 26 comparisons of HPV and cytology are reported. In 25 of these, the HPV test was more sensitive than cytology, whereas cytology had better specificity in 21 studies. The combination of HPV test and cytology increased sensitivity. Variability in results was considerably larger for cytology than for HPV testing. Results of the economic meta-analysis suggest that in health care settings with already established PAP screening programms, cost-effectiveness strongly depends on screening intervals. In analyses comparing HPV screening to conventional PAP screening with two-yearly intervals, only 25% of the HPV strategies were found to be cost-effective, whereas in comparison with one-, three-, and five-yearly PAP screening, the percentage of overall cost-effective HPV strategies was 83%, 55%, and 92%, respectively. Results for annual screening intervals are based on the assumption of complete screening compliance, which has to be further evaluated in decision analyses in the future adapting to the German health care setting. Discussion: Including HPV testing in screening procedures for cervical carcinoma could lead to a reduction in false positive results. Doing so would involve one of the following approaches: a) combining the HPV test with cytology, or b) using cytology as triage in HPV-positive women. The most appropriate interval between screening tests and the best age to start or stop screening remains to be determined. At this point a formal health economic decision analyses may help in resolving those questions, additionally incorporating compliance and adherence within different screening scenarios. Conclusion: Considering medical evidence weighing the question whether HPV testing should be implemented into screening routine may not be if but how to do so. Open questions remain in setting the length of optimal screening intervals, the age range in which to screen, and the combination or sequence of existing cytology and HPV testing. Answers to those questions will be gathered in the very near future through large international clinical trials. Cost-effectiveness of implementing HPV testing is likely to exist in the management of borderline or unclear smears in triage treatment as well as in certain scenarios of primary screening within the German health care setting

Gesundheitsbezogene Lebensqualität bei gastroösophagealer Refluxerkrankung

Ziel der vorliegenden Arbeit ist die Untersuchung der gesundheitsbezogenen Lebensqualität bei Patienten mit gastroösophagealer Refluxerkrankung (GERD) unter „usual care“ Bedingungen über einen Zeitraum von zwei Jahren. Insgesamt wurden 6215 Patienten mit GERD in die Studie eingeschlossen und vier bis acht Wochen mit einem Protonenpumpenhemmer behandelt. Danach begann die Beobachtungsphase, in der keine weiteren Vorgaben zur Behandlung gemacht wurden. Die Lebensqualität wurde mit dem Short Form 36 (SF-36) und dem Quality of Life in Reflux and Dyspepsia (QOLRAD) zu Studienbeginn, nach zwei Wochen und im Anschluss daran einmal jährlich erhoben. Die Ergebnisse zeigen, dass die Lebensqualität von Patienten mit GERD im Vergleich zur Normpopulation deutlich eingeschränkt war. Nach zweiwöchiger Behandlung mit einem PPI stieg die Lebensqualität deutlich in allen gemessenen Bereichen. Nach 12 und 24 Monaten lag die Lebensqualität unter den Werten unmittelbar nach der Behandlungsphase, aber noch immer deutlich über den Ausgangswerten. Die Verbesserung der Lebensqualität war vor allem abhängig von einer Verbesserung der Symptome. Mit dem krankheitsspezifischen Messinstrument QOLRAD konnte die Veränderungen in der Lebensqualität der Patienten genauer erfasst werden als mit dem SF-36. Daher sollte bei Studien zur Lebensqualität bei GERD, insbesondere wenn Therapieeffekte gemessen werden sollen, möglichst ein krankheitsspezifisches Messinstrument zum Einsatz kommen.The aim of this study is to analyse the health-related quality of life in patients with gastro-eosophageal reflux disease (GERD) under routine over a period of two years. 6215 patients with physician diagnosed GERD have been recruited. All patients received treatment with a proton pump inhibitor for four to eight weeks. Afterwards they entered the follow-up, and their treatment is at the discretion of their physicians. Quality of life was assessed with the questionnaires Short Form 36 (SF-36) and Quality of Life in Reflux and Dyspepsia (QOLRAD) at baseline, two weeks, and after one and two years. At baseline, quality of life in patients with GERD was lower than in the norm population. After two weeks treatment with PPI, quality of life improved in all dimensions. After 12 and 24 months, quality of life was lower than after two weeks, but significantly better than at baseline. The improvement of quality of life was particulary correlated with symptom improvement. Changes in quality of life could be more accurately described with the QOLRAD than with the SF-36. Therefore, studies on health related quality of life in GERD patients should include a disease specific questionnaire

Epidemiology and health economics of gastroesophageal reflux disease

Die gastroösophageale Refluxerkrankung (GERD) ist eine der häufigsten gastrointestinalen Störungen. Die Prävalenz wird in Nordamerika und Westeuropa auf etwa 10-20% geschätzt. In Deutschland liegt die Häufigkeit von moderaten oder schweren Refluxsymptomen bei 18%. Die Häufigkeit steigt mit dem Alter an und beträgt in der Alterskategorie der 60- 69jährigen 25%. Frauen und Männer sind etwa gleich oft betroffen. Wichtige Risikofaktoren der Refluxerkrankung sind Adipositas und Rauchen. Die Ergebnisse zu den in diesem Kontext diskutierten Ernährungsgewohnheiten sind unklar. Gründe hierfür können methodische Limitationen der vorliegenden Untersuchungen sein, insbesondere querschnittliche Studiendesigns und Mängel bei der validen Erfassung des Ernährungsverhaltens. Die Lebensqualität von GERD Patienten ist deutlich eingeschränkt, steigt aber durch eine Standarddosierung von PPI auf das Niveau der Normalpopulation. Dieses Niveau bleibt auch unter Bedingungen der Routineversorgung langfristig erhalten. Aufgrund des chronischen Erkrankungsverlaufs ist der überwiegende Teil der GERD Patienten allerdings dauerhaft auf die Einnahme von Medikamenten angewiesen. Dadurch entstehen erhebliche Krankheitskosten. In der ProGERD Kohorte lagen diese Kosten bei €380 pro Patient und Jahr, mit 90% machten die direkten Krankheitskosten, insbesondere die Ausgaben für Medikamente, den größten Teil der Kosten aus.Gastroesophageal reflux disease (GERD) is a common disorder, with a prevalence of 10-20% in North American and Western European countries. In Germany, the prevalence of moderate or severe reflux disease in adults is about 18%, increasing to 25% in the age category of 60-69. The prevalence of reflux symptoms is similar between men and women. Important risk factors for GERD are obesity and smoking. The role of particular foods in the aetiology of heartburn or regurgitation is unclear, due to important limitations like cross-sectional study designs or the assessment of dietary behaviour. Patients with GERD symptoms have a substantially reduced health-related quality of life (QoL). However, PPI therapy leads to rapid symptom control and is associated with improvements in QoL. Achieving wellcontrolled QoL is possible in GERD patients under routine care, though the majority of GERD patients needs long- term medication, thus causing relevant disease-related costs. In the ProGERD study, costs were €380 per patient and year. Direct costs, especially for medication, caused 90% of all disease-related costs