The KORE-INNOVATION trial, a prospective controlled multi-site clinical study to implement and assess the effects of an innovative peri-operative care pathway for patients with ovarian cancer: rationale, methods and trial design.

BACKGROUND: Advanced ovarian cancer is managed by extensive surgery, which could be associated with high morbidity. A personalized pre-habilitation strategy combined with an 'enhanced recovery after surgery' (ERAS) pathway may decrease post-operative morbidity. PRIMARY OBJECTIVE: To analyze the effects of a combined multi-modal pre-habilitation and ERAS strategy on severe post-operative morbidity for patients with ovarian cancer (primary diagnosis or first recurrence) undergoing cytoreductive surgery. STUDY HYPOTHESIS: A personalized multi-modal pre-habilitation algorithm entailing a physical fitness intervention, nutritional and psycho-oncological support, completed by an ERAS pathway, reduces post-operative morbidity. TRIAL DESIGN: This is a prospective, controlled, non-randomized, open, interventional two-center clinical study. Endpoints will be compared with a three-fold control: (a) historic control group (data from institutional ovarian cancer databases); (b) prospective control group (assessed before implementing the intervention); and (c) matched health insurance controls. INCLUSION CRITERIA: Patients with ovarian, fallopian, or primary peritoneal cancer undergoing primary surgical treatment (primary ovarian cancer or first recurrence) can be included. The intervention group receives an additional multi-level study treatment: (1) standardized frailty assessment followed by (2) a personalized tri-modal pre-habilitation program and (3) peri-operative care according to an ERAS pathway. EXCLUSION CRITERIA: Inoperable disease or neoadjuvant chemotherapy, simultaneous diagnosis of simultaneous primary tumors, in case of interference with the overall prognosis (except for breast cancer); dementia or other conditions that impair compliance or prognosis. PRIMARY ENDPOINT: Reduction of severe post-operative complications (according to Clavien- Dindo Classification (CDC) III-V) within 30 days after surgery. SAMPLE SIZE: Intervention group (n=414, of which approximately 20% insure with the participating health insurance); historic control group (n=198); prospective control group (n=50), health insurance controls (for those intervention patients who are members of the participating health insurance). ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: The intervention phase started in December 2021 and will continue until June 2023. As of March 2023, 280 patients have been enrolled in the intervention group. The expected completion of the entire study is September 2024. TRIAL REGISTRATION: NCT05256576.

Desire for biological parenthood and patient counseling on the risk of infertility among adolescents and adults with hemoglobinopathies.

BACKGROUND: Both diagnosis and treatment of hemoglobinopathies have been associated with an increased risk of fertility impairment. German guidelines recommend annual monitoring of fertility parameters to enable early detection of fertility impairment and/or to offer fertility preservation (FP) when indicated. We explored the general desire for parenthood, the frequency of recalling fertility counseling and testing, and the utilization of FP in adolescents and adults with hemoglobinopathies. PROCEDURE: In a cross-sectional study, patients aged 12-50 years, treated in Germany, Austria, or Switzerland, were surveyed on fertility-related aspects. Medical data, including fertility testing results, were collected from patient records. RESULTS: Overall, 116/121 eligible patients, diagnosed with sickle cell disease (70.7%), thalassemia (27.6%), or other hemoglobinopathy (1.7%), participated in our study (57.8% female, median age 17.0 years, range 12-50 years). All participants required treatment of the underlying hemoglobinopathy: 68.1% received hydroxyurea, 25.9% required regular blood transfusions, and 6.0% underwent hematopoietic stem cell transplantation (HSCT). Most patients (82/108, 75.9%) stated a considerable to strong desire for (future) parenthood, independent of sex, education, diagnosis, or subjective health status. Fertility counseling was only recalled by 32/111 patients (28.8%) and least frequently by younger patients (12-16 years) or those treated with regular blood transfusions or hydroxyurea. While fertility testing was documented for 59.5% (69/116) in medical records, only 11.6% (13/112) recalled previous assessments. FP was only used by 5.4% (6/111) of patients. CONCLUSION: Most patients with hemoglobinopathies wish to have biological children, yet only few recalled fertility counseling and testing. Adequate patient counseling should be offered to all patients at risk for infertility.

Acupuncture in chemotherapy-induced dysgeusia (AcuDysg): study protocol of a randomised controlled trial.

INTRODUCTION: Dysgeusia is a common side effect of chemotherapy in patients with cancer, but to date, there is no effective treatment. Many patients with cancer request complementary medicine treatment in addition to their cancer treatments, and acupuncture is highly accepted for patients with cancer; however, evidence regarding the effectiveness of acupuncture for dysgeusia is scarce.The study investigates the effectiveness of an additional dysgeusia-specific acupuncture plus self-acupressure intervention compared with supportive acupuncture plus self-acupressure intervention alone for chemotherapy-induced dysgeusia in patients with cancer. METHODS AND ANALYSIS: This is a multicentre, randomised, controlled and two-armed parallel-group, single-blind trial involving 130 patients. Both groups will receive eight sessions of acupuncture treatment over a period of 8 weeks and will be trained to perform self-acupressure (eLearning combined with therapist instruction) at predefined acupressure points once a day during the whole treatment period. Patients in the control group will receive supportive routine care acupuncture and self-acupressure treatment only; in addition to this treatment, the intervention group will receive the dysgeusia-specific acupuncture and acupressure within the same treatment session. The primary outcome is the perceived dysgeusia over 8 weeks, measured weekly after the acupuncture treatment. Secondary outcomes include the indices from the objective taste and smell test, weight loss, perceived dysgeusia, fatigue, distress, nausea and vomiting, odynophagia, xerostomia and polyneuropathy, as well as quality of life at the different time points. ETHICS AND DISSEMINATION: The study has been approved by the Cantonal Ethics Committee (CEC) (Kanton Zürich Kantonale Ethikkommission) (approval no. KEK-ZH-Nr. 2020-01900). The results will be submitted to a peer-reviewed journal for publication. TRIAL REGISTRATION NUMBERS: DRKS00023348, SNCTP000004128.

Controlled non-randomised before-after study evaluating the impact of a focused recommendation card on vaccination rates of oncological patients-The Easy Vaccination in Oncology (EVO) strategy.

OBJECTIVE: By implementing a focused must-have vaccination strategy (Easy Vaccination in Oncology [EVO]), we aimed to increase rates for high-impact vaccinations (Streptococcus pneumoniae, influenza, herpes zoster and hepatitis B) in the at-risk population of oncological patients. METHODS: In this German multicentre interventional non-randomised controlled two-arm open trial with repeated cross-sectional data collection, we evaluated the EVO strategy as an easy to implement approach. Vaccination rates were assessed in the outpatient setting and re-assessed after 3 months. A generalised linear mixed model (GLMM) was used to assess the primary endpoint (Streptococcus pneumoniae vaccination rates according to recommendations), taking clustering within clinics into account. RESULTS: Vaccination rates substantially increased in the intervention group; Streptococcus pneumoniae +21.5% (+16.7% according to recommendations), influenza +12.2%, herpes zoster +13.3% (+13.6% age group 50+), and hepatitis B +11%. Vaccination rates in the control group tended to decrease or increase only moderately (-5.8% [-3.8%], +7.4%, +2.1% [1.4%], and -1.7%, respectively). GLMM showed significant effect of the intervention (OR 7.50, 95% CI 2.18-25.80, p = 0.001). CONCLUSION: This easy-to-implement and resource-saving approach has the potential to increase vaccination rates in oncological patients and to have a considerable impact protecting oncological patients from preventable infectious diseases. CLINICAL TRIAL REGISTRATION: The study was registered at the German Resister for Clinical Studies (DRKS) under DRKS00020118.

A novel concept of screening for subgrouping factors for the association between socioeconomic status and respiratory allergies.

BACKGROUND: The new subgroup screening tool "subscreen" aims to understand the unclear and complex association between socioeconomic status (SES) and childhood allergy. This software R package has been successfully used in clinical trials but not in large population-based studies. OBJECTIVE: To screen and identify subgrouping factors explaining their impact on the association between SES and respiratory allergies in childhood and youth. METHODS: Using the national German childhood and youth survey dataset (KiGGS Wave 2), we included 56 suspected subgrouping factors to investigate the association between SES (low vs. high) and allergic rhinitis and/or asthma in an exploratory manner. The package enabled a comprehensive overview of odds ratios when considering the SES impact per subgroup and analogously all disease proportions per subgroup. RESULT: Among the 56 candidate factors, striking subgrouping factors were identified; e.g., if mothers were younger and in the low SES group, their children had a higher risk of asthma. In addition children of the teen's age were associated with increased risks in the low SES group. For the crude proportions, factors such as (parental) smoking or having had no "contact with farm animals" were identified as strong risk factors for rhinitis. SIGNIFICANCE: The "subscreen" package enabled the detection of notable subgroups for further investigations exemplarily for similar epidemiological research questions.

Dual-energy X-ray Absorptiometry Does Not Represent Bone Structure in Patients with Osteoporosis: A Comparison of Lumbar Dual-Energy X-Ray Absorptiometry with Vertebral Biopsies.

STUDY DESIGN: Prospective cross-sectional exploratory study. OBJECTIVE: To evaluate the correlation between in vivo lumbar dual-energy x-ray absorptiometry (DXA) and parameters of bone architecture in micro-computed tomography (micro-CT) in patients with osteoporosis. SUMMARY OF BACKGROUND DATA: DXA is the current diagnostic standard for evaluating osteoporosis. However, there are various concerns regarding its validity, especially in the spine. No study has so far investigated whether in vivo DXA correlates with the actual lumbar bone architecture. METHODS: Lumbar DXA scans were compared with micro-CT analysis of vertebral biopsies in patients with osteoporotic vertebral fractures (fracture group) and those without (control group). Preoperatively, all patients underwent a DXA scan (L1-L4). Intraoperative biopsies from nonfractured vertebrae (preferably L3) were analyzed by micro-CT regarding bone quantity and quality. The groups were compared regarding differences in DXA and micro-CT results. In each group, a correlation analysis was performed between DXA and micro-CT. RESULTS: The study included 66 patients (33 per group). Preoperative DXA results were worse in the fracture group than the control group (areal bone mineral density [aBMD] 0.95 vs. 1.31, T-score -1.97 vs. 0.92, each P < 0.001). Micro-CT analysis confirmed differences regarding quantitative parameters (bone/total volume: 0.09 vs. 0.12, P < 0.001) and qualitative parameters (connectivity index: 15.73 vs. 26.67, P < 0.001; structure model index: 2.66 vs. 2.27, P < 0.001; trabecular number: 2.11 vs. 2.28, P = 0.014) of bone architecture between both groups. The DXA results did not correlate with micro-CT parameters in the fracture group. In the control group, correlations were found for some parameters (bone/total volume vs. aBMD: r = 0.51, P = 0.005; trabecular number vs. aBMD: r = 0.56, P = 0.001). CONCLUSION: These data constitute the first comparison of DXA measurements with microstructural analysis of vertebral biopsies in patients with osteoporosis. Our results indicate that lumbar DXA neither qualitatively nor quantitatively represents microstructural bone architecture and is therefore not a reliable tool for the evaluation of bone quality in the spine.Level of Evidence: 3.

Advanced meta-analyses comparing the three surgical techniques total disc replacement, anterior stand-alone fusion and circumferential fusion regarding pain, function and complications up to 3 years to treat lumbar degenerative disc disease.

PURPOSE: The purpose of our meta-analyses is to find the most appropriate surgical technique treating lumbar degenerative disc disease (DDD). Spinal fusion is the conventional treatment for lumbar DDD. Total disc replacement (TDR) has been developed to avoid negative effects of fusions by preserving functionality. To our knowledge, there is no evaluation comparing meta-analytically the clinical results of three different surgical techniques with same inclusion and exclusion criteria for treating DDD. METHODS: The surgical techniques TDR, anterior lumbar interbody fusion (ALIF) and circumferential fusion (CFF) are pairwise meta-analytically compared. Primary outcomes are pain measured by the Visual Analogue Scale (VAS) and function measured by the Oswestry Disability Index (ODI). Secondary outcomes are the mean number of complications per case (MNOC) at surgery and follow-up and the overall MNOC. RESULTS: In our systematic search, we found finally six prospective studies with the minimum follow-up of two years: four randomized controlled trials and two cohort studies. In VAS and ODI, TDR is proved to be superior to ALIF and CCF (p < 0.05), whereat ALIF is more effective than CFF without statistical significance. CFF presents the best result in complications with the lowest overall MNOC (0.1), followed by TDR (1.2) and ALIF (1.5). CONCLUSION: According to our meta-analyses, we regard TDR to be the most appropriate surgical technique treating DDD, followed by ALIF. Further studies with a longer follow-up are needed using the same methodical approach to strengthen the VAS and ODI results and to explain the discrepant result to complications.

Prophylactic acupuncture treatment during chemotherapy with breast cancer: a randomized pragmatic trial with a retrospective nested qualitative study.

PURPOSE: This study investigated the effect of additional prophylactic acupuncture during chemotherapy on quality of life and side effects compared to standard treatment alone in breast cancer patients. METHODS: In a pragmatic trial, newly diagnosed breast cancer patients were randomized to additional acupuncture treatments over 6 months or standard care alone (control group). The primary outcome was the disease-specific quality of life (FACT-B). Twenty qualitative semi-structured interviews were conducted with ten patients from each group regarding their subjective experiences. RESULTS: A total of 150 women (mean age 51.0 (SD 10.0) years) were randomized. For the primary endpoint, FACT-B total score after 6 months, no statistically significant difference was found between groups (acupuncture: 103.5 (95%, CI 88.8 to 107.2); control (101.4 (- 97.5 to 105.4); difference 2.0 (- 3.4 to 7.5) p = 0.458)). Qualitative content analyses showed that patients in the acupuncture group described positive effects on psychological and physical well-being. For both patient groups, coping strategies were more important than reducing side effects. CONCLUSIONS: Breast cancer patients receiving prophylactic acupuncture during chemotherapy did not show better quality of life in the questionnaires in contrast to the reported positive effects in the qualitative interviews. Coping strategies for cancer appear to be important. TRIAL REGISTRATION: clinicaltrials.gov; NCT01727362. Prospectively registered 11 July 2012; https://clinicaltrials.gov/ct2/show/NCT01727362 . The manuscript adheres to CONSORT guidelines.

Evaluation of a blended-learning training concept to train oncology physicians to advise their patients about complementary and integrative medicine (KOKON-KTO): study protocol for a prospective, multi-center, cluster-randomized trial.

BACKGROUND: Many cancer patients are interested in complementary and integrative medicine during and after regular cancer treatment. Given the high number of users it is important that physicians and patients engage in a dialog about useful complementary and integrative medicine therapies during cancer treatment. In a prospective, multi-center, cluster-randomized evaluation study we will develop, implement and evaluate a training program for oncology physicians advising their patients on complementary and integrative medicine. The main objective of the study is to evaluate whether training physicians in a blended-learning approach (e-learning + skills-training workshop) in providing advice to their cancer patients on complementary and integrative medicine, in addition to handing out an information leaflet about reputable websites, has different effects on the outcomes of patients, physicians, and their interaction level, compared to only giving out the information leaflet. METHODS/DESIGN: Forty-eight oncology physicians will be included into a cluster-randomized trial to either participate or not in the blended-learning training. Physicians will then advise 10 cancer patients each, resulting in 480 patients participating in the trial. The blended learning consists of nine units of up to 45 min of e-learning and 18 units of up to 45 min of on-site skills-training workshop focusing. Outcomes will be measured on the physician, patient, and physician-patient-interaction level. DISCUSSION: A blended-learning program for oncology physicians to advise their cancer patients in a systematic way and a reasonable time frame on complementary and integrative medicine will be evaluated in depth in a large cluster-randomized trial. TRIAL REGISTRATION: German Clinical Trials Register, ID: DRKS00012704 . Registered on 28 August 2017.

Long-term effectiveness of a combined student-parent and a student-only smoking prevention intervention among 7th grade school children in Berlin, Germany.

BACKGROUND AND AIMS: In Germany, the smoking prevalence among adolescents is among the highest in Europe. Our aim was to evaluate the long-term effectiveness of a combined student-parent and a student-only smoking prevention programme to reduce the smoking prevalence among 7th grade students in Berlin. DESIGN: Three-armed cluster-randomized controlled trial (RCT). Schools as cluster units were randomized into (i) student intervention, (ii) combined student-parent intervention or (iii) control group, with follow-up after 12 and 24 months. SETTING: High schools and integrated secondary schools in Berlin, Germany. PARTICIPANTS: Seventh grade students aged 11-16 years. We included 47 schools, 161 classes and 2801 students [50.1% girls, mean age ± standard deviation (SD) = 13.0 ± 0.6 years]. MEASUREMENTS: The primary outcome was self-reported regular smoking (at least one cigarette per day) after 24 months (point prevalence). Further self-reported outcomes were other smoking behaviours as well as parental rules and attitudes towards smoking. Comparisons were calculated as odds ratios (OR) with 95% confidence intervals (CI). FINDINGS: At baseline, 2.3% of the students reported that they smoked regularly. After 24 months, 7.8% and 7.0% were regular smokers in the student-only intervention and the student-parent intervention, respectively, compared with 10.1% in the control group. The OR for being a regular smoker was 0.81 (0.34-1.92) for the student-parent intervention versus control, 0.95 (CI = 0.41-2.22) for the student-only intervention versus control and 0.85 (0.38-1.89) for student-parent intervention versus student-only intervention. CONCLUSION: A combined student-parent smoking prevention intervention delivered via secondary schools in Berlin, Germany did not result in a statistically significant reduction in regular smoking compared with a control group or a student-only intervention. The student-only intervention did not result in a significant reduction in regular smoking compared with the control group.

Effect of Short-Term Supplementation with Ready-to-Use Therapeutic Food or Micronutrients for Children after Illness for Prevention of Malnutrition: A Randomised Controlled Trial in Uganda.

BACKGROUND: Globally, Médecins Sans Frontières (MSF) treats more than 300,000 severely malnourished children annually. Malnutrition is not only caused by lack of food but also by illnesses and by poor infant and child feeding practices. Breaking the vicious cycle of illness and malnutrition by providing ill children with nutritional supplementation is a potentially powerful strategy for preventing malnutrition that has not been adequately investigated. Therefore, MSF investigated whether incidence of malnutrition among ill children <5 y old could be reduced by providing a fortified food product or micronutrients during their 2-wk convalescence period. Two trials, one in Nigeria and one in Uganda, were conducted; here, we report on the trial that took place in Kaabong, a poor agropastoral region of Karamoja, in east Uganda. While the region of Karamoja shows an acute malnutrition rate between 8.4% and 11.5% of which 2% to 3% severe malnutrition, more than half (58%) of the population in the district of Kaabong is considered food insecure. METHODS AND FINDINGS: We investigated the effect of two types of nutritional supplementation on the incidence of malnutrition in ill children presenting at outpatient clinics during March 2011 to April 2012 in Kaabong, Karamoja region, Uganda, a resource-poor region where malnutrition is a chronic problem for its seminomadic population. A three-armed, partially-blinded, randomised controlled trial was conducted in children diagnosed with malaria, diarrhoea, or lower respiratory tract infection. Non-malnourished children aged 6 to 59 mo were randomised to one of three arms: one sachet/d of ready-to-use therapeutic food (RUTF), two sachets/d of micronutrient powder (MNP), or no supplement (control) for 14 d for each illness over 6 mo. The primary outcome was the incidence of first negative nutritional outcome (NNO) during the 6 mo follow-up. NNO was a study-specific measure used to indicate progression to moderate or severe acute malnutrition; it was defined as weight-for-height z-score <-2, mid-upper arm circumference (MUAC) <115 mm, or oedema, whichever came first. Of the 2,202 randomised participants, 51.2% were girls, and the mean age was 25.2 (±13.8) mo; 148 (6.7%) participants were lost to follow-up, 9 (0.4%) died, and 14 (0.6%) were admitted to hospital. The incidence rates of NNO (first event/year) for the RUTF, MNP, and control groups were 0.143 (95% confidence interval [CI], 0.107-0.191), 0.185 (0.141-0.239), and 0.213 (0.167-0.272), respectively. The incidence rate ratio was 0.67 (95% CI, 0.46-0.98; p = 0.037) for RUTF versus control; a reduction of 33.3%. The incidence rate ratio was 0.86 (0.61-1.23; p = 0.413) for MNP versus control and 0.77 for RUTF versus MNP (95% CI 0.52-1.15; p = 0.200). The average numbers of study illnesses for the RUTF, MNP, and control groups were 2.3 (95% CI, 2.2-2.4), 2.1 (2.0-2.3), and 2.3 (2.2-2.5). The proportions of children who died in the RUTF, MNP, and control groups were 0%, 0.8%, and 0.4%. The findings apply to ill but not malnourished children and cannot be generalised to a general population including children who are not necessarily ill or who are already malnourished. CONCLUSIONS: A 2-wk nutrition supplementation programme with RUTF as part of routine primary medical care to non-malnourished children with malaria, LRTI, or diarrhoea proved effective in preventing malnutrition in eastern Uganda. The low incidence of malnutrition in this population may warrant a more targeted intervention to improve cost effectiveness. TRIAL REGISTRATION: clinicaltrials.gov NCT01497236.

Screening of COPD patients for abdominal aortic aneurysm.

PURPOSE: Screening for abdominal aortic aneurysm (AAA) in "men aged over 65 years who have ever smoked" is a recommended policy. To reduce the number of screenings, it may be of value to define subgroups with a higher prevalence of AAA. Since chronic obstructive pulmonary disease (COPD) and AAA are associated with several common risk factors, this study investigates the prevalence of AAA in COPD patients. PATIENTS AND METHODS: Patients with COPD were identified via the hospital information system. Inclusion criteria were: COPD stage I-IV, ability to give full consent, and age >18 years; exclusion criteria were: patient too obese for an ultrasound check, previously diagnosed AAA, prior surgery for AAA, or ethical grounds such as concomitant advanced malignant or end-stage disease. The primary endpoint of the study was an aortic diameter measured by ultrasound of ≥30 mm. Defined secondary endpoints were evaluated on the basis of medical records and interviews. RESULTS: Of the 1,180 identified COPD patients, 589 were included in this prospective study. In 22 patients (3.70%), the aortic diameter was ≥30 mm, representing an AAA prevalence of 6.72% among males aged >65 years. The risk of AAA increased with the following comorbidities/risk factors: male sex (odds ratio [OR] 2.98), coronary heart disease (OR 2.81), peripheral arterial occlusive disease (OR 2.47), hyperlipoproteinemia (OR 2.77), AAA in the family history (OR 3.95), and COPD stage I/II versus IV (OR 1.81). CONCLUSION: The overall AAA prevalence of 3.7% in our group of COPD patients is similar to that of the general population aged >65 years. However, the frequency of AAA in male COPD patients aged >65 years is considerably higher (6.72%) and increased further still in those individuals with additional comorbidities/risk factors. Defining subgroups with a higher risk of AAA may increase the efficiency of screening.

Effectiveness of an additional individualized multi-component complementary medicine treatment on health-related quality of life in breast cancer patients: a pragmatic randomized trial.

The aim of this study was to evaluate the effectiveness of an additional, individualized, multi-component complementary medicine treatment offered to breast cancer patients at the Merano Hospital (South Tyrol) on health-related quality of life compared to patients receiving usual care only. A randomized pragmatic trial with two parallel arms was performed. Women with confirmed diagnoses of breast cancer were randomized (stratified by usual care treatment) to receive individualized complementary medicine (CM group) or usual care alone (usual care group). Both groups were allowed to use conventional treatment for breast cancer. Primary endpoint was the breast cancer-related quality of life FACT-B score at 6 months. For statistical analysis, we used analysis of covariance (with factors treatment, stratum, and baseline FACT-B score) and imputed missing FACT-B scores at 6 months with regression-based multiple imputation. A total of 275 patients were randomized between April 2011 and March 2012 to the CM group (n = 136, 56.3 ± 10.9 years of age) or the usual care group (n = 139, 56.0 ± 11.0). After 6 months from randomization, adjusted means for health-related quality of life were higher in the CM group (FACT-B score 107.9; 95 % CI 104.1-111.7) compared to the usual care group (102.2; 98.5-105.9) with an adjusted FACT-B score difference between groups of 5.7 (2.6-8.7, p < 0.001). Thus, an additional individualized and complex complementary medicine intervention improved quality of life of breast cancer patients compared to usual care alone. Further studies evaluating specific effects of treatment components should follow to optimize the treatment of breast cancer patients.

Berlin evaluates school tobacco prevention - BEST prevention: study design and methodology.

BACKGROUND: The hazardous health effects of smoking are established, but there remains a need to evaluate existing smoking prevention strategies and to increase their effectiveness in adolescents. Strategies focusing on parental attitudes and rule setting have been identified as a potentially effective approach. The present manuscript describes objectives, study design and methodology of the BEST Prevention study. METHODS/DESIGN: BEST Prevention is a three-armed cluster randomized-controlled trial among 7th grade (11-16 years) students in Berlin, Germany. Schools were enrolled between 2010 and 2011 and allocated using a centralized randomization list into 1) a student smoking prevention intervention (visit to an established interactive circuit), 2) the same intervention plus a parent intervention, and 3) a control group (visit to an established exercise and nutrition interactive circuit). Students were assessed at baseline, 12 and 24 months via self-report, as well as via carbon monoxide and cotinine in saliva at the 24 month follow-up. Statistical analyses uses multi-level regression models with cluster effects (school and class within school) based on the intention to treat population. Here we report descriptive baseline characteristics of recruited schools, and schools classes. Two schools from the control group dropped out after allocation. Hence, 47 secondary schools from all 12 districts of the city, including 161 school classes and 3023 students are participating in the study. Of those, 2801 students completed the baseline assessment. DISCUSSION: The present manuscript provides details on the study design and methodology of a large school-based smoking prevention trial in a metropolitan area in Germany. Findings from this study will yield important insight into the long-term effectiveness of specific smoking prevention strategies, also in disadvantaged population groups. TRIAL REGISTRATION: NCT01306552 (January 2011).

The effect of attending steiner schools during childhood on health in adulthood: a multicentre cross-sectional study.

BACKGROUND: It is speculated that attending Steiner schools, whose pedagogical principles include an account for healthy psycho-physical development, may have long-term beneficial health effects. We examined whether the current health status differed between former attendees of German Steiner schools and adults from the general population. Furthermore, we examined factors that might explain those differences. METHODS: We included former Steiner school attendees from 4 schools in Berlin, Hanover, Nuremberg and Stuttgart and randomly selected population controls. Using a self-report questionnaire we assessed sociodemographics, current and childhood lifestyle and health status. Outcomes were self-reports on 16 diseases: atopic dermatitis, allergic rhinitis, bronchial asthma, chronic obstructive pulmonary disease (COPD), cardiac arrhythmia, cardiac insufficiency, angina pectoris, arteriosclerosis, hypertension, hypercholesterolemia, osteoarthritis, rheumatism, cancer, diabetes, depression and multiple sclerosis. Furthermore, participants rated the symptom burden resulting from back pain, cold symptoms, headache, insomnia, joint pain, gastrointestinal symptoms and imbalance. Unadjusted and adjusted odds ratios were calculated for each outcome. RESULTS: 1136 Steiner school attendees and 1746 controls were eligible for analysis. Both groups were comparable regarding sex, age and region, but differed in nationality and educational status. After adjusting for possible confounders, we found statistically significant effects of Steiner school attendance for osteoarthritis (OR 0.69 [0.49-0.97]) and allergic rhinitis (OR 0.77, [0.59-1.00]) as well as for symptom burden from back pain (OR 0.80, [0.64-1.00]), insomnia (OR 0.65, [0.50-0.84]), joint pain (OR 0.62, [0.48-0.82]), gastrointestinal symptoms (OR 0.76, [0.58-1.00]) and imbalance (OR 0.60, [0.38-0.93]). CONCLUSIONS: The risk of most examined diseases did not differ between former Steiner school attendees and the general population after adjustment for sociodemographics, current and childhood lifestyle features, but symptom burden from some current health complaints was reported less by former Steiner school attendees. Results must be interpreted with caution since the analysis was exploratory.

Factors determining the quality of screening colonoscopy: a prospective study on adenoma detection rates, from 12,134 examinations (Berlin colonoscopy project 3, BECOP-3).

BACKGROUND: Screening colonoscopy (SC) outcome quality is best determined by the adenoma detection rate (ADR). The substantial variability in the ADRs between endoscopists may reflect different skills, experience and/or equipment. OBJECTIVE: To analyse the potential factors that may influence ADR variance, including case volume. DESIGN: 12,134 consecutive SCs (mean age 64.5 years, 47% men) from 21 Berlin private-practice colonoscopists were prospectively studied during 18 months. The data were analysed using a two-level mixed linear model to adequately address the characteristics of patients and colonoscopists. The ADR was regressed after considering the following factors: sex, age, bowel cleanliness, NSAID intake, annual SC case volume, lifetime experience, instrument withdrawal times, instrument generations used, and the number of annual continuing medical education (CME) meetings attended by the physician. The case volume was also retrospectively analysed from the 2007 national SC registry data (312,903 colonoscopies and 1004 colonoscopists). RESULTS: The patient factors that correlated with the ADR were sex, age (p<0.001) and low quality of bowel preparation (p=0.005). The factors that were related to the colonoscopists were the number of CME meetings attended (p=0.012) and instrument generation (p=0.001); these factors accounted for approximately 40% of the interphysician variability. Within a narrow range (6-11 min), the withdrawal time was not correlated with the ADR. Annual screening case volume did not correlate with the ADR, and this finding was confirmed by the German registry data. CONCLUSIONS: The outcome quality of screening colonoscopies is mainly influenced by individual colonoscopist factors (ie, CME activities) and instrument quality. CLINICAL TRIAL REGISTRATION NUMBER: Clinical Trial Gov Registration number: NCT00860665.

Latest generation, wide-angle, high-definition colonoscopes increase adenoma detection rate.

BACKGROUND & AIMS: Improvements to endoscopy imaging technologies might improve detection rates of colorectal cancer and patient outcomes. We compared the accuracy of the latest generation of endoscopes with older generation models in detection of colorectal adenomas. METHODS: We compared data from 2 prospective screening colonoscopy studies (the Berlin Colonoscopy Project 6); each study lasted approximately 6 months and included the same 6 colonoscopists, who worked in private practice. Participants in group 1 (n = 1256) were all examined by using the latest generation of wide-angle, high-definition colonoscopes that were manufactured by the same company. Individuals in group 2 (n = 1400) were examined by endoscopists who used routine equipment (a mixture of endoscopes from different companies; none of those used to examine group 1). The adenoma detection rate was calculated on the basis of the number of all adenomas/number of all patients. RESULTS: There were no differences in patient parameters or withdrawal time between groups (8.0 vs 8.2 minutes). The adenoma detection rate was significantly higher in group 1 (0.33) than in group 2 (0.27; P = .01); a greater number of patients with least 1 adenoma were identified in group 1 (22.1%) than in group 2 (18.2%; P = .01). A higher percentage of high-grade dysplastic adenomas were detected in group 1 (1.19%) than in group 2 (0.57%), but this difference was not statistically significant (P = .06). CONCLUSIONS: The latest generation of wide-angle, high-definition colonoscopes improves rates of adenoma detection by 22%, compared with mixed, older technology endoscopes used in routine private practice. These findings might affect definitions of quality control parameters for colonoscopy screening for colorectal cancer.

Neuroendocrine tumors of midgut and hindgut origin: tumor-node-metastasis classification determines clinical outcome.

BACKGROUND: Prognostic classification of neuroendocrine tumor (NET) patients is difficult due to the complexity of current classification systems. A recent proposal for a tumor-node-metastasis (TNM) classification and a grading system based on the proliferative fraction proved valid in NETs of foregut origin. The purpose of this study was to test the efficacy of a proposal for TNM staging and grading for midgut and hindgut NETs. METHODS: Two hundred seventy patients with histologically proven midgut and hindgut NETs were investigated. Epidemiological, clinicopathological, and tumor-specific data at initial diagnosis were recorded. Tumors were classified according to the World Health Organization (WHO) and the recent European Neuroendocrine Tumor Society-TNM staging and grading proposal. Survival analysis and statistical testing for independent prognostic factors were performed using log-rank tests and Cox regression. RESULTS: Of 270 NETs originating in the midgut or hindgut, 7% (5-year survival rate [YSR], 100%) were stage 1, 8% (5-YSR, 100%) were stage 2, 19% (5-YSR, 89.5%) were stage 3, and 66% (5-YSR, 83.3%) were stage 4 NETs; 62% (5-YSR 95.2%) were grade 1, 32% (5-YSR 82.0%) were grade 2, and 6% (5-YSR, 51.4%) were grade 3 NETs. WHO classification significantly separated poorly from well-differentiated NET or carcinomas but did not further discriminate. TNM staging significantly separated stages 1, 2, and 3 from stage 4 NETs, as did grading according to proliferative capacity for all grades. Multivariate analysis confirmed these results, particularly for Ki67 grading. CONCLUSIONS: The acquired data confirmed the prognostic relevance of the proposed TNM staging and grading system and demonstrated the applicability of these classification tools. The TNM system can therefore facilitate therapeutic stratification and comparison of data from different institutions.

Impact of pain on health-related quality of life in patients with inflammatory bowel disease.

AIM: To evaluate intensity, localization and cofactors of pain in Crohn's disease and ulcerative colitis patients in connection with health-related quality of life (HRQOL) and disease activity. METHODS: We reviewed and analyzed the responses of 334 patients to a specifically designed questionnaire based on the short inflammatory bowel disease questionnaire (SIBDQ) and the German pain questionnaire. Pain intensity, HRQOL, Crohn's disease activity index (CDAI) and colitis activity index (CAI) were correlated and verified on a visual analog scale (VAS). RESULTS: 87.9% of patients reported pain. Females and males reported comparable pain intensities and HRQOL. Surgery reduced pain in both genders (P = 0.023), whereas HRQOL only improved in females. Interestingly, patients on analgesics reported more pain (P = 0.003) and lower HRQOL (P = 0.039) than patients not on analgesics. A significant correlation was found in UC patients between pain intensity and HRQOL (P = 0.023) and CAI (P = 0.027), and in CD patients between HRQOL and CDAI (P = 0.0001), but not between pain intensity and CDAI (P = 0.35). No correlation was found between patients with low CDAI scores and pain intensity. CONCLUSION: Most IBD patients suffer from pain and have decreased HRQOL. Our study reinforces the need for effective individualized pain therapy in IBD patients.