The use of external controls: To what extent can it currently be recommended?

With more and better clinical data being captured outside of clinical studies and greater data sharing of clinical studies, external controls may become a more attractive alternative to randomized clinical trials (RCTs). Both industry and regulators recognize that in situations where a randomized study cannot be performed, external controls can provide the needed contextualization to allow a better interpretation of studies without a randomized control. It is also agreed that external controls will not fully replace RCTs as the gold standard for formal proof of efficacy in drug development and the yardstick of clinical research. However, it remains unclear in which situations conclusions about efficacy and a positive benefit/risk can reliably be based on the use of an external control. This paper will provide an overview on types of external control, their applications and the different sources of bias their use may incur, and discuss potential mitigation steps. It will also give recommendations on how the use of external controls can be justified.

Effectiveness of a complex intervention on Prioritising Multimedication in Multimorbidity (PRIMUM) in primary care: results of a pragmatic cluster randomised controlled trial.

OBJECTIVES: Investigate the effectiveness of a complex intervention aimed at improving the appropriateness of medication in older patients with multimorbidity in general practice. DESIGN: Pragmatic, cluster randomised controlled trial with general practice as unit of randomisation. SETTING: 72 general practices in Hesse, Germany. PARTICIPANTS: 505 randomly sampled, cognitively intact patients (≥60 years, ≥3 chronic conditions under pharmacological treatment, ≥5 long-term drug prescriptions with systemic effects); 465 patients and 71 practices completed the study. INTERVENTIONS: Intervention group (IG): The healthcare assistant conducted a checklist-based interview with patients on medication-related problems and reconciled their medications. Assisted by a computerised decision support system, the general practitioner optimised medication, discussed it with patients and adjusted it accordingly. The control group (CG) continued with usual care. OUTCOME MEASURES: The primary outcome was a modified Medication Appropriateness Index (MAI, excluding item 10 on cost-effectiveness), assessed in blinded medication reviews and calculated as the difference between baseline and after 6 months; secondary outcomes after 6 and 9 months' follow-up: quality of life, functioning, medication adherence, and so on. RESULTS: At baseline, a high proportion of patients had appropriate to mildly inappropriate prescriptions (MAI 0-5 points: n=350 patients). Randomisation revealed balanced groups (IG: 36 practices/252 patients; CG: 36/253). Intervention had no significant effect on primary outcome: mean MAI sum scores decreased by 0.3 points in IG and 0.8 points in CG, resulting in a non-significant adjusted mean difference of 0.7 (95% CI -0.2 to 1.6) points in favour of CG. Secondary outcomes showed non-significant changes (quality of life slightly improved in IG but continued to decline in CG) or remained stable (functioning, medication adherence). CONCLUSIONS: The intervention had no significant effects. Many patients already received appropriate prescriptions and enjoyed good quality of life and functional status. We can therefore conclude that in our study, there was not enough scope for improvement. TRIAL REGISTRATION NUMBER: ISRCTN99526053. NCT01171339; Results.

A simple heuristic for Internet-based evidence search in primary care: a randomized controlled trial.

BACKGROUND: General practitioners (GPs) are confronted with a wide variety of clinical questions, many of which remain unanswered. METHODS: In order to assist GPs in finding quick, evidence-based answers, we developed a learning program (LP) with a short interactive workshop based on a simple three-step-heuristic to improve their search and appraisal competence (SAC). We evaluated the LP effectiveness with a randomized controlled trial (RCT). Participants (intervention group [IG] n=20; control group [CG] n=31) rated acceptance and satisfaction and also answered 39 knowledge questions to assess their SAC. We controlled for previous knowledge in content areas covered by the test. RESULTS: Main outcome - SAC: within both groups, the pre-post test shows significant (P=0.00) improvements in correctness (IG 15% vs CG 11%) and confidence (32% vs 26%) to find evidence-based answers. However, the SAC difference was not significant in the RCT. OTHER MEASURES: Most workshop participants rated "learning atmosphere" (90%), "skills acquired" (90%), and "relevancy to my practice" (86%) as good or very good. The LP-recommendations were implemented by 67% of the IG, whereas 15% of the CG already conformed to LP recommendations spontaneously (odds ratio 9.6, P=0.00). After literature search, the IG showed a (not significantly) higher satisfaction regarding "time spent" (IG 80% vs CG 65%), "quality of information" (65% vs 54%), and "amount of information" (53% vs 47%). CONCLUSION: Long-standing established GPs have a good SAC. Despite high acceptance, strong learning effects, positive search experience, and significant increase of SAC in the pre-post test, the RCT of our LP showed no significant difference in SAC between IG and CG. However, we suggest that our simple decision heuristic merits further investigation.

Pilot study to test the feasibility of a trial design and complex intervention on PRIoritising MUltimedication in Multimorbidity in general practices (PRIMUMpilot).

OBJECTIVE: To improve medication appropriateness and adherence in elderly patients with multimorbidity, we developed a complex intervention involving general practitioners (GPs) and their healthcare assistants (HCA). In accordance with the Medical Research Council guidance on developing and evaluating complex interventions, we prepared for the main study by testing the feasibility of the intervention and study design in a cluster randomised pilot study. SETTING: 20 general practices in Hesse, Germany. PARTICIPANTS: 100 cognitively intact patients ≥65 years with ≥3 chronic conditions, ≥5 chronic prescriptions and capable of participating in telephone interviews; 94 patients completed the study. INTERVENTION: The HCA conducted a checklist-based interview with patients on medication-related problems and reconciled their medications. Assisted by a computerised decision-support system (CDSS), the GPs discussed medication intake with patients and adjusted their medication regimens. The control group continued with usual care. OUTCOME MEASURES: Feasibility of the intervention and required time were assessed for GPs, HCAs and patients using mixed methods (questionnaires, interviews and case vignettes after completion of the study). The feasibility of the study was assessed concerning success of achieving recruitment targets, balancing cluster sizes and minimising drop-out rates. Exploratory outcomes included the medication appropriateness index (MAI), quality of life, functional status and adherence-related measures. MAI was evaluated blinded to group assignment, and intra-rater/inter-rater reliability was assessed for a subsample of prescriptions. RESULTS: 10 practices were randomised and analysed per group. GPs/HCAs were satisfied with the interventions despite the time required (35/45 min/patient). In case vignettes, GPs/HCAs needed help using the CDSS. The study made no patients feel uneasy. Intra-rater/inter-rater reliability for MAI was excellent. Inclusion criteria were challenging and potentially inadequate, and should therefore be adjusted. Outcome measures on pain, functionality and self-reported adherence were unfeasible due to frequent missing values, an incorrect manual or potentially invalid results. CONCLUSIONS: Intervention and trial design were feasible. The pilot study revealed important limitations that influenced the design and conduct of the main study, thus highlighting the value of piloting complex interventions. TRIAL REGISTRATION NUMBER: ISRCTN99691973; Results.

Medical Assistant-Based Care Management for High-Risk Patients in Small Primary Care Practices: A Cluster Randomized Clinical Trial.

BACKGROUND: Patients with multiple chronic conditions are at high risk for potentially avoidable hospitalizations, which may be reduced by care coordination and self-management support. Medical assistants are an increasingly available resource for patient care in primary care practices. OBJECTIVE: To determine whether protocol-based care management delivered by medical assistants improves care in patients at high risk for future hospitalization in primary care. DESIGN: Two-year cluster randomized clinical trial. (Current Controlled Trials: ISRCTN56104508). SETTING: 115 primary care practices in Germany. PATIENTS: 2076 patients with type 2 diabetes, chronic obstructive pulmonary disease, or chronic heart failure and a likelihood of hospitalization in the upper quartile of the population, as predicted by an analysis of insurance data. INTERVENTION: Protocol-based care management, including structured assessment, action planning, and monitoring delivered by medical assistants, compared with usual care. MEASUREMENTS: All-cause hospitalizations at 12 months (primary outcome) and quality-of-life scores (12-Item Short Form Health Survey [SF-12] and EuroQol instrument [EQ-5D]). RESULTS: Included patients had an average of 4 co-occurring chronic conditions. All-cause hospitalizations did not differ between groups at 12 months (risk ratio [RR], 1.01 [95% CI, 0.87 to 1.18]) and 24 months (RR, 0.98 [CI, 0.85 to 1.12]). Quality of life (differences, 1.16 [CI, 0.24 to 2.08] on SF-12 physical component and 1.68 [CI, 0.60 to 2.77] on SF-12 mental component) and general health (difference on EQ-5D, 0.03 [CI, 0.00 to 0.05]) improved significantly at 24 months. Intervention costs totaled $10 per patient per month. LIMITATION: Small number of primary care practices and low intensity of intervention. CONCLUSION: This low-intensity intervention did not reduce all-cause hospitalizations but showed positive effects on quality of life at reasonable costs in high-risk multimorbid patients. PRIMARY FUNDING SOURCE: AOK Baden-Württemberg and AOK Bundesverband.

A complex nursing intervention of complementary and alternative medicine (CAM) to increase quality of life in patients with breast and gynecologic cancer undergoing chemotherapy: study protocol for a partially randomized patient preference trial.

BACKGROUND: Health-related quality of life (HRQoL) is most adversely affected in cancer patients between diagnosis and the end of chemotherapy. The aim of the Complementary Nursing in Gynecologic Oncology (CONGO) study is to assess the effectiveness of a complex nursing care intervention of CAM to increase HRQoL in cancer patients undergoing chemotherapy. METHODS/DESIGN: CONGO is a prospective partially randomized patient preference (PRPP) trial including adult women diagnosed with breast and gynecologic cancer starting a new chemotherapy regimen. Patients without strong preferences for CAM will be randomized to usual nursing care or complex nursing care; those patients with strong preferences will be allowed their choice. The intervention consists of three interacting and intertwined elements: CAM nursing intervention packet, counseling on CAM using a resource-oriented approach and evidence-based informational material on CAM. Primary outcome data on participants' HRQoL will be collected from baseline until the end of treatment and long-term follow-up using the EORTC-QLQ-C30. Secondary outcomes include nausea, fatigue, pain, anxiety/depression, social support, self-efficacy, patient competence, spiritual wellbeing, and satisfaction with care. Accompanying research on economic outcomes as well as a mixed-methods process evaluation will be conducted. A total of 590 patients (236 patients in the randomized part of the study and 354 patients in the observational part of the study) will be recruited in the two outpatient clinics. The first analysis step will be the intention-to-treat (ITT) analysis of the randomized part of the trial. A linear mixed model will be used to compare the continuous primary endpoint between the intervention and control arm of the randomized group. The observational part of the trial will be analyzed descriptively. External validity will be assessed by comparing randomized with nonrandomized patients. DISCUSSION: Cancer patients are increasingly using CAM as supportive cancer care, however, a patient-centered model of care that includes CAM for the patient during chemotherapy still needs to be evaluated. This protocol has been designed to test if the effects of the intervention go beyond potential benefits in quality-of-life outcomes. TRIAL REGISTRATION: German Clinical Trials Register (DRKS), DRKS00006056 (15 April 2014).

The Ariadne principles: how to handle multimorbidity in primary care consultations.

Multimorbidity is a health issue mostly dealt with in primary care practice. As a result of their generalist and patient-centered approach, long-lasting relationships with patients, and responsibility for continuity and coordination of care, family physicians are particularly well placed to manage patients with multimorbidity. However, conflicts arising from the application of multiple disease oriented guidelines and the burden of diseases and treatments often make consultations challenging. To provide orientation in decision making in multimorbidity during primary care consultations, we developed guiding principles and named them after the Greek mythological figure Ariadne. For this purpose, we convened a two-day expert workshop accompanied by an international symposium in October 2012 in Frankfurt, Germany. Against the background of the current state of knowledge presented and discussed at the symposium, 19 experts from North America, Europe, and Australia identified the key issues of concern in the management of multimorbidity in primary care in panel and small group sessions and agreed upon making use of formal and informal consensus methods. The proposed preliminary principles were refined during a multistage feedback process and discussed using a case example. The sharing of realistic treatment goals by physicians and patients is at the core of the Ariadne principles. These result from i) a thorough interaction assessment of the patient's conditions, treatments, constitution, and context; ii) the prioritization of health problems that take into account the patient's preferences - his or her most and least desired outcomes; and iii) individualized management realizes the best options of care in diagnostics, treatment, and prevention to achieve the goals. Goal attainment is followed-up in accordance with a re-assessment in planned visits. The occurrence of new or changed conditions, such as an increase in severity, or a changed context may trigger the (re-)start of the process. Further work is needed on the implementation of the formulated principles, but they were recognized and appreciated as important by family physicians and primary care researchers.Please see related article: http://www.biomedcentral.com/1741-7015/12/222.

Internal consistency of the readiness for interprofessional learning scale in German health care students and professionals.

BACKGROUND: The implementation of a bachelor degree in "Interprofessional Health Care" at the University of Heidelberg, Germany has fostered the need to evaluate the impact of this innovative programme. The Readiness for Interprofessional Learning Scale (RIPLS) was developed by Parsell and Bligh (1999) to assess student's attitudes towards interprofessional education. The RIPLS consists of 19 items and four subscales were identified by McFadyen (J Interprof Care19:595-603, 2005): "teamwork and collaboration", "negative professional identity", "positive professional identity" and "roles and responsibilities". The RIPLS has been translated into a number of languages and used in a variety of different educational settings. A German version of the RIPLS was not available. Aim of the study was the translation of the RIPLS into German and testing of internal consistency. METHODS: The RIPLS was translated to German according to international guidelines and its psychometric properties were assessed in two online surveys with two different samples a) health care graduates and b) health care students. Descriptive analysis (mean, SD, corrected item-total correlation) of the Readiness for Interprofessional Learning Scale - German (RIPLS-D) was performed for item characteristics and Cronbach's Alpha was calculated for internal consistency of overall and subscales of the RIPLS-D. RESULTS: Each sample consisted of 76 datasets. Reliability for the RIPLS-D overall scale was 0.83 in both samples. The subscales displayed internal consistency between 0.42 and 0.88. Corrected item-total correlation showed low values in two subscales in the sample of graduates. CONCLUSIONS: While the overall RIPLS-D scale is reliable, several subscales showed low values and should be used with caution to measure readiness for interprofessional learning in the German health care context. Internal consistency of the instrument does not seem to be given in health care professionals at different stages of their professional career. In particular the sub-scale "roles and responsibilities" was problematic. For these reasons, the RIPLS-D cannot be recommended for use to assess this concept.

Involving patients in detecting quality gaps in a fragmented healthcare system: development of a questionnaire for Patients' Experiences Across Health Care Sectors (PEACS).

OBJECTIVE: The purpose of this study was to develop and validate a generic questionnaire to evaluate experiences and reported outcomes in patients who receive treatment across a range of healthcare sectors. DESIGN: Mixed-methods design including focus groups, pretests and field test. SETTING: The patient questionnaire was developed in the context of a nationwide program in Germany aimed at quality improvements across the healthcare sectors. PARTICIPANTS: For the field test, 589 questionnaires were distributed to patients via 47 general practices. MAIN MEASUREMENTS: Descriptive item analyzes non-responder analysis and factor analysis (PCA). Retest coefficients (r) calculated by correlation of sum scores of PCA factors. Quality gaps were assessed by the proportion of responders choosing a response category defined as indicating shortcomings in quality of care. RESULTS: The conceptual phase showed good content validity. Four hundred and seventy-four patients who received a range of treatment across a range of sectors were included (response rate: 80.5%). Data analysis confirmed the construct, oriented to the patient care journey with a focus on transitions between healthcare sectors. Quality gaps were assessed for the topics 'Indication', including shared-decision-making (6 items, 24.5-62.9%) and 'Discharge and Transition' (10 items; 20.7-48.2%). Retest coefficients ranged from r = 0.671 until r = 0.855 and indicated good reliability. Low ratios of item-non-response (0.8-9.3%) confirmed a high acceptance by patients. CONCLUSIONS: The number of patients with complex healthcare needs is increasing. Initiatives to expand quality assurance across organizational borders and healthcare sectors are therefore urgently needed. A validated questionnaire (called PEACS 1.0) is available to measure patients' experiences across healthcare sectors with a focus on quality improvement.

Mediation analysis of the relationship between institutional research activity and patient survival.

BACKGROUND: Recent studies have suggested that patients treated in research-active institutions have better outcomes than patients treated in research-inactive institutions. However, little attention has been paid to explaining such effects, probably because techniques for mediation analysis existing so far have not been applicable to survival data. METHODS: We investigated the underlying mechanisms using a recently developed method for mediation analysis of survival data. Our analysis of the effect of research activity on patient survival was based on 352 patients who had been diagnosed with advanced ovarian cancer at 149 hospitals in 2001. All hospitals took part in a quality assurance program of the German Cancer Society. Patient outcomes were compared between hospitals participating in clinical trials and non-trial hospitals. Surgical outcome and chemotherapy selection were explored as potential mediators of the effect of hospital research activity on patient survival. RESULTS: The 219 patients treated in hospitals participating in clinical trials had more complete surgical debulking, were more likely to receive the recommended platinum-taxane combination, and had better survival than the 133 patients treated in non-trial hospitals. Taking into account baseline confounders, the overall adjusted hazard ratio of death was 0.58 (95% confidence interval: 0.42 to 0.79). This effect was decomposed into a direct effect of research activity of 0.67 and two indirect effects of 0.93 each mediated through either optimal surgery or chemotherapy. Taken together, about 26% of the beneficial effect of research activity was mediated through the proposed pathways. CONCLUSIONS: Mediation analysis allows proceeding from the question "Does it work?" to the question "How does it work?" In particular, we have shown that the research activity of a hospital contributes to superior patient survival through better use of surgery and chemotherapy. This methodology may be applied to analyze direct and indirect natural effects for almost any combination of variable types.

Multimorbidity's research challenges and priorities from a clinical perspective: the case of 'Mr Curran'.

Older patients, suffering from numerous diseases and taking multiple medications are the rule rather than the exception in primary care. A manifold of medical conditions are often associated with poor outcomes, and their multiple medications raise additional risks of polypharmacy. Such patients account for most healthcare expenditures. Effective approaches are needed to manage such complex patients in primary care. This paper describes the results of a scoping exercise, including a two-day workshop with 17 professionals from six countries, experienced in general practice and primary care research as well as epidemiology, clinical pharmacology, gerontology and methodology. This was followed by a consensus process investigating the challenges and core questions for multimorbidity research in primary care from a clinical perspective and presents examples of the best research practice. Current approaches in measuring and clustering multimorbidity inform policy-makers and researchers, but research is needed to provide support in clinical decision making. Multimorbidity presents a complexity of conditions leading to individual patient's needs and demanding complex processes in clinical decision making. The identification of patterns presupposes the development of strategies on how to manage multimorbidity and polypharmacy. Interventions have to be complex and multifaceted, and their evaluation poses numerous methodological challenges in study design, outcome measurement and analysis. Overall, it can be seen that complexity is a main underlying theme. Moreover, flexible study designs, outcome parameters and evaluation strategies are needed to account for this complexity.

Health-related quality of life and risk factor control: the importance of educational level in prevention of cardiovascular diseases.

BACKGROUND: This study aimed to describe and to analyse the importance of educational level for controlled risk factors and health-related quality of life (HRQoL). METHODS: This observational study was conducted in nine European countries (5632 patients in 249 practices). We compared patients with a low level of education (up to 9 years) with patients with a high level of education (>9 years), with regard to controlled cardiovascular disease risk factors and HRQoL. A multilevel approach was used for statistical analysis. RESULTS: Patients with a low level of education were older (P < 0.001), more often female (P < 0.001), more often single (P < 0.001) and had a higher number of other conditions (e.g. heart failure) (P < 0.001). Significant differences in terms of controlled risk factors were revealed for blood pressure (RR) ≤ 140/90 mmHg (P = 0.039) and the sum of controlled risk factors (P = 0.027). Higher age, lower education, female gender, living as single, patient group (coronary heart disease patients) and the number of other conditions were negatively associated with HRQoL. A higher sum of controlled risk factors were positively associated with higher HRQoL in the whole sample (r = 0.0086, P < 0.001) as well as in both educational-level groups (r = 0.0075, P = 0.038 in the low-level group and r = 0.0082, P = 0.001 in the high-level group). CONCLUSION: Patients with a lower educational level were more often females, singles, had a higher number of other conditions, a higher number of uncontrolled risk factors and a lower HRQoL. However, the higher the control of risk factors was, the higher the HRQoL was overall as well as in both educational-level groups.

The challenge of cardiovascular prevention in primary care: implications of a European observational study in 8928 patients at different risk levels.

BACKGROUND: Cardiovascular prevention can be provided to patients at different risk levels. The aim of this study was to compare the quality of cardiovascular prevention provided in European primary care between patients with diagnosed coronary heart disease (CHD) and individuals at high risk due to known risk factors but not labelled with a diagnosis of cardiovascular disease (CVD). Additionally, we aimed to identify individual and practice factors to predict risk factor control. METHODS: An international cross-sectional study was conducted in 10 European countries. Clinical record data were abstracted for quality indicators for 8928 patients in 10 countries and patient questionnaires were completed by 7846 patients in nine countries. Information about 320 general practices was assessed using practice questionnaires and interviews. Hierarchical multilevel modelling was used for analyses. RESULTS: Recording of risk factors and advice was higher in the CHD than in the high-risk group. Risk factor control was better in the CHD group: uncontrolled levels of blood pressure (34.2 vs. 49.3%; p < 0.001), cholesterol (32.4 vs. 64.5%; p < 0.001). Predictors of risk factor control were medication adherence (RR 0.97; p = 0.007) and health-related quality of life (RR 0.86; p = 0.005). Being at high risk (RR 1.42; p < 0.001), being single (RR 1.12; p < 0.001), and having lower educational level (RR 1.09; p < 0.001) were associated with poorer risk factor control. Practice factors were not associated with outcomes. CONCLUSIONS: Strategies to improve guidelines adherence in cardiovascular prevention may be stronger focused on individuals at risk before CVD is diagnosed and require organizational and political support to reinforce general practices.

Comparison of physician referral and insurance claims data-based risk prediction as approaches to identify patients for care management in primary care: an observational study.

BACKGROUND: Primary care-based care management (CM) could reduce hospital admissions in high-risk patients. Identification of patients most likely to benefit is needed as resources for CM are limited. This study aimed to compare hospitalization and mortality rates of patients identified for CM either by treating primary care physicians (PCPs) or predictive modelling software for hospitalization risk (PM). METHODS: In 2009, a cohort of 6,026 beneficiaries of a German statutory health insurance served as a sample for patient identification for CM by PCPs or commercial PM (CSSG 0.8, Verisk Health). The resulting samples were compared regarding hospitalization and mortality rates in 2010 and in the two year period before patient selection. No CM-intervention was delivered until the end of 2010 and PCPs were blinded for the assessment of hospitalization rates. RESULTS: In 2010, hospitalization rates of PM-identified patients were 80% higher compared to PCP-identified patients. Mortality rates were also 8% higher in PM-identified patients if compared to PCP-identified patients (10% vs. 2%). The hospitalization rate of patients independently identified by both PM and PCPs was numerically between PM- and PCP-identified patients. Time trend between 2007 and 2010 showed decreasing hospitalization rates in PM-identified patients (-15% per year) compared to increasing rates in PCP-identified patients (+34% per year). CONCLUSIONS: PM identified patients with higher hospitalization and mortality rates compared to PCP-referred patients. But the latter showed increasing hospitalization rates over time thereby suggesting that PCPs may be able to predict future deterioration in patients with relatively good current health status. These patients may most likely benefit from preventive services like CM.

[Guideline compliance in the treatment of patients with chronic heart failure through family doctor-centred health care: results of an evaluation study]. / Leitliniengerechte Behandlung bei chronischer Herzinsuffizienz im Rahmen der Hausarztzentrierten Versorgung. Ergebnisse einer Evaluationsstudie.

PROBLEM: Family doctor centred health care (German abbreviation: HzV) agreements in Baden-Wuerttemberg provides that every year the strategies and results of at least two high-quality guidelines shall be discussed and worked on in quality circles. In this regard, the 'heart failure' guideline by the German Society of General Practice and Family Medicine (DEGAM) is especially important due to the high treatment costs and the continuously increasing prevalence of this medical condition. Another specified objective of the HzV agreements is to increase the DMP participation rate. The study addressed two questions: Is the medical care provided to patients with chronic heart failure who are being treated under HzV more compliant with guidelines than routine care? Does further improvement result from working on the guidelines in quality circles? METHODS: Routine data were provided by the AOK Baden-Wuerttemberg statutory health insurance company. Patients with heart failure receiving treatment under an HzV agreement (HzV group) were compared with patients receiving routine care (control group) with regard to quality of care eight months before and eight months after working on the guideline on heart failure in quality circles. Primary endpoints were the prescription of ACE inhibitors, AT1 antagonists and beta blockers in accordance with guidelines. Adjustment for various covariates was done by means of multivariate multilevel regression. RESULTS: Data were available for 3,667 practices [1,295 HzV practices; 2,158 non-HzV practices]. After applying validated diagnosis criteria, 16,584 patients were included in the intervention group and 28,992 in the control group. The HzV group received significantly better care in terms of the primary endpoint "prescription of ACE inhibitors or AT1 antagonists" (73.1 % vs. 69.3 % of the patients received ACE inhibitors or AT1 antagonists at T0 (OR 1.40; 95% CI [1,25; 1,57]; p < .001). 54.2 % vs. 52.3 % of the patients received beta blockers at T0 (not significant after adjustment, p = .260). No further improvement could be demonstrated to result from working on guidelines in quality circles. DISCUSSION AND CONCLUSION: The treatment of HzV patients with chronic heart failure is more compliant with guidelines than that of patients receiving routine care. Quality of care was already high at the beginning, and working on guidelines in quality circles had no noticeable effect. The increased DMP participation rate, which is one of the specified objectives of the HzV agreements, appears to have a mediation effect.

Family constellation seminars improve psychological functioning in a general population sample: results of a randomized controlled trial.

The study examined the efficacy of nonrecurring family constellation seminars on psychological health. We conducted a monocentric, single-blind, stratified, and balanced randomized controlled trial (RCT). After choosing their roles for participating in a family constellation seminar as either active participant (AP) or observing participant (OP), 208 adults (M = 48 years, SD = 10; 79% women) from the general population were randomly allocated to the intervention group (IG; 3-day family constellation seminar; 64 AP, 40 OP) or a wait-list control group (WLG; 64 AP, 40 OP). It was predicted that family constellation seminars would improve psychological functioning (Outcome Questionnaire OQ-45.2) at 2-week and 4-month follow-ups. In addition, we assessed the impact of family constellation seminars on psychological distress and motivational incongruence. The IG showed significantly improved psychological functioning (d = 0.45 at 2-week follow-up, p = .003; d = 0.46 at 4-month follow-up, p = .003). Results were confirmed for psychological distress and motivational incongruence. No adverse events were reported. This RCT provides evidence for the efficacy of family constellation in a nonclinical population. The implications of the findings are discussed.

Which practice characteristics are associated with the quality of cardiovascular disease prevention in European primary care?

BACKGROUND: Prevention of cardiovascular diseases (CVD) is a major health issue worldwide. Primary care plays an important role in cardiovascular risk management (CVRM). Guidelines and quality of care measures to assess CVRM in primary care practices are available. In this study, we assessed the relationship between structural and organisational practice characteristics and the quality of care provided in individuals at high risk for developing CVD in European primary care. METHODS: An observational study was conducted in 267 general practices from 9 European countries. Previously developed quality indicators were abstracted from medical records of randomly sampled patients to create a composite quality measure. Practice characteristics were collected by a practice questionnaire and face to face interviews. Data were aggregated using factor analysis to four practice scores representing structural and organisational practice features. A hierarchical multilevel analysis was performed to examine the impact of practice characteristics on quality of CVRM. RESULTS: The final sample included 4223 individuals at high risk for developing CVD (28% female) with a mean age of 66.5 years (SD 9.1). Mean indicator achievement was 59.9% with a greater variation between practices than between countries. Predictors at the patient level (age, gender) had no influence on the outcome. At the practice level, the score 'Preventive Services' (13 items) was positively associated with clinical performance (r = 1.92; p = 0.0058). Sensitivity analyses resulted in a 5-item score (PrevServ_5) that was also positively associated with the outcome (r = 4.28; p < 0.0001). CONCLUSIONS: There was a positive association between the quality of CVRM in individuals at high risk for developing CVD and the availability of preventive services related to risk assessment and lifestyle management supported by information technology.

A prospective multicenter phase II study evaluating multimodality treatment of patients with peritoneal carcinomatosis arising from appendiceal and colorectal cancer: the COMBATAC trial.

BACKGROUND: Peritoneal carcinomatosis is regarded as a common sign of advanced tumor stage, tumor progression or local recurrence of appendiceal and colorectal cancer and is generally associated with poor prognosis. Although survival of patients with advanced stage CRC has markedly improved over the last 20 years with systemic treatment, comprising combination chemotherapy +/- monoclonal antibodies, the oncological outcome-especially of the subgroup of patients with peritoneal metastases-is still unsatisfactory. In addition to systemic therapy, cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are specific treatment options for a selected group of these patients and may provide an additional therapeutic benefit in the framework of an interdisciplinary treatment concept. METHODS/DESIGN: The COMBATAC trial is a prospective, multicenter, open-label, single-arm, single-stage phase II trial investigating perioperative systemic polychemotherapy including cetuximab in combination with CRS and HIPEC patients with histologically proven wild-type KRAS colorectal or appendiceal adenocarcinoma and synchronous or metachronous peritoneal carcinomatosis. The planned total number of patients to be recruited is 60. The primary endpoint is progression-free survival (PFS). Secondary endpoints include overall survival (OS), perioperative morbidity and treatment-associated toxicity, feasibility of the combined treatment regimen, quality of life (QoL) and histopathological regression after preoperative chemotherapy. DISCUSSION: The COMBATAC trial is designed to evaluate the feasibility and efficacy of the combined multidisciplinary treatment regimen consisting of perioperative systemic combination chemotherapy plus cetuximab and CRS plus bidirectional HIPEC with intraperitoneal oxaliplatin. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01540344, EudraCT number: 2009-014040-11.

Does the patient with chest pain have a coronary heart disease? Diagnostic value of single symptoms and signs--a meta-analysis.

AIM: To determine the diagnostic value of single symptoms and signs for coronary heart disease (CHD) in patients with chest pain. METHODS: Searches of two electronic databases (EMBASE 1980 to March 2008, PubMed 1966 to May 2009) and hand searching in seven journals were conducted. Eligible studies recruited patients presenting with acute or chronic chest pain. The target disease was CHD, with no restrictions regarding case definitions, eg, stable CHD, acute coronary syndrome (ACS), acute myocardial infarction (MI), or major cardiac event (MCE). Diagnostic tests of interest were items of medical history and physical examination. Bivariate random effects model was used to derive summary estimates of positive (pLR) and negative likelihood ratios (nLR). RESULTS: We included 172 studies providing data on the diagnostic value of 42 symptoms and signs. With respect to case definition of CHD, diagnostically most useful tests were history of CHD (pLR=3.59), known MI (pLR=3.21), typical angina (pLR=2.35), history of diabetes mellitus (pLR=2.16), exertional pain (pLR=2.13), history of angina pectoris (nLR=0.42), and male sex (nLR=0.49) for diagnosing stable CHD; pain radiation to right arm/shoulder (pLR=4.43) and palpitation (pLR=0.47) for diagnosing MI; visceral pain (pLR=2.05) for diagnosing ACS; and typical angina (pLR=2.60) and pain reproducible by palpation (pLR=0.13) for predicting MCE. CONCLUSIONS: We comprehensively reported the accuracy of a broad spectrum of single symptoms and signs for diagnosing myocardial ischemia. Our results suggested that the accuracy of several symptoms and signs varied in the published studies according to the case definition of CHD.