Effects of a team-based assessment and intervention on patient safety culture in general practice: an open randomised controlled trial.

BACKGROUND: The measurement of safety culture in healthcare is generally regarded as a first step towards improvement. Based on a self-assessment of safety culture, the Frankfurt Patient Safety Matrix (FraTrix) aims to enable healthcare teams to improve safety culture in their organisations. In this study we assessed the effects of FraTrix on safety culture in general practice. METHODS: We conducted an open randomised controlled trial in 60 general practices. FraTrix was applied over a period of 9 months during three facilitated team sessions in intervention practices. At baseline and after 12 months, scores were allocated for safety culture as expressed in practice structure and processes (indicators), in safety climate and in patient safety incident reporting. The primary outcome was the indicator error management. RESULTS: During the team sessions, practice teams reflected on their safety culture and decided on about 10 actions per practice to improve it. After 12 months, no significant differences were found between intervention and control groups in terms of error management (competing probability=0.48, 95% CI 0.34 to 0.63, p=0.823), 11 further patient safety culture indicators and safety climate scales. Intervention practices showed better reporting of patient safety incidents, reflected in a higher number of incident reports (mean (SD) 4.85 (4.94) vs 3.10 (5.42), p=0.045) and incident reports of higher quality (scoring 2.27 (1.93) vs 1.49 (1.67), p=0.038) than control practices. CONCLUSIONS: Applied as a team-based instrument to assess safety culture, FraTrix did not lead to measurable improvements in error management. Comparable studies with more positive results had less robust study designs. In future research, validated combined methods to measure safety culture will be required. In addition, more attention should be paid to evaluation of process parameters. Implemented actions and incident reporting may be more appropriate target endpoints. TRIAL REGISTRATION: German Clinical Trials Register (Deutsches Register Klinischer Studien, DRKS) No. DRKS00000145.

Clinical research in epithelial ovarian cancer and patients' outcome.

We evaluated the relationship between the outcome of newly diagnosed ovarian cancer patients treated in 1123 German gynecology departments in 2001, and their participation in clinical trials through two German cooperative study groups. In addition, we evaluated other potential factors predicting outcome including hospital volume. The analysis was based on 476 patients from 165 hospitals and 3-year follow-up. Patients treated in study hospitals had a higher chance of receiving treatment according to national guidelines. This included a higher chance of receiving optimal staging in early stage disease and of receiving the recommended combination of surgical debulking and combination chemotherapy in advanced disease. On multivariable Cox model analysis, overall survival was significantly worse in patients treated in non-study hospitals.

Future research and methodological approaches.

This supplement has explored the evidence for benefits from the participation of healthcare institutions and their patients in clinical research. The questions have been clarified. There is some encouragement that research active healthcare institutions may deliver improved outcomes compared to less research-active or research-inactive institutions but there is a pressing need for further research. In this chapter we explore the methodological challenges to evaluating the impact of the process of clinical research on hospitals and other healthcare organizations. The postulated mechanisms by which benefits may be accrued are important drivers of the types of research needed and these are emphasized. Study designs are explored including formal randomized trials, the stepped wedge randomized design, approaches to the design and analysis of observational studies particularly to examine whether a temporal or spatial relationship exists between changes in research activity and patients' outcomes. It is acknowledged that in most future studies the data available will be cross-sectional and observational, and such studies are susceptible to many types of bias. The importance of identifying and addressing such biases in multivariate analysis is discussed and examples of successful studies are given.

Analysis of risk factors influencing the development of severe dizziness in patients with vestibular schwannomas in the immediate postoperative phase.

OBJECTIVE: Dizziness, a common postoperative symptom in patients with vestibular schwannomas (VSs) has a negative effect on the course of recovery, particularly in patients with severe symptoms. Reports on incidence and possible risk factors contributing to these symptoms are inconsistent and sometimes even contradictory. In order to establish a profile of patients at risk of severe symptoms in the immediate postoperative phase we retrospectively analyzed data of patients with unilateral VSs focusing on the incidence of severe dizziness and nausea during the immediate postoperative period and up to 1 year after surgery. METHODS: In a retrospective study data of 104 consecutive patients with VSs were analyzed. All patients underwent microsurgical tumor resection via a lateral-suboccipital approach. Factors that were assumed to affect the development of severe dizziness, such as age, gender, tumor size, tumor side, and cranial nerve function, were analyzed by means of univariate and multivariate logistic regression analyses. A three step grading system was used to describe symptoms of patients included in this study: 0=no symptoms of dizziness, 1=slight dizziness including light-headedness or feeling of disequilibrium and 2=severe dizziness with nausea including imbalance or insecurity when walking, requiring antiemetic treatment. RESULTS: Data of 92 patients, 41 men and 51 women, were available for analyses. Mean age of treated patients was 53 years (range 17-81). There was no predilection of side (52.2% right/47.8% left). Before surgery 39 patients (42.4%) were symptom free (grade 0), 13 patients (14.1%) had slight symptoms (grade 1) and 40 patients (43.5%) suffered from severe symptoms (grade 2). Immediately after surgery two patients (2.2%) where symptom free (grade 0), 19 patients (20.7%) had slight symptoms (grade 1) and 71 patients (77.2%) suffered from severe symptoms (grade 2). All patients with grade 2 symptoms required antiemetic treatment ranging between 1 and 10 days (mean 4 days). Logistic regression analyses showed young age, large tumor size (T3/T4), female gender, and severe preoperative symptoms to be main factors increasing the odds for patients to develop severe symptoms postoperatively. CONCLUSION: Patients at risk to develop severe symptoms should receive antiemetic treatment even before surgery. If in doubt about the actual risk for a specific patient with a large tumor (T3 or T4) available data suggests that patients will benefit if antiemetic treatment is started early, even before surgery.

Cerebral metastases in metastatic breast cancer: disease-specific risk factors and survival.

BACKGROUND: Survival of patients suffering from cerebral metastases (CM) is limited. Identification of patients with a high risk for CM is warranted to adjust follow-up care and to evaluate preventive strategies. PATIENTS AND METHODS: Exploratory analysis of disease-specific parameter in patients with metastatic breast cancer (MBC) treated between 1998 and 2008 using cumulative incidences and Fine and Grays' multivariable regression analyses. RESULTS: After a median follow-up of 4.0 years, 66 patients (10.5%) developed CM. The estimated probability for CM was 5%, 12% and 15% at 1, 5 and 10 years; in contrast, the probability of death without CM was 21%, 61% and 76%, respectively. A small tumor size, ER status, ductal histology, lung and lymph node metastases, human epidermal growth factor receptor 2 positive (HER2+) tumors, younger age and M0 were associated with CM in univariate analyses, the latter three being risk factors in the multivariable model. Survival was shortened in patient developing CM (24.0 months) compared with patients with no CM (33.6 months) in the course of MBC. CONCLUSION: Young patients, primary with non-metastatic disease and HER2+ tumors, have a high risk to develop CM in MBC. Survival of patients developing CM in the course of MBC is impaired compared with patients without CM.

Prognostic impact of additional extended surgical procedures in advanced-stage primary ovarian cancer.

BACKGROUND: Treatment of advanced-stage ovarian carcinoma includes radical cytoreductive surgery, which aims at removing all visible tumor tissue followed by platinum and paclitaxel chemotherapy. Complete tumor resection may require extended surgical procedures. This paper reports on the prognostic impact of extensive surgery and surgical morbidity in patients with advanced-stage ovarian carcinoma. METHODS: Patients with ovarian carcinoma [Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) stage IIIB-IV] undergoing primary surgery in our tertiary gynecologic oncology unit between 1997 and 2007 were eligible for this study. The impact of established prognostic factors and the interaction with extent of surgical procedures on survival were assessed. RESULTS: A total of 267 patients aged between 29 and 88 years (median 64 years) were eligible for this study. Overall survival time was improved in patients who underwent complete tumor resection [hazard ratio (HR) 3.61 (1.91-6.61), P < 0.001]. No significant survival difference was observed between completely operated patients in whom extended or standard surgical procedures were applied [HR 1.37 (0.70-2.69), P = 0.358], and severe surgical complications were found to be equally distributed between the two patient groups. CONCLUSIONS: Our results may encourage the application of extended surgical procedures in patients who would otherwise be rendered incompletely debulked after primary cytoreduction. We could demonstrate an impact of complete tumor resection on patient prognosis and this was not traded off for extensive additional surgical morbidity.

Pattern of care and impact of participation in clinical studies on the outcome in ovarian cancer.

The purpose of this study was to evaluate the pattern and quality of care for ovarian cancer in Germany and analyze prognostic factors with emphasis on characteristics of treating institutions, hospital volume, and participation in clinical trials. This study utilized national survey including patients with histologically proven invasive epithelial ovarian cancer diagnosed in the third quarter of 2001 including descriptive analysis of pattern of surgical care and systemic treatment in early (FIGO I-IIA) and advanced (FIGO IIB-IV) ovarian cancer and both univariate and multivariate analysis of prognostic factors. One third of all patients diagnosed in the third quarter of 2001 in Germany, 476 patients, were included. Standard care according to German guidelines was provided to only 35.5% of patients with early ovarian cancer. Recommended chemotherapy was given to 78% in advanced disease. Multivariate analysis showed advanced stage, poor performance status, comorbidity, ascites, and treatment in an institution not participating in cooperative studies to be associated with inferior survival. Non-participation was associated with an 82% increase of risk (HR = 1.82; 95% CI, 1.27-2.61; P= 0.001). Hospital volume did not affect treatment outcome. Adherence to treatment guidelines showed remarkable variety among German hospitals, indicating options and need for improvement. Selecting an institution that participates in cooperative trials might be an option for individual patients seizing the chance for better quality of care even when individual factors might hamper enrollment in a study.

[The Quality Assurance Program of the AGO Organkommission OVAR (QS-OVAR): Pattern of Care and Reality in Germany 2001]. / Das Qualitätssicherungsprogramm der AGO Organkommission OVAR (QS-OVAR): Versorgungsstruktur und Realität in Deutschland 2001.

PURPOSE: To evaluate pattern and quality of care for ovarian cancer in Germany and analyze adherence to treatment guidelines as well as prognostic factors for survival. METHODS: Nationwide survey including patients with histological proven invasive epithelial ovarian cancer diagnosed in the third quarter 2001 including descriptive analysis of pattern of surgical care and systemic treatment in early (FIGO I-IIA) and advanced (FIGO IIB-IV) ovarian cancer and both univariate and multivariate analysis of prognostic factors. RESULTS: 476, representing more than one third of all patients diagnosed in Q III 2001 in Germany were included. Standard care according to German guidelines was provided to only 35.5 % of patients with early ovarian cancer. Optimal debulking was reported for 61.4 % patients with FIGO stages IIB-IV. Recommended platinum-paclitaxel chemotherapy was given to 3 out of 4 patients in advanced disease. Multivariate analysis showed advanced stage, poor performance status, co-morbidity, ascites, postoperative tumor residuals, and less than standard care to be associated with inferior survival. CONCLUSIONS: Adherence to treatment guidelines showed remarkable variety among German hospitals indicating options and need for improvement.

[Impact of center characteristics on outcome in ovarian cancer in Germany]. / Welchen Einfluss haben Klinikmerkmale auf die Prognose beim Ovarialkarzinom in Deutschland?

PURPOSE: To evaluate the relationship between hospital characteristics and quality of care and outcome in ovarian cancer in Germany. METHODS: This 2nd national survey in patients with histologically proven epithelial ovarian cancer diagnosed in the 3 (rd) quarter 2001 analyzed pattern of care in early (FIGO I-II A) and advanced (FIGO II B-IV) disease. We performed univariate and multivariate analysis of the role of hospital characteristics, like hospital-volume, participation in cooperative clinical studies, and hospital category (university vs central clinic vs. two lower categories in Germany) as prognostic factor. RESULTS: 165 hospitals documented 476 patients (= about one third of all patients diagnosed in Germany within one quarter). Patients treated in study-centres received more frequently standard care and showed superior survival (multivariate analysis including biologic prognostic factors: HR 1.71; 95 % CI 1.2-2.5; p = 0.007). 2-year-survival was 72 % and 64 % in study-centres and hospitals not participating in studies, respectively. Neither hospital category nor hospital-volume showed any significant impact on survival. Only analysis of surrogate parameters like pattern of care in early ovarian cancer revealed advantages related to hospital category. Furthermore, analysis of some surgical details revealed advantages for high-volume centres and hospital category. CONCLUSION: Participation in clincal studies was the only transparent hospital characteristic with significant impact on prognosis of ovarian cancer. Study participation as criterion for quality of care should be included in counselling ovarian cancer patients and should help guiding selection of hospitals for primary therapy. All German hospitals with information about participation in cooperative clinical studies as well as in this quality assurance program are listed on the web.

1,25-dihydroxyvitamin D3 synthetic analogs inhibit spontaneous metastases in a 1,2-dimethylhydrazine-induced colon carcinogenesis model.

In order to substantiate the role of vitamin D applicability for the prevention of colon cancer and its spontaneous metastases, the effect of 1,25-dihydroxyvitamin D3 and its synthetic analogs, 1, 25-dihydroxy-16,23Z-diene-26,27-hexafluoro-D3 (Ro 25-5317) and 1, 25-dihydroxy-16,23E-diene-26,27-hexafluoro-19-nor-D3 (Ro 25-9022), have been evaluated in a 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis model in Sprague-Dawley rats. In animals maintained on 2.75 nmol/kg 1,25-dihydroxyvitamin D3 diet no statistical difference was seen in tumor incidence when compared with control while in animals on 3.0 nmol/kg 1,25-dihydroxyvitamin D3 diet, the incidence of tumors was significantly lower. In animals maintained on 3.0 nmol/kg Ro 25-5317 diet also no statistical difference was seen in tumor incidence compared with control while in animals on 3. 5 nmol/kg Ro 25-5317 diet the incidence of tumors was significantly lower. The incidence of tumors in the group of animals maintained on 3.0 nmol/kg and 3.5 nmol/kg Ro 25-9022 was significantly lower, at 32.1% and 27.6% respectively, compared to control. In the two groups of animals maintained on the 1,25-dihydroxyvitamin D3 diet no significant difference in the incidence of metastasis was seen. In the group of animals maintained on 3.0 nmol/kg Ro 25-5317 diet only regional metastases were seen. However, no metastases developed in the rats on 3.5 nmol/kg Ro 25-5317 diet. After administration of 3.0 nmol/kg Ro 25-9022 diet, metastases developed in a significantly less number of animals while no metastases occurred in the rats maintained on the 3.5 nmol/kg Ro 25-9022 diet. The above studies will provide a scientific basis for the progression into further clinical trials in the treatment, and/or chemoprevention of human colorectal cancer.

Analyzing bivariate repeated measures for discrete and continuous outcome variables.

A considerable body of literature has arisen over the past 15 years for analyzing univariate repeated measures data. However, it is rare in applied biomedical research for interest to be restricted to a single outcome measure. In this paper, we consider the case of bivariate repeated measures. We apply a generalized estimating equations (GEE) approach to relate each set of repeated measures to important explanatory variables. We then invoke the seemingly unrelated regression paradigm to combine these GEE models into an overall analysis framework. This approach provides a great deal of flexibility in modeling the relationships to fixed and time-dependent covariates for each set of outcome variables. Estimation and hypothesis testing issues are described and the methodology is illustrated with an example.

Methotrexate for the treatment of Crohn's disease. The North American Crohn's Study Group Investigators.

BACKGROUND: Although corticosteroids are highly effective in improving symptoms of Crohn's disease, they may have substantial toxicity. In some patients, attempts to discontinue corticosteroids are unsuccessful. METHODS: We conducted a double-blind, placebo-controlled multicenter study of weekly injections of methotrexate in patients who had chronically active Crohn's disease despite a minimum of three months of prednisone therapy. Patients were randomly assigned to treatment with intramuscular methotrexate (25 mg once weekly) or placebo for 16 weeks. The patients also received prednisone (20 mg once a day), which was tapered over 10 weeks unless their condition worsened. The primary outcome measure was clinical remission at the end of the 16-week trial. Remission was defined by the discontinuation of prednisone and a score of < or = 150 points on the Crohn's Disease Activity Index. RESULTS: A total of 141 patients were randomly assigned in a 2:1 ratio to methotrexate (94 patients) or placebo (47 patients). After 16 weeks, 37 patients (39.4 percent) were in clinical remission in the methotrexate group, as compared with 9 patients (19.1 percent) in the placebo group (P = 0.025; relative risk, 1.95; 95 percent confidence interval, 1.09 to 3.48). The patients in the methotrexate group received less prednisone overall than those in the placebo group (P = 0.026). The mean (+/- SE) score on the Crohn's Disease Activity Index after 16 weeks of treatment was significantly lower in the methotrexate group (162 +/- 12) than in the placebo group (204 +/- 17, P = 0.002). The changes in quality-of-life scores and serum orosomucoid concentrations were similar. In the methotrexate group, 16 patients (17 percent) withdrew from treatment because of adverse events (including asymptomatic elevation of serum aminotransferase in 7 and nausea in 6), as compared with 1 patient (2 percent) in the placebo group. CONCLUSIONS: In a group of patients with chronically active Crohn's disease, methotrexate was more effective than placebo in improving symptoms and reducing requirements for prednisone.

Low-dose cyclosporine for the treatment of Crohn's disease. The Canadian Crohn's Relapse Prevention Trial Investigators.

BACKGROUND: Long-term corticosteroid therapy for Crohn's disease is associated with important types of morbidity, such as osteoporosis. Safe and effective alternative treatments are required. Although a short-term benefit of cyclosporine in active Crohn's disease has been suggested, the long-term safety and efficacy of this treatment have not been established. METHODS: We conducted a randomized, double-blind, placebo-controlled evaluation of the effect of 18 months of low-dose cyclosporine treatment on the course of Crohn's disease. Adult patients whose disease had been active within the previous two years were randomly assigned to receive cyclosporine (151 patients) or placebo (154 patients) in addition to their usual therapy. Randomization was stratified according to center and score on the Crohn's Disease Activity Index (193 patients had scores of 150 or less, and 112 had scores greater than 150). The primary outcome measure was clinically important worsening of Crohn's disease, defined as a 100-point increase in the Crohn's Disease Activity Index from the patient's base-line value. Secondary outcomes were the use of prednisone and 5-amino-salicylates, mean score on the Crohn's Disease Activity Index and mean quality-of-life score, and the need for surgery. RESULTS: The condition of more patients worsened with cyclosporine than with placebo (91 of 151, or 60.3 percent, vs. 80 of 154, or 51.9 percent; P = 0.10). The median time to worsening of disease in patients receiving cyclosporine was 338 days, as compared with 492 days in patients receiving placebo (P = 0.25; relative risk, 1.22; 95 percent confidence interval, 0.86 to 1.72). Analyses of the mean Crohn's Disease Activity Index and quality-of-life scores and of the use of prednisone and 5-aminosalicylates also failed to demonstrate benefit. CONCLUSIONS: In our patient population, the addition of low-dose cyclosporine to conventional treatment for Crohn's disease did not improve symptoms or reduce requirements for other forms of therapy.

Quality of life: a valid and reliable measure of therapeutic efficacy in the treatment of inflammatory bowel disease. Canadian Crohn's Relapse Prevention Trial Study Group.

BACKGROUND/AIMS: Quality of life (QOL), a subjective index of health perception and function, embraces physical, social, and emotional performance but has not had a prominent role in clinical trials of inflammatory bowel disease (IBD). To test the robustness of the Inflammatory Bowel Disease Questionnaire (IBDQ), a disease-specific QOL index, this study assessed its validity, reliability, and responsiveness during a multicenter trial. METHODS: Three hundred five patients with stable Crohn's disease received cyclosporin or placebo for 18 months. IBDQ and dimensional scores (bowel, social, systemic, and emotional) were correlated with disease activity (Crohn's disease activity index [CDAI] and Harvey-Bradshaw index). Concordance of IBDQ scores was tested in 280 stable subjects. Linear regression evaluated change in IBDQ scores over time. RESULTS: IBDQ scores correlated highly with CDAI (r = -0.67; P < 0.0001). The reliability coefficient for IBDQ score was 0.70 vs. 0.66 for CDAI and 0.55 for Harvey-Bradshaw index. Regression line slopes of IBDQ scores were significantly different in patients who deteriorated from those who remained stable ([b] < 0.15; P < 0.0001). QOL scores were lower in patients who required surgery. CONCLUSIONS: The IBDQ is a valid reliable assessment tool that reflects important changes in the health status of patients with IBD. The IBDQ is a robust measure of therapeutic efficacy and should be used in future clinical trials in IBD.

A prospective randomized controlled trial of initial immunosuppression with ALG versus OKT3 in recipients of cardiac allografts.

Thirty-nine heart transplant recipients were randomized prospectively to receive OKT3 or antilymphoblast globulin (ALG) for 7 days, having otherwise identical protocols (group 1: OKT3, n = 20 patients; group 2: ALG, n = 19 patients). No preoperative immunosuppression was given. The protocol consisted of methylprednisolone, 500 mg intraoperatively, followed by 1 mg/kg/day, intravenously or orally, tapering to 0.2 mg/kg/day at 1 month; oral cyclosporine starting 3 to 5 days after transplantation; selective use of azathioprine, 1 to 4 mg/kg/day; and either OKT3, 5 mg/day for 7 days, or ALG, 15 mg/kg/day for 7 days. Of the 39 patients in the study, 34 are alive 6 months to 2 years after transplantation. The actuarial survival at 2 years for the OKT3 and ALG groups was 92% (+/- 0.07%) and 83% (+/- 0.09%), respectively (not significant [NS]). The time to first rejection for group 1 was 5.6 weeks and for group 2 was 5.3 weeks (NS). The mean number of rejections for group 1 and group 2 was 2.1 episodes per patient and 1.4 per patient, respectively (NS). Three patients in each group were free of rejection at 6 months. The total number of infections at 6 months was 1.05 per patient in group 1, 0.74 per patient in group 2 (NS), with 35% of patients receiving OKT3 and 52% of patients receiving ALG actuarially free of infection by 6 months after surgery (NS). During the first 24 hours after surgery, no significant differences were noted in mean blood pressure, central venous pressure, or Po2 between the groups.(ABSTRACT TRUNCATED AT 250 WORDS)

First coronary heart disease event rates in relation to major risk factors: Quebec cardiovascular study.

The incidence of first coronary heart disease (CHD) events was evaluated prospectively in relation to the baseline measurements of systolic and diastolic blood pressure, serum cholesterol, smoking status and education in a cohort of 4576 Quebec men aged 35 to 64 and free from CHD at entry in 1974. From 1974 to 1986, 603 first CHD events were documented. The most frequent first manifestation was angina (6.7/1000 person-years) followed by nonfatal myocardial infarction (4.7/1000) and CHD death 2.2/1000). There was a positive relationship between the first CHD event and systolic (Z = 4.67) and diastolic (Z = 6.50) blood pressure. This relation was observed for angina, nonfatal myocardial infarction and CHD death. Serum cholesterol was also related to all events (Z = 4.99) but more specifically to angina and nonfatal myocardial infarction. Cigarette smoking was significantly related to first CHD manifestations. This relationship for specific CHD events was observed in men who smoked more than 20 cigarettes per day. Men who discontinued smoking one year before the study had a risk not different from those who never smoked. No relationship was observed between years of schooling and CHD events. Blood pressure, cholesterol and smoking constituted nearly two-thirds of the attributable risk of first CHD events.