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Diltiazem is recommended and frequently prescribed in patients with angina and nonobstructive coronary artery disease (ANOCA), suspected of coronary vasomotor dysfunction (CVDys). However, studies substantiating its effect is this patient group are lacking. The randomized, placebo-controlled EDIT-CMD (Efficacy of Diltiazem to Improve Coronary Microvascular Dysfunction: A Randomized Clinical Trial) evaluated the effect of diltiazem on CVDys, as assessed by repeated coronary function testing (CFT), angina, and quality of life. A total of 126 patients with ANOCA were included and underwent CFT. CVDys, defined as the presence of vasospasm (after intracoronary acetylcholine provocation) and/or microvascular dysfunction (coronary flow reserve: <2.0, index of microvascular resistance: ≥25), was confirmed in 99 patients, of whom 85 were randomized to receive either oral diltiazem or placebo up to 360 mg/d. After 6 weeks, a second CFT was performed. The primary end point was the proportion of patients having a successful treatment, defined as normalization of 1 abnormal parameter of CVDys and no normal parameter becoming abnormal. Secondary end points were changes from baseline to 6-week follow-up in vasospasm, index of microvascular resistance, coronary flow reserve, symptoms (Seattle Angina Questionnaire), or quality of life (Research and Development Questionnaire 36). In total, 73 patients (38 diltiazem vs 35 placebo) underwent the second CFT. Improvement of the CFT did not differ between the groups (diltiazem vs placebo: 21% vs 29%; P = 0.46). However, more patients on diltiazem treatment progressed from epicardial spasm to microvascular or no spasm (47% vs 6%; P = 0.006). No significant differences were observed between the diltiazem and placebo group in microvascular dysfunction, Seattle Angina Questionnaire, or Research and Development Questionnaire 36. This first performed randomized, placebo-controlled trial in patients with ANOCA showed that 6 weeks of therapy with diltiazem, when compared with placebo, did not substantially improve CVDys, symptoms, or quality of life, but diltiazem therapy did reduce prevalence of epicardial spasm. (Efficacy of Diltiazem to Improve Coronary Microvascular Dysfunction: A Randomized Clinical Trial [EDIT-CMD]; NCT04777045) [Display omitted] [ABSTRACT FROM AUTHOR]

Repeated sessions of cerebellar anodal transcranial direct current stimulation (tDCS) have been suggested to modulate cerebellar-motor cortex (M1) connectivity and decrease ataxia severity. However, therapeutic trials involving etiologically homogeneous groups of ataxia patients are lacking. The objective of this study was to investigate if a two-week regimen of daily cerebellar tDCS sessions diminishes ataxia and non-motor symptom severity and alters cerebellar-M1 connectivity in individuals with spinocerebellar ataxia type 3 (SCA3). We conducted a randomized, double-blind, sham-controlled trial in which twenty mildly to moderately affected SCA3 patients received ten sessions of real or sham cerebellar tDCS (i.e., five days per week for two consecutive weeks). Effects were evaluated after two weeks, three months, six months, and twelve months. Change in Scale for the Assessment and Rating of Ataxia (SARA) score after two weeks was defined as the primary endpoint. Static posturography, SCA Functional Index tests, various patient-reported outcome measures, the cerebellar cognitive affective syndrome scale, and paired-pulse transcranial magnetic stimulation to examine cerebellar brain inhibition (CBI) served as secondary endpoints. Absolute change in SARA score did not differ between both trial arms at any of the time points. We observed significant short-term improvements in several motor, cognitive, and patient-reported outcomes after the last stimulation session in both groups but no treatment effects in favor of real tDCS. Nonetheless, some of the patients in the intervention arm showed a sustained reduction in SARA score lasting six or even twelve months, indicating interindividual variability in treatment response. CBI, which reflects the functional integrity of the cerebellothalamocortical tract, remained unchanged after ten tDCS sessions. Albeit exploratory, there was some indication for between-group differences in SARA speech score after six and twelve months and in the number of extracerebellar signs after three and six months. Taken together, our study does not provide evidence that a two-week treatment with daily cerebellar tDCS sessions reduces ataxia severity or restores cerebellar-M1 connectivity in early-to-middle-stage SCA3 patients at the group level. In order to potentially increase therapeutic efficacy, further research is warranted to identify individual predictors of symptomatic improvement. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate hand sensibility after transradial access (TRA) in patients with and without radial artery occlusion (RAO).Materials and Methods: In this study, 71 patients with and without RAO after TRA for a coronary intervention were studied (79% male, mean age 65 y ± 9). Sensibility testing of both hands was performed with the Semmes-Weinstein monofilaments test. The primary endpoint was abnormal sensibility, defined as diminished sensibility in at least 1 radial nerve-supplied dermatome. The contralateral hand served as control. The influence of TRA, RAO, and clinical characteristics on hand sensibility was evaluated.Results: In patients with RAO, more abnormal sensibility was observed on the RAO side compared with the control hand (72% vs 17%, P < .01). In patients without RAO, more abnormal sensibility was observed in the TRA hand compared with the control hand (43% vs 10%, P < .01). When analyzing all hands separately, TRA, RAO, and diabetes were independent predictors for abnormal hand sensibility in a multivariate model (odds ratio 3.8, 95% confidence interval 1.4-9.8, P < .01; odds ratio 3.0, 95% confidence interval 1.1-8.5, P = .03; odds ratio 3.5, 95% confidence interval 1.4-8.6, P < .01).Conclusions: TRA and RAO are associated with diminished hand sensibility. [ABSTRACT FROM AUTHOR]

This study evaluated the effect of a tailored, multifaceted improvement strategy on hand hygiene compliance in long-term care facilities (LTCFs). We also performed a process evaluation to explore the mechanisms through which our strategy brought about change. We conducted a stepped-wedge cluster-randomized controlled trial with a sequential rollout of the improvement strategy to all participating LTCFs. The strategy consisted of education, training, reminders, observation sessions (including feedback), and team meetings (including feedback). The study included nursing professionals from 14 LTCFs (23 wards) in the Netherlands. Hand hygiene compliance was observed during 5 measurement periods using WHO's "Five Moments for Hand Hygiene." Multilevel analyses and corresponding tests were completed on an intention-to-treat basis. The absolute intervention effect of overall hand hygiene compliance (primary outcome measure) was 13% (95% CI 9.3-16.7, P <.001), adjusted for time and clustering. The adjusted absolute effect was 23% (95% CI 7-39, P <.002) before a clean and aseptic procedure, 18% (95% CI 10-26, P <.001) after touching a resident, 14% (95% CI 7-22, P <.003) before touching a resident, 10% (95% CI 5-15, P <.001) after contact with body fluid, and 1% (95% CI –11 to 13, P =.8) after touching a resident's surroundings. With the exception of leadership, participants at LTCFs with more exposure to the intervention components showed statistically significantly more improvement than those at facilities with lower exposure scores. Our strategy was successful in improving hand hygiene compliance. LTCFs with more team members exposed to the different intervention components, demonstrated a greater effect from the intervention. To strengthen the impact of our intervention, we recommend that future improvement strategies provide more support to managers to ensure they are better equipped to take on their leadership roles and enable their teams to improve and maintain hand hygiene compliance. [ABSTRACT FROM AUTHOR]

Objective: The effect of an intervention on neuropsychiatric symptoms (NPS), particularly agitation and aggression, and psychotropic drug use (PDU) in institutionalized people with young-onset dementia (YOD) was evaluated.Methods: A randomized controlled trial was conducted using a stepped wedge design. Thirteen YOD special care units were randomly assigned to three groups, which received the intervention at different time points. Four assessments took place every 6 months during a period of 18 months. Two hundred seventy-four people with YOD who resided in YOD special care units participated, of whom 131 took part in all assessments. The intervention consisted of an educational program combined with a care program, which structured the multidisciplinary process of managing NPS. The care program included the following five steps: evaluation of psychotropic drug prescription, detection, analysis, treatment, and evaluation of treatment of NPS. The Cohen-Mansfield Agitation Inventory and the Neuropsychiatric Inventory-Nursing Home version were used to assess NPS. Data on PDU were retrieved from residents' medical files. Multilevel models were used to evaluate the effect of the intervention, which accounted for clustering of measurements in clients within units.Results: No significant differences were found in agitation, aggression, other NPS, or PDU after crossing over to the intervention condition.Conclusion: We found no evidence that the intervention for management of NPS in nursing home residents with YOD was more effective in reducing agitation, aggression, other NPS, or PDU compared with care as usual. [ABSTRACT FROM AUTHOR]

Marketing authorisation application dossiers relating to medicinal products containing new active substances and evaluated by the European Medicines Agency (EMA) over the period 2012–2015 were examined. Major objections and other concerns relating to efficacy and safety of the day 80 assessment reports were reviewed. Overall, approved products have more subgroup concerns than nonapproved products, which seems to be a consistent pattern. Subgroup analyses are mainly assessed to have the insurance that subgroups of patients that might lack a positive benefit: risk ratio will not be wrongly included in the approved treatment indication. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the influence of adherence to the Systematic Care Program for Dementia (SCPD) intervention protocol on patient and caregiver outcomes. Design: Data were drawn from the SCPD study--a single-blind, multicenter, cluster-randomized, controlled trial. Multivariate regression analyses were used to assess the influence of adherence on patient and caregiver outcomes. Setting: Six community mental health services (CMHSs) across the Netherlands. Participants: Forty-eight mental health professionals treating 125 patient--caregiver dyads who were referred to the CMHS because of suspected patient dementia. Intervention: Training of professionals in the SCPD and its subsequent use. The SCPD consists of a systematic assessment of caregiver problems and consequent interventions. Measurements: The dependent variables were caregiver's sense of competence, caregiver's depressive symptoms, caregiver's distress due to the patient's behavioral problems, and the severity of patient's behavioral problems. The main independent variables were adherence to the SCPD intervention protocol and the intensity of the SCPD interventions. The follow-up lasted 12 months. Results: Caregivers treated by adhering professionals had a better sense of competence than caregivers treated by nonadhering professionals at follow-up. No differences between intervention groups and controls were found for the other outcomes. Conclusion: Nonadherence to the intervention protocol might be a reason for the difference found in the sense of competence between the intervention groups. Furthermore, the intensity of the SCPD might have been too low. Moreover, it might be that overburdened caregivers found it difficult to make effective use of the help offered to them. A qualitative process analysis should be executed to explore more in-depth clarifications. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Balance of prognostic factors between treatment groups is desirable because it improves the accuracy, precision, and credibility of the results. In cluster-controlled trials, imbalance can easily occur by chance when the number of cluster is small. If all clusters are known at the start of the study, the “best balance” allocation method (BB) can be used to obtain optimal balance. This method will be compared with other allocation methods. Study Design and Setting: We carried out a simulation study to compare the balance obtained with BB, minimization, unrestricted randomization, and matching for four to 20 clusters and one to five categorical prognostic factors at cluster level. Results: BB resulted in a better balance than randomization in 13–100% of the situations, in 0–61% for minimization, and in 0–88% for matching. The superior performance of BB increased as the number of clusters and/or the number of factors increased. Conclusion: BB results in a better balance of prognostic factors than randomization, minimization, stratification, and matching in most situations. Furthermore, BB cannot result in a worse balance of prognostic factors than the other methods. [Copyright &y& Elsevier]

Objective: To evaluate the effectiveness of the Systematic Care Program for Dementia (SCPD) on patient institutionalization and to determine the predictors of in-stitutionalization. Design: Single-blind, multicenter, cluster-randomized, controlled trial. Setting: Six community mental health services (CMHSs) across the Netherlands. Participants: A total of 295 patient-caregiver dyads referred to a CMHS with suspected patient dementia. Intervention: Training of health professionals in the SCPD and its subsequent use. The SCPD consists of a systematic assessment of caregiver problems and alerts health professionals in flexible, connecting, proactive interventions to them. The intensity of the SCPD depends on the judgment of the health professional, based on individual caregiver needs. Primary Outcome: Institutionalization in long-term care facilities at 12 months of follow-up. Results: No main intervention effect on institutionalization was found. However, a better sense of competence in the control group reduced the chance of institutionalization but not in the intervention group. The caregiver's sense of competence and depressive symptoms and the patient's behavioral problems and severity of dementia were the strongest predictors of institutionalization. The intensity of the program was low, even for dyads exposed to the SCPD. Conclusions: Although no main effect was found, the results suggest that the SCPD might prevent a deterioration of the sense of competence in the intervention group. The intensity of a program is crucial and should be prescribed on the basis of evidence rather than left to the discretion of health professionals. Future controlled trials in daily clinical practice should use a process analysis to control for compliance. [ABSTRACT FROM AUTHOR]

Abstract: The most important consideration in the choice of study design and endpoint is that these two features match and represent the objective and the perspective of the trial as closely as possible. The mechanism may also be helpful, but arguments based on the mechanism, structure or levels of the variables, or based on practical considerations, such as (statistical) efficiency, must always be secondary considerations. [Copyright &y& Elsevier]

Background: No-rinse disposable wash gloves are increasingly implemented in health care to replace traditional soap and water bed baths without proper evaluation of (cost) effectiveness. Objectives: To compare bed baths for effects on skin integrity and resistance against bathing and costs. Design: Cluster randomized trial. Setting: Fifty six nursing home wards in the Netherlands. Participants: Five hundred adult care-dependent residents and 275 nurses from nursing home wards. Methods: The experimental condition 'washing without water' consists of a bed bath with disposable wash gloves made of non-woven waffled fibers, saturated with a no-rinse, quickly vaporizing skin cleaning and caring lotion. The control condition is a traditional bed bath using soap, water, washcloths and towels. Both conditions were continued for 6 weeks. Outcome measures were prevalence of skin damage distinguished in two levels of severity: any skin abnormality/lesion and significant skin lesions. Additional outcomes: resistance during bed baths, costs. Results: Any skin abnormalities/lesions over time decreased slightly in the experimental group, and increased slightly in the control group, resulting in 72.7% vs 77.6% of residents having any skin abnormalities/lesions after 6 weeks, respectively (p = 0.04). There were no differences in significant skin lesions or resistance after 6 weeks. Mean costs for bed baths during 6 weeks per resident were estimated at €218.30 (95%CI 150.52-286.08) in the experimental group and €232.20 (95% CI: 203.80-260.60) in the control group (difference €13.90 (95%CI: 25.61-53.42). Conclusion: Washing without water mildly protects from skin abnormalities/lesions, costs for preparing and performing bed baths do not differ from costs for traditional bed bathing. Thus, washing without water can be considered the more efficient alternative. [ABSTRACT FROM AUTHOR]

Background: National Dutch guidelines have been introduced to improve suboptimal perioperative care. A multifaceted implementation programme (IMPlementatie Richtlijnen Operatieve VEiligheid [IMPROVE]) has been developed to support hospitals in applying these guidelines. This study evaluated the effectiveness of IMPROVE on guideline adherence and the association between guideline adherence and patient safety.Methods: Nine hospitals participated in this unblinded, superiority, stepped-wedge, cluster RCT in patients with major noncardiac surgery (mortality risk ≥1%). IMPROVE consisted of educational activities, audit and feedback, reminders, organisational, team-directed, and patient-mediated activities. The primary outcome of the study was guideline adherence measured by nine patient safety indicators on the process (stop moments from the composite STOP bundle, and timely administration of antibiotics) and on the structure of perioperative care. Secondary safety outcomes included in-hospital complications, postoperative wound infections, mortality, length of hospital stay, and unplanned care.Results: Data were analysed for 1934 patients. The IMPROVE programme improved one stop moment: 'discharge from recovery room' (+16%; 95% confidence interval [CI], 9-23%). This stop moment was related to decreased mortality (-3%; 95% CI, -4% to -1%), fewer complications (-8%; 95% CI, -13% to -3%), and fewer unscheduled transfers to the ICU (-6%; 95% CI, -9% to -3%). IMPROVE negatively affected one other stop moment - 'discharge from the hospital' - possibly because of the limited resources of hospitals to improve all stop moments together.Conclusions: Mixed implementation effects of IMPROVE were found. We found some positive associations between guideline adherence and patient safety (i.e. mortality, complications, and unscheduled transfers to the ICU) except for the timely administration of antibiotics.Clinical Trial Registration: NTR3568 (Dutch Trial Registry). [ABSTRACT FROM AUTHOR]

Neuropsychiatric symptoms are common in nursing home residents with young-onset dementia and burdensome for nursing staff. It is known that neuropsychiatric symptoms are associated with burn-out complaints and low job satisfaction. An intervention aimed at decreasing neuropsychiatric symptoms in nursing home residents with young-onset dementia might also result in less burnout complaints and job demands and improve job satisfaction in nursing staff. The aim was to evaluate the effect of the intervention on nursing staff burnout, job satisfaction and job demands. Cluster randomised controlled trial using a stepped wedge design with a total duration of 18 months, with four assessments. Thirteen young-onset dementia special care units across the Netherlands were, by means of random allocation software, assigned to three groups crossing over at different time points. All nursing staff, in total 391, were invited to participate. 305 nursing staff participated during the course of the study of whom 71 participated in all assessments. An educational program followed by a structured multidisciplinary care program aimed at the management of neuropsychiatric symptoms. The care program consists of evaluation of psychotropic drug prescription followed by detection, analysis, treatment and evaluation of treatment of neuropsychiatric symptoms. Emotional exhaustion, depersonalisation and personal accomplishment were assessed with the Utrecht Burnout Scale. Job satisfaction and job demands were assessed with subscales of the Leiden Quality of Work Questionnaire. The baseline burnout risk on emotional exhaustion and personal accomplishment was average, and low on depersonalisation. The mean scores for job satisfaction were above average and for job demands average. Linear mixed models showed that the intervention had no effect on emotional exhaustion (estimated effect −0.04, 95% confidence interval −1.25 to 1.16), depersonalisation (estimated effect 0.24, 95% confidence interval −0.26 to 0.74), personal accomplishment (estimated effect −0.82, 95% confidence interval −1.86 to 0.22) job satisfaction (estimated effect −0.40, 95% confidence interval −0.98 to 0.17) and job demands (estimated effect −0.04, 95% confidence interval −0.57 to 0.49). A significant difference was found between registered nurses and other nursing staff on emotional exhaustion and job satisfaction. Compared to other staff members, registered nurses' emotional exhaustion scores slightly increased while job satisfaction slightly decreased when using the intervention. The intervention was not effective on three dimensions of burnout, job satisfaction and job demands. Staff scored positive on the outcomes of interest before implementation of the intervention, leaving little opportunity for improvement. [ABSTRACT FROM AUTHOR]

Background Delirium is a common disorder in Intensive Care Unit (ICU) patients and is associated with serious short- and long-term consequences, including re-intubations, ICU readmissions, prolonged ICU and hospital stay, persistent cognitive problems, and higher mortality rates. Considering the high incidence of delirium and its consequences, prevention of delirium is imperative. This study focuses on a program of standardized nursing and physical therapy interventions to prevent delirium in the ICU, called UNDERPIN-ICU (nUrsiNg DEliRium Preventive INterventions in the ICU). Objective : To determine the effect of the UNDERPIN-ICU program on the number of delirium-coma-free days in 28 days and several secondary outcomes, such as delirium incidence, the number of days of survival in 28 and 90 days and delirium-related outcomes. Design and setting A multicenter stepped wedge cluster randomized controlled trial. Methods Eight to ten Dutch ICUs will implement the UNDERPIN-ICU program in a randomized order. Every two months the UNDERPIN-ICU program will be implemented in an additional ICU following a two months period of staff training. UNDERPIN-ICU consists of standardized protocols focusing on several modifiable risk factors for delirium, including cognitive impairment, sleep deprivation, immobility and visual and hearing impairment. Participants ICU patients aged ≥18 years (surgical, medical, or trauma) and at high risk for delirium, E-PRE-DELIRIC ≥35%, will be included, unless delirium was detected prior ICU admission, expected length of ICU stay is less then one day or when delirium assessment is not possible. Discussion For every intervention the balance between putative benefit and potential unwanted side effects needs to be considered. In non-ICU patients, it has been shown that a similar program resulted in a significant reduction of delirium incidence and duration. Recent small studies using multi component interventions to prevent delirium in ICU patients have also shown beneficial effect, without unwanted side effects. We therefore feel that the proportionality of potential positive effects of the UNDERPIN-ICU program, weighed against potential unwanted side effects is favourable. Since this has not been rigorously proven in ICU patients, we will study the effects of this program in ICU patients using a stepped wedge design. Trial registration The study is registered in the clinical trials registry: https://clinicaltrials.gov/ . Reporting method Standard Protocol Items: Recommendations for Interventional Trails (SPIRIT). [ABSTRACT FROM AUTHOR]

A response from the author of the article "Stepped wedge designs could reduce the required sample size in cluster randomized trials" in a previous issue is presented.

Objective: The stepped wedge design is increasingly being used in cluster randomized trials (CRTs). However, there is not much information available about the design and analysis strategies for these kinds of trials. Approaches to sample size and power calculations have been provided, but a simple sample size formula is lacking. Therefore, our aim is to provide a sample size formula for cluster randomized stepped wedge designs. Study Design and Setting: We derived a design effect (sample size correction factor) that can be used to estimate the required sample size for stepped wedge designs. Furthermore, we compared the required sample size for the stepped wedge design with a parallel group and analysis of covariance (ANCOVA) design. Results: Our formula corrects for clustering as well as for the design. Apart from the cluster size and intracluster correlation, the design effect depends on choices of the number of steps, the number of baseline measurements, and the number of measurements between steps. The stepped wedge design requires a substantial smaller sample size than a parallel group and ANCOVA design. Conclusion: For CRTs, the stepped wedge design is far more efficient than the parallel group and ANCOVA design in terms of sample size. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Mucinous histology of metastatic colorectal cancer (CRC) has been associated with poor prognosis, however this has never been assessed in large well-defined study populations treated with the current used systemic agents. We investigated the prognostic value of mucinous histology in two large phase III studies in metastatic CRC. Patients and methods: The study population included 1010 metastatic CRC patients who were treated with chemotherapy and targeted therapies in two phase III studies. Patients were classified according to the histology of the primary tumour in mucinous adenocarcinomas (MC) and non-mucinous adenocarcinomas (AC). Results: Patients with MC (n =99) were older, had more often a normal serum lactate dehydrogenase (LDH), extrahepatic localisation of metastases, larger primary tumour diameter and a higher T classification compared to patients with AC (n =911). A deficient mismatch repair system and BRAF mutations were observed in 17% and 22% of patients with MC, compared to 3% and 7% in patients with AC, respectively. Clinical outcome was investigated in both studies separately, showing a worse overall survival (OS), progression free survival and overall response rate in patients with MC compared to patients with AC. Patients with MC received less cycles of treatment compared to AC, but did not suffer from a higher incidence of grade 3/4 toxicity. In multivariate analysis, mucinous histology was as an independent negative prognostic factor for OS, resulting in a combined hazard ratio of 1.78 (95%confidence interval (CI) 1.35–2.35). Conclusions: Patients with metastatic mucinous CRC have distinct clinicopathological features and poor response to chemotherapy and targeted agents. The strong negative prognostic value of MC warrants the use of this pathological feature as a stratification factor for clinical trials in metastatic CRC. [Copyright &y& Elsevier]

Abstract: Purpose: Obesity is associated with an increased risk of development and recurrence of colorectal cancer. However, the role of obesity in advanced colorectal cancer (ACC) patients is unknown. We investigated the effect of body mass index (BMI) on overall survival (OS) in ACC patients receiving systemic treatment in two large phase III studies (CAIRO and CAIRO2). Patients and methods: Treatment data were obtained and analysed from 796 ACC patients who were treated with chemotherapy in the CAIRO study, and from 730 ACC patients who were treated with chemotherapy plus targeted therapy in the CAIRO2 study. Baseline height and weight were used to assign patients to one of the following BMI categories: A (<18.5kg/m2), B (18.5–24.9kg/m2), C (25.0–29.9kg/m2) and D (⩾30.0kg/m2). Results: In 796 patients of the CAIRO study a high BMI was associated with better median OS (8.0, 14.9, 18.4 and 19.5months for BMI categories A, B, C, and D, respectively; P =0.001), and was an independent prognostic factor for OS in a multivariate analysis. BMI was not associated with OS in 730 patients who participated in the CAIRO2 study, although a trend was observed. Conclusions: These results show that BMI is an independent prognostic factor for survival in patients receiving chemotherapy, but not in patients receiving chemotherapy and targeted therapy. The possible decreased efficacy of bevacizumab in obese patients may explain this discrepant result. The role of BMI in patients receiving targeted therapy should be further tested. [Copyright &y& Elsevier]

Abstract: Objective: When an investigator wants to base the power of a planned clinical trial on the outcome of another trial, the latter study may not have been reported in sufficient detail to allow this. For example, when the outcome is a change from baseline, the power calculation requires the standard deviation of the difference, and it frequently happens that only the standard deviations of the baseline and the follow-up measurements are reported. Also when a complex analysis or an analysis with covariates is planned, the power calculation may be difficult or impossible. The objective was to develop a method to determine the power of a trial, based on minimal information from a previous (reference) trial. Study Design and Setting: We investigated the power calculation for a range of statistical methods, including the t-test, analysis of covariance, analysis of variance, linear regression, logistic regression, Poisson regression, the Wilcoxon test, and the logrank test. Results: A method to calculate the power of a trial solely based on the P-value or the confidence interval of the outcome of the reference study. Conclusion: A power calculation based on an earlier similar trial only requires its P-value. [Copyright &y& Elsevier]

Background: Anti-EGFR monoclonal antibodies in metastatic colorectal cancer (mCRC) treatment are only effective in patients with KRAS wild type tumours. Here we assess the predictive value of other potential relevant markers involved in the epidermal growth factor receptor (EGFR) signalling pathways for response to cetuximab-based treatment. Materials and methods: Formalin-fixed paraffin-embedded colorectal cancer tissue of the primary tumour was obtained from 559 mCRC patients treated with chemotherapy and bevacizumab with or without cetuximab (phase III CAIRO2 study). DNA was isolated for mutation analysis of BRAF (V600E), KRAS (codon 12 and 13) and PIK3CA (exon 9 and 20). Tissue microarray’s (TMA’s) were constructed for the assessment of EGFR and HER2 gene copy number (GCN), and EGFR and PTEN protein expression. The results of these markers, individually or in combination, were correlated with progression-free survival (PFS) and overall survival (OS) in the subgroup of patients with a KRAS wild type tumour treated in the cetuximab-arm. KRAS wild type patients treated without cetuximab were used as a control group. Results: A total of 208 tumours (39.4%) contained a KRAS mutation, 8.7% a BRAF mutation and 9.9% a PIK3CA mutation. Loss of PTEN expression and the presence EGFR protein expression were observed in 42.0% and 61.7% of the samples, respectively. An increased EGFR GCN was observed in 15.3% of the samples, and 11.5% of the evaluable samples contained an increased HER2 GCN. In KRAS wild type patients treated with cetuximab a BRAF mutation was significantly and independently associated with PFS and OS. In patients treated without cetuximab the PFS and OS were also associated with the BRAF genotype. No prognostic or predictive value was observed for any of the other markers when tested individually or in combination. Conclusions: BRAF genotype is correlated with PFS and OS in KRAS wild type mCRC patients, which is independent of cetuximab treatment. PIK3CA mutation, loss of PTEN expression, EGFR GCN and HER2 GCN have no predictive value for response to treatment with cetuximab, neither individually nor in combination with other markers. [Copyright &y& Elsevier]

To explore the course of quality of life (QoL) and possible resident-related predictors associated with this course in institutionalized people with young-onset dementia (YOD). An observational longitudinal study. A total of 278 residents with YOD were recruited from 13 YOD special care units in the Netherlands. Secondary analyses were conducted with longitudinal data from the Behavior and Evolution in Young-ONset Dementia (BEYOND)-II study. QoL was assessed with proxy ratings, using the Quality of Life in Dementia (QUALIDEM) questionnaire at 4 assessment points over 18 months. Predictors included age, gender, dementia subtype, length of stay, dementia severity, neuropsychiatric symptoms, and psychotropic drug use at baseline. Multilevel modeling was used to adjust for the correlation of measurements within residents and clustering of residents within nursing homes. The total QUALIDEM score (range: 0-111) decreased over 18 months with a small change of 0.65 (95% confidence interval −1.27, −0.04) points per 6 months. An increase in several domains of QoL regarding care relationship, positive self-image, and feeling at home was seen over time, whereas a decline was observed in the subscales positive affect, social relations, and having something to do. Residents with higher levels of QoL and more advanced dementia at baseline showed a more progressive decline in QoL over time. Sensitivity analyses indicated a more progressive decline in QoL for residents who died during the follow-up. This study shows that although overall QoL in nursing home residents with YOD was relatively stable over 18 months, there were multidirectional changes in the QoL subscales that could be clinically relevant. Higher levels of QoL and more advanced stages of dementia at baseline predicted a more progressive decline in QoL over time. More longitudinal studies are needed to verify factors influencing QoL in YOD. [ABSTRACT FROM AUTHOR]

Advance care planning (ACP) is seldom initiated with people with dementia (PWD) and mainly focuses on medical end-of-life decisions. We studied the effects of an educational intervention for general practitioners (GPs) aimed at initiating and optimizing ACP, with a focus on discussing medical and nonmedical preferences of future care. A single-blinded cluster randomized controlled trial. In 2016, 38 Dutch GPs (all from different practices) completed the study. They recruited 140 PWD, aged ≥65 years at any stage and with any type of dementia, from their practice. Intervention group GPs were trained in ACP, including shared decision-making and role-playing exercises. Control group GPs provided usual care. The primary outcome was ACP initiation: the proportion of PWD that had at least 1 ACP conversation documented in their medical file. Key secondary outcomes were the number of medical (ie, resuscitation, hospital admission) and nonmedical (ie, activities, social contacts) preferences discussed. At the 6-month follow-up, subjects' medical records were analyzed using random effect logistics and linear models with correction for GP clustering. 38 GP clusters (19 intervention; 19 control) included 140 PWD (intervention 73; control 67). Four PWD (2.9%) dropped out on the primary and key secondary outcomes. After 6 months, intervention group GPs initiated ACP with 35 PWD (49.3%), and control group GPs initiated ACP with 9 PWD (13.9%) [odds ratio (OR) 1.99; P =.002]. Intervention group GPs discussed 0.8 more medical [95% confidence interval (CI) 0.3, 1.3; P =.003] and 1.5 more nonmedical (95% CI 0.8, 2.3; P <.001) preferences per person with dementia than control group GPs. Our educational intervention increased ACP initiation, and the number of nonmedical and medical preferences discussed. This intervention has the potential to better align future care of PWD with their preferences but because of the short follow-up, the GPs' long-term adoption remains unknown. [ABSTRACT FROM AUTHOR]