Physicians' Views and Agreement about Patient- and Context-Related Factors Influencing ICU Admission Decisions: A Prospective Study.

BACKGROUND: Single patient- and context-related factors have been associated with admission decisions to intensive care. How physicians weigh various factors and integrate them into the decision-making process is not well known. OBJECTIVES: First, to determine which patient- and context-related factors influence admission decisions according to physicians, and their agreement about these determinants; and second, to examine whether there are differences for patients with and without advanced disease. METHOD: This study was conducted in one tertiary hospital. Consecutive ICU consultations for medical inpatients were prospectively included. Involved physicians, i.e., internists and intensivists, rated the importance of 13 factors for each decision on a Likert scale (1 = negligible to 5 = predominant). We cross-tabulated these factors by presence or absence of advanced disease and examined the degree of agreement between internists and intensivists using the kappa statistic. RESULTS: Of 201 evaluated patients, 105 (52.2%) had an advanced disease, and 140 (69.7%) were admitted to intensive care. The mean number of important factors per decision was 3.5 (SD 2.4) for intensivists and 4.4 (SD 2.1) for internists. Patient's comorbidities, quality of life, preferences, and code status were most often mentioned. Inter-rater agreement was low for the whole population and after stratifying for patients with and without advanced disease. Kappa values ranged from 0.02 to 0.34 for all the patients, from -0.05 to 0.42 for patients with advanced disease, and from -0.08 to 0.32 for patients without advanced disease. The best agreement was found for family preferences. CONCLUSION: Poor agreement between physicians about patient- and context-related determinants of ICU admission suggests a lack of explicitness during the decision-making process. The potential consequences are increased variability and inequity regarding which patients are admitted. Timely advance care planning involving families could help physicians make the decision most concordant with patient preferences.

How to use likelihood ratios to interpret evidence from randomized trials.

OBJECTIVE: The likelihood ratio is a method for assessing evidence regarding two simple statistical hypotheses. Its interpretation is simple - for example, a value of 10 means that the first hypothesis is 10 times as strongly supported by the data as the second. A method is shown for deriving likelihood ratios from published trial reports. STUDY DESIGN: The likelihood ratio compares two hypotheses in light of data: that a new treatment is effective, at a specified level (alternate hypothesis: for instance, the hazard ratio equals 0.7), and that it is not (null hypothesis: the hazard ratio equals 1). The result of the trial is summarised by the test statistic z (ie, the estimated treatment effect divided by its standard error). The expected value of z is 0 under the null hypothesis, and A under the alternate hypothesis. The logarithm of the likelihood ratio is given by z·A - A2/2. The values of A and z can be derived from the alternate hypothesis used for sample size computation, and from the observed treatment effect and its standard error or confidence interval. RESULTS: Examples are given of trials that yielded strong or moderate evidence in favor of the alternate hypothesis, and of a trial that favored the null hypothesis. The resulting likelihood ratios are applied to initial beliefs about the hypotheses to obtain posterior beliefs. CONCLUSIONS: The likelihood ratio is a simple and easily understandable method for assessing evidence in data about two competing a priori hypotheses.

Evidence of survival benefit was often ambiguous in randomized trials of cancer treatments.

OBJECTIVES: The objective of the study is to estimate the proportion of statistically significant survival improvements reported in randomized trials of cancer treatments that are also compatible with a clinically negligible benefit. STUDY DESIGN AND SETTING: This is a cross-sectional study of reports of randomized clinical trials of cancer treatments that reported a statistically significant increase in overall survival, published in leading journals between 2009 and 2019. The main outcome variable was the hazard ratio (HR) for overall survival and its upper 95% confidence limit. An HR of 0.95 implies an absolute survival gain ≤1.9%, and an HR of 0.90 implies an absolute survival gain ≤3.8%; we reasoned that such survival gains can be considered clinically negligible, given the potential toxicity of oncologic treatments. RESULTS: Among 234 trial results, the mean point estimate of the HR was 0.664, and all HRs were below 0.90. The mean upper 95% confidence limit for the HR was 0.897, but 37.6% of the values were ≥0.95, and 59.0% were ≥0.90. These proportions were lower when overall survival was the primary outcome of the trial (29.9% ≥ 0.95 and 51.3% ≥ 0.90). CONCLUSIONS: Considering only point estimates of HRs, all trials reported clinically meaningful improvements in overall survival. However, the upper confidence limits of a large proportion of HRs were also compatible with clinically negligible survival gains. Acknowledging the uncertainty regarding treatment benefits presents a challenge for the reporting of trial results and for clinical decision-making.

Patient satisfaction and survey response in 717 hospital surveys in Switzerland: a cross-sectional study.

BACKGROUND: The association between patient satisfaction and survey response is only partly understood. In this study, we describe the association between average satisfaction and survey response rate across hospital surveys, and model the association between satisfaction and propensity to respond for individual patients. METHODS: Secondary analysis of patient responses (166'014 respondents) and of average satisfaction scores and response rates obtained in 717 annual patient satisfaction surveys conducted between 2011 and 2015 at 164 Swiss hospitals. The satisfaction score was the average of 5 items scored between 0 and 10. The association between satisfaction and response propensity in individuals was modeled as the function that predicted best the observed response rates across surveys. RESULTS: Among the 717 surveys, response rates ranged from 16.1 to 80.0% (pooled average 49.8%), and average satisfaction scores ranged from 8.36 to 9.79 (pooled mean 9.15). At the survey level, the mean satisfaction score and response rate were correlated (r = 0.61). This correlation held for all subgroups of surveys, except for the 5 large university hospitals. The estimated individual response propensity function was "J-shaped": the probability of responding was lowest (around 20%) for satisfaction scores between 3 and 7, increased sharply to about 70% for those maximally satisfied, and increased slightly for the least satisfied. Average satisfaction scores projected for 100% participation were lower than observed average scores. CONCLUSIONS: The most satisfied patients were the most likely to participate in a post-hospitalization satisfaction survey. This tendency produces an upward bias in observed satisfaction scores, and a positive correlation between average satisfaction and response rate across surveys.

Symptoms of osteoarthritis influence mental and physical health differently before and after joint replacement surgery: A prospective study.

BACKGROUND: Patient-reported outcomes are increasingly used in evaluations of joint replacement surgery, but it is unclear if symptoms of osteoarthritis (i.e., pain and dysfunction) influence health perceptions similarly before and after surgery. METHODS: In this prospective study based on a hospital-based arthroplasty registry, patients with primary total hip or knee arthroplasty (THA, N = 990, and TKA, N = 907) completed the WOMAC Pain and Function scales, and the SF12 Physical and Mental Component Scores (PCS and MCS), before surgery and one year later. Associations between WOMAC and SF12 scales were examined using mixed linear regression models. RESULTS: All patient-reported outcomes improved following total joint arthroplasty, but the associations between symptom scales and global health perceptions were altered. Mental health scores at a given level of pain or function were lower after surgery than before, by about 4-5 points, a clinically meaningful and statistically significant difference. In contrast, the associations between WOMAC scales and the PCS remained stable. These findings were observed in both cohorts of patients. CONCLUSIONS: After total joint arthroplasty, mental health scores were lower than would have been expected given the symptomatic improvement. This suggests that relationships between patient-reported outcomes are context-dependent, and that care should be exerted when interpreting changes in patient-reported outcomes over time.

Internists' and intensivists' roles in intensive care admission decisions: a qualitative study.

BACKGROUND: Intensive care Unit (ICU) admission decisions involve collaboration between internists and intensivists. Clear perception of each other's roles is a prerequisite for good collaboration. The objective was to explore how internists and intensivists perceive their roles during admission decisions. METHODS: Individual in-depth interviews with 12 intensivists and 12 internists working at a Swiss teaching hospital. Interviews were analyzed using a thematic approach. RESULTS: Roles could be divided into practical roles and identity roles. Internist and intensivists had the same perception of each other's practical roles. Internists' practical roles were: recognizing signs of severity when the patient becomes acutely ill, calling the intensivist at the right moment, having the relevant information about the patient and having determined the goals of care. Intensivists' practical roles were: assessing the patient on the ward, giving expert advice, making quick decisions, managing access to the ICU, having the final decision power and, sometimes, deciding whether or not to limit treatment. In complex situations, perceived flaws in performing practical roles could create tensions between the doctors. Intensivists' identity roles included those of leader, gatekeeper, life-death decision maker, and supporting colleague doctors (consultant, senior and helper). These roles could be perceived as emotionally burdensome. Internists' identity roles were those of leader and partner. CONCLUSIONS: Despite a common perception of each other's practical roles, tensions can arise between internists and intensivists in complex situations of ICU admission decisions. Training in communication skills and interprofessional education interventions aimed at a better understanding of each other roles would improve collaboration.

Clinical and radiographic predictors of acute compartment syndrome in the treatment of tibial plateau fractures: a retrospective cohort study.

BACKGROUND: The aim of the study was to evaluate the relation between demographic, injury-related, clinical and radiological factors of patients with tibial plateau fractures and the development of acute compartment syndrome. METHODS: All consecutive adult patients with intra-articular tibial plateau fractures admitted in our urban academic medical centre between January 2005 and December 2009 were included in this retrospective cohort study. The main outcome measurement was the development of acute compartment syndrome. RESULTS: The charts of 265 patients (mean age 48.6 years) sustaining 269 intra-articular tibial plateau fractures were retrospectively reviewed. Acute compartment syndrome occurred in 28 fractures (10.4%). Four patients presented bilateral tibial plateau fractures; of them, 2 had unilateral, but none had bilateral acute compartment syndrome. Non-contiguous tibia fracture or knee dislocation and higher AO/OTA classification (type 41-C) were statistically significantly associated with the development of acute compartment syndrome in multivariable regression analysis, while younger age (<45 years), male sex, higher Schatzker grade (IV-V-VI), higher tibial widening ratio (≥1.05) and higher femoral displacement ratio (≥0.08) were significantly associated in the analysis adjusted for age and sex. CONCLUSIONS: Two parameters related to the occurrence of ACS in tibial plateau fractures were highlighted in this study: the presence of a non-contiguous tibia fracture or knee dislocation, and higher AO/OTA classification. They may be especially useful when clinical findings are difficult to assess (doubtful clinical signs, obtunded, sedated or intubated patients), and should rise the suspicion level of the treating surgeon. In these cases, regular clinical examinations and/or intra-compartmental pressure measurements should be performed before and after surgery, even if acute compartment syndrome seemed unlikely during initial assessment. However, larger studies are mandatory to confirm and refine both factors in predicting the occurrence of acute compartment syndrome.

Thinker, Soldier, Scribe: cross-sectional study of researchers' roles and author order in the Annals of Internal Medicine.

OBJECTIVE: How researchers' contributions relate to author order on the byline remains unclear. We sought to identify researchers' contributions associated with author order, and to explore the existence of author profiles. DESIGN: Observational study. SETTING: Published record. PARTICIPANTS: 1139 authors of 119 research articles published in 2015 in the Annals of Internal Medicine. PRIMARY OUTCOMES: Presence or absence of 10 contributions, reported by each author, published in the journal. RESULTS: On average, first authors reported 7.1 contributions, second authors 5.2, middle authors 4.0, penultimate authors 4.5 and last authors 6.4 (p<0.001). The first author made the greatest contributions to drafting the article, designing the study, analysing and interpreting the data, and providing study materials or patients. The second author contributed to data analysis as well and to drafting the article. The last author was most involved in obtaining the funding, critically revising the article, designing the study and providing support. Factor analysis yielded three author profiles-Thinker (study design, revision of article, obtaining funding), Soldier (providing material or patients, providing administrative and logistical support, collecting data) and Scribe (analysis and interpretation of data, drafting the article, statistical expertise). These profiles do not strictly correspond to byline position. CONCLUSIONS: First, second and last authors of research articles made distinct contributions to published research. Three authorship profiles can be used to summarise author contributions. These findings shed light on the organisation of clinical research teams and may help researchers discuss, plan and report authorship in a more transparent way.

Determinants of the calibration of SAPS II and SAPS 3 mortality scores in intensive care: a European multicenter study.

BACKGROUND: The aim of the Simplified Acute Physiology Score (SAPS) II and SAPS 3 is to predict the mortality of patients admitted to intensive care units (ICUs). Previous studies have suggested that the calibration of these scores may vary across countries, centers, and/or characteristics of patients. In the present study, we aimed to assess determinants of the calibration of these scores. METHODS: We assessed the calibration of the SAPS II and SAPS 3 scores among 5266 patients admitted to ICUs during a 4-week period at 120 centers in 17 European countries. We obtained calibration curves, Brier scores, and standardized mortality ratios. Points attributed to SAPS items were reevaluated and compared with those of the original scores. Finally, we tested associations between the calibration and center characteristics. RESULTS: The mortality was overestimated by both scores: The standardized mortality ratios were 0.75 (95% CI 0.71-0.79) for the SAPS II score and 0.91 (95% CI 0.86-0.96) for the SAPS 3 score. This overestimation was partially explained by changes in associations between some items of the scores and mortality, especially the heart rate, Glasgow Coma Scale score, and diagnosis of AIDS for SAPS II. The calibration of both scores was better in countries with low health expenditures. The between-center variability in calibration curves was much greater than expected by chance. CONCLUSIONS: Both scores overestimate current mortality among European ICU patients. The magnitude of the miscalibration of SAPS II and SAPS 3 scores depends not only on patient characteristics but also on center characteristics. Furthermore, much between-center variability in calibration remains unexplained by these factors. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01422070 . Registered 19 August 2011.

The distribution of P-values in medical research articles suggested selective reporting associated with statistical significance.

OBJECTIVES: Published P-values provide a window into the global enterprise of medical research. The aim of this study was to use the distribution of published P-values to estimate the relative frequencies of null and alternative hypotheses and to seek irregularities suggestive of publication bias. STUDY DESIGN AND SETTING: This cross-sectional study included P-values published in 120 medical research articles in 2016 (30 each from the BMJ, JAMA, Lancet, and New England Journal of Medicine). The observed distribution of P-values was compared with expected distributions under the null hypothesis (i.e., uniform between 0 and 1) and the alternative hypothesis (strictly decreasing from 0 to 1). P-values were categorized according to conventional levels of statistical significance and in one-percent intervals. RESULTS: Among 4,158 recorded P-values, 26.1% were highly significant (P < 0.001), 9.1% were moderately significant (P ≥ 0.001 to < 0.01), 11.7% were weakly significant (P ≥ 0.01 to < 0.05), and 53.2% were nonsignificant (P ≥ 0.05). We noted three irregularities: (1) high proportion of P-values <0.001, especially in observational studies, (2) excess of P-values equal to 1, and (3) about twice as many P-values less than 0.05 compared with those more than 0.05. The latter finding was seen in both randomized trials and observational studies, and in most types of analyses, excepting heterogeneity tests and interaction tests. Under plausible assumptions, we estimate that about half of the tested hypotheses were null and the other half were alternative. CONCLUSION: This analysis suggests that statistical tests published in medical journals are not a random sample of null and alternative hypotheses but that selective reporting is prevalent. In particular, significant results are about twice as likely to be reported as nonsignificant results.

Kappa statistic to measure agreement beyond chance in free-response assessments.

BACKGROUND: The usual kappa statistic requires that all observations be enumerated. However, in free-response assessments, only positive (or abnormal) findings are notified, but negative (or normal) findings are not. This situation occurs frequently in imaging or other diagnostic studies. We propose here a kappa statistic that is suitable for free-response assessments. METHOD: We derived the equivalent of Cohen's kappa statistic for two raters under the assumption that the number of possible findings for any given patient is very large, as well as a formula for sampling variance that is applicable to independent observations (for clustered observations, a bootstrap procedure is proposed). The proposed statistic was applied to a real-life dataset, and compared with the common practice of collapsing observations within a finite number of regions of interest. RESULTS: The free-response kappa is computed from the total numbers of discordant (b and c) and concordant positive (d) observations made in all patients, as 2d/(b + c + 2d). In 84 full-body magnetic resonance imaging procedures in children that were evaluated by 2 independent raters, the free-response kappa statistic was 0.820. Aggregation of results within regions of interest resulted in overestimation of agreement beyond chance. CONCLUSIONS: The free-response kappa provides an estimate of agreement beyond chance in situations where only positive findings are reported by raters.

Short Dental Implants Retaining Two-Implant Mandibular Overdentures in Very Old, Dependent Patients: Radiologic and Clinical Observation Up to 5 Years.

PURPOSE: To describe the survival rate and peri-implant bone loss in very old patients dependent for their activities of daily living (ADL), treated with mandibular two-implant overdentures (IODs) in the context of a previously reported randomized controlled trial. MATERIALS AND METHODS: A total of 19 patients received two interforaminal Straumann implants (Regular Neck, 4.1 mm diameter, 8 mm length) that were subsequently loaded with Locator attachments, transforming their preexisting inferior conventional denture into an IOD. The primary outcome measures were implant survival rate and radiographically assessed peri-implant bone loss. Secondary outcome measures included peri-implant probing depth and Plaque Index scores, as well as implant mobility. Nutritional state (body mass index and blood markers) and cognitive state (Mini-Mental State Examination) were also analyzed. RESULTS: The patient cohort comprised eight men and 11 women with a mean age of 85.7 ± 6.6 years. The implant survival rate up to 5 years was 94.7%, with one early and one late implant failure. The mean loss of peri-implant bone height was 0.17 mm per year (95% confidence interval: 0.09 to 0.24; P < .001). Peri-implant probing depth and Plaque Index scores were low and stable during the first 2 years, and thereafter increased continuously. Correlation analysis suggests that a reduced cognitive function and nutritional state are not a particular risk factor for accelerated peri-implant bone loss. CONCLUSION: The high implant survival and acceptable peri-implant health suggest that neither age nor dependency for the ADLs is a contraindication for the placement of implants. Nevertheless, close monitoring of the patients concerning a potential further functional decline precluding denture management and performing oral hygiene measures is advised.

Health utility indexes in patients with acute coronary syndromes.

BACKGROUND: Acute coronary syndromes (ACS) have been associated with lower health utilities (HUs) compared with the general population. Given the prognostic improvements after ACS with the implementation of coronary angiography (eg, percutaneous coronary intervention (PCI)), contemporary HU values derived from patient-reported outcomes are needed. METHODS: We analysed data of 1882 patients with ACS 1 year after coronary angiography in a Swiss prospective cohort. We used the EuroQol five-dimensional questionnaire (EQ-5D) and visual analogue scale (VAS) to derive HU indexes. We estimated the effects of clinical factors on HU using a linear regression model and compared the observed HU with the average values of individuals of the same sex and age in the general population. RESULTS: Mean EQ-5D HU 1-year after coronary angiography for ACS was 0.82 (±0.16) and mean VAS was 0.77 (±0.18); 40.9% of participants exhibited the highest utility values. Compared with population controls, the mean EQ-5D HU was similar (expected mean 0.82, p=0.58) in patients with ACS, but the mean VAS was slightly lower (expected mean 0.79, p<0.001). Patients with ACS who are younger than 60 years had lower HU than the general population (<0.001). In patients with ACS, significant differences were found according to the gender, education and employment status, diabetes, obesity, heart failure, recurrent ischaemic or incident bleeding event and participation in cardiac rehabilitation (p<0.01). CONCLUSIONS: At 1 year, patients with ACS with coronary angiography had HU indexes similar to a control population. Subgroup analyses based on patients' characteristics and further disease-specific instruments could provide better sensitivity for detecting smaller variations in health-related quality of life.

Patient enrollment and logistical problems top the list of difficulties in clinical research: a cross-sectional survey.

BACKGROUND: Many medical research projects encounter difficulties. The objective of this study was to assess the self-reported frequency of difficulties encountered by medical researchers while conducting research and to identify factors associated with their occurrence. METHODS: The authors conducted a cross-sectional survey in 2010 among principal investigators of 996 study protocols approved by the Research Ethics Committee in Geneva, Switzerland, between 2001 and 2005. The authors asked principal investigators to rate the level of difficulty (1: none, to 5: very great) encountered across the research process. RESULTS: 588 questionnaires were sent back (participation rate 59.0 %). 391 (66.5 %) studies were completed at the time of the survey. Investigators reported that the most frequent difficulties were related to patient enrollment (44.3 %), data collection (26.7 %), data analysis and interpretation (21.5 %), collaboration with caregivers (21.0 %), study design (20.4 %), publication in peer-reviewed journal (20.2 %), hiring of competent study personnel (20.2 %), and getting funding (19.2 %). On average, investigators reported 2.8 difficulties per project (SD 2.8, range 0 to 12). In multivariable analysis, the number of difficulties was higher for studies initiated by public sponsors (vs. private), single center studies (vs. multicenter), and studies about treatment, diagnosis or prognosis (i.e., clinical vs. other studies). CONCLUSIONS: Medical researchers reported substantial logistical difficulties in conducting clinical research.

Healthcare-Related Regret among Nurses and Physicians Is Associated with Self-Rated Insomnia Severity: A Cross-Sectional Study.

To examine the association between healthcare-related regrets and sleep difficulties among nurses and physicians, we surveyed 240 nurses and 220 physicians at the University Hospitals of Geneva. Regret intensity and regret coping were measured using validated scales. Sleep difficulties were measured using the Insomnia Severity Index (ISI), and an additional question assessed the frequency of sleeping pill use. After controlling for sex, profession, years of experience, rate of employment, and depression as well as for all other regret-related variables, the following variables remained significantly associated with self-rated severity of insomnia: regret intensity (slope = 1.32, p = 0.007, 95%CI: [0.36; 2.29], std. coefficient = 0.16) and maladaptive (e.g., rumination) emotion-focused coping (slope = 1.57, p = 0.002, 95%CI: [0.60; 2.55], std. coefficient = 0.17) remained significant predictors of self-rated insomnia severity. If these cross-sectional associations represent causal effects, the development of regret-management programs may represent a promising approach to mitigating sleep difficulties of healthcare professionals.

Comparison of Diagnostic Accuracy of PCR Targeting the 47-Kilodalton Protein Membrane Gene of Treponema pallidum and PCR Targeting the DNA Polymerase I Gene: Systematic Review and Meta-analysis.

Treponema pallidum PCR (Tp-PCR) testing now is recommended as a valid tool for the diagnosis of primary or secondary syphilis. The objectives were to systematically review and determine the optimal specific target gene to be used for Tp-PCR. Comparisons of the performance of the two main targets are tpp47 and polA genes were done using meta-analysis. Three electronic bibliographic databases, representing abstract books from five conferences specialized in infectious diseases from January 1990 to March 2015, were searched. Search keywords included ("syphilis" OR "Treponema pallidum" OR "neurosyphilis") AND ("PCR" OR "PCR" OR "molecular amplification"). We included diagnostic studies assessing the performance of Tp-PCR targeting tpp47 (tpp47-Tp-PCR) or the polA gene (polA-Tp-PCR) in ulcers from early syphilis. All studies were assessed against quality criteria using the QUADAS-2 tool. Of 37 studies identified, 62.2% were judged at low risk of bias or applicability. Most used the U.S. Centers for Disease Control and Prevention (CDC) case definitions for primary or secondary (early) syphilis (89.2%; n = 33); 15 (40.5%) used darkfield microscopy (DFM). We did not find differences in sensitivity and specificity between the two Tp-PCR methods in the subgroup of studies using adequate reference tests. Among studies using DFM as the reference test, sensitivities were 79.8% (95% confidence intervals [CI], 72.7 to 85.4%) and 71.4% (46.0 to 88.0%) for tpp47-Tp-PCR and polA-Tp-PCR (P = 0.217), respectively; respective specificities were 95.3% (93.5 to 96.6%) and 93.7% (91.8 to 95.2%) (P = 0.304). Our findings suggest that the two Tp-PCR methods have similar accuracy and could be used interchangeably.

Online accesses to medical research articles on publication predicted citations up to 15 years later.

OBJECTIVES: To examine whether the number of early online accesses to medical research articles predicts citations in the scientific literature over time. STUDY DESIGN AND SETTING: Cohort study of research articles published in the BMJ between January and June 1999. The number of online assesses within 1 week of publication was examined in relation to citation counts in 1999-2004, 2004-2009, and 2009-2014. RESULTS: The 148 included articles were accessed on average 691 times up publication, and each was cited on average 33 times in 1999-2004, 32 times in 2004-2009, and 26 times in 2009-2014. The logarithm of accesses predicted the logarithm of citations for all three subsequent periods, but the association weakened over time (correlation with citations in 1999-2004: 0.54, 2004-2009: 0.49, 2009-2014: 0.39; all P < 0.001). In addition to online accesses, the presence of an abstract also predicted more citations for all periods. CONCLUSION: Early interest in a medical research article, reflected by online accesses within a week of publication, predicts citations up to 15 years later. This strengthens the validity of online usage as a measure of the scientific merit of publications.

Comparison of noninferiority margins reported in protocols and publications showed incomplete and inconsistent reporting.

OBJECTIVES: To compare noninferiority margins defined in study protocols and trial registry records with margins reported in subsequent publications. STUDY DESIGN AND SETTING: Comparison of protocols of noninferiority trials submitted 2001 to 2005 to ethics committees in Switzerland and The Netherlands with corresponding publications and registry records. We searched MEDLINE via PubMed, the Cochrane Controlled Trials Register (Cochrane Library issue 01/2012), and Google Scholar in September 2013 to identify published reports, and the International Clinical Trials Registry Platform of the World Health Organization in March 2013 to identify registry records. Two readers recorded the noninferiority margin and other data using a standardized data-abstraction form. RESULTS: The margin was identical in study protocol and publication in 43 (80%) of 54 pairs of study protocols and articles. In the remaining pairs, reporting was inconsistent (five pairs, 9%), or the noninferiority margin was either not reported in the publication (five pairs, 9%) or not defined in the study protocol (one pair). The confidence interval or the exact P-value required to judge whether the result was compatible with noninferior, inferior, or superior efficacy was reported in 43 (80%) publications. Complete and consistent reporting of both noninferiority margin and confidence interval (or exact P-value) was present in 39 (72%) protocol-publication pairs. Twenty-nine trials (54%) were registered in trial registries, but only one registry record included the noninferiority margin. CONCLUSION: The reporting of noninferiority margins was incomplete and inconsistent with study protocols in a substantial proportion of published trials, and margins were rarely reported in trial registries.

Doctors' decisions when faced with contradictory patient advance directives and health care proxy opinion: a randomized vignette-based study.

CONTEXT: Sometimes a written advance directive contradicts the opinion of a health care proxy. How this affects doctors' decision making is unknown. OBJECTIVES: To quantify the influence of contradictory instructions on doctors' decisions. METHODS: All the generalists and internists in French-speaking Switzerland were mailed the questionnaire. Respondents (43.5%) evaluated three vignettes that described medical decisions for incapacitated patients. Each vignette was produced in four versions: one with an advance directive, one with a proxy opinion, one with both, and one with neither (control). In the first vignette, the directive and proxy agreed on the recommendation to forgo a medical intervention; in the second, the advance directive opposed, but the proxy favored the intervention; and in the third, the roles were reversed. Each doctor received one version of each vignette, attributed at random. The outcome variables were the doctor's decision to forgo the medical intervention and the rating of the decision as difficult. RESULTS: Written advance directives and proxy opinions significantly influenced doctors' decision making. When both were available and concordant, they reinforced each other (odds ratio [OR] of forgoing intervention 35.7, P < 0.001 compared with no instruction). When the directive and proxy disagreed, the resulting effect was to forgo the intervention (ORs 2.1 and 2.2 for the two discordant vignettes, both P < 0.001). Discordance between instructions was associated with increased odds of doctors rating the decision as difficult (both ORs 2.0, P ≤ 0.001). CONCLUSION: Contradictions between advance directives and proxy opinions result in a weak preference for abstention from treatment and increase the difficulty of the decision.

Sample size for pre-tests of questionnaires.

PURPOSE: To provide guidance regarding the desirable size of pre-tests of psychometric questionnaires, when the purpose of the pre-test is to detect misunderstandings, ambiguities, or other difficulties participants may encounter with instrument items (called «problems¼). METHODS: We computed (a) the power to detect a problem for various levels of prevalence and various sample sizes, (b) the required sample size to detect problems for various levels of prevalence, and (c) upper confidence limits for problem prevalence in situations where no problems were detected. RESULTS: As expected, power increased with problem prevalence and with sample size. If problem prevalence was 0.05, a sample of 10 participants had only a power of 40 % to detect the problem, and a sample of 20 achieved a power of 64 %. To achieve a power of 80 %, 32 participants were necessary if the prevalence of the problem was 0.05, 16 participants if prevalence was 0.10, and 8 if prevalence was 0.20. If no problems were observed in a given sample, the upper limit of a two-sided 90 % confidence interval reached 0.26 for a sample size of 10, 0.14 for a sample size of 20, and 0.10 for a sample of 30 participants. CONCLUSIONS: Small samples (5-15 participants) that are common in pre-tests of questionaires may fail to uncover even common problems. A default sample size of 30 participants is recommended.