Conducting a bayesian multi-armed trial with response adaptive randomization for comparative effectiveness of medications for CSPN.

Background: Response adaptive randomization is popular in adaptive trial designs, but the literature detailing its execution is lacking. These designs are desirable for patients/stakeholders, particularly in comparative effectiveness research, due to the potential benefits including improving participant buy-in by providing more participants with better treatment during the trial. Frequentist approaches have often been used, but adaptive designs naturally fit the Bayesian methodology; it was developed to deal with data as they come in by updating prior information. Methods: PAIN-CONTRoLS was a comparative-effectiveness trial utilizing Bayesian response adaptive randomization to four drugs, nortriptyline, duloxetine, pregabalin, or mexiline, for cryptogenic sensory polyneuropathy (CSPN) patients. The aim was to determine which treatment was most tolerable and effective in reducing pain. Quit and efficacy rates were combined into a utility function to develop a single outcome, which with treatment sample size, drove the adaptive randomization. Prespecified interim analyses allowed the study to stop for early success or update the randomization probabilities to the better-performing treatments. Results: Seven adaptations to the randomization occurred before the trial ended due to reaching the maximum sample size, with more participants receiving nortriptyline and duloxetine. At the end of the follow-up, nortriptyline and duloxetine had lower probabilities of participants that had stopped taking the study medication and higher probabilities were efficacious. Mexiletine had the highest quit rate, but had an efficacy rate higher than pregabalin. Conclusions: Response adaptive randomization has become a popular trial tool, especially for those utilizing Bayesian methods for analyses. By illustrating the execution of a Bayesian adaptive design, using the PAIN-CONTRoLS trial data, this paper continues the work to provide literature for conducting Bayesian response adaptive randomized trials.

DHA, nutrient intake, and maternal characteristics as predictors of pregnancy outcomes in a randomised clinical trial of DHA supplementation.

PURPOSE: To investigate the relationships among docosahexaenoic acid (DHA) intake, nutrient intake, and maternal characteristics on pregnancy outcomes in a phase III randomised clinical trial designed to determine the effect of a DHA dose of 1000 mg/day compared to 200 mg/day on early preterm birth (<34 weeks gestation). METHODS: A secondary aim of the phase III randomised trial was to explore the relationships among pregnancy outcomes (maternal red blood cell phospholipid (RBC-PL) DHA at delivery, preterm birth, gestational age at delivery, labor type, birth anthropometric measures, low birth weight, gestational diabetes, pre-eclampsia, and admission to a neonatal intensive care unit) in participants (n = 1100). We used Bayesian multiple imputation and linear and logistic regression models to conduct an analysis of five general classes of predictor variables collected during the trial: a) DHA intake, b) nutrient intake from food and supplements, c) environmental exposure to tobacco and alcohol, d) maternal demographics, and e) maternal medical history. RESULTS: DHA supplementation lowered the risk of preterm birth and NICU admission, and increased gestation and birth weight as observed in the primary analysis. Higher maternal RBC-PL-DHA at delivery was associated with DHA supplementation and formal education of a bachelor's degree or higher. DHA supplementation and maternal age were associated with a higher risk of gestational diabetes. Total vitamin A intake was associated with longer gestation, while fructose and intake of the long chain omega-6 fatty acid, arachidonic acid, were associated with shorter gestation. Risk of preterm birth was associated with a history of low birth weight, preterm birth, pre-eclampsia, and NICU admission. CONCLUSION: Bayesian models provide a comprehensive approach to relationships among DHA intake, nutrient intake, maternal characteristics, and pregnancy outcomes. We observed previously unreported relationships between gestation duration and fructose, vitamin A, and arachidonic acid that could be the basis for future research. TRIAL REGISTRATION NUMBER AND DATE: ClinicalTrials.gov (NCT02626299); December 10, 2015.

Using a Bayesian model of the joint distribution of pain and time on medication to decide on pain medication for neuropathy.

The PAIN-CONTRoLS trial compared four medications in treating Cryptogenic sensory polyneuropathy. The primary outcome was a utility function that combined two outcomes, patients' pain score reduction and patients' quit rate. However, additional analysis of the individual outcomes could also be leveraged to inform selecting an optimal medication for future patients. We demonstrate how joint modeling of longitudinal and time-to-event data from PAIN-CONTRoLS can be used to predict the effects of medication in a patient-specific manner and helps to make patient-focused decisions. A joint model was used to evaluate the two outcomes while accounting for the association between the longitudinal process and the time-to-event processes. Results suggested no significant association between the patients' pain scores and time to the medication quit in the PAIN-CONTRoLS study, but the joint model still provided robust estimates and a better model fit. Using the model estimates, given patients' baseline characteristics, a drug profile on both the pain reduction and medication time could be obtained for each drug, providing information on how likely they would quit and how much pain reduction they should expect. Our analysis suggested that drugs viable for one patient may not be beneficial for others.

Early Treatment Response in Black Smokers Undergoing Pharmacotherapy for Smoking Cessation: A Secondary Analysis of a Randomized Clinical Trial.

This secondary analysis of a randomized clinical trial investigates the association of early treatment response with smoking cessation among Black smokers.

Micronutrient Gaps and Supplement Use in a Diverse Cohort of Pregnant Women.

BACKGROUND: Micronutrition in pregnancy is critical to impact not only fetal growth and development but also long-term physical and psychiatric health outcomes. OBJECTIVE: Estimate micronutrient intake from food and dietary supplements in a diverse cohort of pregnant women and compare intake to the Dietary Reference Intakes (DRIs). DESIGN: Secondary analysis of women enrolled in a multi-site clinical trial of docosahexaenoic acid (DHA) supplementation who provided their dietary intake using the diet history questionnaire-II (n = 843) or multiple 24 h recalls (n = 178) at baseline and their intake of nutritional supplements at baseline through 30 days postpartum. PARTICIPANTS/SETTING: 1021 participants from the parent trial who had reliable data for dietary intake, supplement intake, or both. MAIN OUTCOME MEASURES: Micronutrient intake from dietary and supplement sources and percentage of intakes meeting the DRIs for pregnancy. STATISTICAL ANALYSES PERFORMED: Percent of participants whose intake was below the estimated average requirement (EAR) or adequate intake (AI) and above the tolerable upper limit (UL). RESULTS: Dietary intakes of choline, folate, iron, vitamin D, zinc, vitamin E, magnesium, and potassium, were below the AI or EAR for 30-91% of the participants; thiamin and vitamin B6 were also below the AI or EAR for non-Hispanic/Latina women. Supplement intake improved the intake for most; however, 80% of the group remained below the AI for choline and 52.5% for potassium while 30% remained below the EAR for magnesium. Folate and iron intakes were above the UL for 80% and 19%, respectively. CONCLUSIONS: Dietary supplements, despite their variability, allowed the majority of this cohort of pregnant women to achieve adequate intakes for most micronutrients. Choline, magnesium, and potassium were exceptions. Of interest, folate intake was above the tolerable UL for the majority and iron for 16.8% of the participants. Clinicians have the opportunity to address the most common nutrient deficits and limits with advice on food sources that provide choline, magnesium, and potassium and to ensure folate is not overabundant. More research is needed to determine if these findings are similar in a cross-sectional population.

The value of a two-armed Bayesian response adaptive randomization trial.

We investigate the value of a two-armed Bayesian response adaptive randomization (RAR) design to investigate early preterm birth rates of high versus low dose of docosahexaenoic acid during pregnancy. Unexpectedly, the COVID-19 pandemic forced recruitment to pause at 1100 participants rather than the planned 1355. The difference in power between number of participants at the pause and planned was 87% and 90% respectively. We decided to stop the study. This paper describes how the RAR was used to execute the study. The value of RAR in two-armed studies is quite high and their use in the future is promising.

Prenatal docosahexaenoic acid effect on maternal-infant DHA-equilibrium and fetal neurodevelopment: a randomized clinical trial.

INTRODUCTION: Maternal-infant equilibrium occurs when cord blood docosahexaenoic acid (DHA) is less than or equal to maternal DHA at delivery. Equilibrium may be an indicator of sufficient DHA for optimal fetal and infant neurodevelopment. The purpose of this study was to test the effect of maternal DHA supplementation on equilibrium status and fetal neurodevelopment. METHODS: Women enrolled between 12 and 20 weeks gestation and were randomized to 200 or 800 mg DHA/day until delivery. Maternal red blood cell (RBC) phospholipids were measured at enrollment, 32 weeks, delivery, and in cord blood at delivery. Fetal neurodevelopment was measured at 32 and 36 weeks gestation. Intent-to-treat analyses were conducted to test differences in equilibrium status by group. Fetal outcomes were assessed by equilibrium status and group. RESULTS: Three hundred women enrolled and 262 maternal-infant dyads provided blood samples at delivery. No maternal-infant dyads with maternal RBC-DHA ≤ 6.96% at delivery achieved equilibrium. The incidence of equilibrium was significantly higher in the 800 mg group. There was no effect of maternal group or equilibrium status on fetal neurodevelopment. CONCLUSION: The significance of maternal-infant DHA equilibrium remains unknown. Ongoing research will test the effect of treatment group, equilibrium, and nutrient status on infant behavior and brain function. IMPACT: Pregnant women who received a higher dose of docosahexaenoic acid (DHA) were more likely to achieve maternal-infant DHA equilibrium at delivery. Equilibrium status had no effect on fetal neurodevelopment in this sample. While DHA is crucial for early life neurodevelopment, the significance of achieving maternal-infant equilibrium above the lower threshold is uncertain. There is a lower threshold of maternal DHA status where maternal-infant DHA equilibrium never occurs. The lack of equilibrium associated with low maternal DHA status may indicate insufficient maternal status for optimal placental transfer.

Higher-Dose DHA Supplementation Modulates Immune Responses in Pregnancy and Is Associated with Decreased Preterm Birth.

Pregnancy and parturition involve extensive changes in the maternal immune system. In our randomized, multi-site, double-blind superiority trial using a Bayesian adaptive design, we demonstrated that 1000 mg/day of docosahexaenoic acid (DHA) was superior to 200 mg/day in preventing both early preterm birth (less than 34 weeks' gestation) and preterm birth (less than 37 weeks' gestation). The goal of this secondary study is to compare the effects of 1000 mg/day versus 200 mg/day on maternal inflammation, a possible mechanism by which DHA may prevent preterm birth. Maternal blood samples were collected at enrollment (12-20 weeks' gestation) and at delivery. Red blood cell DHA levels were measured by gas chromatography, and plasma concentrations of sRAGE, IL-6, IL-1ß, TNFα, and INFγ were measured by ELISA. Data were analyzed for associations with the DHA dose, gestational age at birth, and preterm birth (<37 weeks). Higher baseline and lower delivery levels of maternal sRAGE were associated with a greater probability of longer gestation and delivery at term gestation. Higher-dose DHA supplementation increased the probability of a smaller decrease in delivery sRAGE levels. Higher IL-6 concentrations at delivery were associated with the probability of delivering after 37 weeks, and higher-dose DHA supplementation increased the probability of greater increases in IL-6 concentrations between enrollment and delivery. These data provide a proposed mechanistic explanation of how a higher dose of DHA during pregnancy provides immunomodulatory regulation in the initiation of parturition by influencing sRAGE and IL-6 levels, which may explain its ability to reduce the risk of preterm birth.

Higher dose docosahexaenoic acid supplementation during pregnancy and early preterm birth: A randomised, double-blind, adaptive-design superiority trial.

BACKGROUND: Several meta analyses have concluded n-3 fatty acids, including docosahexaenoic acid (DHA), reduce early preterm birth (EPB, < 34 weeks), however, the amount of DHA required is unclear. We hypothesized that 1000 mg DHA per day would be superior to 200 mg, the amount in most prenatal supplements. METHODS: This randomised, multicentre, double-blind, adaptive-design, superiority trial was conducted in three USA medical centres. Women with singleton pregnancies and 12 to 20 weeks gestation were eligible. randomization was generated in SAS® by site in blocks of 4. The planned adaptive design periodically generated allocation ratios favoring the better performing dose. Managing study personnel were blind to treatment until 30 days after the last birth. The primary outcome was EPB by dose and by enrolment DHA status (low/high). Bayesian posterior probabilities (pp) were determined for planned efficacy and safety outcomes using intention-to-treat. The study is registered with ClinicalTrials.gov (NCT02626299) and closed to enrolment. FINDINGS: Eleven hundred participants (1000 mg, n = 576; 200 mg, n = 524) were enrolled between June 8, 2016 and March 13, 2020 with the last birth September 5, 2020. 1032 (n = 540 and n = 492) were included in the primary analyses. The higher dose had a lower EPB rate [1.7% (9/540) vs 2.4% (12/492), pp=0.81] especially if participants had low DHA status at enrolment [2.0% (5/249) vs 4.1%, (9/219), pp=0.93]. Participants with high enrolment DHA status did not realize a dose effect [1000 mg: 1.4% (4/289); 200 mg: 1.1% (3/271), pp = 0.57]. The higher dose was associated with fewer serious adverse events (maternal: chorioamnionitis, premature rupture of membranes and pyelonephritis; neonatal: feeding, genitourinary and neurologic problems, all pp>0.90). INTERPRETATION: Clinicians could consider prescribing 1000 mg DHA daily during pregnancy to reduce EPB in women with low DHA status if they are able to screen for DHA. FUNDING: The National Institutes of Health Child Health and Human Development (NICHD) funded the study. Life's DHA™-S oil, DSM Nutritional Products LLC, Switzerland provided all capsules.

Effect of Behavioral Therapy With In-Clinic or Telephone Group Visits vs In-Clinic Individual Visits on Weight Loss Among Patients With Obesity in Rural Clinical Practice: A Randomized Clinical Trial.

Importance: Rural populations have a higher prevalence of obesity and poor access to weight loss programs. Effective models for treating obesity in rural clinical practice are needed. Objective: To compare the Medicare Intensive Behavioral Therapy for Obesity fee-for-service model with 2 alternatives: in-clinic group visits based on a patient-centered medical home model and telephone-based group visits based on a disease management model. Design, Setting, and Participants: Cluster randomized trial conducted in 36 primary care practices in the rural Midwestern US. Inclusion criteria included age 20 to 75 years and body mass index of 30 to 45. Participants were enrolled from February 2016 to October 2017. Final follow-up occurred in December 2019. Interventions: All participants received a lifestyle intervention focused on diet, physical activity, and behavior change strategies. In the fee-for-service intervention (n = 473), practice-employed clinicians provided 15-minute in-clinic individual visits at a frequency similar to that reimbursed by Medicare (weekly for 1 month, biweekly for 5 months, and monthly thereafter). In the in-clinic group intervention (n = 468), practice-employed clinicians delivered group visits that were weekly for 3 months, biweekly for 3 months, and monthly thereafter. In the telephone group intervention (n = 466), patients received the same intervention as the in-clinic group intervention, but sessions were delivered remotely via conference calls by centralized staff. Main Outcomes and Measures: The primary outcome was weight change at 24 months. A minimum clinically important difference was defined as 2.75 kg. Results: Among 1407 participants (mean age, 54.7 [SD, 11.8] years; baseline body mass index, 36.7 [SD, 4.0]; 1081 [77%] women), 1220 (87%) completed the trial. Mean weight loss at 24 months was -4.4 kg (95% CI, -5.5 to -3.4 kg) in the in-clinic group intervention, -3.9 kg (95% CI, -5.0 to -2.9 kg) in the telephone group intervention, and -2.6 kg (95% CI, -3.6 to -1.5 kg) in the in-clinic individual intervention. Compared with the in-clinic individual intervention, the mean difference in weight change was -1.9 kg (97.5% CI, -3.5 to -0.2 kg; P = .01) for the in-clinic group intervention and -1.4 kg (97.5% CI, -3.0 to 0.3 kg; P = .06) for the telephone group intervention. Conclusions and Relevance: Among patients with obesity in rural primary care clinics, in-clinic group visits but not telephone-based group visits, compared with in-clinic individual visits, resulted in statistically significantly greater weight loss at 24 months. However, the differences were small in magnitude and of uncertain clinical importance. Trial Registration: ClinicalTrials.gov Identifier: NCT02456636.

Factors Associated With Cannabis Use Among African American Nondaily Smokers.

OBJECTIVES: Cannabis and tobacco dual use is a growing concern in the United States, especially among African Americans (AAs). Dual use increases nicotine dependence and poses negative health effects. Despite decreasing numbers of people who smoke daily, nondaily smokers (NDS) are increasing. Polytobacco use, including blunt use, is higher in AA NDS than AAs who smoke daily. This study examined factors associated with cannabis use among AA NDS. METHODS: Adult AA NDS participated in a randomized controlled trial (n = 278) for smoking cessation. A subset of this sample (n = 262; mean age 48.2 years; 50% male) was analyzed to identify correlates of cannabis use. Logistic regression assessed the associations of demographic, smoking-related, and psychosocial variables with cannabis use. RESULTS: Participants smoked cigarettes on an average of 18 days of the last 30 and used 4.5 cigarettes on smoking days. Of the participants analyzed, 38% used cannabis, including blunts (ie, cigars hollowed out filled with cannabis) at baseline. Cannabis use was associated with polytobacco product use not including blunts (odds ratio [OR] 2.11, 95% confidence interval [CI] 1.18-3.77, P = 0.012), depressive symptoms (OR 1.22, 95% CI 1.05-1.42, P = 0.011), and younger age (OR 0.97, 95% CI 0.94-0.99, P = 0.004). CONCLUSIONS: Rates of cannabis and tobacco dual use in our sample exceed national rates. Dual use poses harmful health effects that exceed the risk of either substance alone. Findings will inform future work in tailoring treatments to vulnerable groups of people who use both tobacco and cannabis.

Verbal Communication During Airway Management and Emergent Endotracheal Intubation: Observations of Team Behavior Among Multi-institutional Pediatric Intensive Care Unit In Situ Simulations.

OBJECTIVE: To assess health-care teams' verbal communication, an observable teamwork behavior, during simulations involving pediatric emergency airway management and intubation. METHODS: We conducted video-recorded, risk-informed in situ simulations at 5 hospitals with pediatric intensive care units in the Chicago, Illinois, area. Clinicians participated in their clinical roles (eg, attending physician, bedside nurse) and had access to hospital operational systems (eg, electronic health record, medical imaging, laboratory services). Video-recordings were transcribed; 3 pediatric critical care physicians analyzed the transcripts to assess preintubation communication: (a) the declaration of an airway emergency, (b) intubation medication request(s), and (c) preintubation medication administration. RESULTS: Ten pediatric intensive care unit simulations were analyzed. Statements to notify the care team of an airway emergency varied widely. In 3 simulations, a dosage for every medication was verbalized in the physician's initial medication request; however, in 4 simulations, a nurse was the first to verbalize the medication dosage(s) before administration. In 6 of the simulations where preintubation medications were administered, multiple requests for medications were verbalized. A clinician verbally confirmed that each medication was administered in only 2 of the simulations. CONCLUSIONS: No uniform statement was identified to declare an airway emergency among the care teams. Preintubation medication dosages were not consistently included in intubation medication orders, and frequently, there were multiple requests to obtain medications. Using standardized language to declare an airway emergency and verbally communicating medication requests and dosages and confirming administration may improve the quality of care in this critical event.

Application of risk factors for venous thromboembolism in patients with multiple myeloma starting chemotherapy, a real-world evaluation.

INTRODUCTION: Within the first year of diagnosis, up to 1 in 3 multiple myeloma (MM) patients will experience a venous thromboembolism (VTE). The International Myeloma Working Group (IMWG) has thromboprophylaxis guidelines that stratify patients into low or high risk for thrombosis and subsequently recommend thromboprophylaxis, but it is unknown if these recommendations are being followed or if they are effective. The purpose of this study was to assess efficacy of the IMWG guidelines and investigate other potential VTE risk factors. METHODS: Study participants were treated at the University of Kansas Medical Center between 2007 and 2013, and charts were reviewed to extract data. Cases (MM and VTE) were matched to controls (MM and no VTE) at approximately 1:3 ratio based on gender, age (±5 years), and time of MM diagnosis (±5 years). RESULTS: A total of 80 cases and 211 controls were matched. Most patients (82%) were considered high risk for experiencing a VTE at the time of their MM diagnosis and 18% were considered low risk. Neither risk category (P = 0.16) nor thromboprophylaxis at baseline (P = 0.37) predicted VTE, though cases were more likely than controls to have an increased risk of thrombosis at the time of clot compared to their baseline risk (P = 0.09). CONCLUSION: Our results suggest that IMWG guidelines are not being consistently followed and therefore could not be validated. Additional risk factors were not identified, but risk for VTE may change over time suggesting patients may require ongoing assessment of VTE risk and thromboprophylaxis throughout the disease course.

Three-Hour Bundle Compliance and Outcomes in Patients With Undiagnosed Severe Sepsis.

BACKGROUND: The aim of this study was to compare completion of the Surviving Sepsis Campaign 3-hour treatment recommendations and patient-centered outcomes between patients with severe sepsis who received a sepsis-specific diagnosis code with those who did not. METHODS: This was a retrospective cohort analysis of adult patients admitted through an academic medical center ED who received an antibiotic and met criteria for severe sepsis. We measured and compared the Surviving Sepsis Campaign 3-hour treatment recommendations along with patient-centered outcomes in patients who were diagnosed with severe sepsis and those who were not. RESULTS: A total of 5,631 patients were identified (60.6 ± 17.2 years of age; 48.9% women). Less than half (32.8%) received an International Classification of Diseases, ninth revision, diagnosis code of 995.92. Completion of all four bundle components in < 3 hours was low for all patients (8.72%). Therapeutic components (a broad-spectrum antibiotic and IV fluids) were completed more often (31.3%). Those with a diagnosis code received all four bundle components (10.2% vs 7.9%; P < .005), as well as therapeutic components at a higher frequency (36.0% vs 29.0%; P < .001). Patients with a diagnosis code had higher mortality (6.3% vs 2.3%), more frequent ICU admissions (44.7% vs 22.5%), and longer hospitalizations (9.2 ± 6.9 days vs 6.9 ± 6.7 days) than did patients with severe sepsis with no diagnosis code (all P < .001). CONCLUSIONS: Severe sepsis continues to be an underdiagnosed and undertreated condition. Patients who were diagnosed had higher treatment rates yet experienced worse outcomes. Continued investigation is needed to identify factors contributing to diagnosis, treatment, and outcomes in patients with severe sepsis.

A Bayesian comparative effectiveness trial in action: developing a platform for multisite study adaptive randomization.

BACKGROUND: In the last few decades, the number of trials using Bayesian methods has grown rapidly. Publications prior to 1990 included only three clinical trials that used Bayesian methods, but that number quickly jumped to 19 in the 1990s and to 99 from 2000 to 2012. While this literature provides many examples of Bayesian Adaptive Designs (BAD), none of the papers that are available walks the reader through the detailed process of conducting a BAD. This paper fills that gap by describing the BAD process used for one comparative effectiveness trial (Patient Assisted Intervention for Neuropathy: Comparison of Treatment in Real Life Situations) that can be generalized for use by others. A BAD was chosen with efficiency in mind. Response-adaptive randomization allows the potential for substantially smaller sample sizes, and can provide faster conclusions about which treatment or treatments are most effective. An Internet-based electronic data capture tool, which features a randomization module, facilitated data capture across study sites and an in-house computation software program was developed to implement the response-adaptive randomization. RESULTS: A process for adapting randomization with minimal interruption to study sites was developed. A new randomization table can be generated quickly and can be seamlessly integrated in the data capture tool with minimal interruption to study sites. CONCLUSION: This manuscript is the first to detail the technical process used to evaluate a multisite comparative effectiveness trial using adaptive randomization. An important opportunity for the application of Bayesian trials is in comparative effectiveness trials. The specific case study presented in this paper can be used as a model for conducting future clinical trials using a combination of statistical software and a web-based application. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02260388 , registered on 6 October 2014.

Failure mode and effects analysis: a comparison of two common risk prioritisation methods.

BACKGROUND: Failure mode and effects analysis (FMEA) is a method of risk assessment increasingly used in healthcare over the past decade. The traditional method, however, can require substantial time and training resources. The goal of this study is to compare a simplified scoring method with the traditional scoring method to determine the degree of congruence in identifying high-risk failures. METHODS: An FMEA of the operating room (OR) to intensive care unit (ICU) handoff was conducted. Failures were scored and ranked using both the traditional risk priority number (RPN) and criticality-based method, and a simplified method, which designates failures as 'high', 'medium' or 'low' risk. The degree of congruence was determined by first identifying those failures determined to be critical by the traditional method (RPN≥300), and then calculating the per cent congruence with those failures designated critical by the simplified methods (high risk). RESULTS: In total, 79 process failures among 37 individual steps in the OR to ICU handoff process were identified. The traditional method yielded Criticality Indices (CIs) ranging from 18 to 72 and RPNs ranging from 80 to 504. The simplified method ranked 11 failures as 'low risk', 30 as medium risk and 22 as high risk. The traditional method yielded 24 failures with an RPN ≥300, of which 22 were identified as high risk by the simplified method (92% agreement). The top 20% of CI (≥60) included 12 failures, of which six were designated as high risk by the simplified method (50% agreement). CONCLUSIONS: These results suggest that the simplified method of scoring and ranking failures identified by an FMEA can be a useful tool for healthcare organisations with limited access to FMEA expertise. However, the simplified method does not result in the same degree of discrimination in the ranking of failures offered by the traditional method.

Evaluating Variables as Unbiased Proxies for Other Measures: Assessing the Step Test Exercise Prescription as a Proxy for the Maximal, High-intensity Peak Oxygen Consumption in Older Adults.

To assess validity of a low-intensity measure of fitness (X) in a population of older adults as a proxy measure for the original, high-intensity measure (Y), we used ordinary least square regression with the new, potential proxy measure (X) as the sole explanatory variable for Y. A perfect proxy measure would be unbiased (i.e., result in a regression line with a y-intercept of zero and a slope of one) with no error (variance equal to zero). We evaluated the properties of potential biases of proxy measures. A two degree-of-freedom approach using a contrast matrix in the setting of simple linear ordinary least squares regression was compared to a one degree-of-freedom paired t test alternative approach. We found that substantial improvements in power could be gained through use of the two degree-of-freedom approach in many settings, while scenarios where no linear bias was present there could be modest gains from the paired t test approach. In general, the advantages of the two degree-of-freedom approach outweighed the benefits of the one degree-of-freedom approach. Using the two degree-of-freedom approach, we assessed the data from our motivating example and found that the low-intensity fitness measure was biased, and thus was not a good proxy for the original, high-intensity measure of fitness in older adults.

Medical ICU admissions during weekday rounds are not associated with mortality: a single-center analysis.

This study investigated whether intensive care unit (ICU) admissions to the research team's tertiary care academic hospital during morning rounds was associated with increased mortality. Discharge data were analyzed on 1912 patients admitted to the ICUs between July 2007 and June 2011. Measures included discharge disposition, time of admission to the ICU, source of admission, and expected mortality score. Descriptive statistics were generated to examine the proportion of subjects who died based on admission time to the ICU, and Pearson's χ(2) test was used to test the null hypothesis that mortality rates for admissions during rounds and those at other times of the day would be similar. No difference in mortality was detected between admissions during rounds and all other times, whether analyzed using a bivariate (P = .55) or multivariable (P = .78) analysis. In this study, mortality was associated with severity of illness and not associated with admission during morning rounds.