Exceedance Probabilities of Log-normal Distributions for One Group, Two Groups, and Meta-analysis of Multiple Two-group Studies, With Application to Analyses of Prolonged Times to Tracheal Extubation.

Many randomized trials measure means and standard deviations of anesthesia recovery time (e.g., times to tracheal extubation). We show how to use generalized pivotal methods to compare the probabilities of exceeding a tolerance limit (e.g., > 15 min, prolonged times to tracheal extubation). The topic is important because the economic benefits of faster anesthesia emergence depend on reducing variability, not means, especially prevention of very long recovery times. Generalized pivotal methods are applied using computer simulation (e.g., using two Excel formulas for one group and three formulas for two group comparisons). The endpoint for each study with two groups is the ratio between groups of the probabilities of times exceeding a threshold or the ratio of the standard deviations. Confidence intervals and variances for the incremental risk ratio of the exceedance probabilities and for ratios of standard deviations are calculated using studies' sample sizes, sample means in the time scale of recovery times, and sample standard deviations in the time scale. Ratios are combined among studies using the DerSimonian-Laird estimate of the heterogeneity variance estimate, with Knapp-Hartung adjustment for the relatively small (N = 15) numbers of studies in the meta-analysis. We show larger absolute variability among studies' results when analyzed based on exceedance probabilities rather than standard deviations. Therefore, if an investigator's primary goal is to quantify reductions in the variability of recovery times (e.g., times until patients are ready for post-anesthesia care unit discharge), we recommend analyzing the standard deviations. When exceedance probabilities themselves are relevant, they can be analyzed from the original studies' summary measures.

Patients in Iowa Counties Lacking Hospitals With Labor and Delivery Services Disproportionately Receive Care at Level III Maternal Care Hospitals When Undergoing Cesarean Delivery: A Retrospective Longitudinal Study.

Introduction Many obstetrical patients from rural areas in the United States lack hospitals that provide labor and delivery care. Our objective was to examine the effects of such patients on caseloads of cesarean deliveries at Iowa hospitals with level III maternal care, as defined by the Iowa Department of Public Health (e.g., with obstetric anesthesiologists). Methods This retrospective longitudinal study included every discharge with cesarean delivery in the state of Iowa from October 2015 through June 2021. There were N=60,534 such deliveries from 76 hospitals, of which three were level III, and the rest were level I or II. Poisson regression models with robust variance estimation and controlling for geography, maternal risk factors, and insurance, were used to evaluate the binary outcome of whether patients received care at the university level III hospital in Eastern Iowa, or not. Similar models were also developed for care at the two private level III hospitals in Central Iowa, or not. Differences in the mean probabilities of receiving care at the level III hospitals were then estimated using logistic regression, with results reported in units of changes in cases per week at the hospitals. Results Statewide, the university level III hospital performed 7.4% of the cesarean deliveries, and the two private level III hospitals performed 23.4%. Patients from counties in which no cesarean deliveries were performed during the quarter of the year when they underwent a cesarean delivery disproportionately received care at level III hospitals versus levels I and II hospitals. Lower 99% confidence limits for incremental risk ratios were 1.46 and 4.20, respectively. Cesarean deliveries among patients residing in counties where no hospital had a labor and delivery ward were distributed unequally between the counties of the hospitals with level III maternal care. There were approximately 1.09 (standard error 0.10) extra cesarean deliveries per week at the university hospital versus 5.81 (standard error 0.11) at the private hospitals. The 1.09 vs 5.81 difference was caused, in part, by the effects of insurance and other hospitals with similar services. Conclusions Patients residing in counties without labor and delivery care disproportionately go to level III hospitals. These results can help anesthesiologists, obstetricians, and analysts at hospitals with large tertiary (level III) programs interpret their annual increases in total obstetric anesthesia activity.

Sex-Specific Differences in Endothelial Function Are Driven by Divergent Mitochondrial Ca2+ Handling.

Background Sex-specific differences in vasodilation are mediated in part by differences in cytosolic Ca2+ handling, but how variations in mitochondrial Ca2+ contributes to this effect remains unknown. Here, we investigated the extent to which mitochondrial Ca2+ entry via the MCU (mitochondrial Ca2+ uniporter) drives sex differences in vasoreactivity in resistance arteries. Methods and Results Enhanced vasodilation of mesenteric resistance arteries to acetylcholine (ACh) was reduced to larger extent in female compared with male mice in 2 genetic models of endothelial MCU ablation. Ex vivo Ca2+ imaging of mesenteric arteries with Fura-2AM confirmed higher cytosolic Ca2+ transients triggered by ACh in arteries from female mice versus male mice. MCU inhibition both strongly reduced cytosolic Ca2+ transients and blocked mitochondrial Ca2+ entry. In cultured human aortic endothelial cells, treatment with physiological concentrations of estradiol enhanced cytosolic Ca2+ transients, Ca2+ buffering capacity, and mitochondrial Ca2+ entry in response to ATP or repeat Ca2+ boluses. Further experiments to establish the mechanisms underlying these effects did not reveal significant differences in the expression of MCU subunits, at either the mRNA or protein level. However, estradiol treatment was associated with an increase in mitochondrial mass, mitochondrial fusion, and the mitochondrial membrane potential and reduced mitochondrial superoxide production. Conclusions Our data confirm that mitochondrial function in endothelial cells differs by sex, with female mice having enhanced Ca2+ uptake capacity, and that these differences are attributable to the presence of more mitochondria and a higher mitochondrial membrane potential in female mice rather than differences in composition of the MCU complex.

Benchmarking Surgeons' Gender and Year of Medical School Graduation Associated With Monthly Operative Workdays for Multispecialty Groups.

Background Female surgeons reportedly receive less surgical block time and fewer procedural referrals than male surgeons. In this study, we compared operative days between female and male surgeons throughout Florida. Our objective was to facilitate benchmarking by multispecialty groups, both the endpoint to use for statistically reliable results and expected differences. Methodology The historical cohort study included all 4,060,070 ambulatory procedural encounters and inpatient elective surgical states performed between January 2017 and December 2019 by 8,472 surgeons at 609 facilities. Surgeons' gender, year of medical school graduation, and surgical specialty were obtained from their National Provider Identifiers. Results Female surgeons operated an average of 1.0 fewer days per month than matched male surgeons (99% confidence interval 0.8 to 1.2 fewer days, P < 0.0001). The mean differences were 0.8 to 1.4 fewer days per month among each of the five quintiles of years of graduation from medical school (all P ≤ 0.0050). Results were comparable when repeated using the number of monthly cases the surgeons performed. Conclusions An average difference of ≤1.4 days per month is a conservative estimate for the current status quo of the workload difference in Florida. Suppose that a group's female surgeons average more than two fewer operative days per month than the group's male surgeons of the same specialty. Such a large average difference would call for investigation of what might reflect systematic bias. While such a difference may reflect good flexibility of the organization, it may show a lack of responsiveness (e.g., fewer referrals of procedural patients to female surgeons or bias when apportioning allocated operating room time).

Decreased Expression of Glial-Derived Neurotrophic Factor Receptors in Glaucomatous Human Retinas.

PURPOSE: The purpose of this study was to examine the expression of glial-derived neurotrophic factor (GDNF), the GDNF receptors GFRα1 and GFRα2, ciliary neurotrophic factor (CNTF), and the CNTF receptor CNTFRα in normal and glaucomatous human tissue. METHODS: Human retinas were collected from 8 donors that had been clinically diagnosed and treated for glaucoma, and also from 9 healthy control donors. Immunohistochemical analysis for each trophic factor and receptor was performed. The percent of each retinal section labeled with each antibody was quantified for the total retinal thickness, and separately for the retinal ganglion cell (RGC) complex + retinal nerve fiber layer (RNFL). The expression of each protein was correlated with measures of the subject's ocular histories. RESULTS: The percentage area immunopositive for GFRα2 was significantly decreased in the total retinal thickness containing all retinal layers and in the combined RGC complex + RNFL in glaucomatous eyes in both the peripapillary region and more peripheral retinal locations. We also observed a decrease in GFRα1 expression in the peripapillary RGC Complex + RNFL in glaucoma patients compared to healthy control patients. We also observed a relationship between GDNF and its receptors with several outcomes obtained from the medical record. No differences in CNTF or CNTFR labeling were observed. CONCLUSION: Decreases in GDNF receptor expression in glaucomatous tissue may limit the potential for neuroprotective therapy by supplementation with GDNF.

Circumferential trabecular meshwork cell density in the human eye.

The cells residing in the trabecular meshwork (TM) fulfill important roles in the maintenance of the tissue and the regulation of intraocular pressure (IOP). Here we examine (i) TM cell distribution along the circumference of the human eye, (ii) differences in TM cell density between regions of high and low outflow, and (iii) whether TM cell distribution in eyes from donors with primary open angle glaucoma (POAG) differs from that of normal eyes. Toward this end, the TM cell density from 12 radial segments around the circumference of the TM of human donor eyes (n = 6) with and without POAG was determined using histochemical methods. Areas of high, median, and low outflow were mapped in a different set of human donor eyes that were perfused in organ culture, and TM cell densities in these areas were determined in normal (n = 11) and POAG eyes (n = 6). Our analysis of 1380 tissue sections taken from the first set of six eyes shows that the average TM cell density of these six eyes ranges from 15.5 to 23.7 cells/100 µm and is negatively correlated to the maximum IOP recorded for each donor eye (R2 = 0.91). Considerable differences in TM cell density exist among sections taken from the same segment of an individual eye (average standard deviation = 2.35 cells/100 µm). Less variability is observed among the segment averages across the eye's circumference (average standard deviation = 1.03 cells/100 µm). Variations in cell density are similar between normal and POAG eyes and are not correlated with the anatomic position of examined segments (p = 0.745). The analysis of the second set of eyes shows that TM regions of high outflow display a TM cell density similar to regions of median or low outflow in both normal and POAG eyes. Together these findings demonstrate that (i) statistically significant differences in TM cell density exist along the circumference of each eye (ii) TM cellularity is not correlated with segmental flow and (iii) eyes with POAG, while displaying reduced TM cellularity, do not exhibit higher TM cell variability than normal eyes. Finally, statistical analysis of sections and segments indicates that measurements from 12 sections taken from 2 segments provide a reliable and cost-effective estimate of a human eye's TM cell density.

Temporal Relationship Between Visual Field, Retinal and Microvascular Pathology Following 125I-Plaque Brachytherapy for Uveal Melanoma.

Purpose: To define the temporal relationship of vascular versus neuronal abnormalities in radiation retinopathy. Methods: Twenty-five patients with uveal melanoma treated with brachytherapy and sixteen controls were tested. Functional outcome measures included visual acuity and threshold perimetry (HVF 10-2), while structural outcomes included retinal thickness by OCT and vascular measures by OCT angiography and digital fundus photography. The degree of structural abnormality was determined by intereye asymmetry compared with normal subject asymmetry. Diagnostic sensitivity and specificity of each measure were determined using receiver operating characteristic curves. The relationships between the outcome measures were quantified by Spearman correlation. The effect of time from brachytherapy on visual function, retinal layer thickness, and capillary density was also determined. Results: Within the first 2 years of brachytherapy, outcome measures revealed visual field loss and microvascular abnormalities in 38% and 31% of subjects, respectively. After 2 years, they became more prevalent, increasing to 67% and 67%, respectively, as did retinal thinning (50%). Visual field loss, loss of capillary density, and inner retinal thickness were highly correlated with one another. Diagnostic sensitivity and specificity were highest for abnormalities in digital fundus photography, visual field loss within the central 10°, and decrease in vessel density. Conclusions: Using quantitative approaches, radiation microvasculopathy and visual field defects were detected earlier than loss of inner retinal structure after brachytherapy. Strong correlations eventually developed between vascular pathology, change in retinal thickness, neuronal dysfunction, and radiation dose. Radiation-induced ischemia seems to be a primary early manifestation of radiation retinopathy preceding visual loss.

High Correlation between Glaucoma Treatment with Topical Prostaglandin Analogs and BDNF Immunoreactivity in Human Retina.

PURPOSE: To examine the expression of brain-derived neurotrophic factor (BDNF) and its high-affinity receptor, tropomyosin-related kinase receptor-B (TrkB), in normal and glaucomatous human retinas. METHODS: Human retinas were collected from 8 donors who had been clinically diagnosed and treated for glaucoma, and from 9 control donors. Immunohistochemical analysis for BDNF and TrkB was performed. The percent of each retina expressing BDNF and TrkB was quantified for the total retinal thickness, and separately for the retinal ganglion cell (RGC) complex + retinal nerve fiber layer (RNFL). The expression of each protein was correlated with clinical outcomes obtained from the subject's ocular histories. RESULTS: There was no significant difference in BDNF or TrkB expression when comparing glaucomatous and control retinas. Correlation analysis revealed a significant relationship between BDNF expression and the use of prostaglandin analogs. TrkB expression was highly correlated with the last-measured intraocular pressure (IOP), the use of carbonic anhydrase inhibitors, the use of beta blockers, and the total number of drugs used for the treatment of glaucoma. CONCLUSION: Topical drugs used to treat glaucoma were associated with an increase in retinal BDNF and TrkB expression in human retina, independent of IOP, which may represent molecular evidence of neuroprotective pathway activation.

Association of Optical Coherence Tomography With Longitudinal Neurodegeneration in Veterans With Chronic Mild Traumatic Brain Injury.

Importance: Mild traumatic brain injury (TBI) may predispose individuals to progressive neurodegeneration. Objective: To identify evidence of neurodegeneration through longitudinal evaluation of changes in retinal layer thickness using optical coherence tomography in veterans with a history of mild TBI. Design, Setting, and Participants: This longitudinal cohort study evaluated veterans who were receiving services at the Minneapolis Veterans Affairs Health Care System. Symptomatic or mild TBI was diagnosed according to the Mayo TBI Severity Classification System. Participants in the age-matched control group had no history of TBI. Participants with any history or evidence of retinal or optic nerve disease that could affect retinal thickness were excluded. Data analysis was performed from July 2019 to February 2020. Exposures: The presence and severity of mild TBI were determined through consensus review of self-report responses during the Minnesota Blast Exposure Screening Tool semistructured interview. Main Outcomes and Measures: Change over time of retinal nerve fiber layer (RNFL) thickness. Results: A total of 139 veterans (117 men [84%]; mean [SD] age, 49.9 [11.1] years) were included in the study, 69 in the TBI group and 70 in the control group. Veterans with mild TBI showed significantly greater RNFL thinning compared with controls (mean [SE] RNFL slope, -1.47 [0.24] µm/y vs -0.31 [0.32] µm/y; F1,122 = 8.42; P = .004; Cohen d = 0.52). Functionally, veterans with mild TBI showed greater declines in visual field mean deviation (mean [SE] slope, -0.09 [0.14] dB/y vs 0.46 [0.23] dB/y; F1,122 = 4.08; P = .046; Cohen d = 0.36) and pattern standard deviation (mean [SE] slope, 0.09 [0.06] dB/y vs -0.10 [0.07] dB/y; F1,122 = 4.78; P = .03; Cohen d = 0.39) and high spatial frequency (12 cycles/degree) contrast sensitivity compared with controls. Cognitively, there was a significantly greater decrease in the number of errors over time during the Groton Maze Learning Test (GMLT) in controls compared with veterans with mild TBI (mean [SE] slope, -9.30 [1.48] errors/y vs -5.23 [1.24] errors/y; F1,127 = 4.43; P = .04; Cohen d = 0.37). RNFL tissue loss was significantly correlated with both worsening performance on the GMLT over time (Spearman ρ = -0.20; P = .03) and mild TBI severity (Spearman ρ = -0.25; P = .006). The more severe the mild TBI (larger Minnesota Blast Exposure Screening Tool severity score), the faster the reduction in RNFL thickness (ie, the more negative the slope) across time. Conclusions and Relevance: This cohort study found longitudinal evidence for significant, progressive neural degeneration over time in veterans with mild TBI, as indicated by greater RNFL tissue loss in patients with mild TBI vs controls, as well as measures of function. These results suggest that these longitudinal measures may be useful biomarkers of neurodegeneration. Changes in this biomarker may provide early detection of subsequent cognitive and functional deficits that may impact veterans' independence and need for care.

Sample times for surveillance of S. aureus transmission to monitor effectiveness and provide feedback on intraoperative infection control.

BACKGROUND: Reductions in perioperative surgical site infections are obtained by a multifaceted approach including patient decolonization, vascular care, hand hygiene, and environmental cleaning. Associated surveillance of S. aureus transmission quantifies the effectiveness of these basic measures to prevent transmission of pathogenic bacteria and viruses to patients and clinicians, including Coronavirus Disease 2019 (COVID-19). To measure transmission, the observational units are pairs of successive surgical cases in the same operating room on the same day. In this prospective cohort study, we measured sampling times for inexperienced and experienced personnel. METHODS: OR PathTrac kits included 6 samples collected before the start of surgery and 7 after surgery. The time for consent also was recorded. We obtained 1677 measurements of time among 132 cases. RESULTS: Sampling times were not significantly affected by technician's experience, type of anesthetic, or patient's American Society of Anesthesiologists' Physical Status. Sampling times before the start of surgery averaged less than 5 min (3.39 min [SE 0.23], P < 0.0001). Sampling times after surgery took approximately 5 min (4.39 [SE 0.25], P = 0.015). Total sampling times averaged less than 10 min without consent (7.79 [SE 0.50], P < 0.0001), and approximately 10 min with consent (10.22 [0.56], P = 0.70). CONCLUSIONS: For routine use of monitoring S. aureus transmission, when done by personnel already present in the operating rooms of the cases, the personnel time budget can be 10 min per case.

Association between leniency of anesthesiologists when evaluating certified registered nurse anesthetists and when evaluating didactic lectures.

Daily evaluations of certified registered nurse anesthetists' (CRNAs') work habits by anesthesiologists should be adjusted for rater leniency. The current study tested the hypothesis that there is a pairwise association by rater between leniencies of evaluations of CRNAs' daily work habits and of didactic lectures. The historical cohorts were anesthesiologists' evaluations over 53 months of CRNAs' daily work habits and 65 months of didactic lectures by visiting professors and faculty. The binary endpoints were the Likert scale scores for all 6 and 10 items, respectively, equaling the maximums of 5 for all items, or not. Mixed effects logistic regression estimated the odds of each ratee performing above or below average adjusted for rater leniency. Bivariate errors in variables least squares linear regression estimated the association between the leniency of the anesthesiologists' evaluations of work habits and didactic lectures. There were 29/107 (27%) raters who were more severe in their evaluations of CRNAs' work habits than other anesthesiologists (two-sided P < 0.01); 34/107 (32%) raters were more lenient. When evaluating lectures, 3/81 (4%) raters were more severe and 8/81 (10%) more lenient. Among the 67 anesthesiologists rating both, leniency (or severity) for work habits was not associated with that for lectures (P = 0.90, unitless slope between logits 0.02, 95% confidence interval -0.34 to 0.30). Rater leniency is of large magnitude when making daily clinical evaluations, even when using a valid and psychometrically reliable instrument. Rater leniency was context dependent, not solely a reflection of raters' personality or rating style.

Focus on Data: Statistical Significance, Effect Size and the Accumulation of Evidence Achieved by Combining Study Results Through Meta-analysis.

Purpose: To provide information and perspectives on statistical significance and on meta-analysis, a statistical procedure for combining estimated effects across multiple studies. Methods: Methods are presented for performing a meta-analysis in which results across multiple studies are combined. An example of a meta-analysis of optical coherence tomography thickness of the retina in patients with multiple sclerosis across multiple studies is provided. We show how to combine individual study results and how to weight the results of each study based on its reliability. The method of a meta-analysis is used to derive from all study results a pooled estimate that is closest to the unknown common effect. Results: Differences between the two most common methods for meta-analysis, the fixed-effects approach and the random-effects approach, are reviewed. Meta-analysis is applied to the study of the differences in the thickness of the retinal nerve fiber layers of healthy controls and patients with multiple sclerosis, showing why this is a useful procedure for combining estimated effects across multiple studies to derive the magnitude of retinal thinning caused by multiple sclerosis. Conclusions: This review provides information and perspectives on statistical significance and on meta-analysis, a statistical procedure for combining estimated effects across multiple studies. A discussion is provided to show why statistical significance and low probability values are not all that matter and why investigators should also look at the magnitude of the estimated effects. Combining estimated effects across multiple studies with proper weighting of individual results is the goal of meta-analysis.

Focus on Data: Statistical Design of Experiments and Sample Size Selection Using Power Analysis.

Purpose: To provide information to visual scientists on how to optimally design experiments and how to select an appropriate sample size, which is often referred to as a power analysis. Methods: Statistical guidelines are provided outlining good principles of experimental design, including replication, randomization, blocking or grouping of subjects, multifactorial design, and sequential approach to experimentation. In addition, principles of power analysis for calculating required sample size are outlined for different experimental designs and examples are given for calculating power and factors influencing it. Results: The interaction between power, sample size and standardized effect size are shown. The following results are also provided: sample size increases with power, sample size increases with decreasing detectable difference, sample size increases proportionally to the variance, and two-sided tests, without preference as to whether the mean increases or decreases, require a larger sample size than one-sided tests. Conclusions: This review outlines principles for good experimental design and methods for power analysis for typical sample size calculations that visual scientists encounter when designing experiments of normal and non-Gaussian sample distributions.

Parametric Statistical Inference for Comparing Means and Variances.

Purpose: The purpose of this tutorial is to provide visual scientists with various approaches for comparing two or more groups of data using parametric statistical tests, which require that the distribution of data within each group is normal (Gaussian). Non-parametric tests are used for inference when the sample data are not normally distributed or the sample is too small to assess its true distribution. Methods: Methods are reviewed using retinal thickness, as measured by optical coherence tomography (OCT), as an example for comparing two or more group means. The following parametric statistical approaches are presented for different situations: two-sample t-test, Analysis of Variance (ANOVA), paired t-test, and the analysis of repeated measures data using a linear mixed-effects model approach. Results: Analyzing differences between means using various approaches is demonstrated, and follow-up procedures to analyze pairwise differences between means when there are more than two comparison groups are discussed. The assumption of equal variance between groups and methods to test for equal variances are examined. Examples of repeated measures analysis for right and left eyes on subjects, across spatial segments within the same eye (e.g. quadrants of each retina), and over time are given. Conclusions: This tutorial outlines parametric inference tests for comparing means of two or more groups and discusses how to interpret the output from statistical software packages. Critical assumptions made by the tests and ways of checking these assumptions are discussed. Efficient study designs increase the likelihood of detecting differences between groups if such differences exist. Situations commonly encountered by vision scientists involve repeated measures from the same subject over time, measurements on both right and left eyes from the same subject, and measurements from different locations within the same eye. Repeated measurements are usually correlated, and the statistical analysis needs to account for the correlation. Doing this the right way helps to ensure rigor so that the results can be repeated and validated.

Sample sizes for surveillance of S. aureus transmission to monitor effectiveness and provide feedback on intraoperative infection control including for COVID-19.

Reductions in perioperative surgical site infections are obtained by a multifaceted approach including patient decolonization, hand hygiene, and hub disinfection, and environmental cleaning. Associated surveillance of S. aureus transmission quantifies the effectiveness of the basic measures to prevent the transmission to patients and clinicians of pathogenic bacteria and viruses, including Coronavirus Disease 2019 (COVID-19). To measure transmission, the observational units are pairs of successive surgical cases in the same operating room on the same day. We evaluated appropriate sample sizes and strategies for measuring transmission. There was absence of serial correlation among observed counts of transmitted isolates within each of several periods (all P ≥.18). Similarly, observing transmission within or between cases of a pair did not increase the probability that the next sampled pair of cases also had observed transmission (all P ≥.23). Most pairs of cases had no detected transmitted isolates. Also, although transmission (yes/no) was associated with surgical site infection (P =.004), among cases with transmission, there was no detected dose response between counts of transmitted isolates and probability of infection (P =.25). The first of a fixed series of tests is to use the binomial test to compare the proportion of pairs of cases with S. aureus transmission to an acceptable threshold. An appropriate sample size for this screening is N =25 pairs. If significant, more samples are obtained while additional measures are implemented to reduce transmission and infections. Subsequent sampling is done to evaluate effectiveness. The two independent binomial proportions are compared using Boschloo's exact test. The total sample size for the 1st and 2nd stage is N =100 pairs. Because S. aureus transmission is invisible without testing, when choosing what population(s) to screen for surveillance, another endpoint needs to be used (e.g., infections). Only 10/298 combinations of specialty and operating room were relatively common (≥1.0% of cases) and had expected incidence ≥0.20 infections per 8 hours of sampled cases. The 10 combinations encompassed ≅17% of cases, showing the value of targeting surveillance of transmission to a few combinations of specialties and rooms. In conclusion, we created a sampling protocol and appropriate sample sizes for using S. aureus transmission within and between pairs of successive cases in the same operating room, the purpose being to monitor the quality of prevention of intraoperative spread of pathogenic bacteria and viruses.

Futility of Cluster Designs at Individual Hospitals to Study Surgical Site Infections and Interventions Involving the Installation of Capital Equipment in Operating Rooms.

Anesthesia workspaces are integral components in the chains of many intraoperative bacterial transmission events resulting in surgical site infections (SSI). Matched cohort designs can be used to compare SSI rates among operating rooms (ORs) with or without capital equipment purchases (e.g., new anesthesia machines). Patients receiving care in intervention ORs (i.e., with installed capital equipment) are matched with similar patients receiving care in ORs lacking the intervention. We evaluate statistical power of an alternative design for clinical trials in which, instead, SSI incidences are compared directly among ORs (i.e., the ORs form the clusters) at single hospitals (e.g., the 5 ORs with bactericidal lights vs. the 5 other ORs). Data used for parameter estimates were SSI for 24 categories of procedures among 338 hospitals in the State of California, 2015. Estimated statistical power was ≅8.4% for detecting a reduction in the incidence of SSI from 3.6% to 2.4% over 1 year with 5 intervention ORs and 5 control ORs. For ≅80% statistical power, >20 such hospitals would be needed to complete a study in 1 year. Matched paired cluster designs pair similar ORs (e.g., 2 cardiac ORs, 1 to intervention and 1 to control). With 5 pairs, statistical power would be even less than the estimated 8.4%. Cluster designs (i.e., analyses by OR) are not suitable for comparing SSI among ORs at single hospitals. Even though matched cohort designs are non-randomized and thus have lesser validity, matching patients by their risk factors for SSI is more practical.

Decision models for distinguishing between clinically insignificant and significant tumors in prostate cancer biopsies: an application of Bayes' Theorem to reduce costs and improve outcomes.

Prostate cancer is the second leading cause of death from cancer, behind lung cancer, for men in the U. S, with nearly 30,000 deaths per year. A key problem is the difficulty in distinguishing, after biopsy, between significant cancers that should be treated immediately and clinically insignificant tumors that should be monitored by active surveillance. Prostate cancer has been over-treated; a recent European randomized screening trial shows overtreatment rates of 40%. Overtreatment of insignificant tumors reduces quality of life, while delayed treatment of significant cancers increases the incidence of metastatic disease and death. We develop a decision analysis approach based on simulation and probability modeling. For a given prostate volume and number of biopsy needles, our rule is to treat if total length of cancer in needle cores exceeds c, the cutoff value, with active surveillance otherwise, provided pathology is favorable. We determine the optimal cutoff value, c*. There are two misclassification costs: treating a minimal tumor and not treating a small or medium tumor (large tumors were never misclassified in our simulations). Bayes' Theorem is used to predict the probabilities of minimal, small, medium, and large cancers given the total length of cancer found in biopsy cores. A 20 needle biopsy in conjunction with our new decision analysis approach significantly reduces the expected loss associated with a patient in our target population about to undergo a biopsy. Longer needles reduce expected loss. Increasing the number of biopsy cores from the current norm of 10-12 to about 20, in conjunction with our new decision model, should substantially improve the ability to distinguish minimal from significant prostate cancer by minimizing the expected loss from over-treating minimal tumors and delaying treatment of significant cancers.

Importance of operating room case scheduling on analyses of observed reductions in surgical site infections from the purchase and installation of capital equipment in operating rooms.

BACKGROUND: We review the impact of the consequences of operating room (OR) management decision making on power analyses for observational studies of surgical site infections (SSIs) among patients receiving care in ORs with interventions versus without interventions involving physical changes to ORs. Examples include ventilation systems, bactericidal lighting, and physical alterations to ORs. METHODS: We performed a narrative review of operating room management and surgical site infection articles. We used 10-years of operating room data to estimate parameters for use in statistical power analyses. RESULTS: Creating pivot tables or monthly control charts of SSI per case by OR and comparing among ORs with or without intervention is not recommended. This approach has low power to detect a difference in SSI rates among the ORs with or without the intervention. The reason is that appropriate OR case scheduling decision making causes risk factors for SSI to differ among ORs, even when stratifying by surgical specialty. Such risk factors include case duration, urgency, and American Society of Anesthesiologists' Physical Status. Instead, analyze SSI controlling for the OR, where the patient had surgery, and matching patients using these variables is preferable. With α = 0.05, 600 cases per OR, 5 intervention ORs, and 5 or 1 control patients for each intervention patient, reasonable power (≅94% or 78%, respectively) can be achieved to detect reductions (3.6% to 2.4%) in the incidence of SSI between ORs with or without the intervention. CONCLUSIONS: By using this matched cohort design, the effect of the purchase and installation of capital equipment in ORs on SSI can be evaluated meaningfully.

Nurse anesthetists' preferences for anesthesiologists' participation in patient care at a large teaching hospital.

STUDY OBJECTIVE: Certified registered nurse anesthetists (CRNAs) can evaluate anesthesiologists with whom they work clinically using a psychometrically reliable and valid scale. Use of such a scale to evaluate performance depends on knowing thresholds for minimum and ideal anesthesiologist performance. DESIGN: Cohort study. SETTING: One large teaching hospital. MEASUREMENTS: 379 CRNA evaluations of anesthesiologists' performance, and associated thresholds for minimum and ideal scores, performed over 15 weeks. MAIN RESULTS: The anesthesiologists' performance score was less than the CRNA's minimum score for the evaluation (i.e., too little anesthesiologist participation in patient care) for 25% (95) of the CRNA evaluations. The score was greater than the CRNA's ideal score for the evaluation (i.e., excessive participation in patient care) for 28% (106) of evaluations. Anesthesiologists' performance was assessed as not meeting expectations 53% of the time. Even if every anesthesiologist performed consistently at the same level, ≥50% of CRNAs would have been dissatisfied (187), not significantly different from observed (P = 0.34). Consistent results were found when the unit of analysis was individual CRNA. Among the 22 CRNAs who provided ≥10 evaluations, the median level of anesthesiologist performance was either less than the individual CRNA's mean minimum acceptable performance (8/22) or greater than their mean ideal performance (9/22), with overall dissatisfaction, 77%. Among the CRNA-anesthesiologist pairs working together, most did so less than once per month (76%, 1242/1635). CONCLUSIONS: In this single-center study at a large teaching hospital, broad heterogeneity among CRNAs in their expectations for anesthesiologist collaborative practice was found. Anesthesiologists adjusting their behavior based on individual CRNA preferences was impractical because specific CRNA-anesthesiologist pairs work together infrequently. Future studies should examine consistency among organizations and whether changes in expectations, and perhaps less dissatisfaction, can be achieved by communication of results for CRNA preferences for anesthesiologists' participation in patient care and discussing shared expectations among the CRNAs and anesthesiologists.