Properties Of Bound Estimators On Treatment Effect Heterogeneity For Binary Outcomes

Variability in individual causal effects, treatment effect heterogeneity (TEH), is important to the interpretation of clinical trial results, regardless of the marginal treatment effect. Unfortunately, it is usually ignored. In the setting of two-arm randomized studies with binary outcomes, there are estimators for bounds on the probability of control success and treatment failure for an individual, or the treatment risk. Here, those bounds were refined and the sampling properties were assessed using simulations of correlated multinomial data via the Dirichlet multinomial. Results indicated low bias and mean squared error. Moderate to high intraclass correlation (ICC) and large numbers of clusters allow narrower confidence interval widths for the treatment risk

Suture-method versus Through-the-needle Catheters for Continuous Popliteal-sciatic Nerve Blocks: A Randomized Clinical Trial.

BACKGROUND:The basic perineural catheter design has changed minimally since inception, with the catheter introduced through or over a straight needle. The U.S. Food and Drug Administration recently cleared a novel perineural catheter design comprising a catheter attached to the back of a suture-shaped needle that is inserted, advanced along the arc of its curvature pulling the catheter past the target nerve, and then exited through the skin in a second location. The authors hypothesized that analgesia would be noninferior using the new versus traditional catheter design in the first two days after painful foot/ankle surgery with a primary outcome of average pain measured with the Numeric Rating Scale. METHODS:Subjects undergoing painful foot or ankle surgery with a continuous supraparaneural popliteal-sciatic nerve block 5 cm proximal to the bifurcation were randomized to either a suture-type or through-the-needle catheter and subsequent 3-day 0.2% ropivacaine infusion (basal 6 ml/h, bolus 4 ml, lockout 30 min). Subjects received daily follow-up for the first four days after surgery, including assessment for evidence of malfunction or dislodgement of the catheters. RESULTS:During the first two postoperative days the mean ± SD average pain scores were lower in subjects with the suture-catheter (n = 35) compared with the through-the-needle (n = 35) group (2.7 ± 2.4 vs. 3.4 ± 2.4) and found to be statistically noninferior (95% CI, -1.9 to 0.6; P < 0.001). No suture-style catheter was completely dislodged (0%), whereas the tips of three (9%) traditional catheters were found outside of the skin before purposeful removal on postoperative day 3 (P = 0.239). CONCLUSIONS:Suture-type perineural catheters provided noninferior analgesia compared with traditional catheters for continuous popliteal-sciatic blocks after painful foot and ankle surgery. The new catheter design appears to be a viable alternative to traditional designs used for the past seven decades

Optimal interval and duration of CAM-ICU assessments for delirium detection after cardiac surgery

STUDY OBJECTIVE: Our goal was to determine when postoperative delirium first occurs, and to assess evaluation strategies that reliably detect delirium with lowest frequency of testing. DESIGN: This was a retrospective study that used a database from a five-center randomized trial. SETTING: Postoperative cardiothoracic ICU and surgical wards. PARTICIPANT: Adults scheduled for elective coronary artery bypass and/or valve surgery. INTERVENTION AND MEASUREMENTS: Postoperative delirium was assessed using CAM-ICU questionnaires twice daily for 5 days or until hospital discharge. Data were analyzed using frequency tables and Kaplan-Meier time-to-event estimators, the latter being used to summarize time to first positive CAM-ICU over POD1-5 for all patients for various evaluation strategies, including all assessments, only morning assessment, and only afternoon assessments. Sensitivity for various strategies were compared using McNemar\u27s test for paired proportions. MAIN RESULTS: A total of 95 of 788 patients (12% [95% CI, 10% to 15%]) had at least 1 episode of delirium within the first 5 postoperative days. Among all patients with delirium, 65% were identified by the end of the first postoperative day. Delirium was detected more often in the mornings (10% of patients) than evenings (7% of patients). Compared to delirium assessments twice daily for five days, we found that twice daily assessments for 4 days detected an estimated 97% (95% CI 91%, 99%) of delirium. Measurements twice daily for three days detected 90% (82%, 95%) of delirium. CONCLUSIONS: Postoperative delirium is common, and CAM-ICU assessments twice daily for 4 days, versus 5 days, detects nearly all delirium with 20% fewer assessments. Four days of assessment may usually be sufficient for clinical and research purposes

Early detection of deterioration in COVID-19 patients by continuous ward respiratory rate monitoring: a pilot prospective cohort study

BackgroundTachypnea is among the earliest signs of pulmonary decompensation. Contactless continuous respiratory rate monitoring might be useful in isolated COVID-19 patients admitted in wards. We therefore aimed to determine whether continuous monitoring of respiratory patterns in hospitalized patients with COVID-19 predicts subsequent need for increased respiratory support.MethodsSingle-center pilot prospective cohort study in COVID-19 patients who were cared for in routine wards. COVID-19 patients who had at least one escalation of pulmonary management were matched to three non-escalated patients. Contactless respiratory monitoring was instituted after patients enrolled, and continued for 15 days unless hospital discharge, initiation of invasive mechanical ventilation, or death occurred. Clinicians were blinded to respiratory rate data from the continuous monitor. The exposures were respiratory features over rolling periods of 30 min, 24 h, and 72 h before respiratory care escalation. The primary outcome was a subsequent escalation in ventilatory support beyond a Venturi mask.ResultsAmong 125 included patients, 13 exhibited at least one escalation and were each matched to three non-escalated patients. A total of 28 escalation events were matched to 84 non-escalation episodes. The 30-min mean respiratory rate in escalated patients was 23 breaths per minute (bpm) ranging from 13 to 40 bpm, similar to the 22 bpm in non-escalated patients, although with less variability (range 14 to 31 bpm). However, higher respiratory rate variability, especially skewness over 1 day, was associated with higher incidence of escalation events. Our overall model, based on continuous data, had a moderate accuracy with an AUC 0.81 (95%CI: 0.73, 0.88) and a good specificity 0.93 (95%CI: 0.87, 0.99).ConclusionOur pilot observational study suggests that respiratory rate variability as detected with continuous monitoring is associated with subsequent care escalation during the following 24 h. Continuous respiratory monitoring thus appears to be a valuable increment over intermittent monitoring.Strengths and limitationsOur study was the initial evaluation of Circadia contactless respiratory monitoring in COVID-19 patients who are at special risk of pulmonary deterioration. The major limitation is that the analysis was largely post hoc and thus needs to be confirmed in an out-of-sample population

Development and Validation of a Risk Quantification Index for 30-Day Postoperative Mortality and Morbidity in Noncardiac Surgical Patients

ABSTRACT Background: Optimal risk adjustment is a requisite precondition for monitoring quality of care and interpreting public reports of hospital outcomes. Current risk-adjustment measures have been criticized for including baseline variables that are difficult to obtain and inadequately adjusting for highrisk patients. The authors sought to develop highly predictive risk-adjustment models for 30-day mortality and morbidity based only on a small number of preoperative baseline characteristics. They included the Current Procedural Terminology code corresponding to the patient'

Diaspirin-crosslinked hemoglobin reduces blood transfusion in noncardiac surgery: a multicenter, randomized, controlled, double-blinded trial.

UNLABELLED: In this randomized, prospective, double-blinded clinical trial, we sought to investigate whether diaspirin-crosslinked hemoglobin (DCLHb) can reduce the perioperative use of allogeneic blood transfusion. One-hundred-eighty-one elective surgical patients were enrolled at 19 clinical sites from 1996 to 1998. Selection criteria included anticipated transfusion of 2-4 blood units, aortic repair, and major joint or abdomino-pelvic surgery. Once a decision to transfuse had been made, patients received initially up to 3 250-mL infusions of 10% DCLHb (n = 92) or 3 U of packed red blood cells (PRBCs) (n = 89). DCLHb was infused during a 36-h perioperative window. On the day of surgery, 58 of 92 (64%; confidence interval [CI], 54%-74%) DCLHb-treated patients received no allogeneic PRBC transfusions. On Day 1, this number was 44 of 92 (48%; CI, 37%-58%) and decreased further until Day 7, when it was 21 of 92 (23%; CI, 15%-33%). During the 7-day period, 2 (1-4) units of PRBC per patient were used in the DCLHb group compared with 3 (2-4) units in the control patients (P = 0.002; medians and 25th and 75th percentiles). Mortality (4% and 3%, respectively) and incidence of suffering at least one serious adverse event (21% and 15%, respectively) were similar in DCLHb and PRBC groups. The incidence of jaundice, urinary side effects, and pancreatitis were more frequent in DCLHb patients. The study was terminated early because of safety concerns. Whereas the side-effect profile of modified hemoglobin solutions needs to be improved, our data show that hemoglobin solutions can be effective at reducing exposure to allogeneic blood for elective surgery. IMPLICATIONS: In a randomized, double-blinded red blood cell controlled, multicenter trial, diaspirin-crosslinked hemoglobin spared allogeneic transfusion in 23% of patients undergoing elective noncardiac surgery. The observed side-effect profile indicates a need for improvement in hemoglobin development

Single-injection thoracic paravertebral block and postoperative analgesia after mastectomy: a retrospective cohort study

BackgroundThe treatment of postoperative pain after mastectomy is an area of increasing interest, as this treatment option is now considered a standard of care for those affected by breast cancer. Thoracic paravertebral nerve block (tPVB) using local anesthetics administered before mastectomy can theoretically provide postoperative analgesia, thereby facilitating a more comfortable and shorter hospitalization.MethodsIn this retrospective cohort study, we aimed to determine the duration and degree to which tPVB provides postoperative analgesia in patients who underwent either unilateral or bilateral mastectomy (n = 182). We retrospectively examined the numeric rating scale (NRS) for pain scores recorded by nursing staff throughout individual patient hospitalizations, looking specifically at the following time points: arrival from the postanesthesia care unit to the surgical wards, noon on postoperative day 1 (POD1), and discharge. We also examined the number of days until patients were discharged from the hospital.ResultsOur results revealed a statistically significant decrease in NRS in pain scores for patients who had received a tPVB (n = 92) on arrival from the postanesthesia care unit to the surgical wards (mean NRS decrease of 1.9 points; 99% confidence interval [CI], -3.0 to -0.8; P < .001) but did not show statistically significant decreases in NRS for pain scores for patients at noon on POD1 (mean NRS decrease of 0.3 points at noon on POD1, P = .43) or at discharge (mean NRS decrease of 0.1 point at discharge, P = .65). Moreover, use of tPVB did not have an impact on time until discharge (average decrease of 0.5 hours; 95% CI, -6 to +5 hours, P = .87).ConclusionsSingle-injection tPVB appears to provide meaningful postoperative analgesia in the immediate postoperative period after mastectomy but not after the first day of surgery

Design and Organization of the Dexamethasone, Light Anesthesia and Tight Glucose Control (DeLiT) Trial: a factorial trial evaluating the effects of corticosteroids, glucose control, and depth-of-anesthesia on perioperative inflammation and morbidity from major non-cardiac surgery

<p>Abstract</p> <p>Background</p> <p>The perioperative period is characterized by an intense inflammatory response. Perioperative inflammation promotes postoperative morbidity and increases mortality. Blunting the inflammatory response to surgical trauma might thus improve perioperative outcomes. We are studying three interventions that potentially modulate perioperative inflammation: corticosteroids, tight glucose control, and light anesthesia.</p> <p>Methods/Design</p> <p>The DeLiT Trial is a factorial randomized single-center trial of dexamethasone vs placebo, intraoperative tight vs. conventional glucose control, and light vs deep anesthesia in patients undergoing major non-cardiac surgery. Anesthetic depth will be estimated with Bispectral Index (BIS) monitoring (Aspect medical, Newton, MA). The primary outcome is a composite of major postoperative morbidity including myocardial infarction, stroke, sepsis, and 30-day mortality. C-reactive protein, a measure of the inflammatory response, will be evaluated as a secondary outcome. One-year all-cause mortality as well as post-operative delirium will be additional secondary outcomes. We will enroll up to 970 patients which will provide 90% power to detect a 40% reduction in the primary outcome, including interim analyses for efficacy and futility at 25%, 50% and 75% enrollment.</p> <p>Discussion</p> <p>The DeLiT trial started in February 2007. We expect to reach our second interim analysis point in 2010. This large randomized controlled trial will provide a reliable assessment of the effects of corticosteroids, glucose control, and depth-of-anesthesia on perioperative inflammation and morbidity from major non-cardiac surgery. The factorial design will enable us to simultaneously study the effects of the three interventions in the same population, both individually and in different combinations. Such a design is an economically efficient way to study the three interventions in one clinical trial vs three.</p> <p>Trial registration</p> <p><b>This trial is registered at </b>Clinicaltrials.gov <b>#</b>: NTC00433251</p

Staffing with disease-based epidemiologic indices may reduce shortage of intensive care unit staff during the COVID-19 pandemic.

PURPOSE Healthcare worker (HCW) safety is of pivotal importance during a pandemic such as Coronavirus Disease 2019 (COVID-19), and employee health and well-being ensures functionality of healthcare institutions. This is particularly true for an intensive care unit (ICU) where highly specialized staff cannot be readily replaced. In the light of lacking evidence for optimal staffing models in a pandemic, we hypothesized that staff shortage can be reduced when staff scheduling takes the epidemiology of a disease epidemic into account. METHODS Various staffing models were constructed and comprehensive statistical modeling performed. A typical, routine staffing model was defined that assumed full-time employment (40 hours/week) in a 40 bed ICU with a 2:1 ratio of patients to staff. The pandemic model assumed staff worked 12-hour shifts for 7 days every other week. Potential in-hospital staff infections were constructed for a total period of 120 days with a probability of 10%, 25%, and 40% being infected per week when at work. Simulations included the probability of infection at work for a given week, of fatality once infected, and the quarantine time, if infected. RESULTS Pandemic-adjusted staffing significantly reduced workforce shortage and the effect progressively increased as the probability of infection increased. Maximum effects were observed at week 4 for each infection probability with a 17%, 32%, and 38% staffing reduction for an infection probability of 0.10, 0.25, and 0.40, respectively. CONCLUSIONS Staffing along epidemiologic considerations may reduce HCW shortage by leveling the nadir from affected workforce. Although this requires considerable efforts and commitment of staff, it may be essential in an effort to best maintain staff health and operational functionality of healthcare facilities and systems