Qualitative and quantitative detection of SARS-CoV-2 antibodies from dried blood spots.

INTRODUCTION: Dried blood spot (DBS) sampling is a minimally invasive method for specimen collection with potential multifaceted uses, particularly for serosurveillance of previous SARS-CoV-2 infection. In this study, we assessed DBS as a potential specimen type for assessing IgG and total (including IgG and IgM) antibodies to SARS-CoV-2 in vaccinated and naturally infected patients. METHODS: Six candidate buffers were assessed for eluting blood from DBS cards. The study utilized one hundred and five paired plasma specimens and DBS specimens from prospectively collected SARS-CoV-2 vaccinated individuals, remnants from those with PCR confirmed SARS-CoV-2 infections, or remnants from those without history of infection or vaccination. All specimens were tested with the Siemens SARS-CoV-2 total assay (COV2T) or IgG assay (sCOVG). RESULTS: The lowest backgrounds were observed with water and PBS, and water was used for elution. Relative to plasma samples, DBS samples had a positive percent agreement (PPA) of 94.4% (95% CI: 94.9-100%) for COV2T and 79.2 (68.4-87.0) for sCOVG using the manufacturer's cutoff. The NPA was 100 % (87.1-100.0 and 85.13-100) for both assays. Dilution studies revealed 100% (95% CI: 90.8-100%) qualitative agreement between specimen types on the COV2T assay and 98.0% (88.0-99.9%) with the sCOVG using study defined cutoffs. CONCLUSION: DBS specimens demonstrated high PPA and NPA relative to plasma for SARS-CoV-2 serological testing. Our data support feasibility of DBS sampling for SARS-CoV-2 serological testing.

Postoperative Outcomes Associated With Procedural Sedation Conducted by Physician and Nonphysician Anesthesia Providers: Findings From the Prospective, Observational African Surgical Outcomes Study.

BACKGROUND: There is an unmet need for essential surgical services in Africa. Limited anesthesia services are a contributing factor. Nonphysician anesthesia providers are utilized to assist with providing anesthesia and procedural sedation to make essential surgeries available. There is a paucity of data on outcomes following procedural sedation for surgery in Africa. We investigated the postoperative outcomes following procedural sedation by nonphysicians and physicians in Africa. We hypothesized that the level of training of the sedation provider may be associated with the incidence of severe postoperative complications and death. METHODS: A secondary analysis of a prospective cohort of inhospital adult surgical patients representing 25 African countries was performed. The primary outcome was a collapsed composite of inhospital severe postoperative complications and death. We assessed the association between receiving procedural sedation conducted by a nonphysician (versus physician) and the composite outcome using logistic regression. We used the inverse probability of treatment weighting propensity score method to adjust for potential confounding variables including patient age, hemoglobin level, American Society of Anesthesiologists (ASA) physiological status, diabetes mellitus, urgency of surgery, severity of surgery, indication for surgery, surgical discipline, seniority of the surgical team, hospital level of specialization, and hospital funding system using public or private funding. All patients who only received procedural sedation for surgery were included. RESULTS: Three hundred thirty-six patients met the inclusion criteria, of which 98 (29.2%) received sedation from a nonphysician provider. The incidence of severe postoperative complications and death was 10 of 98 (10.2%) in the nonphysician group and 5 of 238 (2.1%) in the physician group. The estimated association between procedural sedation conducted by a nonphysician provider and inhospital outcomes was an 8-fold increase in the odds of severe complications and/or death, with an odds ratio (95% confidence interval [CI]) of 8.3 (2.7-25.6). CONCLUSIONS: The modest number of observations in this secondary data analysis suggests that shifting the task of procedural sedation from physicians to nonphysicians to increase access to care may be associated with severe postoperative complications and death in Africa. Research focusing on identifying factors contributing to adverse outcomes associated with procedural sedation is necessary to make this practice safer.

Understanding the performance of a pan-African intervention to reduce postoperative mortality: a mixed-methods process evaluation of the ASOS-2 trial.

BACKGROUND: The African Surgical OutcomeS-2 (ASOS-2) trial tested an enhanced postoperative surveillance intervention to reduce postoperative mortality in Africa. We undertook a concurrent evaluation to understand the process of intervention delivery. METHODS: Mixed-methods process evaluation, including field notes, interviews, and post-trial questionnaire responses. Qualitative analysis used the framework method with subsequent creation of comparative case studies, grouping hospitals by intervention fidelity. A post-trial questionnaire was developed using initial qualitative analyses. Categorical variables were summarised as count (%) and continuous variables as median (inter-quartile range [IQR]). Odds ratios (OR) were used to rank influences by impact on fidelity. RESULTS: The dataset included eight in-depth case studies, and 96 questionnaire responses (response rate 67%) plus intervention fidelity data for each trial site. Overall, 57% (n=55/96) of hospitals achieved intervention delivery using an inclusive definition of fidelity. Delivery of the ASOS-2 interventions and data collection presented a significant burden to the investigators, outstripping limited resources. The influences most associated with fidelity were: surgical staff enthusiasm for the trial (OR=3.0; 95% confidence interval [CI], 1.3-7.0); nursing management support of the trial (OR=2.6; 95% CI, 1.1-6.5); performance of a dummy run (OR=2.6; 95% CI, 1.1-6.1); nursing colleagues seeing the value of the intervention(s) (OR=2.1; 95% CI, 0.9-5.7); and site investigators' belief in the effectiveness of the intervention (OR=3.2; 95% CI, 1.2-9.4). CONCLUSIONS: ASOS-2 has proved that coordinated interventional research across Africa is possible, but delivering the ASOS-2 interventions was a major challenge for many investigators. Future improvement science efforts must include better planning for intervention delivery, additional support to investigators, and promotion of strong inter-professional teamwork. CLINICAL TRIAL REGISTRATION: ClinicalTrials gov NCT03853824.

Survival equivalence in patients treated for borderline resectable and unresectable locally advanced pancreatic ductal adenocarcinoma: a systematic review and network meta-analysis.

BACKGROUND: The clinical relevance of subdivision of non-metastatic pancreatic ductal adenocarcinoma (PDAC) into locally advanced borderline resectable (LA-BR) and locally advanced unresectable (LA-UR) has been questioned. We assessed equivalence of overall survival (OS) in patients with LA-BR and LA-UR PDAC. METHODS: A systematic review was performed of studies published January 1, 2009 to August 21, 2019, reporting OS for LA-BR and LA-UR patients treated with or without neoadjuvant therapy (NAT), with or without surgical resection. A frequentist network meta-analysis was used to assess the primary outcome (hazard ratio for OS) and secondary outcomes (OS in LA-BR, LA-UR, and upfront resectable (UFR) PDAC). RESULTS: Thirty-nine studies, comprising 14,065 patients in a network of eight unique treatment subgroups were analysed. Overall survival was better for LA-BR than LA-UR patients following surgery both with and without NAT. Neoadjuvant therapy prior to surgery was associated with longer OS for UFR, LA-BR, and LA-UR tumours, compared to upfront surgery. CONCLUSION: Survival between the LA-BR and LA-UR subgroups was not equivalent. This subdivision is useful for prognostication, but likely unhelpful in treatment decision making. Our data supports NAT regardless of initial disease extent. Individual patient data assessment is needed to accurately estimate the benefit of NAT.

Core Temperature Monitoring in Obstetric Spinal Anesthesia Using an Ingestible Telemetric Sensor.

BACKGROUND: Perioperative hypothermia may affect maternal and neonatal outcomes after obstetric spinal anesthesia. Core temperature is often poorly monitored during spinal anesthesia, due to the lack of an accurate noninvasive core temperature monitor. The aim of this study was to describe core temperature changes and temperature recovery during spinal anesthesia for elective cesarean delivery. We expected that obstetric spinal anesthesia would be associated with a clinically relevant thermoregulatory insult (core temperature decrease >1.0°C). METHODS: A descriptive study was conducted in 28 women. An ingestible telemetric temperature sensor was used to record core temperature over time (measured every 10 seconds). The primary outcome was the maximum core temperature decrease after spinal anesthetic injection. The secondary outcomes were lowest absolute core temperature, time to lowest temperature, time to recovery of core temperature, hypothermic exposure (degree-hours below 37.0°C), and the time-weighted hypothermic exposure (median number of degrees below 37.0°C per hour). Basic descriptive statistics, median spline smooth, and integration of the area below the 37.0°C line of the temperature-over-time curve were utilized to analyze the data. RESULTS: Intestinal temperature decreased by a mean (standard deviation) of 1.30°C (0.31); 99% confidence interval (CI), 1.14 to 1.46 after spinal anesthetic injection. The median (interquartile range [IQR]) time to temperature nadir was 0.96 (0.73-1.32) hours (95% CI, 0.88-1.22). Fourteen of the 28 participants experienced intestinal temperatures below 36.0°C after spinal injection. Temperature was monitored for a minimum of 8 hours after spinal injection. In 8 of 28 participants, intestinal temperature did not recover to baseline during the monitored period. A median (IQR) of 4.59 (3.38-5.92) hours (95% CI, 3.45-5.90) was required for recovery to baseline intestinal temperature in the remaining 20 patients. Participants experienced a median (IQR) of 1.97 (1.00-2.68) degree-hours of hypothermic exposure (95% CI, 1.23-2.45). The median (IQR) number of degrees below 37.0°C per hour was 0.45 (0.35-0.60) (95% CI, 0.36-0.58). CONCLUSIONS: During cesarean delivery under spinal anesthesia, women experienced a rapid decrease in core temperature. Using an intestinal telemetric sensor, the perioperative thermal insult and recovery were documented with high resolution. Fifty percent of participants in this study became hypothermic. Although the surgical procedure is typically of short duration, women undergoing spinal anesthesia for cesarean delivery experience significant hypothermic exposure and compromised thermoregulation for several hours.

A meta-analysis of the efficacy of preoperative surgical safety checklists to improve perioperative outcomes.

BACKGROUND: Meta-analyses of the implementation of a surgical safety checklist (SSC) in observational studies have shown a significant decrease in mortality and surgical complications. OBJECTIVE: To determine the efficacy of the SSC using data from randomised controlled trials (RCTs). METHODS: This meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and was registered with PROSPERO (CRD42015017546). A comprehensive search of six databases was conducted using the OvidSP search engine. RESULTS: Four hundred and sixty-four citations revealed three eligible trials conducted in tertiary hospitals and a community hospital, with a total of 6 060 patients. All trials had allocation concealment bias and a lack of blinding of participants and personnel. A single trial that contributed 5 295 of the 6 060 patients to the meta-analysis had no detection, attrition or reporting biases. The SSC was associated with significantly decreased mortality (risk ratio (RR) 0.59, 95% confidence interval (CI) 0.42 - 0.85; p=0.0004; I2=0%) and surgical complications (RR 0.64, 95% CI 0.57 - 0.71; p<0.00001; I2=0%). The efficacy of the SSC on specific surgical complications was as follows: respiratory complications RR 0.59, 95% CI 0.21 - 1.70; p=0.33, cardiac complications RR 0.74, 95% CI 0.28 - 1.95; p=0.54, infectious complications RR 0.61, 95% CI 0.29 - 1.27; p=0.18, and perioperative bleeding RR 0.36, 95% CI 0.23 - 0.56; p<0.00001. CONCLUSIONS: There is sufficient RCT evidence to suggest that SSCs decrease hospital mortality and surgical outcomes in tertiary and community hospitals. However, randomised evidence of the efficacy of the SSC at rural hospital level is absent.