Post-Operative Cognitive Dysfunction in Elderly Patients Receiving Propofol Sedation for Gastrointestinal Endoscopies: An Observational Study Utilizing Processed Electroencephalography.

BACKGROUND: Propofol sedation is commonly administered during gastrointestinal (GI) procedures. The Patient State Index (PSI) is a processed electroencephalography (EEG) parameter obtained with the SedLine® Sedation Monitoring system (Masimo Corporation, Irvine, CA). When used to objectively assess the patient's level of consciousness, PSI may provide a more effective, safer titration of sedation during GI procedures. We hypothesize that having more or longer episodes of deep sedation as assessed by PSI (i.e., PSI<26) would correlate with developing new-onset or worsening post-operative cognitive dysfunction (POCD). METHODS: This was a pragmatic, double-blinded observational study of 400 patients aged ≥65 years undergoing upper GI endoscopy, lower GI endoscopy, or a combined procedure utilizing propofol sedation at a tertiary-care [A1] academic medical center. The patients were monitored with the SedLine® Brain Function Monitor, software version 2 (Masimo Corporation, Irvine, CA), throughout the case, starting at baseline (i.e., before administration of propofol) and stopping at case end. We assessed the subjects' cognitive function via an in-person interview at baseline (pre-procedure) and telephone interviews at 1, 7 (±1), and 90 days after study enrollment. Cognitive function was assessed by administering the short blessed test (SBT), which is a validated brief cognitive screening appropriate for in-person and telephone administration. RESULTS: The correlations between the change in SBT score and the pre-defined parameters of PSI were not significant (all p-values >5%). There was a significant drop in SBT scores on day seven. Higher age was also significantly associated with a drop in SBT from baseline. Deep sedation, as evidenced by the number of times PSI was lower than 26, was not predictive of the change in SBT, nor was gender, total propofol dose, or vasoactive drug use during the procedure. CONCLUSIONS: The observed incidence of POCD after GI procedures with propofol sedation was low (1.3% at seven days and 2.95% at 90 days) and lower than at the baseline. Age was associated with a greater average decline in SBT score, although the absolute change was small (-0.067 per year of age increase). Deeper sedation, as documented by the PSI score, was not associated with a change in POCD measured with the SBT.

Remote and semi-automated methods to conduct a decentralized randomized clinical trial.

Introduction: Designing and conducting clinical trials is challenging for some institutions and researchers due to associated time and personnel requirements. We conducted recruitment, screening, informed consent, study product distribution, and data collection remotely. Our objective is to describe how to conduct a randomized clinical trial using remote and automated methods. Methods: A randomized clinical trial in healthcare workers is used as a model. A random group of workers were invited to participate in the study through email. Following an automated process, interested individuals scheduled consent/screening interviews. Enrollees received study product by mail and surveys via email. Adherence to study product and safety were monitored with survey data review and via real-time safety alerts to study staff. Results: A staff of 10 remotely screened 406 subjects and enrolled 299 over a 3-month period. Adherence to study product was 87%, and survey data completeness was 98.5% over 9 months. Participants and study staff scored the System Usability Scale 93.8% and 90%, respectively. The automated and remote methods allowed the study maintenance period to be managed by a small study team of two members, while safety monitoring was conducted by three to four team members. Conception of the trial to study completion was 21 months. Conclusions: The remote and automated methods produced efficient subject recruitment with excellent study product adherence and data completeness. These methods can improve efficiency without sacrificing safety or quality. We share our XML file for researchers to use as a template for learning purposes or designing their own clinical trials.

Healthcare Costs and Healthcare Utilization Outcomes of Vitamin D3 Supplementation at 5000 IU Daily during a 10.9 Month Observation Period within a Pragmatic Randomized Clinical Trial.

Vitamin D insufficiency has been linked to multiple conditions including bone disease, respiratory disease, cardiovascular disease, diabetes, and cancer. Observational studies indicate lower healthcare costs and healthcare utilization with sufficient vitamin D levels. The secondary aims of our previously published pragmatic clinical trial of vitamin D3 supplementation were comparisons of healthcare costs and healthcare utilization. Comparisons were made between the vitamin D3 at 5000 IU supplementation group and a non-supplemented control group. Costs of care between the groups differed but were not statistically significant. Vitamin D3 supplementation reduced healthcare utilization in four major categories: hospitalizations for any reason (rate difference: -0.19 per 1000 person-days, 95%-CI: -0.21 to -0.17 per 1000 person-days, p < 0.0001); ICU admissions for any reason (rate difference: -0.06 per 1000 person-days, 95%-CI: -0.08 to -0.04 per 1000 person-days, p < 0.0001); emergency room visits for any reason (rate difference: -0.26 per 1000 person-days, 95%-CI: -0.46 to -0.05 per 1000 person-days, p = 0.0131; and hospitalizations due to COVID-19 (rate difference: -8.47 × 10-3 per 1000 person-days, 95%-CI: -0.02 to -1.05 × 10-3 per 1000 person-days, p = 0.0253). Appropriately powered studies of longer duration are recommended for replication of these utilization findings and analysis of cost differences.

Postoperative Cognitive Dysfunction in the Elderly: A Role for Modafinil.

Introductionː Postoperative cognitive dysfunction has long-term consequences of increased mortality, loss of autonomy, and prolonged hospitalization. We sought to determine whether exposing patients to modafinil may attenuate or prevent this devastating syndrome from affecting the elderly postoperatively. Methodsː Adults aged 65 and older and American Society of Anesthesiologists (ASA) I-III physical status scheduled for elective noncardiac/non-neurosurgical surgery were included. Subjects were tested with the Trail Making Test (TMT) and Rey Auditory Visual Learning Test (RAVLT) preoperatively as well as in the immediate postoperative period, at 1 week, and at 3 months. After baseline testing, patients were randomized into three groups: 0) placebo pre and post-procedure; 1) modafinil only pre-procedure and placebo post-procedure; and 2) modafinil pre and post-procedure. A nonsurgical control group was also utilized. Resultsː Seventy-six subjects completed the trial 3 months post-surgery. The baseline RAVLT obtained was analyzed with 2-way ANOVA with repeated measures and showed improvement in learning in all groups (p = 0.03). At 1-week post-surgery, Group 0 subjects demonstrated no learning improvement in the RAVLT. However, there was a significant improvement in learning in both groups that received modafinil (p<0.01), and in the nonsurgical controls (p<0.01). This learning benefit normalized at 3 months. Conclusionː In this prospective, double-blind, placebo-controlled trial, we found that patients who received modafinil showed improvement in the RAVLT at 1 week. However, this learning benefit normalized at 3 months. Further study should examine dose effect, timing, and route of administration to determine if the effect can be enhanced and if in fact, wakefulness is improved post-surgically.

The Incidence, Degree, and Timing of Hypocalcemia From Massive Transfusion: A Retrospective Review.

BACKGROUND: Electrolyte administration during massive transfusion without readily available calcium laboratory values is likely ubiquitous but not well standardized. We aimed to quantify the incidence, degree, and timing of hypocalcemia during the first 24 hours after initiation of a massive transfusion with the institutional massive transfusion protocol (MTP). We hypothesized that hypocalcemia is prevalent during acute resuscitation (first six hours) despite efforts of the treatment team to replete calcium during active resuscitation. METHODS: A retrospective chart review of all patients who underwent MTP at our institution between January 1, 2017, and December 31, 2017, was performed. The primary outcome was hypocalcemia from a massive transfusion during the first six hours after the initiation of the MTP. Secondary outcomes of interest included hypercalcemia, hypomagnesemia, hospital mortality, peak and nadir timing of hypocalcemia and hypercalcemia, calcium supplementation, and calcium supplementation timing. Calcium administration and blood product transfusion is reported relative to the start of the MTP. The association between the total amount of calcium administered and the total number of blood products transfused was assessed. RESULTS: Data from 52 massive transfusions were analyzed. Ninety-seven percent of patients were hypocalcemic during the first six hours of resuscitation. The nadir occurred after median of eight units of blood product were given, (interquartile range {IQR}: 4-16). Calcium supplementation correlated with the total number of blood products transfused (ρ = 0.47, p < 0.01). Patients in whom calcium was supplemented received more blood products when compared to patients in whom calcium was not supplemented (median: 16, IQR: 12-26 vs. median: 9, IQR: 7-12, p <0.01). CONCLUSIONS: Hypocalcemia from massive transfusion is common. The incidence of hypocalcemia in MTP has been reported to be 85-97%. Calcium supplementation that is not standardized in MTP may lead to underutilization during massive transfusion and to hypocalcemia in these patients.

Is Calcium Score in the Abdominal Aorta or Renal Arteries Predictive of Acute Kidney Injury After Cardiopulmonary Bypass: An Exploratory Study.

Introduction Acute kidney injury (AKI) remains a serious complication after surgery with cardiopulmonary bypass (CPB). A relationship similar to the one between coronary artery calcification and increased incidence of cardiac complications is hypothesized to exist for aortic calcification and the development of AKI. Elevated pulse pressure (PP) hypertension has been shown to be a predictor of AKI-CPB (AKI after CPB surgery), and calcium deposition and stiffening of the body's conduit arteries may be part of this process. We hypothesized that calcium scores obtained from non-contrast computed tomography (CT) scans of the infrarenal aorta and renal arteries would be independently and significantly associated with AKI-CPB. Methods We conducted a retrospective study of 65 subjects who underwent non-emergent open heart surgery with CPB in a tertiary healthcare center. AKI-CPB was diagnosed using the Acute Kidney Injury Network criteria. Aortic and renal artery calcium (Agatston) scores were obtained and entered into a multivariable logistic regression model alongside other significant predictors of AKI-CPB from a univariable analysis. Results Pulse pressure, body surface area, and pre-operative serum creatinine were significantly associated with the development of AKI-CPB, but the calcium scores were not. For PP, the odds ratio (OR) was 1.062, (95% Wald confidence interval {CI}=1.012 - 1.114). The OR for the calcium score in the aorta was 1.0000 (95% CI=1.0 - 1.0). Conclusions Agatston calcium scores in the renal arteries and infrarenal aorta were not independently associated with AKI-CPB, but arterial stiffening, as indicated by elevated pulse pressure, was predictive of AKI-CPB.

Vitamin D3 Supplementation at 5000 IU Daily for the Prevention of Influenza-like Illness in Healthcare Workers: A Pragmatic Randomized Clinical Trial.

Vitamin D supplementation has been shown to reduce the incidence of acute respiratory infections in populations at risk. The COVID-19 pandemic has highlighted the importance of preventing viral infections in healthcare workers. The aim of this study was to assess the hypothesis that vitamin D3 supplementation at 5000 IU daily reduces influenza-like illness (ILI), including COVID-19, in healthcare workers. We conducted a prospective, controlled trial at a tertiary university hospital. A random group of healthcare workers was invited to receive 5000 IU daily vitamin D3 supplementation for nine months, while other random healthcare system workers served as controls. All healthcare workers were required to self-monitor and report to employee health for COVID-19 testing when experiencing symptoms of ILI. COVID-19 test results were retrieved. Incidence rates were compared between the vitamin D and control groups. Workers in the intervention group were included in the analysis if they completed at least 2 months of supplementation to ensure adequate vitamin D levels. The primary analysis compared the incidence rate of all ILI, while secondary analyses examined incidence rates of COVID-19 ILI and non-COVID-19 ILI. Between October 2020 and November 2021, 255 healthcare workers (age 47 ± 12 years, 199 women) completed at least two months of vitamin D3 supplementation. The control group consisted of 2827 workers. Vitamin D3 5000 IU supplementation was associated with a lower risk of ILI (incidence rate difference: -1.7 × 10-4/person-day, 95%-CI: -3.0 × 10-4 to -3.3 × 10-5/person-day, p = 0.015) and a lower incidence rate for non-COVID-19 ILI (incidence rate difference: -1.3 × 10-4/person-day, 95%-CI -2.5 × 10-4 to -7.1 × 10-6/person-day, p = 0.038). COVID-19 ILI incidence was not statistically different (incidence rate difference: -4.2 × 10-5/person-day, 95%-CI: -10.0 × 10-5 to 1.5 × 10-5/person-day, p = 0.152). Daily supplementation with 5000 IU vitamin D3 reduces influenza-like illness in healthcare workers.

Correlation of Country Characteristics and Government Response Measures With COVID-19 Mortality During the First Phase of the Global COVID-19 Pandemic: A Worldwide Ecological Study.

Introduction It is valuable to know if country demographic, educational, healthcare and other socioeconomic factors were correlated with the COVID-19 mortality rate during the initial phase of the coronavirus disease 2019 (COVID-19) worldwide pandemic (January 1st - August 31st, 2020). Similarly, it is worthwhile understanding whether a country's geographic location or the measures instituted by governments, such as lockdowns and mask-wearing, were associated with an increased or decreased mortality rate. Materials and methods To assess these correlations, we conducted an ecologic study of 178 countries using time-matched data from the Social Progress Index (www.socialprogress.org, produced by the Social Progress Imperative), population data from the World Bank (data.worldbank.org), government response indices from Our World In Data (ourworldindata.org/policy-responses-covid), and COVID-19 mortality data from the Johns Hopkins University CSSE COVID-19 Data repository (github.com/CSSEGISandData/COVID-19), accessed on November 22nd, 2020. Pearson correlation coefficients were derived between potential predictors and countries' COVID-19 population-adjusted crude mortality rates. Select variables were entered in a multivariable regression model. Countries with no data in the social progress index database or those with no COVID-19 cases were excluded (20 in total).  Results The highest positive correlations were found between the proportion of the population older than 75 (Pearson correlation coefficient 0.321), country distance from the equator (0.267), gross domestic product per capita (0.218), health and wellness score (0.388), water and sanitation score (0.384), environmental quality (0.237), and the days between the first reported COVID-19 case and the initial government response (0.238). A previously unreported and unexpected negative correlation was found between gender parity in secondary education attainment and COVID-19 mortality (-0.290). Peak mask-wearing ranging from 'recommended' to 'required outside the home at all times was extremely weakly correlated with lower COVID-19 mortality (-0.046). Conclusions Crude COVID-19 mortality rates during the first phase of the pandemic in 2020, during which no vaccine or specific treatment was available, were higher in wealthier countries that were further away from the equator and had a higher health and wellness score according to the Social Progress Imperative. They were also higher the longer governments delayed their initial response. Gender parity in secondary education and stringency of mask-wearing guidelines were correlated with lower mortality, though the latter correlation was extremely weak. Our findings are consistent with previously published correlations. The correlation between crude COVID-19 mortality rates and gender parity in secondary education has not been previously reported.

Hereditary pseudocholinesterase deficiency discovery after electroconvulsive therapy.

Inherited pseudocholinesterase deficiency refers to an uncommon defect in the butyrylcholinesterase enzyme which can result in prolonged muscle paralysis due to delayed breakdown of choline ester paralytic anaesthetic agents. We describe a 25-year-old woman receiving electroconvulsive therapy (ECT) for treatment of depression in whom motor function did not recover adequately after administration of succinylcholine. Investigated post-ECT, she was found to have severe pseudocholinesterase deficiency. Implications of pseudocholinesterase deficiency for ECT treatment and anaesthetic strategies are discussed.

Comparison of atriocaval shunting with perihepatic packing versus perihepatic packing alone for retrohepatic vena cava injuries in a swine model.

BACKGROUND: Retrohepatic vena cava (RVC) injuries are technically challenging and often lethal. Atriocaval shunting has been promoted as a modality to control haemorrhage from these injuries, but evidence from controlled studies supporting its benefit is lacking. We hypothesised that addition of an atriocaval shunt to perihepatic packing would improve outcomes in our penetrating RVC injury swine model. METHODS: After a survivable atriocaval shunting model was refined in 4 swine without an injury, 13 additional female Yorkshire swine were randomised into either perihepatic packing and atriocaval shunt (PPAS, n=7) or perihepatic packing alone (PP, n=6) treatment arms prior to creating a standardised, 1.5 cm stab wound to the RVC. Haemodynamic parameters, intravenous fluid, and blood loss were recorded until mortality or euthanisation after 4h. Statistical tests used to test differences include the Wilcoxon rank sums test, Fisher exact test and analysis of covariance. A p-value ≤0.05 was considered statistically significant. RESULTS: Immediately before and after RVC injury, no difference in temperature, cardiac output, heart rate, mean arterial pressure or mean pulmonary artery pressure was detected (all p>0.05) between the two groups. While the RVC injury did affect measures parameters in PPAS swine over time, haemodynamic compromise and blood loss were not significantly greater in PPAS than PP swine. Survival time was significantly different with all PPAS swine dying within 2h (mean survival duration 39 (SD 58)min) while all 6 PP swine survived the entire 4h study period. CONCLUSIONS: While perihepatic packing alone slowed haemorrhage to survivable rates during the 4h study period, atriocaval shunt placement led to rapid physiologic decline and death in our standardised, penetrating RVC model.