COVID-19 symptom load as a risk factor for chronic pain: A national cross-sectional study.

INTRODUCTION: Emerging evidence suggests that a COVID-19 infection with a high initial severity may be associated with development of long-COVID conditions such as chronic pain. At the population level, it is unknown if severity of a COVID-19 infection might be a new risk factor for chronic pain above and beyond the traditional slate of pre-established risk factors. The purpose of this study is to examine whether COVID-19 severity of infection may be a new risk factor for chronic pain. METHODS: Using data from the 2021 National Health Interview Survey (n = 15,335), this study examined the adjusted odds of experiencing high frequency levels of pain in the past 3 months for those who reported no/mild symptoms from a COVID-19 infection, and those reporting moderate/severe symptoms from COVID-19, compared to those never infected. A 1:1:1 propensity score matched analysis was also performed to examine the odds of pain. RESULTS: Prevalence of pain was higher in the moderate/severe symptom group compared to the no infection group (25.48% vs 19.44%, p <0.001). Both the adjusted model (odds ratio [OR] = 1.28, 95% confidence interval [CI] = 1.09, 1.51) and matched model (OR = 1.45, CI = 1.14, 1.83) revealed higher odds of pain for those with moderate/high COVID-19 symptoms compared to no infection. CONCLUSIONS: A moderate/highly symptomatic COVID-19 infection may be a new risk factor for chronic pain. As the absolute number of severe COVID-19 infections continues to rise, overall prevalence of chronic pain may also increase. While knowledge continues to unfold on long-haul symptoms, prevention of severe infections remains essential.

Comparing Email, SMS, and Concurrent Mixed Modes Approaches to Capture Quality of Recovery in the Perioperative Period: Retrospective Longitudinal Cohort Study.

BACKGROUND: As patients are discharged from the hospital more quickly, the ability to monitor patient recovery between hospital discharge and the first follow-up clinic visit is becoming increasingly important. Despite substantial increase in both internet use and smartphone ownership over the past 5 years, clinicians have been slow to embrace the use of these devices to capture patient recovery information in the period between hospital discharge and the first clinical follow-up appointment. OBJECTIVE: This study aims to investigate the generalizability of using a web-based platform to capture patient recovery in a broad surgical patient population and compare response rates for 3 different web-based strategies for delivering recovery surveys over the perioperative period: email, SMS text messaging, and a concurrent mixed approach of using both email and SMS text messaging. METHODS: Patients undergoing surgeries managed with an enhanced recovery after surgery pathway were asked to participate in a web-based quality assurance monitoring program at the time of their preoperative surgery appointment. Different follow-up methods were implemented over 3 sequential phases. Patients received Health Insurance Portability and Accountability Act-compliant web-based survey links via email (phase 1), SMS text messaging (phase 2), or concurrently using both email and SMS text messaging (phase 3) using REDCap and Twilio software. Recovery assessments using the established Quality of Recovery-9 instrument were performed 4 days before surgery and at 7 and 30 days postoperatively. Generalizability of the web-based system was examined by comparing characteristics of those who participated versus those who did not. Differences in response rates by the web-based collection method were analyzed using adjusted models. RESULTS: A total of 615 patients were asked to participate, with 526 (85.5%) opting for the follow-up program. Those who opted in were younger, slightly healthier, and more likely to be in a partnership. The concurrent mixed modes method was the most successful for obtaining responses at each time point compared with text or email alone (pre: 119/160, 74.4% vs 116/173, 67.1% vs 56/130, 43.1%, P<.001; 7 days: 115/172, 66.9% vs 82/164, 50.0% vs 59/126, 46.8%, P=.001; 30 days: 152/234, 65.0% vs 52/105, 49.5% vs 53/123, 43.1%, P=.001, respectively). In the adjusted model, the concurrent mixed modes method significantly predicted response compared with using email alone (odds ratio 3.4; P<.001) and SMS text messaging alone (odds ratio 1.9; P<.001). Additional significant predictors of response were race, partnership, and time. CONCLUSIONS: For internet users and smartphone owners, electronic capture of recovery surveys appear to be possible through this mechanism. Discrepancies in both inclusion and response rates still exist among certain subgroups of patients, but the concurrent approach of using both email and text messages was the most effective approach to reach the largest number of patients across all subgroups.

A U.S. survey of pre-operative carbohydrate-containing beverage use in colorectal enhanced recovery after surgery (ERAS) programs.

BACKGROUND: Carbohydrate-containing drinks (CCD) are administered preoperatively in most enhanced recovery after surgery (ERAS) programs. It is not known which types of CCDs are used, e.g., simple vs. complex carbohydrate, and if the choice of drink differs in patients with diabetes. METHODS: A national survey was performed to characterize the use of preoperative CCDs within the context of adult colorectal ERAS programs. The survey had questions regarding the use of preoperative CCDs, the types of beverages used, and the timing of beverage administration. The survey was administered electronically to members of the American Society for Enhanced Recovery (ASER) and manually to participants at the 2018 Perioperative Quality and Enhanced Recovery Conference in San Francisco, CA. RESULTS: Responses were received from 78 unique hospitals with a colorectal ERAS program of which 68 (87.2%) reported administering a preoperative drink. Of these, 98.5%, 80.9%, and 60.3% of hospitals administered a beverage to patients without diabetes, patients with diabetes not taking insulin, and patients with diabetes taking insulin, respectively. Surprisingly, one third of programs that administered a beverage to patients with diabetes used a simple carbohydrate drink. CONCLUSIONS: This survey finds a high use of CHO-containing beverages in colorectal ERAS programs. More than half of all programs administer a CHO-containing beverage to patients with diabetes, and surprisingly, there is significant use of simple carbohydrate beverages in patients with diabetes receiving insulin.

Types of surgical patients enrolled in enhanced recovery after surgery (ERAS) programs in the USA.

BACKGROUND: Enhanced Recovery After Surgery (ERAS) programs have gained traction across US hospitals in the past two decades. Initially implemented for elective colorectal surgical procedures, ERAS has expanded to a variety of surgical service lines. There is little information regarding the extent to which various surgical service lines use ERAS. METHODS: A survey was performed to describe the prevalence of ERAS programs across surgical service lines in the USA. The survey had questions regarding the number of ERAS programs, operating rooms (ORs) and presence of anesthesia and/or surgery residency program at an institution. The survey was administered electronically to members of the American Society for Enhanced Recovery (ASER) and manually to participants at the 2018 Perioperative Quality and Enhanced Recovery Conference in San Francisco, CA. RESULTS: Responses were received from 88 unique institutions. The most commonly reported surgical service lines were colorectal (87%), gynecology (51%), orthopedic (49%), surgical oncology (39%), and urology (35%). A significant positive association was observed between the number of ORs and the number ERAS programs (Spearman's Rho 0.5, p<0.0001). Furthermore, institutions that reported an anesthesia and/or surgery residency program had more ERAS programs (mean 5.0 ± 3.2) compared to those that did not (mean 2.0 ± 2.0) (Wilcoxon rank sum p< 0.001). CONCLUSIONS: ERAS has expanded to a large extent outside of the colorectal surgery service line with increases notable in orthopedic surgery, obstetric/gynecology, surgical oncology, and urology procedures. Institutions with a higher number of ORs and the presence of an anesthesia and/or surgery residency program are associated with an increased number of ERAS programs.

Severe Acute Respiratory Syndrome Coronavirus 2 Convalescent Plasma Versus Standard Plasma in Coronavirus Disease 2019 Infected Hospitalized Patients in New York: A Double-Blind Randomized Trial.

OBJECTIVES: Four peer-reviewed publications have reported results from randomized controlled trials of convalescent plasma for coronavirus disease 2019 infection; none were conducted in the United States nor used standard plasma as a comparator. To determine if administration of convalescent plasma to patients with coronavirus disease 2019 increases antibodies to severe acute respiratory syndrome coronavirus 2 and improves outcome. DESIGN: Double-blind randomized controlled trial. SETTING: Hospital in New York. PATIENTS: Patients with polymerase chain reaction documented coronavirus disease 2019 infection. INTERVENTIONS: Patients were randomized (4:1) to receive 2 U of convalescent plasma versus standard plasma. Antibodies to severe acute respiratory syndrome coronavirus 2 were measured in plasma units and in trial recipients. MEASUREMENTS AND MAIN RESULTS: Enrollment was terminated after emergency use authorization was granted for convalescent plasma. Seventy-four patients were randomized. At baseline, mean (sd) Acute Physiology and Chronic Health Evaluation II score (23.4 [5.6] and 22.5 [6.6]), percent of patients intubated (19% and 20%), and median (interquartile range) days from symptom onset to randomization of 9 (6-18) and 9 (6-15), were similar in the convalescent plasma versus standard plasma arms, respectively. Convalescent plasma had high neutralizing activity (median [interquartile range] titer 1:526 [1:359-1:786]) and its administration increased antibodies to severe acute respiratory syndrome coronavirus 2 by 14.4%, whereas standard plasma administration led to an 8.6% decrease (p = 0.005). No difference was observed for ventilator-free days through 28 days (primary study endpoint): median (interquartile range) of 28 (2-28) versus 28 (0-28; p = 0.86) for the convalescent plasma and standard plasma groups, respectively. A greater than or equal to 2 point improvement in the World Health Organization scale was achieved by 20% of subjects in both arms (p = 0.99). All-cause mortality through 90 days was numerically lower in the convalescent plasma versus standard plasma groups (27% vs 33%; p = 0.63) but did not achieve statistical significance. A key prespecified subgroup analysis of time to death in patients who were intubated at baseline was statistically significant; however, sample size numbers were small. CONCLUSIONS: Administration of convalescent plasma to hospitalized patients with coronavirus disease 2019 infection increased antibodies to severe acute respiratory syndrome coronavirus disease 2 but was not associated with improved outcome.

Prevalence of IgM and IgG antibodies to SARS-CoV-2 in health care workers at a tertiary care New York hospital during the Spring COVID-19 surge.

BACKGROUND: Health care workers (HCW) such as anesthesiologists, surgeons, and intensivists face high rates of exposure to SARS-CoV-2 through direct contact with COVID-19 patients. While there are initial reports of the prevalence of COVID-19 antibodies among the general population, there are few reports comparing the seroprevalence of IgM/IgG COVID-19 antibodies in HCW of different exposure levels as well as different HCW professions. METHODS: A convenience sample of health care workers provided blood for COVID-19 antibody testing and a review of medical history and work exposure for correlative analyses. RESULTS: Overall, 474 HCW were enrolled in April 2020 including 102 front-line physicians (e.g., anesthesiologists, surgeons, intensivists, emergency medicine), 91 other physicians, 135 nurses, 134 other clinical staff, and 12 non-clinical HCW. The prevalence of IgM or IgG antibodies to SARS-CoV-2 was 16.9% (95% CI 13.6-20.6) (80/474). The proportion of positive antibodies in the PCR + group was significantly higher than health care workers without symptoms (84.6% [95% CI 54.6-98.1] vs. 12.3% [95% CI 8.5-17.2], p < 0.001). No significant differences in proportions of COVID-19 antibodies were observed among the different exposure groups (e.g., high vs minimal/no exposure) and among the different HCW professionals. CONCLUSIONS: Despite exposure to COVID-19 patients, the prevalence of antibodies in our HCW was similar to what has been reported for the general population of New York State (14%) and for another New York HCW cohort (13.7%). Health care workers with higher exposure rates were not more likely to have been infected with COVID-19. Therefore, these data suggest that infection of HCW may result from exposure in the community rather than at work. TRIAL REGISTRATION: This investigator-initiated study was observational; therefore, no registration was required. Not applicable.

Mutual dependence of Candida albicans Est1p and Est3p in telomerase assembly and activation.

Telomerase is an RNA-protein complex responsible for extending one strand of the telomere terminal repeats. Analysis of the telomerase complex in budding yeasts has revealed the presence of one catalytic protein subunit (Est2p/TERT) and at least two noncatalytic components (Est1p and Est3p). The TERT subunit is essential for telomerase catalysis, while the functions of Est1p and Est3p have not been precisely elucidated. In an earlier study, we showed that telomerase derived from a Candida est1-null mutant is defective in primer utilization in vitro; it exhibits reduced initiation and processivity on primers that terminate in two regions of the telomere repeat. Here we show that telomerase derived from a Candida est3-null mutant has nearly identical defects in primer utilization and processivity. Further analysis revealed an unexpected mutual dependence of Est1p and Est3p in their assembly into the full telomerase complex, which accounts for the similarity between the mutant enzymes. We also developed an affinity isolation and an in vitro reconstitution protocol for the telomerase complex that will facilitate future mechanistic studies.

Ever shorter telomere 1 (EST1)-dependent reverse transcription by Candida telomerase in vitro: evidence in support of an activating function.

Telomerase is an RNA-protein complex responsible for the extension of one strand of the telomere terminal repeats. Analysis of the telomerase complex in the budding yeast Saccharomyces cerevisiae has revealed the presence of one catalytic protein subunit (Est2p/TERT) and at least two noncatalytic components (Est1p and Est3p). The TERT subunit is essential for telomerase function, both in vitro and in vivo. In contrast, the Est1p and Est3p subunits, although required for telomere extension in vivo, have not been shown to affect enzyme activity in vitro. We recently identified orthologues of the Saccharomyces telomerase subunits in Candida albicans (named CaTERT, CaEst1p, and CaEst3p). Analysis of telomerase from the Candida Caest1-Delta strains revealed a primer-specific defect in its activity in vitro: The mutant enzyme was impaired in its ability to extend some, but not all, telomeric primers. The CaEst1p-responsive primers have 3' ends that are clustered in two loci within the 23-bp Candida telomere repeat. The degree of CaEst1p-dependence was modulated by the length and sequence of the 5' ends. For CaEst1p-dependent primers, the wild-type enzyme consistently exhibited a greater V(max) than the mutant enzyme in kinetic studies. These results suggest that CaEst1p augments the ability of telomerase to reverse-transcribe through selected barriers in the telomere repeat by acting as an allosteric activator and provide the basis for a functional in vitro assay for a noncatalytic protein component of the telomerase complex.

Analysis of telomerase in Candida albicans: potential role in telomere end protection.

Telomerase is a ribonucleoprotein reverse transcriptase responsible for the maintenance of one strand of telomere terminal repeats. Analysis of the telomerase complex in the budding yeast Saccharomyces cerevisiae has revealed the presence of one catalytic protein subunit (Est2p/TERT) and at least two noncatalytic components (Est1p and Est3p). The genome of the pathogenic yeast Candida albicans contains putative orthologues of all three telomerase components. Disruption of each homologue resulted in significant but distinct telomere dysfunction in Candida: Similar to S. cerevisiae, the Candida EST3 disruption strain exhibits progressive telomere loss over many generations, at a rate that is consistent with incomplete replication. In contrast, telomeres in both the Candida TERT and EST1 disruption strains can contract rapidly, followed by partial or nearly complete recovery, suggesting a defect in telomere "capping." We propose that these two telomerase subunits may participate in the protection of chromosomal ends in Candida: Analysis of telomerase-mediated primer extension in vitro indicates that only the TERT protein is absolutely essential for enzyme activity. Our results support the conservation of telomerase protein components beyond the catalytic subunit but reveal species-specific phenotypic alterations in response to loss of individual telomerase component. We also identify potential homologues of Est1p in phylogenetically diverse organisms. The Est1p sequence family possesses a conserved N-terminal domain predicted to be structurally related to tetratricopeptide repeat-containing proteins.