The benefits of antimicrobial prophylaxis are limited to the first 24 hours postoperatively. Little is known about the harms associated with continuing antimicrobial prophylaxis after skin closure.OBJECTIVE To characterize the association of type and duration of prophylaxis with surgical site infection (SSI), acute kidney injury (AKI), and Clostridium difficile infection. DESIGN, SETTING, AND PARTICIPANTSIn this multicenter, national retrospective cohort study, all patients within the national Veterans Affairs health care system who underwent cardiac, orthopedic total joint replacement, colorectal, and vascular procedures and who received planned manual review by a trained nurse reviewer for type and duration of surgical prophylaxis and for SSI from October 1, 2008, to September 30, 2013, were included. Data were analyzed using multivariable logistic regression, with adjustments for covariates determined a priori to be associated with the outcomes of interest. Data were analyzed from December 2016 to December 2018.EXPOSURES Duration of postoperative antimicrobial prophylaxis (<24 hours, 24-<48 hours, 48-<72 hours, and Ն72 hours). MAIN OUTCOMES AND MEASURES Surgical site infection, AKI, and C difficile infection.RESULTS Of the 79 058 included patients, 76 109 (96.3%) were men, and the mean (SD) age was 64.8 (9.4) years. Among 79 058 surgical procedures in the cohort, all had SSI and C difficile outcome data available; 71 344 (90.2%) had AKI outcome data. After stratification by type of surgery and adjustment for age, sex, race, diabetes, smoking, American Society of Anesthesiologists score greater than 2, methicillin-resistant Staphylococcus aureus colonization, mupirocin, type of prophylaxis, and facility factors, SSI was not associated with duration of prophylaxis.

ImportanceFew risk factors for long-lasting (≥4 weeks) COVID-19 symptoms have been identified.ObjectiveTo determine whether high levels of psychological distress before SARS-CoV-2 infection, characterized by depression, anxiety, worry, perceived stress, and loneliness, are prospectively associated with increased risk of developing post–COVID-19 conditions (sometimes called long COVID).Design, Setting, and ParticipantsThis prospective cohort study used data from 3 large ongoing, predominantly female cohorts: Nurses’ Health Study II, Nurses’ Health Study 3, and the Growing Up Today Study. Between April 2020 and November 2021, participants were followed up with periodic surveys. Participants were included if they reported no current or prior SARS-CoV-2 infection at the April 2020 baseline survey when distress was assessed and returned 1 or more follow-up questionnaires.ExposuresDepression, anxiety, worry about COVID-19, perceived stress, and loneliness were measured at study baseline early in the pandemic, before SARS-CoV-2 infection, using validated questionnaires.Main Outcomes and MeasuresSARS-CoV-2 infection was self-reported during each of 6 monthly and then quarterly follow-up questionnaires. COVID-19–related symptoms lasting 4 weeks or longer and daily life impairment due to these symptoms were self-reported on the final questionnaire, 1 year after baseline.ResultsOf 54 960 participants, 38.0% (n = 20 902) were active health care workers, and 96.6% (n = 53 107) were female; the mean (SD) age was 57.5 (13.8) years. Six percent (3193 participants) reported a positive SARS-CoV-2 test result during follow-up (1-47 weeks after baseline). Among these, probable depression (risk ratio [RR], 1.32; 95% CI = 1.12-1.55), probable anxiety (RR = 1.42; 95% CI, 1.23-1.65), worry about COVID-19 (RR, 1.37; 95% CI, 1.17-1.61), perceived stress (highest vs lowest quartile: RR, 1.46; 95% CI, 1.18-1.81), and loneliness (RR, 1.32; 95% CI, 1.08-1.61) were each associated with post–COVID-19 conditions (1403 cases) in generalized estimating equation models adjusted for sociodemographic factors, health behaviors, and comorbidities. Participants with 2 or more types of distress prior to infection were at nearly 50% increased risk for post–COVID-19 conditions (RR, 1.49; 95% CI, 1.23-1.80). All types of distress were associated with increased risk of daily life impairment (783 cases) among individuals with post–COVID-19 conditions (RR range, 1.15-1.51).Conclusions and RelevanceThe findings of this study suggest that preinfection psychological distress may be a risk factor for post–COVID-19 conditions in individuals with SARS-CoV-2 infection. Future work should examine the biobehavioral mechanism linking psychological distress with persistent postinfection symptoms.

This cohort study assesses the association between SARS-CoV-2 vaccination and SARS-CoV-2 infections among a population of Veterans Affairs (VA) patients with cancer.

Despite their infrequent use, current data suggest that the use of prophylactic probiotics and subglottic endotracheal tubes are cost-effective for preventing VAP from the societal and hospital perspectives.

Background National and international guidelines differ about the optimal physical distancing between students for prevention of SARS-CoV-2 transmission; studies directly comparing the impact of ≥3 versus ≥6 feet of physical distancing policies in school settings are lacking. Thus, our objective was to compare incident cases of SARS-CoV-2 in students and staff in Massachusetts public schools among districts with different physical distancing requirements. State guidance mandates masking for all school staff and for students in grades 2 and higher; the majority of districts required universal masking. Methods Community incidence rates of SARS-CoV-2, SARS-CoV-2 cases among students in grades K-12 and staff participating in-person learning, and district infection control plans were linked. Incidence rate ratios (IRR) for students and staff members in districts with ≥3 versus ≥6 feet of physical distancing were estimated using log-binomial regression; models adjusted for community incidence are also reported. Results Among 251 eligible school districts, 537,336 students and 99,390 staff attended in-person instruction during the 16-week study period, representing 6,400,175 student learning weeks and 1,342,574 staff learning weeks. Student case rates were similar in the 242 districts with ≥3 feet versus ≥6 feet of physical distancing between students (IRR, 0.891, 95% CI, 0.594-1.335); results were similar after adjusting for community incidence (adjusted IRR, 0.904, 95% CI, 0.616-1.325). Cases among school staff in districts with ≥3 feet versus ≥6 feet of physical distancing were also similar (IRR, 1.015, 95% CI, 0.754-1.365). Conclusions Lower physical distancing policies can be adopted in school settings with masking mandates without negatively impacting student or staff safety.

BackgroundThe optimal regimen for perioperative antimicrobial prophylaxis is controversial. Use of combination prophylaxis with a beta-lactam plus vancomycin is increasing; however, the relative risks and benefits associated with this strategy are unknown. Thus, we sought to compare postoperative outcomes following administration of 2 antimicrobials versus a single agent for the prevention of surgical site infections (SSIs). Potential harms associated with combination regimens, including acute kidney injury (AKI) and Clostridium difficile infection (CDI), were also considered.Methods and findingsUsing a multicenter, national Veterans Affairs (VA) cohort, all patients who underwent cardiac, orthopedic joint replacement, vascular, colorectal, and hysterectomy procedures during the period from 1 October 2008 to 30 September 2013 and who received planned manual review of perioperative antimicrobial prophylaxis regimen and manual review for the 30-day incidence of SSI were included. Using a propensity-adjusted log-binomial regression model stratified by type of surgical procedure, the association between receipt of 2 antimicrobials (vancomycin plus a beta-lactam) versus either single agent alone (vancomycin or a beta-lactam) and SSI was evaluated. Measures of association were adjusted for age, diabetes, smoking, American Society of Anesthesiologists score, preoperative methicillin-resistant Staphylococcus aureus (MRSA) status, and receipt of mupirocin. The 7-day incidence of postoperative AKI and 90-day incidence of CDI were also measured. In all, 70,101 procedures (52,504 beta-lactam only, 5,089 vancomycin only, and 12,508 combination) with 2,466 (3.5%) SSIs from 109 medical centers were included. Among cardiac surgery patients, combination prophylaxis was associated with a lower incidence of SSI (66/6,953, 0.95%) than single-agent prophylaxis (190/12,834, 1.48%; crude risk ratio [RR] 0.64, 95% CI 0.49, 0.85; adjusted RR 0.61, 95% CI 0.46, 0.83). After adjusting for SSI risk, no association between receipt of combination prophylaxis and SSI was found for the other types of surgeries evaluated, including orthopedic joint replacement procedures. In MRSA-colonized patients undergoing cardiac surgery, SSI occurred in 8/346 (2.3%) patients who received combination prophylaxis versus 4/100 (4.0%) patients who received vancomycin alone (crude RR 0.58, 95% CI 0.18, 1.88). Among MRSA-negative and -unknown cardiac surgery patients, SSIs occurred in 58/6,607 (0.9%) patients receiving combination prophylaxis versus 146/10,215 (1.4%) patients who received a beta-lactam alone (crude RR 0.61, 95% CI 0.45, 0.83). Based on these associations, the number needed to treat to prevent 1 SSI in MRSA-colonized patients is estimated to be 53, compared to 176 in non-MRSA patients. CDI incidence was similar in both exposure groups. Across all types of surgical procedures, risk of AKI was increased in the combination antimicrobial prophylaxis group (2,971/12,508 [23.8%] receiving combination versus 1,058/5,089 [20.8%] receiving vancomycin alone...

The RNA genome of the hepatitis C virus (HCV) undergoes rapid evolutionary change. Efforts to control this virus would benefit from the advent of facile methods to identify characteristic features of HCV RNA and proteins, and to condense the vast amount of mutational data into a readily interpretable form. Many HCV sequences are available in GenBank. To facilitate analysis, consensus sequences were constructed to eliminate the overrepresentation of certain genotypes, such as genotype 1, and a novel package of sequence analysis tools was developed. Mutation Master generates profiles of point mutations in a population of sequences and produces a set of visual displays and tables indicating the number, frequency, and character of substitutions. It can be used to analyze hundreds of sequences at a time. When applied to 255 HCV core protein sequences, Mutation Master identified variable domains and a series of mutations meriting further investigation. It flagged position 4, for example, where 90% or more of all sequences in genotypes 1, 2, 4, and 5, have N4, whereas those in genotypes 3, 6, 7, 8, 9, and 10 have L4. This pattern is noteworthy: L (hydrophobic) to N (polar) substitutions are generally rare, and genotypes 1, 2, 4, and 5 do not form a recognized super family of sequences. Thus, the L4N substitution probably arose independently several times. Moreover, not one member of genotypes 1, 2, 4, or 5 has L4 and not one member of genotypes 3, 6, 7, 8, 9, or 10 has N4. This nonoverlapping pattern suggests that coordinated changes at position 4 and a second site are required to yield a viable virus. The package generated a table of genotype-specific substitutions whose future analysis may help to identify interacting amino acids. Three substitutions were present in 100% of genotype 2 members and absent from all others: A68D, R74K, and R114H. Finally, this study revealed thatARFP, a novel protein encoded in an overlapping reading frame, is as conserved as conventional HCV proteins, a result supporting a role for ARFP in the viral life cycle. Whereas most conventional programs for phylogenetic analysis of sequences provide information about overall relatedness of genes or genomes, this program highlights and profiles point mutations. This is important because determinants of pathogenicity and drug susceptibility are likely to result from changes at only one or two key nucleotides or amino acid sites, and would not be detected by the type of pairwise comparisons that have usually been performed on HCV to date. This study is the first application of Mutation Master, which is now available upon request (http://tandem.biomath.mssm.edu/mutationmaster.html).

ImportanceWith a large proportion of the US adult population vaccinated against SARS-CoV-2, it is important to identify who remains at risk of severe infection despite vaccination.ObjectiveTo characterize risk factors for severe COVID-19 disease in a vaccinated population.Design, Setting, and ParticipantsThis nationwide, retrospective cohort study included US veterans who received a SARS-CoV-2 vaccination series and later developed laboratory-confirmed SARS-CoV-2 infection and were treated at US Department of Veterans Affairs (VA) hospitals. Data were collected from December 15, 2020, through February 28, 2022.ExposuresDemographic characteristics, comorbidities, immunocompromised status, and vaccination-related variables.Main Outcomes and MeasuresDevelopment of severe vs nonsevere SARS-CoV-2 infection. Severe disease was defined as hospitalization within 14 days of a positive SARS-CoV-2 diagnostic test and either blood oxygen level of less than 94%, receipt of supplemental oxygen or dexamethasone, mechanical ventilation, or death within 28 days. Association between severe disease and exposures was estimated using logistic regression models.ResultsAmong 110 760 patients with infections following vaccination (97 614 [88.1%] men, mean [SD] age at vaccination, 60.8 [15.3] years; 26 953 [24.3%] Black, 11 259 [10.2%] Hispanic, and 71 665 [64.7%] White), 10 612 (9.6%) had severe COVID-19. The strongest association with risk of severe disease after vaccination was age, which increased among patients aged 50 years or older with an adjusted odds ratio (aOR) of 1.42 (CI, 1.40-1.44) per 5-year increase in age, such that patients aged 80 years or older had an aOR of 16.58 (CI, 13.49-20.37) relative to patients aged 45 to 50 years. Immunocompromising conditions, including receipt of different classes of immunosuppressive medications (eg, leukocyte inhibitor: aOR, 2.80; 95% CI, 2.39-3.28) or cytotoxic chemotherapy (aOR, 2.71; CI, 2.27-3.24) prior to breakthrough infection, or leukemias or lymphomas (aOR, 1.87; CI, 1.61-2.17) and chronic conditions associated with end-organ disease, such as heart failure (aOR, 1.74; CI, 1.61-1.88), dementia (aOR, 2.01; CI, 1.83-2.20), and chronic kidney disease (aOR, 1.59; CI, 1.49-1.69), were also associated with increased risk. Receipt of an additional (ie, booster) dose of vaccine was associated with reduced odds of severe disease (aOR, 0.50; CI, 0.44-0.57).Conclusions and RelevanceIn this nationwide, retrospective cohort of predominantly male US Veterans, we identified risk factors associated with severe disease despite vaccination. Findings could be used to inform outreach efforts for booster vaccinations and to inform clinical decision-making about patients most likely to benefit from preexposure prophylaxis and antiviral therapy.