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Introduction: Although real-world studies demonstrate that those prescribed nirmatrelvir/ritonavir (and particularly within 5 days of symptom onset) are less likely to experience severe COVID-19 outcomes, prior studies show that only a small fraction of patients with COVID-19 who are eligible for nirmatrelvir/ritonavir receive a prescription. Studies calculating the proportion of nirmatrelvir/ritonavir prescriptions filled and identifying individual- and pharmacy-level correlates of filling nirmatrelvir/ritonavir are lacking., Methods: This retrospective cohort study included individuals aged ≥ 12 years with a nirmatrelvir/ritonavir prescription ordered at a large national retail pharmacy (December 22, 2021-August 12, 2023). Those taking contraindicated medications were excluded. For those with only one nirmatrelvir/ritonavir prescription ordered, the outcome was whether the prescription was filled (yes/no). In a subanalysis of these individuals, the outcome was whether the prescription was filled within 5 days of symptom onset (yes/no). For those with multiple prescriptions ordered, the outcome was whether > 1 (vs. 0 or 1) prescriptions were filled. A log-binomial regression with generalized estimating equations was used to identify individual (clinical and demographic) and pharmacy-level (percentage of trade area that is non-Hispanic white, urbanicity, US Census region, and tract-level area deprivation index) correlates., Results: A total of 2,103,570 unique nirmatrelvir/ritonavir prescriptions were ordered for 1,985,990 individuals. Among the 95% of individuals prescribed only one nirmatrelvir/ritonavir course, 88% filled their prescription. Among those with > 1 prescription ordered, 77% (82,993/108,411) filled one and 13% (13,662/108,411) filled > 1. Patients ≥ 50 years of age and those with documented high-risk conditions were slightly more likely to fill prescriptions, regardless of whether one or multiple courses were ordered. Individuals with cancer, asthma, or taking corticosteroids or immunosuppressive medications were more likely to fill multiple prescriptions., Conclusions: Most patients filled their nirmatrelvir/ritonavir prescriptions. Interventions to improve uptake should focus on increasing patient and provider awareness, reducing nirmatrelvir/ritonavir prescribing disparities, and ensuring treatment initiation within 5 days., (© 2024. The Author(s).)

Objective: To create a data-driven definition of post-COVID conditions (PCC) by directly measure changes in symptomatology before and after a first COVID episode., Materials and Methods: Retrospective cohort study using Optum® de-identified Electronic Health Record (EHR) dataset from the United States of persons of any age April 2020-September 2021. For each person with COVID (ICD-10-CM U07.1 "COVID-19" or positive test result), we selected up to 3 comparators. The final COVID symptom score was computed as the sum of new diagnoses weighted by each diagnosis' ratio of incidence in COVID group relative to comparator group. For the subset of COVID cases diagnosed in September 2021, we compared the incidence of PCC using our data-driven definition with ICD-10-CM code U09.9 "Post-COVID Conditions", first available in the US October 2021., Results: The final cohort contained 588,611 people with COVID, with mean age of 48 years and 38% male. Our definition identified 20% of persons developed PCC in follow-up. PCC incidence increased with age: (7.8% of persons aged 0-17, 17.3% aged 18-64, and 33.3% aged 65+) and did not change over time (20.0% among persons diagnosed with COVID in 2020 versus 20.3% in 2021). For cases diagnosed in September 2021, our definition identified 19.0% with PCC in follow-up as compared to 2.9% with U09.9 code in follow-up., Conclusion: Symptom and U09.9 code-based definitions alone captured different populations. Maximal capture may consider a combined approach, particularly before the availability and routine utilization of specific ICD-10 codes and with the lack consensus-based definitions on the syndrome., Competing Interests: Dr Andersen, Mr Khan, Dr Park, Dr Wiemken, Dr Emir, Ms Malhotra, and Dr McGrath are employees of Pfizer Inc and may hold stock or stock options. Dr Alhanai and Dr Ghassemi are co-founders of Ghamut Corporation which has received consulting fees from Pfizer Inc. This does not alter our adherence to PLOS ONE policies on sharing data and materials, (Copyright: © 2024 Andersen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Data on the effectiveness of BA.4/5 bivalent vaccine stratified by age and prior infection are lacking., Methods: This test-negative study used data from individuals ≥5 years of age testing for SARS-CoV-2 with symptoms (15 September 2022 to 31 January 2023) at a large national retail pharmacy chain. The exposure was receipt of 2-4 wild-type doses and a BNT162b2 BA.4/5 bivalent vaccine (>2 months since last wild-type dose). The outcome was a positive SARS-CoV-2 test. Absolute (vs unvaccinated) and relative (vs 2-4 wild-type doses) vaccine effectiveness (VE) were calculated as (1 - adjusted odds ratio from logistic regression) × 100. VE was stratified by age and self-reported prior infection., Results: Overall, 307 885 SARS-CoV-2 tests were included (7916 aged 5-11, 16 329 aged 12-17, and 283 640 aged ≥18 years). SARS-CoV-2 positivity was 39%; 21% were unvaccinated, 70% received 2-4 wild-type doses with no bivalent vaccine, and 9% received a BNT162b2 BA.4/5 bivalent dose. At a median of 1-2 months after BNT162b2 BA.4/5 bivalent vaccination, depending on age group, absolute VE was 22%-60% and was significantly higher among those reporting prior infection (range, 55%-79%) than not (range, no protection to 50%). Relative VE was 31%-64%., Conclusions: BNT162b2 BA.4/5 bivalent showed early additional protection against Omicron-related symptomatic COVID-19, with hybrid immunity offering greater protection., Competing Interests: Potential conflicts of interest. A. E. R., F. L. K., T. L. W., L. A. P., L. J., and J. M. M. are employees and shareholders of Pfizer. A. S. and T. A. S. are employees and shareholders of Walgreens. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

This research describes the preparation of mixtures of new halogen-substituted phenol derivatives and their effects due to linkages with a fatty amide (pentanamide). The molecules were optimized using DFT, and the vibrational and electronic analysis was done subsequently. The energies of frontier molecular orbitals (FMOs) were used to estimate the global chemical reactivity parameters as we suggest that hydrogen-bonded networks may have contributed to the stability and reactivity of the compound. In addition to the experimental investigation, dielectric parameters were calculated. Fukui functions were analyzed to study the chemical reactivity. To get insight into interactions of σ → π* orbitals, natural bond orbital calculations were done. Additionally, surface analysis of the MEP and Hirshfeld charges were performed at the equivalent DFT levels. The research also indicated that both (interaction region indicator) IRI and (electron delocalize range) EDR would proficiently identify chemical-bonding and weak interaction regions, providing a significant advantage in exploring diverse chemical systems and reactions. This indicated that compounds could diffuse through noncovalent interactions, including intramolecular hydrogen bonding. Dielectric relaxation studies taken at five distinct molar ratios identified significant dielectric properties such as ε', ε″, ε 0 , and ε ∞ . The PA with FP, CP, BP, and IP molecules has potential antiviral and antioxidant benefits for carbonic anhydrase, with favorable drug-like features and diverse biological benefits. Pharmacological effects were forecasted using the PASS server, and these molecules exhibited favorable pharmacokinetic properties., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Importance: Data describing the vaccine effectiveness (VE) and durability of BNT162b2 among children 5 to 11 years of age are needed., Objective: To estimate BNT162b2 VE against SARS-CoV-2 infection among children aged 5 to 11 years during Delta and Omicron variant-predominant periods and to further assess VE according to prior SARS-CoV-2 infection status and by sublineage during the Omicron variant-predominant period., Design, Setting, and Participants: This test-negative case-control study was conducted from November 2 to December 9, 2021 (Delta variant), and from January 16 to September 30, 2022 (Omicron variant), among 160 002 children tested at a large national US retail pharmacy chain, for SARS-CoV-2 via polymerase chain reaction (PCR); 62 719 children were tested during the Delta period, and 97 283 were tested during the Omicron period., Exposure: Vaccination with BNT162b2 before SARS-CoV-2 testing vs no vaccination., Main Outcomes and Measures: The primary outcome was SARS-CoV-2 infection confirmed by PCR (regardless of the presence of symptoms), and the secondary outcome was confirmed symptomatic infection. Adjusted estimated VE was calculated from multilevel logistic regression models., Results: A total of 39 117 children tested positive and 131 686 tested negative for SARS-CoV-2 (total, 170 803; 84 487 [49%] were boys; mean [SD] age was 9 [2] years; 74 236 [43%] were White non-Hispanic or non-Latino; and 37 318 [22%] were Hispanic or Latino). Final VE analyses included 160 002 children without SARS-CoV-2 infection less than 90 days prior. The VE of 2 doses of BNT162b2 against Delta was 85% (95% CI, 80%-89%; median follow-up, 1 month) compared with the Omicron period (20% [95% CI, 17%-23%]; median follow-up, 4 months). The adjusted VE of 2 doses against Omicron at less than 3 months was 39% (95% CI, 36%-42%), and at 3 months or more, it was -1% (95% CI, -6% to 3%). Protection against Omicron was higher among children with vs without infection 90 days or more prior but decreased in all children approximately 3 months after the second dose (58% [95% CI, 49%-66%] with infection vs 37% [95% CI, 34%-41%] without infection at <3 months; 27% [95% CI, 17%-35%] with infection vs -7% [95% CI, -12% to -1%] at ≥3 months without infection). The VE of 2 doses of BNT162b2 at less than 3 months by Omicron sublineage was 40% (95% CI, 36%-43%) for BA.1, 32% (95% CI, 21%-41%) for BA.2/BA.2.12.1, and 50% (95% CI, 37%-60%) for BA.4/BA.5. After 3 months or more, VE was nonsignificant for BA.2/BA.2.12.1 and BA.4/BA.5. The VE of a booster dose was 55% (95% CI, 50%-60%) against Omicron, with no evidence of waning at 3 months or more., Conclusions and Relevance: This study suggests that, among children aged 5 to 11 years, 2 doses of BNT162b2 provided modest short-term protection against Omicron infection that was higher for those with prior infection; however, VE waned after approximately 3 months in all children. A booster dose restored protection against Omicron and was maintained for at least 3 months. These findings highlight the continued importance of booster vaccination regardless of history of prior COVID-19.

Background: Accurate detection of clinically significant prostate cancer (csPCa), Gleason Grade Group ≥ 2, remains a challenge. Prostate MRI radiomics and blood kallikreins have been proposed as tools to improve the performance of biparametric MRI (bpMRI)., Purpose: To develop and validate radiomics and kallikrein models for the detection of csPCa., Study Type: Retrospective., Population: A total of 543 men with a clinical suspicion of csPCa, 411 (76%, 411/543) had kallikreins available and 360 (88%, 360/411) did not take 5-alpha-reductase inhibitors. Two data splits into training, validation (split 1: single center, n = 72; split 2: random 50% of pooled datasets from all four centers), and testing (split 1: 4 centers, n = 288; split 2: remaining 50%) were evaluated., Field Strength/sequence: A 3 T/1.5 T, TSE T2-weighted imaging, 3x SE DWI., Assessment: In total, 20,363 radiomic features calculated from manually delineated whole gland (WG) and bpMRI suspicion lesion masks were evaluated in addition to clinical parameters, prostate-specific antigen, four kallikreins, MRI-based qualitative (PI-RADSv2.1/IMPROD bpMRI Likert) scores., Statistical Tests: For the detection of csPCa, area under receiver operating curve (AUC) was calculated using the DeLong's method. A multivariate analysis was conducted to determine the predictive power of combining variables. The values of P-value < 0.05 were considered significant., Results: The highest prediction performance was achieved by IMPROD bpMRI Likert and PI-RADSv2.1 score with AUC = 0.85 and 0.85 in split 1, 0.85 and 0.83 in split 2, respectively. bpMRI WG and/or kallikreins demonstrated AUCs ranging from 0.62 to 0.73 in split 1 and from 0.68 to 0.76 in split 2. AUC of bpMRI lesion-derived radiomics model was not statistically different to IMPROD bpMRI Likert score (split 1: AUC = 0.83, P-value = 0.306; split 2: AUC = 0.83, P-value = 0.488)., Data Conclusion: The use of radiomics and kallikreins failed to outperform PI-RADSv2.1/IMPROD bpMRI Likert and their combination did not lead to further performance gains., Level of Evidence: 1 TECHNICAL EFFICACY: Stage 2., (© 2021 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC. on behalf of International Society for Magnetic Resonance in Medicine.)

Background: The burden of noninvasive group B Streptococcus (GBS) infections in adults is unknown. We determined population-based rates of hospitalization where invasive or noninvasive GBS infections were identified among US adults in a defined catchment area., Methods: We identified adults with clinical and laboratory-confirmed evidence of GBS infection from January 2014 through December 2016 from 6 hospitals in Louisville, Kentucky. Invasive disease was defined as GBS isolated from a normally sterile site., Results: Among 1076 adults with GBS infection, the median age was 52 years, 51% were male, and 89% had ≥1 chronic medical condition. The most prevalent infection sites were skin and soft tissue (39%), urinary tract (23%), bone and joint (16%), and bloodstream (11%). Forty percent of infections were polymicrobial. The annual incidence of GBS-associated hospitalization was 73 per 100 000 adults and 68 and 100 per 100 000 for patients aged 18-64 and ≥ 65 years, respectively. For every invasive GBS infection, 3.7 noninvasive infections occurred., Conclusions: Our population-based study outlines the full burden of GBS-associated hospitalization in adults and found incidence rates comparable to those of pneumococcal disease, where vaccines are recommended. Noninvasive disease was 3-4 times more common than invasive disease, suggesting that the GBS burden among adults is considerably greater than previously recognized., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Community-acquired pneumonia (CAP) is associated with significant disease burden in adults but has not been measured uniformly. Reconciling differences across studies is critical for understanding the true burden of CAP., Methods: We performed a systematic literature review of the incidence of hospitalized CAP among US adults and described the impact of key study characteristics on these estimates., Results: After review of 8361 articles as of January 31, 2019, we identified 28 studies with 41 unique estimates of hospitalized CAP incidence. Among adults ≥65 years of age, annual rates of hospitalized CAP ranged from 847 to 3500 per 100,000 persons with median = 1830. Rates were lower in studies that excluded patients with healthcare-associated (but community-onset) pneumonia (HCAP; median = 2003 vs 1286; P = 0.02) or immunocompromising conditions (median = 1895 vs 1409; P = 0.27) compared to those that did not. Rates of CAP were also lower in studies that used more restrictive criteria for diagnosing pneumonia (eg, pneumonia coded in any diagnosis position [median = 2270] vs pneumonia coded in the first position only [median = 1375] in studies of administrative claims; P = 0.02). For adults <65 years of age, rates of CAP were lower (range: 89 to 1138 per 100,000; median = 199)., Conclusions: CAP causes a significant disease burden among adults, particularly among those ≥65 years of age. Commonly-applied exclusion criteria (eg, persons with HCAP or immunocompromising conditions) or restrictive case definitions (eg, only including pneumonias coded in the primary diagnosis position) have led to systematic underestimation of CAP incidence in many previous studies. In studies that did not apply these restrictive criteria, the rate of hospitalization was approximately 2000 per 100,000 annually. Understanding the true burden of adult CAP is critical for highlighting the ongoing need for expanded prevention programs, including vaccination., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Khan, FL, Lawal, JM, Kapture, DO, Swingle, JD, and Malek, MH. Revisiting the single-visit protocol for determining the electromyographic fatigue threshold. J Strength Cond Res 31(12): 3503-3507, 2017-The electromyographic fatigue threshold (EMGFT) has been shown to demarcate between nonfatiguing and fatiguing exercise workloads. One potential limitation of incorporating the single EMGFT test in a clinical setting is the 2-minute stage increment inherit to the protocol. In most rehabilitation clinics, time with the client is limited, and any testing procedure needs to consider this factor. The purpose of this study, therefore, was to determine whether or not the estimation of the EMGFT is influenced by reducing the incremental stage to 1-minute intervals. We hypothesized that the 1-minute incremental protocol would provide similar estimates of the EMGFT as the traditional 2-minute incremental protocol. Nine college-aged men performed the single-leg knee-extensor ergometry at 1-minute (3 W) and 2-minute (6 W) stages in random order separated by 7 days. The exercise indices and the EMGFT were determined from the 2 protocols and analyzed using a paired samples t test. The EMG amplitude was assessed from the rectus femoris muscle. The results indicated significant differences between protocols for maximal power output (1 minute: 31.7 ± 2.2 W vs. 2 minutes: 38.0 ± 3.3 W, p = 0.016) and heart rate at end exercise (1 minute: 137 ± 5 b·min vs. 2 minutes: 148 ± 5 b·min, p = 0.024). There were, however, no significant mean differences for the EMGFT (1 minute: 19.8 ± 1.8 vs. 2 minutes: 20.3 ± 1.9 W, p = 0.63) and rating of perceived exertion (RPE) for the exercised leg (1 minute: 9 ± 0 vs. 2 minutes: 9 ± 1, p = 0.68). These results indicate that reducing the exercise protocol by 50% did not change the estimated EMGFT. The practical application of this finding resides in the potential use in sports or rehabilitative settings in which there is limited time with the client and no objective measures to determine neuromuscular fatigue for aerobic exercise.

Air dispersion modeling over coastal regions has proven to be a remarkable challenge in the field of air quality. Many conventional plume dispersion models, such as ISC2 and HYSPLIT, are unable to model such dispersion with the precision that is necessary to accurately predict ground-level concentrations in coastal areas. Considering this, the present work was carried out with two primary objectives: i) to evaluate the effectiveness of currently available mathematical models in predicting plume dispersion over a coastal region and ii) to study the impact of sulfur dioxide emissions from a petroleum refinery over a different community located in the adjacent area. This study demonstrates that CALPUFF predictions are more reliable compared to those of the other models studied, however the operation of CALPUFF is highly data intensive and in many instances, it is difficult to obtain all required input data. This is a particular problem for regions outside ofthe United States of America where sufficient data is difficult to obtain. In addition, the study concluded that the predicted annual average SO2 concentrations in the nearby communities are well within regulatory limits.

Our recent studies have shown that co-activation of Gq and Gi proteins by 5-hydroxytryptamine (5-HT) and adrenaline show synergism in human platelet aggregation. This study was conducted to examine the mechanism(s) of synergistic interaction of 5-HT and platelet activating factor (PAF) in human platelets. We show that PAF, but not 5-HT, increased platelet aggregation in a concentration-dependent manner. However, low concentrations of 5-HT (2 microM) potentiated platelet aggregation induced by subthreshold concentration of PAF (40 nM) indicating a synergistic interaction between the two agonists and this synergism was blocked by receptor antagonists to either 5-HT or PAF. 5-HT also potentiated the effect of PAF on thromboxane A2 (TXA2) formation and phosphorylation of extracellularly regulated mitogen-activated protein kinases (ERK1/2). The synergism of 5-HT and PAF in platelet aggregation was inhibited by calcium (Ca2+) channel blockers, verapamil and diltiazem, phospholipase C (PLC) inhibitor, U73122, cyclooxygenase (COX) inhibitor, indomethacin, and MEK inhibitor, PD98059. These data suggest that synergistic effect of 5-HT and PAF on human platelet aggregation involves activation of PLC/Ca2+, COX and MAP kinase pathways.