Days Of Symptom Onset Research Articles

Non-invasive SARS-CoV-2 RNA detection and human transcriptome analysis using skin surface lipids

There have been several reports of skin manifestations in patients with coronavirus disease 2019 (COVID-19). However, it is unclear whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA can be detected on the skin surface, including the sebum, of these patients. In this study, SARS-CoV-2 RNA was detected using real-time reverse-transcription polymerase chain reaction (RT-PCR) assay of skin surface lipids (SSLs) collected using an oil-blotting film from the faces of hospitalized patients with COVID-19. Human transcriptome analysis was also performed using the same samples. In facial SSLs of patients with COVID-19, the RT-PCR positivity rate was 84.6% (11/13 samples) within 5 days and 30.4% (7/23 samples) by 6–10 days of symptom onset. In the transcriptome analysis, the most characteristic SSL-RNA profile was the upregulation of interferon-stimulated gene (ISG)-related genes, such as ISG15, IFITM1, and MX1. This study presents an alternative technique using SSLs for non-invasive SARS-CoV-2 RNA detection and simultaneous analysis of human molecular pathogenesis in patients with COVID-19.

A multicenter, randomized, double-blind, placebo-controlled trial to evaluate the effect of Tongmai Yangxin pill on ventricular remodeling in acute anterior STEMI patients after primary PCI

BackgroundAcute ST-segment elevation myocardial infarction (STEMI) is a severe form of coronary heart disease and a leading cause of mortality and morbidity. This can mainly be ascribed to adverse ventricular remodeling (VR). However, the efficacy of existing treatment strategies for STEMI is not entirely satisfactory. Tongmai Yangxin Pill (TMYX), a patented traditional Chinese medicine (TCM), has been approved for treating various cardiovascular diseases. PurposeThe purpose was to assess the effect of TMYX on VR in acute STEMI patients undergoing primary percutaneous coronary intervention (PPCI). Study DesignA multicenter, randomized, double-blinded, and placebo-controlled trial conducted across 11 hospitals in China. MethodA total of 270 patients with acute anterior STEMI, undergoing PPCI within 10 days of symptom onset were enrolled and randomly assigned to receive either a placebo or TMYX, in addition to guideline-directed treatments for STEMI. The primary endpoint was a change in left ventricular end-diastolic volume index (LVEDVI) at 12 weeks. ResultAmong the 270 randomized patients, 218 (TMYX: 109 and placebo: 109) were included in the per-protocol analysis. At 4 and 12 weeks, TXMY significantly improved LVEDVI than the placebo group ([-2.17(-9.24, 8.28) vs. 3.76(-2.38, 11.48), p < 0.05] and [-1.17 (-12.19, 12.88) vs. 4.46 (-2.89, 11.99), p < 0.05]). Changes in left ventricular end-diastolic volume (LVEDV) at 4 weeks were superior in the TMYX group than the placebo group (-4.37 (-17, 13.99) vs. 7.41 (-4.56, 21.79), p < 0.05). Cardiac magnetic resonance imaging (CMRI) showed that left ventricular ejection fraction (LVEF) was significantly greater in the TMYX group than in the placebo group at 4 weeks. There were no statistically significant differences between groups for left ventricular end-systolic volume (LVESV), left ventricular end-systolic volume index (LVESVI), 6 min walking distance (6MWD), and major adverse cardiac and cerebrovascular events (MACCEs) (p > 0.05). ConclusionTMYX, as an adjunctive therapy in addition to STEMI guideline-directed treatments, significantly delayed VR in patients with acute anterior STEMI undergoing PPCI within 10 days of symptom onset.

Outcomes and Healthcare Resource Utilization in Patients with COVID-19 Treated with Nirmatrelvir-Ritonavir: Real-World Data Analysis.

Background: Nirmatrelvir-ritonavir was granted emergency use authorization in Israel in January 2022 to treat high-risk patients with mild-to-moderate COVID-19. The aim of the study was to assess the association between nirmatrelvir-ritonavir treatment and COVID-19-related hospitalization and healthcare resource utilization (HCRU) in a country with a high level of vaccinations compared to patients who were offered treatment and declined. Methods: The Maccabi Healthcare Services dataset was used to identify high-risk SARS-CoV-2-positive adults from January to February 2022 who received nirmatrelvir-ritonavir within 5 days of symptom onset (treatment group) or who were offered nirmatrelvir-ritonavir treatment and declined it (reference group). COVID-19-related hospitalizations and all-cause mortality and HCRU within 30 days were compared between treatment and reference groups using inverse probability of treatment weighting. Results: Treatment and reference groups included 3460 (median age, 68.4 years) and 1654 (70.2 years) patients, respectively. Patients with ≥1 dose of COVID-19 vaccine accounted for 89.5% (treatment group) and 72.1% (reference group) of the total. Treatment was associated with a lower risk of COVID-19-related hospitalization (adjusted OR, 0.59 [95% CI, 0.41,0.83]). Results were similar by age group (18-64/≥65 years) and among patients with/without vaccination in the prior 180 days. There were 11 (0.3%) versus 11 (0.7%) deaths in the treatment and reference groups, respectively. Treated patients had lower inpatient HCRU and greater less intensive outpatient HCRU (e.g., telemedicine and emergency room visits). Conclusions: Nirmatrelvir-ritonavir treatment was associated with a reduced risk of COVID-19-related hospitalization and a shift to less intensive outpatient HCRU. Comparison with a reference group of nirmatrelvir-ritonavir-eligible patients who declined treatment enabled an unbiased outcome assessment. Real-world data gathered during the Omicron BA.1 variant wave of COVID-19 in Israel support the continued use of nirmatrelvir-ritonavir for high-risk adults of all ages, regardless of previous vaccinations.

Effectiveness of remdesivir in patients with COVID-19 and severe renal insufficiency: a nationwide cohort study in Japan

Background The effectiveness of remdesivir in patients with coronavirus disease 2019 (COVID-19) and severe renal insufficiency remains underexplored. Objectives To evaluate whether remdesivir reduces the risk of mortality or invasive mechanical ventilation/extracorporeal membrane oxygenation (IMV/ECMO) in this population. Methods This retrospective observational study utilising the COVID-19 Registry Japan (COVIREGI-JP) included noncritical patients with COVID-19 and severe renal insufficiency (defined as serum creatinine levels ≥3 mg/dL, on maintenance dialysis, or kidney transplant recipients) admitted to Japanese hospitals within 7 days of symptom onset between January 1, 2020 and May 8, 2023. Patients were classified into the remdesivir group if remdesivir was initiated within the first 2 days of admission. We estimated the multivariable-adjusted hazard ratio (HR) for mortality and initiation of IMV/ECMO using landmark analysis to address immortal time bias. Results Among the 1,449 patients included in the landmark analysis (median age, 74 years [interquartile range 62–84 years]; 992 [68.5%] were male), 272 initiated remdesivir within the first 2 days of admission. During the 28 days from the landmark timepoint, 19 (7.0%) and 136 (11.6%) patients in the remdesivir and control groups, respectively, had an outcome. The remdesivir group had a lower risk of mortality or IMV/ECMO initiation than the control group (adjusted HR, 0.44; 95% confidence interval, 0.23–0.83). Conclusions In noncritical patients with COVID-19 and severe renal insufficiency at admission, initiating remdesivir early after disease onset, within the first 2 days of admission, led to a lower risk of mortality or IMV/ECMO initiation, compared with non-initiation of remdesivir.

Outcome differences of starting Paxlovid for COVID-19 within or after five days of symptoms onset in the elderly: a retrospective study.

The study aimed to compare the outcomes of nirmatrelvir and ritonavir drug combination (Paxlovid) therapy in patients who received treatment within or after five days of COVID-19 confirmed in the elderly. This was a single-center, retrospective cohort study of older COVID-19 patients (≥ 60 years) admitted from April 7 to May 30, 2022. Patients were categorized into the EP group (starting Paxlovid within five days) and the LP group (starting Paxlovid after five days) following symptoms onset. Length of stay and positive SARS-CoV-2 duration were compared between the two groups. Severe case conversion from mild and moderate COVID-19 patients were also analyzed. In total, 273 patients were included: 137 in the EP group and 136 in the LP group. Compared to the LP group, the EP group had a significantly shorter length of stay (12.4 vs. 14.7 days, p = 0.001) and positive SARS-CoV-2 duration (11.7 vs. 15.8 days, p < 0.001). The EP group had lower severe case conversion (4.4% vs. 15.4%, p = 0.002). Additionally, abnormal IL-6 and lower lymphocyte count indicated increased length of stay. Older age was associated with a decreased risk in SARS-CoV-2 negative test (HR = 0.98) and an increased risk in severe case conversion (OR = 1.11). Starting Paxlovid within five days of COVID-19 symptoms onset reduced the length of stay and SARS-CoV-2 duration compared to initiating treatment after five days. While severe case conversion among mild COVID-19 patients might be comparable whether starting Paxlovid within or after five days.

Effect of brimonidine on visual indices in patients with acute optic neuritis: A single blind randomized clinical trial

PurposeThis study investigates brimonidine's potential effect on visual functions, particularly contrast sensitivity (CS), an indicator of retinal ganglion cell function. MethodsIn this single-blind, randomized clinical trial, 60 patients (aged 23–56) with first-episode acute optic neuritis within seven days of symptom onset were randomly assigned to brimonidine or control groups. The intervention group received brimonidine three times daily for three months, while the control group received synthetic tears with the same dosage and frequency. Primary outcomes were changes in CS, visual acuity (VA), and color vision at one and three months post-treatment. Repeated measures ANOVA was used to assess statistically significant and partial eta squared (η2) values, mean differences, and clinically significance important were reported. ResultsAll participants completed the study without complications. VA improved significantly in both groups by follow-up end (p < 0.001), with significant improvement from first to third month only in the brimonidine group (p < 0.001). The mean VA difference between groups was not statistically and clinically significant. CS showed statistically significant improvement within both groups (p < 0.001) and between groups (p < 0.001), with a large effect size (partial η2 = 0.28). The mean CS difference between groups (14.5) was clinically considerable. No significant changes in color vision were observed between groups (p = 0.96). ConclusionBrimonidine significantly improved contrast sensitivity compared to placebo and was well-tolerated. Its neuroprotective effects suggest it may be beneficial in treating optic neuritis and preserving retinal ganglion cell function. Trial registrationProspectively registered at Iranian Clinical Trial Registration; Registration date 3 December 2022; Registration number: IRCT20221127056631N1

Assessing the Utility of Prediction Scores PAINT, ISARIC4C, CHIS, and COVID-GRAM at Admission and Seven Days after Symptom Onset for COVID-19 Mortality.

The COVID-19 pandemic underscores the need for accurate prognostic tools to predict patient outcomes. This study evaluates the effectiveness of four prominent COVID-19 prediction scores-PAINT, ISARIC4C, CHIS, and COVID-GRAM-at two critical time points: at admission and seven days post-symptom onset, to assess their utility in predicting mortality among hospitalized patients. Conducted at the Clinical Emergency Hospital Pius Brînzeu in Timișoara, this retrospective analysis included adult patients hospitalized with confirmed SARS-CoV-2 infection. Eligible patients had complete data for the scores at both time points. Statistical analysis involved ROC curves and logistic regression to assess the scores' predictive accuracy for mortality. The study included 215 patients, split into 139 survivors and 76 non-survivors. At admission, the PAINT, ISARIC4C, CHIS, and COVID-GRAM scores significantly differentiated between the survival outcomes (p < 0.0001). The best cutoff values at admission were 6.26 for PAINT, 7.95 for ISARIC4C, 5.58 for CHIS, and 0.63 for COVID-GRAM, corresponding to sensitivities of 85.47%, 80.56%, 88.89%, and 83.33% and specificities of 77.34%, 82.12%, 75.01%, and 78.45%, respectively. By day seven, the cutoff values increased, indicating deteriorating conditions in patients who eventually succumbed to the virus. The hazard ratios at admission for exceeding these cutoffs were significant: PAINT (HR = 3.45), ISARIC4C (HR = 2.89), CHIS (HR = 4.02), and COVID-GRAM (HR = 3.15), highlighting the scores' abilities to predict severe outcomes. One week post symptom onset, these scores' predictive values and corresponding hazard ratios increased, further validating their prognostic significance over time. The evaluated COVID-19 prediction scores robustly predict mortality at admission and become more predictive by the seventh day of symptom onset. These findings support the use of these scores in clinical settings to facilitate early identification and intervention for high-risk patients, potentially improving patient outcomes during the ongoing global health crisis.

Rescue therapy of early neurological deterioration in lacunar stroke

BackgroundEarly neurological deterioration (END) occurs in many patients with acute ischemic stroke due to a variety of causes. Although pharmacologically induced hypertension (PIH) and anticoagulants have been investigated in several clinical trials for the treatment of END, the efficacy and safety of these treatments remain unclear. Here, we investigated whether PIH or anticoagulation is better as a rescue therapy for the progression of END in patients with lacunar stroke.MethodsThis study included patients with lacunar stroke who received rescue therapy with END within 3 days of symptom onset between April 2014 and August 2021. In the PIH group, phenylephrine was administered intravenously for 24 h and slowly tapered when symptoms improved or after 5 days of PIH. In the anticoagulation group, argatroban was administered continuously intravenously for 2 days and twice daily for next 5 days. We compared END recovery, defined as improvement in NIHSS from baseline, excellent outcomes (0 or 1 mRS at 3 months), and safety profile.ResultsAmong the 4818 patients with the lacunar stroke, END occurred in 147 patients. Seventy-nine patients with END received PIH (46.9%) and 68 patients (46.3%) received anticoagulation therapy. There was no significant difference in age (P = 0.82) and sex (P = 0.87) between the two groups. Compared to the anticoagulation group, the PIH group had a higher incidence of END recovery (77.2% vs. 51.5%, P < 0.01) and excellent outcomes (34.2% vs. 16.2%, P = 0.04). PIH was associated with END (HR 2.49; 95% CI 1.06–5.81, P = 0.04). PIH remained associated with END recovery (adjusted HR 3.91; 95% CI 1.19–12.90, P = 0.02). Safety outcomes, like hemorrhagic conversion and mortality, were not significantly different between the two groups.ConclusionsAs a rescue therapy for the progression of END in lacunar stroke patients, PIH with phenylephrine was more effective with similar safety compared to anticoagulation with argatroban.

Early antiviral CD4 and CD8 T cell responses and antibodies are associated with upper respiratory tract clearance of SARS-CoV-2.

T cells are involved in protective immunity against numerous viral infections. Data regarding functional roles of human T cells in SARS-CoV-2 (SARS2) viral clearance in primary COVID-19 are limited. To address this knowledge gap, samples were assessed for associations between SARS2 upper respiratory tract viral RNA levels and early virus-specific adaptive immune responses for 95 unvaccinated clinical trial participants with acute primary COVID-19 aged 18-86 years old, approximately half of whom were considered high risk for progression to severe COVID-19. Functionality and magnitude of acute SARS2-specific CD4 and CD8 T cell responses were evaluated, in addition to antibody responses. Most individuals with acute COVID-19 developed SARS2-specific T cell responses within 6 days of COVID-19 symptom onset. Early CD4 T cell and CD8 T cell responses were polyfunctional, and both strongly associated with reduced upper respiratory tract SARS2 viral RNA, independent of neutralizing antibody titers. Overall, these findings provide evidence for protective roles for circulating SARS2-specific CD4 and CD8 T cells during acute COVID-19.

Impact of Systolic Blood Viscosity on Deep White Matter Hyperintensities in Patients With Acute Ischemic Stroke.

Elevated blood viscosity (BV), a critical determinant in blood rheology, is a contributing factor in cerebrovascular diseases. The specific influence of BV on small vessel disease burden remains unexplored. This study aims to examine the relationship between BV and regional white matter hyperintensity (WMH) volume in patients with acute ischemic stroke. We enrolled a cohort of 302 patients with acute ischemic stroke or transient ischemic attack who were admitted to a hospital within 7 days of symptom onset in this study. We measured whole BV using a scanning capillary-tube viscometer and categorized systolic blood viscosity into 3 groups based on established references. We quantified and normalized WMH volumes using automated localization and segmentation software by NEUROPHET Inc. We performed multivariable logistic regression analysis to assess the correlation between systolic BV and WMH. The mean subject age was 66.7±13.4 years, and 38.7% (n=117) of the participants were female. Among a total of 302 patients, patients with higher deep WMH volume (T3) were typically older and had an atrial fibrillation, strokes of cardioembolic or undetermined cause, elevated levels of C-reactive protein, diastolic blood viscosity and systolic BV. A multivariable adjustment revealed a significant association between high systolic BV and increased deep-WMH volume (odds ratio [OR], 2.636 [95% CI, 1.225-5.673]). Elevated systolic BV is more likely to be associated with deep WMH volume in patients with acute ischemic stroke or transient ischemic attack. These findings reveal novel therapeutic strategies focusing on blood rheology to enhance cerebral microcirculation in stroke management.

Clinical and radiological features of a cluster of immunocompetent adolescents with varicella pneumonia: a descriptive study.

Varicella pneumonia is one of the most common and severe complications of chickenpox infection. This study aimed to describe the clinical and radiological features of varicella pneumonia in a cluster of immunocompetent adolescents. A retrospective analysis was conducted on a cohort of adolescent patients diagnosed with varicella pneumonia at Wuhan Jinyintan Hospital between February 2023 and May 2023. The clinical and imaging data were collected and analyzed. A total of 116 patients were divided into two groups by the absence (group 1, n=57) or presence (group 2, n=59) of lower respiratory symptoms for data comparison. Among 116 patients (median age, 16 years; 60 males), rash (100%) was the most prevalent clinical symptom. The most common respiratory symptom and sign were fever (42.2%) and coarse breath sounds (41.4%). Chest computed tomography (CT) performed within five days of symptoms onset revealed multiple (89.7%), peripheral (51.7%), and ill-defined (73.3%) lung nodules in most patients, which gradually improved 6-10 days after symptom onset. Group 2 had higher levels of interleukin-6 (P<0.001), C-reactive protein (P=0.02), serum amyloid-A protein (P=0.002), longer hospital stays (P=0.04), more involved lung lobes (P=0.02), and a higher incidence of multiple nodules (P=0.043) than those of group 1. In immunocompetent adolescents, clustered varicella pneumonia often presents as mild and more uniform in clinical and radiological presentations than sporadic cases. The most common CT findings were multiple pulmonary nodules. Patients with lower respiratory symptoms exhibited more severe clinical and radiological manifestations. Generally, it is not recommended that patients undergo frequent CT scans in a short period.

EVALPAX: Evaluation of a pharmacist-driven protocol for nirmatrelvir/ritonavir prescribing in a community hospital system.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. The purpose of this study was to evaluate pharmacist prescribing of nirmatrelvir/ritonavir to ensure this method of increasing access to treatment is safe and effective. This multicenter, retrospective observational study included patients receiving a prescription for nirmatrelvir/ritonavir by a physician, nurse practitioner (NP), physician assistant (PA), or pharmacist at an Indiana University (IU) Health West Central Region site over a 3-month period. Patients were divided into two groups: those who received nirmatrelvir/ritonavir prescribed by a pharmacist (the pharmacist prescribed group) and those who received nirmatrelvir/ritonavir prescribed by other providers (the physician/NP/PA prescribed group). Electronic health record (EHR) reviews were performed to assess the appropriateness of prescriptions based on the presence of risk factors and symptoms, day of symptom onset, and dosing. The primary endpoint was the overall appropriateness of nirmatrelvir/ritonavir prescriptions in the two study groups based on emergency use authorization inclusion and exclusion requirements. Secondary endpoints included appropriateness of nirmatrelvir/ritonavir dosing and medically attended visits or mortality within 30 days. Statistical analysis of the endpoints occurred post hoc utilizing the Fisher's exact test. A total of 259 patients were included in the pharmacist prescribed group and 265 patients in the physician/NP/PA prescribed group. Overall appropriate nirmatrelvir/ritonavir prescribing occurred in 258 patients (99.6%) and 232 patients (87.5%) in the pharmacist and physician/NP/PA prescribed groups, respectively (P < 0.0001). Nirmatrelvir/ritonavir dosing was appropriate in 256 patients (98.8%) and 240 patients (90.6%) in the pharmacist and physician/NP/PA prescribed groups, respectively (P < 0.0001). The 30-day rates of medically attended visits were similar between groups. No patients died within 30 days of treatment in either group. Pharmacist prescribing of nirmatrelvir/ritonavir may result in a higher likelihood of prescriptions meeting overall appropriateness criteria. Pharmacists represent an important healthcare professional resource to improve nirmatrelvir/ritonavir prescribing and utilization.

Clinical impact of hyperbaric oxygen therapy combined with steroid treatment for sudden sensorineural hearing loss: A case-control study.

The aim of present study was to evaluate the clinical efficacy of hyperbaric oxygen therapy (HBOT) as a primary therapy combined with standard systemic corticosteroid treatment for sudden sensorineural hearing loss (SSNHL) compared to treatment without the use of HBOT (non-HBOT) through clinical data and advanced analytical approaches. Case-control study. Conducted across three Japanese medical centers involving 298 SSNHL patients diagnosed between 2020 and 2023. Inclusion criteria encompassed first onset and treatment, WHO grade 3 or 4 initial hearing impairment, receipt of systemic corticosteroid therapy within 14 days of symptom onset, and initiation of HBOT within the same timeframe for the case group. The primary outcome measure was the difference in hearing improvement (mean hearing level in decibels, dB) between the two groups, assessed by pure-tone audiometry at baseline and 3 months post-treatment, using the inverse probability of treatment weighting (IPTW) method adjusted for covariate differences. The study included 67 patients in the HBOT group and 68 in the non-HBOT group. The HBOT group exhibited significantly greater hearing improvement (IPTW-adjusted difference: 7.6 dB, 95% CI 0.4-14.7; p = 0.038). Patients without vertigo in the HBOT group demonstrated substantial hearing improvement (11.5 dB, 95% CI 2.3-20.6; p = 0.014), whereas those with vertigo showed no significant improvement (-1.8 dB, 95% CI -11.8-8.3; p = 0.729). The HBOT group also had a significantly higher association with complete recovery (IPTW-adjusted odds ratio: 2.57, 95% CI 1.13-5.85; p = 0.025). In SSHNL, HBOT combination therapy yielded slightly but significantly improved hearing outcomes compared to non-HBOT treatment. 4.

Evaluating Serum Copeptin as a Promising Biomarker for Predicting Acute Ischaemic Stroke Severity: A Hospital-Based Study on Strokes.

Stroke is the second cause of mortality and the foremost leading cause of disability globally. Many potential biomarkers have been described to contribute to prognosticating the severity in the acute phase of stroke as well as help with risk stratification. Copeptin, an inactive peptide that is produced in an equimolar ratio to arginine vasopressin and adequately mirrors an individual's stress response to acute illnesses like acute ischaemic stroke as evidenced by elevated or increasing levels is being explored in this study to determine its relationship with acute stroke severity and infarct size on admission. This is a cross-sectional study of 80 neuroimaging-confirmed acute ischaemic patients who presented within seven days of symptom onset and 80 control subjects. The ischaemic stroke cases had stroke severity and infarct volume determined on admission by the National Institute of Health Stroke Scale (NIHSS) and neuroimaging (brain CT/MRI). A baseline serum copeptin level was measured in the study subjects. Spearman correlation and Kruskal Wallis test were used to determine the relationship between serum copeptin level with admission NIHSS and infarct size respectively. The receiver operating characteristic (ROC) curve was calculated to determine the sensitivity and specificity of copeptin to predict severity and outcome. The mean age of the study group was 61.3 ± 12.7 years with 55.0% males and 45.0% females. The serum level of copeptin was significantly higher in the stroke cases with a median of 28.6 pmol/L (interquartile range (IQR)- 15.4-31.6 pmol/L) versus 8.8 pmol/L (IQR- 3.2- 10.7 pmol/L) among the stroke-free controls (p= 0.001) at a statistically significant level. There was a weak correlation between copeptin and NIHSS calculated at admission to measure stroke severity (r- 0.02, p= 0.873). Patients with infarct sizes in the fourth quartile (infarct sizes greater than 18.78 cm3) had higher copeptin levels, though this was not statistically significant (H= 2.88; p= 0.410). Admission serum copeptin did not show a statistically significant prognostic value in predicting stroke severity and mortality in stroke patients who presented within seven days of symptomonset with an area under curve (AUC) of 0.51 (95% CI: 0.36-0.65; p= 0.982). In this study, copeptin was higher among the stroke cases compared with the stroke-free controls which suggests a significant prognostic value in risk stratification in the acute phase of stroke; however, this did not significantly correlate with stroke severity and thus warrants further study in this field to elucidate it's fascinating potential as a prognostic biomarker (especially in the acute period) as this may enable allocation of a better-focused therapy for stroke patients.

Clinical outcomes and considerations in outpatient with COVID-19 receiving remdesivir therapy.

This retrospective cross-sectional study aimed to assess the outcomes of Covid-19 patients who received remdesivir therapy at the outpatient department of Ziaian Hospital. A total of 514 eligible patients were included between May and September 2021. Covid-19 diagnosis was confirmed through positive SARS-COV-2 PCR tests or chest CT scans. Due to limited hospital beds, patients received remdesivir on an outpatient basis. Patients received six daily doses of remdesivir for 5 days. Those referred to a physician within 7 days of symptom onset had similar hospitalization rates compared to later referrals. Lower blood saturation levels were associated with a higher likelihood of hospital admission, indicating that earlier administration of remdesivir may be more effective. Patients with over 50% lung involvement had higher rates of disease progression despite treatment. Corticosteroids did not significantly improve outcomes in patients with saturation above 90%. Discontinuation of remdesivir due to side effects was rare, with only 1% experiencing increased liver enzymes, 1.2% facial redness and tremors, and 1.5% allergies. After 1 week of treatment, patients commonly reported symptoms such as hair loss, fatigue, body pain, lethargy, and anorexia, particularly among hospitalized patients. Patients generally preferred outpatient treatment over hospitalization. Body mass index (BMI) did not significantly impact hospitalization rates, although average weight tended to be higher among inpatients. The study confirmed the effectiveness of remdesivir therapy with a low occurrence of side effects. This retrospective study evaluated the outcomes of Covid-19 patients receiving remdesivir at an outpatient department. Early administration of remdesivir showed better outcomes, while corticosteroids had limited benefits. Outpatient treatment was favored, and BMI did not significantly influence hospitalization rates. Remdesivir demonstrated efficacy with a low incidence of side effects.

A unifying model to explain frequent SARS-CoV-2 rebound after nirmatrelvir treatment and limited prophylactic efficacy

In a pivotal trial (EPIC-HR), a 5-day course of oral ritonavir-boosted nirmatrelvir, given early during symptomatic SARS-CoV-2 infection (within three days of symptoms onset), decreased hospitalization and death by 89.1% and nasal viral load by 0.87 log relative to placebo in high-risk individuals. Yet, nirmatrelvir/ritonavir failed as post-exposure prophylaxis in a trial, and frequent viral rebound has been observed in subsequent cohorts. We develop a mathematical model capturing viral-immune dynamics and nirmatrelvir pharmacokinetics that recapitulates viral loads from this and another clinical trial (PLATCOV). Our results suggest that nirmatrelvir’s in vivo potency is significantly lower than in vitro assays predict. According to our model, a maximally potent agent would reduce the viral load by approximately 3.5 logs relative to placebo at 5 days. The model identifies that earlier initiation and shorter treatment duration are key predictors of post-treatment rebound. Extension of treatment to 10 days for Omicron variant infection in vaccinated individuals, rather than increasing dose or dosing frequency, is predicted to lower the incidence of viral rebound significantly.

Nirmatrelvir and ritonavir for inpatients with severe or critical COVID-19 beyond five days of symptom onset: a propensity score-matched, multicenter, retrospective cohort study

BackgroundThere is an urgent need for therapeutic strategies for inpatients with severe or critical COVID-19. The evaluation of the clinical benefits of nirmatrelvir and ritonavir (Nmr/r) for these patients beyond five days of symptom onset is insufficient.MethodsA new propensity score-matched cohort was constructed by using multicenter data from 6695 adult inpatients with COVID-19 from December 2022 to February 2023 in China after the epidemic control measures were lifted across the country. The severity of disease of the inpatients was based on the tenth trial edition of the Guidelines on the Diagnosis and Treatment of COVID-19 in China. The symptom onset of 1870 enrolled severe or critical inpatients was beyond five days, and they received either Nmr/r plus standard treatment or only standard care. The ratio of patients whose SOFA score improved more than 2 points, crucial respiratory endpoints, changes in inflammatory markers, safety on the seventh day following the initiation of Nmr/r treatment, and length of hospital stay were evaluated.ResultsIn the Nmr/r group, on Day 7, the number of patients with an improvement in SOFA score ≥ 2 was much greater than that in the standard treatment group (P = 0.024) without a significant decrease in glomerular filtration rate (P = 0.815). Additionally, the rate of new intubation was lower (P = 0.004) and the no intubation days were higher (P = 0.003) in the first 7 days in the Nmr/r group. Other clinical benefits were limited.ConclusionsOur study may provide new insight that inpatients with severe or critical COVID-19 beyond five days of symptom onset benefit from Nmr/r. Future studies, particularly randomized controlled trials, are necessary to verify the above findings.

Effectiveness of nirmatrelvir/ritonavir in children and adolescents aged 12–17 years following SARS-CoV-2 Omicron infection: A target trial emulation

Currently there is a lack of randomized trial data examining the use of the antiviral nirmatrelvir/ritonavir in paediatric patients with SARS-CoV-2 infection. This target trial emulation study aims to address this gap by evaluating the use of nirmatrelvir/ritonavir in non-hospitalized paediatric patients aged 12–17 years with SARS-CoV-2 Omicron variant infection. Among paediatric patients diagnosed between 16th March 2022 and 5th February 2023, exposure was defined as outpatient nirmatrelvir/ritonavir treatment within 5 days of symptom onset or COVID-19 diagnosis. Primary outcome was 28 day all-cause mortality or all-cause hospitalization, while secondary outcomes were 28 day in-hospital disease progression, 28 day COVID-19-specific hospitalization, multisystem inflammatory syndrome in children (MIS-C), acute liver injury, acute renal failure, and acute respiratory distress syndrome. Overall, 49,378 eligible paediatric patients were included. Nirmatrelvir/ritonavir treatment was associated with reduced 28 day all-cause hospitalization (absolute risk reduction = 0.23%, 95%CI = 0.19%–0.31%; relative risk = 0.66, 95%CI = 0.56–0.71). No events of mortality, in-hospital disease progression, or adverse clinical outcomes were observed among nirmatrelvir/ritonavir users. The findings confirmed the effectiveness of nirmatrelvir/ritonavir in reducing all-cause hospitalization risk among non-hospitalized pediatric patients with SARS-CoV-2 Omicron variant infection.

A COMPARATIVE STUDY OF ULTRASOUND AND COMPUTED TOMOGRAPHY IN EVALUATION OF ACUTE AND CHRONIC PANCREATITIS, ASSOCIATED COMPLICATIONS AND PREDICTING SEVERITY AND PROGNOSIS

Objectives: (1) The objective of the study was to determine the value of USG and computed tomography (CT) in early diagnosis of acute pancreatitis (AP). (2) The study aimed to compare which of the above two radiological investigations (USG/CT) provides the most important information of the disease process and to determine value of CT in evaluating complications, morbidity/severity, and predicting prognosis of AP using modified CT severity index (MCTSI). Methods: This study included 50 patients diagnosed with pancreatitis, consisting of 38 cases of AP and 12 cases of chronic pancreatitis (CP). Both USG and contrast-enhanced CT (CECT) were used to visualize the pancreas, assess its size, detect peripancreatic inflammation and fluid collections, and identify the extent of necrosis and complications. The sensitivity and specificity of USG and CECT were compared. The severity of AP was classified using the MCTSI within 3 days of symptom onset. Clinical outcomes, including hospital stay duration, organ failure, systemic infection, and the need for surgical intervention, were recorded and correlated with MCTSI scores. Statistical Package for the Social Sciences 22.0 was used for statistical analysis and p&lt;0.05 was taken as statistically significant. Results: The mean age of patients was 37.92±12.14 years. USG had a sensitivity of 58% for detecting AP, significantly lower than the 95% sensitivity of CECT, primarily due to bowel gas interference. Both USG and CECT had high positive predictive values. The MCTSI effectively classified the severity of AP, with 41.5% of cases categorized as mild, 39% as moderate, and 19.5% as severe. Extrapancreatic complications were significantly correlated with adverse clinical outcomes and end-organ failure when included in the MCTSI scoring. USG was adequate for diagnosing CP through visualization of dilated ducts, calcifications, and atrophic pancreas, but CECT demonstrated higher specificity and accuracy, especially for rare forms like groove and mass-forming pancreatitis. The study showed a strong correlation between MCTSI scores and patient outcomes. The mortality rate was 2%, observed only in patients with severe AP. Conclusion: The MCTSI is a valuable tool for accurately classifying the severity of AP and predicting clinical outcomes. CECT is superior to USG in diagnosing and managing pancreatitis, providing better visualization and assessment of complications. While USG is useful for diagnosing CP, CECT offers greater specificity and accuracy. The study supports the use of MCTSI in routine clinical practice to guide the management and predict outcomes in patients with AP.

Imbalance in the vWF – ADAMTS13 axis exists early in acute pancreatitis and predicts persistent organ failure and pancreatic necrosis-a prospective study

BackgroundThe pathophysiology of Acute Pancreatitis (AP) may be complicated by endothelial activation. von Willebrand Factor (vWF)- ADAMTS13 axis is a marker of endothelial activation. The study aimed to investigate the axis in AP, comparing it in patients with and without persistent organ failure (OF), with and without pancreatic necrosis, and correlating it with the standard severity scores (CRP, APACHE II, BISAP, SOFA, and qSOFA) MethodsvWF-Antigen (vWF:Ag), vWF-Collagen-Binding-Assay (vWF:CBA), and ADAMTS13 activity (ADAMTS13:act) levels were measured within 5 days of symptom onset in consecutive patients (n = 98), who were admitted with a first episode of AP (Dec 2021–May 2023). ResultsOf the 98 patients admitted with AP, 78(79.6 %) had no or transient OF; 20(20.4 %) had persistent OF. Age was comparable (43.73 ± 15.36 vs 38.65 ± 13.69) [mean ± SD](years), and males were predominant in both groups (70.5 % vs 80 %). Patientswith persistent OF had higher vWF:CBA(%)[323(279–486.5) vs 199.5(159.1–295.75)] and lower ADAMTS13:act(%)[35.4(23.8–56.85) vs 56.35(44.1–71.9)][median (25th – 75th percentile)](P = 0.001) than those with no or transient OF. Patients with pancreatic necrosis (n = 19) had lower ADAMTS13:act(%)[42.79 ± 18.69] than those without pancreatic necrosis (n = 18) [62.49 ± 22.64] (P < 0.01). ADAMTS13:act had a negative correlation(r = −0.2), whereas vWF:Ag and vWF:CBA had a positive correlation (r = 0.2) with the standard severity scores (P < 0.05). ADAMTS13:act could predict pancreatic necrosis [AUROC-0.737, P < 0.05] and persistent OF [AUROC–0.746, P < 0.001], while vWF:CBA could predict persistent OF [AUROC– 0.73, P < 0.001]. ConclusionvWF-ADAMTS13 axis helps to predict severe disease and is associated with poor outcomes in acute pancreatitis.