BACKGROUND: Antiviral drugs have become crucial in managing COVID-19, reducing complications and mortality. Remdesivir has emerged as an effective therapeutic drug for hospitalized patients at risk of disease progression, especially when alternative treatments are infeasible. While the recommended treatment duration of remdesivir extends up to 7 days post-symptom onset, this study examines how early remdesivir administration impacts clinical outcomes.
METHODS: We conducted a retrospective analysis using clinical data from consecutively PCR confirmed SARS-CoV‑2 adult patients (≥ 18 years) who received remdesivir during their hospitalization at the department of infectious diseases, Klinik Favoriten in Vienna. The data covered the period from July 1, 2021, to April 31, 2022. Patients were divided into two groups based on the timing of remdesivir administration: an early group (0-3 days since symptom onset) and a late group (≥ 4 days since symptom onset). The primary outcome was in-hospital disease progression, assessed using the WHO COVID-19 Clinical Progression Scale (≥ 1 point increase). Multivariable logistic regression, adjusted for age, sex, SARS-CoV‑2 variant, and COVID-19 vaccination status, was used to assess clinical outcomes.
RESULTS: In total 219 patients were included of whom 148 (67.6%) were in the early group and 71 (32.4%) were in the late group. The average age was 66.5 (SD: 18.0) years, 68.9% of the patients were vaccinated, and 72.6% had the Omicron virus variant. Late remdesivir administration was associated with a significantly higher probability of needing high-flow oxygen therapy (OR 2.52, 95% CI 1.40-4.52, p = 0.002) and ICU admission (OR 4.34, 95% CI 1.38-13.67, p = 0.012) after adjusting for confounders. In the late group there was a trend towards a higher risk of clinical worsening (OR 2.13, 95% CI 0.98-4.64, p = 0.056) and need for any oxygen therapy (OR 1.85, 95% CI 0.94-3.64, p = 0.074).
CONCLUSIONS: Compared to patients who received remdesivir within the first 3 days after symptom onset, administering remdesivir after day 3 in hospitalized COVID-19 patients is associated with higher risk for complications, such as the need for high-flow oxygen therapy and ICU admission.

OBJECTIVE: To evaluate the effect of timing of antimicrobial therapy on clinical progress of patients with septic shock.
METHODS: We included 204 adult patients diagnosed with septic shock according to Sepsis-3 criteria between March 2016 and April 2021. One-month survival was evaluated using univariate and logistic regression analysis.
RESULTS: Antibiotic treatment was initiated within 1 h of the vasopressors in 26.4 % of patients. One-month mortality did not differ significantly between patients with and without empirical therapy coverage on etiological agents. Univariate factors that significantly affected one-month survival were starting antibiotics at the first hour, the unit where the case was diagnosed with septic shock, SOFA scores, qSOFA scores, and lactate level. In multivariate analysis, diagnosis of septic shock in the Emergency Service, SOFA score ≥11, qSOFA score of three and lactate level ≥4 were significantly associated with one-month mortality.
CONCLUSIONS: Training programs should be designed to increase the awareness of septic shock diagnosis and treatment in the Emergency Service and other hospital units. Additionally, electronic patient files should have warning systems for earlier diagnosis and consultation.

OBJECTIVE: The timing of initiating biologic therapy in persons with Crohn\'s disease (CD) and ulcerative colitis (UC) is an area of ongoing controversy. In particular, there is concern that delaying the initiation of biologic therapy may lead to more treatment-resistant disease, which can result in more complications and hospitalizations.
METHODS: We used health administrative data from Manitoba, Canada to identify all persons with a new diagnosis of inflammatory bowel disease (IBD) between 2001 and 2018 who received tumor necrosis factor antagonists (anti-TNF) therapy and had at least 1 year of post anti-TNF initiation follow-up. We measured the rates of hospitalization, surgery, and outpatient visits, prior to and for up to 5 years following anti-TNF initiation. We compared the rates of these health care utilization outcomes between persons receiving anti-TNFs within 2 years following diagnosis and those receiving anti-TNFs more than 2 years following IBD diagnosis. We used inverse probability treatment weighting to adjust for baseline differences in risk between the 2 groups.
RESULTS: Among 742 persons with CD, early anti-TNF initiators had fewer IBD-specific and overall hospitalizations over the 5 years following the start of therapy. Incidence of resective surgery was also lower in earlier anti-TNF initiators with CD if the first year following initiation was excluded from the analysis. In 318 cases of UC, there was no impact of the timing of anti-TNF therapy on the rates of hospitalization and surgery.
CONCLUSIONS: Earlier administration of anti-TNF therapy is associated with reduced downstream health care resource utilization in CD, though these impacts are not evident in UC.

More than a third of thyroid carcinoma (TC) patients require treatment with radioactive iodine (RAI), but the timing of initial RAI therapy after thyroidectomy remains controversial.
We included 1224 differentiated thyroid carcinoma (DTC) patients during 2015-2019, divided them into the early (≤3 months) and the delayed (>3 months) groups based on the interval between surgery and the initial RAI. Clinical outcomes were assessed within 6-8 months of treatment with RAI, including excellent response (ER), indeterminate response (IDR), biochemical incomplete (BIR) and structural incomplete response (SIR). Further transformed them into dichotomous outcomes, we therefore introduced the ordered/binary logistic regression to assess the relation of time interval and quaternary/dichotomous outcomes, respectively. Finally, we conducted a meta-analysis for cohort study to investigate the effect of timing of RAI therapy on the prognosis of TC.
Delay RAI therapy beyond 3 months reduced the IR (BIR + SIR) rate in the present cohort study (RR = 0.67, 95% CI: 0.49-91). Following meta-analysis including 38,688 DTC patients confirmed these results (RR = 0.77, 95% CI: 0.66-0.91), further revealed the duration of treatment does not influence OS (pooled RR = 1.05, 95% CI: 0.83-1.33).
Delayed initial RAI therapy beyond 3 months but no later than 6 months did not impair the prognosis of TC.

Remdesivir, a repurposed antiviral, was first accorded approval by the US Food Drug Administration (FDA) for the treatment of COVID-19 which necessitates hospitalization. However, the interim data of SOLIDARITY trial revealed no benefits with remdesivir for COVID-19 patients which led immediate debates in social media and the press about the utility of the drug. Both preclinical and clinical data demonstrated its efficacy in COVID-19. The recently concluded ACTT-1 trial showed its efficacy in reducing the duration of hospital stay which is of utmost importance for a country like India where reduction in bed occupancy can save lives of many and eases the financial burden of patient and government. Our benefit-risk analysis of ACTT-1 trial also favored the use of remdesivir over standard of care. The SOLIDARITY trial was fundamentally different from other clinical trials on remdesivir with respect to its design, adaptive nature, and selection of endpoints. Moreover, the success of antiviral therapy also depends on the timing of initiation and combination with other drugs. Hence we believe that drugs like Remdesivir are very important for countries like India where soft end points such as time to recovery and clinical improvement and early discharge become extremely significant during a pandemic.

Previous studies examining the time to initiate chemoradiation (CRT) after surgical resection of glioblastoma have been conflicting. To better define the effect that the timing of adjuvant treatment may have on outcomes, the authors examined patients within the National Cancer Database (NCDB) stratified by a validated prognostic classification system.
Patients with glioblastoma in the NCDB who underwent surgery and CRT from 2004 through 2013 were analyzed. Radiation Therapy Oncology Group recursive partitioning analysis (RPA) class (III, IV, V) was extrapolated for the cohort. Time intervals were grouped weekly, with weeks 4 to 5 serving as the reference category for analyses. Kaplan-Meier analysis, log-rank testing, and multivariate (MVA) Cox proportional hazards regression were performed.
In total, 30,414 patients were included. RPA classes III, IV, and V contained 5250, 20,855, and 4309 patients, respectively. On MVA, no time point after week 5 was associated with a change in overall survival for the entire cohort or for any RPA class subgroup. The periods of weeks 0 to 1 (hazard ratio [HR], 1.18; 95% CI, 1.02-1.36), >1 to 2 (HR, 1.23; 95% CI, 1.16-1.31), and >2 to 3 (HR, 1.11; 95% CI, 1.07-1.15) demonstrated slightly worse overall survival (all P < .03). The detriment to early initiation was consistent across each RPA class subgroup.
The current data provide insight into the optimal timing of CRT in patients with glioblastoma and describe RPA class-specific outcomes. In general, short delays beyond 5 weeks did not negatively affect outcomes, whereas early initiation before 3 weeks may be detrimental.

OBJECTIVE: Adjuvant hormonal therapy is frequently used in the treatment of women with estrogen receptor (ER)/progesterone receptor (PR) positive breast cancer. When radiotherapy is given, hormone therapy may be delivered in a concurrent or sequential manner. Hormonal blockade with tamoxifen or aromatase inhibitors is thought to arrest hormonally dependent cancer cells in the early G1 phase of the cell cycle. This has been theorized to reduce the efficacy of radiation, which is known to be more effective in cells that are actively dividing. Therefore, there has been a reluctance by many to treat with concurrent hormonal and radiation therapy.
METHODS: We performed a search of the Medline database that led to the identification of 39 studies. Abstract and full-text review of these studies led to the identification of seven English non-review studies in peer-reviewed literature between 1995 and 2015 that addressed the question of timing of radiation and hormonal therapy. Outcome measures were captured from each of the studies.
RESULTS: No difference in survival or local-regional recurrence was identified between concurrent versus sequential treatment. Furthermore, no difference in cosmetic outcome or adverse effects was noted for either approach. However, when comparing radiation alone or radiation and hormonal therapy, there was an increased risk of breast and lung fibrosis with combined treatment.
CONCLUSIONS: Hormone therapy, concurrent or sequential, with radiation results in comparable disease-related outcomes, including survival and recurrence. However, given the theoretical reduction in efficacy and increased rates of fibrosis with concurrent use, it is reasonable to support the use of sequential therapy.

OBJECTIVE: To appraise the evidence behind the Surviving Sepsis Campaign Guidelines on antimicrobial therapy in sepsis and evaluate relevant literature in small animal veterinary critical care.
METHODS: Electronic searches using MEDLINE and EMBASE databases.
RESULTS: Current recommendations are to administer appropriate antimicrobials within 1 hour of a diagnosis of severe sepsis or septic shock. Evidence is supportive of this recommendation in septic shock but the evidence is less compelling in milder forms of critical illness-related infections. It is unclear when the administration of appropriate antimicrobials is most beneficial and when it should be considered essential. Evidence supports shorter courses of antimicrobial therapy for many infections seen in the critical care unit with the biomarkers procalcitonin and C-reactive protein helpful in guiding the duration of therapy.
RESULTS: Current evidence is lacking to support the use of early and aggressive use of antimicrobials in all patients with critical illness-related bacterial infections. Two studies failed to demonstrate improved survival in patients with pulmonary or abdominal infections administered appropriate vs inappropriate empirical antimicrobials. One study failed to show an improved survival when dogs with abdominal infections were administered antimicrobials within 1 hour vs 6 hours of diagnosis of infection. Information regarding ideal duration of antimicrobial therapy and use of biomarkers to guide therapy is currently lacking.
CONCLUSIONS: Clinicians should aim to administer early and appropriate antimicrobials; however, the impact this will have on patient outcome remains uncertain. The ability to administer early and appropriate antimicrobials may be considered a measure of the quality of medical practice rather than a prognostic indicator.