Cost-effectiveness of recombinant influenza vaccine compared with standard dose influenza vaccine in adults 18-64 years of age.

BACKGROUND: The Advisory Committee on Immunization Practices (ACIP) uses the Evidence to Recommendations Framework that includes cost-effectiveness analyses (CEA) for determining vaccine recommendations. ACIP's preference for protecting adults ≥ 65 years is enhanced vaccines, including recombinant influenza vaccine (RIV4), adjuvanted or high dose influenza vaccine. Less is known about the CEA of enhanced vaccines for younger adults. METHODS: We used decision analysis modeling from a societal perspective to determine the cost-effectiveness, measured in quality adjusted life years (QALYs), of RIV4 compared with standard dose quadrivalent influenza vaccine (SD-IIV4) in adults 18-64 years old. Model inputs included 2018-2020 vaccine effectiveness (VE) estimates based on medical record data from a large local health system, 2019-2020 national vaccination and influenza epidemic parameters, with costs and population distributions fitted to the season. RESULTS: Among adults ages 18-64 years, RIV4 cost $94,186/QALY gained, compared to SD-IIV4. Among those 50-64 years old, RIV4 was relatively more cost-effective ($61,329/QALY gained). Cost-effectiveness estimates for 18-64-year-olds were sensitive to the absolute difference in VE between SD-IIV4 and RIV4, among other parameters. Use of RIV4 in 18-64-year-olds would result in fewer cases (669,984), outpatient visits (261,293), hospitalizations (20,046) and deaths (1,018) annually. The majority (59 %; 597 of 1018) of the decreases in deaths occurred in the 50-64-year-olds. CONCLUSIONS: While RIV4 was effective and cost-effective relative to SD-IIV4 for both 50-64-year-old and 18-64-year-old adults, cost-effectiveness was sensitive to small changes in parameters among 18-64-year-olds. Because substantial public health benefits occur with enhanced vaccines, health systems and policy makers may opt for preferential product use in select age/risk groups (e.g., 50-64 year olds) to maximize their cost-benefit ratios.

Low dose insulin infusion versus the standard dose in children with diabetic ketoacidosis: a meta-analysis.

Aim: This systematic review aims to consolidate findings from current clinical trials that compare the effectiveness of insulin infusion at 0.05 IU/kg/h versus 0.1 IU/kg/h in managing pediatric diabetic ketoacidosis. Methods: We searched several databases, including PubMed, Embase, Scopus, Cochrane Central and Web of Science. Our primary outcomes were time to reach blood glucose ≤250 mg/dl and time to resolution of acidosis. Secondary outcomes included rate of blood glucose decrease per hour, incidence of hypoglycemia, hypokalemia, treatment failure, and cerebral edema. Results & conclusion: The present study establishes that a low insulin dose exhibits comparable efficacy to the standard dosage for managing pediatric patients suffering from diabetic ketoacidosis, with a lower incidence of complications.

When kids with type 1 Diabetes (T1DM) face a serious complication called Diabetic Ketoacidosis (DKA), it becomes a life-threatening situation. This condition, responsible for significant mortality, involves high blood sugar, ketone buildup and acidity. Our study delves into a critical aspect of DKA treatment-finding the right insulin dose. By pooling the studies on this point, we discovered that using a lower insulin dose is just as effective as the standard dose in managing DKA in children, with fewer complications. This insight is crucial for improving the care and outcomes for young patients dealing with this challenging condition.

Comparison of stimulation protocols for dose determination of gonadotropins: A systematic review and Bayesian network meta-analysis based on randomized controlled trials.

BACKGROUND: To date, evidence regarding the effectiveness and safety of individualized controlled ovarian stimulation (COS) compared with standard dose COS has been inadequate. OBJECTIVES: To evaluate the updated evidence from published randomized controlled trials (RCTs) about the efficacy and safety of individualized COS with different ovarian reserve test biomarkers or clinical experience versus standard dose COS. SEARCH STRATEGY: Terms and descriptors related to COS, individualized or standard, and RCT were combined to search, and only English language studies were included. Conference abstracts and comments were excluded. SELECTION CRITERIA: RCTs with comparison between different individualized COS strategies and standard starting dose strategy were included. DATA COLLECTION AND ANALYSIS: Two reviews independently assessed the eligibility of retrieved citations in a predefined standardized manner. Relative risk (RRs) and the weighted mean difference (WMD) with 95% confidence intervals (CIs) were pooled using a random-effects model on R software version 4.2.2. MAIN RESULTS: Compared with the standard dose COS strategy in pairwise meta-analysis, the individualized COS strategy was associated with a notable lower risk of ovarian hyperstimulation syndrome (OHSS; 174/2384 [7.30%] vs 114/2412 [4.73%], RR 0.66, 95% CI: 0.47-0.93, I2 = 46%), a significantly lower risk of hyperresponse to stimulation (hyperresponse; 476/2402 [19.82%] vs 331/2437 [13.58%], RR 0.71, 95% CI: 0.57-0.90, I2 = 61%), and a slightly longer ovarian stimulation days (duration of stimulation; WMD 0.20, 95% CI: 0.01-0.40, I2 = 66%). Bayesian network meta-analysis also found that biomarker-tailored strategy had a significantly lower risk of OHSS than standard dose strategy (OHSS; RR 0.63, 95% CI: 0.41-0.97, I2 = 47.5%). CONCLUSION: Compared with standard dose COS strategy, individualized COS strategy could significantly reduce the risks of OHSS and hyperresponse to stimulation, but the duration of stimulation was slightly longer. TRIAL REGISTRATION: PROSPERO: CRD42023358439.

The clinical outcomes of different doses of rivaroxaban in patients with isolated distal deep vein thrombosis.

OBJECTIVE: Isolated distal deep vein thrombosis (IDDVT) is defined as thrombosis involving the infrapopliteal veins. The optimal anticoagulant therapy of IDDVT remains controversial. This study aimed to assess whether reduced dose of rivaroxaban was suitable in patients with IDDVT. METHODS: Consecutive patients with acute IDDVT were identified by reviewing the venous thromboembolism (VTE) registry databases. Outcomes including VTE recurrence, major bleeding, clinically relevant non-major (CRNM) bleeding, and death. Patients were followed until the first occurrence of any outcomes or the study end date (December 31, 2018). Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed. RESULTS: A total of 1246 patients were divided into low-dose (10 or 15 mg/day; n = 716) and standard-dose (20 mg/day; n = 530) groups. The incidences of VTE recurrence, major bleeding, CRNM bleeding, and death between the two groups were 9.64% vs 5.66%, 1.68% vs 3.02%, 4.61% vs 8.68%, and 13.83% vs 10.75%, respectively. After the inverse probability of treatment weighting, HRs for standard-dose vs low-dose of VTE recurrence, major bleeding, CRNM bleeding, and death were 0.54 (95% CI, 0.35-0.84), 1.71 (95% CI, 0.80-3.67), 2.28 (95% CI, 1.40-3.74), and 1.30 (95% CI, 0.91-1.86), respectively. For the subgroup analysis, the interaction with anticoagulation duration and treatment was evident for VTE recurrence (P for interaction = .002), but not for major bleeding. Patients with residual vein thrombosis were associated with an increased risk of VTE recurrence (HR, 1.95; 95% CI, 1.29-2.95). The interaction between risk factors and residual vein thrombosis was evident for VTE recurrence (P for interaction = .085). CONCLUSIONS: Standard-dose rivaroxaban reduced the risk of VTE recurrence without increasing the risk of major bleeding in patients with IDDVT. Anticoagulant therapy for >1.5 months should be preferred over shorter durations. Residual vein thrombosis should be assessed as a predictor of recurrence in patients with IDDVT, especially for patients with non-transient factors.

Efficacy of combination therapy with standard-dose carbapenem for treating nosocomial pneumonia caused by carbapenem-resistant Acinetobacter baumannii in intensive care units: A multicentre retrospective propensity score-matched study.

Carbapenem-resistant Acinetobacter baumannii (CRAB) infection is common worldwide. Despite carbapenem resistance, standard-dose carbapenems are still used in clinical practice. Hence in this study, we aimed to compare the efficacy and outcomes of a regimen containing standard-dose carbapenems with those of a regimen lacking carbapenems during the treatment of critically ill patients with CRAB nosocomial pneumonia in the intensive care unit (ICU). Initially, 735 patients were recruited for this multicentre retrospective cohort study. After exclusion, time-window bias adjustment, and propensity score matching, multiple clinical outcomes were compared between the carbapenem-containing (CC) (n = 166) and no carbapenem-containing (NCC) (n = 166) groups. The CC group showed a higher risk of clinical failure on day 7 than the NCC group (44.6% vs. 33.1%, P = 0.043). The lengths of ICU stay (21 and 16 days, P = 0.024) and hospital stay (61 and 44 days, P = 0.003) were longer in the CC group than in the NCC group. Multivariate analysis showed that the CC regimen was associated with higher clinical failure (adjusted odds ratio (aOR) = 1.64, 95% CI = 1.05-2.56, P = 0.031) and lower microbiological eradication (aOR = 0.48, 95% CI = 0.23-1.00, P = 0.049) at day 7 than the NCC group. Thus, a regimen containing a standard dose of carbapenem should be prescribed with caution for treating CRAB nosocomial pneumonia in the ICU.

Thromboprophylaxis in Hospitalized Non-Critically Ill Patients With Mild-to-Moderate COVID-19 Infection: A Systematic Review and Meta-Analysis.

The prevalence of venous thromboembolism is high in patients with COVID-19, despite prophylactic anticoagulation. The evidence that supports the preferred thromboprophylaxis regimen in non-critically ill patients with mild to moderate COVID-19 is still limited. Therefore, this systematic review and meta-analysis aimed to compare the clinical outcomes of hospitalized patients with mild to moderate COVID-19 who received standard thromboprophylaxis anticoagulation with intermediate to high prophylaxis regimens. We systematically searched MEDLINE and Embase databases for published studies until August 17th, 2022. We included studies on patients with mild to moderate COVID-19 who received thromboprophylaxis during their hospital stay. Patients who received standard prophylaxis dose "control group" were compared to patients who received intermediate to high prophylaxis "intervention group". Random effect models were used when pooling crude numbers and adjusted effect estimates of study outcomes. A comprehensive analysis was conducted, encompassing seven studies involving a total of 1931 patients. The risk of all-cause thrombosis was not statistically different between the two groups (risk ratio [RR] 1.48, 95% confidence interval [CI] [0.11, 20.21]). The risk of minor bleeding was reported to be lower in patients who received intermediate to high prophylaxis (RR 0.64, 95% CI 0.21, 1.97), while had a higher risk of major bleeding compared with the standard prophylaxis (RR 1.40, 95% CI 0.43, 4.61); however, did not reach the statistical significance. The overall risk for all hospital mortality favored the utilization of intermediate to high doses over the standard thromboprophylaxis dosing (RR 0.47, 95%CI 0.29, 0.75). In medically ill patients with COVID-19, there is no difference between standard and intermediate to high prophylaxis dosing regarding thrombosis and bleeding. However, it appears that intermediate to high prophylaxis regimens are linked to additional survival benefits.

Using wastewater-based epidemiology to evaluate the relative scale of use of opioids.

Wastewater analysis (WWA) has been used as a tool to monitor population drug use, both pharmaceutical and illicit, for over 15 years. Policymakers, law enforcement and treatment services may use WWA-derived data to seek an objective understanding of the extent of drug use in specific areas. Therefore, wastewater data should best be reported in a meaningful form to allow those that are not experts in the field to compare the scale within and between drug classes. Excreted drug loads quantified in wastewater describe the mass of drug present in the sewer. Normalisation for wastewater flow and population is standard practice and critical for comparing drug loads between different catchments and indicates a transition to an epidemiological approach (wastewater-based epidemiology (WBE)). A further consideration is necessary to accurately compare the measured level of one drug to another. The standard dose of a drug taken to elicit a therapeutic effect will vary, with some compounds requiring microgram amounts, while others are administered in the gram range. When WBE data is expressed with units representing excreted or consumed loads without considering dose amounts, the scale of drug use when comparing multiple compounds becomes distorted. To demonstrate the utility and significance of including known excretion rates, potency and typical dose amounts into back-calculations of the measured drug load, this paper compares the levels of 5 prescribed (codeine, morphine, oxycodone, fentanyl and methadone) and 1 illicit (heroin) opioid from South Australian wastewater. The data is presented at each stage of the back-calculation starting with the total mass load measured, to consumed amounts factoring in excretion rates and finally the number of doses the load equates to. This is the first paper to describe the levels of 6 opioids measured in wastewater over a 4-year period in South Australia that demonstrate the relative scale of use.

Reply letter to "Vaccine effectiveness of recombinant and standard dose influenza vaccines against outpatient illness during 2018-2019 and 2019-2020 calculated using a retrospective test-negative design".

A recent study by Zimmerman et al. (2023) reported non-significant higher relative vaccine effectiveness of recombinant (RIV4) over the standard-dose influenza vaccines (SDIV) against outpatient illness during the 2018-19 and 2019-20 vaccination seasons. We agree with the authors' conclusions and would like to emphasize minimal difference between RIV4 and SDIV using Number Needed to Vaccinate (NNV). The NNV analysis showed 8.9 for the RIV4 and 10 for the SDIV in the 50-64 age group. In the 65+ age group, the NNV was 10.6 for the RIV4 and 11.4 for the SDIV. This indicates a minimal difference between both vaccines and hence they both can be used in immunization programs to improve vaccine coverage.

Comparison of Effectiveness and Safety of Low-Dose Versus Standard-Dose Intravenous Recombinant Tissue Plasminogen Activator in Patients With Acute Ischemic Stroke: A Meta-Analysis.

The aim of the present meta-analysis is to compare the efficacy and safety of low-dose and standard-dose recombinant tissue plasminogen activators (r-tPA) in patients with acute ischemic stroke. The present meta-analysis was conducted according to the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines. We conducted a systematic search in PubMed, Embase, and the Cochrane Library to identify studies published between January 1, 2010, and January 31, 2023, using the following terms: "stroke," "alteplase," "doses," "efficacy," "tissue plasminogen activator," "r-tPA," and "safety." Primary efficacy outcomes included favorable outcomes (Modified Rankin Scale scores of 0-2), while secondary efficacy outcome was all-cause mortality at 90 days. Safety outcomes included asymptomatic intracerebral hemorrhage (ICH) and symptomatic ICH assessed using the National Institute of Neurological Disorders and Stroke (NINDS) study and the Safe Implementation of Thrombolysis in Stroke-Monitoring (SITS-MOST) study. We also compared parenchymal hematomas as safety outcome between the two groups defined by the authors themselves in their research. A total of 16 studies were included in the present meta-analysis. The meta-analysis did not report any significant difference between low-dose and standard-dose r-tPA in terms of mortality, symptomatic intracranial hemorrhage (SICH), asymptomatic ICH, and parenchymal hematomas. However, the favorable outcome was significantly greater in patients receiving a standard dose of r-tPA.

Ultra-low-dose CT reconstructed with the artificial intelligence iterative reconstruction algorithm (AIIR) in 18F-FDG total-body PET/CT examination: a preliminary study.

PURPOSE: To investigate the feasibility of ultra-low-dose CT (ULDCT) reconstructed with the artificial intelligence iterative reconstruction (AIIR) algorithm in total-body PET/CT imaging. METHODS: The study included both the phantom and clinical parts. An anthropomorphic phantom underwent CT imaging with ULDCT (10mAs) and standard-dose CT (SDCT) (120mAs), respectively. ULDCT was reconstructed with AIIR and hybrid iterative reconstruction (HIR) (expressed as ULDCT-AIIRphantom and ULDCT-HIRphantom), respectively, and SDCT was reconstructed with HIR (SDCT-HIRphantom) as control. In the clinical part, 52 patients with malignant tumors underwent the total-body PET/CT scan. ULDCT with AIIR (ULDCT-AIIR) and HIR (ULDCT-HIR), respectively, was reconstructed for PET attenuation correction, followed by the SDCT reconstructed with HIR (SDCT-HIR) for anatomical location. PET/CT images' quality was qualitatively assessed by two readers. The CTmean, as well as the CT standard deviation (CTsd), SUVmax, SUVmean, and the SUV standard deviation (SUVsd), was recorded. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated and compared. RESULTS: The image quality of ULDCT-HIRphantom was inferior to the SDCT-HIRphantom, but no significant difference was found between the ULDCT-AIIRphantom and SDCT-HIRphantom. The subjective score of ULDCT-AIIR in the neck, chest and lower limb was equivalent to that of SDCT-HIR. Besides the brain and lower limb, the change rates of CTmean in thyroid, neck muscle, lung, mediastinum, back muscle, liver, lumbar muscle, first lumbar spine and sigmoid colon were -2.15, -1.52, 0.66, 2.97, 0.23, 8.91, 0.06, -4.29 and 8.78%, respectively, while all CTsd of ULDCT-AIIR was lower than that of SDCT-HIR. Except for the brain, the CNR of ULDCT-AIIR was the same as the SDCT-HIR, but the SNR was higher. The change rates of SUVmax, SUVmean and SUVsd were within [Formula: see text] 3% in all ROIs. For the lesions, the SUVmax, SUVsd and TBR showed no significant difference between PET-AIIR and PET-HIR. CONCLUSION: The SDCT-HIR could not be replaced by the ULDCT-AIIR at date, but the AIIR algorithm decreased the image noise and increased the SNR, which can be implemented under special circumstances in PET/CT examination.

High versus standard radiation dose of definitive concurrent chemoradiotherapy for esophageal cancer: A systematic review and meta-analysis of randomized clinical trials.

OBJECTIVES: Compare the efficacy and safety of high vs standard radiation dose of definitive concurrent chemoradiotherapy (dCCRT) for esophageal cancer (EC). METHODS AND MATERIALS: This meta-analysis is registered in PROSPERO, and it was followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Eligible randomized clinical trials (RCTs) comparing high dose (HD;≥59.4 Gy/1.8 Gy) and standard doses (SD; 50 Gy/2Gy or 50.4 Gy/1.8 Gy) were identified on electronic databases. STATA16.0 was used for statistical analysis. A meta-analysis was performed to compare treatment effect and toxicity. RESULTS: Four articles with a total of 1014 patients were finally included. The results showed that the two groups had similar 1-, 2-, and 3-year OS rates (RR = 1.08, 95 % CI = 0.90-1.30, P = 0.395; RR = 1.07, 95 % CI = 0.95-1.20, P = 0.272; RR = 1.06, 95 % CI = 0.97-1.17, P = 0.184; respectively) and 2-, and 3-year locoregional progression-free survival (LRPFS) (RR = 0.95, 95 % CI = 0.81-1.10, P = 0.478; RR = 0.97, 95 % CI = 0.85-1.11, P = 0.674; respectively). The HD-RT group had higher grade ≥ 3 treatment-related toxicities (OR = 1.35, 95 % CI = 1.03-1.77, P = 0.029) and treatment-related deaths rates (OR = 1.85, 95 % CI = 1.04-3.28, P = 0.036) compared with the SD-RT group. Results of subgroup analysis also indicated that HD could not bring benefit compared to SD, even with modern radiotherapy techniques. CONCLUSION: SD-RT had similar treatment effect but lower Grade ≥ 3 treatment-related toxicities rates compared with the HD-RT. Therefore, SD (50 Gy/2Gy or 50.4 Gy/1.8 Gy) should be considered as the recommended dose in dCCRT for EC. Further RCTs are needed to verify our conclusions.

Comparison of the efficacy and safety of standard- and high-dose daptomycin: A systematic review and meta-analysis.

AIMS: Standard doses of daptomycin at 4 and 6 mg/kg were used for the treatment of skin and soft tissue for infections and bacteraemia, respectively. However, increased doses of daptomycin are recommended for complicated infections by Gram-positive organisms. METHODS: A systematic review was conducted using 4 databases. We compared treatment success between standard-dose (SD, 4-6 mg/kg) and high-dose (HD, >6 mg/kg) daptomycin in patients with all-cause bacteraemia, complicated bacteraemia, infective endocarditis, osteomyelitis and foreign body/prosthetic infection as the primary outcome. We also compared the success between SD and HD2 (≥8 mg/kg) daptomycin treatments in patients with these diseases as the secondary outcome. The incidence of creatine phosphokinase (CPK) elevation was evaluated as safety. RESULTS: In patients with complicated bacteraemia and infective endocarditis, the treatment success was significantly lower in the SD group than in the HD group (odds ratio [OR] 0.48, 95% confidence interval [CI] 0.30-0.76 and OR 0.50, 95% CI 0.30-0.82) and HD2 group (OR 0.38, 95% CI 0.21-0.69 and OR 0.30, 95% CI 0.15-0.60), respectively. A significant difference was demonstrated only in the HD2 group in patients with bacteraemia, including simple infection. SD did not decrease the success rate for the treatment of osteomyelitis and foreign body/prosthetic infection. The incidence of elevated CPK was significantly lower in SD group than in HD group. CONCLUSION: SD daptomycin was associated with significantly lower treatment success than HD in patients with complicated bacteraemia/infective endocarditis. The CPK elevation should be considered in patients treated with high daptomycin doses.

The Use of Low-Dose Chest Computed Tomography for the Diagnosis and Monitoring of Pulmonary Infections in Patients with Hematologic Malignancies.

The study aimed to assess the image quality and diagnostic performance of low-dose Chest Computed Tomography (LDCCT) in detecting pulmonary infections in patients with hematologic malignancies. A total of 164 neutropenic patients underwent 256 consecutive CT examinations, comparing 149 LDCCT and 107 Standard-Dose Chest CT (SDCCT) between May 2015 and June 2019. LDCCT demonstrated a 47% reduction in radiation dose while maintaining acceptable image noise and quality compared to SDCCT. However, LDCCT exhibited lower sensitivity in detecting consolidation (27.5%) and ground glass opacity (64.4%) compared to SDCCT (45.8% and 82.2%, respectively) with all the respective p-values from unadjusted and adjusted for sex, age, and BMI analyses being lower than 0.006 and the corresponding Odds Ratios of detection ranging from 0.30 to 0.34. Similar trends were observed for nodules ≥3 mm and ground glass halo in nodules but were not affected by sex, age and BMI. No significant differences were found for cavitation in nodules, diffuse interlobular septal thickening, pleural effusion, pericardial effusion, and lymphadenopathy. In conclusion, LDCCT achieved substantial dose reduction with satisfactory image quality but showed limitations in detecting specific radiologic findings associated with pulmonary infections in neutropenic patients compared to SDCCT.

Low dose versus standard dose rituximab for the treatment of antiphospholipid syndrome: A pilot study from a tertiary medical center.

Background: To investigate the therapeutic effects and safety of low-dose and standard-dose rituximab (RTX) in the treatment of antiphospholipid syndrome (APS). Methods: In this real-world study, we included 22 consecutive patients with APS who received RTX. Standard dose (SD) was defined as an overall dosage of RTX ≥ 1000mg in the induction period, and low dose (LD) was defined as an overall dosage of RTX <1000mg. Results: Of included patients, 1 patients died, 2 patients withdrew and 19 patients completed 6-month follow-up. Nine patients received SD-RTX and 13 patients received LD-RTX, and elder patients [LD-RTX vs. SD-RTX: (49.1 ± 15.5) vs. (35.8 ± 12.3) years, p = 0.044] and patients with later-onset [LD-RTX vs. SD-RTX: (46.8 ± 16.3) vs. (31.3 ± 13.6) years, p = 0.029] were more frequently included in LD-RTX than SD-RTX. Following 6 month RTX treatment, 8 patients (42.1%) achieved complete remission, 8 patients (42.1%) achieved partial remission and 3 patients (15.8%) showed no remission. The titers of anticardiolipin antibodies [baseline vs. 6 months: 30.8 (10.7, 90) vs. 19.5 (2.45, 69.10) U/L, p = 0.023] and the levels of erythrocyte sedimentation rate [baseline vs. 6 months: 29 (6, 63) vs. '6 (3, 14) mm/h, p = 0.021] exhibited a significantly decrease in all APS patients. Remission rate and titers of anti-ß2-glycoprotein I and lupus anticoagulant did not differ significantly between two groups. Conclusion: RTX might be a safe and effective option for patients with APS, and low dose confers equal efficacy as standard dose. Further cohort studies are needed to confirm our findings.

Comparison of the reactogenicity and immunogenicity of a reduced and standard booster dose of the mRNA COVID-19 vaccine in healthy adults after two doses of inactivated vaccine.

The coronavirus disease 2019 (COVID-19) pandemic has been a serious healthcare problem worldwide since December 2019. The third dose of heterologous vaccine was recently approved by World Health Organization. The present study compared the reactogenicity and immunogenicity of the reduced and standard third booster dose of the BNT162b2 and mRNA-1273 vaccine in adults who previously received the two-dose CoronaVac vaccine. Results showed that headache, joint pain, and diarrhea were more frequent in the 15 µg- than the 30 µg-BNT162b2 groups, whereas joint pain and chilling were more frequent in the 100 µg- than the 50 µg-mRNA-1273 groups. No significant differences in immunogenicity were detected. These findings demonstrate that the reduced dose of the mRNA vaccines elicited antibody responses against the SARS-CoV-2 delta and omicron variants that were comparable to the standard dose. The reduced dose could be used to increase vaccine coverage in situations of limited global vaccine supply.

Safety and efficacy of low-dose rt-PA with tirofiban to treat acute non-cardiogenic stroke: a single-center randomized controlled study.

BACKGROUND AND PURPOSE: The recanalization rate after intravenous thrombolysis (IVT) is not enough and there is still the possibility of re-occlusion. We aim to investigate the effectiveness and safety of infusing tirofiban after IVT. METHODS: We performed a prospective controlled study of 60 patients with acute non-cardiogenic ischemic stroke who were hospitalized in Yantai Yuhuangding Hospital from January 2018 to December 2019. The patients were divided into 2 groups: those who received tirofiban for 24 h after IVT (rt-PA + T group) and those who did not receive postprocedural intravenous tirofiban (rt-PA group). The rt-PA + T group received low-dose rt-PA (0.6 mg/kg). The rt-PA group received standard dose rt-PA (0.9 mg/kg). The main outcome measure were safety, included the symptomatic intracranial hemorrhage (sICH), any ICH, severe systemic bleeding, and mortality. The secondary outcome measure is curative efficacy which were evaluated by the 7d-NIHSS score and functional outcomes at 90 days. During hospitalization, the deterioration of neurological function was recorded. RESULTS: All patients completed the follow-up with complete data, there were 30 patients in each of groups. The general characteristics between the two group patients had no statistically significant differences. Compared with the rt-PA + T group and the rt-PA group, in terms of safety, the rates of the sICH, severe systemic bleeding, and mortality in both groups were 0, and there was no statistically significant difference in the rates of any ICH between the two groups (10.0% vs. 3.3%, P = 0.306). In terms of efficacy, the rate of the early neurological deterioration events (END) was no statistical significance (0 vs. 6.6%, P = 0.246). There was no significant difference in the NIHSS score between the two groups before the IVT, and also at 24 h, however, the 7d-NIHSS score was lower in the rt-PA + T group compared with the rt-PA group (2.33 ± 1.85 vs. 4.80 ± 4.02, P = 0.004). At 90 days, 83.3% of patients in the rt-PA + T group had favorable functional outcomes compared with 60.0% of patients in the rt-PA group (P = 0.045). CONCLUSIONS: Low-dose rt-PA combined with tirofiban in acute non-cardiogenic ischemic stroke did not increase the risk of ICH, and mortality, and it was associated with neurological improvement. TRIAL REGISTRATION: The trial has been registered at the ChiCTR and identified as ChiCTR1800014666 (28/01/2018).

Reply letter to "Immunogenicity and safety of a quadrivalent high-dose inactivated influenza vaccine compared with a standard-dose quadrivalent influenza vaccine in healthy people aged 60 years or older: a randomized Phase III trial".

A recent study reported that the high-dose quadrivalent influenza vaccine provided superior immunogenicity and efficacy versus the standard-dose quadrivalent vaccine in the elderly. However, we need to view these results in terms of public health benefits as well. The Number Needed to Vaccinate (NNV) is an important tool to measure the benefit of a given vaccine. Further, NNV evaluates the benefits of a vaccine in preventing and controlling communicable diseases. Considering the target of vaccination and coverage of 75% not met in the elderly in Europe, it is important not to prioritize one vaccine over the other, but rather to increase the vaccine coverage with all the available vaccines.

Systematic review and cost-effectiveness of pharmacokinetically guided sunitinib individualized treatment for patients with metastatic renal cell carcinoma.

Background: Sunitinib has a narrow therapeutic window, with considerable differences between patients. Dosing based on pharmacokinetics (PK) may help overcome some of those issues. This study aims to evaluate and compare the cost-effectiveness of PK-guided individualized treatment of sunitinib with its standard dose in patients with metastatic renal cell carcinoma (mRCC). Methods: A comprehensive literature search was performed, and relevant values were used to provide information for the decision analysis model. Utility data were derived from published studies, and costs were obtained from the perspective of payers in China and the United States. A Markov model was established to evaluate the associated costs and health outcomes for patients. The primary outputs of the model included lifetime costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER). One-way and probability sensitivity analyses were conducted to evaluate the potential uncertainties of parameters. Results: Cost-effective analysis showed that the QALY of the PK-guided group increased by 0.83 compared with that in the standard dose group. From the perspective of both countries' health systems, the cost of PK-guided dose was lower than that of standard dose. Hence, PK-guided treatment was the dominant strategy. One-way and probability sensitivity analyses confirmed the reliability of these results. Conclusion: On the basis of currently available data, PK-guided sunitinib treatment may be a safe, effective, and economical intervention for patients with mRCC.

Standard versus high-dose chemotherapy in mediastinal germ cell tumors: a narrative review.

Objective: The aim of this review is to analyze feasibility and toxicities of high-dose chemotherapy (HDCT) in comparison to standard dose chemotherapy (SDCT) in patients affected by mediastinal germ cell tumors (MGCTs), discussing factors that may affect therapeutic choices, such as: management of residual disease, early response predictors for chemotherapeutic efficacy and determinants of chemotherapeutic resistance. In this review, we discuss the main clinical experiences with HDCT and SDCT in germ cell tumor (GCT) patients specifically in those affected by MGCT. Background: MGCTs represent a very small subset characterized by a poor prognosis, despite improvements in their clinical management and in understanding their biology. From early 1970s, HDCT has become an alternative to SDCT for both first-line and salvage therapeutic settings in advanced GCT patients. Several HDCT schedules-either cisplatin or carboplatin-based-have been tested so far, both in clinical randomized trial and in single-center experiences, with divergent results in terms of clinical outcomes and tolerability. Moreover, the majority of these studies included, but were not exclusively designed for, advanced MGCT patients, making difficult to infer data for this specific subset. Methods: an extended review of literature through PubMed was conducted using the keywords "mediastinal germinal cell tumors", "standard dose chemotherapy" and "high dose chemotherapy". Conclusions: HDCT regimens could not be considered to date a standard option as first-line therapy in advanced MGCT patients, whilst they could be an alternative to SDCT regimens in relapsed tumors after proper patient selection.

Comparison between standard Vs. Escalated dose venous thromboembolism (VTE) prophylaxis in critically ill patients with COVID-19: A two centers, observational study.

INTRODUCTION: The risk of mortality in patients with COVID-19 was found to be significantly higher in patients who experienced thromboembolic events. Thus, several guidelines recommend using prophylactic anticoagulants in all COVID-19 hospitalized patients. However, there is uncertainty about the appropriate dosing regimen and safety of anticoagulation in critically ill patients with COVID-19. Thus, this study aims to compare the effectiveness and safety of standard versus escalated dose pharmacological venous thromboembolism (VTE) prophylaxis in critically ill patients with COVID-19. METHODS: A two-center retrospective cohort study including critically ill patients aged ≥ 18-years with confirmed COVID-19 admitted to the intensive care unit (ICU) at two tertiary hospitals in Saudi Arabia from March 1st, 2020, until January 31st, 2021. Patients who received either Enoxaparin 40 mg daily or Unfractionated heparin 5000 Units three times daily were grouped under the "standard dose VTE prophylaxis and patients who received higher than the standard dose but not as treatment dose were grouped under "escalated VTE prophylaxis dose". The primary outcome was the occurance of thrombotic events, and the secondary outcomes were bleeding, mortality, and other ICU-related complications. RESULTS: A total of 758 patients were screened; 565 patients were included in the study. We matched 352 patients using propensity score matching (1:1). In patients who received escalated dose pharmacological VTE prophylaxis, any case of thrombosis and VTE were similar between the two groups (OR 1.22;95 %CI 0.52-2.86; P = 0.64 and OR 0.75; 95% CI 0.16-3.38; P = 0.70 respectively). However, the odds of minor bleeding was higher in patients who received escalated VTE prophylaxis dose (OR 3.39; 95% CI 1.08-10.61; P = 0.04). There was no difference in the 30-day mortality nor in-hospital mortality between the two groups (HR 1.17;95 %CI0.79-1.73; P = 0.43 and HR 1.08;95 %CI 0.76-1.53; P = 0.83, respectively). CONCLUSION: Escalated-dose pharmacological VTE prophylaxis in critically ill patients with COVID-19 was not associated with thrombosis, or mortality benefits but led to an increased risk of minor bleeding. This study supports previous evidence regarding the optimal dosing VTE pharmacological prophylaxis regimen for critically ill patients with COVID-19.