Difference In Serious Adverse Events Research Articles

Effectiveness of polypill for primary and secondary prevention of cardiovascular disease: a pragmatic cluster-randomised controlled trial (PolyPars)

BackgroundWe aimed to investigate the effectiveness of fixed-dose combination therapy (polypill) for primary and secondary prevention of major cardiovascular diseases in a typical rural setting.MethodsThe PolyPars Study is a two-arm...

Efficacy and safety of vaccines to prevent respiratory syncytial virus infection in infants and older adults: A systematic review and meta-analysis

ObjectivesTo determine the efficacy and safety of respiratory syncytial virus (RSV) vaccines in infants and older adults. MethodsWe performed a systematic review and meta-analysis of randomized control trials that evaluated the efficacy of maternal RSV immunization against infections in infants, as well as the efficacy of RSV vaccines in older adults. The primary outcome was the vaccine efficacy against RSV-related lower respiratory tract disease (LRTD). Grading of Recommendations Assessment, Development and Evaluation criteria was used to evaluate the level of evidence. ResultsTen trials were included in the review. For maternal vaccination, the RSV vaccine showed favourable efficacy against RSV-related LRTD (vaccine efficacy 57.3%, 95% confidence interval [CI] 31.3-73.5; low certainty) and RSV-related severe LRTD (vaccine efficacy 81.9%, 95% CI 56.8-92.4; moderate certainty) in infants within 90 days after birth. For older adults, Meta-analysis showed that RSV vaccines could also reduce the risk of RSV-related LRTD (vaccine efficacy 78.3%, 95% CI 65.6-86.3; moderate certainty) and RSV-related severe LRTD (vaccine efficacy 86.5%, 95% CI 68.3-94.3; moderate certainty). There was no significant difference in serious adverse events between RSV vaccines and placebo. ConclusionRSV vaccines have the potential to offer protection against RSV disease in both infants and older adults, without apparent safety concerns.

Short-Term Cardiovascular Complications in Dermatology Patients Receiving JAK-STAT Inhibitors

Evolving evidence suggests that patients receiving Janus kinase-signal transducer and activator of transcription inhibitors (JAK-STATi) may be at higher risk of major adverse cardiovascular events (MACE) and venous thromboembolism (VTE). Most existing literature has focused on indications that may confer a higher MACE and VTE risk than that among patients with isolated dermatological indications. To evaluate risk of MACE, VTE, serious adverse events (SAEs), and tolerability of systemic JAK-STATi compared with placebo, in those with a dermatologic indication. A systematic review of the literature was carried out to June 2023, using databases Embase, MEDLINE, SCOPUS, Cochrane Library of Registered Trials, and registered Clinical Trials. The analysis was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. The analysis itself took place in June 2023. Placebo-controlled randomized clinical trials that compared systemic JAK-STATi with placebo, and investigated the safety in patients with alopecia areata, psoriasis, vitiligo, atopic dermatitis, lichen planus or hidradenitis suppurativa. Study selection and data extraction by 2 authors working independently using a standardized template. Crude numbers for MACE, VTE, SAEs, and study discontinuation due to treatment emergent adverse events (TEAEs) were pooled and underwent meta-analysis. Incidence of MACE, VTE, SAE, and study discontinuation due to TEAEs. Analysis of these values against person exposure years to determine the incidence rate (IR). Risk ratios (RRs) compared incidence rates among treatment and placebo comparator arms. Forty-five randomized clinical trials were eligible for inclusion, with 12 996 patients receiving active JAK-STATi therapy and 4925 allocated to placebo treatment. Meta-analysis found no significant increase in MACE (I2 = 0.00%; RR, 0.47; 95% CI, 0.28-0.80) or VTE (I2 = 0.00%; RR, 0.46; 95% CI, 0.26-0.80) between placebo and JAK-STATi comparator arms. There was also no significant difference in SAEs (I2 = 12.38%; RR, 0.92; 95% CI, 0.72-1.20) and discontinuations between JAK-STATi and placebo (I2 = 23.55%; RR, 0.94; 95% CI, 0.76-1.19). This meta-analysis did not identify a significant increase in the risk of MACE and VTE in dermatology patients receiving JAK-STATi for median duration of 16 weeks. The results of this review suggest there is insufficient evidence that JAK-STATi confer an increased risk of cardiovascular complications in dermatological patients, especially when used for short time frames.

Fecal microbiota transplantation as a therapy for treating ulcerative colitis: an overview of systematic reviews

AimThe current overview on published systematic reviews (SRs) and meta-analysis (MAs) aimed to systematically gather, evaluate, and synthesize solid evidence for using fecal microbiota transplantation (FMT) to treat ulcerative colitis (UC).MethodsRelevant articles published before January 2023 were collected from Web of Science, Embase, PubMed, and Cochrane Library. Two authors used Assessment of Multiple Systematic Reviews 2 (AMSTAR-2) tool, PRISMA checklists, and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system were applied by two authors to independently evaluate the methodological quality, reporting quality, and evidence quality, respectively. Re-meta-analysis on the primary RCTs was conducted after excluding overlapping randomized controlled trials (RCTs).ResultsSix SRs/MAs involving 12 primary RCTs and 544 participants were included. According to the AMSTAR-2 tool and PRISMA checklist, methodological quality and reporting quality of the included studies was overall satisfactory. The evidence quality of a great majority of outcomes was rated as moderate to high according to the GRADE system. Compared to placebo, the re-meta-analysis found a great advantage of use FMT in inducing combined clinical and endoscopic remission (OR 3.83 [2.31, 6.34]), clinical remission (3.31 [2.09, 5.25]), endoscopic remission (OR 3.75 [2.20, 6.39]), clinical response (OR 2.56 [1.64, 4.00]), and endoscopic response (OR 2.18 [1.12, 4.26]). Pooled data showed no significant difference in serious adverse events between patients receiving FMT and those receiving placebo (OR 1.53 [0.74, 3.19]). Evidence quality of the outcomes derived from re-meta-analysis was significantly higher after overcoming the limitations of previous SRs/MAs.ConclusionIn conclusion, moderate- to high-quality evidence supported a promising use of FMT to safely induce remission in UC. However, further trials with larger sample size are still required to comprehensively analyze the delivery route, total dosage, frequency, and donor selection in FMT.

Sex Differences in Serious Adverse Events Reported Following Booster Doses of COVID-19 Vaccination in Thailand: A Countrywide Nested Unmatched Case-Control Study.

A booster dose of a COVID-19 vaccine has been proven effective in restoring vaccine effectiveness and is currently recommended for use in some populations at risk of severe COVID-19 infection. Since sex differences in adverse events are significant in response to the vaccines, the safety of booster selection must be studied to avoid serious adverse events (SAE), such as life-threatening diseases. First, this study aimed to identify sex differences in SAE incidences using a prospective cohort design. Second, a nested unmatched case-control study was used to identify factors associated with reported SAE within 30 days after the booster shot. Multivariable logistic regression indicated the adjusted odds ratio by accounting for host and vaccine variables, thus, policy effects. The findings confirmed that SAE was rare and that age-sex-dominated disease classifications differed. Specific to SAE following the booster dose, we found that females aged 12-40 had a higher risk of being reported with SAE than males of the same age, while males over 50 had a higher risk than females. Other risk factors identified were the presence of metabolic syndrome and the use of certain vaccine brands. Mechanisms could be explained by individual host responses rather than the vaccines' direct effect. Therefore, SAE could be preventable by age-sex-specific vaccine selection, post-vaccination precautions, and early symptom detection. Future vaccine development should aim to limit host-specific reactogenicity for safety concerns.

Effect of Personalized Risk-Reduction Strategies on Cognition and Dementia Risk Profile Among Older Adults

Modifiable risk factors are hypothesized to account for 30% to 40% of dementia; yet, few trials have demonstrated that risk-reduction interventions, especially multidomain, are efficacious. To determine if a personalized, multidomain risk reduction intervention improves cognition and dementia risk profile among older adults. The Systematic Multi-Domain Alzheimer Risk Reduction Trial was a randomized clinical trial with a 2-year personalized, risk-reduction intervention. A total of 172 adults at elevated risk for dementia (age 70-89 years and with ≥2 of 8 targeted risk factors) were recruited from primary care clinics associated with Kaiser Permanente Washington. Data were collected from August 2018 to August 2022 and analyzed from October 2022 to September 2023. Participants were randomly assigned to the intervention (personalized risk-reduction goals with health coaching and nurse visits) or to a health education control. The primary outcome was change in a composite modified Neuropsychological Test Battery; preplanned secondary outcomes were change in risk factors and quality of life (QOL). Outcomes were assessed at baseline and 6, 12, 18, and 24 months. Linear mixed models were used to compare, by intention to treat, average treatment effects (ATEs) from baseline over follow-up. The intervention and outcomes were initially in person but then, due to onset of the COVID-19 pandemic, were remote. The 172 total participants had a mean (SD) age of 75.7 (4.8) years, and 108 (62.8%) were women. After 2 years, compared with the 90 participants in the control group, the 82 participants assigned to intervention demonstrated larger improvements in the composite cognitive score (ATE of SD, 0.14; 95% CI, 0.03-0.25; P = .02; a 74% improvement compared with the change in the control group), better composite risk factor score (ATE of SD, 0.11; 95% CI, 0.01-0.20; P = .03), and improved QOL (ATE, 0.81 points; 95% CI, -0.21 to 1.84; P = .12). There were no between-group differences in serious adverse events (24 in the intervention group and 23 in the control group; P = .59), but the intervention group had greater treatment-related adverse events such as musculoskeletal pain (14 in the intervention group vs 0 in the control group; P < .001). In this randomized clinical trial, a 2-year, personalized, multidomain intervention led to modest improvements in cognition, dementia risk factors, and QOL. Modifiable risk-reduction strategies should be considered for older adults at risk for dementia. ClinicalTrials.gov Identifier: NCT03683394.

Platelet transfusion for spontaneous intracerebral hemorrhage with prior antiplatelet: A systematic review and meta-analysis.

Recent studies have highlighted the unfavorable prognosis of patients with spontaneous intracerebral hemorrhage (ICH) who have received prior antiplatelet therapy (PAP). Platelet infusion therapy (PIT) is commonly administered to such patients at many medical institutions, but its efficacy remains a subject of debate. To address this uncertainty, we conducted a comprehensive search of PubMed, EMBASE, and Cochrane Library databases for eligible studies published before June 30, 2023. Our primary outcomes of interest were favorable functional outcome and mortality, while secondary outcomes included the incidence of hematoma expansion and adverse events associated with PIT. Meta-analysis was performed using Review Manager 5.3. Our analysis included 1 randomized controlled trial (RCT) and 6 retrospective studies, involving a total of 577 patients. Pooled analysis revealed that PIT did not contribute to a better favorable functional outcome at the 3-month follow-up (OR = 0.49, 95% CI 0.27-0.89) among ICH patients with PAP. Furthermore, PIT did not significantly reduce the risk of mortality (OR = 0.79, 95% CI 0.40-1.55) or hematoma expansion (OR = 1.15, 95% CI 0.65-2.01). Notably, no significant differences in serious adverse events were observed between patients who underwent PIT and those who did not. Based on the available evidence, there is no indication that PIT can enhance the prognosis of spontaneous ICH patients with prior antiplatelet therapy, although this treatment approach appears to be safe. Therefore, routine recommendation of PIT for ICH patients with prior antiplatelet therapy is not warranted.

Ablation versus medical therapy for patients with atrial fibrillation: An updated meta-analysis.

To investigate the effect of ablation compared to medical therapy on clinical outcomes of patients with atrial fibrillation (AF). PubMed, Scopus, Embase, and Web of Science databases were searched using ablation, medical treatment, AF, and related words. The effect of ablation and medical therapy was sought to be gathered on stroke or transitional ischemic attack, mortality, hospitalization, recurrence of AF, progression of AF, and left ventricular ejection fraction. Analyses were performed using R software. 31 studies (the results of 27 randomized controlled trials), compromising an overall 6965 patients (Ablation, n = 3643; Medical treatment, n = 3322) were reviewed in our study, revealed that catheter ablation would result in substantial benefits for patients with AF without significant difference in serious adverse events compared to medical management (Risk Ratio: 0.92, [95% Confidence Interval (CI), 0.64-1.33]). Catheter ablation in patients with AF significantly resulted in a 29% reduction in all-cause mortality (RR: 0.71, [95% CI, 0.57-0.88]), a 57% reduction in hospitalization (RR: 0.43, [95% CI, 0.27-0.67]), a 53% reduction in AF recurrence (RR: 0.47, [95% CI, 0.36-0.61]), and a dramatic reduction, 89%, in progression of paroxysmal to persistent AF (RR: 0.11, [95% CI, 0.02-0.65]); also associated with a remarkable improvement in their left ventricular ejection fraction (LVEF) (Mean Difference, MD: 6.84%, [95% CI, 3.27-10.42]) compared to medical therapy. Our study showed that ablation may be superior to medical therapy in patients with AF regarding AF recurrence, mortality, LVEF improvement, hospitalization, and AF progression outcomes.

Efficacy and safety of tripterygium wilfordii Hook F plus TNF inhibitor for active rheumatoid arthritis: A multicentre, randomized, double-blind, triple-dummy controlled trial

An investigator-initiated, multicentre, randomized, double-blind, triple-dummy, controlled trial was conducted at 14 tertiary rheumatology centers in China to evaluate the efficacy and safety of Tripterygium wilfordii Hook F (TwHF) with recombinant human TNF receptor IgGFc fusion protein (rhTNFR-Fc) in active Rheumatoid Arthritis (RA). Primary endpoint was the proportion of patients achieved a 50% improvement of American College of Rheumatology criteria (ACR50) in TwHF+rhTNFR-Fc vs. methotrexate (MTX) group at week 12. ACR50 was achieved in 57.1% (72/126), 41.3% (52/126), 23.0% (29/126), and 26.2% (33/126) patients receiving TwHF+rhTNFR-Fc, MTX + rhTNFR-Fc, TwHF and MTX monotherapy, respectively, at week 12 (TwHF+rhTNFR-Fc vs. other three groups, all p < 0.05). No statistical difference in serious adverse events or adverse events leading to discontinuation of study across all groups was documented. TwHF+rhTNFR-Fc was superior to MTX for active RA, and was more effective than MTX + rhTNFR-Fc on ACR50, with a similar safety profile.Trial registration:ClinicalTrials.govNCT03589833.

Prostaglandins for adult liver transplanted recipients.

Prostaglandins are naturally occurring lipids that are synthesised from arachidonic acid. Multiple studies have evaluated the benefits of prostaglandins in reducing ischaemia reperfusion injury after liver transplantation. New studies have been published since the previous review, and hence it was important to update the evidence for this intervention. To evaluate the benefits and harms of prostaglandins in adults undergoing liver transplantation compared with placebo or standard care. We used standard, extensive Cochrane search methods. The latest search date was 27 December 2022. We included randomised clinical trials evaluating prostaglandins initiated in the perioperative period compared with placebo or standard care for adults undergoing liver transplantation. We included trials irrespective of reported outcomes. We used standard Cochrane methods. Our primary outcomes were 1. all-cause mortality, 2. serious adverse events, and 3. health-related quality of life. Our secondary outcomes were 4. liver retransplantation, 5. early allograft dysfunction, 6. primary non-function of the allograft, 7. acute kidney failure, 8. length of hospital stay, and 9. adverse events considered non-serious. We used GRADE to assess certainty of evidence. We included 11 randomised clinical trials with 771 adult liver transplant recipients (mean age 47.31 years, male 61.48%), of whom 378 people were randomised to receive prostaglandins and 393 people were randomised to either placebo (272 participants) or standard care (121 participants). All trials were published between 1993 and 2016. Ten trials were conducted in high- and upper-middle-income countries. Prostaglandins may reduce all-cause mortality up to one month (risk ratio (RR) 0.86, 95% confidence interval (CI) 0.61 to 1.23; risk difference (RD) 21 fewer per 1000, 95% CI 63 fewer to 36 more; 11 trials, 771 participants; low-certainty evidence). Prostaglandins may result in little to no difference in serious adverse events (RR 0.92, 95% CI 0.60 to 1.40; RD 81 fewer per 1000, 95% CI 148 fewer to 18 more; 6 trials, 568 participants; low-certainty evidence). None of the included trials reported health-related quality of life. Prostaglandins may result in little to no difference in liver retransplantation (RR 0.98, 95% CI 0.49 to 1.96; RD 1 fewer per 1000, 95% CI 33 fewer to 62 more; 6 trials, 468 participants; low-certainty evidence); early allograft dysfunction (RR 0.62, 95% CI 0.33 to 1.18; RD 137 fewer per 1000, 95% CI 241 fewer to 47 more; 1 trial, 99 participants; low-certainty evidence); primary non-function of the allograft (RR 0.58, 95% CI 0.26 to 1.32; RD 23 fewer per 1000, 95% CI 40 fewer to 16 more; 7 trials, 624 participants; low-certainty evidence); and length of hospital stay (mean difference (MD) -1.15 days, 95% CI -5.44 to 3.14; 4 trials, 369 participants; low-certainty evidence). Prostaglandins may result in a large reduction in the development of acute kidney failure requiring dialysis (RR 0.42, 95% CI 0.24 to 0.73; RD 100 fewer per 1000, 95% CI 132 fewer to 49 fewer; 5 trials, 477 participants; low-certainty evidence). The evidence is very uncertain about the effect of prostaglandins on adverse events considered non-serious (RR 1.19, 95% CI 0.42 to 3.36; RD 225 fewer per 1000, 95% CI 294 fewer to 65 fewer; 4 trials, 329 participants; very low-certainty evidence). Two trials reported receiving funding; one of these was with vested interests. We found one registered ongoing trial. Eleven trials evaluated prostaglandins in adult liver transplanted recipients. Based on low-certainty evidence, prostaglandins may reduce all-cause mortality up to one month; may cause little to no difference in serious adverse events, liver retransplantation, early allograft dysfunction, primary non-function of the allograft, and length of hospital stay; and may have a large reduction in the development of acute kidney injury requiring dialysis. We do not know the effect of prostaglandins on adverse events considered non-serious. We lack adequately powered, high-quality trials evaluating the effects of prostaglandins for people undergoing liver transplantation.

Effectiveness and safety of conventional systemic treatments in classical and endemic Kaposi sarcoma: A multicentric retrospective study of 110 patients.

e21584 Background: Apart from post-transplant Kaposi sarcoma (KS), 2 major subtypes of non-HIV-related KS are described: classical Kaposi sarcoma (CKS) in patients originated from Mediterranean countries and endemic KS (EKS) in patients of sub-Saharan Africa origin. Some patients with aggressive EKS or CKS require systemic treatments among which liposomal anthracycline (LA), taxanes and, to a lesser extent, low dose interferon (LDI) are generally recommended as first lines. Recently, anti-PD1 have shown promising results in an early phase II trial. At the dawn of a turning point in therapeutic era, we aim to map the effectiveness and safety of the main conventional systemic treatments usually available in KS. Methods: We performed a national multicentric retrospective study including all patients receiving a systemic treatment for a histologically proven KS between January 1st 2013 to July 1st 2019. HIV infected patients and patients treated with immunosuppressive drugs were excluded. Overall response was defined as a decrease of more than 50% of lesion area and serious adverse events encompassed grade 3 and 4 toxicity. Results: A total of 110 patients were included. Sixty-nine had CKS (62.7%) and 41 had EKS (37.2) with a median age at diagnosis of 69 (IQR: 57-77) and 41 years (37-59) (p = 0.011), respectively. At the time of diagnosis, EKS was associated with greater systemic involvement compared with CKS (36.6% vs 14.9%, p = 0.017). First-line therapy was initiated within a median of 13.8 months (2.9-43) after KS diagnosis. The 3 main regimens were taxanes (27.3%), LA (19.1%) and LDI (19.1%) with response rates of 82.8%, 80% and 52.6% (p = 0.063), respectively. The cumulative incidence of a second line of treatment in the first 2 years of follow-up was 49.5% (CI95% 38.7-59.4), without significant difference according to the different regimens. Toxicity, regardless of grade, was reported more frequently with LDI (55.3%) and taxanes (47.8%) than with LA (30.4%) (p = 0.035). Poor tolerability led to discontinuation of LDI more frequently than LA (OR = 4.17, p = 0.048), without difference for taxanes. There was no difference in serious adverse events between the 3 main regimens. CKS and EKS didn’t differ regarding overall response rate or time to next treatment regardless of treatment regimens. However, response rates tended to decrease as the lines went on for EKS (from 77.5% in 1st to 33.3% in 3rd line, p = 0.005), in contrast to CKS who maintained a sustained response, with more frequent systemic involvement (56% vs 25.4%, p = 0.002) during EKS course. Conclusions: Herein, we highlight LA, taxanes and LDI are safe and effective treatments for non-immunodeficient KS. Furthermore, EKS differed from CKS, occurring in younger patients, with more frequent systemic involvement and response loss through therapeutic lines, emphasizing the need to evaluate new agents in this form of KS.

Lower vs Higher Fluid Volumes in Adult Patients With Sepsis: An Updated Systematic Review With Meta-Analysis and Trial Sequential Analysis

IV fluids are recommended for adults with sepsis. However, the optimal strategy for IV fluid management in sepsis is unknown, and clinical equipoise exists. Do lower vshigher fluid volumes improve patient-important outcomes in adult patients with sepsis? We updated a systematic review with meta-analysis and trial sequential analysis of randomized clinical trials assessing lower vshigher IV fluid volumes in adult patients with sepsis. The coprimary outcomes were all-cause mortality, serious adverse events, and health-related quality of life. We followed the recommendations from the Cochrane Handbook and used the Grading of Recommendations Assessment, Development and Evaluation approach. Primary conclusions were based on trials with low risk of bias if available. We included 13 trials (N= 4,006) with four trials (n= 3,385) added to this update. The meta-analysis of all-cause mortality in eight trials with low risk of bias showed a relative risk of 0.99 (97%CI, 0.89-1.10; moderate certainty evidence). Six trials with predefined definitions of serious adverse events showed a relative risk of 0.95 (97%CI, 0.83-1.07; low certainty evidence). Health-related quality of life was not reported. Among adult patients with sepsis, lower IV fluid volumes probably result in little to no difference in all-cause mortality compared with higher IV fluid volumes, but the interpretation is limited by imprecision in the estimate, which does not exclude potential benefit or harm. Similarly, the evidence suggests lower IV fluid volumes result in little to no difference in serious adverse events. No trials reported on health-related quality of life. PROSPERO; No.: CRD42022312572; URL: https://www.crd.york.ac.uk/prospero/.

Deferoxamine in intracerebral hemorrhage: Systematic review and meta-analysis.

Intracerebral hemorrhage (ICH) is a stroke with a high morbidity and mortality rate. Deferoxamine (DFX) is thought to be effective in treating Intracerebral Hemorrhage. In our study, we performed a meta-analysis to evaluate the treatment effects of DFX. We systematically searched PubMed, Embase, Web of Science, the Cochrane Central Register of Controlled Trials, and Chinese Biomedical Literature Database in Jan 2022 for studies on DFX for ICH patients. Outcome measures included relative hematoma volume, relative edema volume, good neurological functional outcome and adverse events. Odds risk (OR) and weighted mean difference (WMD) were used to evaluate clinical outcomes. After searching 636 articles, 4 RCTs, 2 NRCTs, and 1cohort study were included. We found that DFX was effective in hematoma absorption on day 7 after onset, but the difference was not significant on day 14. DFX could suppress edema expansion on days 3, 7, and 14 after onset. DFX did not contribute to better outcomes after 3 and 6 months when used the modified Rankin Scale and the Glasgow Outcome Scale to evaluate neurological prognosis. The pooled results showed no statistically significant difference in Serious adverse events between the experimental and control groups. DFX could limit edema expansion on days 3, 7, and 14 after commencement and facilitate hematoma absorption at week 1 without significantly increasing the risk of adverse events, but it did not improve neurological prognosis.

MP48-05 SAME-DAY DISCHARGE FOR ROBOTIC ASSISTED LAPAROSCOPIC RADICAL PROSTATECTOMY IS SAFE AND RISING: AN ANALYSIS OF NSQIP DATABASE

You have accessJournal of UrologyCME1 Apr 2023MP48-05 SAME-DAY DISCHARGE FOR ROBOTIC ASSISTED LAPAROSCOPIC RADICAL PROSTATECTOMY IS SAFE AND RISING: AN ANALYSIS OF NSQIP DATABASE Chris Du, Arshia Aalami Harandi, and David M. Golombos Chris DuChris Du More articles by this author , Arshia Aalami HarandiArshia Aalami Harandi More articles by this author , and David M. GolombosDavid M. Golombos More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003294.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Robot assisted laparoscopic radical prostatectomy (RALRP) has demonstrated improved postoperative pain, decreased operative time, and shortened length of stay compared to the open approach. It is now the preferred approach for the surgical management of prostate cancer. Several institutions have shown the feasibility of performing same day discharge (SDD) RALRP. We sought to evaluate trends and assess the safety of SDD RALRP using the National Surgical Quality Improvement Program (NSPIQ) database. METHODS: Subjects were queried between 2012-2020 with CPT code 55866. Patients with a hospital stay of 0 days were defined as SDD RALRP and compared to patients with presumed uncomplicated course discharged postop day 1 or 2. The primary outcome of 30-day readmission rates was compared. SPSS v27.0 was used to perform statistical analysis between the two groups. RESULTS: We identified 65,648 RALRP cases meeting study criteria, of which 1,251 (1.9%) were SDD. There was a significant association of SDD RALRP performed recently (p<.01), with the majority (53.4%) performed in 2020. Significant demographic differences for SDD RALRP included age (61.9 vs 62.8 years, p<.01), smoking history (9.0% vs. 11.0%, p=03), Hispanic (8.0% vs. 5.5%, p<.01), and race (African 15.9% vs 13.7%, Asian 4.3% vs 3.1%, p<.01). SDD RALRP patients were less likely to have hypertension (48.0% vs 51.6%, p<.01). Significant perioperative variables included shorter operation time (183 vs. 202 mins, p<.01) and fewer Level 4 ASA class (0.3% vs. 0.7%, p<.01). Post-operatively, SDD RALRP was associated with fewer 30-day readmissions (2.6% vs 3.6%, p=.04). There were no significant differences in serious adverse events. CONCLUSIONS: In recent years, there has been a significant increase in patients undergoing SDD RALRP. It is associated with fewer 30-day readmissions and does not have increased life-threatening complications. With continued advances in robotic surgery, SDD RALRP is becoming a safe option in the surgical management of prostate cancer. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e656 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Chris Du More articles by this author Arshia Aalami Harandi More articles by this author David M. Golombos More articles by this author Expand All Advertisement PDF downloadLoading ...

Interventions for improving adherence to iron chelation therapy in people with sickle cell disease or thalassaemia.

Interventions for improving adherence to iron chelation therapy in people with sickle cell disease or thalassaemia.

Immunogenicity and Safety of One-Dose Human Papillomavirus Vaccine Compared With Two or Three Doses in Tanzanian Girls (DoRIS): An Open-Label, Randomised, Non-inferiority Trial

ABSTRACT The global burden of cervical cancer remains very high, with more than 340,000 potentially preventable deaths annually and disproportionally affects low-income and middle-income countries. Countries that have adopted HPV vaccination administer a multidose schedule with 2 doses offered to girls younger than 15 years, and 3 offered to girls 15 years and older or immunocompromised individuals. Unfortunately, several barriers to full immunization remain, and only 15% of girls in the target age group worldwide are estimated to be fully vaccinated. A single-dose vaccine would remove many barriers and be significantly cheaper; however, evidence is needed on the immunogenicity and efficacy. This randomized phase 3 clinical trial (DoRIS) aimed to examine immune responses after a single dose of HPV vaccine in the target age group for HPV vaccination in Tanzania. Girls aged 9–14 years who have not been vaccinated for HPV and did not have any history of cervical lesions, treatment for positive cervical cancer screening, or immunocompromised status were invited from Government schools to participate. Participants were randomized to 1 of 6 arms comprising 3 different dose schedules of 2 different HPV vaccines (3 doses over 6 months, 2 doses given 6 months apart, or a single dose for either the 2-valent vaccine or the 9-valent vaccine). Blood samples were collected for immunological assays at 1, 7, 12, and 24 months after vaccination. The primary study outcome was noninferiority of HPV 16 and HPV 18 specific seropositivity after a single dose compared with 2 or 3 doses of the same vaccine 24 months after vaccination. Primary analyses were undertaken in the per-protocol population, including those who received the allocated doses of HPV vaccine in the protocol-defined window. A sensitivity analysis included all participants who received at least 1 dose of HPV vaccine. A total of 930 girls were enrolled and randomized with 155 participants per group. At 24 months, 856 (93%) girls were included in the per-protocol analysis of anti-HPV 16 antibody responses, and 831 (91%) in the per-protocol analysis of anti-HPV 18. All but 2 participants were seropositive for HPV 16 IgG at 24 months (1 participant in each of the 1-dose arms was not), and all but 6 participants were HPV 18 seropositive at 24 months (2 in the 1-dose 2-valent group, 3 in the 1-dose 9-valent group, and 1 in the 3-dose 9-valent group). Noninferiority of HPV 16 seroconversion was met at 24 months for 1 dose compared with 2 doses or 3 doses for both vaccines; however, noninferiority for HPV 18 seroconversion was not met despite 98% of girls in the 1-dose arms of both vaccines testing positive for anti-HPV 18. There was no difference in serious adverse events among study groups or any serious adverse events related to the vaccine. The results of this study demonstrate that, in healthy Tanzanian girls, a single dose of the 2-valent or 9-valent HPV vaccines was well tolerated and resulted in high seropositivity and induced stable vaccine responses that persisted to 24 months.

Pre-emptive TIPS for the treatment of bleeding from gastric fundal varices: Results of a randomised controlled trial

Background & AimsBleeding from gastric fundal varices (isolated gastric varices type 1/gastroesophageal varices type 2) represents a major problem because of a high incidence of rebleeding and death with standard-of-care therapy (endoscopic obliteration with tissue adhesives plus pharmacological therapy). Transjugular intrahepatic portosystemic shunts (TIPSs) are recommended as a rescue therapy. Pre-emptive ‘early’ TIPS (pTIPS) significantly improves control of bleeding and survival in patients at high-risk of dying or rebleeding from esophageal varices. MethodsThis randomised controlled trial investigate whether the use of pTIPS improves rebleeding-free survival in patients with gastric fundal varices (isolated gastric varices type 1 and/or gastroesophageal varices type 2) compared with standard therapy. ResultsThe study did not achieve the predefined sample size because of low recruitment. Nevertheless, pTIPS (n = 11) was more effective compared with combined endoscopic and pharmacological therapy (n = 10) in improving rebleeding-free survival (per protocol analysis: 100 vs. 28%; p = 0.017). This was mainly because of a better outcome in patients with Child-Pugh B or C scores. There were no differences in serious adverse events or in the incidence of hepatic encephalopathy among the different cohorts. ConclusionThe use of pTIPS should be considered in patients with Child-Pugh B or C scores bleeding from gastric fundal varices. Impact and implicationsThe first-line treatment of gastric fundal varices (GOV2 and/or IGV1) is the combination of pharmacological therapy and endoscopic obliteration with glue. TIPS is considered the main rescue therapy. Recent data suggest that, in patients at high-risk of dying or rebleeding (Child-Pugh C or B scores + active bleeding at endoscopy) from esophageal varices, the use of pTIPS, performed during the first 72 h from admission, results in an increased rate of control of bleeding and survival compared with combined endoscopic and pharmacological therapy. Herein, we present a randomised controlled trial comparing pTIPS with combined endoscopic (injection of glue) and pharmacological therapy (first, somatostatin or terlipressin; carvedilol after discharge) in the treatment of patients bleeding from GOV2 and/or IGV1. Although we were not able to include the calculated sample size because of the scarcity of these patients, our results show that the use of pTIPS is associated with a significantly higher actuarial rebleeding-free survival when analysed as per protocol. This is because of the greater efficacy of this treatment in patients with Child-Pugh B or C scores.

Safety and tolerability of monoclonal antibodies targeting the CGRP pathway and gepants in migraine prevention: A systematic review and network meta-analysis.

Direct comparisons of the tolerability and safety of migraine preventive treatments targeting the calcitonin gene-related peptide pathway are lacking. This study aimed to compare the safety and tolerability of anti-calcitonin gene-related peptide monoclonal antibodies and gepants in migraine prevention. A network meta-analysis of phase 3 randomized controlled trials assessing the safety and tolerability of anti-calcitonin gene-related peptide monoclonal antibodies (erenumab, eptinezumab, fremanezumab, or galcanezumab) and gepants (atogepant, rimegepant) in migraine prevention was performed. Primary outcomes were treatment-emergent adverse events and serious adverse events. Secondary outcomes included any adverse events, adverse events leading to treatment discontinuation and individual adverse events. We included 19 randomized controlled trials, comprising 14,584 patients. Atogepant 120 mg (OR 2.22, 95% CI [1.26, 3.91]) and galcanezumab 240 mg (OR 1.63, 95% CI [1.33, 2.00]) showed the largest odds of treatment-emergent adverse events compared to placebo. While eptinezumab 30 mg had greater odds of adverse events leading to treatment discontinuation (OR 2.62, 95% CI [1.03,6.66]). No significant differences in serious adverse events were found between active treatments and placebo. Eptinezumab was associated with the lowest odds of treatment-emergent adverse events and serious adverse events compared to placebo, whereas erenumab was associated with the lowest odds of any adverse events and quarterly fremanezumab with the lowest odds of treatment discontinuation due to adverse events. Monoclonal antibodies targeting the calcitonin gene-related peptide pathway and gepants are a safe and well tolerated option for migraine prevention.

Favipiravir in patients hospitalised with COVID-19 (PIONEER trial): a multicentre, open-label, phase 3, randomised controlled trial of early intervention versus standard care

COVID-19 has overwhelmed health services globally. Oral antiviral therapies are licensed worldwide, but indications and efficacy rates vary. We aimed to evaluate the safety and efficacy of oral favipiravir in patients hospitalised with COVID-19. We conducted a multicentre, open-label, randomised controlled trial of oral favipiravir in adult patients who were newly admitted to hospital with proven or suspected COVID-19 across five sites in the UK (n=2), Brazil (n=2) and Mexico (n=1). Using a permuted block design, eligible and consenting participants were randomly assigned (1:1) to receive oral favipiravir (1800 mg twice daily for 1 day; 800 mg twice daily for 9 days) plus standard care, or standard care alone. All caregivers and patients were aware of allocation and those analysing data were aware of the treatment groups. The prespecified primary outcome was the time from randomisation to recovery, censored at 28 days, which was assessed using an intention-to-treat approach. Post-hoc analyses were used to assess the efficacy of favipiravir in patients aged younger than 60 years, and in patients aged 60 years and older. The trial was registered with clinicaltrials.gov, NCT04373733. Between May 5, 2020 and May 26, 2021, we assessed 503 patients for eligibility, of whom 499 were randomly assigned to favipiravir and standard care (n=251) or standard care alone (n=248). There was no significant difference between those who received favipiravir and standard care, relative to those who received standard care alone in time to recovery in the overall study population (hazard ratio [HR] 1·06 [95% CI 0·89-1·27]; n=499; p=0·52). Post-hoc analyses showed a faster rate of recovery in patients younger than 60 years who received favipiravir and standard care versus those who had standard care alone (HR 1·35 [1·06-1·72]; n=247; p=0·01). 36 serious adverse events were observed in 27 (11%) of 251 patients administered favipiravir and standard care, and 33 events were observed in 27 (11%) of 248 patients receiving standard care alone, with infectious, respiratory, and cardiovascular events being the most numerous. There was no significant between-group difference in serious adverse events per patient (p=0·87). Favipiravir does not improve clinical outcomes in all patients admitted to hospital with COVID-19, however, patients younger than 60 years might have a beneficial clinical response. The indiscriminate use of favipiravir globally should be cautioned, and further high-quality studies of antiviral agents, and their potential treatment combinations, are warranted in COVID-19. LifeArc and CW+.

Efficacy and safety of COVID-19 vaccines.

Efficacy and safety of COVID-19 vaccines.