Background We aimed to assess the efficacy and safety of two neutralising monoclonal antibody therapies (sotrovimab [Vir Biotechnology and GlaxoSmithKline] and BRII-196 plus BRII-198 [Brii Biosciences]) for adults admitted to hospital for COVID-19 (hereafter referred to as hospitalised) with COVID-19. Methods In this multinational, double-blind, randomised, placebo-controlled, clinical trial (Therapeutics for Inpatients with COVID-19 [TICO]), adults (aged ≥18 years) hospitalised with COVID-19 at 43 hospitals in the USA, Denmark, Switzerland, and Poland were recruited. Patients were eligible if they had laboratory-confirmed SARS-CoV-2 infection and COVID-19 symptoms for up to 12 days. Using a web-based application, participants were randomly assigned (2:1:2:1), stratified by trial site pharmacy, to sotrovimab 500 mg, matching placebo for sotrovimab, BRII-196 1000 mg plus BRII-198 1000 mg, or matching placebo for BRII-196 plus BRII-198, in addition to standard of care. Each study product was administered as a single dose given intravenously over 60 min. The concurrent placebo groups were pooled for analyses. The primary outcome was time to sustained clinical recovery, defined as discharge from the hospital to home and remaining at home for 14 consecutive days, up to day 90 after randomisation. Interim futility analyses were based on two seven-category ordinal outcome scales on day 5 that measured pulmonary status and extrapulmonary complications of COVID-19. The safety outcome was a composite of death, serious adverse events, incident organ failure, and serious coinfection up to day 90 after randomisation. Efficacy and safety outcomes were assessed in the modified intention-to-treat population, defined as all patients randomly assigned to treatment who started the study infusion. This study is registered with ClinicalTrials.gov , NCT04501978 . Findings Between Dec 16, 2020, and March 1, 2021, 546 patients were enrolled and randomly assigned to sotrovimab (n=184), BRII-196 plus BRII-198 (n=183), or placebo (n=179), of whom 536 received part or all of their assigned study drug (sotrovimab n=182, BRII-196 plus BRII-198 n=176, or placebo n=178; median age of 60 years [IQR 50–72], 228 [43%] patients were female and 308 [57%] were male). At this point, enrolment was halted on the basis of the interim futility analysis. At day 5, neither the sotrovimab group nor the BRII-196 plus BRII-198 group had significantly higher odds of more favourable outcomes than the placebo group on either the pulmonary scale (adjusted odds ratio sotrovimab 1·07 [95% CI 0·74–1·56]; BRII-196 plus BRII-198 0·98 [95% CI 0·67–1·43]) or the pulmonary-plus complications scale (sotrovimab 1·08 [0·74–1·58]; BRII-196 plus BRII-198 1·00 [0·68–1·46]). By day 90, sustained clinical recovery was seen in 151 (85%) patients in the placebo group compared with 160 (88%) in the sotrovimab group (adjusted rate ratio 1·12 [95% CI 0·91–...

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ObjectiveTo determine the effectiveness of chlorhexidine 0.12% mouthwash (CHX) after tooth extraction for the prevention of alveolar osteitis (AO).Material and methodsWe conducted a double-blind randomised clinical trial stratified by risk factors. We enrolled a cohort of 822 patients who underwent dental extractions, and were considered to be at risk of developing AO (previous surgical site infection, traumatic extraction, and tobacco smoking). After extraction, patients were randomly allocated for CHX group or placebo group, matched by risk factors. The primary outcome was clinical diagnosis of AO: increasing postoperative pain for 4 d within and around the socket, and total or partial breakdown of the blood clot in the socket with or without bone exposure.ResultsFollow-up was completed by 744 participants (372 chlorhexidine and 372 placebo). We detected no significant differences between the two groups at baseline. After completed follow-up, risk factors were equally distributed between the two groups. Overall incidence of OA was 4.97%, in which 27 participants treated with placebo (7.26%) and 10 participants treated with CHX (2.69%) developed AO. CHX reduced the incidence of AO by 63% [Absolute Risk Reduction: 4.57 (95% CI 1.5-7.7), Number Needed to Treat: 21.88 (95% CI 13.0-69.3), Fisher's exact test: p=0.006]. No adverse effects were reported.ConclusionThe use of chlorhexidine 0.12% mouthwash after tooth extraction is safe and effective in reducing the incidence of AO in high-risk patients.

Critical donor shortages have impulsed the need to expand donor heart eligibility through the use of marginal hearts in cardiac transplantation. Donor valvular disease has been considered as an absolute contraindication for transplant. A 39-year-old male patient with end-stage non-compaction cardiomyopathy, an INTERMACS II heart failure, and a left ventricular ejection fraction of 8% was taken to an orthotopic heart transplantation. During donor bench graft examination, a congenital bicuspid and calcified aortic valve was found. The native bicuspid valve was removed and the annular calcification debrided; a #21 bioprosthetic aortic valve was then implanted.

Background Destination left ventricular assist device placement is increasing as a result of donor shortages and changing patient attitudes. As organ shortages become critical, LVAD programs become fundamental even in more remote regions of the world including island states. Here, we provide a look into the current state and availability of LVAD programs in island states. Main body A narrative review was performed using the World Health Organization Global Index Medicus and PubMed/MEDLINE databases to identify articles describing the island states having reported LVAD placements and programs. Additionally, INTERMACS reports were used. Data were retrieved and a review is presented describing the current state of LVADs in island states. The Caribbean region as a whole has a heart failure (HF) prevalence of 814 per 100,000 and Oceania 667 per 100,000 people. We estimate that over 3000 people in these islands need either a heart transplant or an LVAD. Short conclusion For HF patients living in island regions, special attention should be paid to the inability of having access to specialized mainland medical care. The continuous quest for a solution to HF in island regions should include the establishing of high-quality LVAD programs in a transfer-network centralized/regionalized system to care for those patients not candidates for long-distance air-bridging.

Purpose: To evaluate 52-week efficacy and safety of a treat-and-extend regimen of intravitreal aflibercept 2 mg on treatment-naive Type 3 neovascularization lesions. Methods: Phase IV, prospective, open-label, single-arm, multicenter trial including patients with untreated Stage I/II Type 3 neovascularization lesions and baseline best-corrected visual acuity between 78 and 23 Early Treatment Diabetic Retinopathy Study letters. Primary endpoint: mean change in best-corrected visual acuity from baseline at 52 weeks. Results: Thirty-two eyes from 32 patients were included (mean ± SD age: 78.2 ± 7.7 years, 68.8% females, baseline best-corrected visual acuity: 57.9 ± 15.4 [Snellen fraction 20/70]). Best-corrected visual acuity increased by 10.5 ± 15.9 Early Treatment Diabetic Retinopathy Study letters at Week 52 (P = 0.0001). The mean foveal and choroidal thickness decreased by 129.1 ± 80.1 µm (P < 0.0001) and 64.3 ± 96.5 (P = 0.0001), respectively. The proportion of patients with intraretinal/subretinal fluid decreased from 28 (87.5%) at baseline to 3 (11.5%) at Week 52 (P < 0.0001). Pigment epithelial detachment and lesion area showed nonsignificant changes over 52 weeks. The mean number of injections was 8.0 ± 2.0. Seven (21.9%) patients experienced treatment-related adverse events and two (6.3%) experienced serious adverse events; one (3.1%) ocular serious adverse event requiring treatment withdrawal, endophthalmitis, and one (3.1%) nonocular spontaneously resolved serious adverse event, palpitations. One (3.1%) patient experienced an APTC ATE: nonfatal stroke not related to trial treatment. Conclusion: A treat-and-extend regimen of aflibercept improves visual acuity and retinal edema in eyes with Type 3 neovascularization over 52 weeks with good tolerability.

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Purpose: To identify patient-reported outcomes (PROs) and other clinical outcome measures (contrast sensitivity (CS), low-luminance visual acuity (LLVA) and reading acuity or reading speed (RA-RS)), relevant to patients with age-related macular degeneration (AMD) or diabetic retinopathy (DR), which would be recommended for use in clinical practice. Methods: The RAND/UCLA Appropriateness Method, based on the synthesis of the scientific evidence and the collective judgment of an expert panel using the two-round Delphi method, was applied. The evidence synthesis was performed by searching for articles on outcome measures for AMD and/or DR published between 2005 and 2018 in English or Spanish. The expert panel consisted of 14 Spanish ophthalmologists, who rated the recommendation degree for each outcome measure on a scale of 1 (extremely irrelevant) to 9 (maximum relevance). The recommended outcome measures were established according to the panel median score and the level of the panelists’ agreement. Results: Through the evidence search, 33 PRO-specific questionnaires (21 for visual function, six for AMD, three for DR, one for AMD and DR) and two treatment satisfaction questionnaires (one on AMD and one on DR) were identified. In addition, 21 methods were found for measuring CS, five for LLVA, and nine for RA-RS. According to the panel ratings, 11 of the 64 outcome measures evaluated for AMD, and seven of the 61 evaluated for DR were recommended. Conclusion: The AMD and DR outcome measures recommended will help ophthalmologists choose the outcome measure most appropriate for their patients. Furthermore, the use of PROs will contribute to shifting clinical practice towards patient-centered medicine.