Background Surgery is the main modality of cure for solid cancers and was prioritised to continue during COVID-19 outbreaks. This study aimed to identify immediate areas for system strengthening by comparing the delivery of elective cancer surgery during the COVID-19 pandemic in periods of lockdown versus light restriction. Methods This international, prospective, cohort study enrolled 20 006 adult (≥18 years) patients from 466 hospitals in 61 countries with 15 cancer types, who had a decision for curative surgery during the COVID-19 pandemic and were followed up until the point of surgery or cessation of follow-up (Aug 31, 2020). Average national Oxford COVID-19 Stringency Index scores were calculated to define the government response to COVID-19 for each patient for the period they awaited surgery, and classified into light restrictions (index <20), moderate lockdowns (20–60), and full lockdowns (>60). The primary outcome was the non-operation rate (defined as the proportion of patients who did not undergo planned surgery). Cox proportional-hazards regression models were used to explore the associations between lockdowns and non-operation. Intervals from diagnosis to surgery were compared across COVID-19 government response index groups. This study was registered at ClinicalTrials.gov , NCT04384926 . Findings Of eligible patients awaiting surgery, 2003 (10·0%) of 20 006 did not receive surgery after a median follow-up of 23 weeks (IQR 16–30), all of whom had a COVID-19-related reason given for non-operation. Light restrictions were associated with a 0·6% non-operation rate (26 of 4521), moderate lockdowns with a 5·5% rate (201 of 3646; adjusted hazard ratio [HR] 0·81, 95% CI 0·77–0·84; p<0·0001), and full lockdowns with a 15·0% rate (1775 of 11 827; HR 0·51, 0·50–0·53; p<0·0001). In sensitivity analyses, including adjustment for SARS-CoV-2 case notification rates, moderate lockdowns (HR 0·84, 95% CI 0·80–0·88; p<0·001), and full lockdowns (0·57, 0·54–0·60; p<0·001), remained independently associated with non-operation. Surgery beyond 12 weeks from diagnosis in patients without neoadjuvant therapy increased during lockdowns (374 [9·1%] of 4521 in light restrictions, 317 [10·4%] of 3646 in moderate lockdowns, 2001 [23·8%] of 11 827 in full lockdowns), although there were no differences in resectability rates observed with longer delays. Interpretation Cancer surgery systems worldwide were fragile to lockdowns, with one in seven patients who were in regions with full lockdowns not undergoing planned surgery and experiencing longer preoperative delays. Although short-term oncological outcomes were not compromised in those selected for surgery, delays and non-operations might lead to long-term reductions in survival. During current and future periods of societal restriction, the resilience of elective surgery systems requires strengthening, which might include...
RheothRx (Glaxo Wellcome Inc, Research Triangle Park, NC; poloxamer 188) Injection is a nonionic surfactant with hemorrheologic properties that suggest it may be useful in treating acute painful episodes (vasoocclusive crises) of sickle cell disease (SCD). We conducted a randomized, double-blind, placebo-controlled pilot study to evaluate the safety and efficacy of poloxamer, formulated as RheothRx Injection, in 50 patients with SCD. Patients with moderate to severe painful episodes requiring parenteral analgesics were randomized to receive a 48-hour infusion of either RheothRx or placebo. Pain was assessed every 4 hours. Efficacy endpoints included: (1) painful episode duration, (2) days of hospitalization, (3) quantity of analgesics used, and (4) pain intensity scores. Three subgroups of patients were considered for efficacy analyses based on the actual duration of the study drug infusion and the completeness of pain score data collection. Compared with placebo and depending on the subgroup, RheothRx-treated patients showed a 16% to 45% decrease in duration of painful episodes, a 1- to 2-day reduction in hospital stay, a threefold to fivefold reduction in analgesic requirements, and a 1-point reduction (using a 5-point scale) in average pain intensity scores at 72 hours. RheothRx was well tolerated; no clinically significant differences were observed between treatments with respect to adverse experiences or other safety measures. In addition, there were no differences between treatment groups in the incidence of recurrent painful episodes. In this study, RheothRx significantly reduced total analgesic use and pain intensity and showed trends to shorter duration of painful episodes and total days of hospitalization. In patients with moderate to severe vasoocclusive pain, RheothRx was safe and may offer a therapeutic benefit.
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