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...

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Antibiotics are administered to cystic fibrosis patients for chronic endobronchial infection complicated by frequent exacerbations. Agents active against Staphylococcus aureus, Pseudomonas aeruginosa or both are administered. Serum antibiotic concentrations were measured in cystic fibrosis patients in an effort to optimise antibiotic dose and frequency. This led to the observation that cystic fibrosis subjects had (in general) a larger Vd and increased total body clearance of beta-lactams and aminoglycosides than non-cystic fibrosis subjects. The larger Vd is mainly due to the increased amount of lean body mass per kg bodyweight, although increased tissue binding may also account for part of this. The increased total body clearance of beta-lactams appears to be due to increased renal elimination, particularly tubular secretion. Decreased tubular reabsorption and increased non-renal clearance contribute to the increased total body clearance of metabolised beta-lactams and aminoglycosides. However, the lack of concomitant controls in many studies make these generalisations tentative. The result of the apparent cystic fibrosis-specific differences is lower peak serum antibiotic concentrations, a smaller AUC, and a shorter elimination half-life than non-cystic fibrosis subjects. Since sputum (and bronchial mucosal) concentration is dependent on the peak serum concentration (and AUC), cystic fibrosis subjects require larger doses of most antibiotics more frequently. Newer quinolones may be an exception. Studies comparing the efficacy and safety of larger and more frequent antibiotic doses to conventional therapy are not available. Although it appears logical to mimic serum antibiotic concentrations found in non-cystic fibrosis subjects, the lack of information on the ideal sputum concentration versus time curve should temper our enthusiasm for cystic fibrosis-specific dosage regimens.