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Purpose We aimed to compare treatment effect sizes between overall survival (OS) and progression-free survival (PFS) in trials of US Food and Drug Administration-approved oncology immunotherapy drugs with results posted at ClinicalTrials.gov . Methods We searched ClinicalTrials.gov for phase II to IV cancer trials of Food and Drug Administration-approved immunotherapy drugs and selected those reporting results for both OS and PFS. For each trial, we extracted the hazard ratios (HRs) with 95% CIs for both outcomes and evaluated the differences by a ratio of HRs (rHRs): the HR for PFS to that for OS. We performed a random effects meta-analysis across trials to obtain a summary rHR. We also evaluated surrogacy of PFS for OS by the coefficient of determination and the surrogacy threshold effect, the minimal value of HR for PFS to predict a non-null effect on OS. Results We identified 51 trials assessing 14 drugs across 15 conditions. Treatment effect sizes were 17% greater, on average, with PFS than with OS (rHR, 0.83; 95% CI, 0.79 to 0.88; I = 34.4%; P = .01; τ = 0.0129). Nearly one half of the trials (n = 23, 45%) showed statistically significant benefits for PFS but not for OS. Differences were great for trials of obinutuzumab (rHR, 0.21; 95% CI, 0.08 to 0.54), bevacizumab (rHR, 0.75; 95% CI, 0.67 to 0.84), and rituximab (rHR, 0.79; 95% CI, 0.64 to 0.98). The coefficient of determination was 38% and the surrogacy threshold effect was 0.50. Conclusion Treatment effect sizes in trials of immunotherapy drugs were greater for PFS than for OS, with important differences for some drugs, which is consistent with surrogacy metrics. Caution must be taken when interpreting PFS in the absence of OS data.

BackgroundMany women would like to avoid pharmacological or invasive methods of pain management in labour and this may contribute towards the popularity of complementary methods of pain management. This review examined evidence about the use of acupuncture and acupressure for pain management in labour. This is an update of a review last published in 2011. ObjectivesTo examine the e ects of acupuncture and acupressure for pain management in labour. Search methodsFor this update, we searched Cochrane Pregnancy and Childbirth's

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Objective To describe the characteristics of healthcare workers (HCWs) infected with COVID‐19 and to examine their sources of exposure. Methods A descriptive cross‐sectional study using data extracted from the centralized disease notification system comprising individuals confirmed with COVID‐19 in Singapore between 23 January and 17 April 2020. Occupation of HCWs was categorized into six categories. Their job nature was classified into “frontline” or “back‐end” based on the frequency of direct patient contact, and source of exposure was classified as family/household, social interaction or workplace. Chi‐square and median tests were used to identify differences between categorical groups and sample medians, respectively. Results A total of 88 (1.7%) HCWs were identified from 5,050 cases. Their median age was 35 years. Chinese and Indians constituted 42.0% and 31.8%, respectively, and 43.2% were foreigners. The majority (63.6%) was serving at frontlines handling patient‐facing duties, 15.9% were doctors, 11.4% were nurses and 44.3% were ancillary staff. About 81.8% acquired the infection locally, of which 40.3% did not have a clearly identifiable source of exposure. Exposure from the family/household was most common (27.8%), followed by workplace (16.7%) and social interaction (15.3%). All HCWs were discharged well with no mortality; three (3.4%) were ever admitted to intensive care unit and required increased care. Conclusion Healthcare workers accounted for a small proportion of COVID‐19 cases in Singapore with favourable outcomes. The possibility of transmission resulting from family/household exposure and social interactions highlights the need to maintain strict vigilance and precautionary measures at all times beyond the workplace.

Background Personal mobility devices (PMDs) like skate-scooters, electric bicycles (e-bikes) or motorised scooters (e-scooters) have become widely available globally. There are several studies describing the rising incidence of injury from such devices. The aim of our study was to examine PMD user factors between motorised (MotPMDs) vs non-motorised PMDs (NonPMDs) as risk factors for severe injury and the need for hospital admission. Methods We analysed de-identified National Trauma Registry data (2015 to 2017) from all public sector hospitals in Singapore for patients aged 12 and above presenting to emergency departments with PMD-related injuries. Multivariable logistic regression was used to identify risk factors for the primary outcome of interest (higher injury severity, defined as Injury Severity Score / ISS > =9), and the secondary outcome of interest (need for hospital admission). Additional subgroup analysis was conducted comparing only scooters (manual vs electric), the most common sub-type of PMD in our study. Results Of the 614 patients in our study, majority were male (74%), median age 33 years, with 136 (22%) sustaining injuries with ISS > =9; 185 (30%) admitted [median stay length 3 days (IQR: 1–6)] and 93 (15%) required surgery. MotPMDs were more common (480, 78%), with e-scooters being the most common motorised device (393, 64%). There were 6 deaths, all in MotPMD users. On both univariate and multivariable regression, MotPMD users [OR 3.82, 95% CI 1.51–12.9, p = 0.01] and older users (> = 60 years) [OR 9.47, 95% CI 2.45–62.9, p = 0.004] were more likely to sustain injuries with ISS > =9, and more likely to need admission (MotPMD users [OR 1.8, 95% CI 1.04–3.29, p = 0.045], age > =60 years [OR 4.72, 95% CI 1.86–13.0, p = 0.002]). Conclusion MotPMDs tripled the risk of severe injury and doubled the risk of requiring hospitalisation, compared to NonPMDs, likely due to higher travelling speeds. Increased age was also associated with severe injury and requiring hospitalisation.

Background Progression-free survival (PFS) is a surrogate endpoint widely used for overall survival (OS) in oncology. Validation of PFS as a surrogate must be done for each indication and each intervention. We aimed to identify all studies evaluating the validity of PFS as a surrogate for OS in oncology, and to describe their methodological characteristics. Methods We conducted a systematic review by searching MEDLINE via PubMed and the Cochrane Library with no limitation on time, selected relevant studies and extracted data in duplicate on how surrogacy was evaluated (meta-analytic approach, assessment of correlation and level of evaluation). Results We identified 91 studies evaluating the validity of PFS as a surrogate for OS in 24 cancer localisations. Although a meta-analytic approach was used in 83 (91%) studies, the methods used to validate PFS as a surrogate of OS were heterogeneous across studies. Of the 47 studies concluding that PFS is a good surrogate for OS, for 15 (32%), there was no quantitative argument for surrogacy. Conclusions Although most studies used a meta-analytic approach as recommended, our methodological review highlights heterogeneity in methods and reporting, which stresses the importance of developing and applying clear recommendations in this area.

We have isolated two alkaline phosphatases (H-AP and L-AP, for high and low molecular mass, respectively) from Pseudomonas aeruginosa PA01. These two enzymes were found to differ in mobility on sodium dodecyl sulphate polyacrylamide gels (H-AP, M(r) = 51,000 and L-AP, M(r) = 39,500), amino-terminal amino acid sequence and did not cross-react. Both enzymes were active as phosphomonoesterases while only L-AP demonstrated any phosphodiesterase activity. Both enzymes were purified from P. aeruginosa grown in phosphate limiting conditions using the same protocol and were identified in both periplasmic and extracellular locations. A low level of H-AP was produced constitutively whereas L-AP was produced only after induction by reduced phosphate concentration in the growth medium. An L-AP-like enzyme has been previously described, however, this is the first report of a second P. aeruginosa alkaline phosphatase.