METHODS: Solidarity enrolled consenting adults (aged ≥18 years) recently hospitalised with, in the view of their doctor, definite COVID-19 and no contraindication to any of the study drugs, regardless of any other patient characteristics. Participants were randomly allocated, in equal proportions between the locally available options, to receive whichever of the four study drugs (lopinavir, hydroxychloroquine, IFN-β1a, or remdesivir) were locally available at that time or no study drug (controls). All patients also received the local standard of care. No placebos were given. The protocol-specified primary endpoint was in-hospital mortality, subdivided by disease severity. Secondary endpoints were progression to ventilation if not already ventilated, and time-to-discharge from hospital. Final log-rank and Kaplan-Meier analyses are presented for remdesivir, and are appended for all four study drugs. Meta-analyses give weighted averages of the mortality findings in this and all other randomised trials of these drugs among hospital inpatients. Solidarity is registered with ISRCTN, ISRCTN83971151, and ClinicalTrials.gov, NCT04315948.
FINDINGS: Between March 22, 2020, and Jan 29, 2021, 14 304 potentially eligible patients were recruited from 454 hospitals in 35 countries in all six WHO regions. After the exclusion of 83 (0·6%) patients with a refuted COVID-19 diagnosis or encrypted consent not entered into the database, Solidarity enrolled 14 221 patients, including 8275 randomly allocated (1:1) either to remdesivir (ten daily infusions, unless discharged earlier) or to its control (allocated no study drug although remdesivir was locally available). Compliance was high in both groups. Overall, 602 (14·5%) of 4146 patients assigned to remdesivir died versus 643 (15·6%) of 4129 assigned to control (mortality rate ratio [RR] 0·91 [95% CI 0·82-1·02], p=0·12). Of those already ventilated, 151 (42·1%) of 359 assigned to remdesivir died versus 134 (38·6%) of 347 assigned to control (RR 1·13 [0·89-1·42], p=0·32). Of those not ventilated but on oxygen, 14·6% assigned to remdesivir died versus 16·3% assigned to control (RR 0·87 [0·76-0·99], p=0·03). Of 1730 not on oxygen initially, 2·9% assigned to remdesivir died versus 3·8% assigned to control (RR 0·76 [0·46-1·28], p=0·30). Combining all those not ventilated initially, 11·9% assigned to remdesivir died versus 13·5% assigned to control (RR 0·86 [0·76-0·98], p=0·02) and 14·1% versus 15·7% progressed to ventilation (RR 0·88 [0·77-1·00], p=0·04). The non-prespecified composite outcome of death or progression to ventilation occurred in 19·6% assigned to remdesivir versus 22·5% assigned to control (RR 0·84 [0·75-0·93], p=0·001). Allocation to daily remdesivir infusions (vs open-label control) delayed discharge by about 1 day during the 10-day treatment period. A meta-analysis of mortality in all randomised trials of remdesivir versus no remdesivir yielded similar findings.
INTERPRETATION: Remdesivir has no significant effect on patients with COVID-19 who are already being ventilated. Among other hospitalised patients, it has a small effect against death or progression to ventilation (or both).
FUNDING: WHO.
METHODS: The cross-sectional study was conducted in October-November 2017 at five government and two private schools in Bhakkar, Punjab, Pakistan. It comprised children aged 11-12 years. World Health Organisation standards and the modified International Caries Detection and Assessment Systems methods were used were used to determine the dental caries status of each subject. Results of the two methods were compared at all cut- offs where appropriate, using SPSS 17.
RESULTS: Of the 183 subjects, 101(55.2%) were boys. Those aged 12 years were 112(61.2%) while 71(38.8%) were aged 11 years. There was no statistically significant difference in values of the Decayed Missing and Filled Surface / Decayed Missing and Filled Teeth index as well as the prevalence of dental caries between two methods (p>0.05 each). Intra-examiner reproducibility was higher with the World Health Organisation method compared to the other index used (p<0.05).
CONCLUSIONS: Modified International Caries Detection and Assessment Systems method can be used in epidemiological surveys as it was found to provide results similar to the World Health Organisation criteria at cut-off point 2.
METHODS: A historical review of official reports, news articles, and gray literature was undertaken to identify tobacco industry tactics and strategies to hamper government efforts in implementing stronger pictorial health warning regulations in four Asian jurisdictions (Cambodia, Hong Kong, Malaysia, and the Philippines).
RESULTS: Nineteen countries/jurisdictions in the WHO Western Pacific region currently require pictorial health warnings on cigarette packs, including some of the world's largest, in line with the WHO Framework Convention on Tobacco Control Article 11 Guidelines. In the four jurisdictions examined, tobacco industry interference consisted of lobbying and misinformation of high-level government officers and policy-makers, distributing industry-friendly legislative drafts, taking government to court, challenging government timelines for law implementation, and mobilizing third parties. Strong political leadership and strategic advocacy enabled governments to successfully overcome this industry interference.
CONCLUSION: The tobacco industry uses similar tactics in different jurisdictions to derail, delay, and weaken the implementation of effective health warning policies. Identifying and learning from international experiences can help anticipate and defeat such challenges.
Materials and Methods: A cross-sectional study was performed to review the impact of 68Ga-DOTA-peptide (68Ga-DOTATATE or 68Ga-DOTATOC) PET/CT on patients with biopsy-proven GI-NET between January 2011 and December 2015. Suspected NET was excluded. Demographic data, tumoral characteristics, change of disease stage, pre-PET intended management and post-PET management were evaluated.
Results: Over a 5-year period, 82 studies of 68Ga-DOTA-peptide PET/CT were performed on 44 GI-NET patients. The most common primary site was the rectum (50.0%) followed by the small bowel, stomach and colon. Using WHO 2010 grading, 40.9% of patients had low-grade (G1) tumour, 22.7% intermediate (G2) and 4.5% high (G3). Of ten patients scheduled for pre-operative staging, 68Ga-DOTA-peptide PET/CT only led to therapeutic change in three patients. Furthermore, false-negative results of 68Ga-DOTA-peptide PET/CT were reported in one patient after surgical confirmation. However, therapeutic changes were seen in 20/36 patients (55.6%) scheduled for post-surgical restaging or assessment of somatostatin analogue (SSA) eligibility. When 68Ga-DOTA-peptide PET/CT was used for monitoring disease progress during systemic treatment (sandostatin, chemotherapy, everolimus and PRRT) in metastatic disease, impact on management modification was seen in 19/36 patients (52.8%), of which 84.2% had inter-modality change (switch to everolimus, chemotherapy or PRRT) and 15.8% had intra-modality change (increased SSA dosage).
Conclusions: 68Ga-DOTA-peptide PET/CT has a significant impact on management decisions in GI-NET patients as it can provide additional information on occult metastasis/equivocal lesions and supply the clinician an opportunity to select patients for targeted therapy.