Standards for clinical trials for treating TB.

BACKGROUND: The value, speed of completion and robustness of the evidence generated by TB treatment trials could be improved by implementing standards for best practice.METHODS: A global panel of experts participated in a Delphi process, using a 7-point Likert scale to score and revise draft standards until consensus was reached.RESULTS: Eleven standards were defined: Standard 1, high quality data on TB regimens are essential to inform clinical and programmatic management; Standard 2, the research questions addressed by TB trials should be relevant to affected communities, who should be included in all trial stages; Standard 3, trials should make every effort to be as inclusive as possible; Standard 4, the most efficient trial designs should be considered to improve the evidence base as quickly and cost effectively as possible, without compromising quality; Standard 5, trial governance should be in line with accepted good clinical practice; Standard 6, trials should investigate and report strategies that promote optimal engagement in care; Standard 7, where possible, TB trials should include pharmacokinetic and pharmacodynamic components; Standard 8, outcomes should include frequency of disease recurrence and post-treatment sequelae; Standard 9, TB trials should aim to harmonise key outcomes and data structures across studies; Standard 10, TB trials should include biobanking; Standard 11, treatment trials should invest in capacity strengthening of local trial and TB programme staff.CONCLUSION: These standards should improve the efficiency and effectiveness of evidence generation, as well as the translation of research into policy and practice.

Fever as a predictor of adverse outcomes in COVID-19.

BACKGROUND/INTRODUCTION: There are little data on outcomes of COVID-19 patients with the presence of fever compared to the presence of symptoms. AIM: We examined the associations between symptomology, presence of fever and outcomes of a COVID-19 cohort. DESIGN AND METHODS: Between 23 January and 30 April 2020, 554 COVID-19 patients were admitted to a tertiary hospital in Singapore. They were allocated into four groups based on symptomology and fever-Group 1: asymptomatic and afebrile, Group 2: symptomatic but afebrile, Group 3: febrile but asymptomatic and Group 4: symptomatic and febrile. The primary outcomes were intensive care unit (ICU) admissions and mortality. The composite end-point included ICU admissions, mortality or any COVID-19 related end-organ involvement. RESULTS: There were differences in ferritin (P=0.003), C-reactive protein (CRP) levels (P<0.001) and lymphopenia (P=0.033) across all groups, with the most favourable biochemical profile in Group 1, and the least in Group 4. Symptomatic groups (Groups 2 and 4) had higher ICU admissions (1.9% and 6.0%, respectively, P=0.003) than asymptomatic groups (Groups 1 and 3). Composite end-point was highest in Group 4 (24.0%), followed by Group 3 (8.6%), Group 2 (4.8%) and Group 1 (2.4%) (P<0.001). The presence of fever (OR 4.096, 95% CI 1.737-9.656, P=0.001) was associated with the composite end-point after adjusting for age, pulse rate, comorbidities, lymphocyte, ferritin and CRP. Presence of symptoms was not associated with the composite end-point. DISCUSSION/CONCLUSION: In this COVID-19 cohort, presence of fever was a predictor of adverse outcomes. This has implications on the management of febrile but asymptomatic COVID-19 patients.

Rapid publications risk the integrity of science in the era of COVID-19.

BACKGROUND: Preprint manuscripts, rapid publications and opinion pieces have been essential in permitting the lay press and public health authorities to preview data relating to coronavirus disease 2019 (COVID-19), including the range of clinical manifestations and the basic epidemiology early on in the pandemic. However, the rapid dissemination of information has highlighted some issues with communication of scientific results and opinions in this time of heightened sensitivity and global concern. MAIN TEXT: Rapid publication of COVID-19 literature through expedited review, preprint publications and opinion pieces are important resources for the medical scientific community. Yet the risks of unverified information loom large in times when the healthcare community is desperate for information. Information that has not been properly vetted, or opinion pieces without solid evidence, may be used to influence public health policy decisions. We discuss three examples of unverified information and the consequences in this time of high anxiety surrounding COVID-19. CONCLUSIONS: In an era when information can be widely and swiftly disseminated, it is important to ensure that the scientific community is not an inadvertent source of misinformation. This will require a multimodal approach, with buy-in from editors, publishers, preprint servers, authors and journalists. The landscape of medical publications has changed, and a collaborative approach is required to maintain a high standard of scientific communications.

Changes in nutrient intake during the menstrual cycle of overweight women with premenstrual syndrome.

This study presents the nutrient data collected from women who were being screened for premenstrual syndrome (PMS) for entry into an intervention study. Screening was by the Steiner self-rated questionnaire. One hundred and forty-four overweight women completed the screening process and eighty-eight met the criteria for PMS. All women kept 4 d diet diaries pre- and postmenstrually over two menstrual cycles. The mean energy and macronutrient intakes were compared between the pre- and postmenstrual phases. Energy and macronutrient intake was also calculated according to food categories. Goldberg's cut-off limit for the ratio of energy intake to estimated basal metabolic rate was used to exclude data that was incompatible with predicted energy requirements. The diet diaries were also used to determine the mean number of meals or snacks eaten pre- and postmenstrually. Nutrient analysis of the diet diaries of the women with PMS showed a significant increase (P < 0.001) in total energy and all macronutrients premenstrually when compared to nutrient intake postmenstrually. Women who did not meet the criteria for PMS showed a significant increase in energy and fat intake (P < 0.05) but not in the other macronutrients. When adjusted for energy, data collected from women with PMS showed a premenstrual significant increase in fat, carbohydrate (P < 0.05) and simple sugars (P < 0.001). There was a significant decrease (P < 0.001) in protein premenstrually. Women not meeting the PMS criteria showed no significant difference between pre- and postmenstrual intakes when adjusted for energy. Analysis according to food categories in women with PMS showed a significantly greater intake premenstrually of energy and all macronutrients for cereals, cakes and desserts and high-sugar foods (P < 0.001). In women with PMS there was a significantly greater number of 'episodes of eating' premenstrually (P < 0.001). This study provides further evidence, to support the very limited number of earlier studies, that there is a group of women with PMS who increase their nutrient intake during the premenstrual phase. This could potentially be a contributing factor for some women experiencing difficulties adhering to suggested dietary modification and should be considered when counselling premenopausal women.