Background Baricitinib is an oral selective Janus kinase 1/2 inhibitor with known anti-inflammatory properties. This study evaluates the efficacy and safety of baricitinib in combination with standard of care for the treatment of hospitalised adults with COVID-19. Methods In this phase 3, double-blind, randomised, placebo-controlled trial, participants were enrolled from 101 centres across 12 countries in Asia, Europe, North America, and South America. Hospitalised adults with COVID-19 receiving standard of care were randomly assigned (1:1) to receive once-daily baricitinib (4 mg) or matched placebo for up to 14 days. Standard of care included systemic corticosteroids, such as dexamethasone, and antivirals, including remdesivir. The composite primary endpoint was the proportion who progressed to high-flow oxygen, non-invasive ventilation, invasive mechanical ventilation, or death by day 28, assessed in the intention-to-treat population. All-cause mortality by day 28 was a key secondary endpoint, and all-cause mortality by day 60 was an exploratory endpoint; both were assessed in the intention-to-treat population. Safety analyses were done in the safety population defined as all randomly allocated participants who received at least one dose of study drug and who were not lost to follow-up before the first post-baseline visit. This study is registered with ClinicalTrials.gov , NCT04421027 . Findings Between June 11, 2020, and Jan 15, 2021, 1525 participants were randomly assigned to the baricitinib group (n=764) or the placebo group (n=761). 1204 (79·3%) of 1518 participants with available data were receiving systemic corticosteroids at baseline, of whom 1099 (91·3%) were on dexamethasone; 287 (18·9%) participants were receiving remdesivir. Overall, 27·8% of participants receiving baricitinib and 30·5% receiving placebo progressed to meet the primary endpoint (odds ratio 0·85 [95% CI 0·67 to 1·08], p=0·18), with an absolute risk difference of −2·7 percentage points (95% CI −7·3 to 1·9). The 28-day all-cause mortality was 8% (n=62) for baricitinib and 13% (n=100) for placebo (hazard ratio [HR] 0·57 [95% CI 0·41–0·78]; nominal p=0·0018), a 38·2% relative reduction in mortality; one additional death was prevented per 20 baricitinib-treated participants. The 60-day all-cause mortality was 10% (n=79) for baricitinib and 15% (n=116) for placebo (HR 0·62 [95% CI 0·47–0·83]; p=0·0050). The frequencies of serious adverse events (110 [15%] of 750 in the baricitinib group vs 135 [18%] of 752 in the placebo group), serious infections (64 [9%] vs 74 [10%]), and venous thromboembolic events (20 [3%] vs 19 [3%]) were similar between the two groups. Interpretation Although there was no significant reduction in the frequency of disease progression overall, treatment with baricitinib in addition t...

Primary hyperparathyroidism is the third most common endocrine disorder after diabetes and thyroid disease, and women are affected twice as often as men. Hyperparathyroidism in pregnancy was first reported in 1931. Maternal complications in patients with hyperparathyroidism can be as high as 67%. We present a case of a pregnant patient with chronic hypertension that was exacerbated throughout the course of her pregnancy with a concomitant diagnosis of primary hyperparathyroidism and its sequelae for both the mother and fetus.

This is a cross-sectional analysis of spin in randomized controlled trial (RCT) abstracts published in top-ranked obesity and general medicine journals. The top seven obesity and four general medicine journals were searched from 1 January 2016 to 31 December 2017. To be included in this study, a trial must be an RCT with non-significant primary endpoint (P > 0.05), exclusively randomize subjects with overweight or obesity or have a primary endpoint of weight loss. These studies were analysed by two reviewers for spin in the abstract.The primary endpoint of our investigation was the frequency and type of spin. The secondary endpoint was to assess whether funding source was associated with the presence of spin. Our PubMed search yielded 1143 articles. Primary screening excluded 992 articles, and fulltext evaluation excluded an additional 106. Overall, 45 articles were included. Spin was identified in 21 of the 45 (46.7%) abstracts analysed. Evidence of spin was found in 17 (37.8%) abstract result sections and 11 (24.4%) abstract conclusion sections. Of the 39 RCTs reporting a clinical trial registry, 6 (15.4%) had evidence of selective reporting bias. Our study found that obesity medicine RCTs from top-ranked journals with non-significant primary endpoints published in 2016 and 2017 frequently have spin in their abstracts. Abstracts with evidence of spin may influence a reader's perception of new drugs or procedures. These results warrant a careful review of future RCTs, but may not be generalizable to RCTs published in lower-ranked journals. K E Y W O R D S bariatric surgery, cross-sectional review, obesity, weight loss therapy

IntroductionSelective reporting bias occurs when chance or selective outcome reporting rather than the intervention contributes to group differences. The prevailing concern about selective reporting bias is the possibility of results being modified towards specific conclusions. In this study, we evaluate randomized controlled trials (RCTs) published in hematology journals, a group in which selective outcome reporting has not yet been explored.MethodsOur primary goal was to examine discrepancies between the reported primary and secondary outcomes in registered and published RCTs concerning hematological malignancies reported in hematology journals with a high impact factor. The secondary goals were to address whether outcome reporting discrepancies favored statistically significant outcomes, whether a pattern existed between the funding source and likelihood of outcome reporting bias, and whether temporal trends were present in outcome reporting bias. For trials with major outcome discrepancies, we contacted trialists to determine reasons for these discrepancies. Trials published between January 1, 2010 and December 31, 2015 in Blood; British Journal of Haematology; American Journal of Hematology; Leukemia; and Haematologica were included.ResultsOf 499 RCTs screened, 109 RCTs were included. Our analysis revealed 118 major discrepancies and 629 total discrepancies. Among the 118 discrepancies, 30 (25.4%) primary outcomes were demoted, 47 (39.8%) primary outcomes were omitted, and 30 (25.4%) primary outcomes were added. Three (2.5%) secondary outcomes were upgraded to a primary outcome. The timing of assessment for a primary outcome changed eight (6.8%) times. Thirty-one major discrepancies were published with a P-value and twenty-five (80.6%) favored statistical significance. A majority of authors whom we contacted cited a pre-planned subgroup analysis as a reason for outcome changes.ConclusionOur results suggest that outcome changes occur frequently in hematology trials. Because RCTs ultimately underpin clinical judgment and guide policy implementation, selective reporting could pose a threat to medical decision making.

Background: Baricitinib, an oral selective Janus kinase 1 and 2 inhibitor, improved outcomes in a previous randomized controlled trial of hospitalized adults with COVID-19, in combination with remdesivir. Methods: In this phase 3, global, double-blind, randomized, placebo-controlled trial, 1525 hospitalized adults with COVID-19 receiving standard of care (SOC) were randomly assigned (1:1) to once-daily baricitinib 4-mg (N=764) or placebo (N=761) for up to 14 days. SOC included systemic corticosteroids in ~79% of participants (dexamethasone ~90%). The primary endpoint was the proportion who progressed to high-flow oxygen, non-invasive ventilation, invasive mechanical ventilation, or death by day 28. A key secondary endpoint was all-cause mortality by day 28. Results: Overall, 27.8% of participants receiving baricitinib vs 30.5% receiving placebo progressed (primary endpoint, odds ratio 0.85, 95% CI 0.67-1.08; p=0.18). The 28-day all-cause mortality was 8.1% for baricitinib and 13.1% for placebo, corresponding to a 38.2% reduction in mortality (hazard ratio [HR] 0.57, 95% CI 0.41-0.78; nominal p=0.002); 1 additional death was prevented per 20 baricitinib-treated participants. Reduction in mortality was seen for all pre-specified subgroups of baseline severity (most pronounced for participants on high-flow oxygen/non-invasive ventilation at baseline [17.5%, baricitinib vs 29.4%, placebo; HR 0.52, 95% CI 0.33-0.80; nominal p=0.007]). The frequency of adverse events, serious adverse events, serious infections, and venous thromboembolic events was similar between groups. Conclusions: While reduction of disease progression did not achieve statistical significance, treatment with baricitinib in addition to SOC (predominantly dexamethasone) significantly reduced mortality with a similar safety profile between groups of hospitalized COVID-19 participants.