BACKGROUNDMultiple myeloma cells uniformly overexpress CD38. We studied daratumumab, a CD38-targeting, human IgG1κ monoclonal antibody, in a phase 1-2 trial involving patients with relapsed myeloma or relapsed myeloma that was refractory to two or more prior lines of therapy. METHODSIn part 1, the dose-escalation phase, we administered daratumumab at doses of 0.005 to 24 mg per kilogram of body weight. In part 2, the dose-expansion phase, 30 patients received 8 mg per kilogram of daratumumab and 42 received 16 mg per kilogram, administered once weekly (8 doses), twice monthly (8 doses), and monthly for up to 24 months. End points included safety, efficacy, and pharmacokinetics. RESULTSNo maximum tolerated dose was identified in part 1. In part 2, the median time since diagnosis was 5.7 years. Patients had received a median of four prior treatments; 79% of the patients had disease that was refractory to the last therapy received (64% had disease refractory to proteasome inhibitors and immunomodulatory drugs and 64% had disease refractory to bortezomib and lenalidomide), and 76% had received autologous stem-cell transplants. Infusion-related reactions in part 2 were mild (71% of patients had an event of any grade, and 1% had an event of grade 3), with no dose-dependent adverse events. The most common adverse events of grade 3 or 4 (in ≥5% of patients) were pneumonia and thrombocytopenia. The overall response rate was 36% in the cohort that received 16 mg per kilogram (15 patients had a partial response or better, including 2 with a complete response and 2 with a very good partial response) and 10% in the cohort that received 8 mg per kilogram (3 had a partial response). In the cohort that received 16 mg per kilogram, the median progression-free survival was 5.6 months (95% confidence interval [CI], 4.2 to 8.1), and 65% (95% CI, 28 to 86) of the patients who had a response did not have progression at 12 months.

Hemostatic therapy with rFVIIa reduced growth of the hematoma but did not improve survival or functional outcome after intracerebral hemorrhage. (ClinicalTrials.gov number, NCT00127283 [ClinicalTrials.gov].).

Treatment with rFVIIa within four hours after the onset of intracerebral hemorrhage limits the growth of the hematoma, reduces mortality, and improves functional outcomes at 90 days, despite a small increase in the frequency of thromboembolic adverse events.

Background Population-level knowledge on individuals at high risk of severe and fatal coronavirus disease 2019 (COVID-19) is urgently needed to inform targeted protection strategies in the general population. Methods We examined characteristics and predictors of hospitalization and death in a nationwide cohort of all Danish individuals tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from 27 February 2020 until 19 May 2020. Results We identified 11 122 SARS-CoV-2 polymerase chain reaction-positive cases of whom 80% were community-managed and 20% were hospitalized. Thirty-day all-cause mortality was 5.2%. Age was strongly associated with fatal disease {odds ratio [OR] 15 [95% confidence interval (CI): 9–26] for 70–79 years, increasing to OR 90 (95% CI: 50–162) for ≥90 years, when compared with cases aged 50–59 years and adjusted for sex and number of co-morbidities}. Similarly, the number of co-morbidities was associated with fatal disease [OR 5.2 (95% CI: 3.4–8.0), for cases with at least four co-morbidities vs no co-morbidities] and 79% of fatal cases had at least two co-morbidities. Most major chronic diseases were associated with hospitalization, with ORs ranging from 1.3–1.4 (e.g. stroke, ischaemic heart disease) to 2.6–3.4 (e.g. heart failure, hospital-diagnosed kidney disease, organ transplantation) and with mortality with ORs ranging from 1.1–1.3 (e.g. ischaemic heart disease, hypertension) to 2.5–3.2 (e.g. major psychiatric disorder, organ transplantation). In the absence of co-morbidities, mortality was <5% in persons aged ≤80 years. Conclusions In this nationwide population-based COVID-19 study, increasing age and multimorbidity were strongly associated with hospitalization and death. In the absence of co-morbidities, the mortality was, however, <5% until the age of 80 years.

Background Individuals admitted to hospital for COVID-19 might have persisting symptoms (so-called long COVID) and delayed complications after discharge. However, little is known regarding the risk for those not admitted to hospital. We therefore examined prescription drug and health-care use after SARS-CoV-2 infection not requiring hospital admission. Methods This was a population-based cohort study using the Danish prescription, patient, and health insurance registries. All individuals with a positive or negative RT-PCR test for SARS-CoV-2 in Denmark between Feb 27 and May 31, 2020, were eligible for inclusion. Outcomes of interest were delayed acute complications, chronic disease, hospital visits due to persisting symptoms, and prescription drug use. We used data from non-hospitalised SARS-CoV-2-positive and matched SARS-CoV-2-negative individuals from 2 weeks to 6 months after a SARS-CoV-2 test to obtain propensity score-weighted risk differences (RDs) and risk ratios (RRs) for initiation of 14 drug groups and 27 hospital diagnoses indicative of potential post-acute effects. We also calculated prior event rate ratio-adjusted rate ratios of overall health-care use. This study is registered in the EU Electronic Register of Post-Authorisation Studies (EUPAS37658). Findings 10 498 eligible individuals tested positive for SARS-CoV-2 in Denmark from Feb 27 to May 31, 2020, of whom 8983 (85·6%) were alive and not admitted to hospital 2 weeks after their positive test. The matched SARS-CoV-2-negative reference population not admitted to hospital consisted of 80 894 individuals. Compared with SARS-CoV-2-negative individuals, SARS-CoV-2-positive individuals were not at an increased risk of initiating new drugs (RD <0·1%) except bronchodilating agents, specifically short-acting β2-agonists (117 [1·7%] of 6935 positive individuals vs 743 [1·3%] of 57 206 negative individuals; RD +0·4% [95% CI 0·1–0·7]; RR 1·32 [1·09–1·60]) and triptans (33 [0·4%] of 8292 vs 198 [0·3%] of 72 828; RD +0·1% [0·0–0·3]; RR 1·55 [1·07–2·25]). There was an increased risk of receiving hospital diagnoses of dyspnoea (103 [1·2%] of 8676 vs 499 [0·7%] of 76 728; RD +0·6% [0·4–0·8]; RR 2·00 [1·62–2·48]) and venous thromboembolism (20 [0·2%] of 8785 vs 110 [0·1%] of 78 872; RD +0·1% [0·0–0·2]; RR 1·77 [1·09–2·86]) for SARS-CoV-2-positive individuals compared with negative individuals, but no increased risk of other diagnoses. Prior event rate ratio-adjusted rate ratios of overall general practitioner visits (1·18 [95% CI 1·15–1·22]) and outpatient hospital visits (1·10 [1·05–1·16]), but not hospital admission, showed increases among SARS-CoV-2-positive individuals compared with SARS-CoV-2-negative individuals. Interpretation The absolute risk of severe post-acute complications after SARS-CoV-2 infection not requiring hospital admission is lo...