Impact of COVID-19-adapted guidelines on resuscitation quality in out-of-hospital-cardiac-arrest: a manikin study.

BACKGROUND: The aim of this study is to evaluate the effects of European Resuscitation Council (ERC) COVID-19-guidelines on resuscitation quality emphasizing advanced airway management in out-of-hospital-cardiac-arrest. METHODS: In a manikin study paramedics and emergency physicians performed advanced cardiac life support in three settings: ERC guidelines 2015 (control), COVID-19-guidelines as suggested with minimum staff (COVID-19-minimal-personnel); COVID-19-guidelines with paramedics and an emergency physician (COVID-19-advanced-airway-manager). Main outcome measures were no-flow-time, quality metrics as defined by ERC and time intervals to first chest compression, oxygen supply, intubation and first rhythm analysis. Data were presented as mean±standard deviation. RESULTS: Thirty resuscitation scenarios were completed. No-flow-time was markedly prolonged in COVID-19-minimal-personnel (113±37 s) compared to control (55±9 s) and COVID-19-advanced-airway-manager (76±38s; P<0.001 each). In both COVID-19-groups chest compressions started later (COVID-19-minimal-personnel: 32±6 s; COVID-19-advanced-airway-manager: 37±7 s; each P<0.001 vs. control [21±5 s]), but oxygen supply (COVID-19-minimal-personnel: 29±5 s; COVID-19-advanced-airway-manager: 34±7 s; each P<0.001 vs. control [77±19 s]) and first intubation attempt (COVID-19-minimal-personnel: 111±14 s; COVID-19-advanced-airway-manager: 131±20 s; each P<0.001 vs. control [178±44 s]) were performed earlier. However, time interval to successful intubation was similar (control: 198±48 s; COVID-19-minimal-personnel: 181±42 s; COVID-19-advanced-airway-manager: 130±25 s) due to a longer intubation time in COVID-19-minimal-personnel (61±35 s) compared to COVID-19-advanced-airway-manager (P=0.002) and control (19±6 s; P<0.001). Time to first rhythm analysis was more than doubled in COVID-19-minimal-personnel (138±96 s) compared to control (50±12 s; P<0.001). CONCLUSIONS: Delayed chest compressions and prolonged no-flow-time markedly reduced the quality of resuscitation. These negative effects were attenuated by increasing the number of staff and by adding an experienced airway manager. The use of endotracheal intubation for reducing aerosol release during resuscitation should be discussed critically as its priorization is associated with an increase in no-flow-time.

Indatuximab ravtansine plus dexamethasone with lenalidomide or pomalidomide in relapsed or refractory multiple myeloma: a multicentre, phase 1/2a study.

BACKGROUND: Indatuximab ravtansine (BT062) is an antibody-drug conjugate that binds to CD138 and synergistically enhances the antitumor activity of lenalidomide in preclinical models of multiple myeloma. This phase 1/2a study was done to determine the safety, activity, and pharmacokinetics of indatuximab ravtansine in combination with immunomodulatory drugs in patients with relapsed or refractory multiple myeloma. METHODS: This open-label, phase 1/2a study took place at nine hospital sites in the USA. Eligible patients were aged 18 years or older, had relapsed or refractory multiple myeloma, and ECOG performance status or Zubrod score of 2 or below. Patients who received indatuximab ravtansine with lenalidomide and dexamethasone (indatuximab ravtansine plus lenalidomide) had failure of at least one previous therapy. Patients treated with indatuximab ravtansine with pomalidomide and dexamethasone (indatuximab ravtansine plus pomalidomide) had failure of at least two previous therapies (including lenalidomide and bortezomib) and had progressive disease on or within 60 days of completion of their last treatment. In phase 1, patients received indatuximab ravtansine intravenously on days 1, 8, and 15 of each 28-day cycle in escalating dose levels of 80 mg/m2, 100 mg/m2, and 120 mg/m2, with lenalidomide (25 mg; days 1 to 21 every 28 days orally) and dexamethasone (20-40 mg; days 1, 8, 15, and 22 every 28 days). In phase 2, the recommended phase 2 dose of indatuximab ravtansine was given to an expanded cohort of patients in combination with lenalidomide and dexamethasone. The protocol was amended to allow additional patients to be treated with indatuximab ravtansine plus pomalidomide (4 mg; days 1 to 21 every 28 days orally) and dexamethasone, in a more heavily pretreated patient population than in the indatuximab ravtansine plus lenalidomide group. The phase 1 primary endpoint was to determine the dose-limiting toxicities and the maximum tolerated dose (recommended phase 2 dose) of indatuximab ravtansine, and the phase 2 primary endpoint was to describe the objective response rate (ORR; partial response or better) and clinical benefit response (ORR plus minor response). All patients were analysed for safety and all patients with post-treatment response assessments were analysed for activity. This study is registered with ClinicalTrials.gov, number NCT01638936, and is complete. FINDINGS: 64 (86%) of 74 screened patients were enrolled between July 3, 2012, and June 30, 2015. 47 (73%) patients received indatuximab ravtansine plus lenalidomide (median follow-up 24·2 months [IQR 19·9-45·4]) and 17 (27%) received indatuximab ravtansine plus pomalidomide (24·1 months [17·7-36·7]). The maximum tolerated dose of indatuximab ravtansine plus lenalidomide was 100 mg/m2, and defined as the recommended phase 2 dose for indatuximab ravtansine plus pomalidomide. An objective response for indatuximab ravtansine plus lenalidomide was observed in 33 (71·7%) of 46 patients and in 12 (70·6%) of 17 patients in the indatuximab ravtansine plus pomalidomide group. The clinical benefit response for indatuximab ravtansine plus lenalidomide was 85% (39 of 46 patients) and for indatuximab ravtansine plus pomalidomide it was 88% (15 of 17 patients). The most common grade 3-4 adverse events in both groups were neutropenia (14 [22%] of 64 patients), anaemia (10 [16%]), and thrombocytopenia (seven [11%]). Treatment-emergent adverse events (TEAEs) that led to discontinuation occurred in 35 (55%) of the 64 patients. Five (8%) patients with a TEAE had a fatal outcome; none was reported as related to indatuximab ravtansine. INTERPRETATION: Indatuximab ravtansine in combination with immunomodulatory drugs shows preliminary antitumor activity, is tolerated, and could be further evaluated in patients with relapsed or refractory multiple myeloma. FUNDING: Biotest AG.

Screening of Gestational Diabetes and Hypertension Among Antenatal Women in Rural West India.

BACKGROUND: Hypertension and gestational diabetes are among the leading causes of maternal and perinatal mortality, especially in rural areas of developing countries with meager health facilities. With early diagnosis and timely treatment, these adverse events can be decreased. The primary aim of this study was to implement a screening program for gestational diabetes and hypertension, and to assess risk factors associated with these conditions among antenatal women in the rural area of the Gujarat province in India. METHODS: A cross-sectional study was conducted at one of the rural areas of Gujarat province in India. Following a random cluster sampling procedure, the village of Davas was selected. A multistage random sampling method was utilized, resulting in a sample of 346 antenatal women. Screening guidelines from the American Diabetes Association were followed for gestational diabetes screening. RESULTS: The majority of antenatal mothers (55.50%) were between 21-25 years of age. 242 antenatal women were multigravida, and among them, 85.96% had institutional delivery at their last pregnancy. Of the total 346 women, 17.60% were prehypertensive. The prevalence of systolic hypertension was 1.40%, diastolic hypertension was 0.90%, and gestational diabetes was 1.73%. CONCLUSION: Socioeconomically upper class, a family history of hypertension, and BMI ≥ 25 were strong risk factors for hypertension during pregnancy and gestational diabetes. Health education should be made readily available to antenatal mothers by paramedical workers regarding symptoms of hypertension and gestational diabetes mellitus for early self identification.