Brain ultrasonography findings in neonates with exposure to cocaine during pregnancy

Background: Cocaine exposure during pregnancy has been reported to have detrimental effects on the fetus. Objective: To describe the findings on cranial ultrasonography (CUS) as part of a neonatal screening programme for exposed neonates. Materials and methods: The study was a semiprospective analysis of a 12-year cohort of neonates born to mothers who had used cocaine during their pregnancy and who had follow-up according to a strict clinical protocol. Results: In total, 154 neonates (78 boys, 76 girls) were included, of whom 29 (19%) were born preterm, and 125 (81%) were born full-term. Abnormalities on CUS were seen in 37 neonates (24%; 95% CI 18-31%). The abnormalities were classified as minor in 20 (13%; 95% CI 9-19%) and mildly abnormal in 17 (11%; 95% CI 7-17%). None of the infants showed severe abnormalities. The abnormalities were not associated with the duration or maximum amount of cocaine use during pregnancy. Conclusion: None of the infants had severe abnormalities. Detected abnormalities were not correlated with the duration or maximum amount of cocaine use. Given these findings, we feel that routine cranial ultrasonography in this population is not warranted

Ixazomib, daratumumab and low-dose dexamethasone in intermediate-fit patients with newly diagnosed multiple myeloma:an open-label phase 2 trial

Background: The outcome of non-transplant eligible newly diagnosed multiple myeloma (NDMM) patients is heterogeneous, partly depending on frailty level. The aim of this study was to prospectively investigate the efficacy and safety of Ixazomib-Daratumumab-low-dose dexamethasone (Ixa-Dara-dex) in NDMM intermediate-fit patients. Methods: In this phase II multicenter HOVON-143 study, IMWG Frailty index based intermediate-fit patients, were treated with 9 induction cycles of Ixa-Dara-dex, followed by maintenance with ID for a maximum of 2 years. The primary endpoint was overall response rate on induction treatment. Patients were included from October 2017 until May 2019. Trial Registration Number: NTR6297. Findings: Sixty-five patients were included. Induction therapy resulted in an overall response rate of 71%. Early mortality was 1.5%. At a median follow-up of 41.0 months, median progression-free survival (PFS) was 18.2 months and 3-year overall survival 83%. Discontinuation of therapy occurred in 77% of patients, 49% due to progression, 9% due to toxicity, 8% due to incompliance, 3% due to sudden death and 8% due to other reasons. Dose modifications of ixazomib were required frequently (37% and 53% of patients during induction and maintenance, respectively), mainly due to, often low grade, polyneuropathy. During maintenance 23% of patients received daratumumab alone. Global quality of life (QoL) improved significantly and was clinically relevant, which persisted during maintenance treatment. Interpretation: Ixazomib-Daratumumab-low-dose dexamethasone as first line treatment in intermediate-fit NDMM patients is safe and improves global QoL. However, efficacy was limited, partly explained by ixazomib-induced toxicity, hampering long term tolerability of this 3-drug regimen. This highlights the need for more efficacious and tolerable regimens improving the outcome in vulnerable intermediate-fit patients. Funding: Janssen Pharmaceuticals, Takeda Pharmaceutical Company Limited.</p

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Adverse Events in Pediatric Critical Care Nonsurvivors With a Low Predicted Mortality Risk: A Multicenter Case Control Study

OBJECTIVES: Some patients with a low predicted mortality risk in the PICU die. The contribution of adverse events to mortality in this group is unknown. The aim of this study was to estimate the occurrence of adverse events in low-risk nonsurvivors (LN), compared with low-risk survivors (LS) and high-risk PICU survivors and nonsurvivors, and the contribution of adverse events to mortality. DESIGN: Case control study. Admissions were selected from the national Dutch PICU registry, containing 53,789 PICU admissions between 2006 and 2017, in seven PICUs. PICU admissions were stratified into four groups, based on mortality risk (low/high) and outcome (death/survival). Random samples were selected from the four groups. Cases were "LN." Control groups were as follows: "LS," "high-risk nonsurvivors" (HN), and "high-risk survivors" (HS). Adverse events were identified using the validated trigger tool method. SETTING: Patient chart review study. PATIENTS: Children admitted to the PICU with either a low predicted mortality risk (< 1%) or high predicted mortality risk (≥ 30%). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In total, 419 patients were included (102 LN, 107 LS, 104 HN, and 106 HS). LN had more complex chronic conditions (93.1%) than LS (72.9%; p < 0.01), HN (49.0%; p < 0.001), and HS (48.1%; p < 0.001). The occurrence of adverse events in LN (76.5%) was higher than in LS (13.1%) and HN (47.1%) ( p < 0.001). The most frequent adverse events in LN were hospital-acquired infections and drug/fluid-related adverse events. LN suffered from more severe adverse events compared with LS and HS ( p < 0.001). In 30.4% of LN, an adverse event contributed to death. In 8.8%, this adverse event was considered preventable. CONCLUSIONS: Significant and preventable adverse events were found in low-risk PICU nonsurvivors. 76.5% of LN had one or more adverse events. In 30.4% of LN, an adverse event contributed to mortality

Adverse Events in Pediatric Critical Care Nonsurvivors with a Low Predicted Mortality Risk: A Multicenter Case Control Study

OBJECTIVES: Some patients with a low predicted mortality risk in the PICU die. The contribution of adverse events to mortality in this group is unknown. The aim of this study was to estimate the occurrence of adverse events in low-risk nonsurvivors (LN), compared with low-risk survivors (LS) and high-risk PICU survivors and nonsurvivors, and the contribution of adverse events to mortality. DESIGN: Case control study. Admissions were selected from the national Dutch PICU registry, containing 53,789 PICU admissions between 2006 and 2017, in seven PICUs. PICU admissions were stratified into four groups, based on mortality risk (low/high) and outcome (death/survival). Random samples were selected from the four groups. Cases were "LN." Control groups were as follows: "LS," "high-risk nonsurvivors" (HN), and "high-risk survivors" (HS). Adverse events were identified using the validated trigger tool method. SETTING: Patient chart review study. PATIENTS: Children admitted to the PICU with either a low predicted mortality risk (< 1%) or high predicted mortality risk (≥ 30%). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In total, 419 patients were included (102 LN, 107 LS, 104 HN, and 106 HS). LN had more complex chronic conditions (93.1%) than LS (72.9%; p < 0.01), HN (49.0%; p < 0.001), and HS (48.1%; p < 0.001). The occurrence of adverse events in LN (76.5%) was higher than in LS (13.1%) and HN (47.1%) (p < 0.001). The most frequent adverse events in LN were hospital-acquired infections and drug/fluid-related adverse events. LN suffered from more severe adverse events compared with LS and HS (p < 0.001). In 30.4% of LN, an adverse event contributed to death. In 8.8%, this adverse event was considered preventable. CONCLUSIONS: Significant and preventable adverse events were found in low-risk PICU nonsurvivors. 76.5% of LN had one or more adverse events. In 30.4% of LN, an adverse event contributed to mortality

Long-term effects of previous oxandrolone treatment in adult women with Turner syndrome

Objective: Short stature is a prominent feature of Turner syndrome (TS), which is partially overcome by GH treatment. We have previously reported the results of a trial on the effect of oxandrolone (Ox) in girls with TS. Ox in a dose of 0.03 mg/kg per day (Ox 0.03) significantly increased adult height gain, whereas Ox mg/kg per day (0.06) did not, at the cost of deceleration of breast development and mild virilization. The aim of this follow-up study in adult participants of the pediatric trial was to investigate the long-term effects of previous Ox treatment. Design and methods: During the previous randomized controlled trial, 133 girls were treated with GH combined with placebo (Pl), Ox 0.03, or Ox 0.06 from 8 years of age and estrogen from 12 years. Sixty-eight women (Pl, n=23; Ox 0.03, n=27; and Ox 0.06, n=18) participated in the double-blind follow-up study (mean age, 24.0 years; mean time since stopping GH, 8.7 years; and mean time of Ox/Pl use, 4.9 years). We assessed height, body proportions, breast size, virilization, and body composition. Results: Height gain (final minus predicted adult height) was maintained at follow-up (Ox 0.03 10.2 ±4.9 cm, Ox 0.06 9.7±4.4 cm vs Pl 8.0±4.6 cm). Breast size, Tanner breast stage, and body composition were not different between groups. Ox-treated women reported more subjective virilization and had a lower voice frequency. Conclusion: Ox 0.03 mg/kg per day has a beneficial effect on adult height gain in TS patients. Despite previously reported deceleration of breast development during Ox 0.03 treatment, adult breast size is not affected. Mild virilization persists in only a small minority of patients. The long-term evaluation indicates that Ox 0.03 treatment is effective and safe

Ixazomib, Daratumumab, and Low-Dose Dexamethasone in Frail Patients With Newly Diagnosed Multiple Myeloma: The Hovon 143 Study.

Frail patients with newly diagnosed multiple myeloma have an inferior outcome, mainly because of a high discontinuation rate due to toxicity. We designed a phase II trial specifically for frail patients, evaluating the efficacy and tolerability of ixazomib-daratumumab-low-dose-dexamethasone (Ixa-Dara-dex). Sixty-five patients, who were frail according to the International Myeloma Working Group frailty index, were treated with nine induction cycles Ixa-Dara-dex followed by maintenance with Ixa-Dara for a maximum of 2 years. The overall response rate on induction therapy was 78%. After a median follow-up of 22.9 months, median progression-free survival (PFS) was 13.8 months and 12-month overall survival (OS) was 78%. Median PFS and 12-month OS were 21.6 months and 92% in patients who were frail based on age > 80 years alone, versus 13.8 months and 78%, and 10.1 months and 70% in patients who were frail based on additional frailty parameters either ≤ 80 or > 80 years of age, respectively. In 51% of patients, induction therapy had to be discontinued prematurely, of which 6% because of noncompliance to study treatment, 9% because of toxicity, and 9% because of death (8% within 2 months, of which 80% because of toxicity). Quality of life improved during induction treatment, being clinically meaningful already after three induction cycles. Ixa-Dara-dex lead to a high response rate and improved quality of life. However, treatment discontinuation because of toxicity and early mortality, negatively influencing PFS and OS, remains a concern in frail patients. The outcome was heterogeneous across frail subpopulations. This should be taken into account in the design and interpretation of future studies in frail patients, to pave the way for more precise treatment guidance

Clinical auditing as an instrument to improve care for patients with ovarian cancer: The Dutch Gynecological Oncology Audit (DGOA)

Introduction: The Dutch Gynecological Oncology Audit (DGOA) was initiated in 2014 to serve as a nationwide audit, which registers the four most prevalent gynecological malignancies. This study presents the first results of clinical auditing for ovarian cancer in the Netherlands. Methods: The Dutch Gynecological Oncology Audit is facilitated by the Dutch Institute of Clinical Auditing (DICA) an

Effect of Antiplatelet Therapy on Survival and Organ Support–Free Days in Critically Ill Patients With COVID-19

International audienc