Effect of Poloxamer 188 vs Placebo on Painful Vaso-Occlusive Episodes in Children and Adults With Sickle Cell Disease: A Randomized Clinical Trial.

Importance: Although effective agents are available to prevent painful vaso-occlusive episodes of sickle cell disease (SCD), there are no disease-modifying therapies for ongoing painful vaso-occlusive episodes; treatment remains supportive. A previous phase 3 trial of poloxamer 188 reported shortened duration of painful vaso-occlusive episodes in SCD, particularly in children and participants treated with hydroxyurea. Objective: To reassess the efficacy of poloxamer 188 for vaso-occlusive episodes. Design, Setting, and Participants: Phase 3, randomized, double-blind, placebo-controlled, multicenter, international trial conducted from May 2013 to February 2016 that included 66 hospitals in 12 countries and 60 cities; 388 individuals with SCD (hemoglobin SS, SC, S-ß0 thalassemia, or S-ß+ thalassemia disease) aged 4 to 65 years with acute moderate to severe pain typical of painful vaso-occlusive episodes requiring hospitalization were included. Interventions: A 1-hour 100-mg/kg loading dose of poloxamer 188 intravenously followed by a 12-hour to 48-hour 30-mg/kg/h continuous infusion (n = 194) or placebo (n = 194). Main Outcomes and Measures: Time in hours from randomization to the last dose of parenteral opioids among all participants and among those younger than 16 years as a separate subgroup. Results: Of 437 participants assessed for eligibility, 388 were randomized (mean age, 15.2 years; 176 [45.4%] female), the primary outcome was available for 384 (99.0%), 15-day follow-up contacts were available for 357 (92.0%), and 30-day follow-up contacts were available for 368 (94.8%). There was no significant difference between the groups for the mean time to last dose of parenteral opioids (81.8 h for the poloxamer 188 group vs 77.8 h for the placebo group; difference, 4.0 h [95% CI, -7.8 to 15.7]; geometric mean ratio, 1.2 [95% CI, 1.0-1.5]; P = .09). Based on a significant interaction of age and treatment (P = .01), there was a treatment difference in time from randomization to last administration of parenteral opioids for participants younger than 16 years (88.7 h in the poloxamer 188 group vs 71.9 h in the placebo group; difference, 16.8 h [95% CI, 1.7-32.0]; geometric mean ratio, 1.4 [95% CI, 1.1-1.8]; P = .008). Adverse events that were more common in the poloxamer 188 group than the placebo group included hyperbilirubinemia (12.7% vs 5.2%); those more common in the placebo group included hypoxia (12.0% vs 5.3%). Conclusions and Relevance: Among children and adults with SCD, poloxamer 188 did not significantly shorten time to last dose of parenteral opioids during vaso-occlusive episodes. These findings do not support the use of poloxamer 188 for vaso-occlusive episodes. Trial Registration: ClinicalTrials.gov Identifier: NCT01737814.

Clinical course and outcomes of COVID-19 in hematopoietic cell transplant patients, a regional report from the Middle East.

The coronavirus disease-2019 (COVID-19) caused by SARS Coronavirus 2 (SARS-CoV-2) is a potentially lethal infection. Cancer patients, and specifically hematopoietic cell transplant (HCT) recipients are severely immunocompromised and may be at a higher risk of a complicated course with this infection. We aimed to study the COVID-19 outcomes and severity in post HCT patients. We retrospectively reviewed post-HCT patients diagnosed with COVID-19 between March 15, 2020, and December 1, 2020 at 10 transplant centers across the Middle East. We identified 91 patients with confirmed SARS-CoV-2 infection across 10 transplant centers. The median age upon presentation with COVID-19 was 35. Fifty two patients were post allo-HCT while the remaining 39 patients were post auto-HCT. The median time from transplant was 14.9 months. Mortality rate was 4.4%. Hospital admission rate was 53%. ICU admission rate was 14%. Mechanical ventilation rate was 10%. Oxygen supplementation rate was 18%. Time from HCT to COVID-19 >6 months was associated with lower admission rates and lower rates of the "severity" composite endpoint. Antibody responses was seen 67% of evaluable patients. In this series of HCT recipients, we report overall favorable clinical outcomes for patients with COVID-19 and provide preliminary insights into the clinical course of this disease in this specific population.

Knowledge and Attitudes Towards Clinical Trial Participation in Oman: A cross-sectional study.

OBJECTIVES: Clinical trials are prospective studies on human subjects designed to answer various clinical questions. However, only a limited number of clinical trials have been conducted in Oman. This study aimed to assess the knowledge and attitudes of Omani patients and their relatives towards participating in clinical trials. METHODS: This cross-sectional study was conducted between October 2015 and March 2016 among 174 patients and relatives attending the Haematology and Oncology Outpatient Clinics and Day Care Unit of the Sultan Qaboos University Hospital, Muscat, Oman. A self-administered questionnaire was designed to elicit participants' knowledge of and attitudes towards participation in clinical trials. RESULTS: A total of 100 patients and relatives agreed to take part in the study (response rate: 57.5%). The male-to-female ratio was 1:1.2. Only 31.3% of the studied population knew what clinical trials were and only 6.5% had themselves previously participated in a clinical trial. The majority agreed or strongly agreed that they would participate in clinical trials related to their own condition (59.2%). Overall, 89.7% expected to be informed about potential clinical trials by their treating physicians. CONCLUSION: Omanis had a low level of knowledge of clinical trials and a very low rate of previous participation in such trials, despite a moderate level of interest. Patients should therefore be educated and informed of ongoing clinical trials in order to improve participation rates for clinical trials conducted in Oman.

Non-invasive haemoglobin estimation in patients with thalassaemia major.

OBJECTIVES: This study aimed to validate pulse CO-oximetry-based haemoglobin (Hb) estimation in children and adults with thalassaemia major (TM) and to determine the impact of different baseline variables on the accuracy of the estimation. METHODS: This observational study was conducted over a five-week period from March to April 2012. A total of 108 patients with TM attending the daycare thalassaemia centre of a tertiary care hospital in Muscat, Oman, were enrolled. Spot (Sp) Hb measurements were estimated using a Pronto-7(®) pulse CO-oximetry device (Masimo Corp., Irvine, California, USA). These were compared to venous samples of Hb using the CELL-DYN Sapphire Hematology Analyzer (Abbott Diagnostics, Abbott Park, Illinois, USA) to determine the reference (Ref) Hb levels. A multivariable linear regression model was used to assess the impact of baseline variables such as age, gender, weight, height, Ref Hb and blood pressure on the Hb estimations. RESULTS: Of the 108 enrolled patients, there were 54 males and 54 females with a mean age of 21.6 years (standard deviation [SD] = 7.3 years; range: 2.5-38 years). The mean Ref Hb and Sp Hb were 9.4 g/dL (SD = 0.9 g/dL; range: 7.5-12.3 g/dL) and 11.1 g/dL (SD = 1.2 g/dL; range: 7.5-14.7 g/dL), respectively. The coefficient of determination (R(2)) was 21% with a mean difference of 1.7 g/dL (SD = 1.1 g/dL; range: -0.9-4.3 g/dL). In the multivariable model, the Ref Hb level (P = 0.001) was the only statistically significant predictor. CONCLUSION: The Pronto-7(®) pulse CO-oximetry device was found to overestimate Hb levels in patients with TM and therefore cannot be recommended. Further larger studies are needed to confirm these results.

Fetal outcomes in pregnant women with sickle cell disease.

OBJECTIVE: To investigate fetal outcomes in pregnant women with sickle cell disease (SCD), and to analyze the impact of baseline variables on those outcomes. METHODS: This is a retrospective cohort study carried out over 5 years (June 2006 to August 2011) investigating fetal outcomes at Sultan Qaboos University Hospital, Muscat, Oman. Sixty-eight consecutive pregnant women with SCD (62 women with hemoglobin sickle cell anemia [SS] genotype) were included and analyzed in the study. Multivariable logistic regression was used to estimate the impact of baseline variables on major fetal complications (intrauterine growth restriction, intrauterine fetal death, and low birth weight babies, perinatal mortality, and admission to the neonatal unit). RESULTS: The mean maternal age was 30 years +/-3.8. Mean gestational age at delivery was 37 weeks +/-1.8. The initial mean hemoglobin was 9.5 g/dl (standard deviation [SD] 1.1, range 7.2-11.9). The mean baseline hemoglobin F was 10.2 (SD 6.6, range 0.7-29). There were 11 cases (16.2%) of intrauterine growth restriction (95% confidence interval [CI]: 7.2-25.2), and 19 cases of fetal distress (27.9%; 95% CI: 17.0-38.9). Low birth weight was seen in 22 cases (32.4%, 95% CI: 20.9-43.8) with a mean weight of 2.6 Kg (SD: 0.47, range 1.2-3.9). There were 2 neonatal deaths. On multivariate logistic regression for a composite of fetal outcomes, none of those variables were of statistical significance. CONCLUSION: The adverse fetal outcomes in pregnant women with SCD are high compared with the general population. There is no significant difference in fetal outcome between SCD, SS genotype versus others.

Maternal complications and the association with baseline variables in pregnant women with sickle cell disease.

Sickle cell disease is an inherited hemoglobinopathy with multi system complications. It has been associated with multiple maternal complications. A retrospective review of 68 consecutive pregnant women with sickle cell disease, followed in a tertiary center, was conducted over 5 years, to estimate the incidence of different maternal complications and the impact of baseline characteristics. Sixty-eight patients were analyzed (mean age 30 years). Sixty-two patients had a Hb SS genotype. The initial mean hemoglobin (Hb) level was 9.5 g/dL. Twelve patients delivered by Cesarean section. Sixty-five patients required admission for sickle cell disease/pregnancy-related complications [96.0%; 95% confidence interval (95% CI) 91-100]. Infection was seen in 17 patients (25.0%, 95% CI 14-36). Blood transfusions were given to 61 patients (90.0%, 95% CI 82-97). Eight patients had gestational hypertension (18.0%, 95% CI 4-20), while five patients (7.0%, 95% CI 1-14) had pre term labor. One patient developed eclampsia and one had a uterine rupture. One patient died due to post partum hemorrhage. The multi variable logistic regression model on the impact on the major maternal complications revealed none of the baseline factors to be statistically significant. Sickle cell disease patients have low mortality and pregnancy-related morbidity but high sickle cell disease-related morbidity. Prospective studies are needed to confirm these results.