METHODS: In two phase 3 trials, we assessed iptacopan monotherapy over a 24-week period in patients with hemoglobin levels of less than 10 g per deciliter. In the first, anti-C5-treated patients were randomly assigned to switch to iptacopan or to continue anti-C5 therapy. In the second, single-group trial, patients who had not received complement inhibitors and who had lactate dehydrogenase (LDH) levels more than 1.5 times the upper limit of the normal range received iptacopan. The two primary end points in the first trial were an increase in the hemoglobin level of at least 2 g per deciliter from baseline and a hemoglobin level of at least 12 g per deciliter, each without red-cell transfusion; the primary end point for the second trial was an increase in hemoglobin level of at least 2 g per deciliter from baseline without red-cell transfusion.
RESULTS: In the first trial, 51 of the 60 patients who received iptacopan had an increase in the hemoglobin level of at least 2 g per deciliter from baseline, and 42 had a hemoglobin level of at least 12 g per deciliter, each without transfusion; none of the 35 anti-C5-treated patients attained the end-point levels. In the second trial, 31 of 33 patients had an increase in the hemoglobin level of at least 2 g per deciliter from baseline without red-cell transfusion. In the first trial, 59 of the 62 patients who received iptacopan and 14 of the 35 anti-C5-treated patients did not require or receive transfusion; in the second trial, no patients required or received transfusion. Treatment with iptacopan increased hemoglobin levels, reduced fatigue, reduced reticulocyte and bilirubin levels, and resulted in mean LDH levels that were less than 1.5 times the upper limit of the normal range. Headache was the most frequent adverse event with iptacopan.
CONCLUSIONS: Iptacopan treatment improved hematologic and clinical outcomes in anti-C5-treated patients with persistent anemia - in whom iptacopan showed superiority to anti-C5 therapy - and in patients who had not received complement inhibitors. (Funded by Novartis; APPLY-PNH ClinicalTrials.gov number, NCT04558918; APPOINT-PNH ClinicalTrials.gov number, NCT04820530.).
METHODS: We systematically searched Pubmed for population-based studies of chronic kidney disease (CKD) and ESKD epidemiology and management. Population-level data from 23 pre-designated nations were eligible for inclusion if they pertained to people receiving dialysis or kidney transplant for ESKD. When available, government websites were utilized to identify and extract data from relevant kidney registries . Measures gathered included those related to the prevalence and mortality of ESKD; the availability of nephrologists; per capita healthcare expenditures; and use of erythropoietin stimulating agents (ESAs).
RESULTS: We obtained data from the United States (US), 7 nations in Eastern Europe, 4 each in Western Europe, Latin America, and Africa, and 3 in Asia. Documented prevalence of ESKD per million population varied from a high of 3,600 (Malaysia) to a low of 67 (Senegal). Annual mortality associated with ESKD varied from 31% (Ethiopia and Senegal) to 10% (UK). Nephrologist availability per million population varied from 40 (Japan) to <1 (South Africa) and was associated with per capita healthcare expenditures.
CONCLUSIONS: The delivery of kidney care related to ESKD varies widely among countries. Higher per capita healthcare spending is associated with increased delivery of kidney care. However, in part because documentation of kidney disease varies widely, it is difficult to determine how outcomes related to ESKD may vary across nations.
METHODS: A cross-sectional survey study utilising snowball sampling was performed involving doctors, nurses and allied health professions from 23 hospitals in Singapore, Malaysia, India and Indonesia between 29 May 2020 and 13 July 2020. This survey collated demographic data and workplace conditions and included three validated questionnaires: the Safety Attitudes Questionnaire (SAQ), Oldenburg Burnout Inventory and Hospital Anxiety and Depression Scale. We performed multivariate mixed-model regression to assess independent associations with the SAQ total percentage agree rate (PAR).
RESULTS: We obtained 3,163 responses. The SAQ total PARs were found to be 35.7%, 15.0%, 51.0% and 3.3% among the respondents from Singapore, Malaysia, India and Indonesia, respectively. Burnout scores were highest among respondents from Indonesia and lowest among respondents from India (70.9%-85.4% vs. 56.3%-63.6%, respectively). Multivariate analyses revealed that meeting burnout and depression thresholds and shifts lasting ≥12 h were significantly associated with lower SAQ total PAR.
CONCLUSION: Addressing the factors contributing to high burnout and depression and placing strict limits on work hours per shift may contribute significantly towards improving safety culture among HCWs and should remain priorities during the pandemic.
METHODS: Patients with American Spinal Injury Association (ASIA) Impairment Scale (AIS) A and B were included in an open-label cohort study. Each received a course of MLC601/MLC901 for 6 months in addition to standard care and rehabilitation. Key endpoints were safety, AIS grade and motor scores at month 6 (M6).
RESULTS: Among 30 patients included (mean age 42.2 ± 17.6 years, 24 men), 20 patients had AIS A while 10 patients had AIS B at baseline. Ten patients experienced 14 adverse events including one serious adverse event and six deaths, none were considered treatment-related. AIS improved in 25% of AIS A and 50% of AIS B. Improvement in ASIA motor score was seen most with cervical injury (median change from baseline 26.5, IQR: 6-55). These findings appear to be better than reported rates of spontaneous recovery for SCI AIS A and B.
CONCLUSION: MLC601/MLC901 is safe and may have a role in the treatment of patients with SCI. A controlled trial is justified.
METHODS: Data on demographics, comorbidities, and treatments received, as well as mortality for HD patients admitted to hospitals for COVID-19, from 1/March to 31/July 2020, prospectively collected and analyzed.
RESULTS: A total of 141 infected HD patients were admitted (Mean age 58 ± 16.1; Males 56%), representing 7% of the total HD population and 0.2% of all COVID-19 cases during the study period. Of those 141 infected HD patients, 27 (19%) died, and this represents 6% of total COVID-19-related mortality and 27% of the total HD mortality. In contrast, total covid-19-related mortality of all positive cases was only 0.7%, and total HD mortality during the study period was only 5%. COVID-19-positive HD patients who died were older and 59% were males. However, the differences were not statistically significant. Of the 61 infected HD patients who needed to be switched to continuous kidney replacement therapy (CKRT), 34% died, and of the 29 infected HD patients who needed admission to intensive care, 65% died.
CONCLUSION: HD population represents a small fraction of the total population; however, positive HD COVID-19 cases represent a sizable proportion of COVID-19 cases and a significant percentage of total COVID-19-related mortality, and total HD mortality.