Medications and Acute Hemolysis in G6PD-Deficient Patients - A Real-World Study.

Many drug labels contain precautions of use in G6PD-deficient patients due to hemolytic concerns, but much of this is based on scarce clinical, epidemiological, or structural data. In this real-world study, we aimed to examine if the administration of presumably risky medications for G6PD-deficient patients was followed by hemolysis. The study is based on data from Clalit Health Services database that provides inclusive health care for more than half of the Israeli population (~ 4.7 million). Within the database, we identified all G6PD-deficient patients by G6PD <6 U/g Hb. Within the G6PD-deficient cohort, we identified all hospitalizations with a discharge diagnosis of hemolysis (January 1, 2010 to December 31, 2022), validated the cases, and identified the culprit event. For the rest of the G6PD-deficient patients with no-hemolysis, we recorded filled prescriptions of medications listed as presumably risky. We identified 31,962 G6PD-deficient patients. Within the cohort, there were 71 cases of major hemolysis requiring hospitalization (0.2% of the cohort), of whom 51 (71.8%) had been caused by ingestion of fava beans, six (8.5%) were associated with an infection, and three (4.2%) suggested to be associated with medications (nitrofurantoin, phenazopyridine, and a "pain killer"). Within the 31,875 patients with no major hemolysis, nitrofurantoin has been prescribed safely to 1,366 G6PD-deficient males and females; hundreds/thousands of G6PD-deficient patients had been prescribed safely ciprofloxacin, glibenclamide, ofloxacin, phenazopyridine, sulfamethoxazole/cotrimoxazole, sulfasalazine, hydroxychloroquine, glimepiride, mesalazine, and sulfacetamide. In this real-world study, we are showing that a list of medications, suspected previously as carrying risks for hemolysis in G6PD-deficient patients, have been prescribed safely to G6PD-deficient patients, providing reassurance to patients, prescribers, and regulators.

Exploring the Optimal Intertwin Delivery Interval for Vaginal Delivery.

The effect of prolonged intertwin delivery interval (IDI) is not well studied. This work aimed to assess the inflection point for Cesarean delivery (CD) and associated adverse maternal and neonatal outcomes. This was a retrospective cohort study at a single tertiary care center. The study included women with twin pregnancies in 2010-2019 who reached the second stage of labor, and assessed the most predictive cutoff for CD using Youden J statistic and compared adverse maternal and neonatal outcomes between short and prolonged intertwin delivery intervals. A total of 461 gravidas reached the second stage of labor and were included in the study. Using the ROC curve and Youden J statistic, the IDI cutoff was set at 15 min (80% sensitivity, 75% specificity, p < 0.001), with 312 women in the short and 149 in the prolonged IDI groups. Women in the prolonged IDI group were less likely to deliver the second twin vaginally (75.8% vs. 93.3%, p < 0.001). Postpartum hemorrhage (PPH) (39.1% vs. 24.7%, p = 0.01), and placental abruption (4% vs. 1%, p = 0.03) were more likely to occur in the prolonged IDI group. An increased rate of neonatal acidemia and low 5-min Apgar score were also found in the prolonged IDI group (15.7% vs. 4.3%, P = 0.01, 9.7% vs. 3.5%, p = 0.008; respectively). IDIs of more than 15 min are associated with increased risk of adverse maternal and neonatal outcomes. These findings should be used for counseling and managing twin pregnancies attempting vaginal delivery.

Association between SARS-CoV-2 infection and new-onset atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is associated with substantial morbidity and mortality. New-onset AF (NOAF) has been related recently to SARS-CoV-2 infection; however, the evidence supporting this link is still scarce. We aimed to examine the association between SARS-CoV-2 infection and NOAF. METHODS: We conducted a nested-case control study in a cohort of 2,931,046 adults from the largest healthcare provider in Israel. Subjects were followed from March 1st, 2020, until June 30th, 2022, for the occurrence of NOAF. Ten randomly selected controls were matched to each case of NOAF on age, sex, and duration of follow-up. Exposure to SARS-CoV-2 infection in the prior 30 days was assessed in cases and controls. To account for surveillance bias we performed a lag-time analysis and assessed the association with a negative control exposure (low back pain). Data was analyzed using conditional logistic regression. RESULTS: During the follow-up 18,981 patients developed NOAF and were matched to 189,810 controls. The mean age of cases and matched controls was 73.8 ± 13 years, and 51.1% of them were women. Multivariable analysis showed that SARS-CoV-2 infection was associated with an increased risk of NOAF; adjusted-OR, 4.24 (95% CI, 3.89-4.62). The association remained significant on lag-time analysis; however, the strength of the association was gradually attenuated with increasing lag-time but stabilized around a lag-time of 20 days. The negative control exposure (low back pain) was associated only with small increased risk of NOAF; adjusted-OR of 1.13 (95% CI, 1.02-1.26). CONCLUSION: SARS-CoV-2 infection appears to be associated with increased risk of NOAF.

Trends in occurrence of takotsubo syndrome and association with SARS-CoV-2 infection and COVID-19 vaccination.

AIMS: Takotsubo syndrome (TTS) is a serious heart disease associated with significant morbidity and mortality. TTS has been related to SARS-CoV-2 infection and COVID-19 vaccine; however, the current data are scarce. We aimed to examine the associations between SARS-CoV-2 infection and its vaccine with TTS. METHODS: We conducted a nested case-control study in a cohort of 3 237 909 adults from the largest healthcare provider in Israel. Patients were followed from 1 March 2020 until 31 December 2021 for the occurrence of TTS. Ten randomly selected controls were matched to each case of TTS on age, sex, and duration of follow-up. Exposure to SARS-CoV-2 infection and COVID-19 vaccine in the prior 30 days was assessed in cases and controls. RESULTS: During the follow-up 144 patients developed TTS and were matched to 1440 controls. The mean age of cases and their matched controls was 71.4 ±â€Š12 years, and 136 (94.4%) of them were women. Conditional logistic regression analysis showed that SARS-CoV-2 infection and COVID-19 vaccine were not associated with an increased risk of TTS; odds ratio (OR) = 2.04 [95% confidence interval (CI), 0.50-8.2] and 0.87 (0.49-1.54), respectively. The absolute number of TTS cases in the prepandemic period (March-December 2018-2019) was 82 in 2018 and 80 in 2019. The number of TTS cases decreased to 56 during the corresponding period of 2020 (first pandemic year) and increased back to 81 in 2022. CONCLUSION: No significant association was found between SARS-CoV-2 infection or COVID-19 vaccination and TTS occurrence.

Cardiovascular Involvement in Behçet Disease: Clinical Implications.

Behçet disease (BD) is a multisystem disorder, with vasculitis as its underlying pathological process, in contrast to the classic triad of recurrent oral and genital ulcerations, with uveitis. Vascular involvement in BD includes venous thrombosis, arterial occlusion, and pulmonary artery and aortic aneurysm formation. Cardiac involvement is rare and often obscure. It includes intracardiac thrombi formation, and is associated with a poor prognosis. Our objectives are to describe two cases with BD, complicated with vascular and cardiac involvement, and to raise awareness of these rare complications, the needed routine surveillance, and thus to prevent inappropriate interventions, serious outcomes, and mortality. We present two male patients from the Mediterranean Basin with BD. The first was diagnosed early as a BD patient. The second was diagnosed at the time of cardiovascular (CV) involvement. We recommend that patients who are diagnosed, or even suspected of suffering from BD, especially in endemic areas along the Silk Route pathway, should be followed up routinely for CV involvement, even if rare, obscure, or with a bizarre presentation.