Effectiveness and Safety of Direct Oral Anticoagulants for Stroke Prevention in Atrial Fibrillation Patients With Extreme Obesity.

Direct oral anticoagulants (DOACs) are a favored treatment to prevent stroke in patients with atrial fibrillation (AF). There are limited data concerning the efficacy and safety of DOACs in obese. Obesity leads to wide structural and physiological changes that may affect the pharmacokinetics and pharmacodynamics of drugs. The optimal dosing strategies for DOACs in this significant and growing sub-group remain unknown. The study aimed to evaluate on a large scale the safety and efficacy of DOAC treatment in extreme obese patients with AF. In this retrospective cohort study, we included patients with AF treated with DOACs. Patients were divided according to body mass index (BMI). Study outcomes included stroke, major bleeding, and death. Between 2012 and 2017, 5183 patients with AF were included in the analysis (2,688, 2137, and 358 patients had a BMI <30, 30 to 40, and >40 accordingly). There was no significant difference in the prevalence of ischemic events (9.9%, 8.2%, and 7.5% of patients with BMI <30, 30 to 40, and >40, respectively, p = 0.088), major bleeding events (13%, 14.1%, and 11.2% of patients with BMI <30, 30 to 40, and >40, respectively, p value = 0.257) or net ischemic and major bleeding events (18.7%, 18.7%, and 15.4% of patients with BMI <30, 30 to 40, and >40 respectively, p = 0.297) between the BMI groups. In conclusion, DOACs treatment for prevention of ischemic events in AF is effective and safe through the BMI spectrum, including extreme obesity.

Effectiveness of Molnupiravir in High-Risk Patients: A Propensity Score Matched Analysis.

BACKGROUND: Molnupiravir was granted emergency use authorization for the treatment of mild to moderate coronavirus disease 2019 (COVID-19). In this study, we used population-based real-world data to evaluate the effectiveness of molnupiravir. METHODS: The database of the largest healthcare provider in Israel was used to identify all adults with first-ever positive test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) performed in the community during January-February 2022, who were at high risk for severe COVID-19, and had no contraindications for molnupiravir use. Patients were included regardless of SARS-CoV-2 vaccination status. A total of 2661 patients who received molnupiravir were propensity score matched with 2661 patients who have not received molnupiravir (control group). Patients were followed through 10 March 2022 for up to 28 days for the first occurrence of the composite severe COVID-19 or COVID-19-specific mortality. RESULTS: The composite outcome occurred in 50 patients in the molnupiravir group and 60 patients in the control group. Molnupiravir was associated with a nonsignificant reduced risk of the composite outcome: hazard ratio, 0.83 (95% confidence interval, .57-1.21). However, subgroup analyses showed that molnupiravir was associated with a significant decrease in the risk of the composite outcome in older patients 0.54 (0.34-0.86), in females 0.41 (0.22-0.77), and in patients with inadequate COVID-19 vaccination 0.45 (0.25-0.82). The results were similar when each component of the composite outcome was examined separately. CONCLUSIONS: This study suggests that in the era of Omicron and in real-life setting, molnupiravir might be effective in reducing the risk of severe COVID-19 and COVID-19-related mortality, particularly in specific subgroups.

Effectiveness of Paxlovid in Reducing Severe Coronavirus Disease 2019 and Mortality in High-Risk Patients.

BACKGROUND: Paxlovid was granted an Emergency Use Authorization for the treatment of mild to moderate coronavirus disease 2019 (COVID-19), based on the interim analysis of the Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients (EPIC-HR) trial. Paxlovid effectiveness needs to be assessed in a noncontrolled setting. In this study we used population-based real-world data to evaluate the effectiveness of Paxlovid. METHODS: The database of the largest healthcare provider in Israel was used to identify all adults aged 18 years or older with first-ever positive test for severe acute respiratory syndrome coronavirus 2 between January and February 2022, who were at high risk for severe COVID-19 and had no contraindications for Paxlovid use. Patients were included irrespective of their COVID-19 vaccination status. Cox hazard regression was used to estimate the 28-day hazard ratio (HR) for severe COVID-19 or mortality with Paxlovid examined as time-dependent variable. RESULTS: Overall, 180 351 eligible patients were included; of these, only 4737 (2.6%) were treated with Paxlovid, and 135 482 (75.1%) had adequate COVID-19 vaccination status. Both Paxlovid and adequate COVID-19 vaccination status were associated with significant decrease in the rate of severe COVID-19 or mortality with adjusted HRs of 0.54 (95% confidence interval [CI], .39-.75) and 0.20 (95% CI, .17-.22), respectively. Paxlovid appears to be more effective in older patients, immunosuppressed patients, and patients with underlying neurological or cardiovascular disease (interaction P < .05 for all). No significant interaction was detected between Paxlovid treatment and COVID-19 vaccination status. CONCLUSIONS: This study suggests that in the era of Omicron and in real-life settings, Paxlovid is highly effective in reducing the risk of severe COVID-19 or mortality.

Could a Coagulation Nurse Liaison Improve Compliance With Venous Thromboembolism Prophylaxis in Medical Patients?

Medical patients worldwide are undertreated with venous thromboembolism prophylaxis. Our hypothesis was that the rate of prophylactic anticoagulation therapy for high-risk patients would improve with the use of a coagulation nurse liaison. Six months after appointing a nurse for this role, prophylaxis rates significantly improved, and patients were more likely to receive appropriate thromboprophylaxis. A coagulation nurse liaison substantially improves thromboprophylaxis in a medical ward.

Potential risks associated with traditional herbal medicine use in cancer care: A study of Middle Eastern oncology health care professionals.

BACKGROUND: The authors assessed the use of herbal medicine by Middle Eastern patients with cancer, as reported by their oncology health care professionals (HCPs). Herbal products identified by the study HCPs were evaluated for potential negative effects. METHODS: Oncology HCPs from 16 Middle Eastern countries received a 17-item questionnaire asking them to list 5 herbal products in use by their patients with cancer. A literature search (PubMed, Micromedex, AltMedDex, and the Natural Medicine Comprehensive Database) was conducted to identify safety-related concerns associated with the products listed. RESULTS: A total of 339 HCPs completed the study questionnaire (response rate of 80.3%), identifying 44 herbal and 3 nonherbal nutritional supplements. Safety-related concerns were associated with 29 products, including herb-drug interactions with altered pharmacodynamics (15 herbs), direct toxic effects (18 herbs), and increased in vitro response of cancer cells to chemotherapy (7 herbs). CONCLUSIONS: Herbal medicine use, which is prevalent in Middle Eastern countries, has several potentially negative effects that include direct toxic effects, negative interactions with anticancer drugs, and increased chemosensitivity of cancer cells, requiring a reduction in dose-density. Oncology HCPs working in countries in which herbal medicine use is prevalent need to better understand the implications of this practice. The presence of integrative physicians with training in complementary and traditional medicine can help patients and their HCPs reach an informed decision regarding the safety and effective use of these products.

Azithromycin is not associated with QT prolongation in hospitalized patients with community-acquired pneumonia.

PURPOSE: Large data-based studies have reported excess cardiovascular mortality in high-risk patients treated with azithromycin, but whether or not azithromycin causes QT prolongation remains controversial. The purpose of this study was to examine the association of azithromycin treatment on QT prolongation in a cohort of patients hospitalized with community-acquired pneumonia (CAP) METHODS: One-hundred twenty-two hospitalized patients with CAP were enrolled in the study. We compared the baseline QTc, with daily post antibiotic QTc. Other risk factors for QT prolongation such as medication or electrolyte abnormalities were recorded. RESULTS: Ninety (73.8%) patients were treated with azithromycin (usually in combination with ceftriaxone), and 32 (26.2%) patients with other antibiotics (ampicillin-clavulanate, chloramphenicol, doxcycline, or ceftriaxone); 72.1% (88) of the cohort experienced QT lengthening; 72.7% with QT lengthening had a normal baseline QTc. Azithromycin was not associated with the post-antibiotic QTc. Wide (pathological) post-antibiotic QTc was associated with the pneumonia score. Every 10-point increase in the pneumonia score raised the risk for a pathological post antibiotic QTc by 1.249 (95%CI: 1.050-1.486). Analysis of patients with non-pathological baseline QTc revealed that pathological post-antibiotic QTc was only associated with previous stroke and not with the type of antibiotic. CONCLUSIONS: Azithromycin treatment was not associated with QT prolongation in patients with severe CAP. Nonetheless, in a large majority of hospitalized CAP patients, QT prolongation and pathological QTc develop regardless of the antibiotic used, especially in patients with previous stroke or a higher pneumonia score.

Founding an adverse drug reaction (ADR) network: a method for improving doctors spontaneous ADR reporting in a general hospital.

Adverse drug reactions (ADR) are underreported by doctors despite numerous efforts. We aimed to determine if establishing an "ADR reporting doctor's network" within a hospital would increase the quantity of ADRs reported by hospital doctors. One hundred hospital doctors joined the network. Email reminders were sent to network members during the 1 year study period, conveying information about ADRs reported, amusingly and pleasantly reminding them to report ADRs in minimal detail, by phone, email, text message or mail to the Clinical Pharmacology Unit, who would further complete the report. A total of 114 ADRs were reported during the study period in comparison to 48, 26, and 17 in the previous 3 years (2008, 2009, 2010, respectively). In the 3 years prior, doctors reported 41.7% of the reported ADRs whereas in the study period, doctors reported 74.3% of ADRs (P < .001), reflecting an 80% increase in doctors reports. Ninety seven percent of doctors' reports were of ADR network members. Thirty-four (34%) network members reported an ADR during the study period and 31 of the 34 reporters had never reported ADRs before becoming network members. Establishing an ADR network of doctors substantially increases ADR reporting amongst its members.

Medication prescribing errors in the prehospital setting and in the ED.

BACKGROUND: Medication errors are a common cause of iatrogenic adverse drug events. The incidence and nature of medication errors during prehospital treatment have not been fully described. OBJECTIVES: The objectives of this study are to describe the incidence and characteristics of medication errors in adults during prehospital emergency treatment and in the emergency department (ED) and to identify risk factors for medication errors in those settings. METHODS: This is a retrospective study of adult patients transferred by emergency medical services to the ED of a university-affiliated hospital in Israel. The drugs administered in the mobile intensive care unit and in the ED were reviewed by 2 reviewers, who independently decided whether an error had occurred. The primary outcome was the number of drug errors per patient. Secondary outcomes were the type and severity of the errors and variables associated with increased incidence of drug errors. RESULTS: During the study period, 1837 patients were brought to the ED by mobile intensive care unit vehicles. Five hundred thirty-six patient charts (29%) were randomly selected for review; 65 charts (12.12%) could not be found; thus, 471 charts were reviewed. In the emergency vehicle, 188 patients (45.63%) received medications; of those, 12.76% (24 patients) were subject to a medication error. The number of drugs administered and long evacuation times were associated with higher risk for an error (P<.01 and P=.011, respectively). The presence of a physician in the emergency vehicle did not alter the risk of an error (P=.95). In the ED, 332 patients (72.6%) received medications. Of those, medication errors occurred in 120 patients (36.1%). The more medications administered, the higher the risk of error (P<.01). Less errors occurred in trauma patients (P=.041). CONCLUSION: More medication errors occur in the ED than in the emergency vehicles. Patients treated with multiple medications are more prone to medication errors.

Cutaneous nocardiosis: report of two cases and review of the literature.

BACKGROUND: Cutaneous nocardiosis is an uncommon infectious disease that presents as a primary cutaneous infection or as a disseminated disease. It is often misdiagnosed because of its rarity and nonspecific clinical picture. METHODS: We report a case of each type. The first case is an immunocompetent patient who was infected by Nocardia while gardening and developed a superficial skin infection--one of the three clinical manifestations of primary cutaneous nocardiosis. The second case is an immunocompromised patient with pulmonary nocardiosis that extended to the skin as part of a disseminated disease. RESULTS: The immunocompetent patient with primary cutaneous nocardiosis had the classical features of a superficial skin infection. He had a nodular­pustular lesion on the right arm, which appeared 7 days after gardening with bare hands. Nocardia was identified in a skin culture taken from a pustule, unfortunately not to the species level. Treatment with minocycline for 3 months resulted in full remission of the lesion. The immunocompromised patient with disseminated nocardiosis had high fever, productive cough, hemoptysis, and erythematous nodules and pustules on the extremities. N. brasiliensis was isolated from bronchial samples and skin. Treatment with a high dose of trimethoprim and sulfamethoxazole for five months resulted in full recovery from cutaneous and pulmonary complaints. No relapse of the infection was found on follow-up in either patient. CONCLUSION: These cases demonstrate the need for a high degree of suspicion, focused clinical search, and appropriate laboratory procedures in the diagnosis and management of cutaneous nocardiosis.

Effectiveness of oral vs rectal acetaminophen: a meta-analysis.

OBJECTIVE: To determine, on the basis of published studies, the efficacy of rectal vs oral acetaminophen as treatment of fever and pain. DATA SOURCES: MEDLINE, PubMed, and the Cochrane database as well as major pharmacologic textbooks and the references of all included studies were searched for studies comparing oral and rectal administration of acetaminophen. STUDY SELECTION: Randomized and quasi-randomized controlled studies comparing rectal and oral administration of acetaminophen were included. Reviews, letters, and studies that compared combined treatments or additional drugs were excluded. Main Exposure Oral vs rectal acetaminophen. MAIN OUTCOME MEASURES: Standardized measures of temperature and pain reduction. RESULTS: For temperature reduction, 4 studies met the inclusion criteria. The decline in temperature 1 hour after administration of acetaminophen was no different between rectal and oral administration (weighted mean difference [WMD], -0.14 degrees C; 95% confidence interval [CI], -0.36 degrees C to 0.08 degrees C; P for heterogeneity = .49). There was no difference in the decline of temperature 3 hours after administration (WMD, -0.10 degrees C; 95% CI, -0.41 degrees C to 0.21 degrees C; P = .84), the maximum decline in temperature (WMD, -0.10 degrees C; 95% CI, -0.24 degrees C to 0.04 degrees C; P > .99), or the average time to temperature reduction of 1 degrees C (WMD, -0.06 degrees C; 95% CI, -1.34 degrees C to 1.23 degrees C; P < .001). We did not perform a meta-analysis comparing rectal and oral acetaminophen for pain reduction because only 1 study fulfilled the inclusion criteria. CONCLUSIONS: Rectal and oral acetaminophen are comparable with respect to temperature reduction. The American Academy of Pediatrics recommendation to refrain from rectal acetaminophen in children should possibly be revised.

Pregnancy outcome of women exposed to azathioprine during pregnancy.

BACKGROUND: Azathioprine (AZP) interferes with nucleic acid synthesis and is teratogenic in animals. In view of the paucity of information on the use of AZP during pregnancy we investigated this subject in a prospective, controlled, multicenter study. Our objective was too determine whether exposure to AZP during pregnancy increases the risk for major malformations and to determine the effect on pregnancy outcome. METHODS: Pregnant women on AZP who contacted one of seven teratogen information services were compared to a cohort of pregnant women who contacted two of the seven teratogen information services and took nonteratogenic treatments during their pregnancy. RESULTS: Follow-up was completed on 189 women in the AZP group and compared to 230 women in the control group. The rate of major malformations did not differ between groups with six neonates in each; the AZP rate was 3.5% and the control group rate was 3.0% (p = .775; OR 1.17; CI: 0.37, 3.69). The mean birth weight and gestational age were lower in the AZP group (2,995 g vs. 3,252 g [p = .001, difference of mean: 257, 95% CI: 106.3, 408.1] and 37.8 weeks vs. 39.1 weeks [p = .001, difference of mean: 1.3, 95% CI: .5, 2.0], respectively). The AZP group had more cases of prematurity (21.4% vs. 5.2% [p < .001; OR 4.0; 95% CI: 2.0, 8.06]) and low birth weight (23% vs. 6.0% [p < .001; OR 3.81; 95% CI: 2.0, 7.2]). CONCLUSIONS: These results suggest that AZP (50-100 mg/day) does not triple the rate of birth defects; however, it is associated with lower birth weight, gestational age, and prematurity. Larger studies are needed to confirm these observations.