Trends in prescribing and outcomes in obese versus non-obese patients receiving rivaroxaban therapy: an observational study using real-world data.

PURPOSE: To investigate real-world prescribing trends and clinical outcomes based on body mass index (BMI) categorization in patients who received rivaroxaban therapy. METHODS: This was a retrospective cohort study involving all patients who received rivaroxaban therapy across all Hamad Medical Corporation (HMC) hospitals from 2015 to 2020. RESULTS: The number of patients initiated on rivaroxaban therapy significantly increased from 152 (3.3%) in 2015 to 1342 (28.9%) in 2020 (p <0.001). Within BMI categories, a similar increasing trend was observed in underweight, normal, and overweight patients, while from 2018 to 2020, there was a decreasing trend in rivaroxaban prescribing in all obese classes. The prevalence rate of all-cause mortality differed significantly between the BMI groups, with the highest mortality being among morbidly obese patients (BMI ≥ 40 kg/m2) (p< 0.001). On the other hand, no significant differences were found between the BMI groups in terms of bleeding, pulmonary embolism, deep vein thrombosis and stroke incidences. Multivariate logistic regression analyses showed that the likelihood of all-cause mortality was significantly higher in overweight and all categories of obese patients compared to underweight patients: overweight (OR: 5.3, 95% CI: 2.3-11.9, p< 0.001); obese class 1 (OR: 5.4, 95% CI: 2.3 - 12.2, p< 0.001); obese class 2 (OR: 6.5, 95% CI: 2.7 - 15.6, p< 0.001); and obese class 3 (OR: 3.7, 95% CI: 1.6 - 8.7, p = 0.003). CONCLUSIONS: Rivaroxaban prescribing has significantly increased over the years across general population, with a noticeable decline in obese population during the last few years (from 2018 onwards). Furthermore, an appreciable association was evident between all-cause mortality and BMI of these patients.

Hypokalaemia associated with hydrochlorothiazide used in the treatment of hypertension in NHANES 1999-2018.

Hydrochlorothiazide is the most common thiazide diuretic used for hypertension in the US. Yet, hypokalaemia is a well-recognised adverse effect. To evaluate the prevalence and factors associated with hypokalaemia (serum potassium < 3.5 mmol/L) among hydrochlorothiazide users, we included US adults aged ≥20 years in the 1999-2018 National Health and Nutrition Examination Survey. Participants were categorised according to the use of hydrochlorothiazide and other antihypertensive agents. Factors associated with hypokalaemia, including demographics and prescription patterns (monotherapy vs single-pill fixed-dose combination vs polytherapy) were studied using multivariable logistic regression. Hypokalaemia was present in 12.6% of the hydrochlorothiazide users, equivalent to ~2.0 million US adults. Women (adjusted OR, 2.22; 95% CI, 1.74-2.83), non-Hispanic blacks (adjusted OR, 1.65; 95% CI, 1.31-2.08), underweight (adjusted OR, 4.33; 95% CI, 1.34-13.95), and participants taking hydrochlorothiazide for five years or more (adjusted OR, 1.47; 95% CI, 1.06-2.04) had a higher risk of hypokalaemia. Compared to monotherapy, fixed-dose combination therapy (adjusted OR, 0.32; 95% CI, 0.21-0.48) was associated with the lowest risk. Among those taking potassium supplements, hypokalaemia was found in 27.2% of participants on monotherapy and 17.9% on polytherapy. The prevalence of hypokalaemia among hydrochlorothiazide users was considerable, even among participants who also took potassium supplements. Women, ethnic minorities, underweight, monotherapy, and participants with long-term therapy are more likely to have hypokalaemia. Regular monitoring of potassium and combination with potassium-sparing drugs are needed.

Evaluation of safety and efficacy outcomes of direct oral anticoagulants versus warfarin in normal and extreme body weights for the treatment of atrial fibrillation or venous thromboembolism.

Despite evolving evidence, the use of direct oral anticoagulants (DOACs) in patients with extremes of body weight remains controversial. This study aimed to measure the impact of DOACs compared to warfarin on safety and efficacy outcomes in extreme body weight patients. This multi-center, health system, retrospective study examined the outcomes of patients with all body weights and extreme body weights prescribed a DOAC (rivaroxaban, apixaban, dabigatran, edoxaban) or warfarin for atrial fibrillation or venous thromboembolism over a 9-year period. The primary outcome was a composite of thromboembolism, symptomatic recurrent VTE, or severe bleeding; analyzed by pre-determined BMI cutoffs. A total of 19,697 patients were included in the study: 11,604 in the DOAC group and in the 8093 in the warfarin group. 295 patients were underweight and 9108 patients were pre-obese to obese class 3. After adjusting for potential confounders, warfarin patients had higher odds of experiencing the composite outcome compared to DOAC patients (OR 1.337, 95% CI 1.212-1.475). Additionally, obese patients were 24.6% more likely to experience the outcome compared to normal BMI patients. Adjusted modeling showed that warfarin patients experienced higher bleed rates compared to DOAC patients (OR 1.432, 95% CI 1.266-1.620). Obese patients were less likely to be diagnosed with a bleed (OR 0.749, 95% CI 0.658-0.854), and underweight patients were more likely to be diagnosed with a bleed (OR 1.522, 95% CI 1.095-2.115) compared to normal BMI patients. In conclusion, DOACs for atrial fibrillation or VTE in patients with extreme body weights appear safe and effective when compared to warfarin.

Comparative Effects of Dietary Hemp and Poppy Seed Oil on Lipid Metabolism and the Antioxidant Status in Lean and Obese Zucker Rats.

The objective of this study was to compare the effects of the dietary inclusion of hemp seed oil (HO) and poppy seed oil (PO) on the lipid metabolism and antioxidant status of lean and genetically obese Zucker rats. The rats were fed a control diet for laboratory rodents or a modification with HO or PO. Both oils reduced body and epididymal fat and liver cholesterol levels and promoted oxidative stress in the liver of obese rats. The HO reduced plasma triglycerides and had a stronger liver cholesterol-lowering effect in obese rats than PO. In the lean rats, HO and PO had no effects on the body fat content, plasma lipid profile, or lipid metabolism in the liver. HO considerably elevated the content of α-linolenic acid in the liver and increased the liver ratio of reduced glutathione (GSH)/oxidized glutathione (GSSG) in the lean rats. In conclusion, the regular consumption of both oils increases the accumulation of essential fatty acids in the liver of healthy animals, whilst not having any adverse effects on the body, whereas in genetically obese rats, the effects of both dietary oils on the lipid metabolism and antioxidant status are unequivocal and only partially beneficial.

Nicotinamide riboside induces a thermogenic response in lean mice.

AIMS: Nicotinamide Riboside (NR) is a NAD+ booster with wide physiological repercussion including the improvement on glucose and lipid homeostasis, increasing the life expectancy in mammals. However, the effects of NR on metabolism are only partially known. Here, we evaluated the effects of NR on the thermogenic response, highlighting the brown adipose tissue (BAT) in lean mice. MAIN METHODS: Male C57BL/67 mice were supplement with NR (400 mg/Kg/day) during 5 weeks. The Comprehensive Lab Animal Monitoring System (CLAMS) and thermographic images were used to evaluated the physiological effects of NR treatment. The BAT were extracted and analyzed by Western Blotting and qPCR. Also, bioinformatics analyses were performed to establish the connection between the NAD+ synthesis pathway in BAT and thermogenic response in several isogenic strains of BXD mice. KEY FINDINGS: Transcriptomic analysis revealed that genes involved in NAD+ synthesis (Nampt and Nmnat1) in the BAT were negatively correlated with body weight and fat mass. The heat map showed a strong positive correlation between Nampt and Ucp1 mRNA in BAT and body temperature in several strains of BXD lean mice. The experimental approaches demonstrated that oral NR supplementation reduced the abdominal visceral fat depots, with discrete impact on oxygen consumption in C57BL/6J mice. Interestingly, NR significantly increased the body temperature, and this phenomenon was accompanied by high levels of UCP1 protein content and Pgc1α mRNA in BAT. SIGNIFICANCE: This study demonstrated the oral NR supplementation was sufficient to induce the thermogenic response in lean mice changing the BAT metabolism.

Safety and efficacy of a lipid emulsion containing a mixture of soybean oil, medium-chain triglycerides, olive oil, and fish oil: a randomised, double-blind clinical trial in premature infants requiring parenteral nutrition.

OBJECTIVES: Safety, tolerability, and efficacy of a novel lipid emulsion containing a mixture of soybean oil, medium-chain triglycerides, olive oil, and fish oil (SMOFlipid 20%) with reduced n-6 fatty acids (FA), increased monounsaturated and n-3 FA, and enriched in vitamin E were evaluated in premature infants compared with a soybean oil-based emulsion. PATIENTS AND METHODS: Sixty (30/30) premature neonates (age 3-7 days, gestational age ≤ 34 weeks, birth weights 1000-2500 g) received parenteral nutrition (PN) with either SMOFlipid 20% (study group) or a conventional lipid emulsion (Intralipid 20%, control group) for a minimum of 7 up to 14 days. Lipid supply started at 0.5 g · kg body weight(-1) · day(-1) on day 1 and increased stepwise (by 0.5 g) up to 2 g · kg body weight(-1) · day(-1) on days 4 to 14. Safety and efficacy parameters were assessed on days 0, 8, and 15 if PN was continued. RESULTS: Adverse events, serum triglycerides, vital signs, local tolerance, and clinical laboratory did not show noticeable group differences, confirming the safety of study treatment. At study end, γ-glutamyl transferase was lower in the study versus the control group (107.8 ± 81.7 vs 188.8 ± 176.7 IU/L, P < 0.05). The relative increase in body weight (day 8 vs baseline) was 5.0% ± 6.5% versus 5.1% ± 6.6% (study vs control, not significant). In the study group, an increase in n-3 FA in red blood cell phospholipids and n-3:n-6 FA ratio was observed. Plasma α-tocopherol (study vs control) was increased versus baseline on day 8 (26.35 ± 10.03 vs 3.67 ± 8.06 µmol/L, P < 0.05) and at study termination (26.97 ± 18.32 vs 8.73 ± 11.41 µmol/L, P < 0.05). CONCLUSIONS: Parenteral infusion of SMOFlipid was safe and well tolerated and showed a potential beneficial influence on cholestasis, n-3 FA, and vitamin E status in premature infants requiring PN.

Effects of moderate doses of vitamin A as an adjunct to the treatment of pneumonia in underweight and normal-weight children: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Randomized controlled trials have shown inconsistent responses of childhood pneumonia to the use of vitamin A as an adjunct to the standard treatment of pneumonia. OBJECTIVE: We evaluated the effect of a moderate dose of vitamin A as an adjunct to standard antimicrobial treatment on the duration of respiratory signs in children with pneumonia. DESIGN: Children, aged 2-59 mo, with pneumonia and weight-for-age <50th percentile who had been admitted to the Baca Ortíz Children's Hospital in Quito, Ecuador, were randomly assigned to receive 50,000 IU (aged 2-12 mo) or 100,000 IU (aged >12-59 mo) vitamin A or a placebo. RESULTS: Of the 287 children enrolled, 145 received vitamin A and 142 received placebo. No overall differences were observed between the 2 groups in the duration of signs of pneumonia. Multiple linear regression showed a significant interaction between basal serum retinol concentration and vitamin A group for the time (in h) to remission of respiratory signs (beta = -3.57, SE = 1.09, P = 0.001). Duration of clinical signs was less in children with basal serum retinol concentrations >200 microg/L who received vitamin A supplements than in children with similar concentrations who received placebo (69.9 +/- 49.9 h compared with 131.3 +/- 143.9 h; P = 0.049). CONCLUSIONS: Overall, we found no effect of a moderate dose of vitamin A supplementation on the duration of uncomplicated pneumonia in underweight or normal-weight children aged <5 y. However, a beneficial effect was seen in children with high basal serum retinol concentrations.