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.

Effect of Lipid-Based Multiple Micronutrients Supplementation in Underweight Primigravida Pre-Eclamptic Women on Maternal and Pregnancy Outcomes: Randomized Clinical Trial.

Background and Objectives: In pre-eclampsia, restricted blood supply due to the lack of trophoblastic cell invasion and spiral artery remodeling is responsible for adverse pregnancies and maternal outcomes, which is added to by maternal undernutrition. This study was designed to observe the effect of multiple nutritional micronutrient supplements on the pregnancy outcomes of underweight pre-eclamptic women. To investigate the effects of lipid-based multiple micr supplementations (LNS-PLW) on pregnancy and maternal outcomes in underweight primigravida pre-eclamptic women. Materials and Methods: A total of 60 pre-eclamptic, underweight primigravida women from the antenatal units of tertiary care hospitals in the Khyber Pakhtunkhwa Province, Pakistan, were randomly divided into two groups (Group 1 and Group 2). The participants of both groups were receiving routine treatment for pre-eclampsia: iron (60 mgs) and folic acid (400 ug) IFA daily. Group 2 was given an additional sachet of 75 gm LNS-PLW daily till delivery. The pregnancy outcomes of both groups were recorded. The clinical parameters, hemoglobin, platelet count, and proteinuria were measured at recruitment. Results: The percentage of live births in Group 2 was 93% compared to 92% in Group 1. There were more normal vaginal deliveries (NVDs) in Group 2 compared to Group 1 (Group 2, 78% NVD; group 1, 69% NVD). In Group 1, 4% of the participants developed eclampsia. The frequency of cesarean sections was 8/26 (31%) in Group 1 and 6/28 (22%) in Group 2. The number of intrauterine deaths (IUDs) was only 1/28 (4%) in Group 2, while it was 2/26 (8%) in Group 1. The gestational age at delivery significantly improved with LNS-PLW supplementation (Group 2, 38.64 ± 0.78 weeks; Group 1, 36.88 ± 1.55 weeks, p-value 0.006). The Apgar score (Group 2, 9.3; Group 1, 8.4) and the birth weight of the babies improved with maternal supplementation with LNS-PLW (Group 2, 38.64 ± 0.78 weeks: Group 1, 36.88 ± 1.55; p-value 0.003). There was no significant difference in systolic blood pressure, while diastolic blood pressure (Group 2, 89.57 ± 2.08 mmHg; Group 1, 92.17 ± 5.18 mmHg, p-value 0.025) showed significant improvement with LNS-PLW supplementation. The hemoglobin concentration increased with the LNS-PLW supplement consumed in Group 2 (Group 2, 12.15 ± 0.78 g/dL; Group 1, 11.39 ± 0.48 g/dL, p-value < 0.001). However, no significant difference among the platelet counts of the two groups was observed. Conclusions: The pregnancy and maternal outcomes of underweight pre-eclamptic women can be improved by the prenatal daily supplementation of LNS-PLW during pregnancy, along with IFA and regular antenatal care and follow-up.

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.

Longitudinal alterations in nutrient intake and food pattern in patients with non-small cell lung cancer during anti-neoplastic treatment: a cohort study.

BACKGROUND: Unintentional weight loss is frequently observed in cancer patients. Nutritional therapy is essential, and dietary counselling is the first step. The present study aimed to explore the nutrient intake and food patterns in weight-stable and weight-losing patients with non-small cell lung cancer (NSCLC) during anti-neoplastic treatment. METHODS: Patients with NSCLC (n = 62) were observed during first-line systemic anti-neoplastic treatment. Body weight and dietary intake were assessed on the first and second cycle, and after completing three cycles of treatment. Longitudinal changes were analysed in three groups: weight stable, weight losers and mixed weight. RESULTS: Nutrient intake did not change during treatment in weight stable, although weight losers significantly increased the relative protein intake. Weight stable maintained the food pattern during treatment apart from a decreased consumption of oral nutritional support (ONS). At baseline, weight losers were characterised by pretreatment weight loss, high consumption of ONS, as well as low consumption of grains and animal products. During treatment, weight losers increased the consumption of protein, fatty foods and ONS but decreased the consumption of sweets and alcohol. CONCLUSIONS: Large heterogeneity in nutrient and food intake was observed in NSCLC patients during anti-neoplastic treatment. Weight losers and weight stable had a similar nutrient intake although protein intake increased in weight losers. Grains and animal products were lower and ONS higher in weight losers compared to weight stable during treatment. Weight losers further increased the consumption of ONS and fatty foods, while the consumption of sweets and alcohol decreased during treatment.

A selective androgen receptor modulator with minimal prostate hypertrophic activity restores lean body mass in aged orchidectomized male rats.

Androgens are required for the maintenance of normal sexual activity in adulthood and for enhancing muscle growth and lean body mass in adolescents and adults. Androgen receptor (AR) ligands with tissue selectivity (selective androgen receptor modulators, or SARMs) have potential for treating muscle wasting, hypogonadism of aging, osteoporosis, female sexual dysfunction, and other indications. JNJ-37654032 is a nonsteroidal AR ligand with mixed agonist and antagonist activity in androgen-responsive cell-based assays. It is an orally active SARM with muscle selectivity in orchidectomized rat models. It stimulated growth of the levator ani muscle with ED(50) 0.8 mg/kg, stimulating maximal growth at a dose of 3mg/kg. In contrast, it stimulated ventral prostate growth to 21% of its full size at 3mg/kg. At the same time, JNJ-37654032 reduced prostate weight in intact rats by 47% at 3mg/kg, while having no inhibitory effect on muscle. Using magnetic resonance imaging to monitor body composition, JNJ-37654032 restored about 20% of the lean body mass lost following orchidectomy in aged rats. JNJ-37654032 reduced follicle-stimulating hormone levels in orchidectomized rats and reduced testis size in intact rats. JNJ-37654032 is a potent prostate-sparing SARM with the potential for clinical benefit in muscle-wasting diseases.