Evaluation of the incidence of bleeding in patients prescribed rivaroxaban for the treatment and prevention of deep vein thrombosis and pulmonary embolism in UK secondary care: an observational cohort study.

OBJECTIVES: To evaluate the short-term (12 weeks) safety and utilisation of rivaroxaban prescribed to new-user adult patients for the treatment of deep vein thrombosis and pulmonary embolism and for the prevention of recurrent deep vein thrombosis and pulmonary embolism in a secondary care setting in England and Wales. DESIGN: An observational cohort study using the technique of Specialist Cohort Event Monitoring. SETTING: The Rivaroxaban Observational Safety Evaluation study was conducted across 87 participating National Health Service secondary care trusts in England and Wales. PARTICIPANTS: 1532 patients treated with rivaroxaban for the prevention and treatment of deep vein thrombosis/pulmonary embolism from September 2013 to January 2016. INTERVENTIONS: Non-interventional postauthorisation safety study of rivaroxaban. PRIMARY AND SECONDARY OUTCOME MEASURES: (1) Risk of major bleeding in gastrointestinal, intracranial, and urogenital sites and (2) risk of all major and clinically relevant non-major bleeds. RESULTS: Of a total of 4846 patients enrolled in the study from September 2013 to January 2016, 1532 were treated with rivaroxaban for the prevention and treatment of deep vein thrombosis/pulmonary embolism. The median age of the deep vein thrombosis/pulmonary embolism cohort was 63 years, and 54.6% were men. The risk of major bleeding within the gastrointestinal, urogenital and intracranial primary sites was 0.7% (n=11), 0.3% (n=5) and 0.1% (n=1), respectively. The risk of major bleeding in all sites was 1.5% (n=23) at a rate of 8.3 events per 100 patient-years. CONCLUSIONS: In terms of the primary outcome risk of major bleeding in gastrointestinal, intracranial and urogenital sites, the risk estimates in the population using rivaroxaban for deep vein thrombosis/pulmonary embolism were low (<1%) and consistent with the risk estimated from clinical trial data and in routine clinical practice. TRIAL REGISTRATION NUMBERS: ClinicalTrials.gov Registry (NCT01871194); ENCePP Registry (EUPAS3979).

Comparing effectiveness of high-dose Atorvastatin and Rosuvastatin among patients undergone Percutaneous Coronary Interventions: A non-concurrent cohort study in India.

INTRODUCTION: Atorvastatin-80mg/day and Rosuvastatin-40mg/day are the commonest high-dose statin (3-hydroxy-3-methylglutaryl coenzyme-A reductase inhibitors) regimes for post-PCI (Percutaneous Coronary Interventions) patients to lower (by ≥50%) blood low-density-lipoprotein cholesterol (LDL-C). Dearth of conclusive evidence from developing world, regarding overall safety, tolerability and comparative effectiveness (outcome/safety/tolerability/endothelial inflammation control) of Rosuvastatin over Atorvastatin in high-dose, given its higher cost, called for an overall and comparative assessment among post-PCI patients in a tertiary cardiac-care hospital of Kolkata, India. METHODS: A record-based non-concurrent cohort study was conducted involving 942 post-PCI patients, aged 18-75 years, on high-dose statin for three months and followed up for ≥one year. Those on Atorvastatin-80mg (n = 321) and Rosuvastatin-40mg (n = 621) were compared regarding outcome (death/non-fatal myocardial infarction: MI/repeated hospitalization/target-vessel revascularisation/control of LDL and high-sensitivity C-reactive protein: hsCRP), safety (transaminitis/myopathy/myalgia/myositis/rhabdomyolysis), tolerability (gastroesophageal reflux disease: GERD/gastritis) and inflammation control adjusting for socio-demographics, tobacco-use, medications and comorbidities using SAS-9.4. RESULTS: Groups varied minimally regarding distribution of age/gender/tobacco-use/medication/comorbidity/baseline (pre-PCI) LDL and hs-CRP level. During one-year post-PCI follow up, none died. One acute MI and two target vessel revascularizations occurred per group. Repeated hospitalization for angina/stroke was 2.18% in Atorvastatin group vs. 2.90% in Rosuvastatin group. At three-months follow up, GERD/Gastritis (2.18% vs 4.83%), uncontrolled hs-CRP (22.74% vs 31.08%) and overall non-tolerability (4.67% vs. 8.21%) were lower for Atorvastatin group. Multiple logistic regression did show that compared to Atorvastatin-80mg, Rosuvastatin-40mg regime had poorer control of hs-CRP (A3OR = 1.45,p = 0.0202), higher (A3OR = 2.07) adverse effects, poorer safety profile (A3OR = 1.23), higher GERD/Gastritis (A3OR = 1.50) and poorer overall tolerability (A3OR = 1.50). CONCLUSION: Post-PCI high dose statins were effective, safe and well-tolerated. High dose Rosuvastatin as compared to high dose Atorvastatin were similar in their clinical efficacy. Patients treated with Atrovastatin had significantly lower number of patients with hs-CRP (high-sensitivity C-reactive protein)/C-reactive protein (CRP) level beyond comparable safe limit and relatively better tolerated as opposed to Rosuvastatin-40mg.Thus given the lower price, Atorvastatin 80mg/day appeared to be more cost-effective. A head-to-head cost-effectiveness as well as efficacy trial may be the need of the hour.

Prokineticin 2 is a hypothalamic neuropeptide that potently inhibits food intake.

OBJECTIVE: Prokineticin 2 (PK2) is a hypothalamic neuropeptide expressed in central nervous system areas known to be involved in food intake. We therefore hypothesized that PK2 plays a role in energy homeostasis. RESEARCH DESIGN AND METHODS: We investigated the effect of nutritional status on hypothalamic PK2 expression and effects of PK2 on the regulation of food intake by intracerebroventricular (ICV) injection of PK2 and anti-PK2 antibody. Subsequently, we investigated the potential mechanism of action by determining sites of neuronal activation after ICV injection of PK2, the hypothalamic site of action of PK2, and interaction between PK2 and other hypothalamic neuropeptides regulating energy homeostasis. To investigate PK2's potential as a therapeutic target, we investigated the effect of chronic administration in lean and obese mice. RESULTS: Hypothalamic PK2 expression was reduced by fasting. ICV administration of PK2 to rats potently inhibited food intake, whereas anti-PK2 antibody increased food intake, suggesting that PK2 is an anorectic neuropeptide. ICV administration of PK2 increased c-fos expression in proopiomelanocortin neurons of the arcuate nucleus (ARC) of the hypothalamus. In keeping with this, PK2 administration into the ARC reduced food intake and PK2 increased the release of alpha-melanocyte-stimulating hormone (alpha-MSH) from ex vivo hypothalamic explants. In addition, ICV coadministration of the alpha-MSH antagonist agouti-related peptide blocked the anorexigenic effects of PK2. Chronic peripheral administration of PK2 reduced food and body weight in lean and obese mice. CONCLUSIONS: This is the first report showing that PK2 has a role in appetite regulation and its anorectic effect is mediated partly via the melanocortin system.

Fate of human thyroid tissue autotransplants.

PURPOSE: We conducted this study to establish whether human thyroid tissue autografts can survive and function in the absence of their native blood supply in muscle. The benefits of this potential could be incorporated in routine surgery to reduce the incidence of post-operative hypothyroidism. METHODS: Fifteen patients with benign thyroid disorders, seven of whom had Graves' disease and eight, multinodular goiter (MNG), underwent modified subtotal thyroidectomy and the autotransplantation of thyroid tissue in the sternocleidomastoid muscle. About 3-5 g of thyroid tissue was cut and implanted into the sternocleidomastoid muscle. Postoperative clinical assessment, thyroid function tests, and technetium scans of the neck were done to assess the function of remnant and transplanted thyroid tissue. RESULTS: The transplanted tissue was functional in six of the eight patients with MNG and four of the seven with Graves' disease. All the patients with MNG and a functional transplant became euthyroid within 6 months postoperatively. Although the transplanted tissue was functional in four patients with Graves' disease, only one became euthyroid, while the other three required supplemental hormone therapy for postoperative hypothyroidism. CONCLUSIONS: These findings demonstrate the ability of autotransplanted thyroid tissue to survive, function, and grow in muscle.