Cardiovascular Safety During Treatment With Baricitinib in Rheumatoid Arthritis

OBJECTIVE: To assess the frequency of cardiovascular and venous thromboembolic events in clinical studies of baricitinib, an oral, selective JAK1 and JAK2 inhibitor approved in more than 50 countries for the treatment of moderately-to-severely active rheumatoid arthritis (RA). METHODS: Data were pooled from 9 RA studies. Placebo comparison up to 24 weeks included data from 6 studies. Randomized dose comparison between baricitinib doses of 2 mg and 4 mg used data from 4 studies and from the associated long-term extension study. The data analysis set designated "All-bari-RA" included all baricitinib exposures at any dose. RESULTS: Overall, 3,492 RA patients received baricitinib (7,860 patient-years of exposure). No imbalance compared to the placebo group was seen in the incidence of major adverse cardiovascular events (MACE) (incidence rates [IRs] of 0.5 per 100 patient-years for placebo and 0.8 per 100 patient-years for 4 mg baricitinib), arterial thrombotic events (ATE) (IRs of 0.5 per 100 patient-years for placebo and 0.5 per 100 patient-years for 4 mg baricitinib), or congestive heart failure (CHF) broad term (IRs of 4.3 per 100 patient-years for placebo and 2.4 per 100 patient-years for 4 mg baricitinib). Deep vein thrombosis (DVT)/pulmonary embolism (PE) were reported in 0 of 1,070 patients treated with placebo and 6 of 997 patients treated with 4 mg baricitinib during the placebo-controlled period; these events were serious in 2 of 6 patients, while all 6 had risk factors and 1 patient developed DVT/PE after discontinuation of the study drug. In the 2 mg-4 mg-extended data analysis set, IRs of DVT/PE were comparable between the doses across event types (IRs of 0.5 per 100 patient-years in those receiving 2 mg baricitinib and 0.6 per 100 patient-years in those receiving 4 mg baricitinib). In the All-bari-RA data analysis set, the rates were stable over time, with an IR of DVT/PE of 0.5 per 100 patient-years. CONCLUSION: In RA clinical trials, no association was found between baricitinib treatment and the incidence of MACE, ATE, or CHF. With regard to incidence of DVT/PE, 6 events occurred in patients treated with 4 mg baricitinib, but no cases of DVT/PE were reported in the placebo group. During longer-term evaluation, the incidence of DVT/PE was similar between the baricitinib dose groups, with consistent IR values over time, and this was similar to the rates previously reported in patients with RA

Changes in selected haematological parameters associated with JAK1/JAK2 inhibition observed in patients with rheumatoid arthritis treated with baricitinib

Objective To characterise changes in selected haematological parameters following once-daily oral baricitinib dosing.Methods Data were pooled from eight randomised clinical trials (four phase 3, three phase 2, one phase 1b) and one long-term extension. Changes in haematological parameters were evaluated up to 128 weeks (N=2387); overall safety of baricitinib was assessed up to 6 years (N=3492).Results Mean absolute neutrophil counts decreased (-1.36x10(9)/L) within 1 month, followed by stabilisation within the normal reference range through week 128. The incidence of serious infections was not elevated in patients with neutropenia during the 24-week placebo-controlled period. Mean lymphocyte counts increased (+0.30x10(9)/L) within 1 month, then decreased to baseline (weeks 12-24). Mean platelet counts increased at week 2 (+51x10(9)/L), then decreased towards baseline. Overall, mean haemoglobin concentrations decreased (-0.12 mmol/L), then returned to baseline; however, reduced baseline haemoglobin concentrations observed in the highest baseline high-sensitivity C reactive protein quartile increased over time. Permanent drug discontinuation occurred due to laboratory abnormalities related to neutrophil count in 8 (0.2%), lymphocyte counts in 6 (0.2%), platelet counts in 8 (0.2%), and haemoglobin levels in 16 (0.5%) of all baricitinib-treated patients (N=3492 with 7993 total person-years of exposure).Conclusions Moderate decreases in neutrophils were seen during baricitinib treatment; however, serious infection was uncommon in patients with neutropenia. Transient increases were observed in lymphocytes and platelets, which returned to baseline over time. Changes in haemoglobin concentration were generally small. Haematological abnormalities seldom led to drug discontinuation.Pathophysiology and treatment of rheumatic disease

Social Entrepreneurship and Social Innovation in Aging

Social entrepreneurship is usually understood as an economic activity which focuses at social values, goals, and investments that generates surpluses for social entrepreneurs as individuals, groups, and startups who are working for the benefit of communities, instead of strictly focusing mainly at the financial profit, economic values, and the benefit generated for shareholders or owners. Social entrepreneurship combines the production of goods, services, and knowledge in order to achieve both social and economic goals and allow for solidarity building. From a broader perspective, entities that are focused on social entrepreneurship are identified as parts of the social and solidarity economy. These are, for example, social enterprises, cooperatives, mutual organizations, self-help groups, charities, unions, fair trade companies, community enterprises, and time banks. Social innovation is a key element of social entrepreneurship. Social innovation is usually understood as new strategies, concepts, products, services, and organizational forms that allow for the satisfaction of needs. Such innovations are created in particular in the contact areas of various sectors of the social system. For example, these are spaces between the public sector, the private sector, and civil society. These innovations not only allow the solving of problems but also extend possibilities for public action

Hyperhomocysteinemia and vascular access thrombosis in hemodialysis patients: a retrospective study

Chadi Saifan, Elie El-Charabaty, Suzanne El-SayeghStaten Island University Hospital, Staten Island, NY, USABackground: Elevated total plasma homocysteine is an independent risk factor for arterial and venous thrombosis in patients with normal renal function. Patients on hemodialysis have a high prevalence of mild to moderate hyperhomocysteinemia. Conflicting retrospective analyses and prospective studies have been reported regarding the association between total homocysteine levels and hemodialysis vascular thrombosis. The purpose of this retrospective study was to investigate the relationship between hyperhomocysteinemia and vascular access thrombosis (VAT) in patients on hemodialysis.Methods: One hundred and twenty-five patients undergoing dialysis were selected as subjects. The experimental group participants were identified as those having one or more VAT during the previous 13 months and the control group participants had no access thrombosis during the same period. Additional subgroup analysis included the presence of hypertension, diabetes, low-density lipoprotein levels, sex, and use of aspirin.Results: No statistically significant difference was found in total homocysteine levels between the two groups (P = 0.27). No association was found between VAT and sex (P = 0.09), VAT and hypertension (P = 0.96), VAT and diabetes (P = 0.49), nor VAT and low-density lipoprotein level (P = 0.04). A lower rate of VAT was associated with aspirin intake (P = 0.04).Conclusion: This study did not demonstrate a relationship between total homocysteine concentrations and risk of VAT in patients with end-stage renal disease on hemodialysis. There were no significant differences in the number of VAT across additional variables of sex and previous morbidity. Aspirin intake was associated with a lower incidence of VAT.Keywords: hyperhomocysteinemia, vascular access thrombosis, hemodialysi

Effect of hepatitis C virus infection on erythropoiesis in patients on hemodialysis

Chadi Saifan, Elie El-Charabaty, Morton Kleiner, Suzanne El-SayeghDepartment of Medicine, Division of Nephrology, Staten Island University Hospital, Staten Island, NY, USABackground: Erythropoietin is a hormone that regulates erythropoiesis and is mainly produced by the kidneys. Several animal studies as well as a few case reports and case series have demonstrated that regenerating hepatic tissue can produce more erythropoietin than normal hepatic tissue. The purpose of the study was to examine the difference in hemoglobin and hematocrit levels as well as epoetin dosage in patients on hemodialysis with and without hepatitis C (HCV).Methods: A retrospective chart review was performed. Seventy-six patients were included in the study (19 with HCV and 57 without HCV) at a ratio of 1:3. Exclusion criteria were a history of gastrointestinal bleeding or blood transfusion over the previous six months, polycystic kidney disease, and pregnancy. Variables examined included gender, age, duration of hemodialysis, hemoglobin, hematocrit, epoetin dose, aspartate transaminase, and ferritin levels over a three-month period.Results: The patients were divided into two groups. The first consisted of patients with HCV on hemodialysis and the second of patients on hemodialysis without HCV. Mean hemoglobin was 12.6 ± 1.2 g/dL for the HCV-positive group and 11.9 ± 1.1 g/dL for the HCV-negative group. The difference was statistically significant (P = 0.03). Mean hematocrit was higher in the HCV-positive group, but was not significantly different at 39.08% ± 4.06% versus 37.43% ± 3.4% in the HCV-negative group (t-test, P = 0.11). Further, the HCV-positive group required less epoetin, but this was not significantly different from that required in the HCV-negative group at 6258 ± 5208 IU versus 7596 ± 7056 IU, respectively (t-test, P = 0.38).Conclusion: In our study, patients with HCV infection were found to have higher hemoglobin and hematocrit levels and lower epoetin requirements than those without HCV. Although the findings were not statistically significant, the computed values between these two groups of patients did follow a general trend. Further investigation with more patients, a longer duration of follow-up, and incorporation of additional medical variables is needed to clarify the role of HCV on erythropoiesis in hemodialysis patients.Keywords: hepatitis C virus, erythropoiesis, hemodialysis, hematocrit, epoeti

Warfarin-induced calciphylaxis: a case report and review of literature

Chadi Saifan, Marc Saad, Elie El-Charabaty, Suzanne El-SayeghStaten Island University Hospital, Staten Island, NY, USAAbstract: Calciphylaxis is a challenging complication of end-stage renal disease, with an unknown underlying mechanism. Several risk factors have been identified, such as hyperphosphatemia, hypercalcemia, hyperparathyroidism, low serum albumin levels, and history of warfarin therapy. This article presents a case of calciphylaxis provoked by reintroduction of warfarin therapy, introducing the possibility of direct induction.Keywords: warfarin, calciphylaxis, skin necrosis, ESR

Cardiovascular safety during treatment with baricitinib in rheumatoid arthritis

Baricitinib (BARI) is an oral selective inhibitor of Janus kinase (JAK)1 and JAK2 approved in the EU for the treatment of active RA. Patients (pts) with RA have increased cardiovascular risk, including for arterial and venous occlusive events. This abstract examines the effects of BARI on cardiovascular events in RA

Relationship between platelet count and hemodialysis membranes

Rabih Nasr,1 Chadi Saifan,1 Iskandar Barakat,2 Yorg Al Azzi,2 Ali Naboush,2 Marc Saad,2 Suzanne El Sayegh1 1Department of Nephrology, Staten Island University Hospital, Staten Island, NY, USA; 2Department of Medicine, Staten Island University Hospital, Staten Island, NY, USA Background: One factor associated with poor outcomes in hemodialysis patients is exposure to a foreign membrane. Older membranes are very bioincompatible and increase complement activation, cause leukocytosis by activating circulating factors, which sequesters leukocytes in the lungs, and activates platelets. Recently, newer membranes have been developed that were designed to be more biocompatible. We tested if the different “optiflux” hemodialysis membranes had different effects on platelet levels. Methods: Ninety-nine maintenance hemodialysis patients with no known systemic or hematologic diseases affecting their platelets had blood drawn immediately prior to, 90 minutes into, and immediately following their first hemodialysis session of the week. All patients were dialyzed using a Fresenius Medical Care Optiflux polysulfone membrane F160, F180, or F200 (polysulfone synthetic dialyzer membranes, 1.6 m2, 1.8 m2, and 2.0 m2 surface area, respectively, electron beam sterilized). Platelet counts were measured from each sample by analysis using a CBC analyzer. Results: The average age of the patients was 62.7 years; 36 were female and 63 were male. The mean platelet count pre, mid, and post dialysis was 193 (standard deviation ±74.86), 191 (standard deviation ±74.67), and 197 (standard deviation ±79.34) thousand/mm3, respectively, with no statistical differences. Conclusion: Newer membranes have no significant effect on platelet count. This suggests that they are, in fact, more biocompatible than their predecessors and may explain their association with increased survival. Keywords: platelet count, polysulfone membranes, complement activation, electron beam sterilized, cellulosic membranes, bioincompatible event

Is kidney function affecting the management of myocardial infarction? A retrospective cohort study in patients with normal kidney function, chronic kidney disease stage III–V, and ESRD

Marc Saad,1 Boutros Karam,1 Geovani Faddoul,2 Youssef El Douaihy,1 Harout Yacoub,1 Hassan Baydoun,3 Christine Boumitri,1 Iskandar Barakat,1 Chadi Saifan,4 Elie El-Charabaty,4 Suzanne El Sayegh4 1Department of Internal Medicine, Staten Island University Hospital, Staten Island, 2Department of Nephrology, Icahn School of Medicine, New York, NY, 3Department of Cardiology, Tulane University Medical Center, New Orleans, LA, 4Department of Nephrology, Staten Island University Hospital, Staten Island, NY, USA Abstract: Patients with chronic kidney disease (CKD) are three times more likely to have myocardial infarction (MI) and suffer from increased morbidity and higher mortality. Traditional and unique risk factors are prevalent and constitute challenges for the standard of care. However, CKD patients have been largely excluded from clinical trials and little evidence is available to guide evidence-based treatment of coronary artery disease in patients with CKD. Our objective was to assess whether a difference exists in the management of MI (ST-segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction) among patients with normal kidney function, CKD stage III–V, and end-stage renal disease (ESRD) patients. We conducted a retrospective cohort study on patients admitted to Staten Island University Hospital for the diagnosis of MI between January 2005 and December 2012. Patients were assigned to one of three groups according to their kidney function: Data collected on the medical management and the use of statins, platelet inhibitors, beta-blockers, and angiotensin converting enzyme inhibitors/angiotensin receptor blockers were compared among the three cohorts, as well as medical interventions including: catheterization and coronary artery bypass graft (CABG) when indicated. Chi-square test was used to compare the proportions between nominal variables. Binary logistic analysis was used in order to determine associations between treatment modalities and comorbidities, and to account for possible confounding factors. Three hundred and thirty-four patients (mean age 67.2±13.9 years) were included. In terms of management, medical treatment was not different among the three groups. However, cardiac catheterization was performed less in ESRD when compared with no CKD and CKD stage III–V (45.6% vs 74% and 93.9%) (P<0.001). CABG was performed in comparable proportions in the three groups and CABG was not associated with the degree of CKD (P=0.078) in binary logistics regression. Cardiac catheterization on the other hand carried the strongest association among all studied variables (P<0.001). This association was maintained after adjusting for other comorbidities. The length of stay for the three cohorts (non-CKD, CKD stage III–V, and ESRD on hemodialysis) was 16, 17, and 15 days, respectively and was not statistically different. Many observations have reported discrimination of care for patients with CKD considered suboptimal candidates for aggressive management of their cardiac disease. In our study, medical therapy was achieved at high percentage and was comparable among groups of different kidney function. However, kidney disease seems to affect the management of patients with acute MI; percutaneous coronary angiography is not uniformly performed in patients with CKD and ESRD when compared with patients with normal kidney function. Keywords: myocardial infarction, chronic kidney disease, end-stage renal diseas