Polypharmacy and Guideline-Directed Medical Therapy Initiation Among Adults Hospitalized With Heart Failure.

Background: Underprescribing of guideline-directed medical therapy (GDMT) for heart failure (HF) persists. Objectives: The purpose of this study was to assess polypharmacy as a barrier to GDMT. Methods: We examined participants hospitalized for HF with reduced ejection fraction and HF with mildly reduced ejection fraction between 2003 and 2017 from the Reasons for Geographic and Racial Differences in Stroke study. Participants were stratified by admission medication count-0 to 4, 5 to 9, and ≥10 medications. We examined GDMT use at admission, GDMT contraindications, and initiation of eligible indicated GDMT by medication count. We conducted a multivariable Poisson regression with robust standard errors to examine the association between medication count and GDMT initiation. GDMT included agents for HF with reduced ejection fraction/HF with mildly reduced ejection fraction, antiplatelet agents and statins for coronary artery disease, and anticoagulants for atrial fibrillation. Results: Among 545 participants with HF, 34% were not taking a beta-blocker, 39% were not taking an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor-neprilysin inhibitor, or hydralazine-isosorbide dinitrate, and 90% were not taking a mineralocorticoid receptor antagonist at admission; among participants with coronary artery disease, 36% were not taking an antiplatelet agent, and 38% were not taking a statin; and among participants with atrial fibrillation, 49% were not taking an anticoagulant. Polypharmacy was inversely associated with initiation of at least one indicated medication (5-9 medications: relative risk [RR]: 0.67; 95% CI: 0.56-0.82; P < 0.001; ≥10 medications: RR: 0.50; 95% CI: 0.39-0.64; P < 0.001) and initiation of at least half of indicated medications (5-9 medications: RR: 0.64; 95% CI: 0.51-0.81; P < 0.001; ≥10 medications: RR: 0.50; 95% CI: 0.38-0.67; P < 0.001). Conclusions: Polypharmacy is an important barrier to GDMT.

Polypharmacy in Older Adults Hospitalized for Heart Failure.

BACKGROUND: Despite potential harm that can result from polypharmacy, real-world data on polypharmacy in the setting of heart failure (HF) are limited. We sought to address this knowledge gap by studying older adults hospitalized for HF derived from the REGARDS study (Reasons for Geographic and Racial Differences in Stroke). METHODS: We examined 558 older adults aged ≥65 years with adjudicated HF hospitalizations from 380 hospitals across the United States. We collected and examined data from the REGARDS baseline assessment, medical charts from HF-adjudicated hospitalizations, the American Hospital Association annual survey database, and Medicare's Hospital Compare website. We counted the number of medications taken at hospital admission and discharge; and classified each medication as HF-related, non-HF cardiovascular-related, or noncardiovascular-related. RESULTS: The vast majority of participants (84% at admission and 95% at discharge) took ≥5 medications; and 42% at admission and 55% at discharge took ≥10 medications. The prevalence of taking ≥10 medications (polypharmacy) increased over the study period. As the number of total medications increased, the number of noncardiovascular medications increased more rapidly than the number of HF-related or non-HF cardiovascular medications. CONCLUSIONS: Defining polypharmacy as taking ≥10 medications might be more ideal in the HF population as most patients already take ≥5 medications. Polypharmacy is common both at admission and hospital discharge, and its prevalence is rising over time. The majority of medications taken by older adults with HF are noncardiovascular medications. There is a need to develop strategies that can mitigate the negative effects of polypharmacy among older adults with HF.

Efficacy and safety of direct oral anticoagulants in patients with atrial fibrillation and chronic kidney disease.

BACKGROUND: Direct oral anticoagulants (DOACs) are effective alternatives to warfarin for stroke prevention in patients with atrial fibrillation (AF) including patients with CKD III. However, data on patient outcomes with DOACs for advanced CKD are limited, while warfarin use is controversial. METHODS: A retrospective study of patients with AF using DOACs and CKD stages III-V was conducted. The primary outcomes were stroke or systemic embolism and major bleeding while on DOAC therapy among CKD IV and V patients. Rates of outcomes from the DOAC trials and from previous studies of warfarin in CKD were referenced. RESULTS: Of 316 patients reviewed, 152 were included with mean CrCl of 38.8 mL/min. Stroke and systemic embolism occurred at a rate of 1.17 per 100 person-years, with no significant difference between CKD IV/V and CKD III (P = .567). Rates were comparable to DOAC use from the DOAC trials, and lower than rates in studies of warfarin in CKD IV/V patients. There was a nonstatistically significant trend toward increased major bleeding in CKD IV/V patients. Rates of major bleeding in CKD III to V subjects were comparable to published rates for warfarin users with similar levels of renal impairment. CONCLUSIONS: In our study, DOACs appeared to be as efficacious and safe in CKD IV and V as in CKD III. In addition, DOACs appeared to be more effective than, and as safe as warfarin when compared with reference studies of patients with advanced CKD. Our findings support the use of DOACs for thromboembolism prevention in patients with advanced CKD and AF.

The Impact of Systemic Lupus Erythematosus on the Clinical Phenotype of Antiphospholipid Antibody-Positive Patients: Results From the AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Clinical Database and Repository.

OBJECTIVE: Although systemic lupus erythematosus (SLE) is the most common autoimmune disease associated with antiphospholipid antibodies (aPL), limited data exist regarding the impact of SLE on the clinical phenotype of aPL-positive patients. The primary objective of this study was to compare the clinical, laboratory, and treatment characteristics of aPL-positive patients with SLE with those of aPL-positive patients without SLE. METHODS: A secure web-based data capture system was used to store patient demographic characteristics and aPL-related clinical and laboratory characteristics. Inclusion criteria included positive aPL according to the updated Sapporo classification criteria. Antiphospholipid antibody-positive patients fulfilling the American College of Rheumatology criteria for the classification of SLE ("aPL with SLE") and those with no other autoimmune diseases ("aPL only") were included in the analysis. RESULTS: Six hundred seventy-two aPL-positive patients were recruited from 24 international centers; 426 of these patients did not have other autoimmune disease, and 197 had SLE. The frequency of thrombocytopenia, hemolytic anemia, low complement levels, and IgA anti-ß2 -glycoprotein I (anti-ß2 GPI) antibodies was higher in the aPL-positive patients with SLE, whereas the frequency of cognitive dysfunction and IgG anti-ß2 GPI antibodies was higher in the aPL-only group. The frequency of arterial and venous thromboses (including recurrent) as well as pregnancy morbidity was similar in the 2 groups. The prevalence of cardiovascular disease risk factors at the time of entry into the registry entry did not differ between the 2 groups, with the exception of current smoking, which was more frequent in aPL-positive patients with SLE. CONCLUSION: Although the frequencies of thrombosis and pregnancy morbidity are similar in aPL-positive patients with and those without SLE, the diagnosis of SLE in patients with persistently positive aPL is associated with an increased frequency of thrombocytopenia, hemolytic anemia, low complement levels, and positive IgA anti-ß2 GPI antibodies.

Prognostic role of inflammatory biomarkers in metastatic breast cancer.

PURPOSE: The effects of inflammation on the prognosis, life expectancy and several parameters such as response to treatment of breast cancer have been previously studied. The purpose of this study was to investigate the effect of inflammatory markers on prognosis in patients with metastatic breast cancer. METHODS: This study was conducted on 81 patients with metastatic breast cancer who have been followed up at the Department of Medical Oncology, Hacettepe University Institute of Oncology, between December, 2009 and March, 2014. For all studied parameters Kaplan-Meier survival estimates and p values computed by log-rank test were calculated. A p value < 0.05 was considered statistically significant. RESULTS: Median follow-up time was 26 months. There were 38 deaths due to disease progression during the follow up. The levels of serum albumin, and erythrocyte sedimentation rate (ESR) were not associated with a significant effect on overall survival (OS). Among patients with a higher serum C-reactive protein (CRP), the estimated mean survival was 84±36 months, compared to 278±113 months among patients with a normal serum CRP (p=0.032). When patients with higher and normal lactate dehydrogenase (LDH) levels were compared, their 2-year OS survival rates were 68.2 and 87.7%, respectively (p=0.034). Among patients with higher serum ferritin levels, the estimated mean survival was 29±10 months, compared to 212±113 months for normal serum ferritin (p=0.01). Among patients with higher serum beta-2 microglobulin (ß2-M), the estimated mean OS survival was 28±8 months, compared to 84±57 months for those with normal levels (p<0.01). CONCLUSION: Serum CRP, ferritin and ß2-M can be useful prognostic factors for OS in patients with metastatic breast cancer.

Risk factors and histopathological features of breast cancer among women with different menopausal status and age at diagnosis.

PURPOSE: Although there are studies that investigate different risk factors and clinicopathological features of breast cancer in women at different age groups and menopausal status, there is a need for studies with larger study populations due to controversial findings. We conducted this study to identify demographic parameters in breast cancer patients and histopathological features of the tumors for different age groups and compare them to demonstrate significant differences, if any. METHODS: 3325 women diagnosed with breast cancer in Hacettepe University Oncology Hospital Outpatient Clinic between January 1994 and March 2014 were included in this study. RESULTS: Postmenopausal women who were older than 65 were found to have higher number of children, higher rates of oral contraceptive use, greater age at menarche, and have higher rates of first full-time pregnancy before the age of 30. On the other hand, higher rates of grade 3 tumors, advanced lymph node stage, lymphovascular invasion, and triple negative breast cancers were more frequently seen in premenopausal women below the age of 35. Since earlier age at the time of diagnosis is associated with bad prognosis, early diagnosis of breast cancer gains importance in younger women. CONCLUSION: Implementing targeted screening programs of breast cancer for younger women may become a need in the future. Meanwhile, well-education on risks of breast cancer and regular self-examination for early diagnosis need to be emphasized for the prevention of breast cancer and related diseases in young ages.

Correlation of educational status and clinicopathological characteristics of breast cancer: a single center experience.

PURPOSE: Educational status may be an important parameter in assessing breast cancer risk and prognosis. The purpose of this study was to investigate the correlation between the level of education and clinicopathological characteristics of breast cancer, including tumor grade, HER-2 and estrogen receptor (ER) status, tumor size, axillary lymph node involvement and metastasis. METHODS: The study included 1800 women who were diagnosed with invasive breast cancer during 2005-2013 at Hacettepe University Cancer Institute. Patients were divided into three groups according to their educational status at the time of diagnosis as follows: low (illiterate and elementary school, 5 years or less of education), medium (secondary school and upper secondary school, 6-12 years of education) and high (university level, more than 12 years of education). The associations between educational status and clinicopathologic features of breast cancer at the time of diagnosis were evaluated. RESULTS: In all patient, a significant relationship was found between educational status and T stages (p<0.0001). Patients with higher educational levels were reported to have smaller tumor size regardless to their age and were less likely to have axillary lymph node involvement (p=0.001) or metastasis (p=0.001). A significant correlation was found between educational status and ER positivity in patients over 50 years of age (p=0.03). When the patients of all ages were evaluated, no statistically significant correlation was shown (p=0.27) between educational status and ER positivity. A significant relationship was found between educational status and HER-2 status (p=0.003), regardless of the patients' age. HER-2 positivity increased in patients with low educational status, however this significance was lost in patients over the age of 50 (p=0.1). CONCLUSION: The relationship between educational status and biological factors in breast cancer are not conclusive as yet, but this particular study revealed that educational status played a major influence in each of the five breast cancer prognostic factors: ER status, HER-2 status, tumor size, lymph node status and metastasis.

Endoluminal Bariatric Interventions: Where do we stand? Where are we going?

BACKGROUND: Obesity is an epidemic leading to high morbidity, mortality, and therefore health-related costs. Thus, there is a huge need for development of safe and effective treatments. Even though success rates of conservative methods are highly limited, the surgical approaches lead to major complications in as many as 25% of the patients. In this study, we aimed to review the currently available, less-invasive, endoscopic bariatric techniques which provides an option to reduce the risks of the patients and the medical costs. METHODS: A systematic literature review through Pubmed and Medline was performed to find the studies on this topic, and all controlled clinical trials, case reports, and case series were reviewed. RESULTS: Endoluminal bariatric interventions include restrictive, malabsorptive approaches, and other techniques including transpyloric shuttle, botulinum toxin, gastric pacing and vagal nerve stimulation. Restrictive procedures act by limiting the gastric volume and leading to early satiety, while malabsorptive procedures create a malabsorption state. Transpyloric shuttle is a device decreasing the rate of gastric emptying. Botox injection causes a delay in gastric emptying, and vagal nerve stimulation modulates eating behavior. CONCLUSION: Endoluminal bariatric techniques can become the primary choice of therapy in the near future for bariatric care.

Skin cancer in immunosuppressed transplant patients: Vigilance matters.

Liver transplantation (LT) is a widely-accepted, definitive therapy of irreversible liver diseases including hepatitis C, alcoholic liver disease and metabolic liver disease. After transplantation, patients generally use a variety of immunosuppressive medications for the rest of their lives to prevent rejection of transplanted liver. Mortality after LT is mainly caused by recurrence of alcoholic hepatitis which is mostly seen in the patients who resume heavy drinking. On the other hand, de-novo malignancies after LT are not seldom. Skin cancers make up 13.5% of the de-novo malignancies seen in these patients. Malignancies tend to affect survival earlier in the course with a 53% risk of death at 5 years after diagnosis. We aimed to report a case who underwent LT secondary to alcoholic liver disease and developed squamous cell carcinoma of the skin eighteen years after transplantation. In summary, transplant recipients are recommended to be educated on self examination for skin cancer; health care providers should be further suspicious during routine dermatological examinations of the transplant patients and biopsies of possible lesions for skin cancer is warranted even many years after transplantation.

Endoscopic clips for the closure of acute iatrogenic perforations: Where do we stand?

BACKGROUND AND AIM: Iatrogenic perforation of the gut during endoscopy remains an uncommon but critical complication with significant morbidity and probable mortality than usual surgical treatment. Some authors have adopted a non-surgical closure method in chosen cases and, since 1993, endoclips have been used to close perforation in the stomach. The endoscopic practice of endoclips has been commonly used in the gut for hemostasis. Currently, the use of endoscopic techniques is increasing for the closure of endoscopic submucosal dissection or endoscopic mucosal resection. Endoscopic perforations that improved with endoscopic closure in the literature prior to 2008 have been previously described. In the present article, we present a descriptive review of cases with iatrogenic perforation in the gut treated with endoclips between 2008 and 2014. METHODS: Comprehensive literature screening and a systematic review using PubMed and Medline was done for all reports published between January 2008 and December 2014 using the endoclip technique in the closure of iatrogenic perforations. RESULTS: A total of 47 studies published between 2008 and 2014 using endoclips for the closure of iatrogenic perforations of the gut (nine esophagus, 11 stomach, 15 duodenum, 12 colon and rectum) were found. All studies were explained briefly and summarized in a table. CONCLUSIONS: There is strong evidence to show the efficacy of endoclips in the management of iatrogenic perforations, especially when recognized early. Limitations of endoclipping such as inefficiency against large perforations may be overcome by improving novel techniques in the future.