Marija Zdraveska

A comprehensive evaluation of temporal trends in the treatment of patients who have deep vein thrombosis (DVT) may assist with identification of modifiable factors that contribute to short-term outcomes. We assessed temporal trends in length of hospital stay and use of pharmacological and interventional therapies among 26,695 adults with DVT enrolled in the RIETE registry between 2001 and 2014. We also examined temporal trends in risk-adjusted rates of all-cause, PE-related, and bleeding-related death to 30-days after diagnosis. The mean length of hospital stay decreased from 9.0 days in 2001-2005 to 7.6 days in 2010-2014 (P <0.01). For initial DVT treatment, the use of low-molecular weight-heparin decreased from 98% to 90% (P <0.01). Direct oral anticoagulants use increased from 0.5% in 2010 to 13.4% in 2014 (P <0.001). Risk-adjusted rates of 30-day all-cause mortality decreased from 3.9% in 2001-2005 to 2.7% in 2010-2014 (adjusted rate ratio per year, 0.84; 95% confidence interval [CI], 0.74 to 0.96; P <0.01). VTE-related mortality showed a non-statistically significant downward trend (adjusted rate ratio per year, 0.70; 95% CI, 0.44 to 1.10; P =0.13), whereas 30-day bleeding-related mortality significantly decreased from 0.5% in 2001-2005 to 0.1% in 2010-2014 (adjusted rate ratio per year, 0.55; 95% CI, 0.40 to 0.77; P <0.01). This international registry-based temporal analysis identified reductions in length of stay for adults hospitalized for DVT. The study also found a decreasing trend in adjusted rates of all-cause and bleeding-related mortality.

BackgroundPatients with venous thromboembolism (VTE) secondary to transient risk factors may develop VTE recurrences after discontinuing anticoagulation. Identifying at‐risk patients could help to guide the duration of therapy.MethodsWe used the RIETE database to assess the prognostic value of d‐dimer testing after discontinuing anticoagulation to identify patients at increased risk for recurrences. Transient risk factors were classified as major (postoperative) or minor (pregnancy, oestrogen use, immobilization or recent travel).ResultsIn December 2018, 1655 VTE patients with transient risk factors (major 460, minor 1195) underwent d‐dimer measurements after discontinuing anticoagulation. Amongst patients with major risk factors, the recurrence rate was 5.74 (95% CI: 3.19–9.57) events per 100 patient‐years in those with raised d‐dimer levels and 2.68 (95% CI: 1.45–4.56) in those with normal levels. Amongst patients with minor risk factors, the rates were 7.79 (95% CI: 5.71–10.4) an...

Individuals with factor V Leiden or prothrombin G20210A mutations are at a higher risk to develop venous thromboembolism. However, the influence of these polymorphisms on patient outcome during anticoagulant therapy has not been consistently explored. We used the Registro Informatizado de Enfermedad TromboEmbólica database to compare rates of venous thromboembolism recurrence and bleeding events occurring during the anticoagulation course in factor V Leiden carriers, prothrombin mutation carriers, and noncarriers. Between March 2001 and December 2015, 10,139 patients underwent thrombophilia testing. Of these, 1384 were factor V Leiden carriers, 1115 were prothrombin mutation carriers, and 7640 were noncarriers. During the anticoagulation course, 160 patients developed recurrent deep vein thrombosis and 94 patients developed pulmonary embolism (16 died); 154 patients had major bleeding (10 died), and 291 patients had nonmajor bleeding. On multivariable analysis, factor V Leiden carri...

We sought to determine the risk factors for subsequent bleeding and recurrent venous thromboembolism (VTE) events following isolated noncatheter-associated upper extremity deep venous thrombosis (non-CA-UEDVT) to better inform future treatment decisions for this group of patients. The RIETE registry (Registro Informatizado de Enfermedad TromboEmbólica [Computerized Registry of Patients with Venous Thromboembolism]) is a prospective international registry of patients with objectively confirmed symptomatic VTE. Patients with a symptomatic, isolated, proximal UEDVT from March 2001 through March 2015 were analyzed. Any patient with an indwelling catheter or pacemaker lead at the DVT site and at the time of thrombosis was considered to have a CA-UEDVT and was excluded. Patient and treatment characteristics such as age, gender, comorbidities, VTE risk factors, treatment drug, and duration were collected. Outcomes examined included recurrent DVT, subsequent pulmonary embolism (PE), and hem...

The concept of "united airways disease", based on many similar features and mutual interactions in the pathogenesis of asthma (A) and rhinitis (R), has led to an integral approach to their management. We conducted this study to determine the quantity of the problem of joint incidence of A and R in R. Macedonia, and, perhaps to obtain information on a potential causative effect of the two diseases. Three hundred eighty six patients, who presented with wheezing and/or upper respiratory symptoms at the Pulmology and Allergy Clinic, Skopje, were included during a period of 48 months. The presence of bronchial hyperreactivity - BHR (positive histamine challenge), atopy (prick test to seasonal or perennial inhaled allergens), rhinitis symptoms (such as nasal secretion and obstruction) and X-ray of paranasal sinuses was registered by a specially designed questionnaire. R was diagnosed in 106 of the subjects (27.5%), and A in 280 (72.5%). Among the patients with A, co-incidence wi...

A small proportion of patients with deep vein thrombosis develop recurrent venous thromboembolic complications or bleeding during anticoagulant treatment. These complications may occur more frequently if these patients have concomitant cancer. This prospective follow-up study sought to determine whether in thrombosis patients those with cancer have a higher risk for recurrent venous thromboembolism or bleeding during anticoagulant treatment than those without cancer. Of the 842 included patients, 181 had known cancer at entry. The 12-month cumulative incidence of recurrent thromboembolism in cancer patients was 20.7% (95% CI, 15.6%-25.8%) versus 6.8% (95% CI, 3.9%- 9.7%) in patients without cancer, for a hazard ratio of 3.2 (95% CI, 1.9-5.4) The 12-month cumulative incidence of major bleeding was 12.4% (95% CI, 6.5%-18.2%) in patients with cancer and 4.9% (95% CI, 2.5%-7.4%) in patients without cancer, for a hazard ratio of 2.2 (95% CI, 1.2-4.1). Recurrence and bleeding were both re...

Macedonia has one of the highest smoking rates in Europe and ranks among the top ten globally. Although there is a moderately strict anti-smoking legislation, tobacco free policies are not financially supported and smoking cessation activities are not included in the regular educational process of health workers in the country. Smoking cessation is not considered a medical intervention, there is no consistent access to nicotine replacement therapy or other cessation medications, nor are they covered by health insurance. The goal of the partners from Henry Ford Health System and the University St Cyril and Method in Skopje was to develop and adapt a Certified Tobacco Treatment Specialists program (aCTTS). A team of physician champions was created to facilitate implementing the program and to educate respiratory and internal medicine specialists, as well as general practitioners who proceeded treating patients for tobacco dependence. During the first four months of the intervention 64...

BACKGROUND: Dialysis adequacy measured by single pool Kt/V (spKt/V) lower than 1.2 or urea reduction rate (URR) lower than 65% is associated with a significant increase in patient mortality rate. Patients’ adherence to the medical treatment is crucial to achieve recommended targets for spKt/V. Smoking is a recognized factor of non-adherence. AIM: In this study we sought to assess the association of active smoking and dialysis adequacy. METHODS: A total of 134 prevalent dialysis patients from one dialysis center were included in an observational cross-sectional study. Clinical, laboratory and dialysis data were obtained from medical charts in previous 6 months. The number of missed, on purpose interrupted or prematurely terminated dialysis sessions was obtained. Dialysis adequacy was calculated as spKt/V and URR. Patients were questioned about current active smoking status. T-test and Chi-Square test were used for comparative analysis of dialysis adequacy with regard to smoking statu...

Background: Low-molecular-weight heparin (LMWH) is considered to be an anticoagulation therapy for the treatment of cancer-associated thrombosis. The duration of treatment is recommended to maintain at least 3-6 months after the diagnosis. However, the data on continuing LMWH treatment beyond six months remains unclear. Methods: Consecutive cancer-associated thrombosis patients who were enrolled in RIETE Registry were evaluated. We systematically selected the patients who completed treatment with LMWH for 6 months. The patients were divided into two groups whether they continued to receive LMWH or switched to warfarin. The main outcomes were recurrent venous thromboembolism (VTE), major bleeding and total bleeding. Survival curves were generated using Kaplan-Meier method and the curves were compared using the log-rank test. Hazard ratio (HR) with corresponding 95% confidence interval (CI) were calculated using Cox-proportional hazard (PH) model. Outcomes: of the 1,502 eligible patie...

Background: Venous ulcer, the most serious consequence of chronic venous insufficiency (CVI), is associated with a high morbidity, impaired quality of life and high costs. To date, risk factors for venous ulcer after acute VTE have not been characterized. Objective: To identify independent predictors of venous ulcer development one year after an acute VTE event. Methods: Using data from the RIETE international registry, we analysed risk factors for venous ulcers in patients with an objectively confirmed symptomatic acute VTE (DVT and/or pulmonary embolism (PE)) and followed up for at least one year. During follow-up, signs and symptoms of CVI, occurrence of a venous ulcer in the leg ipsilateral to DVT or, in the absence of reported DVT, in any leg were reported by local investigators. Independent predictors of venous ulcers were assessed using a stepwise multivariable model. Results: Of the 34,144 patients included in the RIETE registry, 4,305 were recruited in centres participating...

Introduction. Asthma is a chronic inflammatory disease of the airways in which many cells play a role with secreting a variety of mediators responsible for the clinical manifestation of asthma. It is assumed that IL-33 is one of the earliest-released mediators and can orchestrate the immune cascade of the disease. The aim of this study was to examine the role and clinical significance of IL-33 as a new and insufficiently explored mediator of inflammation in patients with uncontrolled moderate asthma. Methods. The study included 87 patients with asthma. Serum IL-33 was measured in all patients by ELISA method. The obtained data were statistically analyzedusing the Kolmogorov-Smirnov and Shapiro-Wilk's test. Qualitative data were presented in absolute and relative numbers, and quantitative data were presented with measures of descriptive statistics. Statistically significant values were considered forp <0.05. Results. Majority of included patients were female (75.86%). The aver...

Asthma and chronic obstructive pulmonary disease (COPD) have traditionally been viewed as distinct clinical entities. Recently, however, much attention has been focused on patients with overlapping features of both asthma and COPD: those with asthma COPD overlap syndrome (ACOS). A significant proportion of patients who present with symptoms of a chronic airways disease have features of both asthma and COPD. Several diagnostic terms, most including the word “overlap”, have been applied to such patients, and the topic has been extensively reviewed. However, there is no generally agreed term or defining features for this category of chronic airflow limitation, although a definition based upon consensus has been published for overlap in patients with existing COPD. In spite of these uncertainties, there is broad agreement that patients with features of both asthma and COPD experience frequent exacerbations, have poor quality of life, a more rapid decline in lung function and high mortal...

Introduction. The main attribute of asthma is inflammation, which leads to airway remodeling, bronchial hyperreactivity and reversible or partly reversible airway obstruction. According to GINA, asthma is a chronic inflammatory disorder of the airways in which many cells play a role, in particular mast cells, eosinophils (Eo), and T lymphocytes. Many cells and mediators take part in creating the asthmatic inflammatory reaction, but eosinophils play a central role. The aim of this study was to show the values of biological inflammatory markers (IL-5 and Eo). Methods. Patients with severe asthma, 22 (73.33%) female and 8 (26.66%) male, aged 18-65 years were included in the study. The mean age was 35.30 ±9.65 years. Patients were treated with spray Beclomethasone dipropionate of 250 μg at doses from 1000 to 2000 μg/per day. Results. This study included 30 patients of the University Clinic of Pulmology and Allergology, Skopje, with confirmed bronchial asthma, treated with ICS. In all of...

Low-molecular-weight heparin (LMWH) is the treatment of choice in cancer patients with venous thromboembolism. However, data on continuing LMWH treatment beyond six months remain scanty. We used the RIETE (Registro Informatizado Enfermedad TromboEmbólica) registry to compare the rate of venous thromboemblism recurrences and major bleeding appearing beyond the first 6 months of anticoagulant therapy in cancer patients with venous thromboemblism, according to therapy with LMWH or vitamin K antagonists (VKA). We performed a propensity score matched cohort study. After propensity matching, 482 cancer patients continued to receive LMWH and 482 switched to VKA. During the course of anticoagulant therapy (mean 275.5 days), 57 patients developed venous thrombosis recurrences (recurrent pulmonary embolism 26, recurrent deep vein thrombosis29, both 2), 28 had major bleeding, 38 had non-major bleeding and 129 died. No patient died of recurrent venous thrombosis, and 5 patients died of bleeding...

Airway stenting (AS) commenced in Europe circa 1987 with the first placement of a dedicated silicone airway stent. Subsequently, over the last 3 decades, AS was spread throughout Europe, using different insertion techniques and different types of stents. This study is an international survey conducted by the European Association of Bronchology and Interventional Pulmonology (EABIP) focusing on AS practice within 26 European countries. A questionnaire was sent to all EABIP National Delegates in February 2015. National delegates were responsible for obtaining precise and objective data regarding the current AS practice in their country. The deadline for data collection was February 2016. France, Germany, and the UK are the 3 leading countries in terms of number of centres performing AS. These 3 nations represent the highest ranked nations within Europe in terms of gross national income. Overall, pulmonologists perform AS exclusively in 5 countries and predominately in 12. AS is perfor...

... AND LEVOCETIRIZINE IN MODERATE PERSISTENT ASTHMA: A STUDY OF 120 PATIENTS Sandeep Gupta MBBS, MD* Amrit P. Kansal MBBS ... from industry related sources) Clinical re-search: Glaxo, BI, Intermune, Actelion, Novartis, Astra-Zeneca, Altana, Dey; Consultant fee ...

The concept of " united airways disease " , based on many similar features and mutual interactions in the pathogenesis of asthma (A) and rhinitis (R), has led to an integral approach to their management. We conducted this study to determine the quantity of the problem of joint incidence of A and R in R. Macedonia, and, perhaps to obtain information on a potential causative effect of the two diseases. Three hundred eighty six patients, who presented with wheezing and/or upper respiratory symptoms at the Pulmology and Allergy Clinic, Skopje, were included during a period of 48 months. The presence of bronchial hyperreactivity – BHR (positive histamine challenge), atopy (prick test to seasonal or perennial inhaled allergens), rhinitis symptoms (such as nasal secretion and obstruction) and X-ray of paranasal sinuses was registered by a specially designed questionnaire. R was diagnosed in 106 of the subjects (27.5%), and A in 280 (72.5%). Among the patients with A, coincidence with R was found in 219 (76.5%). Including X-ray of paranasal sinuses to the diagnostic protocol increased this percentage to over 90% (256 patients). From the 219 patients with A and R together, 127 (57.99%) had positive atopy. On the other hand, 19 (18.0%) of the rhinitis-only patients had positive BHR without asthma symptoms. The follow up of the rhinitis patients with positive BHR revealed 4 patiets who developed asthma within 36 months, but this was also the case with 2 of the subjects with R and negative BHR. In conclusion, the coincidence of A and R in our material is 78.21%, or 91.4% (including sinusitis); a greater coexistence of A and R is found in atopic patients. The patients with allergic R are at high risk for developing A and should be monitored in the future and the R symptoms should be adequately treated in order to minimize the risk for developing asthma.