What would primary care practitioners do differently after a delayed cancer diagnosis? Learning lessons from their experiences.

OBJECTIVE: Diagnosis of cancer is challenging in primary care due to the low incidence of cancer cases in primary care practice. A prolonged diagnostic interval may be due to doctor, patient or system factors, or may be due to the characteristics of the cancer itself. The objective of this study was to learn from Primary Care Physicians' (PCP) experiences of incidents when they had failed to think of, or act on, a cancer diagnosis. DESIGN: A qualitative, online survey eliciting PCP narratives. Thematic analysis was used to analyse the data. SETTING AND SUBJECTS: A primary care study, with narratives from 159 PCPs in 23 European countries. MAIN OUTCOME MEASURES: PCPs' narratives on the question 'If you saw this patient with cancer presenting in the same way today, what would you do differently? RESULTS: The main themes identified were: thinking broadly; improvement in communication and clinical management; use of other available resources and 'I wouldn't do anything differently'. CONCLUSION (IMPLICATIONS): To achieve more timely cancer diagnosis, PCPs need to provide a long-term, holistic and active approach with effective communication, and to ensure shared decision-making, follow-up and continuing re-assessment of the patients' clinical conditions.

Diagnosing cancer in primary care is challenging due to the low incidence of cancer in practice and the multiple confounding factors that are involved in the diagnostic process.The need to think broadly, make improvements in communication and clinical management, and use other available resources were the main themes from Primary Care Physicians' (PCPs') narratives about their learning experiences from missed or late cancer diagnoses.A long-term, holistic and active approach with effective communication, follow-up and continuing re-assessment of the patients' clinical conditions was another theme for making improvements.Some PCPs, on reflection, would not have done anything differently.

Expression of subtypes of interleukin-17 ligands and receptors in patients with B-cell chronic lymphocytic leukemia.

BACKGROUND: The diversity of biological effects of cytokines from the IL-17 family, as well as the wide range of cells sensitive to their influence, suggests that these molecules might play a significant role in the malignant pro- cess. METHODS: After the cells were initially isolated with Polymorphprep™, they were sorted with a MACS® magnetic separator, CD16 for neutrophils and CD19 for B lymphocytes. The presence of proteins: IL-17A, IL-17E, IL-17F, IL-17D, as well as receptors: IL-17R, IL-17BR, IL-17RC in cell lysates was confirmed by Western blot. The levels of IL-17A, IL-17E, and IL-17F in blood serum were determined with ELISA. RESULTS: The results indicate a lower expression of IL-17A, IL-17E, and IL-17F in PMNs and B lymphocytes of pa- tients with B-cell chronic lymphocytic leukemia compared to cells of healthy subjects. Elevated expression of IL- 17D was observed in the PMNs of patients, with a simultaneous decrease in the expression of this cytokine in leukemic B cells, in comparison to the control group. In patients with B-CLL, there also were observations of decreased expression of IL-17R, IL-17BR, and IL-17RC in leukemic B lymphocytes, compared to their expressions in the cells of healthy subjects. The blood serum of B-CLL patients demonstrated a significantly increased level of IL-17A at stage 0/I, II, and IV of disease; IL-17E at stage 0/I and II; IL-17F at stage 0/I, III, and IV of disease advancement, compared to the data obtained from the control group. CONCLUSIONS: The results clearly support the involvement of the studied proteins from the IL-17 family in the course of B-CLL and indicate that IL-17D may play a significant role in the course of this disease.

TNF superfamily proteins in the serum of patients with B-ALL--preliminary study.

BACKGROUND: TNF superfamily ligands such as B cell-activating factor (BAFF), a proliferation inducing ligand (APRIL) and TNF-related apoptosis inducing ligand (TRAIL), can play an important role in the pathogenesis and development of various B cell malignancies involving B-ALL. METHODS: The study group consisted of 25 children suffering from newly diagnosed B cell precursor ALL (B- ALL), involving immunophenotype pre-B and common-cALL. Peripheral blood samples were collected at the time of diagnosis, before any treatment, and after treatment. Soluble APRIL, soluble BAFF, and soluble TRAIL concentrations were assessed using ELISA kits. RESULTS: The concentrations of sAPRIL and sBAFF in the sera of the patient group were higher compared to the values of the control specimens. Among all molecules examined, the highest concentrations were found for the sAPRIL molecule. Furthermore, sAPRIL and sBAFF concentrations were higher in patients with ALL-pre B than in patients with cALL. After the treatment, the sera of patients with ALL-pre B contained lower concentrations of sAPRIL, sBAFF, and sTRAIL than those of the same patients before therapy. CONCLUSIONS: Contrary to earlier indications of the key function of BAFF in B-ALL, the quantitative dominance of APRIL in the serum suggests that this molecule can play an equivalent or even more significant role in this patient group than BAFF.

Health-Related Quality of Life Using the KIDSCREEN-27 Questionnaire among Adolescents with High Myopia.

Background/Objectives: The aim of the study was to explore Health-Related Quality of Life (HRQoL) using the KIDSCREEN-27 questionnaire among adolescents with high myopia (HM). Methods: Sixty-nine adolescents with HM and 71 healthy participants aged 12-17 years and their parents or legal guardians were enrolled in the study. Results: Adolescents with HM showed significantly lower scores on the Physical Well-Being dimension in comparison with controls (p = 0.003), particularly girls with HM in comparison with girls from the control group (p = 0.008), and 15-17-year-old adolescents in comparison with same-aged controls (p = 0.020). Girls with HM were characterised by significantly worse scores on the Psychological Well-Being dimension compared with boys with HM (p < 0.042). Sociodemographic factors and refractive error, its duration, and acceptance of disease had no impact on HRQoL. Conclusions: HM may have a negative impact on the HRQoL of children, affecting particularly the physical and psychological well-being of girls. It is important that a holistic approach to the treatment of HM in adolescents is taken by measuring their HRQoL as part of the routine diagnostic process. Use of the KIDSCREEN-27 questionnaire seems justified as it allows for determination of the type of intervention required to improve the HRQoL of individuals affected by the disease.

Reduced retinol (vitamin A) and α-tocopherol (vitamin E) blood levels and increased myeloperoxidase (MPO) activity in children with high myopia.

The study assessed selected parameters of redox status in the plasma of patients suffering from high myopia (HM). Thirty-five children with mean age 13.7 ± 2.7 years with HM and 40 healthy children were included. Plasma redox status parameters were determined using colorimetric kits. The levels of retinol, α-tocopherol and coenzyme Q10 were determined with a high-performance liquid chromatograph. Negative correlations were observed between the concentrations of retinol and the axial length of the eye (r = - 0.514 p < 0.001). Increased myeloperoxidase (MPO) activity (p < 0.018), and decreased concentrations of retinol (p < 0.001) and α-tocopherol (p < 0.023) in patients with HM and the axial length of the eye > 26 mm compared to controls were established. Significantly lower retinol and α-tocopherol concentrations were found in patients with the axial length of the eye > 26 mm compared to those with the axial length of the eye ≤ 26 mm (p < 0.001, p < 0.021, respectively). Increased MPO activity in advanced stages of HM may confirm an inflammatory process in HM patients. Reduced retinol and α-tocopherol concentrations and their link to disease progression indicate a need for monitoring their levels and supplementation in children with HM.

Exploring why European primary care physicians sometimes do not think of, or act on, a possible cancer diagnosis. A qualitative study.

BACKGROUND: While primary care physicians (PCPs) play a key role in cancer detection, they can find cancer diagnosis challenging, and some patients have considerable delays between presentation and onward referral. AIM: To explore European PCPs' experiences and views on cases where they considered that they had been slow to think of, or act on, a possible cancer diagnosis. DESIGN & SETTING: A multicentre European qualitative study, based on an online survey with open-ended questions, asking PCPs for their narratives about cases when they had missed a diagnosis of cancer. METHOD: Using maximum variation sampling, PCPs in 23 European countries were asked to describe what happened in a case where they were slow to think of a cancer diagnosis, and for their views on why it happened. Thematic analysis was used to analyse the data. RESULTS: A total of 158 PCPs completed the questionnaire. The main themes were as follows: patients' descriptions did not suggest cancer; distracting factors reduced PCPs' cancer suspicions; patients' hesitancy delayed the diagnosis; system factors not facilitating timely diagnosis; PCPs felt that they had acted wrongly; and problems with communicating adequately. CONCLUSION: The study identified six overarching themes that need to be addressed. Doing so should reduce morbidity and mortality in the small proportion of patients who have a significant, avoidable delay in their cancer diagnosis. The 'Swiss cheese' model of accident causation showed how the themes related to each other.

Lack of relationship between 25-hydoxyvitamin D concentration and a titer of antibodies to hepatitis B surface antigen in children under 12 years of age.

The effect of vitamin D levels on the response to the hepatitis B vaccine in childhood and the induced levels of antibodies against the hepatitis B surface antigen (anti-HBs) is not yet well understood. The study aimed to investigate the relationship between age, serum 25-hydroxyvitamin D (25(OH)D) concentration and anti-HBs titer among children under 12 years old. Serum 25(OH)D concentration and anti-HBs titer were determined in 352 healthy Caucasian children with the average age of 4.2 (2.5; 6.3) years. All children were vaccinated with 3 doses of hepatitis B vaccine (Engerix-B, GlaxoSmithKline Pharmaceuticals Limited) in infancy according to the Centers for Disease Control and Prevention recommendations. Only 14.5% of children had an optimal concentration of 25(OH)D ≥ 30 ng/mL and 71.9% children had a seroprotective anti-HBs titer ≥ 10 mIU/mL. Significant negative correlations were found between 25(OH)D, anti-HBs titer and age (r = -0.420, p = 0.000; r = -0.425, p = 0.000, respectively), and a weak positive correlation between 25(OH)D concentration and anti-HBs titer (r = 0.243, p = 0.000). Analysis of six clusters of children demonstrated that age is the main factor affecting anti-HBs titer. One third of children under 12 years of age had nonprotective anti-HBs titer < 10 mIU/mL and around 40% had vitamin D deficiency. We conclude that vitamin D status has no impact on anti-HBs titer in children vaccinated against hepatitis B virus in infancy. Age, so time since the receipt of the last dose of hepatitis B vaccine, is the main factor influencing a decline in anti-HBs titer.

Reasons for and Scenarios Associated with Failure to Cease Smoking: Results from a Qualitative Study Among Polish Smokers Who Had Unsuccessfully Attempted to Quit.

PURPOSE: Most smokers attempt to quit smoking, but few are successful. Data regarding the reasons for this relapse and the course of the relapse process may be helpful for determining efficient methods of smoking cessation. This study aimed to identify the causes of and scenarios associated with smoking relapse after effective smoking cessation. PATIENTS AND METHODS: We conducted 20 semi-structured interviews with smokers who had previously unsuccessfully attempted to quit. The data underwent qualitative content analysis. RESULTS: Three major themes were identified: reasons for smoking relapse; smoking relapse scenarios; and perception of the influence of personal environments, including family and physicians, on refraining from smoking after cessation. The first theme comprised the following subthemes: insufficient willpower and self-discipline, contact with smokers, exposure to stressful situations, lack of family support, weight gain, and insufficient improvement in one's mental and physical well-being. The second theme contained enjoyable social events, professional life, critical events, and encouragement to smoke from family members. The respondents frequently emphasized the large role of interaction with other smokers. CONCLUSION: The predominant factors underlying smoking relapse include insufficient willpower and self-discipline and exposure to stress. The most frequent relapse scenario concerned experiencing negative or positive emotions when interacting with other smokers.

Endothelin-1 Serum Concentration in Pediatric Chronic Idiopathic Uveitis.

PURPOSE: The aim of our study was to determine endothelin-1 (ET-1) concentration in chronic idiopathic uveitis in children and adolescents depending on anatomical location and grade of inflammation. METHODS: The cross-sectional study was conducted among 17 patients with chronic idiopathic uveitis and 22 healthy controls. Concentration of ET-1 in serum was determined using a commercially available ELISA kit. The concentration of C reactive protein (CRP) in serum was determined by immunoturbidimetric method using CRP4 reagent kit (Roche Diagnostics GmbH, Mannheim, Germany). RESULTS: Statistically significant difference between ET-1 concentration in patients with chronic idiopathic uveitis and controls was found 1.33 (1.22; 1.48) vs 1.93 (1.1; 3.11), p = 0.008). No correlations were found between ET-1 concentration and age, either in chronic idiopathic uveitis patients or controls. Nine out of 17 patients presented with anterior uveitis, 5 with posterior and 3 with panuveitis. There were no differences in ET-1 concentration between anterior, posterior and panuveitis (p = 0.634), and in terms of grade of inflammation. CONCLUSION: ET-1 expression is disturbed in pediatric chronic idiopathic uveitis irrespective of the anatomical location and grade of inflammation. Lower expression of ET-1 plays a crucial role in disturbed vascular tone control and can result in permanent visual impairment in chronic non-infectious uveitis.

[Knowledge of patients from the rural environment on the risk factors and prevention of cardiovascular diseases]. / Wiedza pacjentów ze srodowiska wiejskiego na temat czynników ryzyka i profilaktyki chorób ukladu krazenia.

UNLABELLED: Cardiovascular diseases (CVDs) are the leading cause of death in Poland. The aim of the study was to assess the knowledge of patients from the rural environment on the risk factors and prevention CVDs. MATERIAL AND METHODS: In the period from January to February 2006. one hundred and twenty patients [69 (57.5%) females and 51 (42.5%) males] from Primary Care Practice in Zabludow living in rural areas in the vicinity of Bialystok were interviewed using questionnaires developed by the authors of the work. It contained questions on demographic data (gender, age, education and residence), health status and level of knowledge about risk factors and prevention CVDs. RESULTS: The vast majority of patients had a thorough understanding of risk factors CVDs. The least known factor is diabetes--just as the second test (55.8%) believe that it contributes to the formation of CVDs. As prophylaxis 77.5% of respondents reported a diet low in salt, and 75%--regular physical activity. Advancing our knowledge about the disease as an existing preventive recognized 70.8% of respondents. Comparing knowledge of patients with the knowledge of healthy CVDs participating in the survey stated that they know more about risk factors and prevention CVDs than the differences are statistically significant (p < 0.05). Better educated person knows more about risk factors and prevention of CVDs than the less educated people. These differences were statistically significant (p < 0.05). CONCLUSIONS: Examined patients living in rural areas have a wide knowledge on risk factors and prevention CVDs. This applies especially to people with higher education or with known cardiovascular diseases. People with lower education require more attention and education. Emphasis should be given to promoting information on the impact of diabetes on the development of CVDs.

Endothelin-1 Serum Concentration is Lower in Children and Adolescents with High Myopia, a Preliminary Study.

The aim of this study is to evaluate the levels of enothelin-1 (ET-1) in children and adolescents with high myopia and its association with the axial length of the eye and the presence of myopic retinal degeneration. The cross-sectional study was carried out in 57 patients with high myopia and 29 control subjects. Serum concentrations of ET-1 were measured using enzyme-linked immunosorbent assay (ELISA) kit. A significantly lower concentration of ET-1 in highly myopic patients compared to controls was found (1.47 (0.91; 1.87) vs. 1.94 (1.1; 2.69) pg/mL, p = 0.005). In patients with high myopia, a weak negative correlation between ET-1 concentration and the longest axial length out of the two eyes was found (r = -0.255, p = 0.0558). Further analysis revealed statistically significant differences in ET-1 concentration between patients with the axial length of the eye > 26 and ≤ 26 mm (p < 0.041) and patients with the axial length of the eye > 26 mm and controls (p < 0.001). ET-1 expression is disturbed in highly myopic children and adolescents. Lower ET-1 concentration in patients with the axial length of the eye > 26 mm may co-occur with high myopia and should be considered a risk factor in the pathophysiology of high myopia progression.

Systemic Redox Imbalance in Patients with Chronic Granulomatous Disease.

The aim of our study was to evaluate redox status, enzymatic and non-enzymatic antioxidant barriers, oxidative damage of proteins, lipids and DNA, as well as concentration of coenzyme Q10 and vitamins A and E in patients with chronic granulomatous disease (CGD). The study was performed on fifteen Caucasian individuals (median age 24 years and seven months) diagnosed with CGD. The mutation in the NCF1 gene was confirmed in ten patients, and in the CYBB gene in five patients. We demonstrated high levels of total oxidant status (TOS) and oxidative stress index (OSI), lipids (↑8-isoprostanes (8-isoP), ↑4-hydroxynonenal (4-HNE)), proteins (↑advanced oxidation protein products (AOPP)) and DNA (↑8-hydroxy-2'-deoxyguanosine (8-OHdG)) oxidation products in CGD individuals as compared to sex- and age-matched healthy controls. We showed enhanced serum enzymatic activity of catalase (CAT) and superoxide dismutase-1 (SOD) and significantly decreased coenzyme Q10 concentration. Our study confirmed redox disturbances and increased oxidative damage in CGD patients, and indicated the need to compare redox imbalance depending on the type of mutation and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity. The question regarding effectiveness of antioxidant therapy in patients with CGD is open, and the need to establish guidelines in this area remains to be addressed.

Primary care practitioners' diagnostic action when the patient may have cancer: an exploratory vignette study in 20 European countries.

OBJECTIVES: Cancer survival rates vary widely between European countries, with differences in timeliness of diagnosis thought to be one key reason. There is little evidence on the way in which different healthcare systems influence primary care practitioners' (PCPs) referral decisions in patients who could have cancer.This study aimed to explore PCPs' diagnostic actions (whether or not they perform a key diagnostic test and/or refer to a specialist) in patients with symptoms that could be due to cancer and how they vary across European countries. DESIGN: A primary care survey. PCPs were given vignettes describing patients with symptoms that could indicate cancer and asked how they would manage these patients. The likelihood of taking immediate diagnostic action (a diagnostic test and/or referral) in the different participating countries was analysed. Comparisons between the likelihood of taking immediate diagnostic action and physician characteristics were calculated. SETTING: Centres in 20 European countries with widely varying cancer survival rates. PARTICIPANTS: A total of 2086 PCPs answered the survey question, with a median of 72 PCPs per country. RESULTS: PCPs' likelihood of immediate diagnostic action at the first consultation varied from 50% to 82% between countries. PCPs who were more experienced were more likely to take immediate diagnostic action than their peers. CONCLUSION: When given vignettes of patients with a low but significant possibility of cancer, more than half of PCPs across Europe would take diagnostic action, most often by ordering diagnostic tests. However, there are substantial between-country variations.

[Platelets haemostatic in patients with multiple myeloma]. / Hemostaza plytkowa u chorych na szpiczaka mnogiego.

Multiple myeloma (MM) is a type of disseminated cancer which derive plasma cells that are immune system cells in bone marrow and produce monoclonal protein. It represents approximately 1% of all cancers, but recent statistics indicate both increasing incidence and earlier age of onset. Haemostatic disorders are an important clinical problem in patients with MM. The most common disturbances symptoms are bleeding and deep-vein thrombosis can due to platelet dysfunction, inhibition of fibrin and increased clearance of coagulation factors connected with monoclonal protein presence. The aim of study is a presentation of disturbances haemostatic in patients with MM, which make up important clinical and diagnostic problems.

[Educational role of community nurse in care of patients treated with oral anticoagulation therapy]. / Edukacyjna rola pielegniarki srodowiskowej w opiece nad pacjentami leczonymi acenokumarolem w poradni lekarza rodzinnego.

UNLABELLED: Different methods allowing for assessment of anticoagulation effects in patients receiving oral anticoagulants (OAC) are applied. Among them estimation of total time of international normalized ratio (INR) within the therapeutic range (time in therapeutic range--TTR) is used. The aim of the study was to assess the knowledge of patients about safety measures when on acenocumarol (AC) therapy as well as to measure TTR and potential impact of education provided by community nurse on TTR. MATERIAL AND METHODS: The study lasted for 20 months since August 2006 till March 2008. Twenty-five patients remaining under care of a family physician were interviewed about safety rules while on treatment with AC. In May 2007 an educational intervention was provided by a trained community nurse. RESULTS: We have shown that older age was related to lower number of correct responses to questions (p < 0.064). Individuals with higher number of correct responses measured their INR more frequently, statistically significant difference (p < 0.045). TTR of all subjects before education was 48% and increased after education to 52%. We have shown that changes of TTR after education were related to education, age group and gender. The biggest improvement of TTR was observed among people younger than 75 years of age and those with higher education (not statistically significant differences). CONCLUSIONS: Education has biggest effect in persons under 75 years and with higher education. Older persons and those less educated require longer education and monitoring by health care professionals to maintain INR in the therapeutic range. Patients with better knowledge about DAK--monitor INR more frequently and their anticoagulation is better controlled.

Antioxidant Defense, Redox Homeostasis, and Oxidative Damage in Children With Ataxia Telangiectasia and Nijmegen Breakage Syndrome.

Ataxia-telangiectasia (AT) and Nijmegen breakage syndrome (NBS) belong to a group of primary immunodeficiency diseases (PI) characterized by premature aging, cerebral degeneration, immunoglobulin deficiency and higher cancer susceptibility. Despite the fact that oxidative stress has been demonstrated in vitro and in animal models of AT and NBS, the involvement of redox homeostasis disorders is still unclear in the in vivo phenotype of AT and NBS patients. Our study is the first to compare both enzymatic and non-enzymatic antioxidants as well as oxidative damage between AT and NBS subjects. Twenty two Caucasian children with AT and twelve patients with NBS were studied. Enzymatic and non-enzymatic antioxidants - glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase-1 (SOD) and uric acid (UA); redox status-total antioxidant capacity (TAC) and ferric reducing ability of plasma (FRAP); and oxidative damage products-8-hydroxy-2'-deoxyguanosine (8-OHdG), advanced glycation end products (AGE), advanced oxidation protein products (AOPP), 4-hydroxynonenal (4-HNE) protein adducts, and 8-isoprostanes (8-isop) were evaluated in serum or plasma samples. We showed that CAT, SOD and UA were significantly increased, while TAC and FRAP levels were statistically lower in the plasma of AT patients compared to controls. In NBS patients, only CAT activity was significantly elevated, while TAC was significantly decreased as compared to healthy children. We also showed higher oxidative damage to DNA (↑8-OHdG), proteins (↑AGE, ↑AOPP), and lipids (↑4-HNE, ↑8-isop) in both AT and NBS patients. Interestingly, we did not demonstrate any significant differences in the antioxidant defense and oxidative damage between AT and NBS patients. However, in AT children, we showed a positive correlation between 8-OHdG and the α-fetoprotein level as well as a negative correlation between 8-OHdG and IgA. In NBS, AGE was positively correlated with IgM and negatively with the IgG level. Summarizing, we demonstrated an imbalance in cellular redox homeostasis and higher oxidative damage in AT and NBS patients. Despite an increase in the activity/concentration of some antioxidants, the total antioxidant capacity is overwhelmed in children with AT and NBS and predisposes them to more considerable oxidative damage. Oxidative stress may play a major role in AT and NBS phenotype.

How European primary care practitioners think the timeliness of cancer diagnosis can be improved: a thematic analysis.

BACKGROUND: National European cancer survival rates vary widely. Prolonged diagnostic intervals are thought to be a key factor in explaining these variations. Primary care practitioners (PCPs) frequently play a crucial role during initial cancer diagnosis; their knowledge could be used to improve the planning of more effective approaches to earlier cancer diagnosis. OBJECTIVES: This study sought the views of PCPs from across Europe on how they thought the timeliness of cancer diagnosis could be improved. DESIGN: In an online survey, a final open-ended question asked PCPs how they thought the speed of diagnosis of cancer in primary care could be improved. Thematic analysis was used to analyse the data. SETTING: A primary care study, with participating centres in 20 European countries. PARTICIPANTS: A total of 1352 PCPs answered the final survey question, with a median of 48 per country. RESULTS: The main themes identified were: patient-related factors, including health education; care provider-related factors, including continuing medical education; improving communication and interprofessional partnership, particularly between primary and secondary care; factors relating to health system organisation and policies, including improving access to healthcare; easier primary care access to diagnostic tests; and use of information technology. Re-allocation of funding to support timely diagnosis was seen as an issue affecting all of these. CONCLUSIONS: To achieve more timely cancer diagnosis, health systems need to facilitate earlier patient presentation through education and better access to care, have well-educated clinicians with good access to investigations and better information technology, and adequate primary care cancer diagnostic pathway funding.

[Factors influencing activity of oral anticoagulants. Interactions with drugs and food]. / Czynniki wplywajace na dzialanie doustnych antykoagulantów. Interakcje z lekami i pozywieniem.

Oral anticoagulants (OAC) are commonly used as a life-long therapy in prevention of systemic embolism in patients with atrial fibrillation, valvular heart disease and prosthetic hart valves and in the primary and secondary prevention of venous thromboembolism. They are also used for the prevention of thromboembolic events in patients with acute myocardial infarction and with angina pectoris, in patients with biological hart valves and after some types of orthopaedics surgery. The International Normalized Ratio (INR) is used to evaluate the efficacy of anti-coagulant therapy. The risk of thromboembolic and haemorrhagic complications increases when the INR is out of the therapeutic range. The aim of this study was to present information about the factors influencing activity of oral anticoagulants and interactions between oral anticoagulants and drugs or food. The effect of oral anticoagulants is influenced by genetic and environmental factors such as: medicines, food, diseases and pre-existing conditions. A common mutation in the gene coding for the cytochrome P450 (CYP2C9), with one or more combinations of its polymorphisms, is responsible for the reduced warfarin requirements or for the resistance to warfarin. A mutation in the factor IX is responsible for the risk of bleeding during OAC therapy without excessive prolongation of the prothrombin time (PT). Drugs, herbs and multivitamin supplements can alter the absorption, pharmacokinetics or pharmakodynamics of OAC. Nonsteroid anti-inflammatory drugs and paracetamol in combination with OAC seem to be the most dangerous because they are available without prescription and are used without medical consultation. Patients on OAC therapy are sensitive to changing dietary intake of vitamin K, which is supplied from phylloquinones in plants or from vitamin K-containing medicines. The effect of OAC can be influenced by other existing factors like: fever, diarrhoea, alcohol abuse or physical hyperactivity. Some malignancies or other diseases like cardiac insufficiency, hyperthyroidism and hypothyroidism or hepatic dysfunction may also affect OAC therapy. This treatment requires patients and doctors to be knowledgeable about factors influencing the activity of oral anticoagulants. For this reason educational programme on OAC therapy should be conducted among patients and doctors.

[Use of oral anticoagulants in outpatient setting]. / Stosowanie doustnych antykoagulantów w ramach opieki ambulatoryjnej.

Oral anticoagulants (OAC) have been used for more than 60 years and are being prescribed to a steadily increasing number of patients as a life-long therapy The Intenational Normalized Ratio (INR) is used to evaluate the efficacy of anti-coagulant therapy. The risk of thromboembolic and haemorrhagic complications increases when the INR is above the therapeutic range. The aim of our study was to provide information about oral anticoagulant therapy and how to treat patients on OAC therapy in specific situations such as: pregnancy, intramuscular injection, tooth extraction and small invasive procedures performed in outpatient setting. INR needs to be frequently monitored during treatment and in many countries this is done in specialist anticoagulant clinics. Such clinics do not presently exist in Poland and patients on OAC treatment typically fall under the care of doctors of different specialization including general practitioners. OAC therapy is safe until fourth--sixth week of pregnancy, after his time anticoagulant treatment should be replaced by heparins. Intramuscular injections are contra-indicated during OAC therapy. In most cases general dental treatment and straightforward single dental extractions can be performed without discontinuing OAC, provided INR is in the therapeutic range of 2,0-3,5. Risk of bleeding can be minimized by the use of mouthwashes (used three or four times a day for 2 days) containing 4,8% tranexamid or 25% e-aminocapronicum acid. Prior to undergoing invasive procedures with a middle risk of bleeding and single extraction in patients with a risk of major bleeding should consult with a physician specializing in the use of anticoagulants to discuss the treatment and to assess the risk of bleeding and thromboembolism. This is why education about the therapeutic range of INR and procedures which need to be adopted in specific situations, is very important and the educational programme on OAC therapy should be targeted at patients and doctors of different specialization including general practitioners.

[Haemorrhagic complications among patients on life-long acenocumarol therapy]. / Powiklania krwotoczne u pacjentów przewlekle leczonych acenokumarolem.

The aim of our study was to determine factors influencing occurrence of haemorrhagic events during acenocumarol therapy. A total of one hundred and forty patients were interviewed using a questionnaire. From one hundred forty (100%) of interviewed patients, forty one (29.3%) had haemorrhagic events and in eighteen (12.9%) cases the event followed the use of nonsteroid anti-inflammatory drugs (NSAID's) or paracetamol in combination with acenocumarol (AC). We found eleven cases of major bleeding in eight (5.7%) of patients Eight cases of bleeding were followed the use of NSAID's or paracetamol in combination with (AC). We found that there is a statistical relationship between the higher frequency of INR examination (at least as every four weeks) and decreased occurrence of haemorrhagic events (p<0.05). The frequency of INR examination should be done once every four weeks or more often, if there is evidence to suggest that testing more frequently. Monitoring of INR with frequency less than once in 4 weeks may increase the risk of bleeding in those patients. Concomitant use of NSAID's or paracetamol in combination with acenocumarol in patients without medical consultation can be associated with growing number of bleeding. Patients on AC therapy need to be inform about frequency of INR examination and acaenocumarol interactions with other medications, which are available without the prescription, to avoid haemorrhagic events.