Systemic thrombolysis with recombinant tissue plasminogen activator in acute ischemic stroke: first Croatian experiences.

In September 2003, recombinant tissue plasminogen activator (rt-PA) for acute treatment of ischemic stroke was finally approved by the Croatian Ministry of Health. For the next 5 years, only three stroke units in the country implemented this therapy in their routine practice until summer 2008, when neurological wards in most Croatian hospitals started to treat acute stroke patients with systemic thrombolysis. We present a 2-year experience of thrombolytic therapy (2006-2008) in the stroke unit of the University Hospital in Zagreb, Croatian largest hospital, serving nearly one-fifth of the citizens of Croatia. Obtained data (vitals at admission and before administration of rt-PA; NIHSS and MRS scores at admission, 2 h and 7th day after rt-PA treatment, "time to door" and "door to needle" intervals, duration of hospital treatment as well as outcomes and complications of our 66 thrombolysed patients) are presented and discussed. We also present our results regarding benefits of this therapy as well as possible reasons for complications noticed.

Unaided general practitioners' clinical diagnosis in evaluation of depressive patients: a pilot study.

BACKGROUND: In this study we wished to determine the diagnostic accuracy of unaided general practitioners' (GPs') clinical diagnosis in the evaluation of depression in depressed patients under their care compared with the Beck Depression Inventory II (BDI-II). SUBJECTS AND METHODS: From 17,000 patients in 10 GPs' offices as representative sample in the city of Zagreb, 5100 patients from three GPs' offices were selected. The sample consisted of 53 out of 76 depressed patients with a diagnosis of Depressive episode (F32) or Recurrent depressive disorder (F33) classified according to ICD-10 and assessed by review of the GP's standardized medical records. Cross-sectional investigation was performed during February 2008. GPs classified depressed patients as either nondepressed without therapy, nondepressed with therapy or depressed with therapy. Within a two-week period, the unaided GPs' diagnosis was compared with BDI-II performed by psychologists unfamiliar with the GPs' assessment. Based on the GP vs. BDI-II comparison, patients were classified as either positive, false positive, false negative or negative. Sensitivity, specificity, PPV, and NPV associated with physician identification of depression were calculated by standard methods. RESULTS: Depressiveness was found by BD-II in the group 'depressed with therapy' (24.39±10.91). ANOVA found a significant difference in BDI-II means between the outcome groups (P<0.001). Scheffe's procedure found a significant difference in BDI-II in patients with therapy (nondepressed vs. depressed) (P<0.001) and nondepressed without therapy vs. depressed with therapy (P<0.001). There were 16 depressed patients, 27 nondepressed, 2 false positive, and 8 false negative. Unaided GPs' clinical diagnosis showed 66% sensitivity, 93%, specificity, 88% PPV, and 77% NPV. CONCLUSION: Unaided GPs' clinical diagnosis with 88% PPV outperforms other measures of patient depression and is easier to implement when compared to the psychiatric model of caseness, which is based on screening instruments.

Long-Term Prognosis for Patients with Metabolic Syndrome after Recanalization Therapy for Stroke.

Background: Metabolic syndrome (MetS) is defined as a cluster of interrelated factors that significantly increase the risk of cardiovascular diseases, including stroke. The aim of this study was to investigate the connection between MetS and its diagnostic criteria with the severity and outcome of stroke after recanalization therapy. Methods: Ninety four patients with acute ischemic stroke were included in the study. Patients were categorized into two groups: with (n = 47) or without MetS (n = 47). We analyzed their demographic data, medical history, individual criteria for MetS, anthropometric characteristics, stroke severity (National Institute of Health Stroke Scale [NIHSS], neuroimaging criteria, laboratory), recanalization treatment method (thrombolysis and/or thrombectomy), recanalization rate, and in-hospital complications rate. Late outcome (in 12 months follow-up) was measured by modified Rankin scale, followed by functional evaluation of plegic hand, walking assessment, self-care ability, physical therapy days, and major adverse cardiovascular events. MetS was determined, in case the participant had three of the five criteria using National Cholesterol Education Program (NCEP) guidelines. A probability value of <0.05 was considered statistically significant. Results: 92.6% of all patients had hypertension and 63.8% were obese. Despite the fact that there were no statistically significant differences in stroke severity and/or recanalization rate between two groups, MetS patients had to use devices more, while performing hand functions (P = 0.027). Nonassisted walking was proved to be more frequent among patients without MetS (P = 0.020). MetS patients proved less ability for self-care (44.4% vs. 75%, P = 0.031) and spent more days in physical therapy (median 30.0 vs. 16.5, P = 0.043). Conclusion: MetS in poststroke patients is related with poorer recovery of hand function, walking abilities, and more days spent in physical therapy.

Depression prevalence and estimation of psychosocial parameters within adult population in city of Zagreb.

BACKGROUND: There is no data on depression prevalence in Croatia. The aim of this study was to establish the prevalence and psychosocial risk factors of depression in the adult population of the Croatian capital Zagreb, particularly in patients suffering from Depressive episode (F32) and Recurrent depressive disorder (F33). SUBJECTS AND METHODS: A cross-sectional study was preformed on a representative sample for city of Zagreb drawn from 10 family physicians' offices with 17290 patients. From standardized medical files, the family physicians sorted out data of patients with depression, both Depressive episodes (F32) and Recurrent depressive disorder (F33), classified according to ICD 10. Psychosocial parameters were assessed according to the core questions for the management of psychosocial risk factors recommended by the European Guidelines on Cardiovascular Disease Prevention in Clinical Practice. RESULTS: The prevalence of depression was 2.2%. Recognized socioeconomical parameters were: female sex (74.7%), middle age 45-65 years (40.7%), married (55.3%), high school education (59.2%), retired (54.5%), and average economical status (73.6%). As regards social isolation: depressive patients were not living alone (71.5%), they had help in case of illness (80.9%), and had no problems with their partner (36.8%). Work stress parameters were estimated between 5 and 6. Life satisfaction was estimated mean +/- SD=4.57+/-1.72. Logistic regression analysis showed a significant association between higher education and physicians' perception as "more depressed and more difficult" patients with Recurrent depressive disorder (F33). Family physicians were unfamiliar with the genealogical disease burden for 45% of depressive patients, whether they had closed confident for 21.93% and problems with partner for 30.80%. CONCLUSION: Depression had a prevalence of 2.2%. It was poorly recognized, as were some psychosocial factors especially genealogical disease burden. This suggests the need for implementation of special intervention methods of developing the family physicians'skills in adopting the psychosocial approach to depressive patients with a focus on recognized psychosocial risk factors.

A multimodal pharmacological agent in combination with recanalization therapy (thrombolysis and thrombectomy) in severe stroke patients.

This case report highlights a case of large ischemic stroke and indication for anticoagulant therapy treated with thrombolysis and pharmacological intervention for neurological recovery with a multimodal agent (Cerebrolysin) as add-on therapy to recanalization techniques, including IV thrombolysis. We observed a significant clinical improvement after one year of follow-up. Based on our experience, we can assert that Cerebrolysin can be safely administered in stroke patients, even in complicated cases, with a good chance for improvement of their clinical status.

Subacute brainstem angioencephalopathy: favorable outcome with anticoagulation therapy.

We present a patient who developed progressive neurological disease caused by lesions histologically compatible with those observed in subacute brainstem angioencephalopathy. The patient was treated with low-molecular weight heparin, and treatment response was monitored clinically and with MRI. Anticoagulation therapy stopped progression of the neurological deficit and led to improvement of MRI findings. This report further supports the existence of subacute brainstem angioencephalopathy as a characteristic disease entity and gives insight into possible therapeutic approach with anticoagulation treatment.

["Training cum research" an obligatory form of continuing medical education in Croatia]. / "Training cum research"--obavezni oblik kontinuirane medicinske edukacije u Hrvatskoj.

Family medicine as a discipline is more than other specialties oriented to holistic approach to patient. The physician has to know and use the possibilities of clinical, first of all somatic but also psychosociological medicine, and to continuously evaluate and follow-up results of his/her own work. The aim of the article is to present differences in clinical judgment before and after postgraduate study in family medicine. A 60-year-old woman living with her disabled son is presented. She visited her family physician many times complaining of a number of symptoms: itching, hypertension, sleep disturbance, poor general condition, trembling. It took ten months to diagnose hyperthyroidism and to begin appropriate therapy. Polysymptomatolgy of the disease based on the patient's psychological and family situation was the reason for the long-lasting wandering to definitive diagnosis. Analysis of the case revealed that neither clinical nor holistic approach was properly used in family medicine. The wrong clinical approach could be explained by fact that this physician worked for years without specialization or continuing education in family medicine. The authors conclude that postgraduate education as part of professional training in family medicine enables physicians to recognize and distinguish the interference of psychological, somatic and environmental factors, which is a major characteristic of good family practice.

Series of seizures as a sign of development of recurrent malignant neuroleptic syndrome - a case report.

Neuroleptic malignant syndrome (NMS) is an uncommon but sometimes fatal complication of neuroleptics and other medications that involve the central dopaminergic system. Many diagnostic criteria have been proposed for NMS but because of its variable presentation, universal criteria have not been established yet. Hyperthermia, disturbances of consciousness, extrapyramidal and autonomic symptoms are common features of NMS. We report the case of a 36 years old woman suffering from chronic schizophrenia and treated with flufenazine and olanzapine, who presented with series of generalised tonic-clonic seizures as the acute onset of recurrent malignant neuroleptic syndrome. Although atypical neuroleptics were previously thought to have less risk for MNS, combination of conventional and atypical neuroleptics in therapy increases the risk of NMS development and olanzapine might be responsible for the epileptic manifestations at the onset of fulminant NMS.

Family physicians' views on disclosure of a diagnosis of cancer and care of terminally ill patients in Croatia.

INTRODUCTION: Family physicians have a crucial role in communication and palliative care for terminally ill patients. AIMS: To examine family physicians' views about the disclosure of the diagnosis and information about cancer to their patients and to their families; to establish the most appropriate person to deliver the diagnosis of cancer to the patient; to examine whether family physicians cooperate with palliative care associations, and to assess their opinions about euthanasia and emotional support to dying patients. SUBJECTS AND METHODS: One hundred and thirty four family physicians participated in the study. The data was collected by questionnaire designed for this survey about cancer care. RESULTS: The majority of respondents 96 (71.64%) delivered the cancer diagnosis to their patients sometimes, and 69 (51.5%) told the truth about the cancer diagnosis to the family without the patient's permission. The respondents 90 (70.3%) considered that the family physician was the most appropriate person to disclose the cancer diagnosis and 107 (80.5%) considered that the patients' home was the most appropriate place for terminal care. The majority of physicians 61 (45.5%) thought that they did not cooperate enough with palliative care associations. In working with terminal patients, 42 (32.1%) respondents considered communication with the patients to be particularly difficult and 122 (93.8%) thought that emotional support of family and friends was most important. CONCLUSION: The majority of physicians deliver a diagnosis of cancer to their patients occasionally, and they also tell it to the patient's family. They considered family physician to be the most appropriate person to disclose a diagnosis of cancer and the patient's home was considered the most appropriate place for terminal care. In caring for terminally ill patients communication is considered particularly difficult, and the emotional support of family and friends is considered most important.

Sensibility to the unconscious (Balint approach).

The physician-patient relationship is recognized as having an essential role in the process of medical care, providing the context in which caring and healing can occur. Good patient-doctor relationship goes far deeper than the behaviour of physicians, particularly those behaviours recognized in popular culture as acting in a professional manner, being respectful of the patients' circumstances and bedside manner. The therapeutic relationship is a relationship between two persons--on one side is the patient who is psychologically modified in his illness, in regression, with resistance mechanisms, defences, fears and need for gratification, care and also for secondary profit. On the other side is the physician with his authority, knowledge, personality, habits, defences, unconscious of his own pharmacological effect on the patient, as the most potent drug. In the patient-centred medical model, based on contemporary scientific knowledge of disease, the physician has to understand the patient's "world of illness", and to accept the patient as a person with his whole conscious and unconscious reasons for suffering and not only as a"collection of symptoms".

Clinical Application of Genotype-guided Dosing of Warfarin in Patients with Acute Stroke.

BACKGROUND: Patients with certain types of stroke need urgent anticoagulation and it is extremely important for them to achieve fast and stable anticoagulant effect and receive individualized treatment during the initiation of warfarin therapy. METHODS: We conducted a prospective study among 210 acute stroke patients who had an indication for anticoagulation and compared the impact of CYP2C9 and VKORC1 genotype-guided warfarin dosing (PhG) with fixed dosing (NPhG) on anticoagulation control and clinical outcome between groups. RESULTS: PhG achieved target INR values earlier, i.e., on average in 4.2 (4.1-4.7, 95% CI) days compared to NPhG (5.2 days [4.7-6.4, 95% CI]) (p = 0.0009), spent a higher percentage of time in the therapeutic INR range (76.3% [74.7-78.5, 95% CI] vs. 67.1% [64.5-69.6, 95% CI] in NPhG), and spent less time overdosed (INR > 3.1) (PhG 0.4 [0.1-0.7, 95% CI], NPhG 1.7 [1.1-2.3, 95% CI] days; p >0.000). PhG reached stable maintenance dose faster (10 [9.9-10.7, 95% CI] vs. 13.9 [13.3-14.7, 95% CI] days in controls; p = 0.0049) and had a better clinical outcome in relation to neurological deficit on admission as compared to NPhG. CONCLUSION: We confirmed that warfarin therapy with genotype-guided dosing instead of fixed dosing reduces the time required for stabilization and improves anticoagulant control with better clinical outcome in early stages of warfarin therapy introduction among acute stroke patients, which is essential for clinical practice.

Economic evaluation of pharmacogenomic-guided warfarin treatment for elderly Croatian atrial fibrillation patients with ischemic stroke.

BACKGROUND & METHODS: Economic evaluation in genomic medicine is an emerging discipline to assess the cost-effectiveness of genome-guided treatment. Here, we developed a pharmaco-economic model to assess whether pharmacogenomic (PGx)-guided warfarin treatment of elderly ischemic stroke patients with atrial fibrillation in Croatia is cost effective compared with non-PGx therapy. The time horizon of the model was set at 1 year. RESULTS: Our primary analysis indicates that 97.07% (95% CI: 94.08-99.34%) of patients belonging to the PGx-guided group have not had any major complications, compared with the control group (89.12%; 95% CI: 84.00-93.87%, p < 0.05). The total cost per patient was estimated at €538.7 (95% CI: €526.3-551.2) for the PGx-guided group versus €219.7 (95% CI: €137.9-304.2) for the control group. In terms of quality-adjusted life-years (QALYs) gained, total QALYs was estimated at 0.954 (95% CI: 0.943-0.964) and 0.944 (95% CI: 0.931-0.956) for the PGx-guided and the control groups, respectively. The true difference in QALYs was estimated at 0.01 (95% CI: 0.005-0.015) in favor of the PGx-guided group. The incremental cost-effectiveness ratio of the PGx-guided versus the control groups was estimated at €31,225/QALY. CONCLUSION: Overall, our data indicate that PGx-guided warfarin treatment may represent a cost-effective therapy option for the management of elderly patients with atrial fibrillation who developed ischemic stroke in Croatia.

Prevalence of genetic polymorphisms of CYP2C9 and VKORC1 - implications for warfarin management and outcome in Croatian patients with acute stroke.

BACKGROUND: Data on the prevalence of CYP2C9 and VKORC1 genes and their influence on anticoagulant effect and warfarin dose in stroke patients are scarce. The aim of this study was to determine the occurrence and significance of these gene polymorphisms and to establish pharmacogenetic algorithm to estimate the dose of introduction. Also, the goal was to determine tailored safety and intensity of anticoagulation response depending on the allelic variants and their impact on the clinical outcome in acute stroke patients in Croatia. METHODS: A total of 106 consented acute stroke patients were tested for CYP2C9 2, 3 and VKORC1 1173C>T gene polymorphisms. We estimated the dose of introduction and monitored anticoagulant effect obtained by INR values, time to reach stable dose, stable maintenance dose, time spent within the therapeutic/supratherapeutic INR range, occurrence of dosage side effects and clinical outcome depending on genotypes. RESULTS: We found that 83% of stroke patients in our study were carriers of multiple allelic variants. The predicted initial dose correlated with the stable warfarin maintenance dose (p=0.0311) and we correctly estimated the dose for 81.5% of 61.3% of study patients who required higher/lower doses than average. Warfarin dosage complications were slightly more frequent among the carriers of CYP2C9 2, 3 compared to the carriers of VKORC1 1173T alleles (68. 9% versus 62.5%), but their occurrence did not affect the final clinical outcome. CONCLUSION: Our data indicated rapid and safe anticoagulation achieved by using pharmacogenetically-predicted warfarin dose in high-risk acute stroke patients without increasing the risk of warfarin dosage complications in an elderly population.

An infrequent type of stroke with an unusual cause and successful therapy: basilar artery occlusion caused by a cardiac papillary fibroelastoma recanalized 12 hours after onset.

We herein report the case of a 32-year-old woman with sudden onset ataxia, limb dysmetria and somnolence. Emergency radiological findings showed bilateral cerebellar and thalamic infarctions as a result of a basilar artery occlusion. The patient was treated with intra-arterial (IA) and mechanical thrombolysis 12 hours after symptom onset and showed an excellent recovery. A diagnostic workup revealed a tumor mass on the mitral valve that was surgically removed, while a histological analysis confirmed a diagnosis of cardiac papillary fibroelastoma.