Amantadine in unvaccinated patients with early, mild to moderate COVID-19: A randomized, placebo-controlled, double-blind trial.

BACKGROUND AND PURPOSE: Adamantanes were listed as an interesting option as an early intervention against COVID-19. We aimed to evaluate the effectiveness of amantadine in preventing the progression of COVID-19 and its neurological sequelae. METHODS: Unvaccinated patients with confirmed SARS-CoV-2 infection within 5 days were enrolled. Subjects were randomized (50:50) to amantadine (AMD; 100 mg twice daily) or placebo (PLB) for 14 days. The Ordinal Scale for Clinical Improvement of the World Health Organization (OSCI-WHO) was the primary measure. Secondary endpoints included assessment for fatigue; depression, disorders of smell and taste, and sleepiness on Days 1 and 15. RESULTS: We enrolled 99 patients (49 AMD and 50 PLB). Disease progression (OSCI-WHO = 4) was observed in 6% (AMD) and 8% (PLB) patients (p > 0.05) with further deterioration (OSCI-WHO〉4) in 0% (AMD) and 8% (PLB) patients (p > 0.05). Complete recovery on Day 15 was 60% higher in the AMD compared with the PLB group (p = 0.025). There was improvement in taste (AMD: p = 0.003; PLB: p = 0.0001) and smell (AMD: p = 0.005; PLB: p = 0.0004) but not in fatigue in both groups. Improvement was observed in the AMD (p = 0.010) but not in the PLB group (p = 0.058) when assessing depression as well as sleepiness (AMD: p = 0.0002; PLB: p = 0.341). There was one death in the PLB group (2.0%) and none in the AMD group (p > 0.05) until Day 210. Overall, the drug was well tolerated. CONCLUSION: The central effects of amantadine on the nervous system with reduction of sleepiness and depression might have had a supportive effect on faster recovery in early COVID-19 patients.

Study of Polonium (210Po) Activity Concentration in Fruit Wines Derived from Different Locations in Poland.

This study aimed at assessing the activity concentration and the annual effective dose of polonium-210 (210Po) in fruit wines derived from four locations in Poland (Warmian−Masurian, Podlaskie, Lubelskie and Malopolskie voivodeships). The fruit wines differed significantly (p < 0.05) in 210Po activity depending on the production site, with the Malopolskie site having the highest activity (61.4−221.4 mBq/L) and the Podlaskie having the lowest (3.5−97.1 mBq/L). The site differentiation was due to environmental conditions­soil parameters (uranium concentration), precipitations and terrain characteristics, e.g., the proximity of the lakes. The increased activity concentration of 210Po in samples from Malopolska compared with the other sites probably derived from the environment polluted with aqueous wastes and particulate air pollution. The annual effective dose due to the ingestion of fruit wines ranged from 0.112 to 1.214 µSv/year. These levels of exposure are safe according to the WHO criterion (0.1 mSv per year for ingestion) and to the IAEA reference level for public exposure including food (1 mSv per year). Summing up, the data obtained provide information on the activity concentration of 210Po in fruit wines and increase databases on the natural radioactivity of foodstuffs. Future work is needed to examine 210Po activity in samples from all vineyard regions in Poland.

Systematic review and network meta-analysis (NMA) for cladribine tablets in achieving sustained disability improvement (SDI) in multiple sclerosis.

INTRODUCTION: This study was performed to compare probabilities of SDI on the Expanded Disability Status Scale (EDSS) in patients with relapsing-remitting multiple sclerosis (RRMS), treated with cladribine tablets (CT) or fingolimod (FTY), natalizumab (NAT), alemtuzumab (ALE) and ocrelizumab (OCR). CLINICAL RATIONALE FOR THE STUDY: Progression of neurological disability as measured by the EDSS has been a common endpoint in multiple sclerosis (MS) trials. Novel therapies can not only slow this process, but in some patients even reverse it. This effect can be measured by the sustained disability improvement (SDI) - an endpoint that seems to continuously gain importance in clinical practice. Despite that, SDI has rarely been explored as an outcome in MS clinical studies, mostly as post-hoc analyses from randomised trials or as retrospective analyses based on patient registry records. MATERIAL AND METHODS: A systematic review was conducted in Medline, Embase and Cochrane to identify clinical trials (RCT or non-RCT) evaluating 6-month SDI. An indirect comparison via network meta-analysis (NMA) was performed. Bayesian inference with Markov chains Monte Carlo methods were applied. RESULTS: Eight trials presenting SDI results and applicable for NMA were included: six non-RCTs, with control groups selected by propensity score matching, and two RCTs. NMA results revealed that probability of achieving 6-month SDI with CT was significantly higher compared to all other high efficacy disease-modifying drugs with available data - HR (95% Crl - Bayesian Credibility Interval) vs. FTY: 4.98 (2.11-11.79); vs. NAT: 3.12 (1.31-7.27); vs. ALE: 9.29 (3.40-25.21). The main results were confirmed in the sensitivity analyses. CONCLUSIONS: Of all considered therapies, treatment with cladribine tablets was associated with a higher probability of sustained disability improvement in RRMS patients. As this conclusion is based on available clinical data of limited quality, future studies, as well as real-world data, would be valuable to provide further evidence regarding the comparative effectiveness of RRMS therapies.

Determination of 210Po and 210Pb in cannabis (Cannabis sativa L.) plants and products.

The concentrations of polonium 210Po and radio-lead 210Pb in cannabis (Cannabis sativa L.) plants and products now legally available in Poland were determined. Limiting the delivery of radionuclides to the body is an important aspect of civil protection in many countries. Reduction in use and awareness of the risks associated with tobacco and cannabis smoking have a great impact. The 210Po and 210Pb concentrations in 44 hemps, 20 hashish and 8 hemp tea samples, as well as in 3 types of cannabis plants (highest parts of mature hemp plant Fenola, Fedora and Futura) were determined. Each of the sample names means a different type and cross of C. sativa L. Being numerous, the are recognized on the market precisely by these names. Effective doses were calculated and compared to the doses of the other combustion products, such as tobacco. In the case of hemp, the highest concentration of 210Po was found in samples of dried Sweet Carmel (34.7 ± 0.23 mBq·g-1), while the lowest in the Hemp Berry (0.57 ± 0.23 mBq·g-1). In the case of 210Pb, the highest concentration was in Strawberry Kush (2.32 ± 0.05 mBq·g-1), while the lowest in Strawberry Haze (0.19 ± 0.03 mBq·g-1). In hashish, the highest and lowest concentrations of 210Po were in Strawberry Diesel 164 ± 3 mBq·g-1 and in Mango Kush 2.5 ± 0.2 mBq·g-1. The highest and lowest concentrations in the case of 210Pb in hashish were in Pollen Hashish 45.1 ± 0.2 mBq·g-1 and in Mango Kush Hashish 0.45 ± 0.05 mBq·g-1, respectively. These radionuclides did not constitute a radioactive equilibrium (210Po/210Pb).

Assessment of intake of 210Po and 210Pb isotopes from cow's milk in Poland.

Milk has been known for its nutritional properties for centuries and is often the staple of the diet in many countries. Therefore, monitoring of milk composition seems to be a relevant task as it was the purpose of this study to compare levels of 210Po and 210Pb in several Polish voivodeships. The methodology was based on mineralization, loss on an inorganic matrix and concentration measurement on an alpha spectrometer. The concentrations of 210Po and 210Pb in collected milk samples were measured using alpha spectrometry and calculations, respectively. The results showed that the lowest concentration of 210Po is 2.8 ± 0.2 mBq l-1 and the highest is 56.3 ± 0.7 mBq l-1 while the 210Pb concentrations are in the range from 2.8 ± 0.2 to 44.0 ± 1.7 mBq l-1. The associated annual effective doses for adults jmrange from 3.5 ± 0.1 to 11.0 ± 0.2 µSv a-1 for 210Po and from 2.0 ± 0.1 to 5.0 ± 0.1 µSv a-1 for 210Pb. The lowest doses were noticed in Kuyavian-Pomeranian Voivodeship and the highest values were found in Lesser Poland Voivodeship. The results show that the annual effective dose in individual provinces is not dangerous to health. However, there are significant differences between highly and lowly industrialized voivodeships.

Cladribine tablets versus other disease-modifying oral drugs in achieving no evidence of disease activity (NEDA) in multiple sclerosis-A systematic review and network meta-analysis.

INTRODUCTION: Assuming full control of the relapsing-remitting multiple sclerosis (RRMS) is the main target for practitioners. Disease control could be defined as no clinical relapse, absence of 3-month confirmed disability progression expressed on the Expanded Disability Status Scale (EDSS), as well as no disease activity on magnetic resonance imaging (MRI). NEDA-3 (no evidence of disease activity) is a composite endpoint used primarily in clinical trials, comprising these 3 measurements of disease activity. The aim of this study is to compare cladribine tablets (CT) with oral disease-modifying drugs (DMDs) - fingolimod (FTY), dimethyl fumarate (DMF), and teriflunomide (TERI) - with regard to NEDA-3 and its clinical (relapse and disability progression) and MRI (no new T1 Gd+ lesions or no new T2 lesions or no enlargement of existing lesions) components occurrence during a 24-month follow-up. METHODS: In June 2018, a systematic review of MEDLINE, Embase and Cochrane database was performed. Due to the lack of head-to-head trials directly comparing cladribine tablets to oral drugs of interest, an indirect network meta-analysis (NMA) was applied, with placebo as a common comparator. NMA was performed with Bayesian approach and Markov chain Monte Carlo (MCMC) method for estimating posterior distributions. Additional data used in the analysis were taken from conference abstracts or post hoc analyses of pooled data from the clinical studies. RESULTS: Six randomised clinical trials (RCTs) presenting NEDA, with active treatment compared to placebo, were included in the NMA: CLARITY (CT), FREEDOMS and FREEDOMS II (FTY), CONFIRM and DEFINE (DMF) and TEMSO (TERI). The rate of NEDA-3 was significantly higher in cladribine tablets vs DMF: OR (odds ratio)=1.76 (95% CrI [credible intervals]: 1.02-3.03) and TERI: OR=2.78 (95% CrI: 1.60-4.83), but not vs FTY. For the MRI NEDA results were as follows - cladribine tablets vs DMF: OR=1.87 (95% CrI: 1.18-2.97); cladribine tablets vs TERI: OR=6.59 (95% CrI: 4.32-10.09); cladribine tablets vs FTY: OR=1.58 (95% CrI: 1.10-2.29). The comparison of clinical NEDA did not reach significance vs either DMF or TERI and evaluation vs FTY was not possible because of lack of data. CONCLUSIONS: Cladribine in the form of tablets was significantly more effective in achieving NEDA-3 than DMF and TERI, but there was no significant difference vs FTY. Cladribine tablets was more effective than all oral comparators considering the MRI NEDA. For clinical NEDA, the superiority vs DMF and vs TERI was not confirmed, and vs FTY evaluation was not possible.

Radioactivity of honey in central and southern Poland.

In 2017, the Polish public consumed on average 0.61 kg of honey, while the European average consumption was 0.7 kg (Data on honey consumption in Poland, 2014) [http://www.portalspozywczy.pl]. The main point of this study was to investigate the 210Po activity concentrations in different types of floral and non-floral honey, type of clad honey is made of and honey yield in honey available on the Polish market. Activity of 210 Po in honey ranged from 0.006 ± 0.001 to 0.384 ± 0.004 Bq kg-1 with effective dose 0.005 ± 0.001 to 0.281 ± 0.003 µSv/year. The activity in honey was measured by alpha-spectrometry. The concentration of radionuclide depends on the raw material used by bees and plant type. The highest concentration of 210Po was observed in the honeydew honey and herbal honey.

210Po in popular medicinal herbs from Poland.

Herbs are an important part of traditional medicine in Poland. Therefore, the aim of this study was the determination of polonium 210Po in 48 selected medicinal herb samples from the Polish market. The activity concentrations of 210Po were measured using alpha spectrometry. The activity concentration of 210Po was in the range from 0.3 ± 0.1 to 28.2 ± 0.4 Bq kg-1. The obtained results were compared with corresponding studies conducted worldwide. A higher 210Po activity concentration was observed in the above-ground part of plants. The obtained results show that the highest 210Po activity concentration was observed in evergreen plants and winter-hardy plants. Yet even infusions with 2 g of the most contaminated herbs examined were considered to be radiologically safe.

Evaluation of serum microRNA biomarkers for gastric cancer based on blood and tissue pools profiling: the importance of miR-21 and miR-331.

BACKGROUND: High stability and disease-specific disarrangements suggest that microRNA molecules (miRNAs) present in body fluids are ideally suited for diagnostic applications, including gastric cancer (GC). However, the actual source of circulating miRNA biomarkers in GC has not been adequately evaluated, particularly in the Western populations that have some distinct characteristics compared with Asian patients. METHODS: Twenty treatment-naive patients with GC along with 20 cancer-free controls were recruited. miRCURY LNA miRNA microarrays were used for miRNA expression profiling in primary tumours and adjacent healthy mucosa. Differentially expressed serum miRNAs were identified with a high throughput TaqMan OpenArray technology in tumour-draining veins of the portal system, as well as peripheral blood of the patients and controls. RESULTS: Tissue profiling identified 108 sequences differentially expressed between primary tumours and adjacent mucosa (87 upregulated and 21 downregulated). Twenty miRNAs found in serum of GC patients showed expression levels higher than in controls. However, only seven of these molecules were overexpressed in primary tumours (miR-130a, miR-331, miR-19a, miR-223, miR-106a, miR-21, and miR-374). Moreover, expression of miR-331 and miR-21 was significantly higher in the peripheral circulation compared to tumour-draining veins of the portal system. CONCLUSIONS: The results indicate that the majority of potential serum miRNA biomarkers may originate from tissues other than the primary tumour.

Clinical significance of anti-domain 1 ß2-glycoprotein I antibodies in antiphospholipid syndrome.

BACKGROUND: Antiphospholipid syndrome (APS) is characterized by the presence of circulating antiphospholipid antibodies (aPL) in patients with thrombosis and/or pregnancy morbidity. In APS patients anti-domain 1 ß2-glycoprotein I (anti-D1 ß2GPI) IgG antibodies correlate strongly with thrombosis and to the lesser extent, with pregnancy complications. The aim of this study was to assess clinical utility of the anti-D1 ß2GPI antibodies in the diagnosis and risk stratification of antiphospholipid syndrome. PATIENTS/METHODS: In this retrospective study 202 autoimmune patients were studied (primary APS - 58, secondary - 45 SLE - 99). Anticardiolipin (aCL) and anti-ß2GPI (aß2GPI antibodies) (IgG and IgM class) together with anti-D1 IgG were tested with QUANTA Flash chemiluminescent immunoassay and lupus anticoagulant (LA) with coagulometric methods. RESULTS: The highest anti-D1 values were observed in triple positive patients as compared to patients with other antiphospholipid antibody profiles. A strong correlation was found between levels of anti-D1 IgG and a ß2GPI IgG antibodies for all patients analyzed (Spearman's ρ=0.87; p<0.0001). Anti-D1 IgG antibodies increase specificity resulting from classic aPL positivity but at the expense of sensitivity. Anti-D1 test does not add accuracy in predicting APS thrombotic complications on the top of accuracy offered by classic aPL tests and their profiles. CONCLUSIONS: Anti-D1 IgG antibodies did not add diagnostic power to the standard laboratory aPL tests as assessed by this retrospective study. A true clinical significance of anti-D1 antibodies in thrombotic risk stratification of aPL positive patients will require a properly designed clinical prospective trials.

Identification of patients with triple antiphospholipid antibody positivity is platform and method independent.

INTRODUCTION: The risk of clinical complications in antiphospholipid syndrome (APS) increases when a patient is positive for all 3 types of antiphospholipid (aPL) antibodies. However, there is a considerable disagreement between various platforms for aCL and anti-ß2-glycoprotein I (anti-ß2GPI) measurement, which leads to discrepancies between these platforms in assessing aPL antibody positivity. OBJECTIVES: The aim of this retrospective cross-sectional study was to assess whether 2 different platforms, the QUANTA Lite enzyme-linked immunosorbent assay and the QUANTA Flash chemiluminescent immunoassay, identify the same subjects as triple positive in a group of patients with APS and comorbid autoimmune diseases. PATIENTS AND METHODS: The study included 220 patients with systemic autoimmune diseases (74 with primary APS; 47 with secondary APS; and 99 with systemic lupus erythematosus without APS). All patients were tested for IgG and IgM aCL and anti-ß2GPI antibodies using both platforms. RESULTS: The agreement between the positive results for individual antibodies obtained using both platforms was not full, ranging from 81.8% to 90.9% in a pair-wise comparison. However, the number of patients with triple aPL antibody positivity was similar (80 by QUANTA Lite and 86 by QUANTA Flash); the agreement between the 2 platforms for the identification of patients with triple antibody positivity was 95.5% (Cohen's kappa coefficient = 0.90). This resulted in a similar risk for APS-related clinical complications: an odds ratio of 24.9 for QUANTA Lite and of 24.7 for QUANTA Flash. CONCLUSIONS: Our results confirm a strong association between triple aPL antibody positivity and APS and indicate that the identification of patients with triple antibody positivity is platform independent. When aPL antibody profiles are assessed, the agreement between various methods is much higher than that for individual antibodies.

Clinical utility of automated chemiluminescent antiphospholipid antibody assay.

BACKGROUND: The threshold for clinically relevant levels of antiphospholipid (aPL) antibodies for the diagnosis of antiphospholipid syndrome (APS) remains a matter of debate. As new technologies for antibody detection are introduced, their performance characteristics must be clearly understood and compared to traditional assays. OBJECTIVES: To assess the analytical performance and clinical utility of fully automated anticardiolipin (aCL) and anti-ß2 glycoprotein I (aß2GPI) chemiluminescent immunoassays (CIA) in comparison to the traditional ELISA tests. PATIENTS/METHODS: Samples from 220 autoimmune patients were studied (primary APS - 74; secondary APS - 47, systemic lupus erythematosus (SLE) without APS - 99). All samples were tested for IgG and IgM aCL and ß2GPI antibodies using both CIA and ELISA, and for lupus anticoagulant (LAC). RESULTS: Good qualitative agreement and quantitative correlation were found between methods in regard to individual antibodies and their categories (profiles). All assays showed good clinical performance in APS, and strong correlation with APS-related clinical symptoms. Importance of determining individual laboratory 99 percentile values for a healthy population as normal cut-off values was shown. Additionally, based on a clinical approach, this study has established the low/medium threshold for QUANTA Flash aCL IgG and IgM assays. CONCLUSIONS: This study showed good clinical performance and strong correlation of the new automated CIA aPL assays with APS clinical symptoms. It also enabled us to determine the corresponding low/medium antibody threshold for the aCL antibody methods with different unit types.

IL28B polymorphism (rs12979860) associated with clearance of HCV infection in Poland: systematic review of its prevalence in chronic hepatitis C patients and general population frequency.

BACKGROUND: A common single nucleotide polymorphism (rs12979860) of the interleukin-28B (IL28B) gene is strongly associated with spontaneous and treatment-related eradication of HCV infection. In this study we estimated rs12979860 genotypes distribution among chronic hepatitis C patients in Poland using a systematic review of published studies and compared this data with the prevalence of rs12979860 variants of IL28B in representative sample of the Southern Poland population. METHODS: Systematic review on rs12979860 variant prevalence in the Polish chronic HCV subjects was performed. Additionally, age- and gender-stratified population sample was recruited from inhabitants of Kraków using a randomized municipal census data, DNA samples available for 538 individuals were genotyped using a real-time PCR method. RESULTS: The frequency of homozygotes TT was from 15 to 27% and carriers of unfavorable T alleles (genotypes CT and TT) were present in 70-80% of chronic HCV subjects. In the general population, 47% individuals were CC homozygous, 42% CT heterozygous and 11% TT homozygous. The population frequency of T allele was 0.318 (95% CI: 0.291-0.347) and the variant was in Hardy-Weinberg equilibrium. Distributions of IL28B genotypes in chronic HCV patients were characterized by a departure from the genetic equilibrium and differed significantly from the random population sample. CONCLUSIONS: Events of spontaneous viral clearance can fully explain differences between genotype distributions in general population and chronic HCV subjects and a departure from the genetic equilibrium. This is the first study estimating the prevalence of IL28B rs12979860 SNP in the Southern Poland population based on a random representative sample.

Effectiveness of an e-learning course in evidence-based medicine for foundation (internship) training.

AIM: To evaluate the educational effectiveness of a clinically integrated e-learning course for teaching basic evidence-based medicine (EBM) among postgraduate medical trainees compared to a traditional lecture-based course of equivalent content. METHODS: We conducted a cluster randomized controlled trial to compare a clinically integrated e-learning EBM course (intervention) to a lecture-based course (control) among postgraduate trainees at foundation or internship level in seven teaching hospitals in the UK West Midlands region. Knowledge gain among participants was measured with a validated instrument using multiple choice questions. Change in knowledge was compared between groups taking into account the cluster design and adjusted for covariates at baseline using generalized estimating equations (GEE) model. RESULTS: There were seven clusters involving teaching of 237 trainees (122 in the intervention and 115 in the control group). The total number of postgraduate trainees who completed the course was 88 in the intervention group and 72 in the control group. After adjusting for baseline knowledge, there was no difference in the amount of improvement in knowledge of EBM between the two groups. The adjusted post course difference between the intervention group and the control group was only 0.1 scoring points (95% CI -1.2-1.4). CONCLUSION: An e-learning course in EBM was as effective in improving knowledge as a standard lecture-based course. The benefits of an e-learning approach need to be considered when planning EBM curricula as it allows standardization of teaching materials and is a potential cost-effective alternative to standard lecture-based teaching.

The effectiveness of a clinically integrated e-learning course in evidence-based medicine: a cluster randomised controlled trial.

BACKGROUND: To evaluate the educational effects of a clinically integrated e-learning course for teaching basic evidence-based medicine (EBM) among postgraduates compared to a traditional lecture-based course of equivalent content. METHODS: We conducted a cluster randomised controlled trial in the Netherlands and the UK involving postgraduate trainees in six obstetrics and gynaecology departments. Outcomes (knowledge gain and change in attitude towards EBM) were compared between the clinically integrated e-learning course (intervention) and the traditional lecture based course (control). We measured change from pre- to post-intervention scores using a validated questionnaire assessing knowledge (primary outcome) and attitudes (secondary outcome). RESULTS: There were six clusters involving teaching of 61 postgraduate trainees (28 in the intervention and 33 in the control group). The intervention group achieved slightly higher scores for knowledge gain compared to the control, but these results were not statistically significant (difference in knowledge gain: 3.5 points, 95% CI -2.7 to 9.8, p = 0.27). The attitudinal changes were similar for both groups. CONCLUSION: A clinically integrated e-learning course was at least as effective as a traditional lecture based course and was well accepted. Being less costly than traditional teaching and allowing for more independent learning through materials that can be easily updated, there is a place for incorporating e-learning into postgraduate EBM curricula that offer on-the-job training for just-in-time learning. TRIAL REGISTRATION NUMBER: ACTRN12609000022268.

How far did we get? How far to go? A European survey on postgraduate courses in evidence-based medicine.

BACKGROUND: Over the past decade, evidence-based medicine (EBM) has gained recognition as a means to improve the quality of health care provision. However, little is known about learning opportunities to acquire EBM-associated skills. The EUebm-Unity partnership explored current educational activities for EBM practice for doctors across Europe. METHODS: We surveyed organizations offering postgraduate EBM courses across Europe inquiring about their course programme, teaching content and strategies, and interest in a Europe-wide curriculum in EBM. RESULTS: One hundred and fifty-six organizers in eight European countries reported 403 courses that had started first-time from 1996 to 2006. Despite a steady increase, in absolute terms, the frequency of courses was low and varied from 1 first-time offering of a course per 640 doctors (Spain) to 1 first-time offering per 5600 doctors (Austria) over 10 years. Most adopted the McMaster EBM teaching concept of small group, problem-based learning focussing on interventions, diagnostic tests and guidelines, and included efforts to link EBM to patient care. Teaching staff consisted of doctors from academic and non-academic settings, supported by methodologists. Efforts to formally integrate EBM in postgraduate activities were only partially successful. Most organizations welcomed a standardized European qualification in EBM. A limitation of the survey is the lack of follow-up information about the continuation of courses following the first-time offering. CONCLUSIONS: All countries offer some EBM courses with varying teaching intensity. Learning opportunities are insufficient to ensure widespread dissemination of knowledge and skills. Most countries welcome more efforts to develop inexpensive and feasible educational activities at a postgraduate level.

Harmonising evidence-based medicine teaching: a study of the outcomes of e-learning in five European countries.

BACKGROUND: We developed and evaluated the outcomes of an e-learning course for evidence based medicine (EBM) training in postgraduate medical education in different languages and settings across five European countries. METHODS: We measured changes in knowledge and attitudes with well-developed assessment tools before and after administration of the course. The course consisted of five e-learning modules covering acquisition (formulating a question and search of the literature), appraisal, application and implementation of findings from systematic reviews of therapeutic interventions, each with interactive audio-visual learning materials of 15 to 20 minutes duration. The modules were prepared in English, Spanish, German and Hungarian. The course was delivered to 101 students from different specialties in Germany (psychiatrists), Hungary (mixture of specialties), Spain (general medical practitioners), Switzerland (obstetricians-gynaecologists) and the UK (obstetricians-gynaecologists). We analysed changes in scores across modules and countries. RESULTS: On average across all countries, knowledge scores significantly improved from pre- to post-course for all five modules (p < 0.001). The improvements in scores were on average 1.87 points (14% of total score) for module 1, 1.81 points (26% of total score) for module 2, 1.9 points (11% of total score) for module 3, 1.9 points (12% of total score) for module 4 and 1.14 points (14% of total score) for module 5. In the country specific analysis, knowledge gain was not significant for module 4 in Spain, Switzerland and the UK, for module 3 in Spain and Switzerland and for module 2 in Spain. Compared to pre-course assessment, after completing the course participants felt more confident that they can assess research evidence and that the healthcare system in their country should have its own programme of research about clinical effectiveness. CONCLUSION: E-learning in EBM can be harmonised for effective teaching and learning in different languages, educational settings and clinical specialties, paving the way for development of an international e-EBM course.

A clinically integrated curriculum in evidence-based medicine for just-in-time learning through on-the-job training: the EU-EBM project.

BACKGROUND: Over the last years key stake holders in the healthcare sector have increasingly recognised evidence based medicine (EBM) as a means to improving the quality of healthcare. However, there is considerable uncertainty about the best way to disseminate basic knowledge of EBM. As a result, huge variation in EBM educational provision, setting, duration, intensity, content, and teaching methodology exists across Europe and worldwide. Most courses for health care professionals are delivered outside the work context ('stand alone') and lack adaptation to the specific needs for EBM at the learners' workplace. Courses with modern 'adaptive' EBM teaching that employ principles of effective continuing education might fill that gap. We aimed to develop a course for post-graduate education which is clinically integrated and allows maximum flexibility for teachers and learners. METHODS: A group of experienced EBM teachers, clinical epidemiologists, clinicians and educationalists from institutions from eight European countries participated. We used an established methodology of curriculum development to design a clinically integrated EBM course with substantial components of e-learning. An independent European steering committee provided input into the process. RESULTS: We defined explicit learning objectives about knowledge, skills, attitudes and behaviour for the five steps of EBM. A handbook guides facilitator and learner through five modules with clinical and e-learning components. Focussed activities and targeted assignments round off the learning process, after which each module is formally assessed. CONCLUSION: The course is learner-centred, problem-based, integrated with activities in the workplace and flexible. When successfully implemented, the course is designed to provide just-in-time learning through on-the-job-training, with the potential for teaching and learning to directly impact on practice.

The prevalence of alpha(1)-antitrypsin deficiency in a representative population sample from Poland.

AIM: Severe alpha(1)-antitrypsin (AAT) deficiency is one of the most common genetic disorders in Caucasians. The aim of the present study was to assess an unbiased frequencies of PI*S and PI*Z alleles using genotyping of a representative sample from the general population of Poland. METHODS: A random sample of age- and gender-stratified residents, aged 20 years or older, was drawn from the municipal directory of Kraków, Poland. The two most common deficiency alleles: PI*S and PI*Z were genotyped with qualitative real-time PCR using degenerative dual-labeled allele-specific fluorescent probes. RESULTS: In the total population of 859 adult subjects (mean age: 49.5 years; range: 20-90), 28 heterozygotes MS, 18 heterozygotes MZ and one homozygote S were diagnosed. The frequency of PI*S allele was 17.5 (95% CI: 11.6-23.9) per 1000; and that of PI*Z was 10.5 (95% CI: 5.8-15.7) per 1000. Therefore, the estimated prevalence of inherited severe AAT deficiency (homozygotes Z) in Poland is 1/9110 (95% CI: 1/4057-1/29,727). CONCLUSIONS: In the whole population of Poland comprising 38 millions, one may expect of about 4189 (95% CI: 1284-9406) subjects with severe AAT deficiency. These numbers are high enough to consider genetic testing being introduced into a common clinical practice.

Rapid and inexpensive detection of alpha1-antitrypsin deficiency-related alleles S and Z by a real-time polymerase chain reaction suitable for a large-scale population-based screening.

alpha(1)-Antitrypsin (AAT) deficiency is one of the most common genetic disorders in Caucasians, leading to early onset pulmonary emphysema and/or liver disorders. Accumulating data suggest that AAT deficiency is commonly under-recognized or misdiagnosed by physicians. The need for a rapid, timesaving, and relatively inexpensive but reliable detection method for the two most common deficiency alleles was developed using real-time polymerase chain reaction (PCR) genotyping. We designed and validated a 5'-nuclease assay for typing of the PI*S and PI*Z alleles using dual-labeled target-specific fluorescent probes. As a reference method, we used restriction fragment length polymorphism. The real-time PCR method was tested on a large, cross-sectional epidemiological trial. Overall, we genotyped about 1200 samples and found a very good concordance with AAT serum levels and restriction fragment length polymorphism results. In addition, external interlaboratory validation confirmed the accuracy of the real-time PCR method. In our experience, the real-time qualitative PCR using 5'-nuclease assay is suitable as a genetic test for AAT deficiency. This method offers an acceptable balance between reliability and expenses. It seems appropriate for both population-based screening and clinical diagnosis of the deficiency.