Effectiveness of tixagevimab/cilgavimab (Evusheld) in antiCD20­treated patients with multiple sclerosis and neuromyelitis optica spectrum disorder.

BACKGROUND: AntiCD20 therapy, such as rituximab, ocrelizumab, or ofatumumab, effectively treats patients with multiple sclerosis (pwMS) or neuromyelitis optica spectrum disorder (pwNMOSD) but negatively affects the humoral immune response to COVID-19 vaccination. One strategy to protect these patients is using tixagevimab/cilgavimab (T/C) as pre-exposure prophylaxis. This study aimed to evaluate the effect of T/C on the incidence of COVID-19 in pwMS and pwNMOSD. METHODS: Data in this observational cohort study were collected in two Czech MS centres through ReMuS registry between March 1, 2020 and December 31, 2022. Adult pwMS and pwNMOSD who were (1) treated with antiCD20 therapy at least six months before T/C administration, or at least from February 1, 2022 in the control group; (2) were already on antiCD20 therapy at the time of vaccination or COVID-19 infection; and (3) were on antiCD20 therapy at least 100 days after T/C, or at least 90 days after August 1, 2022 in the control group, were included. Analysis was performed using frequency-based (propensity score matching) and Bayesian statistical methods (informative and non-informative priors). RESULTS: Using propensity score matching 1:1, 47 patients who received T/C (mean age 45.7 years, median disease duration 12.5 years) were matched with those who did not receive T/C (n = 341; mean age 46.6 years, median disease duration 11.4 years) based on age, MS/NMOSD duration, and number of vaccine doses. None of the T/C patients and three in the control matched group, developed COVID-19 between 10 and 100 days after receiving T/C, August 1, 2022, respectively. The frequency of COVID-19 was not significantly different between groups (p = 0.242). Due to the low number of patients, a Bayesian analysis was also added. Using a non-informative Bayesian prior, the median relative risk of COVID-19 after T/C was 7.6 % (95 % CrI 0.02-115.9 %). The posterior probability of risk difference lower than zero was 96.4 %. Using an informative prior (based on the registration study of Evusheld), the median relative risk of COVID-19 after T/C was 20.2 % (95 % CI 8.4-43.8 %). The posterior probability of the risk difference lower than zero was 100 %. CONCLUSION: This work highlights the possible good efficacy of T/C in antiCD20-treated pwMS and pwNMSOD. Based on Bayesian analysis with an informative prior, the T/C group's risk of COVID-19 infection was approximately 20.2 % of the control group's risk. However, given the low frequency of COVID-19, the results of this pilot analysis must be interpreted with caution.

Comparative effectiveness and cost-effectiveness of natalizumab and fingolimod in rapidly evolving severe relapsing-remitting multiple sclerosis in the United Kingdom.

AIM: To evaluate the real-world comparative effectiveness and the cost-effectiveness, from a UK National Health Service perspective, of natalizumab versus fingolimod in patients with rapidly evolving severe relapsing-remitting multiple sclerosis (RES-RRMS). METHODS: Real-world data from the MSBase Registry were obtained for patients with RES-RRMS who were previously either naive to disease-modifying therapies or had been treated with interferon-based therapies, glatiramer acetate, dimethyl fumarate, or teriflunomide (collectively known as BRACETD). Matched cohorts were selected by 3-way multinomial propensity score matching, and the annualized relapse rate (ARR) and 6-month-confirmed disability worsening (CDW6M) and improvement (CDI6M) were compared between treatment groups. Comparative effectiveness results were used in a cost-effectiveness model comparing natalizumab and fingolimod, using an established Markov structure over a lifetime horizon with health states based on the Expanded Disability Status Scale. Additional model data sources included the UK MS Survey 2015, published literature, and publicly available sources. RESULTS: In the comparative effectiveness analysis, we found a significantly lower ARR for patients starting natalizumab compared with fingolimod (rate ratio [RR] = 0.65; 95% confidence interval [CI], 0.57-0.73) or BRACETD (RR = 0.46; 95% CI, 0.42-0.53). Similarly, CDI6M was higher for patients starting natalizumab compared with fingolimod (hazard ratio [HR] = 1.25; 95% CI, 1.01-1.55) and BRACETD (HR = 1.46; 95% CI, 1.16-1.85). In patients starting fingolimod, we found a lower ARR (RR = 0.72; 95% CI, 0.65-0.80) compared with starting BRACETD, but no difference in CDI6M (HR = 1.17; 95% CI, 0.91-1.50). Differences in CDW6M were not found between the treatment groups. In the base-case cost-effectiveness analysis, natalizumab dominated fingolimod (0.302 higher quality-adjusted life-years [QALYs] and £17,141 lower predicted lifetime costs). Similar cost-effectiveness results were observed across sensitivity analyses. CONCLUSIONS: This MSBase Registry analysis suggests that natalizumab improves clinical outcomes when compared with fingolimod, which translates to higher QALYs and lower costs in UK patients with RES-RRMS.

There are several medications used to treat people with relapsing remitting multiple sclerosis, such as interferon-based therapies (Betaferon/Betaseron (US), Rebif, Avonex, Extavia), glatiramer acetate (Copaxone), teriflunomide (Aubagio), and dimethyl fumarate (Tecfidera), collectively named BRACETD. Other treatments for multiple sclerosis (MS) have a narrower use, such as natalizumab (Tysabri) or fingolimod (Gilenya), among others.This study objective was to assess how well natalizumab and fingolimod helped treating MS (clinical effectiveness) and subsequently estimate what the cost of these treatments is in comparison to the benefit they bring to people with rapidly evolving severe MS that use them in the United Kingdom (UK) (cost-effectiveness).We used an international disease registry (MSBase), which collects clinical data from people with MS in various centers around the world to compare the effectiveness of natalizumab, fingolimod and BRACETD treatments. We used a technique called propensity score matching to obtain results from comparable patient groups. People treated with natalizumab had better disease control, namely with fewer relapses and higher improvement on their disability level, than patients on fingolimod or BRACETD. Conversely, there were no differences between each group of people on a measure called disability worsening.Based on these clinical results, we built an economic model that simulates the lifetime costs and consequences of treating people with MS with natalizumab in comparison with fingolimod. We found that using natalizumab was less costly and was more effective compared to using fingolimod in UK patients.

Secondary prevention of lung cancer in the Czech Republic - pitfalls, risks, benefits.

Lung cancer (LC) is one of the most frequently diagnosed cancers and one of the leading causes of cancer deaths in the Czech Republic, the prevalence of which is steadily increasing. There is scientific evidence that LC screening through low-dose computed tomography (LDCT) reduces the risk of death from LC. No systematic LC screening strategy has been currently in place in the Czech Republic. Since the beginning of 2022, the methodology of early detection of LC using LDCT has been piloted to test the feasibility of the screening program. The primary purpose of the project is an early and accurate diagnosis of the disease, which, in combination with follow-up treatment, will lead to a reduction in LC mortality. The pilot data will definitely serve as a basis for an expert discussion of the acceptability of the program to the Czech population and its impact on the healthcare system. It is clear that by introducing such a screening program, we will join the countries that, based on scientific data, enable the population to profit from an actively implemented LC prevention strategy. Public awareness of the benefits of early non-invasive LC detection can contribute to higher compliance of at-risk persons and their willingness to participate in the program. The key role in the entire process is played by general practitioners and/or outpatient pulmologists who address at-risk individuals and can positively influence their involvement in the program.

Assessing clinical utility of machine learning and artificial intelligence approaches to analyze speech recordings in multiple sclerosis: A pilot study.

BACKGROUND: An early diagnosis together with an accurate disease progression monitoring of multiple sclerosis is an important component of successful disease management. Prior studies have established that multiple sclerosis is correlated with speech discrepancies. Early research using objective acoustic measurements has discovered measurable dysarthria. METHOD: The objective was to determine the potential clinical utility of machine learning and deep learning/AI approaches for the aiding of diagnosis, biomarker extraction and progression monitoring of multiple sclerosis using speech recordings. A corpus of 65 MS-positive and 66 healthy individuals reading the same text aloud was used for targeted acoustic feature extraction utilizing automatic phoneme segmentation. A series of binary classification models was trained, tuned, and evaluated regarding their Accuracy and area-under-the-curve. RESULTS: The Random Forest model performed best, achieving an Accuracy of 0.82 on the validation dataset and an area-under-the-curve of 0.76 across 5 k-fold cycles on the training dataset. 5 out of 7 acoustic features were statistically significant. CONCLUSION: Machine learning and artificial intelligence in automatic analyses of voice recordings for aiding multiple sclerosis diagnosis and progression tracking seems promising. Further clinical validation of these methods and their mapping onto multiple sclerosis progression is needed, as well as a validating utility for English-speaking populations.

Impact of methodological choices in comparative effectiveness studies: application in natalizumab versus fingolimod comparison among patients with multiple sclerosis.

BACKGROUND: Natalizumab and fingolimod are used as high-efficacy treatments in relapsing-remitting multiple sclerosis. Several observational studies comparing these two drugs have shown variable results, using different methods to control treatment indication bias and manage censoring. The objective of this empirical study was to elucidate the impact of methods of causal inference on the results of comparative effectiveness studies. METHODS: Data from three observational multiple sclerosis registries (MSBase, the Danish MS Registry and French OFSEP registry) were combined. Four clinical outcomes were studied. Propensity scores were used to match or weigh the compared groups, allowing for estimating average treatment effect for treated or average treatment effect for the entire population. Analyses were conducted both in intention-to-treat and per-protocol frameworks. The impact of the positivity assumption was also assessed. RESULTS: Overall, 5,148 relapsing-remitting multiple sclerosis patients were included. In this well-powered sample, the 95% confidence intervals of the estimates overlapped widely. Propensity scores weighting and propensity scores matching procedures led to consistent results. Some differences were observed between average treatment effect for the entire population and average treatment effect for treated estimates. Intention-to-treat analyses were more conservative than per-protocol analyses. The most pronounced irregularities in outcomes and propensity scores were introduced by violation of the positivity assumption. CONCLUSIONS: This applied study elucidates the influence of methodological decisions on the results of comparative effectiveness studies of treatments for multiple sclerosis. According to our results, there are no material differences between conclusions obtained with propensity scores matching or propensity scores weighting given that a study is sufficiently powered, models are correctly specified and positivity assumption is fulfilled.

Associations Between Homeostasis Model Assessment (HOMA) and Routinely Examined Parameters in Individuals With Metabolic Syndrome.

The aim of the study was to investigate whether routine clinical parameters, including visceral adiposity index (VAI) and atherogenic index of plasma (AIP), could become widely applicable predictors of insulin resistance (IR), evaluated using homeostasis model assessment (HOMA-IR, HOMA-ß), with regard to presence of metabolic syndrome (MS). The study comprised 188 individuals identified to meet the MS criteria during regular health examinations and an equal number of age, sex-matched controls without MS. The strongest correlations were noted between HOMA-IR and waist circumference (WC) in the MS group (r=0.57) as well as between HOMA-IR and alanine aminotransferase (ALT, r=0.57) or aspartate aminotransferase (r=0.56) in the controls, with a statistical significance of p<0.001. In a multivariate linear regression model, the predictors of HOMA-IR were WC (linear coefficient ß=0.1, p<0.001), ALT (ß=2.28, p<0.001) and systolic blood pressure (ß=0.04, p<0.001). HOMA-ß was determined by WC (ß=1.97, p=0.032) and ALT (ß=99.49, p=0.004) and inversely associated with age (ß=-1.31, p=0.004). Neither VAI nor AIP were significant predictors. The presence of MS was significantly associated with both HOMA-IR and HOMA-ß. These results indicate that WC and ALT appear to be reliable predictors of IR. Comprehensive assessment of these parameters may serve for estimating the level of IR.

Initiation of first disease-modifying treatment for multiple sclerosis patients in the Czech republic from 2013 to 2016: Data from the national registry ReMuS.

BACKGROUND: Proper management of multiple sclerosis (MS) requires feedback from clinical practice via registries. OBJECTIVE: To introduce the Czech national multiple sclerosis registry, ReMuS, and explore the availability and use of disease-modifying drugs (DMD). METHODS: The analysis focused on patients who started their first DMD, either with first-line or second-line medication and was based on reimbursement criteria set by Czech regulators. Baseline information was used to predict relapses after DMD initiation and to compare patients that started DMD in different years. RESULTS: A total of 3,328 patients started DMD treatment for MS between 2013 and 2016; 3,203 on first-line and 125 on second-line medication. The proportion of patients starting on second-line drugs increased from 1.8% in 2013 to 4.7% in 2016. The occurrence of a relapse within one year of DMD initiation was significantly related to (1) the Expanded Disability Status Scale (EDSS) score immediately prior to starting DMD and (2) the number of previous relapses. Both parameters were significantly lower in patients starting in later years of the explored interval. CONCLUSION: Data from the ReMuS registry highlights improvements made in the management of MS in the Czech Republic. However, a relatively low percentage of patients started treatment using second-line drugs, in contrast to trends in other countries.

A Serial 10-Year Follow-Up Study of Atrophied Brain Lesion Volume and Disability Progression in Patients with Relapsing-Remitting MS.

BACKGROUND AND PURPOSE: Disappearance of T2 lesions into CSF spaces is frequently observed in patients with MS. Our aim was to investigate temporal changes of cumulative atrophied brain T2 lesion volume and 10-year confirmed disability progression. MATERIALS AND METHODS: We studied 176 patients with relapsing-remitting MS who underwent MR imaging at baseline, 6 months, and then yearly for 10 years. Occurrence of new/enlarging T2 lesions, changes in T2 lesion volume, and whole-brain, cortical and ventricle volumes were assessed yearly between baseline and 10 years. Atrophied T2 lesion volume was calculated by combining baseline lesion masks with follow-up CSF partial volume maps. Ten-year confirmed disability progression was confirmed after 48 weeks. ANCOVA detected MR imaging outcome differences in stable (n = 76) and confirmed disability progression (n = 100) groups at different time points; hierarchic regression determined the unique additive variance explained by atrophied T2 lesion volume regarding the association with confirmed disability progression, in addition to other MR imaging metrics. Cox regression investigated the association of early MR imaging outcome changes and time to development of confirmed disability progression. RESULTS: The separation of stable-versus-confirmed disability progression groups became significant even in the first 6 months for atrophied T2 lesion volume (140% difference, Cohen d = 0.54, P = .004) and remained significant across all time points (P ≤ .007). The hierarchic model, including all other MR imaging outcomes during 10 years predicting confirmed disability progression, improved significantly after adding atrophied T2 lesion volume (R 2 = 0.27, R 2 change 0.11, P = .009). In Cox regression, atrophied T2 lesion volume in 0-6 months (hazard ratio = 4.23, P = .04) and 0-12 months (hazard ratio = 2.41, P = .022) was the only significant MR imaging predictor of time to confirmed disability progression. CONCLUSIONS: Atrophied T2 lesion volume is a robust and early marker of disability progression in relapsing-remitting MS.

Anti-inflammatory disease-modifying treatment and disability progression in primary progressive multiple sclerosis: a cohort study.

BACKGROUND AND PURPOSE: Treatment options in primary progressive multiple sclerosis (PPMS) are scarce and, with the exception of ocrelizumab, anti-inflammatory agents have failed to show efficacy in ameliorating disability progression. The aim of this study was to investigate a potential effect of anti-inflammatory disease-modifying treatment on disability outcomes in PPMS. METHODS: Using MSBase, a large, international, observational database, we identified patients with PPMS who were either never treated or treated with a disease-modifying agent. Propensity score matching was used to select subpopulations with similar baseline characteristics. Expanded Disability Status Scale (EDSS) outcomes were compared with an intention-to-treat and an as-treated approach in paired, pairwise-censored analyses. RESULTS: Of the 1284 included patients, 533 were matched (treated, n = 195; untreated n = 338). Median on-study pairwise-censored follow-up was 3.4 years (quartiles 1.2-5.5). No difference in the hazard of experiencing 3-month confirmed EDSS progression events was observed between the groups [hazard ratio (HR), 1.0; 95% confidence interval (CI), 0.6-1.7, P = 0.87]. We did not find significant differences in the hazards of confirmed EDSS improvement (HR, 1.0; 95% CI, 0.6-1.6, P = 0.91) or reaching a confirmed EDSS step ≥7 (HR, 1.1; 95% CI, 0.7-1.6, P = 0.69). CONCLUSION: Our pooled analysis of disease-modifying agents suggests that these therapies have no substantial effect on short- to medium-term disability outcomes in PPMS.

[The common bed bug (Cimex lectularius) - biology, medical relevance, possibilities for the detection and control]. / Stenice domácí (Cimex lectularius) - biologie, zdravotnický význam, moznosti detekce a hubení.

Bed bugs have become a major concern worldwide in the 21st century and are therefore intensively investigated. The new findings not only extend the knowledge of their biology, medical relevance, and causes of the resurgence, but also can be used in bed bug management. A brief overview is provided of some of the most important research results and opinions, published in the last few years in prestigious international journals.

Thalamic Iron Differentiates Primary-Progressive and Relapsing-Remitting Multiple Sclerosis.

BACKGROUND AND PURPOSE: Potential differences between primary progressive and relapsing remitting multiple sclerosis are the subject of ongoing controversial discussions. The aim of this work was to determine whether and how primary-progressive and relapsing-remitting multiple sclerosis subtypes differ regarding conventional MR imaging parameters, cerebral iron deposits, and their association with clinical status. MATERIALS AND METHODS: We analyzed 24 patients with primary-progressive MS, 80 with relapsing-remitting MS, and 20 healthy controls with 1.5T MR imaging for assessment of the conventional quantitative parameters: T2 lesion load, T1 lesion load, brain parenchymal fraction, and corpus callosum volume. Quantitative susceptibility mapping was performed to estimate iron concentration in the deep gray matter. RESULTS: Decreased susceptibility within the thalamus in relapsing-remitting MS compared with primary-progressive MS was the only significant MR imaging difference between these MS subtypes. In the relapsing-remitting MS subgroup, the Expanded Disability Status Scale score was positively associated with conventional parameters reflecting white matter lesions and brain atrophy and with iron in the putamen and caudate nucleus. A positive association with putaminal iron and the Expanded Disability Status Scale score was found in primary-progressive MS. CONCLUSIONS: Susceptibility in the thalamus might provide additional support for the differentiation between primary-progressive and relapsing-remitting MS. That the Expanded Disability Status Scale score was associated with conventional MR imaging parameters and iron concentrations in several deep gray matter regions in relapsing-remitting MS, while only a weak association with putaminal iron was observed in primary-progressive MS suggests different driving forces of disability in these MS subtypes.

Identification of multiple sclerosis patients at highest risk of cognitive impairment using an integrated brain magnetic resonance imaging assessment approach.

BACKGROUND AND PURPOSE: While impaired cognitive performance is common in multiple sclerosis (MS), it has been largely underdiagnosed. Here a magnetic resonance imaging (MRI) screening algorithm is proposed to identify patients at highest risk of cognitive impairment. The objective was to examine whether assessment of lesion burden together with whole brain atrophy on MRI improves our ability to identify cognitively impaired MS patients. METHODS: Of the 1253 patients enrolled in the study, 1052 patients with all cognitive, volumetric MRI and clinical data available were included in the analysis. Brain MRI and neuropsychological assessment with the Brief International Cognitive Assessment for Multiple Sclerosis were performed. Multivariable logistic regression and individual prediction analysis were used to investigate the associations between MRI markers and cognitive impairment. The results of the primary analysis were validated at two subsequent time points (months 12 and 24). RESULTS: The prevalence of cognitive impairment was greater in patients with low brain parenchymal fraction (BPF) (<0.85) and high T2 lesion volume (T2-LV) (>3.5 ml) than in patients with high BPF (>0.85) and low T2-LV (<3.5 ml), with an odds ratio (OR) of 6.5 (95% CI 4.4-9.5). Low BPF together with high T2-LV identified in 270 (25.7%) patients predicted cognitive impairment with 83% specificity, 82% negative predictive value, 51% sensitivity and 75% overall accuracy. The risk of confirmed cognitive decline over the follow-up was greater in patients with high T2-LV (OR 2.1; 95% CI 1.1-3.8) and low BPF (OR 2.6; 95% CI 1.4-4.7). CONCLUSIONS: The integrated MRI assessment of lesion burden and brain atrophy may improve the stratification of MS patients who may benefit from cognitive assessment.

Evaluation of Dietary Habits in the Study of Pancreatic Cancer.

BACKGROUND: Pancreatic cancer is serious and rapidly progressing condition. Little is known about the role of diet in etiology of pancreatic cancer. The study focused on the role of selected dietary factors related to pancreatic cancer. MATERIAL AND METHODS: The case-control study was performed in the Czech Republic in 2006- 2009, involving three centers in Olomouc, Ostrava and Ceske Budejovice. It comprised a total of 530 persons, of whom 310 had pancreatic cancer and 220 were controls. Data were obtained directly from each participant in an interview with a trained interviewer and entered into a standardized questionnaire. The data were analyzed using a crude odds ratio (OR) and multivariate logistic regression with an adjusted OR and 95% CI. The statistical analysis was performed with the STATA v. 10 software. RESULTS: A very strong protective effect was found in pickled cabbage (OR 0.32; 95% CI 0.19- 0.55), broccoli (OR 0.37; 95% CI 0.25- 0.53), cooked onion (OR 0.14; 95% CI 0.08- 0.27), tomatoes (OR 0.28; 95% CI 0.13- 0.60), raw carrot (OR 0.33; 95% CI 0.20- 0.56), cooked carrot (OR 0.35; 95% CI 0.19- 0.62). In logistic regression model, statistically significant protective associations were found in consumption of more than three portions of cooked vegetables per week (OR 0.16; 95% CI 0.05- 0.55) and high consumption of citrus fruit (OR 0.46; 95% CI 0.23- 0.90). CONCLUSION: The study found statistically significant protective effect of consumption of more than three portions of cooked vegetables per week and high consumption of citrus fruit.

Risk of early relapse following the switch from injectables to oral agents for multiple sclerosis.

BACKGROUND AND PURPOSE: Early relapse outcomes in long-term stable patients switching from interferon ß/glatiramer acetate (IFNß/GA) to oral therapy are unknown. OBJECTIVE: The objective of this study was to compare early relapse and progression in multiple sclerosis (MS) patients switching to oral therapy following a period of stable disease on IFNß/GA, relative to a propensity-matched comparator of patients remaining on IFNß/GA. METHODS: The MSBase cohort study is a global, longitudinal registry for MS. Time to first 6-month relapse in previously stable MS patients switching from platform injectables ('switchers') to oral agents were compared with propensity-matched patients remaining on IFNß/GA ('stayers') using a Cox marginal model. RESULTS: Three-hundred and ninety-six switchers were successfully matched to 396 stayers on a 1:1 basis. There was no difference in the proportion of patients recording at least one relapse in the first 1-6 months by treatment arm (7.3% switchers, 6.6% stayers; P = 0.675). The mean annualized relapse rate (P = 0.493) and the rate of first 6-month relapse by treatment arm (hazard ratio 1.22, 95% confidence interval 0.70, 2.11) were also comparable. There was no difference in the rate of disability progression by treatment arm (hazard ratio 1.43, 95% confidence interval 0.63, 3.26). CONCLUSION: This is the first study to compare early relapse switch probability in the period immediately following switch to oral treatment in a population previously stable on injectable therapy. There was no evidence of disease reactivation within the first 6 months of switching to oral therapy.

[Epidemiological significance of the metabolic syndrome]. / Epidemiologický význam metabolického syndromu.

From an epidemiological point of view, the metabolic syndrome is a group of risk factors causally, rather than coincidentally, related to insulin resistance. The metabolic syndrome is a condition with relatively high prevalence rates in both the Czech Republic and in other developed countries. There is a clear trend of increasing prevalence in both sexes depending on age. In the Czech Republic, the syndrome is less common in females (25.5%) than in males (37.6%). Epidemiological studies found white (Europoid race) males to be at higher risk due to abdominal obesity. The definition of the metabolic syndrome has evolved over time and helps to identify individuals at high risk of developing cardiovascular disease and type 2 diabetes, hence the use of the term cardiometabolic syndrome. Early detection of metabolic syndrome symptoms including insulin resistance should be performed mainly by general practitioners as part of regular check-ups.

Longitudinal Mixed-Effect Model Analysis of the Association between Global and Tissue-Specific Brain Atrophy and Lesion Accumulation in Patients with Clinically Isolated Syndrome.

BACKGROUND AND PURPOSE: The relationship between lesion formation and brain atrophy development in the early phase of multiple sclerosis is unclear. We investigated the association between new lesion accumulation and brain atrophy progression in patients with clinically isolated syndrome over 48 months. MATERIALS AND METHODS: Patients with clinically isolated syndrome (n = 210) were evaluated with 1.5T MR imaging at baseline and at 6, 12, 24, 36, and 48 months as part of a multicenter observational study of early administration of intramuscular interferon ß-1a. Mixed-effect model analyses, adjusted for age, sex, and treatment status, investigated the association between accumulation of contrast-enhancing and T2 lesions and brain-volume percent changes in a 48-month period. RESULTS: In patients with clinically isolated syndrome, the average whole-brain volume decreased 2.5%, the mean lateral ventricle volume increased 16.9%, and a mean of 7.7 new/enlarging T2 lesions accumulated over the follow-up period. Patients with clinically isolated syndrome who showed greater percentages of change in whole-brain, white and gray matter, cortical, and lateral ventricle volumes over the follow-up period had more severe lesion outcomes at baseline (all P < .007). There were significant associations between decreased individual brain-volume measures at baseline and greater percentages of change during follow-up (P < .05). We found a significant association between the total cumulative number of new/enlarging T2 lesions and the evolution of whole-brain (P < .001), lateral ventricle (P = .007), gray matter and thalamic (P = .013), subcortical deep gray matter (P = .015), and cortical (P = .036) volumes over the follow-up period. CONCLUSIONS: Lesion accumulation and brain-volume changes occur simultaneously in the early phase of clinically isolated syndrome. More severe lesion and brain-volume outcomes at baseline were associated with greater development of brain atrophy over the follow-up period in patients with clinically isolated syndrome.

[West Nile virus transmission risk in the Czech Republic]. / Rizika sírení viru západonilské horecky v Ceské republice.

West Nile Virus (WNV) belongs to the family Flaviviridae. It is transmitted to humans by mosquitoes, capable of sucking blood on birds and mammals, most often by mosquitoes of the genus Culex. In humans, the virus was first identified in 1937 in the West Nile region, Uganda, Africa. Later, the virus spread and caused more or less severe epidemics of West Nile fever in North Africa, Europe, Asia, and North and South America. During the last two decades, WNV has been on the rise and is currently ranked as one of the most prevalent arboviruses in the world. In humans, WNV infection mostly occurs as asymptomatic, but may have a more severe or even fatal course in older and weakened patients. Humans may become infected not only by mosquitoes that acquire the virus from infected birds, but also through a blood transfusion, organ transplant, breast milk and transplacental transmission, or contact with infected animals, their blood, and tissues. The first autochthonous human case of West Nile fever in the Czech Republic was reported from South Moravia in 1997. In 2013, another case of West Nile fever emerged in this country, in the Ostrava area. The issue of WNV has recently been studied from many different perspectives, as evidenced by many original and review papers. This article briefly reviews the essential knowledge about this virus and its spread.

Early magnetic resonance imaging predictors of clinical progression after 48 months in clinically isolated syndrome patients treated with intramuscular interferon ß-1a.

BACKGROUND AND PURPOSE: Our aim was to identify early imaging surrogate markers of clinical progression in patients after the first demyelinating event suggestive of multiple sclerosis treated with weekly intramuscular interferon ß-1a. In a prospective observational study, the predictive role of baseline and 6-month changes in magnetic resonance imaging outcomes was investigated with respect to relapse activity and development of confirmed disability progression in patients after 48 months. METHODS: This study examined 210 patients. Multivariate Cox proportional hazard models were used to analyse predictors of relapse activity and confirmed disability progression after 48 months. RESULTS: Greater T2 lesion volume [hazard ratio (HR) 1.81; P = 0.005] and the presence of contrast-enhancing lesions (HR 2.13; P < 0.001) at baseline were significantly associated with increased cumulative risk of a second clinical attack over 48 months. A greater decrease of the corpus callosum volume (HR 2.74; P = 0.001) and greater lateral ventricle volume enlargement (HR 2.43; P = 0.002) at 6 months relative to baseline were associated with increased cumulative risk of a second clinical attack between months 6 and 48. In addition, increased risk of confirmed disability progression over 48 months in patients with greater lateral ventricle volume enlargement between baseline and 6 months (HR 4.70; P = 0.001) was detected. CONCLUSIONS: A greater T2 lesion volume, the presence of contrast-enhancing lesions at baseline, decrease of corpus callosum volume and lateral ventricle volume enlargement over the first 6 months in patients after the first demyelinating event treated with weekly intramuscular interferon ß-1a may assist in identification of patients with the highest risk of a second clinical attack and progression of disability.

[A multifactor epidemiological analysis of risk factors for pancreatic cancer in women]. / Multifaktorová epidemiologická analýza rizikových faktoru karcinomu pankreatu u zen.

STUDY OBJECTIVE: A multifactor analysis of risk factors for pancreas cancer in women. MATERIAL AND METHODS: A case-control study was conducted in three centres in the Czech Republic (Olomouc, Ostrava, and Ceské Budejovice) in 2006-2009. In total, 226 women (129 pancreas cancer cases, 97 controls) were included in the study. Statistical analysis was performed, the crude odds ratio (OR) was calculated, and logistic regression analysis was used at a 5% level of statistical significance. RESULTS: A statistically significant inverse association was found between pancreatic cancer and oral contraceptives (OR 0.21; 95% CI: 0.07-0.69). Pregnancy and number of pregnancies or gynecological surgical procedures did not show any association with pancreatic cancer. No significant difference in the first menstrual period was found between pancreatic cancer patients and controls. CONCLUSIONS: The study results showed inverse association between pancreatic cancer and oral contraceptives (OR 0.21; 95% CI: 0.07-0.69), controlled alcohol consumption (OR 0.26; 95% CI: 0.12-0.55), and anti-inflamatory drug use (OR 0.10; 95% CI: 0.02-0.41).