Aleš Urban

Visual mismatch negativity among patients with schizophrenia

Event related potentials (ERPs) provide an insight into sensory and cognitive processes in health and disease. Studies of an ERP negative amplitude deflection elicited by a change in a series of auditory stimuli is known as mismatch negativity (MMN). The generation of MMN is impaired in schizophrenia. Its deficit is associated with lower everyday functioning and may be also interpreted as the marker of progression in schizophrenia. MMN elicited by visual stimuli (vMMN) was described by several research teams, but it has not been investigated in schizophrenia as yet. Using a motion-direction paradigm, we elicited visual MMN in 24 patients with schizophrenia and schizoaffective disorder. The vMMN was computed as differences in areas under curve of visual ERPs to standard and deviant motion-direction stimuli recorded from midline derivations at the interval of 100-200 ms. They were compared between groups of patients with schizophrenia and healthy controls. The significantly smaller vMMN indicated an impaired generation of mismatch negativity in patients with schizophrenia. In secondary analyses there was an association of vMMN impairment among patients with higher dose of medication, lower level of functioning and the presence of deficit syndrome. This impairment appears analogous to the impairment of MMN in the auditory domain and is probably related to early visual information processing. Its relationship to cognitive functioning of patients with schizophrenia deserves further attention.

Comparison of UTCI with other thermal indices in the assessment of heat and cold effects on cardiovascular mortality in the Czech Republic.

We compare the recently developed Universal Thermal Climate Index (UTCI) with other thermal indices in analysing heat- and cold-related effects on cardiovascular (CVD) mortality in two different (urban and rural) regions in the Czech Republic during the 16-year period from 1994–2009. Excess mortality is represented by the number of deaths above expected daily values, the latter being adjusted for long-term changes, annual and weekly cycles, and epidemics of influenza/acute respiratory infections. Air temperature, UTCI, Apparent Temperature (AT) and Physiologically Equivalent Temperature (PET) are applied to identify days with heat and cold stress. We found similar heat effects on CVD mortality for air temperature and the examined thermal indices. Responses of CVD mortality to cold effects as characterised by different indices were much more varied. Particularly important is the finding that air temperature provides a weak cold effect in comparison with the thermal indices in both regions, so its application—still widespread in epidemiological studies—may underestimate the magnitude of cold-related mortality. These findings are important when possible climate change effects on heat- and cold-related mortality are estimated. AT and PET appear to be more universal predictors of heat- and cold- related mortality than UTCI when both urban and rural environments are of concern. UTCI tends to select windy rather than freezing days in winter, though these show little effect on mortality in the urban population. By contrast, significant cold-related mortality in the rural region if UTCI is used shows potential for UTCI to become a useful tool in cold exposure assessments.

Heat- and cold-stress effects on cardiovascular mortality and morbidity among urban and rural populations in the Czech Republic

Several studies have examined the relationship of high and low air temperatures to cardiovascular mortality in the Czech Republic. Much less is understood about heat-/cold-related cardiovascular morbidity and possible regional differences. This paper compares the effects of warm and cold days on excess mortality and morbidity for cardiovascular diseases (CVDs) in the city of Prague and a rural region of southern Bohemia during 1994–2009. Population size and age structure are similar in the two regions. The results are evaluated for selected population groups (men and women). Excess mortality (number of deaths) and morbidity (number of hospital admissions) were determined as differences between observed and expected daily values, the latter being adjusted for long-term changes, annual and weekly cycles, and epidemics of influenza/acute respiratory infections. Generally higher relative excess CVD mortality on warm days than on cold days was identified in both regions. In contrast to mortality, weak excess CVD morbidity was observed for both warm and cold days. Different responses of individual CVDs to heat versus cold stress may be caused by the different nature of each CVD and different physiological processes induced by heat or cold stress. The slight differences between Prague and southern Bohemia in response to heat versus cold stress suggest the possible influence of environmental and socioeconomic factors such as the effects of urban heat island and exposure to air pollution, lifestyle differences, and divergence in population structure, which may result in differing vulnerability of urban versus rural population to temperature extremes.

Projections of temperature-related excess mortality under climate change scenarios

Summary Background Climate change can directly affect human health by varying exposure to non-optimal outdoor temperature. However, evidence on this direct impact at a global scale is limited, mainly due to issues in modelling and projecting complex and highly heterogeneous epidemiological relationships across different populations and climates. Methods We collected observed daily time series of mean temperature and mortality counts for all causes or non-external causes only, in periods ranging from Jan 1, 1984, to Dec 31, 2015, from various locations across the globe through the Multi-Country Multi-City Collaborative Research Network. We estimated temperature–mortality relationships through a two-stage time series design. We generated current and future daily mean temperature series under four scenarios of climate change, determined by varying trajectories of greenhouse gas emissions, using five general circulation models. We projected excess mortality for cold and heat and their net change in 1990–2099 under each scenario of climate change, assuming no adaptation or population changes. Findings Our dataset comprised 451 locations in 23 countries across nine regions of the world, including 85 879 895 deaths. Results indicate, on average, a net increase in temperature-related excess mortality under high-emission scenarios, although with important geographical differences. In temperate areas such as northern Europe, east Asia, and Australia, the less intense warming and large decrease in cold-related excess would induce a null or marginally negative net effect, with the net change in 2090–99 compared with 2010–19 ranging from −1·2% (empirical 95% CI −3·6 to 1·4) in Australia to −0·1% (−2·1 to 1·6) in east Asia under the highest emission scenario, although the decreasing trends would reverse during the course of the century. Conversely, warmer regions, such as the central and southern parts of America or Europe, and especially southeast Asia, would experience a sharp surge in heat-related impacts and extremely large net increases, with the net change at the end of the century ranging from 3·0% (−3·0 to 9·3) in Central America to 12·7% (−4·7 to 28·1) in southeast Asia under the highest emission scenario. Most of the health effects directly due to temperature increase could be avoided under scenarios involving mitigation strategies to limit emissions and further warming of the planet. Interpretation This study shows the negative health impacts of climate change that, under high-emission scenarios, would disproportionately affect warmer and poorer regions of the world. Comparison with lower emission scenarios emphasises the importance of mitigation policies for limiting global warming and reducing the associated health risks. Funding UK Medical Research Council.

Four cases of venous thromboembolism associated with olanzapine

Aims:  Psychiatric disorders and treatment with conventional antipsychotic medications have been associated with venous thromboembolism, but only a few data on recent antipsychotics such as olanzapine are available.

Antipsychotic drugs as a risk factor for venous thromboembolism

Objective. We assessed whether antipsychotic drugs represent a risk factor for venous thromboembolism by comparing the prevalence of antipsychotic drugs use in a population of patients with venous thromboembolism versus a group of individuals treated for hypertension. Methods. We identified 266 patients (141 women) diagnosed as having venous thromboembolism at the average age of 43.1±11 years who had been hospitalized in the University Hospital in Hradec Králové from 1 January 1996 to 31 December 2004. Two hundred and seventy-four patients (140 women) with arterial hypertension, with an average age of 48.3±8.8 years, represented the control population. Results. Use of antipsychotic drugs was moderately more frequent in the group of patients with venous thromboembolism as compared with the control group subjects (4.89 vs. 1.82%; odds ratio 2.76; 95% confidence interval=1.01–7.55). Discussion. We discuss the possible mechanisms of venous thromboembolism induced by antipsychotic agents – hypoactivity, blood status, obesity, abnormal coagulation, autoimmune mechanisms, and hyperhomocysteinemia. Conclusion. Our results indicate the possibility of an increased risk for venous thromboembolism in patients using antipsychotic drugs. It is necessary to seriously consider this possible adverse effect owing to its potentially fatal consequences.

An Electrophysiological Study of Visual Processing in Spinocerebellar Ataxia Type 2 (SCA2)

Reports of visual functional impairment in spinocerebellar ataxia type 2 (SCA2) have been studied previously using pattern reversal visually evoked potentials (VEPs) with contradictory results. To provide additional evidence to this area, visual functions were studied using VEPs and event-related potentials (ERPs) in a group of ten patients with genetically verified SCA2. The electrophysiological examination included pattern reversal and motion-onset VEPs as well as visually driven oddball ERPs with an evaluation of a target and a pre-attentive response. In six patients, we found abnormal visual/cognitive processing that differed from normal values in latency, but not in the amplitude of the dominant VEP/ERP peaks. Among the VEPs/ERPs used, the motion-onset VEPs exhibited the highest sensitivity and showed a strong Spearman correlation to SCA2 duration (from r = 0.82 to r = 0.90, p < 0.001) and clinical state assessed by Brief Ataxia Rating Scale (from r = 0.71 (p = 0.022) to r = 0.80 (p < 0.001)). None of the VEP/ERP latencies showed a correlation to the triplet repeats of the SCA2 gene. In three patients, we did not find any visual/cognitive pathology, and one subject showed only a single subtle prolongation of the VEP peak. The observed visual/cognitive deficit was related to the subjects’ clinical state and the illness duration, but no relationship to the genetic marker of SCA2 was found. From the VEP/ERP types used, the motion-onset VEPs seems to be the most promising candidate for clinical state monitoring rather than a tool for early diagnostic use.

Comorbidity of parkinsonism and schizophrenia in a patient treated with clozapine.

Clozapine is the least likely anti-psychotic to induce extrapyramidal symptoms (EPS). We present a surprising case of a woman schizophrenic patient treated with clozapine suffering from EPS. Single photon emission computed tomography (SPECT) revealed a low density of presynaptic dopamine transporters in our patients brain. A comorbid diagnosis of Parkinsons disease in schizophrenia was confirmed in this way. This helped us to find a proper therapeutic strategy for our patient.

Spatial Patterns of Heat-Related Cardiovascular Mortality in the Czech Republic

The study examines spatial patterns of effects of high temperature extremes on cardiovascular mortality in the Czech Republic at a district level during 1994–2009. Daily baseline mortality for each district was determined using a single location-stratified generalized additive model. Mean relative deviations of mortality from the baseline were calculated on days exceeding the 90th percentile of mean daily temperature in summer, and they were correlated with selected demographic, socioeconomic, and physical-environmental variables for the districts. Groups of districts with similar characteristics were identified according to socioeconomic status and urbanization level in order to provide a more general picture than possible on the district level. We evaluated lagged patterns of excess mortality after hot spell occurrences in: (i) urban areas vs. predominantly rural areas; and (ii) regions with different overall socioeconomic level. Our findings suggest that climatic conditions, altitude, and urbanization generally affect the spatial distribution of districts with the highest excess cardiovascular mortality, while socioeconomic status did not show a significant effect in the analysis across the Czech Republic as a whole. Only within deprived populations, socioeconomic status played a relevant role as well. After taking into account lagged effects of temperature on excess mortality, we found that the effect of hot spells was significant in highly urbanized regions, while most excess deaths in rural districts may be attributed to harvesting effects.

Impacts of the 2015 Heat Waves on Mortality in the Czech Republic—A Comparison with Previous Heat Waves

This study aimed to assess the impacts of heat waves during the summer of 2015 on mortality in the Czech Republic and to compare them with those of heat waves back to the previous record-breaking summer of 1994. We analyzed daily natural-cause mortality across the country’s entire population. A mortality baseline was determined using generalized additive models adjusted for long-term trends, seasonal and weekly cycles, and identified heat waves. Mortality deviations from the baseline were calculated to quantify excess mortality during heat waves, defined as periods of at least three consecutive days with mean daily temperature higher than the 95th percentile of annual distribution. The summer of 2015 was record-breaking in the total duration of heat waves as well as their total heat load. Consequently, the impact of the major heat wave in 2015 on the increase in excess mortality relative to the baseline was greater than during the previous record-breaking heat wave in 1994 (265% vs. 240%). Excess mortality was comparable among the younger age group (0–64 years) and the elderly (65+ years) in the 1994 major heat wave while it was significantly larger among the elderly in 2015. The results suggest that the total heat load of a heat wave needs to be considered when assessing its impact on mortality, as the cumulative excess heat factor explains the magnitude of excess mortality during a heat wave better than other characteristics such as duration or average daily mean temperature during the heat wave. Comparison of the mortality impacts of the 2015 and 1994 major heat waves suggests that the recently reported decline in overall heat-related mortality in Central Europe has abated and simple extrapolation of the trend would lead to biased conclusions even for the near future. Further research is needed toward understanding the additional mitigation measures required to prevent heat-related mortality in the Czech Republic and elsewhere.