BACKGROUND: There is now a general attempt in developed countries to implement strategic plans to fight against Alzheimer's disease and other dementia disorders. Among others, attention is paid to the issues of registers and calculations of economic burden. Currently available calculations of costs are difficult to compare. The problem is a different breakdown of cost categories and non-unified monitoring of cost types. OBJECTIVE: The aim of this paper is to note the problem of poor availability and inconsistencies in cost monitoring. Furthermore, the intersection of cost items that are comparable and consistently monitored in expert studies are specified. METHODS: The Web of Science, Elsevier Science Direct, PubMed, and Scopus databases are used in a systematic review. Two independent reviewers screened the identified records and selected relevant articles published in the period from 2010 to 2016. A meta-analysis of costs is performed in four categories related to patients suffering from Alzheimer's disease. RESULTS: The resulting estimation of total costs per patient per month through meta-analysis is € 3,896, with 95% CI [2078, 5713]. The highest costs arise from informal care following non-medical and medical care. CONCLUSION: The results confirm assumption that inconsistencies in cost monitoring of the treatment and care of people with dementia exists in Europe. Homogeneity could be assumed only in the medical costs of severe patients. Heterogeneity is assumed in non-medical costs, informal costs. Cost items should be defined and collected more precisely for future more precise monitoring of the economic burden.

• Klíčová slova
• Alzheimer’s disease, data collection uniformity, developed countries, meta-analysis,
• MeSH
• Alzheimerova nemoc ekonomika   terapie   MeSH
• analýza nákladů a výnosů MeSH
• databáze bibliografické statistika a číselné údaje   MeSH
• lidé MeSH
• osobní újma zaviněná nemocí * MeSH
• poskytování zdravotní péče ekonomika   metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

BACKGROUND: Alzheimer´s disease (AD) is a serious and complex neurodegenerative disease. Currently, there are about 44 million people suffering from AD all over the world and this number is expected to rapidly grow due to demographic changes. The disease can be treated both pharmacologically and non-pharmacologically. Unfortunately, it cannot be cured yet. Nevertheless, the drugs for the treatment of AD are quite expensive, have different side effects and only delay symptoms of this disease. Therefore researchers suggest the use of various non-pharmacological therapies. Apart from relatively popular in western world such as physical activities, cognitive training or healthy diet, Chinese medicine starts to be practiced in Europe. OBJECTIVE: The purpose of this mini-review is to discuss the concept of Chinese medicine and explore its most common and effective forms in the treatment of AD. METHODS: This was done by conducting a literature search in the world´s acknowledged databases such as Web of Science, Scopus, PubMed and Springer. RESULTS: Five randomized controlled clinical trial studies were analyzed and their findings were discussed. CONCLUSION: The authors of this mini-review list the key benefits (e.g., positive results of the reviewed randomized clinical trials studies for the improvement of cognitive decline in AD) and limitations (e.g., low awareness of benefits of TCM in Europe) of Chinese medicine therapy for the treatment of AD.

• Klíčová slova
• Alzheimer's disease, Chinese medicine, benefits, concept, findings, limitations,
• MeSH
• Alzheimerova nemoc terapie   MeSH
• databáze bibliografické statistika a číselné údaje   MeSH
• léky rostlinné čínské terapeutické užití   MeSH
• lidé MeSH
• randomizované kontrolované studie jako téma MeSH
• tradiční čínská medicína metody   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• léky rostlinné čínské MeSH

BACKGROUND: Alemtuzumab, an anti-CD52 antibody, is proven to be more efficacious than interferon beta-1a in the treatment of relapsing-remitting multiple sclerosis, but its efficacy relative to more potent immunotherapies is unknown. We compared the effectiveness of alemtuzumab with natalizumab, fingolimod, and interferon beta in patients with relapsing-remitting multiple sclerosis treated for up to 5 years. METHODS: In this international cohort study, we used data from propensity-matched patients with relapsing-remitting multiple sclerosis from the MSBase and six other cohorts. Longitudinal clinical data were obtained from 71 MSBase centres in 21 countries and from six non-MSBase centres in the UK and Germany between Nov 1, 2015, and June 30, 2016. Key inclusion criteria were a diagnosis of definite relapsing-remitting multiple sclerosis, exposure to one of the study therapies (alemtuzumab, interferon beta, fingolimod, or natalizumab), age 65 years or younger, Expanded Disability Status Scale (EDSS) score 6·5 or lower, and no more than 10 years since the first multiple sclerosis symptom. The primary endpoint was annualised relapse rate. The secondary endpoints were cumulative hazards of relapses, disability accumulation, and disability improvement events. We compared relapse rates with negative binomial models, and estimated cumulative hazards with conditional proportional hazards models. FINDINGS: Patients were treated between Aug 1, 1994, and June 30, 2016. The cohorts consisted of 189 patients given alemtuzumab, 2155 patients given interferon beta, 828 patients given fingolimod, and 1160 patients given natalizumab. Alemtuzumab was associated with a lower annualised relapse rate than interferon beta (0·19 [95% CI 0·14-0·23] vs 0·53 [0·46-0·61], p<0·0001) and fingolimod (0·15 [0·10-0·20] vs 0·34 [0·26-0·41], p<0·0001), and was associated with a similar annualised relapse rate as natalizumab (0·20 [0·14-0·26] vs 0·19 [0·15-0·23], p=0·78). For the disability outcomes, alemtuzumab was associated with similar probabilities of disability accumulation as interferon beta (hazard ratio [HR] 0·66 [95% CI 0·36-1·22], p=0·37), fingolimod (1·27 [0·60-2·70], p=0·67), and natalizumab (0·81 [0·47-1·39], p=0·60). Alemtuzumab was associated with similar probabilities of disability improvement as interferon beta (0·98 [0·65-1·49], p=0·93) and fingolimod (0·50 [0·25-1·01], p=0·18), and a lower probability of disability improvement than natalizumab (0·35 [0·20-0·59], p=0·0006). INTERPRETATION: Alemtuzumab and natalizumab seem to have similar effects on annualised relapse rates in relapsing-remitting multiple sclerosis. Alemtuzumab seems superior to fingolimod and interferon beta in mitigating relapse activity. Natalizumab seems superior to alemtuzumab in enabling recovery from disability. Both natalizumab and alemtuzumab seem highly effective and viable immunotherapies for multiple sclerosis. Treatment decisions between alemtuzumab and natalizumab should be primarily governed by their safety profiles. FUNDING: National Health and Medical Research Council, and the University of Melbourne.

• MeSH
• alemtuzumab MeSH
• databáze bibliografické statistika a číselné údaje   MeSH
• dospělí MeSH
• fingolimod hydrochlorid terapeutické užití   MeSH
• humanizované monoklonální protilátky terapeutické užití   MeSH
• imunologické faktory terapeutické užití   MeSH
• interferon beta terapeutické užití   MeSH
• kohortové studie MeSH
• lidé MeSH
• mladý dospělý MeSH
• natalizumab terapeutické užití   MeSH
• posuzování pracovní neschopnosti MeSH
• relabující-remitující roztroušená skleróza farmakoterapie   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• alemtuzumab MeSH
• fingolimod hydrochlorid MeSH
• humanizované monoklonální protilátky MeSH
• imunologické faktory MeSH
• interferon beta MeSH
• natalizumab MeSH

BACKGROUND: Histaminergic neurons are crucial to maintain wakefulness, but their role in cataplexy is unknown. We assessed the safety and efficacy of pitolisant, a histamine H3 receptor inverse agonist, for treatment of cataplexy in patients with narcolepsy. METHODS: For this randomised, double-blind, placebo-controlled trial we recruited patients with narcolepsy from 16 sleep centres in nine countries (Bulgaria, Czech Republic, Hungary, Macedonia, Poland, Russia, Serbia, Turkey, and Ukraine). Patients were eligible if they were aged 18 years or older, diagnosed with narcolepsy with cataplexy according to version two of the International Classification of Sleep Disorders criteria, experienced at least three cataplexies per week, and had excessive daytime sleepiness (defined as an Epworth Sleepiness Scale score ≥12). We used a computer-generated sequence via an interactive web response system to randomly assign patients to receive either pitolisant or placebo once per day (1:1 ratio). Randomisation was done in blocks of four. Participants and investigators were masked to treatment allocation. Treatment lasted for 7 weeks: 3 weeks of flexible dosing decided by investigators according to efficacy and tolerance (5 mg, 10 mg, or 20 mg oral pitolisant), followed by 4 weeks of stable dosing (5 mg, 10 mg, 20 mg, or 40 mg). The primary endpoint was the change in the average number of cataplexy attacks per week as recorded in patient diaries (weekly cataplexy rate [WCR]) between the 2 weeks of baseline and the 4 weeks of stable dosing period. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01800045. FINDINGS: The trial was done between April 19, 2013, and Jan 28, 2015. We screened 117 patients, 106 of whom were randomly assigned to treatment (54 to pitolisant and 52 to placebo) and, after dropout, 54 patients from the pitolisant group and 51 from the placebo group were included in the intention-to-treat analysis. The WCR during the stable dosing period compared with baseline was decreased by 75% (WCRfinal=2·27; WCRbaseline=9·15; WCRfinal/baseline=0·25) in patients who received pitolisant and 38% (WCRfinal=4·52; WCRbaseline=7·31; WCRfinal/baseline=0·62) in patients who received placebo (rate ratio 0·512; 95% CI 0·43-0·60, p<0·0001). Treatment-related adverse events were significantly more common in the pitolisant group than in the placebo group (15 [28%] of 54 vs 6 [12%] of 51; p=0·048). There were no serious adverse events, but one case of severe nausea in the pitolisant group. The most frequent adverse events in the pitolisant group (headache, irritability, anxiety, and nausea) were mild or moderate except one case of severe nausea. No withdrawal syndrome was detected following pitolisant treatment; one case was detected in the placebo group. INTERPRETATION: Pitolisant was well tolerated and efficacious in reducing cataplexy. If confirmed in long-term studies, pitolisant might constitute a useful first-line therapy for cataplexy in patients with narcolepsy, for whom there are currently few therapeutic options. FUNDING: Bioprojet, France.

• MeSH
• antagonisté histaminového receptoru H3 terapeutické užití   MeSH
• databáze bibliografické statistika a číselné údaje   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• kataplexie farmakoterapie   etiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• narkolepsie komplikace   MeSH
• následné studie MeSH
• piperidiny terapeutické užití   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• stupeň závažnosti nemoci MeSH
• výsledek terapie * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• antagonisté histaminového receptoru H3 MeSH
• piperidiny MeSH
• pitolisant MeSH Prohlížeč

INTRODUCTION: Perineural spread (PNS) is an unusual mechanism of tumor extension and has been typically reported in squamous cell carcinoma, adenocystic carcinoma, and desmoplastic melanoma. Our group has previously demonstrated PNS in rectal, prostate, bladder, and cervical cancer from the primary site along the autonomic nerves to the major somatic nerves and even intradurally. We believe similar principles apply to renal cell carcinoma (RCC) as well, despite the different anatomy. CASE DESCRIPTION: We performed a retrospective search to identify cases of intradural-extramedullary metastases of RCC caused by PNS. Strict anatomic and imaging inclusion criteria were defined: only lesions located between T6 and L3 were included, and PNS as a potential cause had to be supported by imaging evidence. Although 3 cases of spinal intradural metastases were identified, only one met our strict inclusion criteria. A 61-year-old woman developed a late intradural-extramedullary metastasis of RCC 16 years after the original diagnosis that we believe represents an example of visceral organ PNS. CONCLUSIONS: RCC can propagate via PNS from the primary tumor along the autonomic nerves to the aorticorenal, celiac, and mesenteric ganglia and then along the thoracic and lumbar splanchnic nerves to the corresponding spinal nerves and intradurally. We present radiologic evidence together with the review of the literature to support the premise that PNS of RCC not only occurs but goes unrecognized.

• Klíčová slova
• Metastasis, Perineural spread, Renal cell carcinoma, Spinal,
• MeSH
• databáze bibliografické statistika a číselné údaje   MeSH
• karcinom z renálních buněk komplikace   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• míšní nervy diagnostické zobrazování   MeSH
• nádory ledvin komplikace   patologie   MeSH
• nádory míchy diagnostické zobrazování   sekundární   MeSH
• retrospektivní studie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• přehledy MeSH

The impact of statin therapy on dementia has been a hot topic of debate over the last decade and still remains highly controversial. Among all causes of dementia, vascular dementia (VaD) is the one type that is more likely to benefit from statins. To date no randomized clinical trials have been published and no systematic review has investigated a possible preventive effect of statins on the VaD subtype. In the present literature review, we tried to identify all available data on the effect of statins specifically in patients with VaD, and to further discuss this possible association. Our literature search highlighted two cross-sectional studies, two prospective cohort studies, and one retrospective cohort study. Two of the studies found a significant positive effect of statin treatment on VaD, depicted by the lower incidence of VaD in statin users, while the others reported non-significant associations. The relatively small numbers of VaD patients and statin users, as well as the presence of confounders and biases, make the interpretation of results extremely difficult. Statins may exert a benefit in the prevention of all-type dementia and VaD, through several mechanisms except for hyperlipidemia reduction. A well-designed randomized clinical trial is the ideal study design to address the effect of statin therapy in VaD and to draw final conclusions.

• Klíčová slova
• Cholesterol, HMG-CoA inhibitors, lipid lowering agents, statins, vascular dementia,
• MeSH
• anticholesteremika terapeutické užití   MeSH
• databáze bibliografické statistika a číselné údaje   MeSH
• lidé MeSH
• statiny terapeutické užití   MeSH
• vaskulární demence farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• systematický přehled MeSH
• Názvy látek
• anticholesteremika MeSH
• statiny MeSH

OBJECTIVES: Impaired response inhibition underlies symptoms and altered functioning in patients with bipolar disorders (BD). The interpretation of fMRI studies requires an accurate estimation of neurocognitive performance, for which individual studies are typically underpowered. Thus, we performed the first combined meta-analysis of fMRI activations and neurocognitive performance in studies investigating response inhibition in BD. METHODS: We used signed differential mapping to combine anatomical coordinates of activation and standardized differences between means to evaluate neurocognitive performance in 30 fMRI studies of response inhibition comparing controls (n = 667) and patients with BD (n = 635). RESULTS: Relative to controls, BD patients underactivated the right inferior frontal gyrus (rIFG) regardless of current mood state and behavioral performance. Unique to euthymia were cortical hyperactivations (left superior temporal, right middle frontal gyri) combined with subcortical hypoactivations (basal ganglia), whereas unique to mania were subcortical hyperactivations (bilateral basal ganglia), combined with cortical hypoactivations (right inferior and medial frontal gyri). The fMRI changes in euthymia were associated with normal cognitive performance, whereas manic patients committed more errors during response inhibition. CONCLUSIONS: The rIFG hypoactivations were congruent with a BD trait, which may underlie the impaired response inhibition in mania. Euthymic BD subjects may compensate for the rIFG hypoactivations by hyperactivations of adjacent cortical areas, yielding comparable performance in inhibitory functions and suggesting possibilities for neuromodulation treatment of these cognitive impairments. The reversal of the activation pattern between mania and euthymia has implications for monitoring of treatment response and identification of imminent relapse.

• Klíčová slova
• Bipolar disorders, Inferior frontal gyrus, Response inhibition, fMRI,
• MeSH
• bipolární porucha komplikace   patologie   MeSH
• čelní lalok krevní zásobení   patologie   MeSH
• databáze bibliografické statistika a číselné údaje   MeSH
• inhibice (psychologie) * MeSH
• kognitivní poruchy komplikace   patologie   MeSH
• kyslík krev   MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• počítačové zpracování obrazu MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• práce podpořená grantem MeSH
• Názvy látek
• kyslík MeSH

• MeSH
• bibliometrie * MeSH
• databáze bibliografické statistika a číselné údaje   MeSH
• publikování statistika a číselné údaje   MeSH
• veterinární lékařství statistika a číselné údaje   MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH