Raspodjela rizičnih čimbenika za moždani udar u istočnoj Hrvatskoj

The aim of this study was to determine the distribution of risk factors according to age, gender, subtypes and recurrence of stroke in eastern Croatia. The study included 250 acute stroke patients admitted to University Department of Neurology, Osijek University Hospital Centre in 2011. Patients were grouped according to age, gender, subtypes and recurrence of stroke. The study showed significant differences in the distribution of cigarette smoking, diabetes, cardiomyopathy and hyperuricemia according to patient age. According to gender, male patients had a significantly higher prevalence of smoking and alcohol abuse, whereas in female patients the prevalence of arterial hypertension, atrial fibrillation and hyperuricemia was significantly higher. Regarding stroke subtypes, significant differences were noticed in the prevalence of arterial hypertension, atrial fibrillation, cardiomyopathy and cerebral blood vessel stenosis. Atrial fibrillation was significantly more common in first-ever than in recurrent stroke. Study results identified the groups of patients requiring special attention regarding particular risk factors in eastern Croatia and emphasized the need of developing regional strategies of screening, prevention and holistic care for stroke patients.Cilj ovoga istraživanja bio je odrediti raspodjelu rizičnih čimbenika u bolesnika s moždanim udarom u istočnoj Hrvatskoj prema dobi, spolu, podtipovima i ponovnom javljanju. U istraživanje bilo je uključeno 250 bolesnika koji su pretrpjeli akutni moždani udar i primljeni su na Kliniku za neurologiju Kliničkoga bolničkog centra Osijek u 2011. godini. Bolesnici su podijeljeni prema dobi, spolu, podtipovima i ponovnom javljanju. Istraživanje je pokazalo značajne razlike u raspodjeli pušenja cigareta, dijabetesa, kardiomiopatije i hiperuricemije prema dobi bolesnika. Prema spolu, učestalost pušenja i zlouporabe alkohola bila je značajno veća kod muških bolesnika, dok je učestalost arterijske hipertenzije, atrijske fibrilacije i hiperuricemije bila značajno veća kod žena. Prema podtipovima moždanog udara, značajne razlike uočene su kod učestalosti arterijske hipertenzije, atrijske fibrilacije, kardiomiopatije i stenoze cerebralnih krvnih žila. Atrijska fibrilacija bila je značajno češća u prvom nego u ponovljenom moždanom udaru. Naši rezultati pokazuju koje skupine bolesnika u istočnoj Hrvatskoj zahtijevaju posebnu pozornost s obzirom na pojedine rizične čimbenike te naglašavaju potrebu osmišljavanja regionalnih strategija za probir, prevenciju i holističku brigu za oboljele od moždanog udara

Do Nutrition Habits Influence on Parkinson`\u27s Disease Clinical Presentation?

Introduction: Parkinson\u27s disease (PD) is the second most common neurodegenerative disorder characterized with alpha-synuclein pathology. For the majority of patients, except for some genetic forms, etiology is still unknown. There are some implications that food intake and gut microbiota could contribute to PD. Aim: The aim of this paper is to analyze the influence of protein, fruit and vegetable intake on the clinical presentation of idiopathic Parkinson disease Patients and methods: Patients with idiopathic PD were surveyed for demographic data and nutritional habits in regards to protein, fruit and vegetable intake. Motor symptoms were evaluated using the Unified Parkinson Disease Rating Scale (UPDRS) part III and IV, cognitive impairment using Mini Mental State Examination (MMSE) and depression using Beck Depression Inventory (BDI). Results: We have analyzed data of 96 patients. Patients using fewer dairy products have more often tremor type of PD (p<0.040). We did not find any differences in severity of motor symptoms, disease stage, age when disease start, frequency of motor complications and fluctuation of therapy, depression and cognitive impairment according to protein, fruit and vegetable ingestion. Conclusion: Higher intake of dairy products could influence the appearance of less favorable forms of Parkinson\u27s disease (rigor type). Protein, fruit and vegetable intake do not influence the disease appearance, severity of motor symptoms, motor fluctuation and complication of therapy, disease stage, the appearance of cognitive impairment nor depression in Parkinson\u27s disease patients. (Tomic S, Pekic V, Popijac Z, Pucic T, Petek Vinkovic M, Popovic Z, Resan B, Gilman Kuric T. Do Nutrition Habits Influence the Clinical Presentation of Parkinson’s Disease?. SEEMEDJ 2019; 3(2); 11-21

Distribution of Stroke Risk Factors in Eastern Croatia

The aim of this study was to determine the distribution of risk factors according to age, gender, subtypes and recurrence of stroke in eastern Croatia. The study included 250 acute stroke patients admitted to University Department of Neurology, Osijek University Hospital Centre in 2011. Patients were grouped according to age, gender, subtypes and recurrence of stroke. The study showed significant differences in the distribution of cigarette smoking, diabetes, cardiomyopathy and hyperuricemia according to patient age. According to gender, male patients had a significantly higher prevalence of smoking and alcohol abuse, whereas in female patients the prevalence of arterial hypertension, atrial fibrillation and hyperuricemia was significantly higher. Regarding stroke subtypes, significant differences were noticed in the prevalence of arterial hypertension, atrial fibrillation, cardiomyopathy and cerebral blood vessel stenosis. Atrial fibrillation was significantly more common in first-ever than in recurrent stroke. Study results identified the groups of patients requiring special attention regarding particular risk factors in eastern Croatia and emphasized the need of developing regional strategies of screening, prevention and holistic care for stroke patients

The influence of smoking and parity on serum markers for Down's syndrome screening

Objective: To evaluate the impact of smoking and number of previous births on maternal serum levels of α-fetoprotein and free β-subunit of human chorionic gonadotropin (free β-hCG). Methods: The study included 3,252 completed unaffected singleton pregnancies that proceeded beyond 37 weeks’ gestation and resulted with a birth of healthy child. Smoking status of mothers and data concerning gravidity and parity were collected at the sampling date. Serum markers were measured between 13 and 22 gestational weeks, corrected for maternal weight, and converted to multiples of median (MoM) for unaffected pregnancy of the corresponding gestational age. Median MoM values for both markers were examined in relation to both: smoking habits and number of previous births. Results: Smokers had significantly decreased free β-hCG MoM values compared to nonsmokers (p < 0.001). The median levels showed a negative relationship with the number of previous births. The significance of a decreasing trend was proved, both in smokers (p < 0.001) and nonsmokers (p < 0.001). The median maternal serum α-fetoprotein MoM values did not show any significant dependence, neither with regard to smoking (p = 0.65) nor with regard to parity (p = 0.07). Conclusions: The recommendable adjustment of serum markers to smoking habits, especially concerning the free β-hCG levels, would be worthwhile. The evidence of the coexisting influence of parity on serum levels of free β-hCG, both in smokers and nonsmokers, should perhaps be a stimulus for reconsideration of which corrections the screening performance is dependent on

Statins and cognitive decline in patients with Alzheimer’s and mixed dementia: a longitudinal registry-based cohort study

Abstract Background Disturbances in brain cholesterol homeostasis may be involved in the pathogenesis of Alzheimer’s disease (AD). Lipid-lowering medications could interfere with neurodegenerative processes in AD through cholesterol metabolism or other mechanisms. Objective To explore the association between the use of lipid-lowering medications and cognitive decline over time in a cohort of patients with AD or mixed dementia with indication for lipid-lowering treatment. Methods A longitudinal cohort study using the Swedish Registry for Cognitive/Dementia Disorders, linked with other Swedish national registries. Cognitive trajectories evaluated with mini-mental state examination (MMSE) were compared between statin users and non-users, individual statin users, groups of statins and non-statin lipid-lowering medications using mixed-effect regression models with inverse probability of drop out weighting. A dose-response analysis included statin users compared to non-users. Results Our cohort consisted of 15,586 patients with mean age of 79.5 years at diagnosis and a majority of women (59.2 %). A dose-response effect was demonstrated: taking one defined daily dose of statins on average was associated with 0.63 more MMSE points after 3 years compared to no use of statins (95% CI: 0.33;0.94). Simvastatin users showed 1.01 more MMSE points (95% CI: 0.06;1.97) after 3 years compared to atorvastatin users. Younger (< 79.5 years at index date) simvastatin users had 0.80 more MMSE points compared to younger atorvastatin users (95% CI: 0.05;1.55) after 3 years. Simvastatin users had 1.03 more MMSE points (95% CI: 0.26;1.80) compared to rosuvastatin users after 3 years. No differences regarding statin lipophilicity were observed. The results of sensitivity analysis restricted to incident users were not consistent. Conclusions Some patients with AD or mixed dementia with indication for lipid-lowering medication may benefit cognitively from statin treatment; however, further research is needed to clarify the findings of sensitivity analyses

A 12-gene pharmacogenetic panel to prevent adverse drug reactions: an open-label, multicentre, controlled, cluster-randomised crossover implementation study

© 2023Background: The benefit of pharmacogenetic testing before starting drug therapy has been well documented for several single gene–drug combinations. However, the clinical utility of a pre-emptive genotyping strategy using a pharmacogenetic panel has not been rigorously assessed. Methods: We conducted an open-label, multicentre, controlled, cluster-randomised, crossover implementation study of a 12-gene pharmacogenetic panel in 18 hospitals, nine community health centres, and 28 community pharmacies in seven European countries (Austria, Greece, Italy, the Netherlands, Slovenia, Spain, and the UK). Patients aged 18 years or older receiving a first prescription for a drug clinically recommended in the guidelines of the Dutch Pharmacogenetics Working Group (ie, the index drug) as part of routine care were eligible for inclusion. Exclusion criteria included previous genetic testing for a gene relevant to the index drug, a planned duration of treatment of less than 7 consecutive days, and severe renal or liver insufficiency. All patients gave written informed consent before taking part in the study. Participants were genotyped for 50 germline variants in 12 genes, and those with an actionable variant (ie, a drug–gene interaction test result for which the Dutch Pharmacogenetics Working Group [DPWG] recommended a change to standard-of-care drug treatment) were treated according to DPWG recommendations. Patients in the control group received standard treatment. To prepare clinicians for pre-emptive pharmacogenetic testing, local teams were educated during a site-initiation visit and online educational material was made available. The primary outcome was the occurrence of clinically relevant adverse drug reactions within the 12-week follow-up period. Analyses were irrespective of patient adherence to the DPWG guidelines. The primary analysis was done using a gatekeeping analysis, in which outcomes in people with an actionable drug–gene interaction in the study group versus the control group were compared, and only if the difference was statistically significant was an analysis done that included all of the patients in the study. Outcomes were compared between the study and control groups, both for patients with an actionable drug–gene interaction test result (ie, a result for which the DPWG recommended a change to standard-of-care drug treatment) and for all patients who received at least one dose of index drug. The safety analysis included all participants who received at least one dose of a study drug. This study is registered with ClinicalTrials.gov, NCT03093818 and is closed to new participants. Findings: Between March 7, 2017, and June 30, 2020, 41 696 patients were assessed for eligibility and 6944 (51·4 % female, 48·6% male; 97·7% self-reported European, Mediterranean, or Middle Eastern ethnicity) were enrolled and assigned to receive genotype-guided drug treatment (n=3342) or standard care (n=3602). 99 patients (52 [1·6%] of the study group and 47 [1·3%] of the control group) withdrew consent after group assignment. 652 participants (367 [11·0%] in the study group and 285 [7·9%] in the control group) were lost to follow-up. In patients with an actionable test result for the index drug (n=1558), a clinically relevant adverse drug reaction occurred in 152 (21·0%) of 725 patients in the study group and 231 (27·7%) of 833 patients in the control group (odds ratio [OR] 0·70 [95% CI 0·54–0·91]; p=0·0075), whereas for all patients, the incidence was 628 (21·5%) of 2923 patients in the study group and 934 (28·6%) of 3270 patients in the control group (OR 0·70 [95% CI 0·61–0·79]; p <0·0001). Interpretation: Genotype-guided treatment using a 12-gene pharmacogenetic panel significantly reduced the incidence of clinically relevant adverse drug reactions and was feasible across diverse European health-care system organisations and settings. Large-scale implementation could help to make drug therapy increasingly safe. Funding: European Union Horizon 2020

Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study

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Ofatumumab versus Teriflunomide in Multiple Sclerosis

BACKGROUND: Ofatumumab, a subcutaneous anti-CD20 monoclonal antibody, selectively depletes B cells. Teriflunomide, an oral inhibitor of pyrimidine synthesis, reduces T-cell and B-cell activation. The relative effects of these two drugs in patients with multiple sclerosis are not known. METHODS: In two double-blind, double-dummy, phase 3 trials, we randomly assigned patients with relapsing multiple sclerosis to receive subcutaneous ofatumumab (20 mg every 4 weeks after 20-mg loading doses at days 1, 7, and 14) or oral teriflunomide (14 mg daily) for up to 30 months. The primary end point was the annualized relapse rate. Secondary end points included disability worsening confirmed at 3 months or 6 months, disability improvement confirmed at 6 months, the number of gadolinium-enhancing lesions per T1-weighted magnetic resonance imaging (MRI) scan, the annualized rate of new or enlarging lesions on T2-weighted MRI, serum neurofilament light chain levels at month 3, and change in brain volume. RESULTS: Overall, 946 patients were assigned to receive ofatumumab and 936 to receive teriflunomide; the median follow-up was 1.6 years. The annualized relapse rates in the ofatumumab and teriflunomide groups were 0.11 and 0.22, respectively, in trial 1 (difference, -0.11; 95% confidence interval [CI], -0.16 to -0.06; P<0.001) and 0.10 and 0.25 in trial 2 (difference, -0.15; 95% CI, -0.20 to -0.09; P<0.001). In the pooled trials, the percentage of patients with disability worsening confirmed at 3 months was 10.9% with ofatumumab and 15.0% with teriflunomide (hazard ratio, 0.66; P = 0.002); the percentage with disability worsening confirmed at 6 months was 8.1% and 12.0%, respectively (hazard ratio, 0.68; P = 0.01); and the percentage with disability improvement confirmed at 6 months was 11.0% and 8.1% (hazard ratio, 1.35; P = 0.09). The number of gadolinium-enhancing lesions per T1-weighted MRI scan, the annualized rate of lesions on T2-weighted MRI, and serum neurofilament light chain levels, but not the change in brain volume, were in the same direction as the primary end point. Injection-related reactions occurred in 20.2% in the ofatumumab group and in 15.0% in the teriflunomide group (placebo injections). Serious infections occurred in 2.5% and 1.8% of the patients in the respective groups. CONCLUSIONS: Among patients with multiple sclerosis, ofatumumab was associated with lower annualized relapse rates than teriflunomide. (Funded by Novartis; ASCLEPIOS I and II ClinicalTrials.gov numbers, NCT02792218 and NCT02792231.)