Longitudinal assessment of ventricular volume trajectories in early-stage schizophrenia: evidence of both enlargement and shrinkage.

BACKGROUND: Lateral ventricular enlargement represents a canonical morphometric finding in chronic patients with schizophrenia; however, longitudinal studies elucidating complex dynamic trajectories of ventricular volume change during critical early disease stages are sparse. METHODS: We measured lateral ventricular volumes in 113 first-episode schizophrenia patients (FES) at baseline visit (11.7 months after illness onset, SD = 12.3) and 128 age- and sex-matched healthy controls (HC) using 3T MRI. MRI was then repeated in both FES and HC one year later. RESULTS: Compared to controls, ventricular enlargement was identified in 18.6% of patients with FES (14.1% annual ventricular volume (VV) increase; 95%CI: 5.4; 33.1). The ventricular expansion correlated with the severity of PANSS-negative symptoms at one-year follow-up (p = 0.0078). Nevertheless, 16.8% of FES showed an opposite pattern of statistically significant ventricular shrinkage during ≈ one-year follow-up (-9.5% annual VV decrease; 95%CI: -23.7; -2.4). There were no differences in sex, illness duration, age of onset, duration of untreated psychosis, body mass index, the incidence of Schneiderian symptoms, or cumulative antipsychotic dose among the patient groups exhibiting ventricular enlargement, shrinkage, or no change in VV. CONCLUSION: Both enlargement and ventricular shrinkage are equally present in the early stages of schizophrenia. The newly discovered early reduction of VV in a subgroup of patients emphasizes the need for further research to understand its mechanisms.

mHealth intervention delivered in general practice to increase physical activity and reduce sedentary behaviour of patients with prediabetes and type 2 diabetes (ENERGISED): rationale and study protocol for a pragmatic randomised controlled trial.

BACKGROUND: The growing number of patients with type 2 diabetes and prediabetes is a major public health concern. Physical activity is a cornerstone of diabetes management and may prevent its onset in prediabetes patients. Despite this, many patients with (pre)diabetes remain physically inactive. Primary care physicians are well-situated to deliver interventions to increase their patients' physical activity levels. However, effective and sustainable physical activity interventions for (pre)diabetes patients that can be translated into routine primary care are lacking. METHODS: We describe the rationale and protocol for a 12-month pragmatic, multicentre, randomised, controlled trial assessing the effectiveness of an mHealth intervention delivered in general practice to increase physical activity and reduce sedentary behaviour of patients with prediabetes and type 2 diabetes (ENERGISED). Twenty-one general practices will recruit 340 patients with (pre)diabetes during routine health check-ups. Patients allocated to the active control arm will receive a Fitbit activity tracker to self-monitor their daily steps and try to achieve the recommended step goal. Patients allocated to the intervention arm will additionally receive the mHealth intervention, including the delivery of several text messages per week, with some of them delivered just in time, based on data continuously collected by the Fitbit tracker. The trial consists of two phases, each lasting six months: the lead-in phase, when the mHealth intervention will be supported with human phone counselling, and the maintenance phase, when the intervention will be fully automated. The primary outcome, average ambulatory activity (steps/day) measured by a wrist-worn accelerometer, will be assessed at the end of the maintenance phase at 12 months. DISCUSSION: The trial has several strengths, such as the choice of active control to isolate the net effect of the intervention beyond simple self-monitoring with an activity tracker, broad eligibility criteria allowing for the inclusion of patients without a smartphone, procedures to minimise selection bias, and involvement of a relatively large number of general practices. These design choices contribute to the trial's pragmatic character and ensure that the intervention, if effective, can be translated into routine primary care practice, allowing important public health benefits. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05351359, 28/04/2022).

Pregnancy-induced brain magnetic resonance imaging changes in women with multiple sclerosis.

BACKGROUND AND PURPOSE: The effect of pregnancy on brain changes and radiological disease activity in women with multiple sclerosis (MS) is not well understood. This study was undertaken to describe the dynamics of lesion activity and brain volume changes during the pregnancy and postpartum periods. METHODS: This observational study of 62 women with relapsing-remitting MS included magnetic resonance imaging (221 scans) as well as clinical visits at baseline (<24 and >6 months before pregnancy), prepregnancy (<6 months before pregnancy), postpartum (<3 months after delivery), and follow-up (>12 and <24 months after delivery) periods. RESULTS: The majority of women had a mild disability and a short disease duration (median = 5.5 years). Eighteen (29.0%) women had a relapse during the year preceding pregnancy onset, nine (14.5%) during pregnancy, and 20 (32.3%) in the year following delivery. Disability status remained unchanged during follow-up. Women in the postpartum period (n = 62) had higher T2 lesion volume (median = 1.18 ml vs. 0.94 ml), greater annualized T2 lesion volume increase (0.23 ml vs. 0.0 ml), lower brain parenchymal fraction (85.6% vs. 86.4%), and greater annualized brain volume loss (-1.74% vs. -0.16%) compared with the prepregnancy period (all p < 0.001). At 12-24 months after delivery, women (n = 41) had higher T2 lesion volume (1.16 ml vs. 1.0 ml) and lower brain parenchymal fraction (86.0% vs. 86.5%) compared to the prepregnancy period (both p < 0.001). CONCLUSIONS: The postpartum period was associated with an increase in T2 lesion volume and accelerated brain volume loss in a considerable proportion of women. This should be considered in treatment decision-making and designing clinical trials.

ChildTalks+: a study protocol of a pre-post controlled, paired design study on the use of preventive intervention for children of parents with a mental illness with focus on eating disorders.

BACKGROUND: Children of parents with a mental illness are at high risk of developing a mental disorder as a result of transgenerational transmission. Without effective intervention, they could form the next generation of psychiatric patients. ChildTalks+ is a preventive intervention involving four structured psychoeducational sessions designed for parents affected by a mental disorder and their children. Its aim is to reduce the risk of mental disorders in children of parents with mental illness. This study draws on our clinical practice and involves a group of patients with eating disorders. The aim of the project, which will run in the Czech Republic, is to evaluate the effectiveness of ChildTalks+ methodology. METHODS: ChildTalks+ therapists (professionals from health, social, and educational facilities) will recruit 66 families where a parent is treated for a mental disorder and the family includes children aged 6-18. Paired allocation into an intervention group (N = 33) and a control group (N = 33) will be based on the number of risk factors identified in the family. Both groups will complete questionnaires at the baseline, post-test, and follow-up assessments after six and 12 months. The intervention group will receive the ChildTalks+ intervention within 2 months of the baseline assessment; the control group after the last assessment. Questionnaires will be completed by parents and children aged 12+ and, in two cases, 15+ years. Quantitative data will be supplemented with qualitative data from ChildTalks+ therapists working with patients with eating disorders. DISCUSSION: The ChildTalks+ intervention is expected to strengthen parenting competencies and family protective factors, improve family communication, increase awareness of parental mental health issues, and improve the wellbeing of children of parents with mental illness with long-term sustainable outcomes. The study should contribute to the evidence base for the ChildTalks+ program and help identify key themes in the implementation of similar preventive interventions. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05554458. Registered 26 September 2022. Retrospectively registered.

The molecular epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) in the Czech Republic.

OBJECTIVES: To gain data on the current molecular epidemiology and resistance of MRSA in the Czech Republic. METHODS: Between September 2017 and January 2018, a total of 441 single-patient MRSA isolates were collected from 11 Czech hospitals and analysed by spa typing, SCCmec typing, antibiotic susceptibility testing, detection of the PVL toxin and the arcA gene. RESULTS: Of all MRSA isolates, 81.41% (n = 359) belonged to the CC5-MRSA clone represented by the spa types t003 (n = 136), t586 (n = 92), t014 (n = 81), t002 (n = 20) and other spa types (n = 30); a majority of the CC5 isolates (n = 348, 96.94%) carried SCCmec type II. The occurrence of CC5-MRSA was more likely in older inpatients and associated with a healthcare origin (P < 0.001). The CC5-MRSA isolates were resistant to more antimicrobial drugs compared with the other MRSAs (P < 0.001). Interestingly, t586 was detected in blood samples more often than the other spa types and, contrary to other spa types belonging to CC5-MRSA, t586 was not associated with patients of advanced age. Other frequently found lineages were CC8 (n = 17), CC398 (n = 11) and CC59 (n = 10). The presence of the PVL was detected in 8.62% (n = 38) of the MRSA isolates. CONCLUSIONS: The healthcare-associated CC5-MRSA-II lineage (t003, t586, t014) was found to be predominant in the Czech Republic. t586 is a newly emerging spa type in the Czech Republic, yet reported rarely in other countries. Our observations stress the need for MRSA surveillance in the Czech Republic in order to monitor changes in MRSA epidemiology.

A Real-World Study on the Use of the Alcohol Use Disorders Identification Test (AUDIT) in Men Admitted to a Psychiatric Hospital.

BACKGROUND This real-world study aimed to investigate the use of the Alcohol Use Disorders Identification Test (AUDIT) in men admitted to a psychiatric hospital. MATERIAL AND METHODS The AUDIT questionnaire (10 items) was consecutively administered for a period of 3 years to male patients admitted to a psychiatric hospital (n=636). Laboratory blood tests of biochemical parameters were measured as biomarkers of alcohol consumption. Data were evaluated using linear models with mixed effects in the case of continuous dependent variables and logistic regression models with mixed effects in the case of categorical dependent variables. RESULTS We found that 45.3% of the patients had a high risk of alcohol consumption or alcohol dependence and 54.7% had a low risk of alcohol consumption. The ICD-10 diagnoses of alcohol-related disorders (F1x), psychotic disorders (F2x), affective disorders (F3x), neurotic and psychosomatic disorders (F4x) were statistically significantly associated with total AUDIT score (P<0.001). There was a statistically significant association between the total AUDIT score and length of hospitalization (P=0.004) and the incidence of suicidal thoughts (P=0.003). Plasma concentrations of alanine aminotransferase (P=0.005), aspartate aminotransferase (P<0.001), gamma glutamyltransferase (P=0.001), total cholesterol (P=0.027) and mean corpuscular value of erythrocytes (P<0.001) were statistically significantly increased with a higher AUDIT score. CONCLUSIONS This real-world study showed that the AUDIT questionnaire evaluated the severity of disorders caused by alcohol and their impact on comorbid mental disorders. These results may be helpful in improving targeted interventions in this group of patients.

Semen analysis and treatment risk factors in long-term survivors of childhood cancer.

The objective of this study was to compare semen quality (sperm density, progressive motility and spermia) between long-term childhood cancer survivors and a control group of males. The second objective was to correlate the semen analysis of the survivors with cancer treatment and endocrine status. The semen quality of 143 survivors (median age, 23.6 years) was compared to 200 men (median age, 27.9 years) who had not been diagnosed with cancer. The cancer-related risk factors and gonadotrophin levels were compared. Overall, 65% of the survivors had abnormal semen analysis compared to 26.5% of the controls (p < 0.0001). Survivors with nonaspermia had lower sperm density than the controls (p < 0.001). Other observed correlations were not significant. Survivors who were treated with alkylating agents were more likely to have abnormal semen analysis (p < 0.008). Follicle-stimulating hormone and luteinising hormone levels were significantly elevated (p < 0.0001) in survivors with abnormal semen analysis. The semen quality parameters, except for low sperm density, did not differ in survivors with nonaspermia compared to the controls. The risk factors included treatment with alkylating agents. Elevated gonadotrophin levels correlated with abnormal semen analysis. All cancer survivors should be made aware of the possibility of suffering from cancer treatment-related infertility.

International cooperative study identifies treatment strategy in childhood ambiguous lineage leukemia.

Despite attempts to improve the definitions of ambiguous lineage leukemia (ALAL) during the last 2 decades, general therapy recommendations are missing. Herein, we report a large cohort of children with ALAL and propose a treatment strategy. A retrospective multinational study (International Berlin-Frankfurt-Münster Study of Leukemias of Ambiguous Lineage [iBFM-AMBI2012]) of 233 cases of pediatric ALAL patients is presented. Survival statistics were used to compare the prognosis of subsets and types of treatment. Five-year event-free survival (EFS) of patients with acute lymphoblastic leukemia (ALL)-type primary therapy (80% ± 4%) was superior to that of children who received acute myeloid leukemia (AML)-type or combined-type treatment (36% ± 7.2% and 50% ± 12%, respectively). When ALL- or AML-specific gene fusions were excluded, 5-year EFS of CD19+ leukemia was 83% ± 5.3% on ALL-type primary treatment compared with 0% ± 0% and 28% ± 14% on AML-type and combined-type primary treatment, respectively. Superiority of ALL-type treatment was documented in single-population mixed phenotype ALAL (using World Health Organization and/or European Group for Immunophenotyping of Leukemia definitions) and bilineal ALAL. Treatment with ALL-type protocols is recommended for the majority of pediatric patients with ALAL, including cases with CD19+ ALAL. AML-type treatment is preferred in a minority of ALAL cases with CD19- and no other lymphoid features. No overall benefit of transplantation was documented, and it could be introduced in some patients with a poor response to treatment. As no clear indicator was found for a change in treatment type, this is to be considered only in cases with ≥5% blasts after remission induction. The results provide a basis for a prospective trial.

Serum mannose-binding lectin (MBL) concentrations are reduced in non-pregnant women with previous adverse pregnancy outcomes.

Mannose-binding lectin (MBL) is an important component of the innate immunity, and it is responsible not only for opsonization of micro-organisms, but also for efferocytosis. The aim of this study was to investigate whether MBL concentrations and lectin complement pathway activity are altered in non-pregnant women with previous adverse pregnancy outcomes. Patients were divided into four groups on the basis of their history of pregnancy complications, including control patients who had uncomplicated pregnancies and term deliveries (control, n = 33), and three groups of patients with a history of pregnancy complications, including preterm labour (n = 29), recurrent miscarriage (n = 19) or unexplained intrauterine foetal death (IUFD; n = 17). All women enrolled in the study had an interval of three to six months following their previous pregnancy, and they agreed to have a blood sample taken. We found significantly higher MBL concentrations and functional activity of the lectin complement pathway in healthy controls who had previous uneventful term pregnancies (1341 ng/mL; activity 100% (IQR: 62%-100%)), compared to women with the history of IUFD (684 ng/mL, P = .008; activity 8.5% (IQR: 0%-97.8%), P = .011), recurrent miscarriage (524 ng/mL, P = .022; activity 44% (IQR: 4%-83%), P = .011) or preterm labour (799 ng/mL, P = .022; activity 62.5% (IQR: 0%-83%), P = .003). Our results suggest that inadequate function of the complement lectin pathway is associated with a higher risk of preterm labour, recurrent miscarriage and unexplained intrauterine foetal death.

What matters in chronic Burkholderia cenocepacia infection in cystic fibrosis: Insights from comparative genomics.

Burkholderia cenocepacia causes severe pulmonary infections in cystic fibrosis (CF) patients. Since the bacterium is virtually untreatable by antibiotics, chronic infections persist for years and might develop into fatal septic pneumonia (cepacia syndrome, CS). To devise new strategies to combat chronic B. cenocepacia infections, it is essential to obtain comprehensive knowledge about their pathogenesis. We conducted a comparative genomic analysis of 32 Czech isolates of epidemic clone B. cenocepacia ST32 isolated from various stages of chronic infection in 8 CF patients. High numbers of large-scale deletions were found to occur during chronic infection, affecting preferentially genomic islands and nonessential replicons. Recombination between insertion sequences (IS) was inferred as the mechanism behind deletion formation; the most numerous IS group was specific for the ST32 clone and has undergone transposition burst since its divergence. Genes functionally related to transition metal metabolism were identified as hotspots for deletions and IS insertions. This functional category was also represented among genes where nonsynonymous point mutations and indels occurred parallelly among patients. Another category exhibiting parallel mutations was oxidative stress protection; mutations in catalase KatG resulted in impaired detoxification of hydrogen peroxide. Deep sequencing revealed substantial polymorphism in genes of both categories within the sputum B. cenocepacia ST32 populations, indicating extensive adaptive evolution. Neither oxidative stress response nor transition metal metabolism genes were previously reported to undergo parallel evolution during chronic CF infection. Mutations in katG and copper metabolism genes were overrepresented in patients where chronic infection developed into CS. Among professional phagocytes, macrophages use both hydrogen peroxide and copper for their bactericidal activity; our results thus tentatively point to macrophages as suspects in pathogenesis towards the fatal CS.

Pavement patterns can be designed to improve gait in Parkinson's disease patients.

BACKGROUND: Public spaces are usually designed with respect to various patient populations, but not Parkinson's disease. The objective of this study was to explore what type of easily applicable visual cueing might be used in public spaces and some interiors to improve gait in people with Parkinson's disease. METHODS: Thirty-two patients with freezing of gait walked an 8-meter track on 6 different floor patterns in single- and dual-task conditions in random sequence. The reference pattern was a virtual large transverse chessboard, and the other patterns differed either in size (small floor stones), orientation (diagonal), nature (real paving), regularity (irregular), or no pattern. Time, number of steps, velocity, step length, cadence, and dual-task effect were calculated. The number and total duration of freezing episodes were analyzed. RESULTS: Virtual, large, transverse floor stones improve time (P = 0.0101), velocity (P = 0.0029), number of steps (P = 0.0291), and step length (P = 0.0254) in Parkinson's disease patients compared with walking on no pattern. Virtual floor stones were superior in time and velocity to the real ones. Transverse floor stones were better than diagonal, whereas regular pattern stones were superior to irregular in some gait parameters. Subjectively, the reference pattern was preferred to the irregular one and to no pattern. No direct effect on freezing of gait was observed. CONCLUSIONS: Parkinson's disease patients may benefit from floor patterns incorporating transverse oriented large rectangular visual cues. Because public space can be regulated with respect to people with medical conditions, the relevant legislative documents should be extended to allow for parkinsonian gait disorder. © 2019 International Parkinson and Movement Disorder Society.

A pedometer-based walking intervention with and without email counseling in general practice: a pilot randomized controlled trial.

BACKGROUND: General practitioners play a fundamental role in combatting the current epidemic of physical inactivity, and pedometer-based walking interventions are able to increase physical activity levels of their patients. Supplementing these interventions with email counseling driven by feedback from the pedometer has the potential to further improve their effectiveness but it has to be yet confirmed in clinical trials. Therefore, the aim of our pilot randomized controlled trial is to evaluate the feasibility and potential efficacy of future trials designed to assess the additional benefit of email counseling added to a pedometer-based intervention in a primary care setting. METHODS: Physically inactive patients were opportunistically recruited from four general practices and randomized to a 12-week pedometer-based intervention with or without email counseling. To explore the feasibility of future trials, we assessed the speed and efficiency of recruitment, adherence to wearing the pedometer, and engagement with email counseling. To evaluate the potential efficacy, daily step-count was the primary outcome and blood pressure, waist and hip circumference, and body mass were the secondary outcomes. Additionally, we conducted a qualitative analysis of structured interviews with the participating general practitioners. RESULTS: The opportunistic recruitment has been shown to be feasible and acceptable, but relatively slow and inefficient; moreover, general practitioners selectively recruited overweight and obese patients. Patients manifested high adherence, wearing the pedometer on 83% (± 20) of days. All patients from the counseling group actively participated in email communication and responded to 46% (± 22) of the emails they received. Both groups significantly increased their daily step-count (pedometer-plus-email, + 2119, p = 0.002; pedometer-alone, + 1336, p = 0.03), but the difference between groups was not significant (p = 0.18). When analyzing both groups combined, there was a significant decrease in body mass (- 0.68 kg, p = 0.04), waist circumference (- 1.73 cm, p = 0.03), and systolic blood pressure (- 3.48 mmHg, p = 0.045). CONCLUSIONS: This study demonstrates that adding email counseling to a pedometer-based intervention in a primary care setting is feasible and might have the potential to increase the efficacy of such an intervention in increasing physical activity levels. TRIAL REGISTRATION: The trial was retrospectively registered at ClinicalTrials.gov (ID: NCT03135561 , date: April 26, 2017).

Peripheral blood lymphocytes immunophenotyping predicts disease activity in clinically isolated syndrome patients.

BACKGROUND: Clinically isolated syndrome (CIS) represents first neurological symptoms suggestive of demyelinating lesion in the central nervous system (CNS). Currently, there are no sufficient immunological or genetic markers predicting relapse and disability progression, nor there is evidence of the efficacy of registered disease modifying treatments (DMTs), such as intramuscular interferon beta1a. The aim of the study is to evaluate immunological predictors of a relapse or disability progression. METHODS: One hundred and eighty one patients with CIS were treated with interferon beta1a and followed over the period of 4 years. Lymphocyte subsets were analyzed by flow cytometry. A Kaplan-Meier estimator of survival probability was used to analyze prognosis. For statistical assessment only individual differences between baseline values and values at the time of relapse or confirmed disability progression were analysed. RESULTS: Higher levels of B lymphocytes predicted relapse-free status. On the other hand, a decrease of the naïve subset of cells (CD45RA+ in CD4+) after 12, 24, and 36 months of follow-up were associated with an increased risk of confirmed disability progression. CONCLUSION: Our data suggest that the quantification of lymphocyte subsets in patients after the first demyelinating event suggestive of MS may be an important biomarker.

The aging effect on prostate metabolite concentrations measured by 1H MR spectroscopy.

OBJECTIVE: The effects of aging, magnetic field and the voxel localization on measured concentrations of citrate (Cit), creatine (Cr), cholines (Cho) and polyamines (PA) in a healthy prostate were evaluated. MATERIALS AND METHODS: 36 examinations at both 1.5T and 3T imagers of 52 healthy subjects aged 19-71 years were performed with PRESS 3D-CSI sequences (TE = 120 and 145 ms). Concentrations in laboratory units and their ratios to citrate were calculated using the LCModel technique. Absolute concentrations were also obtained after the application of correction coefficients. Statistical analysis was performed using a robust linear mixed effects model. RESULTS: Significant effects of aging, the magnetic field strength and the voxel position in central (CZ) or peripheral (PZ) zones on all measured metabolites were found. The concentrations (mmol/kg wet tissue) including prediction intervals in a range of 20-70 years were found: Cit: 7.9-17.2; Cho: 1.4-1.7; Cr: 2.8-2.5; PA (as spermine): 0.6-2.1 at 3T in CZ. In PZ, the concentrations were higher by about 10 % as compared to CZ. CONCLUSION: Increasing citrate and spermine concentrations with age are significant and correlate well with a recently described increase of zinc in the prostate. These findings should be considered in decision-making if the values obtained from a subject are in the range of control values.

Azithromycin promotes proliferation, and inhibits inflammation in nasal epithelial cells in primary ciliary dyskinesia.

Primary ciliary dyskinesia (PCD) is a genetic disorder associated with recurrent and chronic respiratory infections due to functional defects of motile cilia. In this study, we aimed to elucidate inflammatory and proliferative responses in PCD respiratory epithelium and evaluate the effect of Azithromycin (AZT) on these responses. Airway basal cells (BCs) were isolated from nasal samples of Wild-type (WT) epitope of healthy donors and PCD donors with bi-allelic mutations in DNAH5, DNAH11 and CCDC39. Cells were expanded in vitro and stimulated with either Lipopolysaccharide (LPS) or vehicle control. Post stimulation, cells were treated with either Azithromycin (AZT) or vehicle control. Cell proliferation was imaged in real-time. Separately, BCs from the same donors were expanded and grown at an air-liquid interface (ALI) to generate a multi-ciliated epithelium (MCE). Once fully mature, cells were stimulated with LPS, AZT, LPS + AZT or vehicle control. Inflammatory profiling was performed on collected media by cytokine Luminex assay. At baseline, there was a significantly higher mean production of pro-inflammatory cytokines by CCDC39 BCs and MCEs when compared to WT, DNAH11 and DNAH5 cells. AZT inhibited production of cytokines induced by LPS in PCD cells. Differences in cell proliferation were noted in PCD and this was also corrected with AZT treatment.

Clostridioides difficile infections were predominantly driven by fluoroquinolone-resistant Clostridioides difficile ribotypes 176 and 001 in Slovakia in 2018-2019.

AIM: To investigate the epidemiology of Clostridioides difficile infection (CDI) in Slovakian hospitals after the emergence of ribotype 176 (027-like) in 2016. METHODS: Between 2018 and 2019, European Centre for Disease Control and Prevention CDI surveillance protocol v2.3 was applied to 14 hospitals, with additional data collected on recent antimicrobial use and the characterization of C. difficile isolates. RESULTS: The mean hospital incidence of CDI was 4.1 cases per 10,000 patient bed-days. One hundred and five (27.6%) in-hospital deaths were reported among the 381 cases. Antimicrobial treatment within the previous 4 weeks was recorded in 90.5% (333/368) of cases. Ribotype (RT)176 was detected in 50% (n=185/370, 14 hospitals) and RT001 was detected in 34.6% (n=128/370,13/14 hospitals) of cases with RT data. Overall, 86% (n=318/370) of isolates were resistant to moxifloxacin by Thr82Ile in GyrA (99.7%). Multi-locus variable tandem repeat analysis showed clonal relatedness of predominant RTs within and between hospitals. Seven of 14 sequenced RT176 isolates and five of 13 RT001 isolates showed between zero and three allelic differences by whole-genome multi-locus sequence typing. The majority of sequenced isolates (24/27) carried the erm(B) gene and 16/27 also carried the aac(6')-aph(2'') gene with the corresponding antimicrobial susceptibility phenotypes. Nine RT176 strains carried the cfr(E)gene and one RT001 strain carried the cfr(C) gene, but without linezolid resistance. CONCLUSIONS: The newly-predominant RT176 and endemic RT001 are driving the epidemiology of CDI in Slovakia. In addition to fluoroquinolones, the use of macrolide-lincosamide-streptogramin B antibiotics can represent another driving force for the spread of these epidemic lineages. In C. difficile, linezolid resistance should be confirmed phenotypically in strains with detected cfr gene(s).

Thermal quantitative sensory testing as a screening tool for cardiac autonomic neuropathy in patients with diabetes mellitus.

INTRODUCTION: Electrophysiological diagnosis of cardiac autonomic neuropathy (CAN) is based on the evaluation of cardiovascular autonomic reflex tests (CARTs). CARTs are relatively time consuming and must be performed under standardized conditions. This study aimed to determine whether thermal quantitative sensory testing (TQST) can be used as a screening tool to identify patients with diabetes at a higher risk of CAN. METHODS: Eighty-five patients with diabetes and 49 healthy controls were included in the study. Neurological examination, CARTs, TQST, biochemical analyses, and neuropathy symptom questionnaires were performed. RESULTS: CAN was diagnosed in 46 patients with diabetes (54%). CAN-positive patients with diabetes had significantly higher warm detection thresholds (WDT) and significantly lower cold detection thresholds (CDT) in all tested regions (thenar, tibia, and the dorsum of the foot). CDT on the dorsum < 21.8°C in combination with CDT on the tibia < 23.15°C showed the best diagnostic ability in CAN prediction, with 97.4 % specificity, 60.9% sensitivity, 96.6% positive predictive value, and 67.3% negative predictive value. CONCLUSION: TQST can be used as a screening tool for CAN before CART.

Long-term effect of transcranial direct current stimulation in the treatment of chronic tinnitus: A randomized, placebo-controlled trial.

Introduction: Tinnitus is an intrusive and chronic illness affecting a significant portion of the population, decreasing affected individuals' quality of life and socioeconomic functioning. Transcranial Direct Current Stimulation (tDCS) is a non-invasive neuromodulatory method utilizing weak electrical currents to elicit short and long-term central nervous system changes. Several studies have proven its effect on tinnitus. We aimed to broaden the knowledge and provide data on the effect and its retention. Methods: In the randomized, double-blinded, sham-controlled trial, 39 patients (active n = 19, sham n = 20) underwent bifrontal tDCS (anode over right dorsolateral prefrontal cortex (DLPFC), cathode left DLPFC, current of 1.5 mA, 20 min, 6 sessions in 2 weeks). Tinnitus Functional Index (TFI), Iowa Tinnitus Handicap Questionnaire (ITHQ), Beck Anxiety Inventory (BAI), Zung Self-Rating Depression Scale (SDS), and WHO-Quality of Life-BREF were employed in 4 evaluation points, including the follow-ups of 6 weeks and 6 months. Results: We reached a delayed, significant long-term improvement (p < 0.05) in auditory difficulties associated with tinnitus and noticed it even after 6 months compared to placebo. We also reached a short-term, negative effect in the psychological domain of WHO-Quality of Life-BREF (p < 0.05). Not all subdomains of TFI and ITHQ reached statistical significance during the data analysis, even though specific positive trends were noticed. Conclusion: We proved partial, positive, long-term effects of tDCS on tinnitus and short-term, negative, transient effect on a specific aspect of the general quality of life. We expanded upon the results of previous trials and provided data concerning the longevity and the precise effect of multiple sessions, bifrontal DLPFC tDCS. Our sample size (n = 39) was limited, which might have contributed to the lesser statistical power of the analyzed items. Clinical trial registration: [www.ClinicalTrials.gov], identifier [NCT05437185].

Fidaxomicin versus metronidazole, vancomycin and their combination for initial episode, first recurrence and severe Clostridioides difficile infection - An observational cohort study.

PURPOSE: We aimed to evaluate the efficacy of different antibiotic regimens for the treatment of Clostridioides difficile infection (CDI) with regard to the CDI episode number and disease severity. METHODS: An observation cohort study included 271 CDI patients hospitalised between 2013-2016. Univariate logistic regression was used to evaluate the association between patients' clinical outcome (sustained clinical cure or recurrence) in a 60-day follow-up and the antibiotic regimen used (oral metronidazole, oral vancomycin, combination of oral vancomycin and metronidazole, oral fidaxomicin). Subgroup analyses, based on CDI episode number and severity, were performed. RESULTS: In the overall population, fidaxomicin was superior to metronidazole, vancomycin or their combination, for a sustained clinical response and in the prevention of recurrent CDI (rCDI). In the subgroup analyses, fidaxomicin was superior to vancomycin or metronidazole for a sustained clinical response and in the prevention of rCDI in the initial episode, first recurrence and non-severe cases. In the oral treatment of severe CDI, fidaxomicin had a similar treatment outcome to vancomycin and none of the antibiotic treatments were superior in the prevention of rCDI. Fidaxomicin, vancomycin, or a combination of metronidazole and vancomycin, had similar outcomes for sustained clinical response and prevention of rCDI in patients with multiple rCDI. CONCLUSION: Fidaxomicin was superior to metronidazole or vancomycin for the treatment of the initial episode, first recurrence, and non-severe CDI.

Evaluation of a Clinical Index as a Predictive Tool for Primary Ciliary Dyskinesia.

BACKGROUND: In primary ciliary dyskinesia (PCD) there is no single diagnostic test. Different predictive tools have been proposed to guide referral of high-risk patients for further diagnostic workup. We aimed to test clinical index (CI) on a large unselected cohort and compare its characteristics with other widely used tools-PICADAR and NA-CDCF. METHODS: CI, PICADAR, and NA-CDCF scores were calculated in 1401 patients with suspected PCD referred to our center. Their predictive characteristics were analyzed using receiver operating characteristics (ROC) curves and compared to each other. Nasal nitric oxide (nNO) was measured in 569 patients older than 3 years. RESULTS: PCD was diagnosed in 67 (4.8%) patients. CI, PICADAR, and NA-CDCF scores were higher in PCD than in nonPCD group (all p < 0.001). The area under the ROC curve (AUC) for CI was larger than for NA-CDCF (p = 0.005); AUCPICADAR and AUCNA-CDCF did not differ (p = 0.093). An overlap in signs and symptoms among tools was identified. PICADAR could not be assessed in 86 (6.1%) patients without chronic wet cough. For CI laterality or congenital heart defects assessment was not necessary. nNO further improved predictive power of all three tools. CONCLUSION: CI is a feasible predictive tool for PCD that may outperform PICADAR and NA-CFCD.