Summary
Objective
To analyze the effectiveness and tolerability of perampanel across different seizure types in routine clinical care of patients with idiopathic generalized epilepsy (IGE).
Methods
...This multicenter, retrospective, 1‐year observational study collected data from patient records at 21 specialist epilepsy units in Spain. All patients who were aged ≥12 years, prescribed perampanel before December 2016, and had a confirmed diagnosis of IGE were included.
Results
The population comprised 149 patients with IGE (60 with juvenile myoclonic epilepsy, 51 generalized tonic–clonic seizures GTCS only, 21 juvenile absence epilepsy, 10 childhood absence epilepsy, 6 adulthood absence epilepsy, and one Jeavons syndrome). Mean age was 36 years. The retention rate at 12 months was 83% (124/149), and 4 mg was the most common dose. At 12 months, the seizure‐free rate was 59% for all seizures (88/149); 63% for GTCS (72/115), 65% for myoclonic seizures (31/48), and 51% for absence seizures (24/47). Seizure frequency was reduced significantly at 12 months relative to baseline for GTCS (78%), myoclonic (65%), and absence seizures (48%). Increase from baseline seizure frequency was seen in 5.2% of patients with GTCS seizures, 6.3% with myoclonic, and 4.3% with absence seizures. Perampanel was effective regardless of epilepsy syndrome, concomitant antiepileptic drugs (AEDs), and prior AEDs, but retention and seizure freedom were significantly higher when used as early add‐on (after ≤2 prior AEDs) than late (≥3 prior AEDs). Adverse events were reported in 50% of patients over 12 months, mostly mild or moderate, and irritability (23%), somnolence (15%), and dizziness (14%) were most frequent.
Significance
In routine clinical care of patients with IGE, perampanel improved seizure outcomes for GTCS, myoclonic seizures, and absence seizures, with few discontinuations due to adverse events. This is the first real‐world evidence with perampanel across different seizure types in IGE.
We evaluated treatment outcomes in a prospective registry of human immunodeficiency virus/hepatitis C virus (HCV)–coinfected patients treated with interferon‐free direct‐acting antiviral agent–based ...therapy in hospitals from the region of Madrid between November 2014 and August 2016. We assessed sustained viral response at 12 weeks after completion of treatment and used multivariable logistic regression to identify predictors of treatment failure. We evaluated 2,369 patients, of whom 59.5% did not have cirrhosis, 33.9% had compensated cirrhosis, and 6.6% had decompensated cirrhosis. The predominant HCV genotypes were 1a (40.9%), 4 (22.4%), 1b (15.1%), and 3 (15.0%). Treatment regimens included sofosbuvir (SOF)/ledipasvir (61.9%), SOF plus daclatasvir (14.6%), dasabuvir plus ombitasvir/paritaprevir/ritonavir (13.2%), and other regimens (10.3%). Ribavirin was used in 30.6% of patients. Less than 1% of patients discontinued therapy owing to adverse events. The frequency of sustained viral response by intention‐to‐treat analysis was 92.0% (95% confidence interval, 90.9%‐93.1%) overall, 93.8% (92.4%‐95.0%) for no cirrhosis, 91.0% (88.8%‐92.9%) for compensated cirrhosis, and 80.8% (73.7%‐86.6%) for decompensated cirrhosis. The factors associated with treatment failure were male sex (adjusted odds ratio, 1.75; 95% confidence interval, 1.14‐2.69), Centers for Diseases Control and Prevention category C (adjusted odds ratio, 1.65; 95% confidence interval, 1.12‐2.41), a baseline cluster of differentiation 4–positive (CD4+) T‐cell count <200/mm3 (adjusted odds ratio, 2.30; 95% confidence interval, 1.35‐3.92), an HCV RNA load ≥800,000 IU/mL (adjusted odds ratio, 1.63; 95% confidence interval, 1.14‐2.36), compensated cirrhosis (adjusted odds ratio, 1.35; 95% confidence interval, 0.96‐1.89), decompensated cirrhosis (adjusted odds ratio, 2.92; 95% confidence interval, 1.76‐4.87), and the use of SOF plus simeprevir, SOF plus ribavirin, and simeprevir plus daclatasvir. Conclusion: In this large real‐world study, direct‐acting antiviral agent–based therapy was safe and highly effective in coinfected patients; predictors of failure included gender, human immunodeficiency virus–related immunosuppression, HCV RNA load, severity of liver disease, and the use of suboptimal direct‐acting antiviral agent–based regimens. (Hepatology 2018;68:32‐47).
Framed within Self-Determination Theory, the purpose of the present study was to test the effects of a training program with physical education (PE) teachers. Participants were 21 high school PE ...teachers (experimental group, n = 10; control group, n = 11), and their 836 students, aged 12 to 16 years. Teachers in the experimental group received a training program consisting of strategies to support autonomy, competence, and relatedness need satisfaction. A repeated measures ANCOVA was carried out for each dependent variable. After the intervention, students in the experimental group significantly increased their scores on autonomy support, relatedness support, autonomy satisfaction, autonomous motivation, controlled motivation, and intention to be physically active, as compared to the control group. These findings emphasize the utility of a training program with PE teachers to promote the students' psychological need satisfaction, and hence, self-determined motivation toward PE classes.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
ABSTRACTRodríguez-Rosell, D, Mora-Custodio, R, Franco-Márquez, F, Yáñez-García, JM, González-Badillo, JJ. Traditional vs. sport-specific vertical jump testsreliability, validity, and relationship ...with the legs strength and sprint performance in adult and teen soccer and basketball players. J Strength Cond Res 31(1)196–206, 2017—The vertical jump is considered an essential motor skill in many team sports. Many protocols have been used to assess vertical jump ability. However, controversy regarding test selection still exists based on the reliability and specificity of the tests. The main aim of this study was to analyze the reliability and validity of 2 standardized (countermovement jump CMJ and Abalakov jump AJ) and 2 sport-specific (run-up with 2 2-LEGS or 1 leg 1-LEG take-off jump) vertical jump tests, and their usefulness as predictors of sprint and strength performance for soccer (n = 127) and basketball (n = 59) players in 3 different categories (Under-15, Under-18, and Adults). Three attempts for each of the 4 jump tests were recorded. Twenty-meter sprint time and estimated 1 repetition maximum in full squat were also evaluated. All jump tests showed high intraclass correlation coefficients (0.969–0.995) and low coefficients of variation (1.54–4.82%), although 1-LEG was the jump test with the lowest absolute and relative reliability. All selected jump tests were significantly correlated (r = 0.580–0.983). Factor analysis resulted in the extraction of one principal component, which explained 82.90–95.79% of the variance of all jump tests. The 1-LEG test showed the lowest associations with sprint and strength performance. The results of this study suggest that CMJ and AJ are the most reliable tests for the estimation of explosive force in soccer and basketball players in different age categories.
IMPORTANCE More than 70% of patients with resistant hypertension have obstructive sleep apnea (OSA). However, there is little evidence about the effect of continuous positive airway pressure (CPAP) ...treatment on blood pressure in patients with resistant hypertension. OBJECTIVE To assess the effect of CPAP treatment on blood pressure values and nocturnal blood pressure patterns in patients with resistant hypertension and OSA. DESIGN, SETTING, AND PARTICIPANTS Open-label, randomized, multicenter clinical trial of parallel groups with blinded end point design conducted in 24 teaching hospitals in Spain involving 194 patients with resistant hypertension and an apnea-hypopnea index (AHI) of 15 or higher. Data were collected from June 2009 to October 2011. INTERVENTIONS CPAP or no therapy while maintaining usual blood pressure control medication. MAIN OUTCOMES AND MEASURES The primary end point was the change in 24-hour mean blood pressure after 12 weeks. Secondary end points included changes in other blood pressure values and changes in nocturnal blood pressure patterns. Both intention-to-treat (ITT) and per-protocol analyses were performed. RESULTS A total of 194 patients were randomly assigned to receive CPAP (n = 98) or no CPAP (control; n = 96). The mean AHI was 40.4 (SD, 18.9) and an average of 3.8 antihypertensive drugs were taken per patient. Baseline 24-hour mean blood pressure was 103.4 mm Hg; systolic blood pressure (SBP), 144.2 mm Hg; and diastolic blood pressure (DBP), 83 mm Hg. At baseline, 25.8% of patients displayed a dipper pattern (a decrease of at least 10% in the average nighttime blood pressure compared with the average daytime blood pressure). The percentage of patients using CPAP for 4 or more hours per day was 72.4%. When the changes in blood pressure over the study period were compared between groups by ITT, the CPAP group achieved a greater decrease in 24-hour mean blood pressure (3.1 mm Hg 95% CI, 0.6 to 5.6; P = .02) and 24-hour DBP (3.2 mm Hg 95% CI, 1.0 to 5.4; P = .005), but not in 24-hour SBP (3.1 mm Hg 95% CI, −0.6 to 6.7; P = .10) compared with the control group. Moreover, the percentage of patients displaying a nocturnal blood pressure dipper pattern at the 12-week follow-up was greater in the CPAP group than in the control group (35.9% vs 21.6%; adjusted odds ratio OR, 2.4 95% CI, 1.2 to 5.1; P = .02). There was a significant positive correlation between hours of CPAP use and the decrease in 24-hour mean blood pressure (r = 0.29, P = .006), SBP (r = 0.25; P = .02), and DBP (r = 0.30, P = .005). CONCLUSIONS AND RELEVANCE Among patients with OSA and resistant hypertension, CPAP treatment for 12 weeks compared with control resulted in a decrease in 24-hour mean and diastolic blood pressure and an improvement in the nocturnal blood pressure pattern. Further research is warranted to assess longer-term health outcomes. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00616265
In recent years, honeybees (Apis mellifera) have been strangely disappearing from their hives, and strong colonies have suddenly become weak and died. The precise aetiology underlying the ...disappearance of the bees remains a mystery. However, during the same period, Nosema ceranae, a microsporidium of the Asian bee Apis cerana, seems to have colonized A. mellifera, and it's now frequently detected all over the world in both healthy and weak honeybee colonies. For first time, we show that natural N. ceranae infection can cause the sudden collapse of bee colonies, establishing a direct correlation between N. ceranae infection and the death of honeybee colonies under field conditions. Signs of colony weakness were not evident until the queen could no longer replace the loss of the infected bees. The long asymptomatic incubation period can explain the absence of evident symptoms prior to colony collapse. Furthermore, our results demonstrate that healthy colonies near to an infected one can also become infected, and that N. ceranae infection can be controlled with a specific antibiotic, fumagillin. Moreover, the administration of 120 mg of fumagillin has proven to eliminate the infection, but it cannot avoid reinfection after 6 months. We provide Koch's postulates between N. ceranae infection and a syndrome with a long incubation period involving continuous death of adult bees, non-stop brood rearing by the bees and colony loss in winter or early spring despite the presence of sufficient remaining pollen and honey.
Objective
Gain‐of‐function NLRP3 mutations cause cryopyrin‐associated periodic syndrome (CAPS), with gene mosaicism playing a relevant role in the pathogenesis. This study was undertaken to ...characterize the genetic cause underlying late‐onset but otherwise typical CAPS.
Methods
We studied a 64‐year‐old patient who presented with recurrent episodes of urticaria‐like rash, fever, conjunctivitis, and oligoarthritis at age 56 years. DNA was extracted from both unfractionated blood and isolated leukocyte and CD34+ subpopulations. Genetic studies were performed using both the Sanger method of DNA sequencing and next‐generation sequencing (NGS) methods. In vitro and ex vivo analyses were performed to determine the consequences that the presence of the variant have in the normal structure or function of the protein of the detected variant.
Results
NGS analyses revealed the novel p.Gln636Glu NLRP3 variant in unfractionated blood, with an allele frequency (18.4%) compatible with gene mosaicism. Sanger sequence chromatograms revealed a small peak corresponding to the variant allele. Amplicon‐based deep sequencing revealed somatic NLRP3 mosaicism restricted to myeloid cells (31.8% in monocytes, 24.6% in neutrophils, and 11.2% in circulating CD34+ common myeloid progenitor cells) and its complete absence in lymphoid cells. Functional analyses confirmed the gain‐of‐function behavior of the gene variant and hyperactivity of the NLRP3 inflammasome in the patient. Treatment with anakinra resulted in good control of the disease.
Conclusion
We identified the novel gain‐of‐function p.Gln636Glu NLRP3 mutation, which was detected as a somatic mutation restricted to myeloid cells, as the cause of late‐onset but otherwise typical CAPS. Our results expand the diversity of CAPS toward milder phenotypes than previously reported, including those starting during adulthood.
Background EUS-guided cholangiopancreatography (ESCP) allows transmural access to biliopancreatic ducts when ERCP fails. Data regarding technical details, safety, and outcomes of ESCP are still ...unknown. Objective To evaluate outcomes of ESCP in community and referral centers at the initial development phase of this procedure, to identify the ESCP stages with higher risk of failure, and to evaluate the influence on outcomes of factors related to the endoscopist. Design Multicenter retrospective study. Setting Public health system hospitals with experience in ESCP in Spain. Patients A total of 125 patients underwent ESCP in 19 hospitals, with an experience of <20 procedures. Intervention ESCP. Main Outcome Measurements Technical success and complication rates in the initial phase of implantation of ESCP are described. The influence of technical characteristics and endoscopist features on outcomes was analyzed. Results A total of 125 patients from 19 hospitals were included. Biliary ESCP was performed in 106 patients and pancreatic ESCP was performed in 19. Technical success was achieved in 84 patients (67.2%) followed by clinical success in 79 (63.2%). Complications occurred in 29 patients (23.2%). Unsuccessful manipulation of the guidewire was responsible for 68.2% of technical failures, and 58.6% of complications were related to problems with the transmural fistula. Limitations Retrospective study. Conclusion Outcomes of ESCP during its implantation stage reached a technical success rate of 67.2%, with a complication rate of 23.2%. Intraductal manipulation of the guidewire seems to be the most difficult stage of the procedure.
Dysbalance in gut microbiota has been linked to increased microbial translocation, leading to chronic inflammation in HIV-patients, even under effective HAART. Moreover, microbial translocation is ...associated with insufficient reconstitution of CD4+T cells, and contributes to the pathogenesis of immunologic non-response. In a double-blind, randomised, placebo-controlled trial, we recently showed that, compared to placebo, 12 weeks treatment with probiotic Saccharomyces boulardii significantly reduced plasma levels of bacterial translocation (Lipopolysaccharide-binding protein or LBP) and systemic inflammation (IL-6) in 44 HIV virologically suppressed patients, half of whom (n = 22) had immunologic non-response to antiretroviral therapy (<270 CD4+Tcells/μL despite long-term suppressed viral load). The aim of the present study was to investigate if this beneficial effect of the probiotic Saccharomyces boulardii is due to modified gut microbiome composition, with a decrease of some species associated with higher systemic levels of microbial translocation and inflammation. In this study, we used 16S rDNA gene amplification and parallel sequencing to analyze the probiotic impact on the composition of the gut microbiome (faecal samples) in these 44 patients randomized to receive oral supplementation with probiotic or placebo for 12 weeks. Compared to the placebo group, in individuals treated with probiotic we observed lower concentrations of some gut species, such as those of the Clostridiaceae family, which were correlated with systemic levels of bacterial translocation and inflammation markers. In a sub-study of these patients, we observed significantly higher parameters of microbial translocation (LBP, soluble CD14) and systemic inflammation in immunologic non-responders than in immunologic responders, which was correlated with a relative abundance of specific gut bacterial groups (Lachnospiraceae genus and Proteobacteria). Thus, in this work, we propose a new therapeutic strategy using the probiotic yeast S. boulardii to modify gut microbiome composition. Identifying pro-inflammatory species in the gut microbiome could also be a useful new marker of poor immune response and a new therapeutic target.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We assessed the prognostic value of minimal residual disease (MRD) detection in multiple myeloma (MM) patients using a sequencing-based platform in bone marrow samples from 133 MM patients in at ...least very good partial response (VGPR) after front-line therapy. Deep sequencing was carried out in patients in whom a high-frequency myeloma clone was identified and MRD was assessed using the IGH-VDJH, IGH-DJH, and IGK assays. The results were contrasted with those of multiparametric flow cytometry (MFC) and allele-specific oligonucleotide polymerase chain reaction (ASO-PCR). The applicability of deep sequencing was 91%. Concordance between sequencing and MFC and ASO-PCR was 83% and 85%, respectively. Patients who were MRD– by sequencing had a significantly longer time to tumor progression (TTP) (median 80 vs 31 months; P < .0001) and overall survival (median not reached vs 81 months; P = .02), compared with patients who were MRD+. When stratifying patients by different levels of MRD, the respective TTP medians were: MRD ≥10−3 27 months, MRD 10−3 to 10−5 48 months, and MRD <10−5 80 months (P = .003 to .0001). Ninety-two percent of VGPR patients were MRD+. In complete response patients, the TTP remained significantly longer for MRD– compared with MRD+ patients (131 vs 35 months; P = .0009).
•MRD assessment by sequencing is prognostic of TTP and OS in multiple myeloma patients.•Among patients in complete response, MRD assessment by sequencing enables identification of 2 distinct subgroups with different TTP.
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