Levetiracetam Prophylaxis Therapy for Brain Tumor-Related Epilepsy (BTRE) Is Associated With a Higher Psychiatric Burden

Purpose: Brain tumor-related epilepsy (BTRE) is a condition characterized by the development of seizures in the context of an undergoing oncological background. Levetiracetam (LEV) is a third-generation anti-seizure medication (ASM) widely used in BTRE prophylaxis. The study evaluated LEV neuropsychiatric side effects (SEs) in BTRE prophylaxis.Method: Twenty-eight patients with brain tumors were retrospectively selected and divided into two groups. In one group, we evaluated patients with a BTRE diagnosis using LEV (BTRE-group). The other group included patients with brain tumors who never had epilepsy and used a prophylactic ASM regimen with LEV (PROPHYLAXIS-group). Neuropsychiatric SEs of LEV were monitored using the Neuropsychiatric Inventory Questionnaire (NPI-Q) at the baseline visit and the 6- and 12-month follow-up.Results: Eighteen patients of the BTRE-group and 10 patients of the PROPHYLAXIS-group were included. Compared to the BTRE-group, the PROPHYLAXIS-group showed a higher severity of neuropsychiatric symptoms. According to Linear Mixed Models (LMM), a multiplicative effect was observed for the interaction between group treatment and time. For the caregiver distress score (CDS), only a time-effect was observed.Conclusion: Prophylactic ASM with LEV is associated with an increased frequency of neuropsychiatric SE. Accurate epileptological evaluations in patients with brain tumors are mandatory to select who would benefit most from ASM.

From Undetectable Equals Untransmittable (U=U) to Breastfeeding: Is the Jump Short?

Background: Vertical transmission of HIV infection can occur during pregnancy, during childbirth or through breastfeeding. The recommendations issued by the various international guidelines (WHO 2010, EACS 2017, DHHS 2017) on the safety of breastfeeding of HIV-infected women in effective antiretroviral treatment do not provide univocal indications referring to individual countries the choice to advise or advise against such procedure. Methods: A retrospective study was conducted in a small cohort of HIV-infected pregnant women who, despite the information received, decided to breastfeed their children. The observation was carried out in the period between March 2017 and June 2021. In all newborns, prophylaxis therapy was initiated at birth, according to the treatment guidelines, the scheme adopted involved the administration of zidovudine (AZT) orally for 4 weeks, started immediately after the childbirth. Breastfeeding time was, on average, 5 months. Results: No contagion was diagnosed. All infants were tested for HIV-RNA at birth, 1, 3, and 6 months after birth, and 1, 3 and 3 months after stopping breastfeeding. Conclusions: The data obtained represent, in our opinion, a solicitation to discuss and re-evaluate scientific evidence that starting from "Undetectable Equals Untransmittable" (U = U) can open a scientific and cultural review of breastfeeding.

Sports and Children with Hemophilia: Current Trends

Hemophilia is a sex-linked recessive disorder characterized by a lack of blood factors necessary for clotting. This review aims to investigate the benefits of sports activities in children with hemophilia in terms of both physical and psychological wellness. Sports activity is necessary for children with hemophilia to preserve joints’ range of motion, reduce joint bleeding, improve muscle mass and strength, enhance proprioception and prevent secondary chronic diseases. In the past, high-impact sports were usually forbidden in children with hemophilia because of their high bleeding risk. Recent studies, however, have shown that prophylaxis therapy can allow a hemophilic child to take part in vigorous activities or high-impact sports. The benefits of sports activity in children with hemophilia are expressed by a better muscular trophism and an improved bone mineral density. Moreover, physical activity has a positive impact on children’s psychosocial well-being. Due to prophylaxis therapy, the quality of life of children with hemophilia is similar to their peers, and this has allowed an improvement in sports participation, including team sports.

Clinical Predictors and Prediction Models for Frequency of Total and Joint Hemorrhage in Severe-Type Patients with Hemophilia a (PwHA) with/without Intermediate-Dose Prophylaxis Therapy with rFVIII

Introduction: It was well-known that severe-type patients with hemophilia A (PwHA) had great variability in bleeding phenotypes. Factors effecting bleeding patterns of PwHA include at least treatment modality and interindividual various procoagulant and anticoagulant levels. We aimed to investigate what clinical variables could predict bleeding frequency of severe PwHA and to develop models for predicting bleeding phenotypes among severe PwHA with/without FVIII prophylaxis therapy. Methods and materials: Totally 51 severe-type previously-treated PwHA from two Hemophilia Centers in Taiwan were enrolled, who received standard half life (SHL) rFVIII products with complete consecutive bleeding records at least more than 6 months, and their medical charts 2017－2018 were retrospectively viewed. The clinical data were collected for analysis, including age, body mass index (BMI), body weight (BW), ABO blood groups, hemoglobin (Hb), hematocrit (Hct), HCV infecton, HIV infection, treatment modality, baseline VWF levels, and genetic defects. Baseline VWF activity meant the data via VWF:ACL activity or VWF:RCo. Clinical variables for annualized bleeding rate (ABR) and annualized joint bleeding rate (AJBR) were evaluated by multivariate linear regression (MVLR) analysis. Results: The cohort of 51 severe-type PwHA included 8 boys and 43 adults, aged 8-64. For treatment modality, there were 19 patients receiving episodic treatment (ET) and 32 receiving prophylaxis therapy (PT) with intermediate-dose standard half life (SHL) rFVIII. The mean study period was 11.9 months, range 10－14.5 months. Among them, there were 31 with HCV infection and 4 with HIV infection. PwHA with non-O blood group were 31 and those with O blood group 20. The mean baseline VWF:Ag was 115.6±55.5%, range 50%－294.7%. The mean baseline VWF:activity was 105.4±52.1%, range 41.3%－307%. ABR of ET group and PT group were 46.1±29.2 and 6.8±7.1, respectively. (p<0.0001***) AJBR of ET group and PT group were 37.3±27.7 and 6.0±6.8, respectively. (p=0.0001***) By MVLR analysis, both treatment modality and baseline VWF:Ag were recognized as inverse predictors of ABR and AJBR, and HCV infection recognized a predictor for AJBR. Age, inhibitor histroy, BMI, BW, ABO blood groups, Hct, Hb, HIV infection, and missense mutation or not were eliminated as predictors. The predictive equations by MVLR were as the following two: (1) Predictive ABR = 56.5 - 37.8 * (Treatment model) - 11.8 * baseline VWF:Ag (IU/mL). (2) Predictive e AJBR = 41.9 - 28.6 * (Treatment model) - 12.0 * baseline VWF:Ag (IU/mL) + 10.0 * (HCV infection). (1 if Treatment model is PT, 0 if Treatment model is ET. 1 if HCV infection or anti-HCV antibody is positive, 0 if HCV infection or HCV antibody is negative.) Separate prediction models developed from MVLR analysis could explain 52.51% of the ABR variability and 50.56% of the AJBR variability. The correlation between predicted and observed bleeding frequency was significantly strong.(P-rank>0.7, p-value<0.0001***) Mean difference between predicted ABRs and observed ABRs was 1.75 and that between predicted AJBRs and observed AJBRs was 1.27. Predicted ABR deviated <21 (<2 per month) of observed ABR in 42/50 patients (84%). Predicted AJBR deviated < 24 (<2 per month) ofobserved AJBR in 44/50 patients (88%). Conclusion: Prophylaxis therapy and baseline VWF:Ag levels were the strongest two inverse predictors for ABR and AJBR. Positive HCV infection was another predictor for AJBR. The prediction models provided with an insight into personal bleeding quantified patterns and may identify PwHA with high bleeding risks based on individual characteristics of treatment modality, baseline VWF:Ag, and HCV infection. Our approach is of help for individualized treatment and refining of dosing strategies. Disclosures No relevant conflicts of interest to declare.

Real-World Bleeding Outcomes, Weekly Factor Consumption Doses, Annualized Factor Costs in Severe-Type Patients with Hemophilia a (PwHA) before and after Switching to Extended Half-Life rFVIII-Fc Prophylaxis

Introduction: Stand half-life (SHL) rFVIII had been used in patients with hemophilia A (PwHA) for episodic treatment (ET) and prophylaxis therapy (PT) for years. Extended half-life (EHL) rFVIII had been available since 2014, also available in Taiwan since 2018, and resulted in markedly increased willingness for PT because it reduced injection burden. We aimed to investigate the real-world bleeding outcomes, weekly factor doses, and factor costs of severe-type PwHA with pre-switch SHL rFVIII and post-switch EHL rFVIIIFc prophylaxis in Taiwan, and made a pre-switch and post-switch comparison. Methods and Materials: There were totally 51 non-inhibitor, severe-type PwHA, with complete bleeding records before and after switching from SHL rFVIII to EHL rFVIII-Fc, enrolled from two hemophilia centers during Nov, 2018－July, 2019. Most of them had various degree of one to more major joints arthropathy, except children. The medical charts were retrospective reviewed and data were collected, including body features and factor regimen, etc. Patients' annualized bleeding/joint-bleeding rate (ABR/AJBR), weekly doses (WD), annualized factor costs (AFC) were obtained from the chart records of pre-switch 12 months and post-switch at least more-than 6-month until July, 2019. Data from scheduled operation or hospitalization due to trauma or accidence were excluded. Results: There were 8 boys and 43 adults, the median age of all PwHA when switching was 35.6 years (10.5-62). Before switching, these 51 PTP treated with SHL rFVIII who received ET (ET group), irregular prophylaxis (IP group), and regular prophylaxis (RP group) were 19 (37.3%), 7 (13.7%), and 25 (49%), respectively. Bleeding records of 51 PTP treated with SHL rFVIII were traced back with 11.8±0.9 months. After switching to rFVIII-Fc, 3 PwHA receiving ET were excluded, and bleeding records of 48 received RP were obtained with 14.7±4.6 months. Pre-switch and post-switch prophylaxis rate were 62.7% (32/51) and 94.1% (48/51), respectively. For comparison of pre-switch and post-switch outcomes: Median ABR was reduced from 48, 12, and 4 to 1.15, 1.9, and 1.5 for ET, IP, and RP group, respectively. Median AJBR was reduced from 32, 11, and 4 to 0.95, 0.7, and 1.2 for ET, IP, and RP group, respectively. Median WD was increased from 38.4, 52.9, and 63.6 IU/kg/wk to 84.6, 84.5, and 84.9 IU/kg/wk for ET, IP, and RP group, respectively. Median AFC was increased from 4,141,800, 4,064,000 and 5,129,700 NTD to 7,042,325, 5,835,450, and 5,762,810 NTD for ET, IP, and RP group, respectively. Comparing pre-switch and post-switch outcomes of children and adults who received pre-switch and post-switch prophylaxis, median ABR was reduced from 3 and 5 to 1.35 and 1.85 for children and adults, respectively. Median AJBR was reduced from 3 and 4 to 1.35 and 1.15 for children and adults, respectively. Median WD was increased from 58.8 and 58.3 IU/kg/wk to 87.85 and 83.85 IU/kg/wk for children and adults, respectively. Median AFC was increased from 4,104,225 and 5,879,025 NTD to 4,419,800 and 6,024,916 NTD for children and adults, respectively. For all PwHA, zero ABR accounted for 5.9% (3/51) with pre-switch SHL rFVIII treatment and for 20.8% (10/48) with post-switch rFVIII-Fc prophylaxis. Zero AJBR accounted for 9.8% (5/51) with SHL rFVIII treatment and for 33.3% (16/48) with rFVIII-Fc prophylaxis. For PwHA with pre- and post-switch prophylaxis, zero ABR accounted for 12.5% (1/8) and 8.3% (2/24), respectively, for children and adults on SHL rFVIII prophylaxis and 25% (2/8) and 25% (6/24) respectively, for children and adults on rFVIII-Fc prophylaxis. Zero AJBR accounted for 12.5% (1/8) and 16.7% (4/24), respectively, for children and adults on SHL rFVIII prophylaxis and 25% (2/8) and 37.5% (9/24) respectively, for children and adults on rFVIII-Fc prophylaxis. Conclusion: In real-world setting, for pre-switch ET group, switch to rFVIII-Fc prophylaxis made both mean ABR and AJBR reduced >95%, and mean WD increased >50%. For pre-switch IP group, switch to rFVIII-Fc prophylaxis made both mean ABR and AJBR reduced >80%, and mean WD increased >35%. For pre-switch RP group, switch to rFVIII-Fc prophylaxis made both mean ABR and AJBR also reduced >45%, and mean WD increased >20%. The proportions in zero ABR and zero AJBR as post-switch rFVIII-Fc prophylaxis were increased. No matter in ET, IP, or RP group, after switching to RP with rFVIII-Fc, improvement for bleeding outcomes was quite evident. Disclosures No relevant conflicts of interest to declare.

Effect of alkalized urine on renal calculi in patients with gout: a protocol for a placebo-controlled, double-blinded randomized controlled trial

Background The prevalence of renal calculi in patients with gout is high. Alkalized urine has been recommended by the 2020 European Association of Urology (EAU) guidelines to promote calculus dissolution. However, randomized controlled trials are lacking. Methods In the protocol of this randomized, placebo-controlled, double-blinded trial, patients with gout combined with renal calculi are randomized (1:1) to the placebo and sodium bicarbonate groups. The intervention would be performed for 24 weeks, the 1–12 weeks are double-blinded, and the 13–24 weeks are open-labeled. Sodium bicarbonate (1 g tid) will be performed for 24 weeks in the sodium bicarbonate group. The placebo will be performed for 12 weeks and not be performed from 13 weeks to 24 weeks in the placebo group. All subjects will be administered febuxostat (40 mg/day) for 24 weeks and receive concomitant anti-inflammatory prophylaxis therapy for 12 weeks. The primary outcome is the proportion of patients whose renal calculus volume will be reduced after 12 weeks of treatment. The secondary outcomes include the volume changes of renal calculi, uric acid changes, the proportion of patients with serum uric acid (sUA) levels < 360 μmol/L, the changes in estimated glomerular filtration rate (eGFR), the pH value of urine, and the incidence of adverse events after treatment for 12 and 24 weeks. Discussion This study will evaluate the efficacy and safety of sodium bicarbonate-alkalized urine on renal calculi in patients with gout. Trial registration ClinicalTrials.gov ChiCTR2100045183. Registered on April 7, 2021, with ChiCTR.

Risk factors of cerebral toxoplasmosis in HIV patients: A systematic review

Introduction. Cerebral toxoplasmosis is one of the diseases of the central nervous system that can occur in people with AIDS. Cerebral toxoplasmosis occupies third place among fatal diseases that can occur in people with AIDS. Prevalence of toxoplasmosis is about 25-30% of the world’s human population, and in Asia it is as high as 40%. Risk factors for developing cerebral toxoplasmosis is needed to be sought to to find out risk factors that triggers and acts as protective factors for toxoplasmosis cerebral in HIV-positive patients Methods. Two reviewers searched PubMed and Medline to identify cohort, case-control and cross-sectional studies. Two independent reviewers searched the databases, identified studies and extracted data. Inclusion and exclusion criteria were applied for the data screening. Results. Four studies were included. Two prospective cohort studies, one multicenter cohort study and one case control study. Age was not found to have a role as a risk factor. Gender was shown to have significant in one study (Male vs female OR 0.47 95% CI 0.25-0.88, p = 0.02). CD4 <100 increased the risk of toxoplasmosis by 27.94 times, while CD4 0-50 increased the risk by 10.82 times. HIV viral load > 100.000 was associated with 5.10 times higher to develop cerebral toxoplasma. Prophylaxis therapy using cotrimoxazole can reduce the risk of cerebral toxoplasmosis. Conclusion. Age, female sex, low CD4 cell count, and high HIV viral load increase the risk of cerebral toxoplasmosis, whereas ART therapy and prophylaxis with cotrimoxazole can reduce the risk.

BoNT-A efficacy in high frequency migraine: an open label, single arm, exploratory study applying the PREEMPT paradigm

Introduction In this open label, single-arm trial we evaluated the efficacy of onabotulinum toxin-A in the prevention of high-frequency episodic migraine (8–14 migraine days/month). Methods We enrolled 32 high-frequency episodic migraine subjects (age 44.8 ± 11.9 years, 11.0 ± 2.2 migraine days, 11.5 ± 2.1 headache days, 7 females). After a 28-day baseline period, subjects underwent 4 subsequent onabotulinum toxin-A treatments according to the phase III research evaluating migraine prophylaxis therapy (PREEMPT) paradigm, 12-weeks apart. The primary outcome was the reduction of monthly migraine days from baseline in the 12-week period following the last onabotulinum toxin-A treatment Results Onabotulinum toxin-A reduced monthly migraine days by 3.68 days (−33.1%, p < 0.01). Thirty-nine percent of the patients experienced a ≥50% reduction in monthly migraine days. Onabotulinum toxin-A also reduced the number of headache days (−33.9%, p < 0.01) and the intake of acute medications (−22.9%, p = 0.03). Disability and quality of life (QoL) scores improved markedly (migraine disability assessment (MIDAS) −41.7%; migraine specific questionnaire (MSQ) −31.7%, p < 0.01). Conclusions The findings suggest that, when administered according to the PREEMPT paradigm, onabotulinum toxin-A is effective in the prevention of high-frequency episodic migraine. Trial Registration: NCT04578782