Association of earlier surgery with improved postoperative language development in children with tuberous sclerosis complex.

OBJECTIVE: The authors evaluated the impact of the timing of epilepsy surgery on postoperative neurocognitive outcomes in a cohort of children followed in the multiinstitutional Tuberous Sclerosis Complex (TSC) Autism Center of Excellence Research Network (TACERN) study. METHODS: Twenty-seven of 159 patients in the TACERN cohort had drug-refractory epilepsy and underwent surgery. Ages at surgery ranged from 15.86 to 154.14 weeks (median 91.93 weeks). Changes in patients' first preoperative (10-58 weeks) to last postoperative (155-188 weeks) scores on three neuropsychological tests-the Mullen Scales of Early Learning (MSEL), the Vineland Adaptive Behavior Scales, 2nd edition (VABS-2), and the Preschool Language Scales, 5th edition (PLS-5)-were calculated. Pearson correlation and multivariate linear regression models were used to correlate test outcomes separately with age at surgery and duration of epilepsy prior to surgery. Analyses were separately conducted for patients whose seizure burdens decreased postoperatively (n = 21) and those whose seizure burdens did not (n = 6). Regression analysis was specifically focused on the 21 patients who achieved successful seizure control. RESULTS: Age at surgery was significantly negatively correlated with the change in the combined verbal subtests of the MSEL (R = -0.45, p = 0.039) and predicted this score in a multivariate linear regression model (ß = -0.09, p = 0.035). Similar trends were seen in the total language score of the PLS-5 (R = -0.4, p = 0.089; ß = -0.12, p = 0.014) and in analyses examining the duration of epilepsy prior to surgery as the independent variable of interest. Associations between age at surgery and duration of epilepsy prior to surgery with changes in the verbal subscores of VABS-2 were more variable (R = -0.15, p = 0.52; ß = -0.05, p = 0.482). CONCLUSIONS: Earlier surgery and shorter epilepsy duration prior to surgery were associated with greater improvement in postoperative language in patients with TSC. Prospective or comparative effectiveness clinical trials are needed to further elucidate surgical timing impacts on neurocognitive outcomes.

Impact of visual rotations on heading direction and center of mass control during steady-state gait.

Visual information is essential to navigate the environment and maintain postural stability during gait. Visual field rotations alter the perceived heading direction, resulting in gait trajectory deviations, known as visual coupling. It is unclear how center of mass (CoM) control relative to a continuously changing base of support (BoS) is adapted to facilitate visual coupling. This study aimed to characterize mediolateral (ML) balance control during visual coupling in steady-state gait. Sixteen healthy participants walked on an instrumented treadmill, naive to sinusoidal low-frequency (0.1 Hz) rotations of the virtual environment around the vertical axis. Rotations were continuous with 1) high or 2) low amplitude or were 3) periodic with 10-s intervals. Visual coupling was characterized with cross-correlations between CoM trajectory and visual rotations. Balance control was characterized with the ML margin of stability (MoSML) and by quantifying foot placement control as the relation between CoM dynamics and lateral foot placement. Visual coupling was strong on a group level (continuous low: 0.88, continuous high: 0.91, periodic: 0.95) and moderate to strong on an individual level. Higher rotation amplitudes induced stronger gait trajectory deviations. The MoSML decreased toward the deviation direction and increased at the opposite side. Foot placement control was similar compared with regular gait. Furthermore, pelvis and foot reorientation toward the rotation direction was observed. We concluded that visual coupling was facilitated by reorientating the body and shifting the extrapolated CoMML closer to the lateral BoS boundary toward the adjusted heading direction while preserving CoM excursion and foot placement control.NEW & NOTEWORTHY Healthy, naive participants were unaware of subtle, low-frequency rotations of the visual field but still coupled their gait trajectory to a rotating virtual environment. In response, participants decreased their margin of stability toward the new heading direction, without changing the center of mass excursion magnitude and foot placement strategy.

Hepatitis Delta Virus Reporting Requirements in the United States and Territories: A Systematic Review.

Hepatitis D virus (HDV) is a rare coinfection with hepatitis B virus. Currently, HDV is not a nationally notifiable disease in the United States. Only 55% of states and territories require HDV reporting, and most lack defined case definitions. Standardization of reporting requirements is crucial for monitoring HDV epidemiology.

Is the Walking Adaptability Ladder test for Kids (WAL-K) reliable and valid in ambulatory children with Cerebral Palsy?

PURPOSE: Walking adaptability is essential for children to participate in daily life. We studied whether the Walking Adaptability Ladder test for Kids (WAL-K) is reliable and valid for assessing walking adaptability in 6-12 year old ambulatory children with Cerebral Palsy (CP). MATERIALS AND METHODS: Thirty-six children with CP (26 GMFCS-level I, 10 GMFCS-level II) completed the single and double run of the WAL-K. Intra- and inter-rater reliability were determined by Intraclass Correlation Coefficients (ICCs). Construct validity was determined by comparing WAL-K scores between 122 typically developing (TD) and CP children taking age into account, comparing WAL-K scores between CP children in GMFCS-levels I and II, and correlating WAL-K scores with scores of the 10 times 5 m Sprint Test (10 × 5mST). RESULTS: ICCs for reliability varied between 0.997 and 1.000. WAL-K scores were significantly higher (i.e., worse) in CP children compared to TD children (p < 0.001), and in children in GMFCS-level II compared to GMFCS-level I (p = 0.001). Significant positive correlations were found between the WAL-K and 10 × 5 mST (single run r = .89, double run r = .84). CONCLUSIONS: The WAL-K shows to be a promising reliable, valid, and easy-to-use tool for assessing walking adaptability in children with CP. Responsiveness to change has yet to be evaluated.

Walking adaptability is an essential skill for children to participate in daily life, yet there is no validated clinical test for children with Cerebral Palsy (CP).We recently developed the Walking Adaptability Ladder test for Kids (WAL-K) and we here tested its reliability and validity in children with CP.Application of the WAL-K in children with CP yielded excellent intra- and inter-rater reliability and a good construct validity.The WAL-K shows to be a promising reliable, valid, and easy-to-use tool to assess walking adaptability in children with CP.

Approach, complications, and outcomes for 37 consecutive pediatric patients undergoing laser ablation for medically refractory epilepsy at Stanford Children's Health.

OBJECTIVE: The objective of this study was to better understand the safety and efficacy of laser interstitial thermal therapy (LITT) for children with medically refractory epilepsy. METHODS: Thirty-seven consecutive pediatric epilepsy patients at a single pediatric center who underwent LITT ablation of epileptogenic foci between May 2017 and December 2021 were retrospectively reviewed. Patient demographics, medication use, seizure frequency, prior surgical interventions, procedural details, and pre- and postoperative seizure history were analyzed. RESULTS: Thirty-seven pediatric patients (24 male, 13 female) with severe medically refractory epilepsy were included; all underwent stereo-electroencephalography (SEEG) prior to LITT. The SEEG electrode placement was based on the preoperative workup and tailored to each patient by the epileptologist and neurosurgeons working together to identify the epileptic network and hopefully quiet borders. Seizure onset was at a mean age of 2.70 ± 2.82 years (range 0.25-12 years), and the mean age at the time of LITT was 9.46 ± 5.08 years (range 2.41-17.86 years). Epilepsy was lesional in 23 patients (18 tuberous sclerosis, 4 focal cortical dysplasia, 1 gliosis) and nonlesional in 14. Eighteen patients had prior surgical interventions including open resections (n = 13: 11 single and 2 multiple), LITT (n = 4), or both (n = 1). LITT targeted a region adjacent to the previous target in 5 cases. The median number of lasers placed during the procedure was 3 (range 1-5). Complications occurred in 14 (37.8%) cases, only 3 (8.11%) of which resulted in a permanent deficit: 1 venous hemorrhage requiring evacuation following laser ablation, 1 aseptic meningitis, 2 immediate postoperative seizures, and 10 neurological deficits (7 transient and 3 permanent). Postoperatively, 22 (59.5%) patients were seizure free at the last follow-up (median follow-up 18.35 months, range 7.40-48.76 months), and the median modified Engel class was I (Engel class I in 22 patients, Engel class II in 2, Engel class III in 2, and Engel class IV in 11). Patients having tried a greater number of antiseizure medications before LITT were less likely to achieve seizure improvement (p = 0.046) or freedom (p = 0.017). Seizure improvement following LITT was associated with a shorter duration of epilepsy prior to LITT (p = 0.044), although postoperative seizure freedom was not associated with a shorter epilepsy duration (p = 0.667). Caregivers reported postoperative neurocognitive improvement in 17 (45.9%) patients. CONCLUSIONS: In this large single-institution cohort of pediatric patients with medically refractory seizures due to various etiologies, LITT was a relatively safe and effective surgical approach for seizure reduction and seizure freedom at 1 year of follow-up.

Expanding eligibility for intracranial electroencephalography using Dexmedetomidine Hydrochloride in children with behavioral dyscontrol.

INTRODUCTION: Invasive intracranial electroencephalography (IEEG) is advantageous for identifying epileptogenic foci in pediatric patients with medically intractable epilepsy. Patients with behavioral challenges due to autism, intellectual disabilities, and hyperactivity have greater difficulty tolerating prolonged IEEG recording and risk injuring themselves or others. There is a need for therapies that increase the safety of IEEG but do not interfere with IEEG recording or prolong hospitalization. Dexmedetomidine Hydrochloride's (DH) use has been reported to improve safety in patients with behavioral challenges during routine surface EEG recording but has not been characterized during IEEG. Here we evaluated DH administration in pediatric patients undergoing IEEG to assess its safety and impact on the IEEG recordings. METHODS: A retrospective review identified all pediatric patients undergoing IEEG between January 2016 and September 2022. Patient demographics, DH administration, DH dose, hospital duration, and IEEG seizure data were analyzed. The number of seizures recorded for each patient was divided by the days each patient was monitored with IEEG. The total number of seizures, as well as seizures per day, were compared between DH and non-DH patients via summary statistics, multivariable linear regression, and univariate analysis. Other data were compared across groups with univariate statistics. RESULTS: Eighty-four pediatric patients met the inclusion criteria. Eighteen (21.4 %) received DH treatment during their IEEG recording. There were no statistical differences between the DH and non-DH groups' demographic data, length of hospital stays, or seizure burden. Non-DH patients had a median age of 12.0 years (interquartile range: 7.25-15.00), while DH-receiving patients had a median age of 8.0 years old (interquartile range: 3.00-13.50) (p = 0.07). The non-DH cohort was 57.6 % male, and the DH cohort was 50.0 % male (p = 0.76). The median length of IEEG recordings was 5.0 days (interquartile range: 4.00-6.25) for DH patients versus 6.0 days (interquartile range: 4.00-8.00) for non-DH patients (p = 0.25). Median total seizures recorded in the non-DH group was 8.0 (interquartile range: 5.00-13.25) versus 15.0 in the DH group (interquartile range: 5.00-22.25) (p = 0.33). Median total seizures per day of IEEG monitoring were comparable across groups: 1.50 (interquartile range: 0.65-3.17) for non-DH patients compared to 2.83 (interquartile range: 0.89-4.35) (p = 0.25) for those who received DH. Lastly, non-DH patients were hospitalized for a median of 8.0 days (interquartile range: 6.00-11.25), while DH patients had a median length of stay of 7.00 days (interquartile range: 5.00-8.25) (p = 0.27). No adverse events were reported because of DH administration. CONCLUSIONS: Administration of DH was not associated with adverse events. Additionally, the frequency of seizures captured on the IEEG, as well as the duration of hospitalization, were not significantly different between patients receiving and not receiving DH during IEEG. Incorporating DH into the management of patients with behavioral dyscontrol and intractable epilepsy may expand the use of IEEG to patients who previously could not tolerate it, improve safety, and preserve epileptic activity during the recording period.

Lessons learned from over a decade of data audits in international observational HIV cohorts in Latin America and East Africa.

Introduction: Routine patient care data are increasingly used for biomedical research, but such "secondary use" data have known limitations, including their quality. When leveraging routine care data for observational research, developing audit protocols that can maximize informational return and minimize costs is paramount. Methods: For more than a decade, the Latin America and East Africa regions of the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium have been auditing the observational data drawn from participating human immunodeficiency virus clinics. Since our earliest audits, where external auditors used paper forms to record audit findings from paper medical records, we have streamlined our protocols to obtain more efficient and informative audits that keep up with advancing technology while reducing travel obligations and associated costs. Results: We present five key lessons learned from conducting data audits of secondary-use data from resource-limited settings for more than 10 years and share eight recommendations for other consortia looking to implement data quality initiatives. Conclusion: After completing multiple audit cycles in both the Latin America and East Africa regions of the IeDEA consortium, we have established a rich reference for data quality in our cohorts, as well as large, audited analytical datasets that can be used to answer important clinical questions with confidence. By sharing our audit processes and how they have been adapted over time, we hope that others can develop protocols informed by our lessons learned from more than a decade of experience in these large, diverse cohorts.

Early Treatment with Vigabatrin Does Not Decrease Focal Seizures or Improve Cognition in Tuberous Sclerosis Complex: The PREVeNT Trial.

OBJECTIVE: This study was undertaken to test the hypothesis that early vigabatrin treatment in tuberous sclerosis complex (TSC) infants improves neurocognitive outcome at 24 months of age. METHODS: A phase IIb multicenter randomized double-blind placebo-controlled trial was conducted of vigabatrin at first epileptiform electroencephalogram (EEG) versus vigabatrin at seizure onset in infants with TSC. Primary outcome was Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) cognitive assessment score at 24 months. Secondary outcomes were prevalence of drug-resistant epilepsy, additional developmental outcomes, and safety of vigabatrin. RESULTS: Of 84 infants enrolled, 12 were screen failures, 4 went straight to open label vigabatrin, and 12 were not randomized (normal EEG throughout). Fifty-six were randomized to early vigabatrin (n = 29) or placebo (n = 27). Nineteen of 27 in the placebo arm transitioned to open label vigabatrin, with a median delay of 44 days after randomization. Bayley-III cognitive composite scores at 24 months were similar for participants randomized to vigabatrin or placebo. Additionally, no significant differences were found between groups in overall epilepsy incidence and drug-resistant epilepsy at 24 months, time to first seizure after randomization, and secondary developmental outcomes. Incidence of infantile spasms was lower and time to spasms after randomization was later in the vigabatrin group. Adverse events were similar across groups. INTERPRETATION: Preventative treatment with vigabatrin based on EEG epileptiform activity prior to seizure onset does not improve neurocognitive outcome at 24 months in TSC children, nor does it delay onset or lower the incidence of focal seizures and drug-resistant epilepsy at 24 months. Preventative vigabatrin was associated with later time to onset and lower incidence of infantile spasms. ANN NEUROL 2023.

Common rituals in obsessive-compulsive disorder and implications for treatment: A mixed-methods study.

Obsessive-compulsive disorder (OCD) is characterized by engagement in rituals that serve to obtain certainty and prevent feared outcomes. Exposure and response prevention is most effective when rituals are resisted, yet existing self-report measures of OCD limit identification of the full range of possible rituals, and little is known about how rituals might cluster together and predict worsened severity and poorer treatment outcomes. In a retrospective sample of 641 adult patients who received intensive OCD treatment, the present study used a mixed-methods approach to (a) identify and validate treatment provider-identified rituals using the Yale-Brown Obsessive-Compulsive Scale, (b) identify clustering patterns of rituals, and (c) examine the impact of these clusters on severity and treatment outcomes. Sixty-two discrete rituals clustered into eight higher order ritual clusters: avoidance, reassurance, checking, cleaning/handwashing, just right, rumination, self-assurance, and all other rituals. At admission, reassurance predicted greater intolerance of uncertainty (IU) and rumination predicted less OCD severity. Only one ritual cluster-just right-predicted treatment outcomes; patients with just right rituals had worse IU at discharge and significantly longer length of treatment (average 7.0 days longer). Clinical observation can identify more nuanced and individualized rituals than self-report assessment alone. Patients presenting with just right rituals may benefit less from treatment focused on harm avoidance and habituation; instead, treatment should be tailored to the idiosyncrasies of incompleteness and not just the right experiences. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The effect of functional calibration methods on gait kinematics in adolescents with idiopathic rotational deformity of the femur.

BACKGROUND: Due to anatomical deviations, assumptions of the conventional calibration method for gait analysis may be violated in individuals with rotational deformities of the femur. Functional calibration methods were compared with conventional methods in this group for 1) localization of the hip joint center and orientation of the knee axis, and 2) gait kinematics. METHODS: Twenty-four adolescents with idiopathic rotational deformity of the femur underwent gait analysis and a CT scan. During standing, distance between hip joint centers and knee axis orientation were compared between calibration methods, with CT serving as reference for hip joint center estimation. Gait kinematics were compared using statistical parametric mapping. FINDINGS: The conventional calibration method estimated the hip joint center closer to the CT reference (4±12 mm more lateral) than the functional calibration method (26 ± 20 mm more lateral). Orientation of the knee joint axis was 2.6° less internal in the functional calibration method. During gait, statistical parametric mapping revealed significantly more hip flexion, less external hip rotation during the swing phase, less knee varus-valgus motion, and larger knee flexion angles when applying the functional method. INTERPRETATION: Functional calibration methods were less accurate in determining the hip joint center location than the conventional calibration method and resulted in a knee joint axis that was less internally rotated. Importantly, there was less knee joint angle crosstalk during gait when using the functional method. Although differences between methods on gait kinematics were within clinically acceptable limits for the sagittal plane, relatively larger differences on transversal hip kinematics may hold clinical importance.

Characterization of data-driven geriatric syndrome clusters in older people with HIV: a Mexican multicenter cross-sectional study.

Background: As living with HIV has been proposed as a condition that may accelerate aging, the main objective of this work was to estimate the prevalence of geriatric syndromes (GS) among older Mexicans with HIV dwelling in the community. Secondly, to evaluate whether the accumulation of GS could be associated with an adverse HIV-related clinical profile, independent of chronological age. Methods: Multicenter, cross-sectional study including 501 community-dwelling people aged ≥50 years with HIV. The overall prevalence of nine selected GS and their cumulative number were estimated. An Age-Independent Cumulative Geriatric Syndromes scale (AICGSs) was constructed, and correlations between the AICGSs and HIV-related parameters assessed. Finally, k-mean clustering analyses were performed to test the secondary objective. Findings: Median age 56 (IQR: 53-61) years, 81.6% of men. Polypharmacy (74.8%), sensorial deficit (71.2%), cognitive impairment (53.6%), physical disability (41.9%), pre-frailty (27.9%), and falls (29.7%), were the more prevalent GS. A significant negative correlation was found between the AICGSs and normalized values of CD4+ nadir cell counts (r = -0.126; 95%: CI: -0.223 to -0.026, p < 0.05). Similarly, a significant inverse adjusted association between the CD4+ nadir cells and the AICGSs was observed on linear regression analysis (ß -0.058; 95%: CI: -0.109 to -0.007, p = 0.03). Cluster analysis identified three differentiated groups varying by age, metabolic comorbidities, AICGSs, and HIV-related parameters. Interpretation: An elevated prevalence of GS was observed in the studied population. Moreover, the accumulation of GS was associated with adverse HIV-related profiles, independent of age. Thus, early detection and management of GS are crucial to promote healthier aging trajectories in people with HIV. Funding: This work was funded in part by the National Center for the Prevention and Control of HIV/AIDS in Mexico (CENSIDA)-National Ministry of Health.

Characterizing a rare neurogenetic disease, SLC13A5 citrate transporter disorder, utilizing clinical data in a cloud-based medical record collection system.

Introduction: SLC13A5 citrate transporter disorder is a rare autosomal recessive genetic disease that has a constellation of neurologic symptoms. To better characterize the neurologic and clinical laboratory phenotype, we utilized patient medical records collected by Ciitizen, an Invitae company, with support from the TESS Research Foundation. Methods: Medical records for 15 patients with a suspected genetic and clinical diagnosis of SLC13A5 citrate transporter disorder were collected by Ciitizen, an Invitae company. Genotype, clinical phenotypes, and laboratory data were extracted and analyzed. Results: The 15 patients reported all had epilepsy and global developmental delay. Patients continued to attain motor milestones, though much later than their typically developing peers. Clinical diagnoses support abnormalities in communication, and low or mixed tone with several movement disorders, including, ataxia and dystonia. Serum citrate was elevated in the 3 patients in whom it was measured; other routine laboratory studies assessing renal, liver and blood function had normal values or no consistent abnormalities. Many electroencephalograms (EEGs) were performed (1 to 35 per patient), and most but not all were abnormal, with slowing and/or epileptiform activity. Fourteen of the patients had one or more brain magnetic resonance imaging (MRI) reports: 7 patients had at least one normal brain MRI, but not with any consistent findings except white matter signal changes. Discussion: These results show that in addition to the epilepsy phenotype, SLC13A5 citrate transporter disorder impacts global development, with marked abnormalities in motor abilities, tone, coordination, and communication skills. Further, utilizing cloud-based medical records allows industry, academic, and patient advocacy group collaboration to provide preliminary characterization of a rare genetic disorder. Additional characterization of the neurologic phenotype will be critical to future study and developing treatment for this and related rare genetic disorders.

Graft-versus-host disease and relapse/rejection-free survival after allogeneic transplantation for idiopathic severe aplastic anemia: a comprehensive analysis from the SAAWP of the EBMT.

Survival after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for severe idiopathic aplastic anemia (SAA) has improved in recent years, approaching 75% at 5 years. However, an SAA-adapted composite endpoint, graft-versus-host disease (GvHD) and relapse/rejection-free survival (GRFS), may more accurately assess patient outcomes beyond survival. We analyzed GRFS to identify risk factors and specific causes of GRFS failure. Our retrospective analysis from the Severe Aplastic Anemia Working Party of the European Society for Blood and Marrow Transplantation included 479 patients with idiopathic SAA who underwent allo-HSCT in two conventional situations: i) upfront allo-HSCT from a matched related donor (MRD) (upfront cohort), and ii) allo-HSCT for relapsed or refractory SAA (rel/ref cohort). Relevant events for GRFS calculation included graft failure, grade 3-4 acute GvHD, extensive chronic GvHD, and death. In the upfront cohort (n=209), 5-year GRFS was 77%. Late allo-HSCT (i.e., >6 months after SAA diagnosis) was the main poor prognostic factor, specifically increasing the risk of death as the cause of GRFS failure (hazard ratio [HR]=4.08; 95% confidence interval [CI]: 1.41-11.83; P=0.010). In the rel/ref cohort (n=270), 5-year GRFS was 61%. Age was the main factor significantly increasing the risk of death (HR=1.04; 95% CI: 1.02-1.06; P<0.001), acute GvHD (HR=1.03; 95% CI: 1.00-1.07; P=0.041), and chronic GvHD (HR=1.04; 95% CI: 1.01-1.08; P=0.032) as the cause of GRFS failure. GRFS after upfront MRD allo-HSCT was very good, notably with early allo-HSCT, confirming that younger patients with an MRD should be transplanted immediately. GRFS was worse in cases of salvage allo-HSCT, most notably in older patients, questioning the utility of allo-HSCT earlier in the disease course.

Incomplete Antiretroviral Therapy Adherence Is Associated with Lower CD4-CD8 Ratio in Virally Suppressed Patients with HIV Infection in Mexico.

Suboptimal adherence to antiretroviral therapy (ART) in people with HIV, even during sustained viral suppression, is associated with persistent inflammation, immune activation, and coagulopathy. Persistently low CD4-CD8 Ratio has been also associated with residual inflammation, is a good predictor of increased risk of death and more widely available than inflammatory biomarkers. We tested the hypothesis that the CD4-CD8 Ratio is associated with ART adherence during periods of complete viral suppression. We used the Medication Possession Ratio based in pharmacy registries as measure of adherence and time-varying, routine care CD4 and CD8 measurements as outcome. We used a linear mixed model for longitudinal data, including fixed effects for sex, age, education, date of ART initiation, AIDS-related conditions, and baseline CD4 to model the outcome. In 988 adults with a median follow-up of 4.13 years, higher ART adherence was independently associated with a modest increase in CD4-CD8. For each increasing percentage point in adherence, the CD4-CD8 Ratio increased 0.000857 (95% confidence interval [CI] -0.000494 to 0.002209, p = .213731) in the first year after achieving viral suppression; 0.001057 (95% CI 0.000262-0.001853, p = .009160) in years 1 to 3; 0.000323 (95% CI -0.000448 to 0.001095, p = .411441) in years 3 to 5; and 0.000850 (95% CI 0.000272-0.001429, p = .003946) 5-10 years after achieving viral suppression. The magnitude of the effect of adherence over CD4-CD8 Ratios varied over time and by baseline CD4 count, with increasing adherence having a larger effect early after ART initiation in people with higher baseline CD4 (>500 cells/µL) and in later years in people with lower baseline CD4 count (≥200 cells/µL). Our findings expand on previous evidence suggesting that the benefits of optimal adherence to modern ART regimens goes beyond maintaining viral suppression. These results highlight the importance of including objective measurements of adherence as part of routine care, even in patients with complete HIV suppression over long-term follow-up.

Multisensory Stimulation and Priming (MuSSAP) in 4-10 Months Old Infants with a Unilateral Brain Lesion: A Pilot Randomised Clinical Trial.

Aim: To explore the effect of an Early Intensive-Upper Limb intervention (EI-UL) compared to EI-UL with integrated Multisensory Stimulation And Priming (MuSSAP) training on improving manual ability in infants with a unilateral brain lesion. Method: A pilot randomised clinical trial with pre- and postintervention and follow-up measurements (T0, T1, and T2) was conducted. Sixteen infants with a unilateral brain lesion (corrected age is 4-10 months) received home-based intervention with video coaching. Eight infants received EI-UL and eight infants received EI-UL with integrated MuSSAP training. Primary outcome was the Hand Assessment for Infants (HAI) score. Additionally, effects were explored on initiation of goal-directed movements in both groups and on attention in the EI-UL with integrated MuSSAP training group. Results: No significant group differences in HAI scores were found. Overall, HAI 'Affected hand score' increased between T0 and T1 (p = 0.001, Cohen's d = 1.04) and between T0 and T2 (p < 0.001, Cohen's d = 1.28); and the HAI 'Both Hands Measure' increased between T0 and T1 (p < 0.001, Cohen's d = 1.72) and between T0 and T2 (p < 0.001, Cohen's d = 1.81). At the start of the intervention, six infants (three in both groups) did not demonstrate initiation of goal-directed contralesional upper limb movements. During the intervention one infant receiving EI-UL and all three infants receiving EI-UL with integrated MuSSAP training started to initiate goal-directed movements. Conclusion: The results suggest manual ability of infants with unilateral brain lesion improved with both interventions. We hypothesize that the integrated MuSSAP training may facilitate attention and initiation of contralesional upper limb goal-directed movements. This trial is registered with NCT05533476).

Alcohol, drugs, and road traffic injuries in an emergency department in Mexico City.

There have been no studies reporting on the use of biological specimens in Mexico to analyze the prevalence of alcohol and drug use among Emergency Department (ED) patients with a road traffic injury (RTI). We report here on a sample of 304 adult patients, admitted to the ED of a public hospital in Mexico City from January to April 2022, after being involved in an RTI. Patients gave informed consent for a breath test measuring breath alcohol concentration (BAC) and a saliva screening test for six classes of drugs (amphetamines, barbiturates, benzodiazepines, cannabis, cocaine, and methamphetamine). We found that at least one in every four patients (27.6%) had traces of alcohol or drugs in their body upon arrival in the ED. The breath test found a positive BAC in 16.1% of the sample; the most common substances detected in saliva were amphetamines or methamphetamine (8.6%), followed by cocaine (7.0%) and cannabis (6.9%). Only a few variables differentiated those with positive BAC from those with negative BAC (male, arriving on a weekend day or night, and arriving by ambulance), and even fewer variables differentiated those testing positives for drugs than those testing negative (less than 13 years of education and drivers of cars, bicycles, or other vehicles). While alcohol continues to be the single most used substance, our findings indicate that stimulants are of great concern. Since those testing positives for alcohol or drugs are so similar in their demographic pattern to those testing negative, the introduction of biological testing as a routine practice in the ED is highly recommended. Routine testing makes it possible to provide the patient with the best treatment and is also the best way to assess substance use.

GNAO1-related neurodevelopmental disorder: Literature review and caregiver survey.

Background: GNAO1-related neurodevelopmental disorder is a heterogeneous condition characterized by hypotonia, developmental delay, epilepsy, and movement disorder. This study aims to better understand the spectrum of epilepsy associated with GNAO1 variants and experience with anti-seizure medications, and to review published epilepsy phenotypes in GNAO1. Methods: An online survey was distributed to caregivers of individuals diagnosed with GNAO1 pathogenic variants, and a literature review was conducted. Results: Fifteen respondents completed the survey with the median age of 39 months, including a novel variant p.Q52P. Nine had epilepsy - six had onset in the first week of life, three in the first year of life - but two reported no ongoing seizures. Seizure types varied. Individuals were taking a median of 3 seizure medications without a single best treatment. Our cohort was compared to a literature review of epilepsy in GNAO1. In 86 cases, 38 discrete variants were described; epilepsy is reported in 53 % cases, and a developmental and epileptic encephalopathy in 36 %. Conclusions: While GNAO1-related epilepsy is most often early-onset and severe, seizures may not always be drug resistant or lifelong. Experience with anti-seizure medications is varied. Certain variant "hotspots" may correlate with epilepsy phenotype though genotype-phenotype correlation is poorly understood.

Gaps in the continuum of care in HIV-positive adults and the need for caution in those returning to care after loss to follow-up.

Loss to follow-up (LTFU) and interruption of antiretroviral therapy (ART) are associated with worse outcomes in people with HIV (PWH). Little is known about gaps in the continuum of care. We conducted a retrospective cohort study including adult PWH with at least one clinical visit during 2000-2017. Three groups of care were defined: those constantly retained in care (constantly-RIC), definitively LTFU (dLTFU), and those who returned to care (RTC) after being LTFU for 1 year. We analyzed characteristics of individuals at enrollment. Among 2967 patients, 1565 (53%) were constantly-RIC, 826 (28%) dLTFU, and 576 (19%) RTC. CD4+ ≥350 cells/µL at enrollment was more frequent in RTC patients (43% vs 28% in both constantly-RIC and dLTFU groups, p < 0.01). Time since enrollment to ART initiation was longer in dLTFU (3.3 weeks) and RTC groups (6.0 weeks) in comparison with constantly-RIC patients (2.0 weeks, p < 0.01). Multivariate analysis showed significant differences between groups. Older and ART-naïve patients at enrollment were less likely to have gaps in the continuum of care. Those with non-MSM transmission were less likely to RTC. Patients with CD4+ ≥350 cells/µL at enrollment were more likely to reengage in care. Interventions should be tailored for those at risk of LTFU.

Clinical Features, Neuropathology, and Surgical Outcome in Patients With Refractory Epilepsy and Brain Somatic Variants in the SLC35A2 Gene.

BACKGROUND AND OBJECTIVES: The SLC35A2 gene, located at chromosome Xp11.23, encodes for a uridine diphosphate-galactose transporter. We describe clinical, genetic, neuroimaging, EEG, and histopathologic findings and assess possible predictors of postoperative seizure and cognitive outcome in 47 patients with refractory epilepsy and brain somatic SLC35A2 gene variants. METHODS: This is a retrospective multicenter study where we performed a descriptive analysis and classical hypothesis testing. We included the variables of interest significantly associated with the outcomes in the generalized linear models. RESULTS: Two main phenotypes were associated with brain somatic SLC35A2 variants: (1) early epileptic encephalopathy (EE, 39 patients) with epileptic spasms as the predominant seizure type and moderate to severe intellectual disability and (2) drug-resistant focal epilepsy (DR-FE, 8 patients) associated with normal/borderline cognitive function and specific neuropsychological deficits. Brain MRI was abnormal in all patients with EE and in 50% of those with DR-FE. Histopathology review identified mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy in 44/47 patients and was inconclusive in 3. The 47 patients harbored 42 distinct mosaic SLC35A2 variants, including 14 (33.3%) missense, 13 (30.9%) frameshift, 10 (23.8%) nonsense, 4 (9.5%) in-frame deletions/duplications, and 1 (2.4%) splicing variant. Variant allele frequencies (VAFs) ranged from 1.4% to 52.6% (mean VAF: 17.3 ± 13.5). At last follow-up (35.5 ± 21.5 months), 30 patients (63.8%) were in Engel Class I, of which 26 (55.3%) were in Class IA. Cognitive performances remained unchanged in most patients after surgery. Regression analyses showed that the probability of achieving both Engel Class IA and Class I outcomes, adjusted by age at seizure onset, was lower when the duration of epilepsy increased and higher when postoperative EEG was normal or improved. Lower brain VAF was associated with improved postoperative cognitive outcome in the analysis of associations, but this finding was not confirmed in regression analyses. DISCUSSION: Brain somatic SLC35A2 gene variants are associated with 2 main clinical phenotypes, EE and DR-FE, and a histopathologic diagnosis of MOGHE. Additional studies will be needed to delineate any possible correlation between specific genetic variants, mutational load in the epileptogenic tissue, and surgical outcomes.