HTLV-1-associated myelopathy in Spain.

BACKGROUND: HTLV-1 infection is a neglected disease. Over 10 million people are infected worldwide, with hot spots of high endemicity across all continents. Roughly 5% of HTLV-1 carriers develop HTLV-1-associated myelopathy (HAM), a progressive subacute neurological disabling disease. METHODS: We report the main features of patients diagnosed with HAM up to date in Spain, a non-endemic country with a relatively high migrant flow from Latin America and Equatorial Africa, where HTLV-1 is endemic. RESULTS: A total of 451 cases of HTLV-1 had been recorded in Spain until the end of year 2022. HAM had been diagnosed in 58 (12.9%). The current incidence is of 2-3 new cases per year. Women represent 76%. Mean age at diagnosis is 49 years-old. Nearly 60% are Latin Americans. Although sexual transmission is the most likely route of HTLV-1 acquisition, up to 6 individuals had been infected following solid organ transplantation. Rapid onset myelopathy developed in all but one of these transplant recipients from three HTLV-1-positive donors. HTLV-1 subtype 1a transcontinental was the only variant recognized in HAM patients. HTLV-1 proviral load was significantly greater in HAM patients than in asymptomatic HTLV-1 carriers (677 vs 104 HTLV-1 DNA copies/104 PBMC; p = 0.012). Symptom relief medications and physiotherapy have been the only treatment providing some benefit to HAM patients. Neither significant clinical nor virological efficacy was noticed using antiretrovirals in at least 9 HAM patients. Two thirds of HAM patients ended up in a wheelchair and with urinary/fecal sphincter incontinence. CONCLUSION: HAM is the most frequent clinical manifestation of HTLV-1 infection in Spain, a non-endemic country. Middle aged women migrants from Latin America are the most frequently affected. Two thirds end up in a wheelchair despite using antiretroviral therapy.

Executive functioning skills and (low) math achievement in primary and secondary school.

Schoolchildren with better executive functioning skills achieve better mathematics results. It is less clear how inhibition, cognitive flexibility, and working memory combine to predict mathematics achievement and difficulty throughout primary and secondary school. This study aimed to find the best combination of executive function measures for predicting mathematical achievement in Grades 2, 6, and 10 and to test whether this combination predicts the probability of having mathematical difficulties across school grades even when fluid intelligence and processing speed were included in the models. A total of 426 students-141 2nd graders (72 girls), 143 6th graders (72 girls), and 142 10th graders (79 girls)-were cross-sectionally assessed with 12 executive tasks, one standardized mathematical task, and a standardized test of intelligence. Bayesian regression analyses found various combinations of executive predictors of mathematical achievement for each school grade spanning Grade 2 to measures of cognitive inhibition (negative priming) and cognitive flexibility (verbal fluency); Grade 6 to measures of inhibition: resistance to distractor interference (receptive attention), cognitive flexibility (local-global), and working memory (counting span); and Grade 10 to measures of inhibition: resistance to distractor interference (receptive attention) and prepotent response inhibition (stop signal) and working memory (reading span). Logistic regression showed that the executive models derived from the Bayesian analyses had a similar ability to classify students with mathematical difficulty and their peers with typical achievement to broader cognitive models that included fluid intelligence and processing speed. Measures of processing speed, cognitive flexibility (local-global), and prepotent response inhibition (stop signal) were the main risk factors in Grades 2, 6, and 10, respectively. Cognitive flexibility (verbal fluency) in Grade 2 and fluid intelligence, which was more stable in all three grades, acted as protective factors against mathematical difficulty. These findings inform practical considerations for establishing preventive and intervention proposals.

Late presentation of human T-lymphotropic virus type 1 infection in Spain reflects suboptimal testing strategies.

OBJECTIVES: Although only 10% of persons infected with human T-lymphotropic virus type 1 (HTLV-1) may develop virus-associated illnesses over their lifetime, missing the earlier diagnosis of asymptomatic carriers frequently leads to late presentation. METHODS: A nationwide HTLV-1 register was created in Spain in 1989. We examined the main demographics and clinical features at the time of the first diagnosis for more than three decades. RESULTS: A total of 428 individuals infected with HTLV-1 had been reported in Spain until the end of 2021. Up to 96 (22%) individuals presented clinically with HTLV-1-associated conditions, including subacute myelopathy (57%), T-cell lymphoma (34%), or Strongyloides stercoralis infestation (8%). Since 2008, HTLV-1 diagnosis has been made at blood banks (44%) or clinics (56%). Native Spaniards and Sub-Saharan Africans are overrepresented among patients presenting with HTLV-1-associated illnesses suggesting that poor epidemiological and/or clinical suspicion, which led to the late presentation are more frequent in them than carriers from Latin America (LATAM) (31.7% vs 20.4%, respectively; P = 0.015). CONCLUSION: HTLV-1 infection in Spain is frequently diagnosed in patients presenting with characteristic illnesses. Although screening in blood banks mostly identifies asymptomatic carriers from LATAM, a disproportionately high number of Spaniards and Africans are diagnosed too late at the time of clinical manifestations. Expanding testing to all pregnant women and clinics for sexually transmitted infections could help to unveil HTLV-1 asymptomatic carriers.

Post-COVID-19 syndrome. SARS-CoV-2 RNA detection in plasma, stool, and urine in patients with persistent symptoms after COVID-19.

BACKGROUND: There is a paucity of knowledge on the long-term outcome in patients diagnosed with COVID-19. We describe a cohort of patients with a constellation of symptoms occurring four weeks after diagnosis causing different degrees of reduced functional capacity. Although different hypothesis have been proposed to explain this condition like persistent immune activation or immunological dysfunction, to date, no physiopathological mechanism has been identified. Consequently, there are no therapeutic options besides symptomatic treatment and rehabilitation. METHODS: We evaluated patients with symptoms that persisted for at least 4 weeks after COVID-19. Epidemiological and clinical data were collected. Blood tests, including inflammatory markers, were conducted, and imaging studies made if deemed necessary. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcription polymerase chain reaction (RT-PCR) in plasma, stool, and urine were performed. Patients were offered antiviral treatment (compassionate use). RESULTS: We evaluated 29 patients who reported fatigue, muscle pain, dyspnea, inappropriate tachycardia, and low-grade fever. Median number of days from COVID-19 to positive RT-PCR in extra-respiratory samples was 55 (39-67). Previous COVID-19 was mild in 55% of the cases. Thirteen patients (45%) had positive plasma RT-PCR results and 51% were positive in at least one RT-PCR sample (plasma, urine, or stool). Functional status was severely reduced in 48% of the subjects. Eighteen patients (62%) received antiviral treatment. Improvement was seen in most patients (p = 0.000) and patients in the treatment group achieved better outcomes with significant differences (p = 0.01). CONCLUSIONS: In a cohort of COVID-19 patients with persistent symptoms, 45% of them have detectable plasma SARS-CoV-2 RNA. Our results indicate possible systemic viral persistence in these patients, who may benefit of antiviral treatment strategies.

Incidence of cardiovascular events and changes in the estimated risk and treatment of familial hypercholesterolemia: the SAFEHEART registry.

INTRODUCTION AND OBJECTIVES: The SAFEHEART study was designed to analyze the situation of familial heterozygous hypercholesterolemia (FHH) and improve knowledge of this disease in Spain. Our objective was to determine the incidence rate of cardiovascular events, the estimated risk of developing an event and its modification, the use of lipid-lowering treatment, and the achievement of low-density lipoprotein cholesterol targets in patients with FHH. METHODS: SAFEHEART is a prospective, open, multicenter, nationwide cohort study, with long-term protocol-based follow-up in a population of individuals with molecularly-characterized FHH. We analyzed patients older than 18 years with complete follow-up. RESULTS: We included 2648 patients with FHH. The median follow-up was 6.6 (4.8-9.7) years. The overall incidence rate of cardiovascular events was 1.3 events/100 patient-years. After the follow-up, the 10-year estimated risk of developing a cardiovascular event was reduced from 1.6% to 1.3% (P <.001). In the last follow-up, 20.6% and 22.2% of the patients in primary and secondary prevention achieved low-density lipoprotein cholesterol values <100mg/dL and <70mg/dL, respectively. CONCLUSIONS: This study was performed in the largest population of patients with FHH in Spain. We identified the incidence rate of cardiovascular events, the estimated risk of developing a cardiovascular event and its modification, the achievement of low-density lipoprotein cholesterol targets, and the therapeutic management in this population. Although the cardiovascular risk of FHH is high, appropriate treatment reduces the likelihood of an event. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Identifier: NCT02693548.

Mathematical Difficulties vs. High Achievement: An Analysis of Arithmetical Cognition in Elementary School.

This study analyzed the contribution of cognitive processes (planning, attention, simultaneous and successive processing) and domain-specific skills (counting, number processing and conceptual comprehension) to the arithmetic performance achieved in the last three grades (4th, 5th, and 6th) of elementary school. Three groups of students with a different arithmetic achievement level were characterized. The predictive value of the cognitive processes and the math specific skills are explored through diverse covariance and discriminant analyses. Participants were 110 students (M = 10.5 years, SD = 1.17) classified in three groups: mathematical difficulties (MD; n = 26), high achieving (HA; n = 26), and typical achieving (TA; n = 58). Cognitive processes and domain-specific skills were evaluated in two individual sessions at the end of the school year. Nonverbal intelligence was assessed in a final collective session with each class. The mathematical difficulties group's achievement was deficient in simultaneous and successive processing, number processing, and conceptual comprehension compared to the typical achievement group. High achievement children obtained significantly better results than the typical achievement children in simultaneous processing, counting, number processing, and conceptual comprehension. Number processing and conceptual comprehension were the most consistent classifiers, although successive and simultaneous processing, respectively, also contributed to identifying students with mathematical difficulties and high achievement. These findings have practical implications for preventive and intervention proposals linked to the observed profiles.

Clinical and microbiological effects of the use of a cetylpyridinium chloride dentifrice and mouth rinse in orthodontic patients: a 3-month randomized clinical trial.

Objective: To assess the clinical, microbiological, and patient-based effects of using a cetylpyridinium chloride (CPC) toothpaste and mouth rinse in orthodontic patients. Design: Parallel randomized controlled, triple-blinded trial (participants, examiners, outcomes' assessors). A computer-generated list was used to allocate treatments. Central allocation was used for concealment. Participants: Thirty-one placebo (10 males, 21 females; mean age 15.2 ± 2.1) and 32 test patients (15 males, 17 females; mean age 15.0 ± 1.8) with fixed orthodontic appliance were included in the study. Interventions: Patients were randomly assigned to both brush and rinse with placebo or with CPC-based products. Products were purposely prepared in white opaque bottles. After screening and professional prophylaxis, patients received a baseline examination, and started to use the assigned products. Patients were monthly assessed during a 3-month period. Main outcome measures: Plaque (PlI) and gingival (GI) indexes. Secondary outcome variables: Calculus index, tooth staining, subgingival microbiological samples, patient-based variables (questionnaire, compliance, and remaining mouth rinse), side-effects (debonded braces or mucosal injuries). Results: Sixty-three patients were randomized, 13 patients were excluded from analysis because of early dropout, leaving 50 patients for intention to treat analysis. PlI in the upper jaw diminished (0.18; SD = 0.82) after 1 month in the test group, while it increased (0.26; SD = 0.62) in the placebo group (P = 0.024). Statistically significant higher GI values were observed in the placebo group at 1 month (mean increase = 0.05; SD = 0.33 versus mean decrease = 0.03; SD = 0.38) and 3 months (mean = 0.05; SD = 0.43 versus mean = 0.02; SD = 0.34). The taste of the test product was rated higher than the placebo at 2- and 3-month visits (P < 0.05). Non-significant changes were observed in microbiological parameters, overgrowth of opportunistic species or remaining secondary outcome variables, including side-effects. Conclusion: The use of CPC-based toothpaste and mouth rinse in orthodontic patients had limited effect in reducing plaque accumulation and gingival inflammation. Effects were little and highly variable. The use of the test products was not associated with relevant adverse effects. Trial registration: Trial registration: Local internal reference: P07/133.