Influence of the Extraction Method on the Polyphenolic Profile and the Antioxidant Activity of Psidium guajava L. Leaf Extracts.

The leaves of Psidium guajava L. are an agro-industrial by-product with an outstanding content of polyphenolic compounds; however, there are many factors which can affect the phytochemical profile when valuing this type of plant material, such as temperatures and extraction times involving in the extraction methods applied. In this context, this study analyzed the impact of different extraction methods (Soxhlet, maceration and ultrasound-assisted extraction) on the phytochemical profile (FTIR and UPLC-MS) and the antioxidant activity (ABTS, FRAP and Folin-Ciocalteu) of guava leaf extracts. A yield of phenolic compounds per gram of guava leaf was obtained within the range of 16 to 45 mg/g; on the other hand, the IC50 values determined with the ABTS assay ranged between 78 ± 4 to 152 ± 12 µg/mL. The methanolic extract obtained by Soxhlet was the one with the best reducing power, both in the FRAP assay and in the Folin-Ciocalteu assay. Finally, bioactive compounds such as quercetin, kaempferol and avicularin were identified in the guava leaf extract. It was concluded that the purification of polyphenolics compounds improves the antioxidant capacity, and that the extraction method greatly influences the phytochemical profile and activity of the extracts.

Monitoring System of the Mar Menor Coastal Lagoon (Spain) and Its Watershed Basin Using the Integration of Massive Heterogeneous Data.

The tool created aims at the environmental monitoring of the Mar Menor coastal lagoon (Spain) and the monitoring of the land use of its watershed. It integrates heterogeneous data sources ranging from ecological data obtained from a multiparametric oceanographic sonde to agro-meteorological data from IMIDA's network of stations or hydrological data from the SAIH network as multispectral satellite images from Sentinel and Landsat space missions. The system is based on free and open source software and has been designed to guarantee maximum levels of flexibility and scalability and minimum coupling so that the incorporation of new components does not affect the existing ones. The platform is designed to handle a data volume of more than 12 million records, experiencing exponential growth in the last six months. The tool allows the transformation of a large volume of data into information, offering them through microservices with optimal response times. As practical applications, the platform created allows us to know the ecological state of the Mar Menor with a very high level of detail, both at biophysical and nutrient levels, being able to detect periods of oxygen deficit and delimit the affected area. In addition, it facilitates the detailed monitoring of the cultivated areas of the watershed, detecting the agricultural use and crop cycles at the plot level. It also makes it possible to calculate the amount of water precipitated on the watershed and to monitor the runoff produced and the amount of water entering the Mar Menor in extreme events. The information is offered in different ways depending on the user profile, offering a very high level of detail for research or data analysis profiles, concrete and direct information to support decision-making for users with managerial profiles and validated and concise information for citizens. It is an integrated and distributed system that will provide data and services for the Mar Menor Observatory.

The SQ House Dust Mite SLIT-Tablet Is Well Tolerated in Patients with House Dust Mite Respiratory Allergic Disease.

BACKGROUND: The SQ house dust mite (HDM) SLIT-tablet (ALK, Denmark) addresses the underlying cause of HDM respiratory allergic disease, and a clinical effect has been demonstrated for both HDM allergic rhinitis and allergic asthma. Here, we present pooled safety data from an adult population with HDM respiratory allergy, with particular focus on the impact of asthma on the SQ HDM SLIT-tablet tolerability profile. METHODS: Safety data from 2 randomised double-blind, placebo-controlled clinical trials were included: MT-04: 834 adults with HDM allergic asthma not well controlled by inhaled corticosteroids and with HDM allergic rhinitis, and MT-06: 992 adults with moderate-to-severe HDM allergic rhinitis despite the use of allergy pharmacotherapy and with or without asthma. RESULTS: The proportion of subjects experiencing adverse events (AEs) was greater in the active treatment group (12 SQ-HDM; 73% of subjects) compared to placebo (53%). The most common treatment-related AEs were local allergic reactions. No AEs were reported as systemic allergic reactions. Regardless of asthma status, most AEs were mild or moderate (>97% of AEs) and the frequency of serious AEs was low. Subgroup analysis revealed no statistically significant difference in the risk of experiencing moderate or severe treatment-related AEs for subjects with asthma compared to subjects without asthma (p = 0.88). In addition, subjects with partly controlled or uncontrolled asthma were no more likely to experience moderate or severe treatment-related AEs than subjects with controlled asthma (p = 0.42). CONCLUSION: The SQ HDM SLIT-tablet is well tolerated, and the safety profile was comparable for subjects with HDM respiratory allergic disease irrespective of asthma status.

Association between different obesity measures and the risk of stroke in the EPIC Spanish cohort.

INTRODUCTION: There is still a scientific debate on the exact role played by obesity on stroke risk. OBJECTIVE: The aim of the study was to analyze the association between obesity, measured by different indices such as body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR) and a new one called A Body Shape Index (ABSI) and the risk of total and ischemic stroke. SUBJECTS/METHODS: A total of 41,020 subjects (15,490 men and 25,530 women) aged 29-69 years participated in the study. All participants were recruited between 1992 and 1996 and followed up until 2008 to ascertain incident cerebrovascular disease events. Cox proportional hazards models were designed to estimate the relative risk and 95% CI between obesity and cerebrovascular disease incidence. RESULTS: After 13.8 years of follow-up, a total of 674 stroke cases (55.3% in men) were registered (531 ischemic, 79 hemorrhagic, 42 subarachnoid hemorrhage and 22 unspecified). WC fourth quartile (HR 1.95; 95% CI 1.20-3.19) and WHR fourth quartile (HR 1.58; 95% CI 1.12-2.25) were positively associated with total stroke only in men. BMI was not associated with stroke incidence. The new index, ABSI, was significantly associated with total stroke incidence only in men (HR 1.54; 95% CI 1.06-2.23). CONCLUSIONS: Data from the Spanish EPIC cohort study show a strong association of WC and WHR with the relative risk of suffering a stroke only in men, while no associations were found for BMI. It supports the suggestion of other authors of using more than one obesity index in the study of stroke risk prediction.

Health Claims for Sports Drinks-Analytical Assessmentaccording to European Food Safety Authority's Scientific Opinion.

In Europe, sports food supplements (SSFs) are subject to specific laws and regulations. Up to 70% of athletes are highly influenced by the information on the label or the advertisement of the SSF, which often does not correspond to the scientific evidence, such as health claims. The aim is to analyze such claims relating to sports drinks (SDs) in commercial messages. To this end, an observational and cross-sectional study was conducted based on the analysis of the content and degree of adequacy of the health claims indicated on the labelling or technical data sheet of the SDs with those established by the European legislation in force according to the European Food Safety Authority (EFSA). The SSFs were searched for via Amazon and Google Shopping. A total of 114 health claims were evaluated. No claim fully conformed with the recommendations. A total of 14 claims (n = 13 products) almost conformed to the recommendations; they were "Maintain endurance level in exercises requiring prolonged endurance", "Improve water absorption during physical exercise", and "Improved physical performance during high intensity, high duration physical exercise in trained adults", representing 12.3% of the total (n = 114). The vast majority of the claims identified indicated an unproven cause-effect and should be modified or eliminated, which amounts to food fraud towards the consumer.

Worldwide prevalence of obsessive-compulsive symptoms during the COVID-19 pandemic: A systematic review and meta-analysis.

During the COVID-19 pandemic governments worldwide implemented contagion-containing measures (i.e., physical distancing, hand sanitizing, mask wearing and quarantine). The similarities between these measures and obsessive-compulsive phenomenology (e.g., contamination concerns and repetitive washing and/or checking) led to inquiries about the frequency with which obsessive-compulsive symptoms (OCS) were encountered during the COVID-19 pandemic. We conducted a systematic review and meta-analysis to ascertain the prevalence of OCS in individuals of any age during the pandemic (i.e., any obsessive-compulsive symptoms that are clinically significant as shown by a score above the cut-off score of a scale, without necessarily fulfilling the diagnostic threshold for a diagnosis of OCD). A systematic search of relevant databases identified 35 studies, which were included in the systematic review following our inclusion and exclusion criteria. Most of the studies were conducted in adults from the general population and adopted an online assessment method, with 32 studies being eligible for meta-analysis. The meta-analysis resulted in a 20% average prevalence of OCS during the pandemic, with very high heterogeneity among the included studies (I2 99.6%). The highest prevalence of OCS was found in pregnant women (36%, n = 5), followed by individuals diagnosed with COVID-19 (22%, n = 4) and general population (22%, n = 19), undergraduates (21%, n = 5), and healthcare workers (5%, n = 5). The prevalence rates of OCS were higher in Asia (26%, n = 17) and North America (25%, n = 3) than in Europe (13%, n = 12) and Africa (7%, n = 4). Among the studies included, rates appeared higher in certain countries, though this difference did not reach statistical significance and was limited by very few studies conducted in certain countries. When compared to pre-pandemic rates, there seemed to be higher rates of OCS during the COVID-19 pandemic in Asia, Europe, and pregnant women. These findings are discussed considering the impact of the pandemic and contagion-containing measures on the perception and reporting of OCS, and susceptibility of the vulnerable population groups to experiencing OCS during the pandemic.

PSMB8 encoding the ß5i proteasome subunit is mutated in joint contractures, muscle atrophy, microcytic anemia, and panniculitis-induced lipodystrophy syndrome.

We performed homozygosity mapping in two recently reported pedigrees from Portugal and Mexico with an autosomal-recessive autoinflammatory syndrome characterized by joint contractures, muscle atrophy, microcytic anemia, and panniculitis-induced lipodystrophy (JMP). This revealed only one homozygous region spanning 2.4 Mb (5818 SNPs) on chromosome 6p21 shared by all three affected individuals from both families. We directly sequenced genes involved in immune response located in this critical region, excluding the HLA complex genes. We found a homozygous missense mutation c.224C>T (p.Thr75Met) in the proteasome subunit, beta-type, 8 (PSMB8) gene in affected patients from both pedigrees. The mutation segregated in an autosomal-recessive fashion and was not detected in 275 unrelated ethnically matched healthy subjects. PSMB8 encodes a catalytic subunit of the 20S immunoproteasomes called ß5i. Immunoproteasome-mediated proteolysis generates immunogenic epitopes presented by major histocompatibility complex (MHC) class I molecules. Threonine at position 75 is highly conserved and its substitution with methionine disrupts the tertiary structure of PSMB8. As compared to normal lymphoblasts, those from an affected patient showed significantly reduced chymotrypsin-like proteolytic activity mediated by immunoproteasomes. We conclude that mutations in PSMB8 cause JMP syndrome, most probably by affecting MHC class I antigen processing.

Characterisation of pks15/1 in clinical isolates of Mycobacterium tuberculosis from Mexico.

Tuberculosis (TB) is an infectocontagious respiratory disease caused by members of the Mycobacterium tuberculosis complex. A 7 base pair (bp) deletion in the locus polyketide synthase (pks)15/1 is described as polymorphic among members of the M. tuberculosis complex, enabling the identification of Euro-American, Indo-Oceanic and Asian lineages. The aim of this study was to characterise this locus in TB isolates from Mexico. One hundred twenty clinical isolates were recovered from the states of Veracruz and Estado de Mexico. We determined the nucleotide sequence of a ± 400 bp fragment of the locus pks15/1, while genotypic characterisation was performed by spoligotyping. One hundred and fifty isolates contained the 7 bp deletion, while five had the wild type locus. Lineages X (22%), LAM (18%) and T (17%) were the most frequent; only three (2%) of the isolates were identified as Beijing and two (1%) EAI-Manila. The wild type pks15/1 locus was observed in all Asian lineage isolates tested. Our results confirm the utility of locus pks15/1 as a molecular marker for identifying Asian lineages of the M. tuberculosis complex. This marker could be of great value in the epidemiological surveillance of TB, especially in countries like Mexico, where the prevalence of such lineages is unknown.

Longitudinal Course of Obsessive-Compulsive Symptoms During the Covid-19 Pandemic: A Systematic Review of Three Years of Prospective Cohort Studies.

Objective: During the pandemic, there has been a slight increase in obsessive-compulsive symptoms in both clinical and non-clinical samples. Three years after the pandemic, we conducted the first systematic review of prospective cohort studies assessing temporal changes in obsessive-compulsive symptoms and their extent in both patients with obsessive-compulsive disorder (OCD) and community samples, regardless of age or socio-cultural background, during any phase of the pandemic. Method: Prospective cohort studies were included if validated self-report questionnaires or standardized interviews for obsessive-compulsive symptoms were used. Studies that enrolled OCD patients were included if OCD was diagnosed before the outbreak of the pandemic. The following were our exclusion criteria: cross-sectional and case-control studies, single case studies, editorials, commentaries, and reviews. Studies assessing the effectiveness of an intervention were excluded. Results: 15 studies were included. Overall, studies showed a small upsurge in obsessive-compulsive symptoms, especially washing/contamination symptoms, during the coronavirus outbreak. The severity of symptoms seemed to follow the pattern of restriction measures and the increase in the number of COVID-19 cases. Conclusions: Factors contributing to the worsening of obsessive-compulsive symptoms during the pandemic were discussed.

Severity and Changes in OCD Dimensions during COVID-19: A Two-Year Longitudinal Study.

BACKGROUND: The COVID-19 pandemic appears to be associated with a worsening of obsessive-compulsive symptoms in both young people and adults with OCD and it is necessary to analyze the variables involved in this worsening over time. The main aim of this study was to examine long-term changes in total severity and obsessive-compulsive dimensions in obsessive-compulsive patients during the COVID-19 pandemic. METHOD: A total 250 OCD patients were selected from various associations, clinical centers and hospitals. We discarded 75 as they did not meet the inclusion criteria. A total of 175 obsessive-compulsive participants aged between 16 and 58 years old (M = 33.33, SD = 9.42) were evaluated in obsessive-compulsive symptom severity and dimensions OCD assessed using the Y-BOCS and D-YBOCS scales in T1 (April-June 2020) and in T2 (March-April 2022). The evaluation was carried out through an online survey and face-to-face with a professional clinician at both time points. RESULTS: Intragroup differences in severity were observed, reaching higher scores for patients with contamination, somatic, aggressive and religious. Some patients changed their main dimension, increasing the percentage of patients with contamination and somatic obsessions. CONCLUSIONS: COVID-19 was associated with both changes in severity and also affected some dimensions more than others, particularly those related to the virus itself (contamination and somatic).

The distribution and diversity of eukaryotic phytoplankton in the Icelandic marine environment.

Phytoplankton play a crucial role in the marine food web and are sensitive indicators of environmental change. Iceland is at the center of a contrasting hydrography, with cold Arctic water coming in from the north and warmer Atlantic water from the south, making this geographical location very sensitive to climate change. We used DNA metabarcoding to determine the biogeography of phytoplankton in this area of accelerating change. Seawater samples were collected in spring (2012-2018), summer (2017) and winter (2018) together with corresponding physico-chemical metadata around Iceland. Amplicon sequencing of the V4 region of the 18S rRNA gene indicates that eukaryotic phytoplankton community composition is different between the northern and southern water masses, with some genera completely absent from Polar Water masses. Emiliania was more dominant in the Atlantic-influenced waters and in summer, and Phaeocystis was more dominant in the colder, northern waters and in winter. The Chlorophyta picophytoplankton genus, Micromonas, was similarly dominant to the dominant diatom genus, Chaetoceros. This study presents an extensive dataset which can be linked with other 18s rRNA datasets for further investigation into the diversity and biogeography of marine protists in the North Atlantic.

Remdesivir plus dexamethasone is associated to improvement in the clinical outcome of COVID-19 hospitalized patients regardless of their vaccination status.

INTRODUCTION: Remdesivir seems to reduce the risk of hospitalization and improve clinical outcome in hospitalized patients with COVID-19. OBJECTIVES: To compare the clinical outcome of COVID-19 hospitalized patients treated with remdesivir plus dexamethasone versus dexamethasone alone, according to their vaccination status. MATERIAL AND METHODS: A retrospective observational study was carried out in 165 patients hospitalized for COVID-19 from October 2021 to January 2022. Multivariate logistic regression, Kaplan-Meier and the log-rank tests were used to evaluate the event (need for ventilation or death). RESULTS: Patients treated with remdesivir plus dexamethasone (n=87) compared with dexamethasone alone (n=78) showed similar age (60±16, 47-70 vs. 62±37, 51-74 years) and number of comorbidities: 1 (0-2) versus 1.5 (1-3). Among 73 fully vaccinated patients, 42 (47.1%) were in remdesivir plus dexamethasone and 31 (41%) in dexamethasone alone. Patients treated with remdesivir plus dexamethasone needed intensive care less frequently (17.2% vs. 31%; p=0.002), high-flow oxygen (25.3% vs. 50.0%; p=0.002) and non-invasive mechanical ventilation (16.1% vs. 47.4%; p<0.001). Furthermore, they had less complications during hospitalization (31.0% vs. 52.6%; p=0.008), need of antibiotics (32.2% vs. 59%; p=0.001) and radiologic worsening (21.8% vs. 44.9%; p=0.005). Treatment with remdesivir plus dexamethasone (aHR, 0.26; 95% CI: 0.14-0.48; p<0.001) and vaccination (aHR 0.39; 95% CI: 0.21-0.74) were independent factors associated with lower progression to mechanical ventilation or death. CONCLUSIONS: Remdesivir in combination with dexamethasone and vaccination independently and synergistically protects hospitalized COVID-19 patients requiring oxygen therapy from progression to severe disease or dead.

Coping Strategies, Anxiety and Depression in OCD and Schizophrenia: Changes during COVID-19.

BACKGROUND: The main aim was to examine changes in coping strategies, anxiety and depression in obsessive-compulsive and schizophrenia patients during COVID-19, in addition to controlling the influence of intolerance to uncertainty and experiential avoidance. METHOD: The first time, the study comprised (15-30 April 2020) 293 patients, 113 of whom were diagnosed with obsessive-compulsive disorder, 61 with schizophrenia and 119 healthy controls, aged 13-77 years (M = 37.89, SD = 12.65). The second time (15-30 November), the study comprised 195 participants (85 obsessive-compulsive patients, 42 schizophrenic patiens and 77 healthy controls participants). The evaluation was carried out through an online survey. RESULTS: The clinical groups worsened over time in cognitive coping, anxiety and depression, while the control group only worsened in depression. Intergroup differences in anxiety, depression and coping strategies were maintained, highlighting the use of some maladaptive strategies (avoidance, spiritual) in clinical groups. Experiential avoidance and tolerance for uncertainty mainly affected coping. CONCLUSIONS: The duration of COVID-19 not only produced changes in anxiety and depression in clinical groups but also in coping strategies to face this pandemic and its consequences.

Coping strategies in obsessive-compulsive patients during Covid-19 lockdown.

The main aim of this study was to compare coping strategies in obsessive-compulsive disorder (OCD) patients and a healthy control group during COVID-19 lockdown and to analyze the relationship with some variables which may influence results (depression, anxiety, comorbidity, subtype of obsession-compulsion). METHOD: There were 237 participants, 122 OCD and 115 healthy controls, aged 17-61 years old (M = 33.48, SD = 11.13). RESULTS: Groups showed differences in the use of some adaptive strategies (positive reinterpretation, acceptance, humor) and maladaptive (denial, self-blame). Within obsessive-compulsive group, comorbidity affected the greater use of inappropriate strategies (denial, substance abuse and self-blame) while type of obsession-compulsion did not influence use. Anxiety and depression levels were related to the use of less adaptive strategies. CONCLUSIONS: These findings strengthen the need for training in the use of effective and adaptive coping strategies, making it necessary to improve clinical follow-up of these patients. It is relevant to be in contact with healthcare professionals, review medication and observe the anxiety and depression levels.

El objetivo de este estudio fue comparar las estrategias de afrontamiento utilizadas por pacientes con Trastorno obsesivo-compulsivo (TOC) durante el confinamiento debido a la COVID-19 frente a controles sanos y analizar su relación con algunas variables que pueden influir en los resultados (ansiedad, depresión, comorbilidad, tipo de obsesiones-compulsiones). Método: Los participantes fueron 237, 122 diagnosticados de Trastorno obsesivo-compulsivo y 115 controles sanos, con edades comprendidas entre 13 y 58 años (M = 34,60, DT = 10,41). Resultados: Los grupos presentaron diferencias en el uso de algunas estrategias adaptativas (reinterpretación positiva, aceptación, humor) y desadaptativas (negación, autoculpa). Dentro del grupo TOC, la comorbilidad afectó para el mayor uso de estrategias inadecuadas (negación, abuso de sustancias y autoculpa), mientras que el tipo de obsesiones-compulsiones no influyó en el uso de las mismas. Los niveles de ansiedad y depresión estaban relacionadas con el uso de estrategias menos adaptativas. Conclusiones: Estos hallazgos refuerzan la necesidad de entrenar en la utilización de estrategias de afrontamiento eficaces y adaptativas, siendo necesario mejorar el seguimiento clínico de estos pacientes. Es importante estar en contacto con profesionales de la salud, revisar la medicación y observar los niveles de ansiedad y depresión.

Hereditary angioedema due to C1 inhibitor deficiency: real-world experience from the Icatibant Outcome Survey in Spain.

BACKGROUND: The Icatibant Outcome Survey (IOS) is an international registry monitoring the use of icatibant, a bradykinin B2 receptor antagonist indicated for the acute treatment of hereditary angioedema (HAE) attacks. Our goal was to assess disease characteristics and icatibant treatment outcomes in patients with HAE due to C1 inhibitor deficiency (HAE type 1 or 2 (HAE-1/2)) from Spain relative to other countries participating in IOS. METHODS: Descriptive retrospective analyses of data are reported from 10 centers in Spain vs 51 centers in 12 other participating countries (July 2009 to January 2019). RESULTS: No meaningful differences were identified between patients in Spain (n = 119) and patients across other countries (n = 907) regarding median age at symptom onset (15.0 vs 12.0 years) or diagnosis (22.3 vs 20.5 years). Overall HAE attack rates (total attacks/total years of follow-up) were 2.66 in Spain and 1.46 across other countries. Patients in Spain reported fewer severe/very severe HAE attacks before treatment (41.0% vs 45.9%; P < 0.0001) and, for icatibant-treated attacks, longer median time to treatment (2.9 vs 1.0 h), time to attack resolution (18.0 vs 5.5 h), and total attack duration (24.6 vs 8.0 h). Use of androgens for long-term prophylaxis was higher in Spain (51.2% vs 26.7%). CONCLUSION: Patients with HAE-1/2 in Spain reported fewer severe/very severe attacks, administered icatibant later, and had longer-lasting attacks than did patients across other countries in IOS. These differences may indicate varying disease management practices (e.g., delayed icatibant treatment) and reporting. Efforts to raise awareness on the benefits of early on-demand treatment may be warranted. TRIAL REGISTRATION: NCT01034969.

Norms for Testing Visual Binding Using the Memory Associative Test (TMA-93) in Older Educationally-Diverse Adults.

BACKGROUND: TMA-93 examines binding by images, a potential advantage for less-educated individuals. OBJECTIVE: To obtain norms from older Spanish adults for TMA-93. METHODS: A cross-sectional normative study was undertaken in a general neurology outpatient clinic of a university hospital in the Southern Spanish region of Andalusia. Partners of patients who attended the clinic were systematically recruited when eligible: aged 50 and over, no memory complaints, and a total score equal or above percentile 10 on Phototest. Age, gender, and educational attainment were considered as sociodemographic variables. TMA-93 was administered and the total score was registered. RESULTS: The final sample contained 1,131 participants (mean age = 65.7, SD = 9.2), including 305 individuals (27%) who did not completed primary studies. The total score on TMA-93 showed a non-normal, left asymmetric, and leptokurtic distribution (median = 29, interquartile range = 27-30, range = 16-30) mitigated by lower education and older age. Stratified analysis by age and education showed wide variations of the scores for the 5-percentile. CONCLUSION: TMA-93 runs with a ceiling effect in non-cognitively impaired older Spanish adults. The score for the 5-percentile depends on age and education. The test is feasible for low-educated individuals.

Olefin metathesis-iodoetherification-dehydroiodination strategy for spiroketal subunits of polyether antibiotics.

The convergent synthesis of two pentacyclic analogues of the polyether monensin A is described. Although different with respect to the configuration of the alcohol at the 3 position of the six-membered ring of the spiroketal subunit, the configuration at the acetal center in both structures is unchanged and is consistent with the anomeric effect. The key synthetic steps are the coupling of two complex segments via an olefin metathesis, and the subsequent conversion of a dihydroxyalkene to the spiroketal through an iodoetherification-dehydroiodination sequence. The compatibility of these transformations with a variety of functional groups makes the overall strategy appropriate for highly substituted frameworks.

TMA-93 for Diagnosing Amnestic Mild Cognitive Impairment: A Comparison With the Free and Cued Selective Reminding Test.

BACKGROUND: TMA-93 examines binding by images, an advantage for the less educated individuals. AIM: To compare the discriminative validity of TMA-93 against the picture version of Free and Cued Selective Reminding Test (FCSRT) to distinguish patients with amnestic mild cognitive impairment (aMCI) from normal controls (NCs) without excluding less educated individuals. DESIGN: Phase I diagnostic evaluation study. PARTICIPANTS: A total of 30 patients with aMCI and 30 NCs matched for sociodemographics variables. STATISTICAL ANALYSIS: The diagnostic accuracy for each test was calculated by conducting receiver operating characteristic curve analysis. Hanley and McNeil method was used to compare diagnostic accuracy of different tests on the same sample. RESULTS: Up to 41.7% of the sample had less than a first grade of education. Both tests showed excellent diagnostic accuracy. The comparisons did not show significant differences. CONCLUSIONS: TMA-93 is so accurate as FCSRT to differentiate aMCI from controls including less educated individuals. The test could be considered as a choice in this sociodemographic context.

Long-Term Outcomes with Subcutaneous C1-Inhibitor Replacement Therapy for Prevention of Hereditary Angioedema Attacks.

BACKGROUND: For the prevention of attacks of hereditary angioedema (HAE), the efficacy and safety of subcutaneous human C1-esterase inhibitor (C1-INH[SC]; HAEGARDA, CSL Behring) was established in the 16-week Clinical Study for Optimal Management of Preventing Angioedema with Low-Volume Subcutaneous C1-Inhibitor Replacement Therapy (COMPACT). OBJECTIVE: To assess the long-term safety, occurrence of angioedema attacks, and use of rescue medication with C1-INH(SC). METHODS: Open-label, randomized, parallel-arm extension of COMPACT across 11 countries. Patients with frequent angioedema attacks, either study treatment-naive or who had completed COMPACT, were randomly assigned (1:1) to 40 IU/kg or 60 IU/kg C1-INH(SC) twice per week, with conditional uptitration to optimize prophylaxis (ClinicalTrials.gov registration no. NCT02316353). RESULTS: A total of 126 patients with a monthly attack rate of 4.3 in 3 months before entry in COMPACT were enrolled and treated for a mean of 1.5 years; 44 patients (34.9%) had more than 2 years of exposure. Mean steady-state C1-INH functional activity increased to 66.6% with 60 IU/kg. Incidence of adverse events was low and similar in both dose groups (11.3 and 8.5 events per patient-year for 40 IU/kg and 60 IU/kg, respectively). For 40 IU/kg and 60 IU/kg, median annualized attack rates were 1.3 and 1.0, respectively, and median rescue medication use was 0.2 and 0.0 times per year, respectively. Of 23 patients receiving 60 IU/kg for more than 2 years, 19 (83%) were attack-free during months 25 to 30 of treatment. CONCLUSIONS: In patients with frequent HAE attacks, long-term replacement therapy with C1-INH(SC) is safe and exhibits a substantial and sustained prophylactic effect, with the vast majority of patients becoming free from debilitating disease symptoms.