Lipodystrophy syndromes are a group of disorders characterized by a loss of adipose tissue once other situations of nutritional deprivation or exacerbated catabolism have been ruled out. With the ...exception of the HIV-associated lipodystrophy, they have a very low prevalence, which together with their large phenotypic heterogeneity makes their identification difficult, even for endocrinologists and pediatricians. This leads to significant delays in diagnosis or even to misdiagnosis. Our group has developed an algorithm that identifies the more than 40 rare lipodystrophy subtypes described to date. This algorithm has been implemented in a free mobile application, LipoDDx®. Our aim was to establish the effectiveness of LipoDDx®. Forty clinical records of patients with a diagnosis of certainty of most lipodystrophy subtypes were analyzed, including subjects without lipodystrophy. The medical records, blinded for diagnosis, were evaluated by 13 physicians, 1 biochemist and 1 dentist. Each evaluator first gave his/her results based on his/her own criteria. Then, a second diagnosis was given using LipoDDx®. The results were analysed based on a score table according to the complexity of each case and the prevalence of the disease.
LipoDDx® provides a user-friendly environment, based on usually dichotomous questions or choice of clinical signs from drop-down menus. The final result provided by this app for a particular case can be a low/high probability of suffering a particular lipodystrophy subtype. Without using LipoDDx® the success rate was 17 ± 20%, while with LipoDDx® the success rate was 79 ± 20% (p < 0.01).
LipoDDx® is a free app that enables the identification of subtypes of rare lipodystrophies, which in this small cohort has around 80% effectiveness, which will be of help to doctors who are not experts in this field. However, it will be necessary to analyze more cases in order to obtain a more accurate efficiency value.
We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) allele groups and alleles by PCR-SSP based typing in a total of 15,318 mixed ancestry Mexicans from all the states of the country ...divided into 78 sample sets, providing information regarding allelic and haplotypic frequencies and their linkage disequilibrium, as well as admixture estimates and genetic substructure. We identified the presence of 4268 unique HLA extended haplotypes across Mexico and find that the ten most frequent (HF > 1%) HLA haplotypes with significant linkage disequilibrium (Δ’≥0.1) in Mexico (accounting for 20% of the haplotypic diversity of the country) are of primarily Native American ancestry (A*02~B*39~DRB1*04~DQB1*03:02, A*02~B*35~DRB1*08~DQB1*04, A*68~B*39~DRB1*04~DQB1*03:02, A*02~B*35~DRB1*04~DQB1*03:02, A*24~B*39~DRB1*14~DQB1*03:01, A*24~B*35~DRB1*04~DQB1*03:02, A*24~B*39~DRB1*04~DQB1*03:02, A*02~B*40:02~DRB1*04~DQB1*03:02, A*68~B*35~DRB1*04~DQB1*03:02, A*02~B*15:01~DRB1*04~DQB1*03:02). Admixture estimates obtained by a maximum likelihood method using HLA-A/-B/-DRB1 as genetic estimators revealed that the main genetic components in Mexico as a whole are Native American (ranging from 37.8% in the northern part of the country to 81.5% in the southeastern region) and European (ranging from 11.5% in the southeast to 62.6% in northern Mexico). African admixture ranged from 0.0 to 12.7% not following any specific pattern. We were able to detect three major immunogenetic clusters correlating with genetic diversity and differential admixture within Mexico: North, Central and Southeast, which is in accordance with previous reports using genome-wide data. Our findings provide insights into the population immunogenetic substructure of the whole country and add to the knowledge of mixed ancestry Latin American population genetics, important for disease association studies, detection of demographic signatures on population variation and improved allocation of public health resources.
La evaluación varía según la metodología y alumnado al que va dirigido el proceso de enseñanza, ya que esta se adapta a su contexto y nivel de instrucción. En relación con el objeto de nuestro ...estudio, los SPOC (del inglés Small Private Online Course), mantienen diferentes variaciones en cuanto a los modelos e instrumentos de evaluación. La forma de evaluar en los SPOC varía según el alumnado al que va dirigido el curso, el propio diseño del SPOC y el enfoque que el propio docente quiera darle. El objetivo principal de esta investigación es analizar los modelos e instrumentos de evaluación que se implementan en los SPOC. Se pretende comprender como se desarrolla la evaluación en los SPOC, a través de las líneas de investigación más actuales. Para ello, la investigación se ha llevado a cabo a través de un estudio teórico de la bibliografía actual y especifica en la materia. Los resultados reflejan una preferencia, en lo que respecta a la finalidad, por la evaluación sumativa. En relación con el momento de recogida de información, la evaluación inicial junto con la final, son los modelos más utilizados. En cuanto al agente evaluador, la autoevaluación es el modelo más implementado. Entre los instrumentos, las autoevaluaciones y las pruebas tipo test son las herramientas más implementadas para recoger evidencias sobre el proceso de aprendizaje. Como conclusión, pese a que las características pedagógicas de los SPOC favorecen la adopción de unos modelos e instrumentos de evaluación, el acuerdo sobre modelos y herramientas de evaluación queda subordinado a la intención concreta de cada SPOC.
Background and objectives
Intermittent theta-burst stimulation (iTBS) is a patterned form of excitatory transcranial magnetic stimulation that has yielded encouraging results as an adjunctive ...therapeutic option to alleviate the emergence of clinical deficits in Parkinson’s disease (PD) patients. Although it has been demonstrated that iTBS influences dopamine-dependent corticostriatal plasticity, little research has examined the neurobiological mechanisms underlying iTBS-induced clinical enhancement. Here, our primary goal is to verify whether iTBS bilaterally delivered over the primary motor cortex (M1) is effective as an add-on treatment at reducing scores for both motor functional impairment and nonmotor symptoms in PD. We hypothesize that these clinical improvements following bilateral M1-iTBS could be driven by endogenous dopamine release, which may rebalance cortical excitability and restore compensatory striatal volume changes, resulting in increased striato-cortico-cerebellar functional connectivity and positively impacting neuroglia and neuroplasticity.
Methods
A total of 24 PD patients will be assessed in a randomized, double-blind, sham-controlled crossover study involving the application of iTBS over the bilateral M1 (M1 iTBS). Patients on medication will be randomly assigned to receive real iTBS or control (sham) stimulation and will undergo 5 consecutive sessions (5 days) of iTBS over the bilateral M1 separated by a 3-month washout period. Motor evaluation will be performed at different follow-up visits along with a comprehensive neurocognitive assessment; evaluation of M1 excitability; combined structural magnetic resonance imaging (MRI), resting-state electroencephalography and functional MRI; and serum biomarker quantification of neuroaxonal damage, astrocytic reactivity, and neural plasticity prior to and after iTBS.
Discussion
The findings of this study will help to clarify the efficiency of M1 iTBS for the treatment of PD and further provide specific neurobiological insights into improvements in motor and nonmotor symptoms in these patients. This novel project aims to yield more detailed structural and functional brain evaluations than previous studies while using a noninvasive approach, with the potential to identify prognostic neuroprotective biomarkers and elucidate the structural and functional mechanisms of M1 iTBS-induced plasticity in the cortico-basal ganglia circuitry. Our approach may significantly optimize neuromodulation paradigms to ensure state-of-the-art and scalable rehabilitative treatment to alleviate motor and nonmotor symptoms of PD.
Monopolar radiofrequency ablation (MRFA) of the genicular nerves has been considered the main interventional treatment for chronic knee pain. However, the variable locations of these nerves could ...suggest that traditional MRFA of genicular nerves may be insufficient to cover the area needed to provide complete sensory denervation. For these reasons, some alternatives have been proposed to achieve an increase in the lesion area that offers better outcomes such a bipolar radiofrequency ablation (BRFA).
To describe the efficacy and safety of the bipolar radiofrequency ablation (BRFA) of the genicular nerves in the patients with chronic knee pain.
A retrospective study was conducted in the Pain Medicine Department. Institutional review board approval from the Hospital Ethical Committee and informed consent were obtained. We reviewed our database for BRFA of genicular nerves from January 2018 to December 2021 for patients with chronic knee pain. The cannulas were placed using ultrasound guidance (10 cm, 22-gauge and 10 mm active curved tip), and each pair of cannulas were subjected to BRFA for 90 seconds at 80∘C. Data analysis was conducted using T-test for paired variables (Visual analogue scale and EuroQol, an instrument intended to complement other forms of quality-of-life measures).
Twenty-five patients met inclusion criteria after excluding 7 based on the study design. The mean improvement of our patients according to the VAS was -3.98 (95%CI: -4.37 to -3.59) p< 0.0001 and EuroQol +0.416 (95%CI: 0.364 to 0.468) p< 0.0001. The mean duration of improvement was 8 (6-11) months after BRFA. There were no reported serious adverse events related to the procedure, only local pain for 24 to 48 hours in 3 patients.
We can conclude that BRFA reduces procedural pain and increases the treatment area, providing more complete sensory denervation and improved clinical outcomes.
Azole resistance screening in
can be routinely carried out by using azole-containing agar plates (E.Def 10.2 procedure); however, conidial suspension filtering and inoculum adjustment before inoculum ...preparation are time-consuming. We evaluated whether skipping the filtration and inoculum adjustment steps negatively influenced the performance of the E.Def 10.2 procedure.
isolates (
= 98), previously classified as azole susceptible or azole resistant (E.Def 9.4 method), were studied. Azole-resistant isolates had either the wild-type
gene sequence (
= 1) or the following
gene substitutions: TR
-L98H (
= 41), G54R (
= 5), TR
-Y121F-T289A (
= 1), or G448S (
= 1). In-house azole-containing agar plates were prepared according to the EUCAST E.Def 10.2 procedure. Conidial suspensions obtained by adding distilled water (Tween 20 0.1%) were either filtered and the inocula adjusted to 0.5 McFarland or left unfiltered and unadjusted. Agreements between the agar screening methods using inocula prepared by each procedure were high for itraconazole (99%), voriconazole (100%), and posaconazole (94.9%). Sensitivity and specificity (considering the susceptibility category as per the microdilution E.Def 9.4 method as the gold standard) of E.Def 10.2 were 100% to rule in or rule out resistance when unfiltered and unadjusted suspensions were used; the resistance phenotype of isolates harboring the TR
-L98H, G54R, or TR
-Y121F-T289A substitutions was correctly detected. Unfiltered and unadjusted conidial suspensions do not negatively influence the performance of the E.Def 10.2 method when screening for azole resistance in
.
Azole resistance screening in
can be routinely carried out by using azole-containing plates (E.Def 10.2 procedure); however, conidial suspension filtering and inoculum adjustment before inoculation of plates are time-consuming. We, here, showed that unfiltered and unadjusted conidial suspensions do not negatively influence the performance of the E.Def 10.2 method when screening for azole resistance in
.
The omicron (B.1.1.529) variant of SARS-CoV-2 has increased capacity to elude immunity and cause breakthrough infections. The aim of this study was to estimate the effectiveness of mRNA-based vaccine ...boosters (third dose) against infection with the omicron variant by age, sex, time since complete vaccination, type of primary vaccine, and type of booster.
In this nationwide cohort study, we linked data from three nationwide population registries in Spain (Vaccination Registry, Laboratory Results Registry, and National Health System registry) to select community-dwelling individuals aged 40 years or older, who completed their primary vaccine schedule at least 3 months before the start of follow-up, and had not tested positive for SARS-CoV-2 since the start of the pandemic. On each day between Jan 3, and Feb 6, 2022, we matched individuals who received a booster mRNA vaccine and controls of the same sex, age group, postal code, type of vaccine, time since primary vaccination, and number of previous tests. We estimated risk of laboratory-confirmed SARS-CoV-2 infection using the Kaplan-Meier method and compared groups using risk ratios (RR) and risk differences. Vaccine effectiveness was calculated as one minus RR.
Between Jan 3, and Feb 6, 2022, 3 111 159 matched pairs were included in our study. Overall, the estimated effectiveness from day 7 to 34 after a booster was 51·3% (95% CI 50·2–52·4). Estimated effectiveness was 52·5% (51·3–53·7) for an mRNA-1273 booster and 46·2% (43·5–48·7) for a BNT162b2 booster. Effectiveness was 58·6% (55·5–61·6) if primary vaccination had been with ChAdOx1 nCoV-19 (Oxford–AstraZeneca), 55·3% (52·3–58·2) with mRNA-1273 (Moderna), 49·7% (48·3–51·1) with BNT162b2 (Pfizer–BioNTech), and 48·0% (42·5–53·7) with Ad26.COV2.S (Janssen). Estimated effectiveness was 43·6% (40·0–47·1) when the booster was administered between 151 days and 180 days after complete vaccination and 52·2% (51·0–53·3) if administered more than 180 days after primary scheduled completion.
Booster mRNA vaccine-doses were moderately effective in preventing infection with the omicron variant of SARS-CoV-2 for over a month after administration, which indicates their suitability as a strategy to limit the health effects of COVID-19 in periods of omicron variant domination. Estimated effectiveness was higher for mRNA-1273 compared with BNT162b2 and increased with time between completed primary vaccination and booster.
None.
HeartLogic es un algoritmo multiparamétrico incorporado a desfibriladores automáticos implantables (DAI). La alerta asociada predice descompensaciones de insuficiencia cardiaca (IC). Nuestro objetivo ...es analizar la asociación entre alertas y eventos clínicos bajo un protocolo de seguimiento común en un registro multicéntrico.
Se evaluaron la fase 1 (investigadores ciegos al estado de la alerta) y las fases 2 y 3 (tras la activación de HeartLogic, según práctica local y un protocolo común respectivamente).
Se incluyó a 288 pacientes en 15 centros. En fase 1, tras una media de observación de 10 meses, hubo 73 alertas (0,72 alertas/paciente-año), con 8 hospitalizaciones y 2 visitas a urgencias por IC (0,10 eventos/año-paciente). No hubo hospitalizaciones fuera del periodo de alerta. Las fases activas tuvieron una media de seguimiento de 16 (IC95%, 15-22) meses, con 277 alertas (0,89 alertas/año-paciente); 33 se asociaron con hospitalizaciones o muerte por IC, 46 con descompensaciones menores y 78 con otros eventos. La tasa de alertas inexplicables fue 0,39/año-paciente. Fuera del estado de alerta solo hubo una hospitalización y una descompensación menor. La mayoría de las alertas (el 82% en fase 2 y el 81% en fase 3; p=0,861) se gestionaron a distancia. La mediana de NT-proBNP fue superior en estado de alerta que fuera de él (7.378 frente a 1.210 pg/ml; p <0,001).
El índice HeartLogic se asoció con descompensaciones de IC y otros eventos relevantes, con baja tasa de alertas inexplicables. Un protocolo estandarizado permitió detectar y actuar a distancia con seguridad sobre las alertas.
HeartLogic is a multiparametric algorithm incorporated into implantable cardioverter-defibrillators (ICD). The associated alerts predict impending heart failure (HF) decompensations. Our objective was to analyze the association between alerts and clinical events and to describe the implementation of a protocol for remote management in a multicenter registry.
We evaluated study phase 1 (the investigators were blinded to the alert state) and phases 2 and 3 (after HeartLogic activation, managed as per local practice and with a standardized protocol, respectively).
We included 288 patients from 15 centers. In phase 1, the median observation period was 10 months and there were 73 alerts (0.72 alerts/patient-y), with 8 hospitalizations and 2 emergency room admissions for HF (0.10 events/patient-y). There were no HF hospitalizations outside the alert period. In the active phases, the median follow-up was 16 (95%CI, 15-22) months and there were 277 alerts (0.89 alerts/patient-y); 33 were associated with HF hospitalizations or HF death (n=6), 46 with minor decompensations, and 78 with other events. The unexplained alert rate was 0.39 alerts/patient-y. Outside the alert state, there was only 1 HF hospitalization and 1 minor HF decompensation. Most alerts (82% in phase 2 and 81% in phase 3; P=.861) were remotely managed. The median NT-proBNP value was higher within than outside the alert state (7378 vs 1210 pg/mL; P <.001).
The HeartLogic index was frequently associated with HF-related events and other clinically relevant situations, with a low rate of unexplained events. A standardized protocol allowed alerts to be safely and remotely detected and appropriate action to be taken on them.
Full English text available from:www.revespcardiol.org/en
HeartLogic is a multiparametric algorithm incorporated into implantable cardioverter-defibrillators (ICD). The associated alerts predict impending heart failure (HF) decompensations. Our objective ...was to analyze the association between alerts and clinical events and to describe the implementation of a protocol for remote management in a multicenter registry.
We evaluated study phase 1 (the investigators were blinded to the alert state) and phases 2 and 3 (after HeartLogic activation, managed as per local practice and with a standardized protocol, respectively).
We included 288 patients from 15 centers. In phase 1, the median observation period was 10 months and there were 73 alerts (0.72 alerts/patient-y), with 8 hospitalizations and 2 emergency room admissions for HF (0.10 events/patient-y). There were no HF hospitalizations outside the alert period. In the active phases, the median follow-up was 16 (95%CI, 15-22) months and there were 277 alerts (0.89 alerts/patient-y); 33 were associated with HF hospitalizations or HF death (n=6), 46 with minor decompensations, and 78 with other events. The unexplained alert rate was 0.39 alerts/patient-y. Outside the alert state, there was only 1 HF hospitalization and 1 minor HF decompensation. Most alerts (82% in phase 2 and 81% in phase 3; P=.861) were remotely managed. The median NT-proBNP value was higher within than outside the alert state (7378 vs 1210 pg/mL; P <.001).
The HeartLogic index was frequently associated with HF-related events and other clinically relevant situations, with a low rate of unexplained events. A standardized protocol allowed alerts to be safely and remotely detected and appropriate action to be taken on them.
HeartLogic es un algoritmo multiparamétrico incorporado a desfibriladores automáticos implantables (DAI). La alerta asociada predice descompensaciones de insuficiencia cardiaca (IC). Nuestro objetivo es analizar la asociación entre alertas y eventos clínicos bajo un protocolo de seguimiento común en un registro multicéntrico.
Se evaluaron la fase 1 (investigadores ciegos al estado de la alerta) y las fases 2 y 3 (tras la activación de HeartLogic, según práctica local y un protocolo común respectivamente).
Se incluyó a 288 pacientes en 15 centros. En fase 1, tras una media de observación de 10 meses, hubo 73 alertas (0,72 alertas/paciente-año), con 8 hospitalizaciones y 2 visitas a urgencias por IC (0,10 eventos/año-paciente). No hubo hospitalizaciones fuera del periodo de alerta. Las fases activas tuvieron una media de seguimiento de 16 (IC95%, 15-22) meses, con 277 alertas (0,89 alertas/año-paciente); 33 se asociaron con hospitalizaciones o muerte por IC, 46 con descompensaciones menores y 78 con otros eventos. La tasa de alertas inexplicables fue 0,39/año-paciente. Fuera del estado de alerta solo hubo una hospitalización y una descompensación menor. La mayoría de las alertas (el 82% en fase 2 y el 81% en fase 3; p=0,861) se gestionaron a distancia. La mediana de NT-proBNP fue superior en estado de alerta que fuera de él (7.378 frente a 1.210 pg/ml; p <0,001).
El índice HeartLogic se asoció con descompensaciones de IC y otros eventos relevantes, con baja tasa de alertas inexplicables. Un protocolo estandarizado permitió detectar y actuar a distancia con seguridad sobre las alertas.
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