RESUMEN
Introduction: Parkinson's disease (PD) is characterized by high-rates of depression with limited evidence-based treatment options to improve mood. Objective: To expand therapeutic options, we evaluated the feasibility and effect of a telehealth mindfulness-based cognitive therapy intervention adapted for PD (MBCT-PD) in a sample of participants with DSM-5 depressive disorders. Methods: Fifteen participants with PD and clinically-significant depression completed 9 sessions of MBCT-PD. Depression, anxiety, and quality of life were evaluated at baseline, endpoint, and 1-month follow-up. Results: Telehealth MBCT-PD was feasible and beneficial. Completion rates exceeded 85% and treatment satisfaction rates were high. Notable improvements were observed for depression, anxiety, and quality of life over the course of the trial. Conclusion: Telehealth MBCT-PD shows promise and warrants further evaluation via randomized clinical trial with more diverse participants. Such research holds the potential to expand the range of therapeutic options for depression in PD, thereby setting the stage for personalized care.
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Terapia Cognitivo-Conductual , Atención Plena , Enfermedad de Parkinson , Telemedicina , Humanos , Proyectos Piloto , Depresión/terapia , Depresión/psicología , Calidad de Vida/psicología , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/terapia , Resultado del TratamientoRESUMEN
BACKGROUND: With the emergence of SARS-CoV-2, influenza surveillance systems in Spain were transformed into a new syndromic sentinel surveillance system. The Acute Respiratory Infection Surveillance System (SiVIRA in Spanish) is based on a sentinel network for acute respiratory infection (ARI) surveillance in primary care and a network of sentinel hospitals for severe ARI (SARI) surveillance in hospitals. METHODS: Using a test-negative design and data from SARI admissions notified to SiVIRA between January 1 and October 3, 2021, we estimated COVID-19 vaccine effectiveness (VE) against hospitalization, by age group, vaccine type, time since vaccination, and SARS-CoV-2 variant. RESULTS: VE was 89% (95% CI: 83-93) against COVID-19 hospitalization overall in persons aged 20 years and older. VE was higher for mRNA vaccines, and lower for those aged 80 years and older, with a decrease in protection beyond 3 months of completing vaccination, and a further decrease after 5 months. We found no differences between periods with circulation of Alpha or Delta SARS-CoV-2 variants, although variant-specific VE was slightly higher against Alpha. CONCLUSIONS: The SiVIRA sentinel hospital surveillance network in Spain was able to describe clinical and epidemiological characteristics of SARI hospitalizations and provide estimates of COVID-19 VE in the population under surveillance. Our estimates add to evidence of high effectiveness of mRNA vaccines against severe COVID-19 and waning of protection with time since vaccination in those aged 80 or older. No substantial differences were observed between SARS-CoV-2 variants (Alpha vs. Delta).
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COVID-19 , Infecciones del Sistema Respiratorio , COVID-19/epidemiología , COVID-19/prevención & control , Vacunas contra la COVID-19 , Hospitalización , Humanos , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/prevención & control , SARS-CoV-2/genética , Vigilancia de Guardia , España/epidemiología , Eficacia de las VacunasRESUMEN
OBJECTIVE: To test whether Mindfulness-Based Cognitive Therapy to Prevent Suicide (MBCT-S) is associated with improvement in attentional control, an objective marker of suicide attempt. METHOD: In the context of a randomized clinical trial targeting suicide risk in Veterans, computerized Stroop and emotion Stroop (E-Stroop) tasks were administered 3 times over 6-months follow-up to 135 high suicide risk Veterans. Seventy were randomized to receive MBCT-S in addition to enhanced treatment as usual (eTAU), and 65 were randomized to eTAU only. E-Stroop word types included positively- and negatively-valenced emotion, suicide, and combat-related words. Interference scores and mixed effects linear regression analyses were used. RESULTS: Veterans receiving MBCT-S showed a more favorable trajectory of attentional control over time, as indicated by performance on two E-Stroop tasks. Combat-stress interference scores improved over time among Veterans in MBCT-S. Interference processing time for negative affective words deteriorated over time among Veterans receiving eTAU only. CONCLUSIONS: MBCT-S may effectively target attentional control, and in particular reduce processing time during affective interference, in high suicide risk Veterans. Future studies to replicate these findings are warranted.
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Terapia Cognitivo-Conductual , Atención Plena , Veteranos , Atención , Humanos , Intento de Suicidio , Resultado del TratamientoRESUMEN
Objective: This study evaluated whether Mindfulness-Based Cognitive Therapy for Preventing Suicide Behavior (MBCT-S) effectively augmented treatment-as-usual enhanced for suicide prevention (eTAU).Methods: From December 2013 through March 2018, veterans (N = 140) at high risk for suicide were recruited mostly (88.6%) during a suicide-related inpatient admission and randomly assigned to either (1) eTAU augmented with MBCT-S or (2) eTAU only. MBCT-S began during inpatient treatment (2 individual sessions emphasizing safety planning) and continued post-discharge (8 group sessions emphasizing mindfulness skills and elaborated safety planning). Four follow-up evaluations occurred over 12 months, and primary outcomes were (1) time to suicide event and (2) number of suicide events. Secondary outcomes were time to and number of suicide attempts, proportion with acute psychiatric hospitalization, and change in suicide-related factors (eg, depression, hopelessness, suicidal ideation).Results: Relative to eTAU, MBCT-S did not significantly delay time to suicide event (hazard ratio = 0.86; 95% CI, 0.52-1.41; P = .54), but did reduce total number of suicide events (MBCT-S: 56 events; eTAU: 92 events; incident rate ratio = 0.59; 95% CI, 0.36-0.99; P < .05). There were no significant differences in time to or number of suicide attempts. In a post hoc analysis, however, MBCT-S significantly reduced the proportion of participants attempting suicide (P < .05). MBCT-S also reduced the proportion with a psychiatric hospitalization. No significant between-group differences emerged on any suicide-related factors.Conclusions: Adding MBCT-S to system-wide suicide prevention efforts produced mixed findings on the primary outcome (suicide events) and promising findings on other important outcomes (suicide attempts, psychiatric hospitalizations). MBCT-S should continue to be examined in future research.Trial Registration: ClinicalTrials.gov identifier: NCT01872338.
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Atención Plena/métodos , Prevención del Suicidio , Veteranos/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ideación Suicida , Intento de Suicidio/prevención & control , Resultado del Tratamiento , Estados UnidosRESUMEN
Suicide-related coping refers to strategies for adaptively managing suicidal urges and can be important an important factor for assessing risk and targeting intervention. The current study evaluated whether suicide-related coping predicted a suicidal event within 90-days, independently of other known risk factors. Veterans (N = 64) were evaluated shortly after a suicidal crisis and completed several assessments, including a measure of suicide-related coping. Multivariate analyses showed that suicide-related coping remained protective of a suicidal event (OR = 0.93; p = .047) after adjusting for suicidal ideation, previous suicide attempts, mood disorder, distress tolerance, and gender. Suicide-related coping may augment commonly assessed clinical factors in prediction of a suicidal event and is a suitable target for suicide prevention efforts.
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Ideación Suicida , Veteranos , Adaptación Psicológica , Humanos , Medición de Riesgo , Factores de Riesgo , Intento de SuicidioRESUMEN
BACKGROUND: Metformin, a ï¬rst-line oral antidiabetic agent that has shown promising results in terms of treating childhood and adolescent obesity, might influence the composition of the gut microbiota. We aimed to evaluate whether the gut microbiota of non-diabetic children with obesity changes after a metformin intervention. METHODS: The study was a multicenter and double-blind randomized controlled trial in 160 children with obesity. Children were randomly assigned to receive either metformin (1 g/day) or placebo for 6 months in combination with healthy lifestyle recommendations in both groups. Then, we conducted a metagenomic analysis in a subsample obtained from 33 children (15 metformin, 18 placebo). A linear mixed-effects model (LMM) was used to determine the abundance changes from baseline to six months according to treatment. To analyze the data by clusters, a principal component analysis was performed to understand whether lifestyle habits have a different influence on the microbiota depending on the treatment group. RESULTS: Actinobacteria abundance was higher after placebo treatment compared with metformin. However, the interaction time x treatment just showed a trend to be significant (4.6% to 8.1% after placebo vs. 3.8 % to 2.6 % after metformin treatment, p = 0.055). At genus level, only the abundance of Bacillus was significantly higher after the placebo intervention compared with metformin (2.5% to 5.7% after placebo vs. 1.5 % to 0.8 % after metformin treatment, p = 0.044). Furthermore, different ensembles formed by Firmicutes, Bacteroidetes, and Verrucomicrobia were found according to the interventions under a similar food consumption. CONCLUSION: Further studies with a large sample size controlled by lifestyle patterns are required in obese children and adolescents to clarify whether metformin might trigger gut microbiota alterations. TRIAL REGISTRATION: Registered on the European Clinical Trials Database (EudraCT, ID: 2010-023061-21) on 14 November 2011.
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Bacterias/efectos de los fármacos , Microbioma Gastrointestinal/efectos de los fármacos , Hipoglucemiantes/uso terapéutico , Intestinos/microbiología , Metagenoma , Metagenómica , Metformina/uso terapéutico , Obesidad Infantil/tratamiento farmacológico , Adolescente , Factores de Edad , Bacterias/genética , Bacterias/crecimiento & desarrollo , Niño , Método Doble Ciego , Femenino , Humanos , Estilo de Vida , Masculino , Obesidad Infantil/diagnóstico , Obesidad Infantil/microbiología , España , Factores de Tiempo , Resultado del TratamientoRESUMEN
Neurocognitive detection of suicidal states has the potential to significantly advance objective risk assessment. This goal requires establishing that neurocognitive deficits fluctuate around the time of a suicide attempt. The current study therefore evaluated whether neurocognitive performance is temporally related to suicide attempt, in a sample at highrisk for suicide (nâ¯=â¯141). Evaluations consisted of a clinician-administered interview, self-report questionnaires, and neurocognitive tasks assessing response inhibition, attentional control, and memory recognition. Analyses examined whether neurocognitive scores significantly differed according to the following temporal suicide attempt categories: (a) past-week attempt; (b) past-year attempt (not in past week); and (c) no past-year attempt. Univariate results showed that response inhibition and memory recognition were significantly related to suicide attempt recency. Post-hoc pairwise tests showed that participants with a past-week suicide attempt showed greater impairments than those without a past-year attempt. Multivariate tests showed the same pattern of results, adjusting for age, suicide attempts prior to past year, mood disturbance, and suicidal ideation. These results show that neurocognitive assessment of response inhibition and memory recognition shows sensitivity to the recency of a suicide attempt. While future prospective studies are needed, results suggest that phasic neurocognitive deficits may serve as objective markers of short-term suicide risk.
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Trastornos Neurocognitivos/diagnóstico , Pruebas Neuropsicológicas/normas , Ideación Suicida , Intento de Suicidio/psicología , Adulto , Femenino , Humanos , Masculino , Trastornos Neurocognitivos/psicología , Estudios Prospectivos , Factores de RiesgoRESUMEN
The main purpose of this study was to test the relationship between past-year suicide attempt (SA) and past-year opioid misuse among Veterans at high risk of suicide who reported using at least one illicit substance or alcohol in the past year. Baseline data from 130 high suicide-risk Veterans (nâ¯=â¯39 past-year opioid misusers; nâ¯=â¯91 past-year users of other substances) who enrolled in a randomized controlled trial testing adjunctive Mindfulness-Based Cognitive Therapy to Prevent Suicidal Behavior were used. Information was collected on a semi-structured interview that included the Columbia-Suicide Severity Rating Scale to collect suicide attempt history. Past-year opioid misusers, compared to those who used at least one other illicit substance or alcohol in the past year, were more likely to have made a past-year SA. Past-year opioid misuse remained associated with past-year SA in multivariate analysis that included other known risk factors for SA. Our findings show a robust link between near-term SA and opioid misuse in Veterans.
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Analgésicos Opioides , Trastornos Relacionados con Opioides/epidemiología , Mal Uso de Medicamentos de Venta con Receta/estadística & datos numéricos , Intento de Suicidio/estadística & datos numéricos , Suicidio/estadística & datos numéricos , Veteranos/estadística & datos numéricos , Adulto , Anciano , Consumo de Bebidas Alcohólicas/epidemiología , Trastornos Relacionados con Cocaína/epidemiología , Terapia Cognitivo-Conductual , Trastorno Depresivo Mayor/epidemiología , Femenino , Dependencia de Heroína/epidemiología , Humanos , Masculino , Uso de la Marihuana/epidemiología , Persona de Mediana Edad , Atención Plena , Factores de Riesgo , Ideación Suicida , Estados Unidos/epidemiología , Adulto Joven , Prevención del SuicidioRESUMEN
Efforts to better understand and prevent suicide have increasingly pointed to the prospective assessment of suicidal behaviors in clinical trials. These assessments are aided by instruments such as the Columbia-Suicide Severity Rating Scale (C-SSRS), which have sought to improve the conceptual uniformity and ease by which suicidal behaviors are classified. At the same time, assessment and classification of suicidal behaviors has been a longtime challenge in the field. To aid users of the C-SSRS, this article illustrates the use of the C-SSRS in instances where classification complexities arise. Illustrations are presented based on cases encountered during a clinical trial for a suicide prevention intervention. Key decision points are summarized and classification issues that warrant consideration for future refinement of such decisions are discussed.
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Síntomas Conductuales/clasificación , Escalas de Valoración Psiquiátrica , Ideación Suicida , Suicidio/psicología , Comités de Monitoreo de Datos de Ensayos Clínicos , Ensayos Clínicos como Asunto/métodos , Humanos , Reproducibilidad de los Resultados , Proyectos de Investigación , Medición de Riesgo/métodosRESUMEN
OBJECTIVES: Metformin has shown its effectiveness in treating obesity in adults. However, little research has been conducted in children, with a lack of attention on pubertal status. The objectives were to determine whether oral metformin treatment reduces BMI z score, cardiovascular risk, and inflammation biomarkers in children who are obese depending on pubertal stage and sex. METHODS: This was a randomized, prospective, double-blind, placebo-controlled, multicenter trial, stratified according to pubertal stage and sex, conducted at 4 Spanish clinical hospitals. Eighty prepubertal and 80 pubertal nondiabetic children who were obese aged 7 to 14 years with a BMI >95th percentiles were recruited. The intervention included 1 g/d of metformin versus placebo for 6 months. The primary outcome was a reduction in BMI z score. Secondary outcomes comprised insulin resistance, cardiovascular risk, and inflammation biomarkers. RESULTS: A total of 140 children completed the study (72 boys). Metformin decreased the BMI z score versus placebo in the prepubertal group (-0.8 and -0.6, respectively; difference, 0.2; P = .04). Significant increments were observed in prepubertal children treated with metformin versus placebo recipients in the quantitative insulin sensitivity check index (0.010 and -0.007; difference, 0.017; P = .01) and the adiponectin-leptin ratio (0.96 and 0.15; difference, 0.81; P = .01) and declines in interferon-γ (-5.6 and 0; difference, 5.6; P = .02) and total plasminogen activator inhibitor-1 (-1.7 and 2.4; difference, 4.1; P = .04). No serious adverse effects were reported. CONCLUSIONS: "Metformin decreased the BMI z score and improved inflammatory and cardiovascular-related obesity parameters only in prepubertal children, but a differential effect of metformin was not observed in prepubertal compared to pubertal children. Nevertheless, the doses per kilogram of weight administrated may have had an impact on the metformin effect. Further investigations are necessary."
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Metformina/uso terapéutico , Obesidad Infantil/tratamiento farmacológico , Adolescente , Biomarcadores/sangre , Índice de Masa Corporal , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/prevención & control , Niño , Método Doble Ciego , Femenino , Humanos , Inflamación/etiología , Inflamación/prevención & control , Masculino , Obesidad Infantil/sangre , Obesidad Infantil/complicaciones , Estudios Prospectivos , Pubertad , Factores SexualesRESUMEN
BACKGROUND: Although suicide ranks 10th as a cause of death in the United States, and 1st among active military personnel, there are surprisingly few evidence-based therapies addressing suicidality, and development of new treatments is limited. This paper describes a clinical trial testing a novel therapy for reducing suicide risk in military veterans. The intervention, Mindfulness-Based Cognitive Therapy for Preventing Suicide Behavior (MBCT-S), is a 10-week group intervention adapted from an existing treatment for depression (Mindfulness-Based Cognitive Therapy - MBCT). MBCT-S incorporates the Safety Planning Intervention, which is currently implemented throughout the Veterans Health Administration (VHA) for veterans at high suicide risk. METHODS: MBCT-S is being tested in a VHA setting using an intention-to-treat, two-group randomized trial design in which 164 high suicide risk veterans are randomized to either VHA Treatment As Usual (TAU; n=82) or TAU+MBCT-S (n=82). Our primary outcome measure, suicide-related event, defined to include suicide preparatory behaviors, self-harm behavior with suicidal or indeterminate intent, suicide-related hospitalizations and Emergency Department (ED) visits, will be measured through five assessments administered by blinded assessors between baseline and 12months post-baseline. We will measure suicide attempts and suicide deaths as a secondary outcome, because of their anticipated low incidence during the study period. Secondary outcomes also include severity of suicidal ideation, hopelessness and depression. SIGNIFICANCE: This study has the potential to significantly enhance the quality and efficiency of VHA care for veterans at suicide risk and to substantially improve the quality of life for veterans and their families.
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Terapia Cognitivo-Conductual/métodos , Atención Plena/métodos , Proyectos de Investigación , Prevención del Suicidio , Veteranos , Humanos , Calidad de Vida , Factores de Riesgo , Conducta Autodestructiva/prevención & control , Método Simple Ciego , Ideación Suicida , Intento de Suicidio/prevención & controlRESUMEN
This article describes the rationale for using mindfulness-based interventions (MBIs) to prevent suicidal behavior in high suicide-risk individuals. A narrative review of studies testing the feasibility of MBIs with individuals at risk for suicidal behavior and the effectiveness of MBIs for reducing suicidality was conducted. Studies testing the effectiveness of MBIs for reducing deficits specific to suicide attempters among depressed individuals were also reviewed as were studies examining moderators of MBI treatment adherence and effectiveness to the extent that these might suggest possible limitations to using MBIs with high suicide-risk individuals. Findings from the handful of available studies support targeting suicidal ideation with MBI. Additional studies show deficits associated with suicide attempt, namely attentional dyscontrol, problem solving deficits, and abnormal stress response, are improved by MBI and thus strengthen the rationale for using MBIs with high suicide-risk individuals.
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Depresión , Atención Plena/métodos , Prevención del Suicidio , Suicidio , Depresión/complicaciones , Depresión/psicología , Depresión/terapia , Humanos , Ideación Suicida , Suicidio/psicología , Resultado del TratamientoRESUMEN
To test whether a turnlike arrangement is involved in the bioactive conformation of CCK4 analogues upon CCK1 receptor recognition, we describe the preparation of two series of CCK4 derivatives, in which the central dipeptide Met-Asp has been replaced by recognized beta-turn mimetics {(2S,5S,11bR)- and (2R,5R,11bS)-2-amino-5-carboxy-3-oxo-2,3,5,6,11,11b-hexahydro-1H-indolizino[8,7-b]indole (IBTM) and beta-turn dipeptide, 2-oxo-7-thio-1-azabicyclo[4.3.0]nonane (BTD)}. The incorporation of the indolizinoindole IBTM type II beta-turn mimetic is preferred over its type II' counterpart for efficient CCK1 receptor recognition, while BTD derivatives were completely inactive. The structure-conformation-activity relationship study in the IBTM series has shown some essential requirement of these CCK4 derivatives to favorably interact with CCK1 receptors: (a) the adoption of turnlike conformations, (b) the presence of an L-Phe residue and a C-terminal carboxamide moiety, and (c) the indole ring of the IBTM skeleton. Moreover, the existence of pi-pi interactions between the phenyl ring of d-Phe residues and the indole ring of IBTM framework is detrimental for binding affinity. A series of potent and selective CCK1 receptor antagonists, exemplified by compounds 8a and 8b, emerges among these IBTM-containing derivatives.
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Compuestos Bicíclicos Heterocíclicos con Puentes/química , Dipéptidos/química , Indoles/química , Tetragastrina/análogos & derivados , Tetragastrina/síntesis química , Amilasas/metabolismo , Animales , Corteza Cerebral/metabolismo , Técnicas In Vitro , Ligandos , Espectroscopía de Resonancia Magnética , Modelos Moleculares , Imitación Molecular , Páncreas/efectos de los fármacos , Páncreas/metabolismo , Estructura Secundaria de Proteína , Ensayo de Unión Radioligante , Ratas , Receptor de Colecistoquinina A/antagonistas & inhibidores , Relación Estructura-Actividad , Tetragastrina/química , Tetragastrina/farmacologíaRESUMEN
2-Oxopiperazine derivatives 1 have been designed as mimetics of gamma-turn conformationally constrained tripeptides. The synthetic pathway devised for the preparation of both epimers of 1 at C(5) involves a reductive amination of cyanomethyleneamino pseudopeptides with amino acid derivatives, followed by regiospecific lactamization of the resulting C-backbone branched pseudopeptides. The versatility of this methodology is illustrated in the synthesis of analogues of the tetrapeptides Boc-[Nle(31)]-CCK-4 and Boc-[Lys(o-tolylaminocarbonyl)(31)]-CCK-4. The introduction of the new conformational restriction into these Boc-CCK-4 analogues led to a loss of 2 or 3 orders of magnitude in the affinity at CCK receptors. These results suggest the absence of a gamma-turn in the bioactive conformation of the C-terminal tripeptide of CCK-4.
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Péptidos/síntesis química , Piperazinas/química , Tetragastrina/análogos & derivados , Animales , Corteza Cerebral/metabolismo , Modelos Moleculares , Imitación Molecular , Resonancia Magnética Nuclear Biomolecular , Páncreas/metabolismo , Péptidos/química , Péptidos/metabolismo , Piperazinas/síntesis química , Piperazinas/metabolismo , Conformación Proteica , Ratas , Receptor de Colecistoquinina B , Receptores de Colecistoquinina/metabolismo , Tetragastrina/metabolismoRESUMEN
Replacement of the 2-Adoc-D-alphaMeTrp residue in the non-selective CCK(1) receptor agonist PD 170292 by the Z-(2R,5R,11bS)-IBTM skeleton, able to fix a type II beta-turn-like conformation, led to a conformationally restricted dipeptoid analogue, namely 3a, which exhibited a notable increase in the CCK(1) selectivity and antagonist properties.