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BACKGROUND: Necrotizing enterocolitis (NEC) is common in preterm infants, especially infants less than 32 weeks gestation. Mortality from NEC is 7% and occurs in 1 out of 1000 preterm infants. Studies have shown the efficacy of an exclusive milk from mother diet in decreasing rates of NEC and associated mortality. PURPOSE: To evaluate the effectiveness of an existing exclusive human milk diet (EHMD) protocol on the incidence of NEC in extremely premature infants. EHMD, for the purposes of this project is defined as breast milk of mother, with or without human milk-based fortifier. METHODS: A single-center retrospective quasi-experimental study. The sample included 201 infants born less than 32 weeks gestation, weighing less than 1250 grams, small for gestational age (SGA) and with low Apgar scores. Outcomes measured included incidences of NEC, mortality, and co-morbidities in infants pre- and postinitiation of an EHMD protocol. RESULTS: Just 4.8% of the EHMD group had a NEC diagnosis compared to 10.5% of the bovine-based (BOV) group. There was a 1% mortality rate of the EHMD group as compared to 6% in the BOV group. The EHMD group had a statistically significant greater weight gain during hospitalization as compared to infants fed BOV (P = < .05). IMPLICATIONS FOR PRACTICE AND RESEARCH: Neonatal intensive care units should consider EHMDs for use in this infant population. Future research is needed to support dissemination of the use of EHMD as standard of practice.
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Recent years have seen the rapid proliferation of clinical prediction models aiming to support risk stratification and individualized care within psychiatry. Despite growing interest, attempts to synthesize current evidence in the nascent field of precision psychiatry have remained scarce. This systematic review therefore sought to summarize progress towards clinical implementation of prediction modeling for psychiatric outcomes. We searched MEDLINE, PubMed, Embase, and PsychINFO databases from inception to September 30, 2020, for English-language articles that developed and/or validated multivariable models to predict (at an individual level) onset, course, or treatment response for non-organic psychiatric disorders (PROSPERO: CRD42020216530). Individual prediction models were evaluated based on three key criteria: (i) mitigation of bias and overfitting; (ii) generalizability, and (iii) clinical utility. The Prediction model Risk Of Bias ASsessment Tool (PROBAST) was used to formally appraise each study's risk of bias. 228 studies detailing 308 prediction models were ultimately eligible for inclusion. 94.5% of developed prediction models were deemed to be at high risk of bias, largely due to inadequate or inappropriate analytic decisions. Insufficient internal validation efforts (within the development sample) were also observed, while only one-fifth of models underwent external validation in an independent sample. Finally, our search identified just one published model whose potential utility in clinical practice was formally assessed. Our findings illustrated significant growth in precision psychiatry with promising progress towards real-world application. Nevertheless, these efforts have been inhibited by a preponderance of bias and overfitting, while the generalizability and clinical utility of many published models has yet to be formally established. Through improved methodological rigor during initial development, robust evaluations of reproducibility via independent validation, and evidence-based implementation frameworks, future research has the potential to generate risk prediction tools capable of enhancing clinical decision-making in psychiatric care.
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Modelos Estadísticos , Psiquiatría , Sesgo , Humanos , Pronóstico , Reproducibilidad de los ResultadosRESUMEN
In their annual research review, McAdams, Cheesman, and Ahmadzadeh (2023) provide a thorough overview of how the use of novel genetically informative approaches can increase our knowledge about the intergenerational transmission of psychopathology. Many JCPP readers will already be familiar with genetically sensitive family-based designs, such as twin and adoption studies, as well as with newer molecular-genetic approaches, such as polygenic-score studies. McAdams et al.'s (2023) review discusses the innovative combination of family-based and molecular-genetic methods, and what this combination can reveal about developmental psychopathology.
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Salud Mental , Psicopatología , Humanos , GenómicaRESUMEN
Childhood adversities are major preventable risk factors for poor mental and physical health. Scientific advances in this area are not matched by clinical gains for affected individuals. We reflect on novel research directions that could accelerate clinical impact.
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Experiencias Adversas de la Infancia , Humanos , Factores de RiesgoRESUMEN
BACKGROUND/AIMS: There are increasing pressures for anonymised datasets from clinical trials to be shared across the scientific community, and differing recommendations exist on how to perform anonymisation prior to sharing. We aimed to systematically identify, describe and synthesise existing recommendations for anonymising clinical trial datasets to prepare for data sharing. METHODS: We systematically searched MEDLINE®, EMBASE and Web of Science from inception to 8 February 2021. We also searched other resources to ensure the comprehensiveness of our search. Any publication reporting recommendations on anonymisation to enable data sharing from clinical trials was included. Two reviewers independently screened titles, abstracts and full text for eligibility. One reviewer extracted data from included papers using thematic synthesis, which then was sense-checked by a second reviewer. Results were summarised by narrative analysis. RESULTS: Fifty-nine articles (from 43 studies) were eligible for inclusion. Three distinct themes are emerging: anonymisation, de-identification and pseudonymisation. The most commonly used anonymisation techniques are: removal of direct patient identifiers; and careful evaluation and modification of indirect identifiers to minimise the risk of identification. Anonymised datasets joined with controlled access was the preferred method for data sharing. CONCLUSIONS: There is no single standardised set of recommendations on how to anonymise clinical trial datasets for sharing. However, this systematic review shows a developing consensus on techniques used to achieve anonymisation. Researchers in clinical trials still consider that anonymisation techniques by themselves are insufficient to protect patient privacy, and they need to be paired with controlled access.
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Confidencialidad , Anonimización de la Información , Humanos , Difusión de la Información/métodos , InvestigadoresRESUMEN
BACKGROUND: Although coronary computed tomographic angiography (CTA) improves diagnostic certainty in the assessment of patients with stable chest pain, its effect on 5-year clinical outcomes is unknown. METHODS: In an open-label, multicenter, parallel-group trial, we randomly assigned 4146 patients with stable chest pain who had been referred to a cardiology clinic for evaluation to standard care plus CTA (2073 patients) or to standard care alone (2073 patients). Investigations, treatments, and clinical outcomes were assessed over 3 to 7 years of follow-up. The primary end point was death from coronary heart disease or nonfatal myocardial infarction at 5 years. RESULTS: The median duration of follow-up was 4.8 years, which yielded 20,254 patient-years of follow-up. The 5-year rate of the primary end point was lower in the CTA group than in the standard-care group (2.3% [48 patients] vs. 3.9% [81 patients]; hazard ratio, 0.59; 95% confidence interval [CI], 0.41 to 0.84; P=0.004). Although the rates of invasive coronary angiography and coronary revascularization were higher in the CTA group than in the standard-care group in the first few months of follow-up, overall rates were similar at 5 years: invasive coronary angiography was performed in 491 patients in the CTA group and in 502 patients in the standard-care group (hazard ratio, 1.00; 95% CI, 0.88 to 1.13), and coronary revascularization was performed in 279 patients in the CTA group and in 267 in the standard-care group (hazard ratio, 1.07; 95% CI, 0.91 to 1.27). However, more preventive therapies were initiated in patients in the CTA group (odds ratio, 1.40; 95% CI, 1.19 to 1.65), as were more antianginal therapies (odds ratio, 1.27; 95% CI, 1.05 to 1.54). There were no significant between-group differences in the rates of cardiovascular or noncardiovascular deaths or deaths from any cause. CONCLUSIONS: In this trial, the use of CTA in addition to standard care in patients with stable chest pain resulted in a significantly lower rate of death from coronary heart disease or nonfatal myocardial infarction at 5 years than standard care alone, without resulting in a significantly higher rate of coronary angiography or coronary revascularization. (Funded by the Scottish Government Chief Scientist Office and others; SCOT-HEART ClinicalTrials.gov number, NCT01149590 .).
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Dolor en el Pecho/diagnóstico por imagen , Angiografía por Tomografía Computarizada , Enfermedad Coronaria/mortalidad , Infarto del Miocardio/epidemiología , Adulto , Anciano , Dolor en el Pecho/terapia , Angiografía Coronaria/estadística & datos numéricos , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Infarto del Miocardio/prevención & control , Intervención Coronaria Percutánea/estadística & datos numéricos , RiesgoRESUMEN
Background: Complex traumas are traumatic experiences that involve multiple interpersonal threats during childhood or adolescence, such as repeated abuse. Complex traumas are hypothesized to lead to more severe psychopathology and poorer cognitive function than other non-complex traumas. However, empirical testing of this hypothesis has been limited to clinical/convenience samples and cross-sectional designs. Aims: To investigate psychopathology and cognitive function in young people exposed to complex, non-complex, or no trauma from a population-representative longitudinal cohort, and to consider the role of pre-existing vulnerabilities. Method: Participants were from the Environmental Risk (E-Risk) Longitudinal Twin Study, a population-representative birth-cohort of 2,232 British children. At age 18 years (93% participation), we assessed lifetime exposure to complex and non-complex trauma, past-year psychopathology, and current cognitive function. We also prospectively assessed early childhood vulnerabilities: internalizing and externalizing symptoms at age 5, IQ at age 5, family history of mental illness, family socioeconomic status, and sex. Results: Participants exposed to complex trauma had more severe psychopathology and poorer cognitive function at age 18 compared to both trauma-unexposed participants and those exposed to non-complex trauma. Early childhood vulnerabilities predicted risk of later complex trauma exposure, and largely explained associations of complex trauma with cognitive deficits, but not with psychopathology. Conclusions: By conflating complex and non-complex traumas, current research and clinical practice under-estimate the severity of psychopathology, cognitive deficits, and pre-existing vulnerabilities linked with complex trauma. A better understanding of the mental health needs of people exposed to complex trauma could inform the development of new effective interventions.
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Trastornos Mentales , Psicopatología , Adolescente , Niño , Preescolar , Cognición , Estudios de Cohortes , Estudios Transversales , Humanos , Estudios Longitudinales , Trastornos Mentales/epidemiologíaRESUMEN
AIMS: The relative benefits of computed tomography coronary angiography (CTCA)-guided management in women and men with suspected angina due to coronary heart disease (CHD) are uncertain. METHODS AND RESULTS: In this post hoc analysis of an open-label parallel-group multicentre trial, we recruited 4146 patients referred for assessment of suspected angina from 12 cardiology clinics across the UK. We randomly assigned (1:1) participants to standard care alone or standard care plus CTCA. Fewer women had typical chest pain symptoms (n = 582, 32.0%) when compared with men (n = 880, 37.9%; P < 0.001). Amongst the CTCA-guided group, more women had normal coronary arteries [386 (49.6%) vs. 263 (26.2%)] and less obstructive CHD [105 (11.5%) vs. 347 (29.8%)]. A CTCA-guided strategy resulted in more women than men being reclassified as not having CHD {19.2% vs. 13.1%; absolute risk difference, 5.7 [95% confidence interval (CI): 2.7-8.7, P < 0.001]} or having angina due to CHD [15.0% vs. 9.0%; absolute risk difference, 5.6 (2.3-8.9, P = 0.001)]. After a median of 4.8 years follow-up, CTCA-guided management was associated with similar reductions in the risk of CHD death or non-fatal myocardial infarction in women [hazard ratio (HR) 0.50, 95% CI 0.24-1.04], and men (HR 0.63, 95% CI 0.42-0.95; Pinteraction = 0.572). CONCLUSION: Following the addition of CTCA, women were more likely to be found to have normal coronary arteries than men. This led to more women being reclassified as not having CHD, resulting in more downstream tests and treatments being cancelled. There were similar prognostic benefits of CTCA for women and men.
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Enfermedad de la Arteria Coronaria , Enfermedad Coronaria , Angina de Pecho/epidemiología , Dolor en el Pecho/epidemiología , Dolor en el Pecho/etiología , Angiografía por Tomografía Computarizada , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad Coronaria/complicaciones , Enfermedad Coronaria/diagnóstico por imagen , Femenino , Humanos , Masculino , Valor Predictivo de las PruebasRESUMEN
BACKGROUND: Premature infants experience stressors such as external stimulation with sounds, light, touch, and open positioning in NICU that negatively affect outcomes. PURPOSE: The purpose of this study was to measure the effectiveness of a developmental positioning intervention on length of stay, weight gain, and tone/flexion compared with neonates without structured positioning. METHODS: Study design was quasi-experimental with nonequivalent groups. A retrospective chart review of 50 neonates with the inclusion criteria of 34 weeks of gestation or less and no anomalies provided a preintervention sample. After the education in-service on positioning, a convenience sample of 27 infants was enrolled. Infant Position Assessment Tool was used as a visual guide for positioning and scoring by the researcher for intervention fidelity. Hammersmith scoring was completed by the occupational therapist prior to discharge. FINDINGS: The postintervention group was younger and sicker than the control group (P < .05). The postintervention sample (M = 7.05 where 7 = 29 to <30 weeks of gestation) was younger than the preintervention sample (M = 7.22). The postintervention sample was smaller (M = 1302.15 g) than the preintervention sample (M = 1385.94 g). Results showed that the postintervention group had clinically significant weight gain and mean Hammersmith score (3.28) was higher showing positioning positively affected tone and flexion scores. IMPLICATIONS FOR PRACTICE: With greater structure and consistent attention to developmental positioning, outcomes are positively affected. IMPLICATIONS FOR FUTURE RESEARCH: Further research with larger sample sizes will identify stronger associations and relationships between positioning and outcome measures.
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Tiempo de Internación/estadística & datos numéricos , Tono Muscular , Enfermería Neonatal/métodos , Posicionamiento del Paciente/métodos , Aumento de Peso , Femenino , Estudio Históricamente Controlado , Humanos , Recien Nacido Extremadamente Prematuro , Recién Nacido , Recien Nacido Prematuro , Capacitación en Servicio , Unidades de Cuidado Intensivo Neonatal , Masculino , Enfermería Neonatal/educación , Terapeutas Ocupacionales/educación , Profesionales de Enfermería Pediátrica/educación , Proyectos Piloto , Mejoramiento de la CalidadRESUMEN
BACKGROUND: Rigorous, informative meta-analyses rely on availability of appropriate summary statistics or individual participant data. For continuous outcomes, especially those with naturally skewed distributions, summary information on the mean or variability often goes unreported. While full reporting of original trial data is the ideal, we sought to identify methods for handling unreported mean or variability summary statistics in meta-analysis. METHODS: We undertook two systematic literature reviews to identify methodological approaches used to deal with missing mean or variability summary statistics. Five electronic databases were searched, in addition to the Cochrane Colloquium abstract books and the Cochrane Statistics Methods Group mailing list archive. We also conducted cited reference searching and emailed topic experts to identify recent methodological developments. Details recorded included the description of the method, the information required to implement the method, any underlying assumptions and whether the method could be readily applied in standard statistical software. We provided a summary description of the methods identified, illustrating selected methods in example meta-analysis scenarios. RESULTS: For missing standard deviations (SDs), following screening of 503 articles, fifteen methods were identified in addition to those reported in a previous review. These included Bayesian hierarchical modelling at the meta-analysis level; summary statistic level imputation based on observed SD values from other trials in the meta-analysis; a practical approximation based on the range; and algebraic estimation of the SD based on other summary statistics. Following screening of 1124 articles for methods estimating the mean, one approximate Bayesian computation approach and three papers based on alternative summary statistics were identified. Illustrative meta-analyses showed that when replacing a missing SD the approximation using the range minimised loss of precision and generally performed better than omitting trials. When estimating missing means, a formula using the median, lower quartile and upper quartile performed best in preserving the precision of the meta-analysis findings, although in some scenarios, omitting trials gave superior results. CONCLUSIONS: Methods based on summary statistics (minimum, maximum, lower quartile, upper quartile, median) reported in the literature facilitate more comprehensive inclusion of randomised controlled trials with missing mean or variability summary statistics within meta-analyses.
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Algoritmos , Biometría/métodos , Metaanálisis como Asunto , Evaluación de Resultado en la Atención de Salud/métodos , Evaluación de Resultado en la Atención de Salud/estadística & datos numéricos , Teorema de Bayes , Ensayos Clínicos como Asunto/métodos , Ensayos Clínicos como Asunto/estadística & datos numéricos , HumanosRESUMEN
This work sought to assess optimal extraction conditions in the study of the metalloproteome of the dimorphic fungus Histoplasma capsulatum. One of the body's responses to H. capsulatum infection is sequestration of zinc within host macrophage (MØ), as reported by Vignesh et al. (Immunity 39:697-710, 2013) and Vignesh et al. (PLOS Pathog 9:E1003815, 2013). Thus, metalloproteins containing zinc were of greatest interest as it plays a critical role in survival of the fungus. One challenge in metalloproteomics is the preservation of the native structure of proteins to retain non-covalently bound metals. Many of the conventional cell lysis, separation, and identification techniques in proteomics are carried out under conditions that could lead to protein denaturation. Various cell lysis techniques were investigated in an effort to both maintain the metalloproteins during lysis and subsequent analysis while, at the same time, serving to be strong enough to break the cell wall, allowing access to cytosolic metalloproteins. The addition of 1% Triton x-100, a non-ionic detergent, to the lysis buffer was also studied. Seven lysis methods were considered and these included: Glass Homogenizer (H), Bead Beater (BB), Sonication Probe (SP), Vortex with 1% Triton x-100 (V, T), Vortex with no Triton x-100 (V, NT), Sonication Bath, Vortex, and 1% Triton x-100 (SB, V, T) and Sonication Bath, Vortex, and no Triton x-100 (SB, V, NT). A Qubit® Assay was used to compare total protein concentration and inductively coupled plasma-mass spectrometry (ICP-MS) was utilized for total metal analysis of cell lysates. Size exclusion chromatography coupled to ICP-MS (SEC-HPLC-ICP-MS) was used for separation of the metalloproteins in the cell lysate and the concentration of Zn over a wide molecular weight range was examined. Additional factors such as potential contamination sources were also considered. A cell lysis method involving vortexing H. capsulatum yeast cells with 500 µm glass beads in a 1% Triton x-100 lysis buffer (V, T) was found to be most advantageous to extract intact zinc metalloproteins as demonstrated by the highest Zn to protein ratio, 1.030 ng Zn/µg protein, and Zn distribution among high, mid, and low molecular weights suggesting the least amount of protein denaturation. Graphical abstract In this work, several cell lysis techniques and two lysis buffers were investigated to evaluate the preservation of the zinc metalloproteome of H. capsulatum while maintaining compatibility with the analytical techniques employed.
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Proteínas Fúngicas/aislamiento & purificación , Histoplasma/química , Metaloproteínas/aislamiento & purificación , Zinc/aislamiento & purificación , Detergentes/química , Proteínas Fúngicas/química , Histoplasma/citología , Histoplasmosis/microbiología , Humanos , Metaloproteínas/química , Octoxinol/química , Proteómica/métodos , Sonicación/métodos , Zinc/químicaRESUMEN
BACKGROUND: The effect of interscalene block (ISB) on pulmonary function of obese participants has not been investigated. The goal of this study is to assess the association of obesity (body mass index [BMI] >29 kg/m vs BMI <25 kg/m) and change in forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) after ISB in participants undergoing outpatient shoulder surgery. METHODS: This prospective, observational cohort study compared obese (BMI >29 kg/m) and normal-weight (BMI <25 kg/m) groups undergoing ISB for ambulatory shoulder surgery, on preblock and postblock FVC and FEV1, at 30 minutes postblock and in the postanesthesia care unit (PACU). The primary outcome in this study was FVC% change (percentage change from preblock to postblock values of FVC) at 30 minutes postblock in the supine position. Secondary outcomes included FVC% change at PACU and in the sitting position, FEV1% change (percentage change from preblock to postblock values of FEV1), FVC, FEV1, incidence of diaphragmatic paresis, modified Borg scale for perceived dyspnea, Richmond Agitation-Sedation Scale scores for sedation, and intraoperative airway events. RESULTS: Fourteen participants were recruited to each group. The mean (standard deviation) BMI in the normal-weight and obese groups was 23 (1.7) and 33 (3.1) kg/m, respectively. ISB success rate was 100%. All participants demonstrated hemidiaphragmatic paresis after ISB. Compared to the normal-weight group, in the sitting position, the obese group had a significant decrease in FVC% change at 30 minutes (-30 [10.5] vs -23 [7.2], P = .046) and an FEV1% change in the PACU (-40 [12.6] vs -27 [13.9], P = .02). No difference was found for measurements taken in the supine position. A repeated-measures analysis demonstrated that, adjusted for position, there is no significant group effect on FVC% change or FEV1% change from 30 minutes to PACU. The 2 groups were not different in terms of breathlessness and sedation at 30 minutes (P = .67, P = .48, respectively) and in the PACU (P = .69, P > .99, respectively) nor in the occurrence of intraoperative airway events (P > .99). CONCLUSIONS: ISB is associated with greater FVC and FEV1 reductions in obese participants undergoing shoulder surgery compared to normal-weight participants. Neither time (30 minutes versus PACU) nor position (sitting versus supine) affected this relationship. Despite these changes, obesity was not associated with increased clinical respiratory symptoms or events.
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Procedimientos Quirúrgicos Ambulatorios/efectos adversos , Bloqueo del Plexo Braquial/efectos adversos , Pulmón/fisiopatología , Obesidad/complicaciones , Parálisis Respiratoria/etiología , Hombro/cirugía , Adulto , Periodo de Recuperación de la Anestesia , Índice de Masa Corporal , Femenino , Volumen Espiratorio Forzado , Humanos , Masculino , Persona de Mediana Edad , Obesidad/diagnóstico , Obesidad/fisiopatología , Posicionamiento del Paciente , Estudios Prospectivos , Recuperación de la Función , Parálisis Respiratoria/diagnóstico , Parálisis Respiratoria/fisiopatología , Factores de Riesgo , Hombro/inervación , Posición Supina , Factores de Tiempo , Resultado del Tratamiento , Capacidad Vital , Adulto JovenRESUMEN
BACKGROUND: The survival rate for infants born with life-threatening problems has improved greatly over the last few decades. Nevertheless, infants still die in neonatal intensive care units (NICUs) every day. Despite existing standards of care, some aspects of end-of-life care (EOLC) are still not delivered consistently. Little is known about how NICU nurses' individual experiences affect EOLC. PURPOSE: The purpose of this study was to explore, through lived and told stories, the affective, interactional, and meaning-related responses that NICU nurses have while caring for dying infants and their families. Coping strategies and changes in practice were also explored. METHODS: Thirty-six members of the National Association of Neonatal Nurses submitted written narratives about an EOLC experience during which the nurse experienced strong emotions. FINDINGS: Narrative analysis revealed many affective responses, but 3 were the most frequent: responsibility, moral distress, and identification. Coping methods included healthy and less healthy strategies, such as colleague support, informal and formal debriefing, practicing intentional gratefulness, avoidance, and compartmentalization. Changes in practice identified were universally described as professional growth through the use of reflective practice. IMPLICATIONS FOR PRACTICE & RESEARCH: Educators should discuss the range of emotions experienced by caregivers related to EOLC and healthy coping strategies and encourage the use of reflective practice as a facilitator of professional growth. Nurse leaders should promote supportive environments in NICUs and ensure debriefing opportunities for nurses who have recently cared for a dying infant. Future research should focus on formulating interventions to utilize debriefing with NICU nurses and perhaps the development of EOLC mentors.
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Afecto , Cuidado Intensivo Neonatal , Narración , Enfermeras Neonatales/psicología , Cuidado Terminal/psicología , Adaptación Psicológica , Adulto , Anciano , Ira , Femenino , Culpa , Humanos , Identificación Psicológica , Unidades de Cuidado Intensivo Neonatal , Persona de Mediana Edad , Investigación Cualitativa , Estrés PsicológicoRESUMEN
BACKGROUND: Self-monitoring of blood glucose among people with type 2 diabetes not treated with insulin does not appear to be effective in improving glycemic control. We investigated whether health professional review of telemetrically transmitted self-monitored glucose results in improved glycemic control in people with poorly controlled type 2 diabetes. METHODS AND FINDINGS: We performed a randomized, parallel, investigator-blind controlled trial with centralized randomization in family practices in four regions of the United Kingdom among 321 people with type 2 diabetes and glycated hemoglobin (HbA1c) >58 mmol/mol. The supported telemonitoring intervention involved self-measurement and transmission to a secure website of twice-weekly morning and evening glucose for review by family practice clinicians who were not blinded to allocation group. The control group received usual care, with at least annual review and more frequent reviews for people with poor glycemic or blood pressure control. HbA1c assessed at 9 mo was the primary outcome. Intention-to-treat analyses were performed. 160 people were randomized to the intervention group and 161 to the usual care group between June 6, 2011, and July 19, 2013. HbA1c data at follow-up were available for 146 people in the intervention group and 139 people in the control group. The mean (SD) HbA1c at follow-up was 63.0 (15.5) mmol/mol in the intervention group and 67.8 (14.7) mmol/mol in the usual care group. For primary analysis, adjusted mean HbA1c was 5.60 mmol/mol / 0.51% lower (95% CI 2.38 to 8.81 mmol/mol/ 95% CI 0.22% to 0.81%, p = 0·0007). For secondary analyses, adjusted mean ambulatory systolic blood pressure was 3.06 mmHg lower (95% CI 0.56-5.56 mmHg, p = 0.017) and mean ambulatory diastolic blood pressure was 2.17 mmHg lower (95% CI 0.62-3.72, p = 0.006) among people in the intervention group when compared with usual care after adjustment for baseline differences and minimization strata. No significant differences were identified between groups in weight, treatment pattern, adherence to medication, or quality of life in secondary analyses. There were few adverse events and these were equally distributed between the intervention and control groups. In secondary analysis, there was a greater number of telephone calls between practice nurses and patients in the intervention compared with control group (rate ratio 7.50 (95% CI 4.45-12.65, p < 0.0001) but no other significant differences between groups in use of health services were identified between groups. Key limitations include potential lack of representativeness of trial participants, inability to blind participants and health professionals, and uncertainty about the mechanism, the duration of the effect, and the optimal length of the intervention. CONCLUSIONS: Supported telemonitoring resulted in clinically important improvements in control of glycaemia in patients with type 2 diabetes in family practice. Current Controlled Trials, registration number ISRCTN71674628. TRIAL REGISTRATION: Current Controlled Trials ISRCTN 71674628.
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Diabetes Mellitus Tipo 2/terapia , Telemedicina/métodos , Telemetría , Adulto , Anciano , Anciano de 80 o más Años , Automonitorización de la Glucosa Sanguínea/métodos , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/fisiopatología , Femenino , Hemoglobina Glucada/análisis , Humanos , Masculino , Persona de Mediana Edad , Telemetría/métodosRESUMEN
[This corrects the article DOI: 10.1371/journal.pmed.1002098.].
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Peroxisome proliferator-activated receptor-gamma (PPARγ) is a nuclear hormone receptor involved in regulating various metabolic and immune processes. The PPAR family of receptors possesses a large binding cavity that imparts promiscuity of ligand binding not common to other nuclear receptors. This feature increases the challenge of using computational methods to identify PPAR ligands that will dock favorably into a structural model. Utilizing both ligand- and structure-based pharmacophore methods, we sought to improve agonist prediction by grouping ligands according to pharmacophore features, and pairing models derived from these features with receptor structures for docking. For 22 of the 33 receptor structures evaluated we observed an increase in true positive rate (TPR) when screening was restricted to compounds sharing molecular features found in rosiglitazone. A combination of structure models used for docking resulted in a higher TPR (40 %) when compared to docking with a single structure model (<20 %). Prediction was also improved when specific protein-ligand interactions between the docked ligands and structure models were given greater weight than the calculated free energy of binding. A large-scale screen of compounds using a marketed drug database verified the predictive ability of the selected structure models. This study highlights the steps necessary to improve screening for PPARγ ligands using multiple structure models, ligand-based pharmacophore data, evaluation of protein-ligand interactions, and comparison of docking datasets. The unique combination of methods presented here holds potential for more efficient screening of compounds with unknown affinity for PPARγ that could serve as candidates for therapeutic development.
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Descubrimiento de Drogas , Ensayos Analíticos de Alto Rendimiento , Modelos Moleculares , PPAR gamma/química , Bibliotecas de Moléculas Pequeñas/química , Bases de Datos de Compuestos Químicos , Humanos , Simulación del Acoplamiento Molecular , Simulación de Dinámica MolecularRESUMEN
The goal of this work was to explore associations of constituent factors of alexithymia on mental health and potential mediating effects of emotion regulation strategies, specifically suppression and reappraisal. Data were collected through the crowd-sourcing platform Amazon Mechanical Turk (MTURK). Three hundred seventy-seven individuals completed questionnaires related to distress (Depression Anxiety Stress Scales [DASS]), emotion regulation (Emotion Regulation Questionnaire [ERQ]) and Alexithymia (Bermond-Vorst Alexithymia Questionnaire [BVAQ]). Three mediation models were constructed for depression, anxiety and stress, with BVAQ subscales (verbalizing, identifying, emotionalizing, fantasizing, and analyzing) as predictors and ERQ subscales (suppression and reappraisal) as mediators. Results indicated 37.3 % variance in depression, 25.2 % variance in anxiety, and 35.3 % variance in stress was explained by each model. Direct associations revealed emotionalizing and fantasizing were negatively associated with depression, anxiety, and stress, while verbalizing was additionally associated with depression, identifying was additionally associated with anxiety, and all four BVAQ subscales were associated with stress. BVAQ subscales demonstrated negative associations with reappraisal and positive associations with suppression that mediated anxiety and depression. However, suppression did not mediate relationships between BVAQ subscales with stress. Findings support the importance of examining multiple factors of alexithymia and associations with emotion regulation strategies and distress.
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Síntomas Afectivos , Depresión , Humanos , Síntomas Afectivos/epidemiología , Síntomas Afectivos/psicología , Depresión/epidemiología , Trastornos de Ansiedad/epidemiología , Encuestas y Cuestionarios , Ansiedad/epidemiologíaRESUMEN
OBJECTIVE: More than 200 million children and adolescents live in countries affected by violent conflict, are likely to have complex mental health needs, and struggle to access traditional mental health services. Digital mental health interventions have the potential to overcome some of the barriers in accessing mental health support. We performed a scoping review to map existing digital mental health interventions relevant for children and adolescents affected by war, to examine the strength of the evidence base, and to inform the development of future interventions. METHOD: Based on a pre-registered strategy, we systematically searched MEDLINE, Embase, Global Health, APA PsychInfo, and Google Scholar from the creation of each database to September 30, 2022, identifying k = 6,843 studies. Our systematic search was complemented by extensive consultation with experts from the GROW Network. RESULTS: The systematic search identified 6 relevant studies: 1 study evaluating digital mental health interventions for children and adolescents affected by war, and 5 studies for those affected by disasters. Experts identified 35 interventions of possible relevance. The interventions spanned from universal prevention to specialist-guided treatment. Most interventions directly targeted young people and parents or carers/caregivers and were self-guided. A quarter of the interventions were tested through randomized controlled trials. Because most interventions were not culturally or linguistically adapted to relevant contexts, their implementation potential was unclear. CONCLUSION: There is very limited evidence for the use of digital mental health interventions for children and adolescents affected by war at present. The review provides a framework to inform the development of new interventions. DIVERSITY & INCLUSION STATEMENT: We actively worked to promote sex and gender balance in our author group. STUDY PREREGISTRATION INFORMATION: Digital mental health interventions for children and young people affected by war: a scoping review; https://osf.io/; hrny9.
RESUMEN
The purpose of this study was to determine the effects of an acute oral dose of 3 mg·kg(-1) of Rhodiola rosea on endurance exercise performance, perceived exertion, mood, and cognitive function. Subjects (n = 18) ingested either R. rosea or a carbohydrate placebo 1 hour before testing in a double-blind, random crossover manner. Exercise testing consisted of a standardized 10-minute warm-up followed by a 6-mile time trial (TT) on a bicycle ergometer. Rating of perceived exertion (RPE) was measured every 5 minutes during the TT using a 10-point Borg scale. Blood lactate concentration, salivary cortisol, and salivary alpha amylase were measured before warm-up, 2 minutes after warm-up, and 2 minutes after TT (n = 15). A Profile of Mood States questionnaire and a Stroop Color Test were completed before warm-up and after TT. Testing was repeated 2-7 days later with the other condition. Rhodiola rosea ingestion significantly decreased heart rate during the standardized warm-up (R. rosea = 136 ± 17 b·min(-1); placebo = 140 ± 17 b·min(-1); mean ± SD; p = 0.001). Subjects completed the TT significantly faster after R. rosea ingestion (R. rosea = 25.4 ± 2.7 minutes; placebo = 25.8 ± 3.0 minutes; p = 0.037). The mean RPE was lower in the R. rosea trial (R. rosea = 6.0 ± 0.9; placebo = 6.6 ± 1.0; p = 0.04). This difference was even more pronounced when a ratio of the RPE relative to the workload was calculated (R. rosea = 0.048 ± 0.01; placebo = 0.057 ± 0.02; p = 0.007). No other statistically significant differences were observed. Acute R. rosea ingestion decreases heart rate response to submaximal exercise and appears to improve endurance exercise performance by decreasing the perception of effort.
Asunto(s)
Prueba de Esfuerzo/efectos de los fármacos , Resistencia Física/efectos de los fármacos , Fitoterapia , Rhodiola , Afecto , Análisis de Varianza , Estudios Cruzados , Método Doble Ciego , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Hidrocortisona/análisis , Ácido Láctico/sangre , Esfuerzo Físico/fisiología , Saliva/química , Encuestas y Cuestionarios , Adulto Joven , alfa-Amilasas/análisisRESUMEN
Trauma-exposed young people are about twice as likely as their unexposed peers to develop mental health problems, which, if left untreated, can have long-term negative consequences.1 There is robust evidence for the effectiveness of individual trauma-focused psychological therapies to improve trauma-related psychopathology, particularly posttraumatic stress disorder (PTSD), in young people.2 However, there are minimal services that provide such specialist treatments in low/middle-income countries where most young people live,3 and services may be severely disrupted at times of extreme stressors, such as war, natural disasters, and other humanitarian crises, when need is greatest.4 Moreover, even in high-income stable regions where child mental health services are established and treatments are available, these health care resources are limited, and can only be accessed by a minority of affected trauma-exposed young people.5 There is therefore a need for research to indicate effective interventions that are more accessible and can be delivered on a greater scale to treat more young people with trauma-related psychopathology.6 The recent meta-analysis by Davis et al.7 focused on the more accessible intervention of group-based psychological treatment for child PTSD symptoms, and found evidence of effectiveness compared with control conditions. The study provides an important advancement in this field, and also highlights the need for further research to better understand how group interventions can be most usefully implemented.