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1.
Soc Psychiatry Psychiatr Epidemiol ; 59(8): 1367-1377, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38311705

RESUMEN

PURPOSE: Characterizing trends and correlates of adolescent psychological distress is important due to observed global increases over the last 20 years. Substance use is a commonly discussed correlate, though we lack an understanding about how co-occurrence of these concerns has been changing over time. METHODS: Data came from repeated, representative, cross-sectional surveys of grade 7-12 students across Ontario, Canada conducted biennially from 2013 to 2019. Poisson regression with robust standard errors was used to examine changes in the joint association between psychological distress (operationalized as Kessler-6 [K6] scores ≥ 13) and substance use over time. Weighted prevalence ratios (PR) and their 99% confidence intervals were estimated, where p < 0.01 denotes statistical significance. RESULTS: The prevalence of psychological distress doubled between 2013 and 2019, with adjusted increases of about 1.2 times each survey year. This biennial increase did not differ based on sex, perceived social standing, school level, or any substance use. Students using substances consistently reported a higher prevalence of psychological distress (between 1.2 times and 2.7 times higher). There were similarly no differential temporal trends based on substance use for very high distress (K6 ≥ 19) or K6 items explored individually. CONCLUSION: Psychological distress steeply increased among adolescents and substance use remains important to assess and address alongside distress. However, the magnitude of temporal increases appears to be similar for adolescents reporting and not reporting substance use.


Asunto(s)
Distrés Psicológico , Estudiantes , Trastornos Relacionados con Sustancias , Humanos , Femenino , Masculino , Adolescente , Trastornos Relacionados con Sustancias/epidemiología , Ontario/epidemiología , Estudios Transversales , Estudiantes/psicología , Estudiantes/estadística & datos numéricos , Prevalencia , Encuestas y Cuestionarios , Estrés Psicológico/epidemiología , Conducta del Adolescente/psicología
2.
Psychol Med ; 48(8): 1316-1324, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-28967345

RESUMEN

BACKGROUND: Many measures are available for measuring psychological distress in the community. Limited research has compared these scales to identify the best performing tools. A common metric for distress measures would enable researchers and clinicians to equate scores across different measures. The current study evaluated eight psychological distress scales and developed crosswalks (tables/figures presenting multiple scales on a common metric) to enable scores on these scales to be equated. METHODS: An Australian online adult sample (N = 3620, 80% female) was administered eight psychological distress measures: Patient Health Questionnaire-4, Kessler-10/Kessler-6, Distress Questionnaire-5 (DQ5), Mental Health Inventory-5, Hopkins Symptom Checklist-25 (HSCL-25), Self-Report Questionnaire-20 (SRQ-20) and Distress Thermometer. The performance of each measure in identifying DSM-5 criteria for a range of mental disorders was tested. Scale fit to a unidimensional latent construct was assessed using Confirmatory Factor Analysis (CFA). Finally, crosswalks were developed using Item Response Theory. RESULTS: The DQ5 had optimal performance in identifying individuals meeting DSM-5 criteria, with adequate fit to a unidimensional construct. The HSCL-25 and SRQ-20 also had adequate fit but poorer specificity and/or sensitivity than the DQ5 in identifying caseness. The unidimensional CFA of the combined item bank for the eight scales showed acceptable fit, enabling the creation of crosswalk tables. CONCLUSIONS: The DQ5 had optimal performance in identifying risk of mental health problems. The crosswalk tables developed in this study will enable rapid conversion between distress measures, providing more efficient means of data aggregation and a resource to facilitate interpretation of scores from multiple distress scales.


Asunto(s)
Trastornos Mentales/diagnóstico , Psicometría/métodos , Estrés Psicológico/diagnóstico , Adolescente , Adulto , Anciano , Australia , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Análisis Factorial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Curva ROC , Reproducibilidad de los Resultados , Encuestas y Cuestionarios , Adulto Joven
3.
Psychol Med ; 47(2): 267-278, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-27702422

RESUMEN

BACKGROUND: Parents are a major supplier of alcohol to adolescents, yet there is limited research examining the impact of this on adolescent alcohol use. This study investigates associations between parental supply of alcohol, supply from other sources, and adolescent drinking, adjusting for child, parent, family and peer variables. METHOD: A cohort of 1927 adolescents was surveyed annually from 2010 to 2014. Measures include: consumption of whole drinks; binge drinking (>4 standard drinks on any occasion); parental supply of alcohol; supply from other sources; child, parent, family and peer covariates. RESULTS: After adjustment, adolescents supplied alcohol by parents had higher odds of drinking whole beverages [odds ratio (OR) 1.80, 95% confidence interval (CI) 1.33-2.45] than those not supplied by parents. However, parental supply was not associated with bingeing, and those supplied alcohol by parents typically consumed fewer drinks per occasion (incidence rate ratio 0.86, 95% CI 0.77-0.96) than adolescents supplied only from other sources. Adolescents obtaining alcohol from non-parental sources had increased odds of drinking whole beverages (OR 2.53, 95% CI 1.86-3.45) and bingeing (OR 3.51, 95% CI 2.53-4.87). CONCLUSIONS: Parental supply of alcohol to adolescents was associated with increased risk of drinking, but not bingeing. These parentally-supplied children also consumed fewer drinks on a typical drinking occasion. Adolescents supplied alcohol from non-parental sources had greater odds of drinking and bingeing. Further follow-up is necessary to determine whether these patterns continue, and to examine alcohol-related harm trajectories. Parents should be advised that supply of alcohol may increase children's drinking.


Asunto(s)
Bebidas Alcohólicas/estadística & datos numéricos , Consumo Excesivo de Bebidas Alcohólicas/epidemiología , Responsabilidad Parental , Consumo de Alcohol en Menores/estadística & datos numéricos , Adolescente , Australia/epidemiología , Femenino , Humanos , Estudios Longitudinales , Masculino
4.
Psychol Med ; 47(10): 1761-1770, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28222825

RESUMEN

BACKGROUND: No existing models of alcohol prevention concurrently adopt universal and selective approaches. This study aims to evaluate the first combined universal and selective approach to alcohol prevention. METHOD: A total of 26 Australian schools with 2190 students (mean age: 13.3 years) were randomized to receive: universal prevention (Climate Schools); selective prevention (Preventure); combined prevention (Climate Schools and Preventure; CAP); or health education as usual (control). Primary outcomes were alcohol use, binge drinking and alcohol-related harms at 6, 12 and 24 months. RESULTS: Climate, Preventure and CAP students demonstrated significantly lower growth in their likelihood to drink and binge drink, relative to controls over 24 months. Preventure students displayed significantly lower growth in their likelihood to experience alcohol harms, relative to controls. While adolescents in both the CAP and Climate groups demonstrated slower growth in drinking compared with adolescents in the control group over the 2-year study period, CAP adolescents demonstrated faster growth in drinking compared with Climate adolescents. CONCLUSIONS: Findings support universal, selective and combined approaches to alcohol prevention. Particularly novel are the findings of no advantage of the combined approach over universal or selective prevention alone.


Asunto(s)
Conducta del Adolescente , Consumo Excesivo de Bebidas Alcohólicas/prevención & control , Educación en Salud/métodos , Evaluación de Resultado en la Atención de Salud/métodos , Psicoterapia de Grupo/métodos , Consumo de Alcohol en Menores/prevención & control , Adolescente , Australia , Niño , Terapia Combinada , Femenino , Humanos , Masculino
5.
Psychol Med ; 46(5): 981-94, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26620582

RESUMEN

BACKGROUND: Most empirical studies into the covariance structure of psychopathology have been confined to adults. This work is not developmentally informed as the meaning, age-of-onset, persistence and expression of disorders differ across the lifespan. This study investigates the underlying structure of adolescent psychopathology and associations between the psychopathological dimensions and sex and personality risk profiles for substance misuse and mental health problems. METHOD: This study analyzed data from 2175 adolescents aged 13.3 years. Five dimensional models were tested using confirmatory factor analysis and the external validity was examined using a multiple-indicators multiple-causes model. RESULTS: A modified bifactor model, with three correlated specific factors (internalizing, externalizing, thought disorder) and one general psychopathology factor, provided the best fit to the data. Females reported higher mean levels of internalizing, and males reported higher mean levels of externalizing. No significant sex differences emerged in liability to thought disorder or general psychopathology. Liability to internalizing, externalizing, thought disorder and general psychopathology was characterized by a number of differences in personality profiles. CONCLUSIONS: This study is the first to identify a bifactor model including a specific thought disorder factor. The findings highlight the utility of transdiagnostic treatment approaches and the importance of restructuring psychopathology in an empirically based manner.


Asunto(s)
Modelos Psicológicos , Trastornos de la Personalidad/diagnóstico , Personalidad , Pensamiento , Adolescente , Adulto , Investigación Empírica , Análisis Factorial , Femenino , Humanos , Masculino , Nueva Zelanda , Escalas de Valoración Psiquiátrica , Instituciones Académicas , Estudiantes
6.
Psychol Med ; 46(2): 327-43, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26511595

RESUMEN

BACKGROUND: Considerable research has documented that exposure to traumatic events has negative effects on physical and mental health. Much less research has examined the predictors of traumatic event exposure. Increased understanding of risk factors for exposure to traumatic events could be of considerable value in targeting preventive interventions and anticipating service needs. METHOD: General population surveys in 24 countries with a combined sample of 68 894 adult respondents across six continents assessed exposure to 29 traumatic event types. Differences in prevalence were examined with cross-tabulations. Exploratory factor analysis was conducted to determine whether traumatic event types clustered into interpretable factors. Survival analysis was carried out to examine associations of sociodemographic characteristics and prior traumatic events with subsequent exposure. RESULTS: Over 70% of respondents reported a traumatic event; 30.5% were exposed to four or more. Five types - witnessing death or serious injury, the unexpected death of a loved one, being mugged, being in a life-threatening automobile accident, and experiencing a life-threatening illness or injury - accounted for over half of all exposures. Exposure varied by country, sociodemographics and history of prior traumatic events. Being married was the most consistent protective factor. Exposure to interpersonal violence had the strongest associations with subsequent traumatic events. CONCLUSIONS: Given the near ubiquity of exposure, limited resources may best be dedicated to those that are more likely to be further exposed such as victims of interpersonal violence. Identifying mechanisms that account for the associations of prior interpersonal violence with subsequent trauma is critical to develop interventions to prevent revictimization.


Asunto(s)
Accidentes de Tránsito/estadística & datos numéricos , Víctimas de Crimen/estadística & datos numéricos , Enfermedad Crítica/epidemiología , Estado Civil/estadística & datos numéricos , Trauma Psicológico/epidemiología , Trastornos por Estrés Postraumático/epidemiología , Adulto , Anciano , Análisis Factorial , Femenino , Humanos , Cooperación Internacional , Modelos Logísticos , Masculino , Persona de Mediana Edad , Prevalencia , Factores Protectores , Factores de Riesgo , Encuestas y Cuestionarios , Adulto Joven
7.
Psychol Med ; 45(5): 1103-13, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25229417

RESUMEN

BACKGROUND: Co-morbidity among use of different substances can be explained by a shared underlying dimensional factor. What remains unknown is whether the relationship between substance use and various co-morbid mental disorders can be explained solely by the general factor or whether there remain unique contributions of specific substances. METHOD: Data were from the 2007 Australian National Survey of Mental Health and Wellbeing (NSMHWB). A unidimensional latent factor was constructed that represented general substance use. The shared and specific relationships between lifetime substance use indicators and internalizing disorders, suicidality and psychotic-like experiences (PLEs) were examined using Multiple Indicators Multiple Causes (MIMIC) models in the total sample. Additional analyses then examined the shared and specific relationships associated with substance dependence diagnoses as indicators of the latent trait focusing on a subsample of substance users. RESULTS: General levels of latent substance use were significantly and positively related to internalizing disorders, suicidality and psychotic-like experiences. Similar results were found when examining general levels of latent substance dependence in a sample of substance users. There were several direct effects between specific substance use/dependence indicators and the mental health correlates that significantly improved the overall model fit but they were small in magnitude and had relatively little impact on the general relationship. CONCLUSIONS: The majority of pairwise co-morbid relationships between substance use/dependence and mental health correlates can be explained through a general latent factor. Researchers should focus on investigating the commonalities across all substance use and dependence indicators when studying mental health co-morbidity.


Asunto(s)
Trastornos Mentales/epidemiología , Modelos Estadísticos , Trastornos Relacionados con Sustancias/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Trastornos Relacionados con Alcohol/epidemiología , Trastornos Relacionados con Anfetaminas/epidemiología , Australia/epidemiología , Causalidad , Comorbilidad , Femenino , Humanos , Masculino , Abuso de Marihuana/epidemiología , Persona de Mediana Edad , Trastornos Relacionados con Opioides/epidemiología , Adulto Joven
8.
Eur J Clin Pharmacol ; 70(5): 549-55, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24522409

RESUMEN

PURPOSE: Frailty, a multifactorial biological syndrome characterized by a cumulative dysregulation of physiological processes, is associated with changes in pharmacokinetics and pharmacodynamics. The aim of this study was to quantify the effect of frailty on glomerular filtration of drugs, using the probe drug gentamicin. METHODS: Gentamicin concentrations and clinical data including the Reported Edmonton Frail Scale score were pooled from two prospective observational inpatient studies, one on prophylactic gentamicin for urologic surgery and one on therapeutic gentamicin for the empiric treatment of sepsis. Population pharmacokinetic modeling was performed using non-linear mixed effects modeling (NONMEM program) to determine the impact of frailty on gentamicin clearance. RESULTS: A one-compartment linear pharmacokinetic model best described the data and the addition of frailty to the model reduced the random variability in gentamicin clearance by 12 % after adjustment for renal function (estimated creatinine clearance using lean body weight) and lean body weight. Frail patients had an approximately 12 % lower (bootstrapping results: 14 % median) gentamicin clearance than non-frail patients (calculated as a fractional effect of frailty). CONCLUSIONS: Frailty may independently predict reduced clearance of gentamicin in older patients. Frailty could be considered in the development of dosing guidelines for drugs that undergo significant excretion through glomerular filtration.


Asunto(s)
Envejecimiento/metabolismo , Anciano Frágil , Gentamicinas/farmacocinética , Tasa de Filtración Glomerular/fisiología , Riñón/metabolismo , Modelos Biológicos , Anciano , Anciano de 80 o más Años , Femenino , Gentamicinas/administración & dosificación , Gentamicinas/sangre , Gentamicinas/uso terapéutico , Humanos , Riñón/fisiopatología , Masculino , Tasa de Depuración Metabólica
9.
Curr Res Toxicol ; 7: 100183, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39021404

RESUMEN

Quantitative Structure Activity Relationship modelling methodologies need to incorporate relevant mechanistic information to have high predictive performance and validity. Electrophilic reactivity is a common mechanistic feature of skin sensitization endpoints which could be concisely characterized with electronic descriptors which is key to enabling the modelling of small datasets in this domain. However, quantum mechanical methodologies have previously featured high computational costs which would exclude the use of large datasets. Consequently, we investigate the use of electronic descriptors calculated using the Hartree Fock with 3 corrections (Hf-3c) method, a low-cost ab initio methodology that has higher chemical accuracy than previous semiempirical methodologies for modelling in vitro skin sensitization assay outcomes. We also model the Ames assay as a surrogate for determining skin sensitization outcomes. The quantum chemical descriptors calculated using the Hf-3c method with conductor-like polarizable continuum model (CPCM) implicit solvation found improved QSAR model performance for the in vitro Ames (n = 6049, 0.770 AUC), KeratinoSens (n = 164, 0.763 AUC), and Direct Peptide Reactivity Assay (n = 122, 0.750 AUC) datasets, with their combination producing high predictive performance for unseen in vivo Local Lymph Node Assay (n = 86, 0.789 AUC) and Human Repeated Insult Patch Test (n = 86, 0.791 AUC) assay toxicant outcomes.

10.
Acta Psychiatr Scand ; 127(5): 381-93, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-22906117

RESUMEN

OBJECTIVE: The World Mental Health Version of the Composite International Diagnostic Interview (WMH-CIDI) DSM-IV bipolar disorder diagnostic algorithms were recalibrated in about 2006 following evidence of over-diagnosis of bipolar I disorder. There have been no reports of the impact of this recalibration on epidemiological findings. METHOD: Data were taken from the 2007 Australian National Survey of Mental Health and Wellbeing. Findings for cases identified by the recalibrated bipolar disorder definition were contrasted against those identified by the un-recalibrated definition. RESULTS: The 12-month prevalence of recalibrated bipolar disorder and un-recalibrated bipolar disorder were 0.9% and 1.7% respectively. The un-recalibrated bipolar disorder group was younger and more likely to have never married than the recalibrated bipolar disorder group. They were also more likely to have a comorbid alcohol use disorder, substance use disorder and asthma or arthritis. While they were more likely to have at least severe interference in at least one of the Sheehan Scale domains of functioning, they were less likely to have made a suicide attempt. Similarly, they were less likely to have consulted a psychiatrist. CONCLUSION: It is not possible to be certain about the nature of these differences. Some may be artifactual (reflecting greater statistical power to detect differences with the larger un-recalibrated bipolar disorder defined sample), while others may be indicative of the inclusion of a clinically distinct subpopulation with the un-recalibrated bipolar disorder definition, thereby producing a more heterogeneous sample. These findings indicate the need for clarity in the diagnostic algorithm used in epidemiological reports on bipolar disorder using the World Mental Health Version of the Composite International Diagnostic Interview.


Asunto(s)
Trastorno Bipolar/diagnóstico , Entrevista Psicológica , Actividades Cotidianas/psicología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Alcoholismo/epidemiología , Algoritmos , Artritis/epidemiología , Asma/epidemiología , Australia/epidemiología , Trastorno Bipolar/epidemiología , Trastorno Bipolar/psicología , Comorbilidad , Femenino , Humanos , Entrevista Psicológica/métodos , Masculino , Estado Civil , Persona de Mediana Edad , Prevalencia , Trastornos Relacionados con Sustancias/epidemiología , Adulto Joven
11.
Psychol Med ; 42(8): 1695-703, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22166813

RESUMEN

BACKGROUND: Few studies have focused on post-traumatic stress disorder (PTSD) remission in the population, none have modelled remission beyond age 54 years and none have explored in detail the correlates of remission from PTSD. This study examined trauma experience, symptom severity, co-morbidity, service use and time to PTSD remission in a large population sample. METHOD: Data came from respondents (n=8841) of the 2007 Australian National Survey of Mental Health and Wellbeing (NSMHWB). A modified version of the World Health Organization's World Mental Health Composite International Diagnostic Interview (WMH-CIDI) was used to determine the presence and age of onset of DSM-IV PTSD and other mental and substance use disorders, type, age, and number of lifetime traumas, severity of re-experiencing, avoidance and hypervigilance symptoms and presence and timing of service use. RESULTS: Projected lifetime remission rate was 92% and median time to remission was 14 years. Those who experienced childhood trauma, interpersonal violence, severe symptoms or a secondary anxiety or affective disorder were less likely to remit from PTSD and reported longer median times to remission compared to those with other trauma experiences, less severe symptoms or no co-morbidity. CONCLUSIONS: Although most people in the population with PTSD eventually remit, a significant minority report symptoms decades after onset. Those who experience childhood trauma or interpersonal violence should be a high priority for intervention.


Asunto(s)
Acontecimientos que Cambian la Vida , Trastornos Mentales/epidemiología , Trastornos por Estrés Postraumático/epidemiología , Adolescente , Adulto , Edad de Inicio , Anciano , Australia/epidemiología , Niño , Comorbilidad , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Métodos Epidemiológicos , Femenino , Humanos , Entrevista Psicológica , Masculino , Servicios de Salud Mental/estadística & datos numéricos , Persona de Mediana Edad , Remisión Espontánea , Factores de Tiempo , Violencia , Adulto Joven
12.
Epidemiol Psychiatr Sci ; 31: e44, 2022 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-35726614

RESUMEN

AIMS: There is currently little nationally representative diagnostic data available to quantify how many Aboriginal and Torres Strait Islander people may need a mental health service in any given year. Without such information, health service planners must rely on less direct indicators of need such as service utilisation. The aim of this paper is to provide a starting point by estimating the prevalence ratio of 12-month common mental disorders (i.e. mood and anxiety disorders) for Indigenous peoples compared to the general Australian population. METHODS: Analysis of the four most recent Australian Indigenous and corresponding general population surveys was undertaken. Kessler-5 summary scores by 10-year age group were computed as weighted percentages with corresponding 95% confidence intervals. A series of meta-analyses were conducted to pool prevalence ratios of Indigenous to general population significant psychological distress by 10-year age groups. The proportion of respondents with self-reported clinician diagnoses of mental disorders was also extracted from the most recent survey iterations. RESULTS: Indigenous Australians are estimated to have between 1.6 and 3.3 times the national prevalence of anxiety and mood disorders. Sensitivity analyses found that the prevalence ratios did not vary across age group or survey wave. CONCLUSIONS: To combat the current landscape of inequitable mental health in Australia, priority should be given to populations in need, such as Indigenous Australians. Having a clear idea of the current level of need for mental health services will allow planners to make informed decisions to ensure adequate services are available.


Asunto(s)
Pueblos Indígenas , Trastornos Mentales , Australia/epidemiología , Humanos , Trastornos Mentales/diagnóstico , Trastornos Mentales/epidemiología , Nativos de Hawái y Otras Islas del Pacífico , Prevalencia
13.
Psychol Med ; 40(7): 1113-23, 2010 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-19891809

RESUMEN

BACKGROUND: Large community-based epidemiological surveys have consistently identified high co-morbidity between major depressive episode (MDE) and generalized anxiety disorder (GAD). Some have suggested that this co-morbidity may be artificial and the product of the current diagnostic system. Because of the added direct and indirect costs associated with co-morbidity, it is important to investigate whether methods of diagnostic classification are artificially increasing the level of observed co-morbidity. METHOD: The item response theory (IRT) log-likelihood ratio procedure was used to test for differential item functioning (DIF) of MDE symptoms between respondents with and without a diagnosis of GAD in the 2001-2002 National Epidemiological Survey on Alcohol and Related Conditions (NESARC). RESULTS: The presence of GAD significantly increased the chances of reporting any symptom of MDE, with odds ratios ranging from 2.54 to 5.36. However, there was no indication of significant DIF of MDE symptoms in respondents with and without GAD. CONCLUSIONS: The lack of any significant DIF indicates that cases with GAD do not present with a distinct MDE symptom profile, one that is consistent with the endorsement of symptoms that are conceptually similar in nature between the two disorders, compared to cases without GAD. This does not support the hypothesis that co-morbidity between MDE and GAD is artificially inflated because of the similar symptom criteria required by the current diagnostic system. Instead, MDE and GAD may be thought of as two distinct diagnostic entities that frequently co-occur because of a shared underlying trait.


Asunto(s)
Trastornos de Ansiedad/epidemiología , Trastorno Depresivo Mayor/epidemiología , Trastornos de Ansiedad/diagnóstico , Trastornos de Ansiedad/psicología , Comorbilidad , Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/psicología , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Prevalencia , Teoría Psicológica , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , Factores de Tiempo , Adulto Joven
15.
J Med Genet ; 44(8): 516-20, 2007 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-17483304

RESUMEN

BACKGROUND: Reports of differential mutagen sensitivity conferred by a defect in the mismatch repair (MMR) pathway are inconsistent in their conclusions. Previous studies have investigated cells established from immortalised human colorectal tumour lines or cells from animal models. METHODS: We examined primary human MSH2-deficient neonatal cells, bearing a biallelic truncating mutation in MSH2, for viability and chromosomal damage after exposure to DNA-damaging agents. RESULTS: MSH2-deficient cells exhibit no response to interstrand DNA cross-linking agents but do show reduced viability in response to irradiation. They also show increased chromosome damage and exhibit altered RAD51 foci kinetics after irradiation exposure, indicating defective homologous recombinational repair. DISCUSSION: The cellular features and sensitivity of MSH2-deficient primary human cells are broadly in agreement with observations of primary murine cells lacking the same gene. The data therefore support the view that the murine model recapitulates early features of MMR deficiency in humans, and implies that the variable data reported for MMR-deficient immortalised human cells may be due to further genetic or epigenetic lesions. We suggest caution in the use of radiotherapy for treatment of malignancies in individuals with functional loss of MSH2.


Asunto(s)
Proteína 2 Homóloga a MutS/genética , Mutación , Recombinasa Rad51/genética , Tolerancia a Radiación/genética , Preescolar , Reparación del ADN , Femenino , Tamización de Portadores Genéticos , Genotipo , Humanos , Linfoma no Hodgkin/genética , Masculino , Proteína 2 Homóloga a MutS/deficiencia , Neoplasias/genética , Núcleo Familiar , Linaje , Polimorfismo de Nucleótido Simple , Recombinación Genética
16.
Emerg Med J ; 25(9): 611-2, 2008 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-18723723

RESUMEN

Symptomatic sinus bradycardia is routinely treated in the emergency department with atropine and pacing. Two cases are presented that illustrate the importance of considering hyperkalaemia, particularly in the presence of atropine-resistant symptomatic bradycardia. The administration of calcium in such cases acts to stabilise the myocardium and resolve the bradycardia. Blood gas analysis provides a rapid estimate of serum potassium concentrations, facilitating timely treatment.


Asunto(s)
Antiarrítmicos/uso terapéutico , Atropina/uso terapéutico , Bradicardia/tratamiento farmacológico , Bradicardia/etiología , Hiperpotasemia/complicaciones , Anciano , Anciano de 80 o más Años , Resistencia a Medicamentos , Electrocardiografía , Humanos , Masculino
17.
J Inherit Metab Dis ; 30(1): 23-8, 2007 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-17186413

RESUMEN

We report nine new patients with malonic aciduria associated with enzyme-confirmed malonyl-CoA decarboxylase (MCD) deficiency in eight. Clinical details were available on eight, and molecular genetic characterization was obtained for nine. As for 15 previously described patients, cardinal clinical manifestations included developmental delay and cardiomyopathy; metabolic perturbations (e.g. acidosis) and seizures, however, were infrequent or not observed in our patients. For all, detection of elevated malonic acid in urine (+/- increased C3DC acylcarnitine by analysis employing tandem mass spectrometry) led to pursuit of enzyme studies. MCD activities (nmol/h PER mg protein) revealed: control (n = 22), 16.2 +/- 1.8 (SEM; range 5.7-46.2); patients (n = 8, assayed in duplicate), 1.7 +/- 0.3 (10% of parallel control; range 0.6-2.8). Molecular characterization by DNA sequence analysis and multiplex ligation-dependent probe amplification revealed nine novel mutations (c.796C>T; p.Gln266X, c.481delC; p.Leu161CysfsX18, c.1367A>C; p.Tyr456Ser, c.1319G>T; p.Ser440Ile, c.1430C>T; p.Ser477Phe, c.899G>T; p.Gly300Val, c.799-1683_949-1293del3128, and two other large genomic deletions comprising exons 1 or the complete gene) and two known mutations in the MLYCD gene. Our findings increase the number of enzyme-confirmed MCD-deficient patients by >50%, and expand our understanding of the phenotypic and molecular heterogeneity of this rare disorder.


Asunto(s)
Carboxiliasas/deficiencia , Carboxiliasas/genética , Errores Innatos del Metabolismo/diagnóstico , Errores Innatos del Metabolismo/genética , Mutación , Adolescente , Niño , Preescolar , Exones , Femenino , Eliminación de Gen , Humanos , Lactante , Masculino , Malonatos/orina , Errores Innatos del Metabolismo/sangre , Modelos Biológicos , Modelos Genéticos , Fenotipo , Reacción en Cadena de la Polimerasa
18.
Epidemiol Psychiatr Sci ; 24(1): 45-53, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24229508

RESUMEN

Aims. To date, very few studies have examined the bi-directional associations between mood disorders (MDs), anxiety disorders (ADs) and substance use disorders (SUDs), simultaneously. The aims of the current study were to determine the rates and patterns of comorbidity of the common MDs, ADs and SUDs and describe the onset and temporal sequencing of these classes of disorder, by sex. Methods. Data came from the 2007 Australian National Survey of Mental Health and Wellbeing, a nationally representative household survey with 8841 (60% response rate) community residents aged 16-85. Results. Pre-existing mental disorders increase the risk of subsequent mental disorders in males and females regardless of the class of disorder. Pre-existing SUDs increase the risk of subsequent MDs and ADs differentially for males and females. Pre-existing MDs increase the risk of subsequent ADs differentially for males and females. Conclusions. Comorbidity remains a significant public health issue and current findings point to the potential need for sex-specific prevention and treatment responses.

19.
Epidemiol Psychiatr Sci ; 24(3): 210-26, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25720357

RESUMEN

BACKGROUND: To examine cross-national patterns and correlates of lifetime and 12-month comorbid DSM-IV anxiety disorders among people with lifetime and 12-month DSM-IV major depressive disorder (MDD). METHOD: Nationally or regionally representative epidemiological interviews were administered to 74 045 adults in 27 surveys across 24 countries in the WHO World Mental Health (WMH) Surveys. DSM-IV MDD, a wide range of comorbid DSM-IV anxiety disorders, and a number of correlates were assessed with the WHO Composite International Diagnostic Interview (CIDI). RESULTS: 45.7% of respondents with lifetime MDD (32.0-46.5% inter-quartile range (IQR) across surveys) had one of more lifetime anxiety disorders. A slightly higher proportion of respondents with 12-month MDD had lifetime anxiety disorders (51.7%, 37.8-54.0% IQR) and only slightly lower proportions of respondents with 12-month MDD had 12-month anxiety disorders (41.6%, 29.9-47.2% IQR). Two-thirds (68%) of respondents with lifetime comorbid anxiety disorders and MDD reported an earlier age-of-onset (AOO) of their first anxiety disorder than their MDD, while 13.5% reported an earlier AOO of MDD and the remaining 18.5% reported the same AOO of both disorders. Women and previously married people had consistently elevated rates of lifetime and 12-month MDD as well as comorbid anxiety disorders. Consistently higher proportions of respondents with 12-month anxious than non-anxious MDD reported severe role impairment (64.4 v. 46.0%; χ 2 1 = 187.0, p < 0.001) and suicide ideation (19.5 v. 8.9%; χ 2 1 = 71.6, p < 0.001). Significantly more respondents with 12-month anxious than non-anxious MDD received treatment for their depression in the 12 months before interview, but this difference was more pronounced in high-income countries (68.8 v. 45.4%; χ 2 1 = 108.8, p < 0.001) than low/middle-income countries (30.3 v. 20.6%; χ 2 1 = 11.7, p < 0.001). CONCLUSIONS: Patterns and correlates of comorbid DSM-IV anxiety disorders among people with DSM-IV MDD are similar across WMH countries. The narrow IQR of the proportion of respondents with temporally prior AOO of anxiety disorders than comorbid MDD (69.6-74.7%) is especially noteworthy. However, the fact that these proportions are not higher among respondents with 12-month than lifetime comorbidity means that temporal priority between lifetime anxiety disorders and MDD is not related to MDD persistence among people with anxious MDD. This, in turn, raises complex questions about the relative importance of temporally primary anxiety disorders as risk markers v. causal risk factors for subsequent MDD onset and persistence, including the possibility that anxiety disorders might primarily be risk markers for MDD onset and causal risk factors for MDD persistence.

20.
Clin Neurophysiol ; 111(9): 1531-43, 2000 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-10964062

RESUMEN

OBJECTIVES: To study working memory function in untreated major depression using a digit probe identification and matching task. METHODS: We compared behavioural performance and event-related potentials during processing of the Sternberg working memory task in 14 depressed patients and 14 healthy matched control subjects. RESULTS: Patients made more mistakes than controls as the memory load was increased from one to 5 digits and had significantly slower reaction times at all levels of memory load. The patients' event-related potentials (ERPs) differed significantly from controls. Pathological changes were similar for auditory and visual presentation. Surface negative activity in the 157-210 ms section of the waveform was reduced for all levels of memory load, suggesting abnormal sensory/perceptual processing in the modality-specific association cortices, possibly due to a failure of selective attention mechanisms. In the 375-840 ms epoch, the patients' responses showed large amplitude sustained negative activity, maximal at Cz and a reduced late positive wave. The large prolonged negativity in the patients' ERPs suggests activation of additional neuronal assemblies than those normally participating in the task. This could reflect either compensatory mechanism or dysfunction of inhibitory systems. These changes were sensitive to memory load, suggesting that they reflect alterations of memory-related processes. CONCLUSIONS: This study provides objective evidence that major depression significantly affects working memory. The ERP changes in depression could be accounted for by dysfunction of the central executive control of working memory.


Asunto(s)
Trastorno Depresivo Mayor/fisiopatología , Potenciales Evocados/fisiología , Memoria a Corto Plazo/fisiología , Adulto , Encéfalo/fisiopatología , Trastorno Depresivo Mayor/psicología , Electroencefalografía , Electrooculografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Tiempo de Reacción/fisiología , Análisis y Desempeño de Tareas
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