RESUMEN
INTRODUCTION: Pulmonary embolism (PE) is the major complication of thromboembolic disease. While a few qualitative studies have explored patient experience after PE, to our knowledge no literature review is available to date. The aim of this work was to explore patient experience after a PE episode through a systematic review of the literature comprising: patient experience, clinicians' perception of the patients' attitude and knowledge, and the patients' perception of VTE prevention strategies. METHODS: A search of PubMed, Web of science, Cochrane and EMBASE databases. The search was conducted without filters. Search results were combined and duplicates were removed. The selection was blinded by two independent researchers using the Rayyan application. RESULTS: Fifty studies were assessed for quality and 23 were included. Individual semi-structured interviews and focus groups were widely used to explore patient experience after a PE episode. Patients described deterioration in their quality of life, their psychological state and an initial feeling of carer abandonment. The trends observed appear to be more pronounced in patients with an episode characterized as unprovoked. CONCLUSION: These preliminary results call for further longitudinal studies, the objective being to better understand the evolution of these factors in the short and long terms.
Asunto(s)
Embolia Pulmonar , Calidad de Vida , Humanos , Bases de Datos Factuales , Emociones , Embolia Pulmonar/etiología , Evaluación del Resultado de la Atención al PacienteAsunto(s)
Cardiopatías , Diagnóstico Prenatal , Embarazo , Femenino , Humanos , Atención Prenatal , Corazón , Ultrasonografía PrenatalRESUMEN
BACKGROUND: Transversal grouping of addictions under the heading "Substance related and addictive disorders" in the DSM-5 has led to a common policy on addictions and the promotion of addiction services covering all types of addictions, including behavioral addictions. MATERIAL AND METHODS: The main objective of this study was to describe the prevalence of problem gambling in a population of patients seeking treatment in addictive disorders center. Secondary objectives were: to describe the use of Internet and the prevalence of gaming disorder, sexual addiction and compulsive buying online ; to describe a population of patients consulting in addictive disorders center; to explore associated factors related to problem gambling. A self-questionnaire was built, evaluating the socio-demographic elements, the addiction pathway, problem gambling and Internet use with a focus on video game disorder, sexual addiction and compulsive buying. It was offered to consultants from five addictology centers in Brittany. RESULTS: 252 patients seeking treatment for addictive disorders were included. Problem gambling was present in 9.9 % of patients. Problem gamblers were more likely to have been asked about their gambling by the addictology team than other patients. The rate of identification of gambling habits, whether in addiction or outside, was generally low. Internet use was 83 %. The prevalence of other online behavioral addictions was low. DISCUSSION AND CONCLUSION: The prevalence of problem gambling is almost 4 times higher among addictology consultants, compared to the general population, probably related to addictive comorbidities. The identification of gambling habits concerned a small proportion of the patients included, whether in specialized care or outside. There is significant room for improvement in the identification of problem gambling, in addictology and beyond. It is important to question gambling habits for any reason for addiction consultation and to repeat this identification over time. As the Internet is widely used by addictology consultants, it can represent a key element in care, both in the identification of behavioral addictions and in follow-up.
Asunto(s)
Conducta Adictiva , Juego de Azar , Juegos de Video , Conducta Adictiva/epidemiología , Conducta Adictiva/terapia , Juego de Azar/epidemiología , Juego de Azar/terapia , Hábitos , Humanos , InternetRESUMEN
BACKGROUND: Cardiovascular diseases are the world's leading cause of morbidity and mortality. An active lifestyle is one of the cornerstones in the primary prevention of cardiovascular disease. An initial step in guiding primary prevention programs is to refer to clinical guidelines. We aimed to systematically review clinical practice guidelines on primary prevention of cardiovascular disease and their recommendations regarding physical activity. METHODS: We systematically searched Trip Medical Database, PubMed and Guidelines International Network from January 2012 up to December 2020 using the following search strings: 'cardiovascular disease', 'prevention', combined with specific cardiovascular disease risk factors. The identified records were screened for relevance and content. We methodologically assessed the selected guidelines using the AGREE II tool. Recommendations were summarized using a consensus-developed extraction form. RESULTS: After screening, 27 clinical practice guidelines were included, all of which were developed in Western countries and showed consistent rigor of development. Guidelines were consistent about the benefit of regular, moderate-intensity, aerobic physical activity. However, recommendations on strategies to achieve and sustain behavior change varied. Multicomponent interventions, comprising education, counseling and self-management support, are recommended to be delivered by various providers in primary health care or community settings. Guidelines advise to embed patient-centered care and behavioral change techniques in prevention programs. CONCLUSIONS: Current clinical practice guidelines recommend similar PA lifestyle advice and propose various delivery models to be considered in the design of such interventions. Guidelines identify a gap in evidence on the implementation of these recommendations into practice.
Asunto(s)
Enfermedades Cardiovasculares , Enfermedades Cardiovasculares/prevención & control , Consejo , Ejercicio Físico , Humanos , Estilo de Vida , Guías de Práctica Clínica como Asunto , Prevención PrimariaRESUMEN
OBJECTIVES: With increasing global interest in hospital antimicrobial stewardship (AMS) programmes, there is a strong demand for core elements of AMS to be clearly defined on the basis of principles of effectiveness and affordability. To date, efforts to identify such core elements have been limited to Europe, Australia, and North America. The aim of this study was to develop a set of core elements and their related checklist items for AMS programmes that should be present in all hospitals worldwide, regardless of resource availability. METHODS: A literature review was performed by searching Medline and relevant websites to retrieve a list of core elements and items that could have global relevance. These core elements and items were evaluated by an international group of AMS experts using a structured modified Delphi consensus procedure, using two-phased online in-depth questionnaires. RESULTS: The literature review identified seven core elements and their related 29 checklist items from 48 references. Fifteen experts from 13 countries in six continents participated in the consensus procedure. Ultimately, all seven core elements were retained, as well as 28 of the initial checklist items plus one that was newly suggested, all with ≥80% agreement; 20 elements and items were rephrased. CONCLUSIONS: This consensus on core elements for hospital AMS programmes is relevant to both high- and low-to-middle-income countries and could facilitate the development of national AMS stewardship guidelines and adoption by healthcare settings worldwide.
Asunto(s)
Programas de Optimización del Uso de los Antimicrobianos/organización & administración , Consenso , Salud Global , Antibacterianos/administración & dosificación , Programas de Optimización del Uso de los Antimicrobianos/normas , Australia , Lista de Verificación , Europa (Continente) , Hospitales , América del Norte , Pobreza , Encuestas y CuestionariosRESUMEN
Folic acid supplementation confers modest benefit in schizophrenia, but its effectiveness is influenced by common genetic variants in the folate pathway that hinder conversion to its active form. We examined physiological and clinical effects of l-methylfolate, the fully reduced and bioactive form of folate, in schizophrenia. In this randomized, double-blind trial, outpatients with schizophrenia (n=55) received l-methylfolate 15 mg or placebo for 12 weeks. Patients were maintained on stable doses of antipsychotic medications. The pre-defined primary outcome was change in plasma methylfolate at 12 weeks. Secondary outcomes included change in symptoms (Positive and Negative Syndrome Scale (PANSS), Scale for Assessment of Negative Symptoms, Calgary Depression Scale for Schizophrenia), cognition (Measurement and Treatment Research to Improve Cognition in Schizophrenia composite) and three complementary magnetic resonance imaging measures (working memory-related activation, resting connectivity, cortical thickness). Primary, mixed model, intent-to-treat analyses covaried for six genetic variants in the folate pathway previously associated with symptom severity and/or response to folate supplementation. Analyses were repeated without covariates to evaluate dependence on genotype. Compared with placebo, l-methylfolate increased plasma methylfolate levels (d=1.00, P=0.0009) and improved PANSS Total (d=0.61, P=0.03) as well as PANSS Negative and General Psychopathology subscales. Although PANSS Total and General Psychopathology changes were influenced by genotype, significant PANSS Negative changes occurred regardless of genotype. No treatment differences were seen in other symptom rating scales or cognitive composite scores. Patients receiving l-methylfolate exhibited convergent changes in ventromedial prefrontal physiology, including increased task-induced deactivation, altered limbic connectivity and increased cortical thickness. In conclusion, l-methylfolate supplementation was associated with salutary physiological changes and selective symptomatic improvement in this study of schizophrenia patients, warranting larger clinical trials. ClinicalTrials.gov, NCT01091506.
Asunto(s)
Esquizofrenia/tratamiento farmacológico , Tetrahidrofolatos/farmacología , Adulto , Antipsicóticos/uso terapéutico , Cognición/efectos de los fármacos , Método Doble Ciego , Femenino , Ácido Fólico/metabolismo , Ácido Fólico/farmacología , Humanos , Masculino , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Tetrahidrofolatos/uso terapéutico , Resultado del TratamientoRESUMEN
OBJECTIVE: This study examined the effect of adjunctive telmisartan on psychopathology and cognition in olanzapine- or clozapine-treated patients with schizophrenia. METHOD: In a 12-week randomized, double-blind, placebo-controlled study, patients diagnosed with schizophrenia or schizoaffective disorder received either telmisartan (80 mg once per day) or placebo. Psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS) and the Scale for Assessment of Negative Symptoms (SANS), and a neuropsychological battery was used to assess cognitive performance. Assessments for psychopathology and cognition were conducted at baseline and week 12. RESULTS: Fifty-four subjects were randomized, and 43 completed the study (22 in the telmisartan group, 21 in the placebo group). After 12-weeks of treatment, the telmisartan group had a significant decrease in PANSS total score compared withthe placebo group (mean ± SD: - 4.1 ± 8.1 vs. 0.4 ± 7.5, P = 0.038, SCohen's d = 0.57). There were no significant differences between the two groups in change from baseline to week 12 in PANSS subscale scores, SANS total score, or any cognitive measures (P > 0.100). CONCLUSION: The present study suggests that adjunctive treatment with telmisartan may improve schizophrenia symptoms. Future trials with larger sample sizes and longer treatment durations are warranted.
Asunto(s)
Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacología , Antipsicóticos/farmacología , Bencimidazoles/farmacología , Benzoatos/farmacología , Evaluación de Resultado en la Atención de Salud , Trastornos Psicóticos/tratamiento farmacológico , Esquizofrenia/tratamiento farmacológico , Adulto , Bloqueadores del Receptor Tipo 1 de Angiotensina II/administración & dosificación , Antipsicóticos/administración & dosificación , Bencimidazoles/administración & dosificación , Benzoatos/administración & dosificación , Benzodiazepinas/administración & dosificación , Benzodiazepinas/farmacología , Clozapina/administración & dosificación , Clozapina/farmacología , Método Doble Ciego , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Olanzapina , TelmisartánRESUMEN
OBJECTIVES: There is currently no consensus on the optimal feeding route for an oropharyngeal squamous cell cancer (OPSCC) patient without pre-existing dysphagia undergoing chemoradiotherapy. This study aimed to compare the swallowing outcomes for OPSCC patients fed via either prophylactic RIG (pRIG) or reactive nasogastric tube (rNGT). DESIGN: A prospective cohort study. SETTING: Four head and neck cancer centres in the North of England Cancer Network. PARTICIPANTS: Fifty-three participants with OPSCC, on a normal diet pre-(chemo) radiotherapy. MAIN OUTCOME MEASURE: Swallowing outcomes for patients with rNGT and pRIG were compared using the following outcome measures administered prospectively at pre-treatment, three and 12 months post-treatment: MD Anderson Dysphagia Inventory (MDADI), Performance Status Scales (Normalcy of Diet), timed water swallow test. RESULTS: Twenty-three patients received pRIG while 30 were planned for a rNGT. No differences in demographics were found between the groups. The rNGT group had a clinically significant higher score on MDADI at 12 months post-treatment. No significant difference was found on a timed water swallow test or diet texture scale. CONCLUSIONS: There is no statistical difference for swallowing outcomes in either group. However, patients' in the rNGT group reported a clinically meaningful difference at 1 year, with a trend for them to do better across all measures. Neither group returned to their baseline swallowing function. Further research with a larger sample size is indicated.
Asunto(s)
Carcinoma de Células Escamosas/terapia , Quimioradioterapia , Trastornos de Deglución/epidemiología , Trastornos de Deglución/prevención & control , Deglución/fisiología , Gastrostomía , Intubación Gastrointestinal , Neoplasias Orofaríngeas/terapia , Anciano , Carcinoma de Células Escamosas/complicaciones , Carcinoma de Células Escamosas/patología , Estudios de Cohortes , Trastornos de Deglución/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Orofaríngeas/complicaciones , Neoplasias Orofaríngeas/patología , Resultado del TratamientoRESUMEN
The ketamine model for schizophrenia has led to several therapeutic strategies for enhancing N-methyl d-aspartate (NMDA) receptor activity, including agonists directed at the glycine receptor site and inhibitors of glycine reuptake. Because ketamine may primarily block NMDA receptors on inhibitory interneurons, drugs that reduce glutamate release have also been investigated as a means of countering a deficit in inhibitory input. These approaches have met with some success for the treatment of negative and positive symptoms, but results have not been consistent. An emerging approach with the NMDA partial agonist, d-cycloserine (DCS), aims to enhance plasticity by intermittent treatment. Early trials have demonstrated benefit with intermittent DCS dosing for negative symptoms and memory. When combined with cognitive remediation, intermittent DCS treatment enhanced learning on a practiced auditory discrimination task and when added to cognitive behavioral therapy, DCS improved delusional severity in subjects who received DCS with the first CBT session. These studies require replication, but point toward a promising strategy for the treatment of schizophrenia and other disorders of plasticity.
Asunto(s)
Cicloserina/uso terapéutico , Esquizofrenia/tratamiento farmacológico , Terapia Cognitivo-Conductual , Humanos , Memoria/efectos de los fármacos , Receptores de N-Metil-D-Aspartato/metabolismoRESUMEN
BACKGROUND AND AIMS: Pericardial adipose tissue (PAT) is located on both sides of the pericardium. We tested whether PAT was associated with prevalent diabetes at the year 25 exam of the Coronary Artery Risk Development in Young Adults (CARDIA) study. METHODS AND RESULTS: The CARDIA Year 25 exam (2010-2011) included complete data for all covariates on 3107 participants. Prevalent diabetes (n = 436) was defined as high fasting (≥126 mg/dl) or 2-h postload glucose (≥200 mg/dl) or HbA1c (≥6.5%) or use of diabetes medications. Volume of PAT was measured from computed tomographic scans. Logistic regression was performed to examine the relationship between quartiles of PAT and diabetes. In regression models adjusted for field center, sex, race, age, systolic blood pressure, total cholesterol, log triglycerides, and treatment with blood pressure and cholesterol lowering medication, PAT volume in the 4th quartile was significantly associated with diabetes status after adjustment for BMI (OR 2.57, 95% CI 1.66, 3.98) or visceral adipose tissue (OR 2.08, 95% CI 1.32, 3.29). PAT volume in the 2nd and 3rd quartiles was not significantly associated with diabetes status relative to the first quartile. CONCLUSIONS: Metabolically active pericardial adipose tissue is associated with prevalent diabetes only at higher volumes independent of overall obesity.
Asunto(s)
Adiposidad , Diabetes Mellitus Tipo 2/epidemiología , Obesidad/epidemiología , Tejido Adiposo/metabolismo , Adolescente , Adulto , Presión Sanguínea , Índice de Masa Corporal , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Enfermedad de la Arteria Coronaria/etiología , Estudios Transversales , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Humanos , Grasa Intraabdominal/metabolismo , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Obesidad/complicaciones , Pericardio/metabolismo , Prevalencia , Triglicéridos/sangre , Circunferencia de la Cintura , Adulto JovenRESUMEN
OBJECTIVES: To assess the between-group change in swallowing function from baseline to 12 months following treatment, for patients treated for resectable stage III and IVA oropharyngeal squamous cell carcinoma. To assess the within-group change in swallowing function between 3 and 12 months following treatment. DESIGN: Non-randomised cohort study. SETTING: A single head and neck cancer unit with oncology services held at the nearby regional treatment centre. PARTICIPANTS: Twenty-five patients treated with Transoral Laser Microsurgery +/- adjuvant (chemo)radiotherapy (Transoral Laser Microsurgery) observed alongside an historic cohort of 33 patients treated with (chemo)radiotherapy. MAIN OUTCOME MEASURES: The patient reported MD Anderson Dysphagia Inventory (MDADI), an objective timed Water Swallow Test, and the clinician rated normalcy of diet subsection of the Performance of Swallowing Scale . RESULTS: Between baseline and 12 months, patients treated with primary (chemo)radiotherapy demonstrated greater deterioration in swallowing function compared to Transoral Laser Microsurgery for all 3 swallowing measures. Between 3 and 12 months, the only significant change was an improvement in Performance of Swallowing Scale scores in the (chemo)radiotherapy group. CONCLUSIONS: This is the first study to report the results of a complimentary set of swallowing measures for patients treated with Transoral Laser Microsurgery, observed alongside a cohort of (chemo)radiotherapy patients. The preliminary results suggest a benefit in swallowing function for Transoral Laser Microsurgery over (chemo)radiotherapy during the year following treatment.
Asunto(s)
Quimioradioterapia , Trastornos de Deglución/etiología , Trastornos de Deglución/fisiopatología , Terapia por Láser/métodos , Microcirugia/métodos , Neoplasias Orofaríngeas/patología , Neoplasias Orofaríngeas/terapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Prospectivos , Resultado del TratamientoRESUMEN
OBJECTIVE: The objective of this study was to identify predictors of mortality in infants with omphalocele. METHODS: Medical records of infants with omphalocele born between January 1992 and June 2012, with follow-up toDecember 2012, were retrospectively reviewed. Survivors and non-survivors were compared. Evidence for pulmonary hypertension was sought between the second and seventh day after birth. All included infants had increased right ventricular pressures (RVP >40âmmhg) on echocardiogram on the second day of life with increased oxygen requirements, therefore, the finding of increased pressure was not considered a result of the transitional circulation. Logistic regression was used to evaluate the importance and independence of various factors. RESULTS: Of 51 infants whose records were reviewed, 13 died (25%) and 38 survived (75%). The median time to death was 34 days (range: 4 -408 days). The median follow-up time for those who died was 1.5 years (range: 0.01-15 years) and for survivors was 2.6 years (range: 0.08-15 years). Logistic regression revealed that respiratory insufficiency at birth (OR: 14.8; 95% CI: 2.5-85.0) and pulmonary hypertension (OR: 6.4; 95% CI: 1.1-39.0) were independently associated with mortality. CONCLUSION: Respiratory insufficiency after birth and pulmonary hypertension are independent predictors of mortality in infants with omphalocele.
Asunto(s)
Hernia Umbilical/mortalidad , Hipertensión Pulmonar/epidemiología , Insuficiencia Respiratoria/epidemiología , Preescolar , Comorbilidad , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Factores de TiempoRESUMEN
OBJECTIVE: The aim of the present study was to determine whether serum urate (sUA) concentration is positively associated with subclinical atherosclerosis, independent of body mass index (BMI), amongst generally healthy adults. DESIGN AND SETTING: The CARDIA study followed 5115 Black and White individuals aged 18-30 years in 1985-1986 (year 0). Subclinical atherosclerosis comprised coronary artery calcified plaque (CAC; years 15, 20 and 25), and maximum common carotid intima-media thickness (IMT; year 20). sUA (years 0, 10, 15 and 20) was modelled as gender-specific quartiles that were pooled. Discrete-time hazard regressions and generalized linear regressions were used for analyses. RESULTS: Mean sUA concentration was lower in women than in men and increased with age. Adjusting for demographic and lifestyle factors, the highest versus lowest quartile of sUA at year 0 was associated with a 44% [95% confidence interval (CI) 20%, 73%] greater risk of CAC progression from years 15 to 25 (Ptrend < 0.001), which was attenuated by adjustment for BMI at year 0 (Ptrend = 0.45). A stronger association was found between sUA at year 15 and CAC progression at year 20 or 25 (hazard ratio 2.07, 95% CI 1.66, 2.58 for the highest versus lowest sUA quartile Ptrend < 0.001), which was attenuated, but remained significant with additional adjustment for BMI at year 15 (Ptrend = 0.01). A greater increment in sUA concentration from year 0 to year 15, independent of change in BMI, was related to a higher risk of CAC progression (Ptrend < 0.001). Similar associations were found between sUA and IMT, but only in men. CONCLUSION: sUA may be an early biomarker for subclinical atherosclerosis in young adults; starting in early middle age, sUA predicts subclinical atherosclerosis independently of BMI.
Asunto(s)
Aterosclerosis/sangre , Enfermedad de la Arteria Coronaria/sangre , Ácido Úrico/sangre , Adolescente , Adulto , Factores de Edad , Aterosclerosis/diagnóstico , Aterosclerosis/etiología , Biomarcadores/sangre , Índice de Masa Corporal , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/etiología , Femenino , Humanos , Estudios Longitudinales , Masculino , Valor Predictivo de las Pruebas , Factores de Riesgo , Factores Sexuales , Adulto JovenRESUMEN
OBJECTIVE: This study examined the effects of adjunctive aripiprazole therapy on metabolism in clozapine-treated patients with schizophrenia. METHOD: In an 8-week randomized, double-blind, placebo-controlled study, subjects received either aripiprazole (15 mg/day) or placebo. At baseline and week 8, metabolic parameters were assessed by the frequently sampled intravenous glucose tolerance test, nuclear magnetic resonance spectroscopy and whole-body dual-energy X-ray absorptiometry (DXA). RESULTS: Thirty subjects completed the study (16 in the aripiprazole group and 14 in the placebo group). Glucose effectiveness measured by the frequently sampled intravenous glucose tolerance test improved significantly in the aripiprazole group (0.003 ± 0.006 vs. -0.005 ± 0.007/min, P = 0.010). The aripiprazole group showed significant reductions in both plasma low-density lipoprotein (LDL) levels (-15.1 ± 19.8 vs. 4.4 ± 22.5 mg/dl, P = 0.019) and LDL particle numbers (-376 ± 632 vs. -36 ± 301 nm, P = 0.035). Further, there was a significant reduction in the lean mass (-1125 ± 1620 vs. 607 ± 1578 g, P = 0.011) measured by whole-body DXA scan in the aripiprazole group. All values were expressed as mean ± standard deviation, aripiprazole vs. placebo. CONCLUSION: Adjunctive therapy with aripiprazole may have some metabolic benefits in clozapine-treated patients with schizophrenia.
Asunto(s)
Antipsicóticos/metabolismo , Clozapina/metabolismo , Piperazinas/metabolismo , Quinolonas/metabolismo , Esquizofrenia/metabolismo , Absorciometría de Fotón/métodos , Adulto , Antipsicóticos/uso terapéutico , Aripiprazol , Composición Corporal/efectos de los fármacos , Clozapina/uso terapéutico , Método Doble Ciego , Quimioterapia Combinada/métodos , Femenino , Estudios de Seguimiento , Glucosa/metabolismo , Prueba de Tolerancia a la Glucosa/métodos , Humanos , Lipoproteínas LDL/sangre , Espectroscopía de Resonancia Magnética/métodos , Masculino , Piperazinas/uso terapéutico , Quinolonas/uso terapéutico , Esquizofrenia/tratamiento farmacológicoRESUMEN
AIMS: Post-hoc evaluation of relationships between first-year change in glycaemic control (HbA(1c) ) and change in patient-reported outcomes among ACCORD health-related quality of life (HRQoL) substudy participants. METHODS: Data from 2053 glycaemia-trial subjects were analysed. We assessed physical and mental health status (36-Item Short Form Health Survey, Version-2), symptom count and severity (Diabetes Symptoms Distress Checklist) and treatment satisfaction (Diabetes Treatment Satisfaction Questionnaire). Linear mixed models were used to test relationships between 1-year changes in HbA(1c) and patient reported outcomes sequentially adjusting for correlates (baseline characteristics, baseline patient reported outcomes, treatment assignment, frequency of clinical contact and post-randomization weight change plus new complications). RESULTS: Poorer baseline control of HbA(1c) and cardiovascular disease risk factors predicted greater one-year improvements in treatment satisfaction. Similarly, poorer baseline patient reported outcome scores all individually predicted greater 1-year improvement in that same outcome. Accounting for baseline and post-randomization characteristics and treatment arm, 1-year change in HbA(1c) was unrelated to changes in overall physical or mental health; however, every one percentage-point (10.9 mmol/mol) reduction in HbA(1c) was associated with lower symptom count (ß = 0.599; P = 0.012), lower symptom distress (ß = 0.051; P = 0.001), and higher treatment satisfaction (ß = -2.514; P < 0.001). CONCLUSIONS: Independent of all relevant covariates, better glycaemic control over 1 year was associated with reduced patient-reported diabetes symptoms and symptom distress, and increased treatment satisfaction, but not overall physical and mental health. Further investigation is required to understand the specific psychosocial mechanisms that affect how patients value health and treatments.
Asunto(s)
Glucemia/metabolismo , Diabetes Mellitus Tipo 2/sangre , Hemoglobina Glucada/metabolismo , Hipoglucemiantes/uso terapéutico , Satisfacción del Paciente , Adulto , Anciano , Peso Corporal , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/epidemiología , Femenino , Estado de Salud , Encuestas Epidemiológicas , Humanos , Masculino , Salud Mental , Persona de Mediana Edad , Satisfacción del Paciente/estadística & datos numéricos , Calidad de Vida , Resultado del TratamientoRESUMEN
BACKGROUND: Previous studies have suggested that motivational aspects of executive functioning, which may be disrupted in schizophrenia patients with negative symptoms, are mediated in part by the striatum. Negative symptoms have been linked to impaired recruitment of both the striatum and the dorsolateral prefrontal cortex (DLPFC). Here we tested the hypothesis that negative symptoms are associated primarily with striatal dysfunction, using functional magnetic resonance imaging (fMRI). METHOD: Working-memory load-dependent activation and gray matter volumes of the striatum and DLPFC were measured using a region-of-interest (ROI) approach, in 147 schizophrenia patients and 160 healthy controls. In addition to testing for a linear relationships between striatal function and negative symptoms, we chose a second, categorical analytic strategy in which we compared three demographically and behaviorally matched subgroups: patients with a high burden of negative symptoms, patients with minimal negative symptoms, and healthy subjects. RESULTS: There were no differences in striatal response magnitudes between schizophrenia patients and healthy controls, but right DLPFC activity was higher in patients than in controls. Negative symptoms were inversely associated with striatal, but not DLPFC, activity. In addition, patients with a high burden of negative symptoms exhibited significantly lower bilateral striatal, but not DLPFC, activation than schizophrenia patients with minimal negative symptoms. Working memory performance, antipsychotic exposure and changes in gray matter volumes did not account for these differences. CONCLUSIONS: These data provide further evidence for a robust association between negative symptoms and diminished striatal activity. Future work will determine whether low striatal activity in schizophrenia patients could serve as a reliable biomarker for negative symptoms.
Asunto(s)
Memoria a Corto Plazo/fisiología , Neostriado/fisiopatología , Corteza Prefrontal/fisiopatología , Esquizofrenia/fisiopatología , Adulto , Femenino , Neuroimagen Funcional , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana EdadRESUMEN
In Ph-positive (Ph(+)) leukemia, the quiescent cell state is one of the reasons for resistance to the BCR-ABL-kinase inhibitor, imatinib. In order to examine the mechanisms of resistance due to quiescence and the effect of the mammalian target of rapamycin inhibitor, everolimus, for such a resistant population, we used Ph(+) acute lymphoblastic leukemia patient cells serially xenotransplanted into NOD/SCID/IL2rγ(null) (NOG) mice. Spleen cells from leukemic mice showed a higher percentage of slow-cycling G(0) cells in the CD34(+)CD38(-) population compared with the CD34(+)CD38(+) and CD34(-) populations. After ex vivo imatinib treatment, more residual cells were observed in the CD34(+)CD38(-) population than in the other populations. Although slow-cycling G(0) cells were insensitive to imatinib in spite of BCR-ABL and CrkL dephosphorylation, combination treatment with everolimus induced substantial cell death, including that of the CD34(+)CD38(-) population, with p70-S6 K dephosphorylation and decrease of MCL-1 expression. The leukemic non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mouse system with the in vivo combination treatment with imatinib and everolimus showed a decrease of tumor burden including CD34(+) cells. These results imply that treatment with everolimus can overcome resistance to imatinib in Ph(+) leukemia due to quiescence.
RESUMEN
OBJECTIVE: The primary purpose of this 8-week double-blind, placebo-controlled trial of rosiglitazone 4 mg/day was to examine its effect on insulin sensitivity index (SI) and glucose utilization (SG) in clozapine-treated subjects with schizophrenia with insulin resistance. METHOD: Eighteen subjects were randomized and accessed with a Frequently Sampled Intravenous Glucose Tolerance Test (FSIVGTT) at baseline and at week 8 to estimate SG and SI. RESULTS: Controlling for the baseline, comparing the rosiglitazone group with placebo group, there was a non-significant improvement in SG (0.016 +/- 0.006-0.018 +/- 0.008, effect size = 0.23, P = 0.05) with a trend of improvement in SI in the rosiglitazone group (4.6 +/- 2.8-7.8 +/- 6.7, effect size = 0.18, P = 0.08). There was a significant reduction in small low-density lipoprotein cholesterol (LDL-C) particle number (987 +/- 443-694 +/- 415, effect size = 0.30, P = 0.04). CONCLUSION: Rosiglitazone may have a role in addressing insulin resistance and lipid abnormalities associated with clozapine.
Asunto(s)
Clozapina/efectos adversos , Hipoglucemiantes/uso terapéutico , Síndrome Metabólico/inducido químicamente , Esquizofrenia/tratamiento farmacológico , Tiazolidinedionas/uso terapéutico , Adolescente , Adulto , Anciano , Glucemia/metabolismo , LDL-Colesterol/metabolismo , Clozapina/uso terapéutico , Método Doble Ciego , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Resistencia a la Insulina , Masculino , Síndrome Metabólico/tratamiento farmacológico , Persona de Mediana Edad , Placebos , Rosiglitazona , Esquizofrenia/metabolismoRESUMEN
UNLABELLED: This study sought to examine the effectiveness of sibutramine, a weight loss agent, on clozapine-associated weight gain. METHOD: This was a 12-week double-blind, placebo controlled, randomized trial of sibutramine for weight loss in obese clozapine-treated schizophrenia or schizoaffective disorder subjects. RESULTS: Ten patients were enrolled into the placebo group and 11 patients into the sibutramine group. There were no significant baseline differences between the two groups on age, gender, education, ethnicity, diagnosis, weight, body mass index (BMI), and blood pressure. At week 12, there were no significant differences in changes in weight, BMI, abdominal and waist circumferences, Hba1c, fasting glucose, or cholesterol levels. CONCLUSION: Sibutramine treatment did not show significant weight loss compared with placebo in clozapine-treated patients with schizophrenia or schizoaffective disorder. Further research with a larger sample size and longer follow-up duration is warranted.
Asunto(s)
Antipsicóticos/efectos adversos , Depresores del Apetito/farmacología , Depresores del Apetito/uso terapéutico , Clozapina/efectos adversos , Ciclobutanos/farmacología , Ciclobutanos/uso terapéutico , Obesidad/inducido químicamente , Obesidad/tratamiento farmacológico , Esquizofrenia/tratamiento farmacológico , Aumento de Peso/efectos de los fármacos , Adulto , Antropometría , Antipsicóticos/uso terapéutico , Glucemia/metabolismo , Índice de Masa Corporal , Peso Corporal/efectos de los fármacos , Colesterol/sangre , Clozapina/uso terapéutico , Método Doble Ciego , Ayuno , Femenino , Hemoglobina Glucada , Hemoglobinas/metabolismo , Humanos , Masculino , Obesidad/metabolismo , Trastornos Psicóticos/tratamiento farmacológicoRESUMEN
OBJECTIVE: We studied a sample of schizophrenia out-patients to test the hypotheses that serum homocysteine concentrations would correlate positively with measures of glucose metabolism. METHOD: Subjects underwent a nutritional assessment and fasting plasma, serum insulin and homocysteine tests. RESULTS: Males had a significantly higher homocysteine levels than females (7.69 +/- 1.42 microM vs. 6.63 +/- 1.40 microM; P = 0.02). Comparing subjects with normal fasting glucose (NFG) (glucose < 100 mg/dl) and impaired fasting glucose (IFG) (> or = 100 mg/dl) subjects with IFG (mean 8.2 +/- 1.5 microM) had significantly higher homocysteine levels than those with NFG (mean 7.2 +/- 1.4 microM, P = 0.03). IFG was also associated with greater mean values for a Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) (P = 0.002) and diastolic blood pressure (P = 0.045). CONCLUSION: The group with IFG had higher fasting serum homocysteine concentrations than those with NFG which supports a connection to an important cardiovascular risk factor.