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OBJECTIVE: Symptomatic long-term hypoparathyroidism following thyroid surgery requires an alternative and permanent therapy that would effectively restore parathyroid function and eliminate the need for substitution drug therapy. The aim of this study was to systematically review the literature on the efficacy and safety of parathyroid allotransplantation to treat post-operative hypoparathyroidism. METHODS: MEDLINE, Embase, BIOSIS and the Cochrane Library were searched for published articles (from inception of each database to September 30, 2018). A total of 9 studies comprising 146 patients (177 allotransplantations) with post thyroidectomy hypoparathyroidism were identified. RESULTS: Parathyroid tissues used for allotransplant were cultured parathyroid cells, cryopreserved parathyroid cells and encapsulated microspheres. Post-transplant immunosuppression was only reported in three studies, mainly with oral prednisolone for 2 weeks to 6 months. Mean graft survival following allotransplantation was 47% (95% CI 24%-71%) when patients were followed-up to 6 months and 41% (95% CI 2.3%-80%) at 12 months. There was significant unexplained heterogeneity observed between studies in both these groups (I2 > 50%). Parathyroid hormone (PTH) levels, and serum calcium levels post intervention was not reported in all studies, but available evidence suggests the levels remains higher (PTH level around 12 pg/ml; Ca level around 8 mg/dl) post-allotransplantation for up to 24 months. CONCLUSIONS: Long-term benefit and harms of allotransplantation is still unclear due to the clinical and statistical heterogeneity observed among the studies. Therefore, conduct of a well-designed controlled clinical trial in the immediate future on allotransplantation is of paramount importance.

Asunto(s)

Hipocalcemia , Hipoparatiroidismo , Humanos , Hipoparatiroidismo/tratamiento farmacológico , Hipoparatiroidismo/etiología , Hipoparatiroidismo/cirugía , Glándulas Paratiroides/cirugía , Hormona Paratiroidea , Complicaciones Posoperatorias , Glándula Tiroides , Tiroidectomía/efectos adversos

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Introduction: Sickle cell disease (SCD) children are at increased risk of invasive pneumococcal disease and rely on penicillin prophylaxis and vaccination for infection prevention. Post-vaccination antibody levels in SCD may wane overtime. HbSC are believed to have better immunological response than HbSS. Objective: To compare antibody response to 23-valent pneumococcal polysaccharide vaccine (PPSV-23) between HbSS and HbSC. Methods: Patients with HbSS (n = 33) and HbSC (n = 11), aged 7-18 years, were prospectively recruited. Luminex pneumococcal antibody levels were measured for 23-serotypes, after two PPSV-23 doses. Results: Absolute median titer for 20 of the 23 serotypes was higher in HbSC than HbSS and significantly higher for serotypes 22 (3.9 vs. 1.6mcg/ml; p=0.039) and 43 (2.9 vs. 0.8mcg/ml; p = 0.007). HbSC mounted a better immune anti-pneumococcal response compared to HbSS (≥ 1.3 mcg/ml) for 18 of 23 serotypes, albeit not significant for any of the serotypes. More HbSC (64%) than HbSS (42%) were good vaccine responders (p = 0.303). Two of 21 (10%) good vaccine responders and nine of 23 (39%) poor vaccine responders SCD participants subsequently developed acute chest syndrome or pneumonia (p = 0.036). None of the HbSC patients developed ACS after receiving PPSV-23. HbSS poor vaccine responders were at increased future recurrence risk for ACS (p = 0.003), pneumonia (p = 0.036) or both (p = 0.011), compared to good vaccine responders. Conclusion: HbSC possess better pneumococcal vaccine response than HbSS. Poor vaccine response is concerning for future acute pulmonary events. Current vaccination strategy for SCD sub-types are lacking, therefore further study to evaluate utility of vaccine boosters is necessary

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Asunto(s)

Humanos , Femenino , Niño , Adolescente , Enfermedad de la Hemoglobina SC/inmunología , Vacunas Neumococicas/inmunología , Anemia de Células Falciformes , Relación Dosis-Respuesta Inmunológica , Streptococcus pneumoniae/inmunología , Estudios Prospectivos

RESUMEN

INTRODUCTION: Sickle cell disease (SCD) children are at increased risk of invasive pneumococcal disease and rely on penicillin prophylaxis and vaccination for infection prevention. Post-vaccination antibody levels in SCD may wane overtime. HbSC are believed to have better immunological response than HbSS. OBJECTIVE: To compare antibody response to 23-valent pneumococcal polysaccharide vaccine (PPSV-23) between HbSS and HbSC. METHODS: Patients with HbSS (n=33) and HbSC (n=11), aged 7-18 years, were prospectively recruited. Luminex pneumococcal antibody levels were measured for 23-serotypes, after two PPSV-23 doses. RESULTS: Absolute median titer for 20 of the 23 serotypes was higher in HbSC than HbSS and significantly higher for serotypes 22 (3.9 vs. 1.6mcg/ml; p=0.039) and 43 (2.9 vs. 0.8mcg/ml; p=0.007). HbSC mounted a better immune anti-pneumococcal response compared to HbSS (≥1.3mcg/ml) for 18 of 23 serotypes, albeit not significant for any of the serotypes. More HbSC (64%) than HbSS (42%) were good vaccine responders (p=0.303). Two of 21 (10%) good vaccine responders and nine of 23 (39%) poor vaccine responders SCD participants subsequently developed acute chest syndrome or pneumonia (p=0.036). None of the HbSC patients developed ACS after receiving PPSV-23. HbSS poor vaccine responders were at increased future recurrence risk for ACS (p=0.003), pneumonia (p=0.036) or both (p=0.011), compared to good vaccine responders. CONCLUSION: HbSC possess better pneumococcal vaccine response than HbSS. Poor vaccine response is concerning for future acute pulmonary events. Current vaccination strategy for SCD sub-types are lacking, therefore further study to evaluate utility of vaccine boosters is necessary.

Asunto(s)

Anemia de Células Falciformes/inmunología , Hemoglobina C/metabolismo , Hemoglobina Falciforme/metabolismo , Infecciones Neumocócicas/inmunología , Vacunas Neumococicas/inmunología , Streptococcus pneumoniae/fisiología , Adolescente , Formación de Anticuerpos , Niño , Femenino , Humanos , Masculino , Infecciones Neumocócicas/prevención & control , Estudios Prospectivos , Vacunación

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Introduction The use of corticosteroids in systemic lupus erythematosus (SLE) patients requires difficult trade-offs between efficacy and risk of toxicity. This qualitative study examined SLE patients' most desired outcomes and their concerns with corticosteroid use in SLE treatment. Methods SLE patients with current/past experience with using corticosteroids were recruited from the clinics at the Johns Hopkins Lupus Center and the University of Maryland Medical Center. Five in-depth interviews ( N = 5) and four focus groups ( N = 15) were conducted during which discussions were transcribed and analyzed based on a grounded theory approach. Results We identified five major themes describing SLE patients' most desired outcomes: reduction in flares, maintenance of normal activities, minimization of treatment side effects, prevention of future organ damage, and finding a cure. Further, SLE patients reported these primary concerns with the adverse effects of corticosteroids: weight gain, organ damage (particularly bone-related damage), mood swings/irritability, sleep disturbances, and dental issues. Patients appeared to be more concerned with adverse effects that immediately affected their day-to-day lives. Conclusion Knowledge gained during this study better informs how patients view the benefits and risks of corticosteroids. This can facilitate discussions between physicians and patients as they work together to determine the appropriate use of corticosteroids.

Asunto(s)

Corticoesteroides/uso terapéutico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Conocimientos, Actitudes y Práctica en Salud , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/psicología , Corticoesteroides/efectos adversos , Adulto , Anciano , Femenino , Grupos Focales , Humanos , Masculino , Maryland , Persona de Mediana Edad , Investigación Cualitativa , Índice de Severidad de la Enfermedad , Adulto Joven

RESUMEN

BACKGROUND: This study aimed to evaluate parental perception of neighbourhood environments and safety in association with children's physical activity among primary school children in Klang, Selangor, Malaysia. METHODS: A total of 250 children (9-12 years of age) and their parents participated in this cross-sectional study. Physical Activity Questionnaire for Older Children and Neighbourhood Environmental Walkability Scale as well as questions on constrained behaviours (avoidance and defensive behaviours) were used to assess the children's physical activity and parental perception of neighbourhood environment and safety, respectively. RESULTS: More than one-third (36.0%) of the children were physically inactive compared with only a small percentage (4.8%) who were physically active, with boys achieving higher physical activity levels than girls (t = 2.564, P = 0.011). For the environmental scale, parents' perception of land-use mix (access) (r = 0.173, P = 0.006), traffic hazards (r = -0.152, P = 0.016) and defensive behaviour (r = -0.024, P = 0.143) correlated significantly with children's physical activity. In multiple linear regression analysis, child's gender (ß = -0.226; P = 0.003), parent's education (ß = 0.140; P = 0.001), household income (ß = 0.151; P = 0.024), land-use mix (access) (ß = 0.134; P = 0.011) and defensive behaviour (ß = -0.017; P = 0.038) were significantly associated with physical activity in children (R = 0.349, F = 6.760; P < 0.001), contributing 12.2% of the variances in physical activity of the children. CONCLUSION: Results highlight the links between parental perception of neighbourhood environments, safety and constrained behaviours with their children's participation in active play. Interventions aimed to increase actual and perceived safety and reduce perceptions of risk by parents in safe neighbourhoods can be targeted to increase children's physical activity in their local neighbourhoods.

Asunto(s)

Accidentes/estadística & datos numéricos , Actitud Frente a la Salud , Conducta Infantil , Planificación Ambiental/estadística & datos numéricos , Ejercicio Físico , Padres/psicología , Medio Social , Heridas y Lesiones/epidemiología , Prevención de Accidentes , Adulto , Factores de Edad , Niño , Estudios Transversales , Femenino , Conductas Relacionadas con la Salud , Humanos , Malasia/epidemiología , Masculino , Relaciones Padres-Hijo , Padres/educación , Percepción , Características de la Residencia , Encuestas y Cuestionarios , Heridas y Lesiones/psicología

RESUMEN

BACKGROUND: High normal albuminuria is associated with higher cardiovascular risk in patients with diabetes. Increased aortic stiffness is an established risk factor of vascular events. However, the relationship between albuminuria within the normal range (0-30 mg/g) and aortic stiffness in patients with Type 2 diabetes is unknown. METHODS: A total of 614 normoalbuminuric subjects with Type 2 diabetes with spot urinary albumin:creatinine ratio ≤ 30 mg/g and estimated glomerular filtration rate ≥ 60 ml min⁻¹ 1.73 m⁻² were included in the study. Aortic stiffness was assessed by carotid-femoral pulse wave velocity. RESULTS: Pulse wave velocity increased progressively with the increase of albumin:creatinine ratio within the normoalbuminuric range (0-30 mg/g). Only 2.6% of the subjects with an albumin:creatinine ratio in the lowest quartile (0.7-3.4 mg/g) were classified as having aortic stiffness (pulse wave velocity ≥12 m/s). In contrast, the proportion of subjects with aortic stiffness increased significantly with the increase of albumin:creatinine ratio level (11.0%, 10.4% and 13.6% in albumin:creatinine ratio quartiles 2, 3 and 4, respectively, P = 0.008). A logistic regression model revealed that the odds of having aortic stiffness were increased by 56% with a 1-SD increase of log albumin:creatinine ratio after adjustment for age, gender, duration of diabetes, HbA1c , blood pressure, HDL and LDL cholesterol, estimated glomerular filtration rate, BMI, usage of renin-angiotensin system antagonists, statins and insulin. CONCLUSIONS: High normal albuminuria is associated with aortic stiffness in patients with Type 2 diabetes, which may in part explain their increased cardiovascular risk.

Asunto(s)

Albuminuria/complicaciones , Enfermedades Cardiovasculares/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Angiopatías Diabéticas/complicaciones , Cardiomiopatías Diabéticas/complicaciones , Nefropatías Diabéticas/complicaciones , Rigidez Vascular , Anciano , Albuminuria/diagnóstico , Albuminuria/fisiopatología , Albuminuria/orina , Aorta/fisiopatología , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/fisiopatología , Estudios Transversales , Angiopatías Diabéticas/epidemiología , Angiopatías Diabéticas/fisiopatología , Cardiomiopatías Diabéticas/epidemiología , Cardiomiopatías Diabéticas/fisiopatología , Nefropatías Diabéticas/diagnóstico , Nefropatías Diabéticas/fisiopatología , Nefropatías Diabéticas/orina , Femenino , Tasa de Filtración Glomerular , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis de la Onda del Pulso , Factores de Riesgo , Índice de Severidad de la Enfermedad , Singapur/epidemiología

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Correction of perinatally lethal neurogenetic diseases requires efficient transduction of several cell types within the relatively inaccessible CNS. Intravenous AAV9 delivery in mouse has achieved development stage-specific transduction of neuronal cell types, with superior neuron-targeting efficiency demonstrated in prenatal compared with postnatal recipients. Because of the clinical relevance of the non-human primate (NHP) model, we investigated the ability of AAV9 to transduce the NHP CNS following intrauterine gene therapy (IUGT). We injected two macaque fetuses at 0.9 G with 1 × 10(13) vg scAAV9-CMV-eGFP through the intrahepatic continuation of the umbilical vein. Robust green fluorescent protein (GFP) expression was observed for up to 14 weeks in the majority of neurons (including nestin-positive cells), motor neurons and oligodendrocytes throughout the CNS, with a significantly lower rate of transduction in astrocytes. Photoreceptors and neuronal cell bodies in the plexiform and ganglionic retinal layers were also transduced. In the peripheral nervous system (PNS), widespread transduction of neurons was observed. Tissues harvested at 14 weeks showed substantially lower vector copy number and GFP levels, although the percentage of GFP-expressing cells remained stable. Thus, AAV9-IUGT in late gestation efficiently transduces both the CNS and PNS with neuronal predilection, of translational relevance to hereditary disorders characterized by perinatal onset of neuropathology.

Asunto(s)

Corteza Cerebral/metabolismo , Dependovirus/genética , Vectores Genéticos/administración & dosificación , Sistema Nervioso Periférico/metabolismo , Transducción Genética , Animales , Animales Recién Nacidos , Astrocitos/metabolismo , Citomegalovirus/genética , Femenino , Feto/metabolismo , Terapia Genética , Proteínas Fluorescentes Verdes/análisis , Proteínas Fluorescentes Verdes/genética , Macaca , Oligodendroglía/metabolismo , Embarazo , Retina/metabolismo

RESUMEN

OBJECTIVES: Folate status and/or genes have been linked to depression in a number of studies. This may be via a direct action (or actions) on neuronal membranes or indirect effects through the metabolism of methyl groups involved in neurotransmitter synthesis. This study examines folate and related thiol metabolism that might underpin either phenomenon. DESIGN: Cohort study describing the relationship between several genetic and nutritional aspects of folic acid homeostasis and depression assessed by the HADS psychometric index in an elderly cohort. SETTING: New South Wales (Australia) retirement village. PARTICIPANTS: 118 elderly participants (age 65-90 years). RESULTS: Stepwise multiple regression was used to determine the best statistical model to predict depression; C677T-MTHFR (p=0.0103) was found to be positively associated with depression, while the thiol dipeptide Cys-Gly was negatively associated (p=0.0403). The statistical models used accounted for the major folate related indices (genetic and biochemical) that are most often evaluated in the context of health and disease. When only genetic data were examined for interactions, C677T-MTHFR was found to be negatively associated with the HADS Depression Index Score (p=0.0191). CONCLUSION: The potential influence of Cys-Gly on this phenotype is novel, and of considerable interest given that it has been linked to altered spontaneous activity and sedation in an animal model. Cys-Gly is a recognised ligand at the N-methyl-D-aspartatic acid (NMDA) subclass of glutamate receptor, a system associated with depression. In addition, the C677T-MTHFR association adds further support to existing findings underscoring the potential role of folate in depression.

Asunto(s)

Depresión/epidemiología , Depresión/genética , Dipéptidos/sangre , Ácido Fólico/metabolismo , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Anciano , Anciano de 80 o más Años , Australia/epidemiología , Estudios de Cohortes , Depresión/sangre , Dieta , Femenino , Ácido Fólico/administración & dosificación , Ácido Fólico/sangre , Deficiencia de Ácido Fólico/epidemiología , Estudios de Asociación Genética , Homeostasis , Viviendas para Ancianos , Humanos , Masculino , Polimorfismo de Nucleótido Simple , Escalas de Valoración Psiquiátrica , Encuestas y Cuestionarios