RESUMEN
Background Charcot-Marie-Tooth disease is a common inherited neuropathy where patients may be sensitive to adverse effects of certain medicines; however, information about medication safety in this group of people is limited. Objective This study aimed to investigate the experience of Australian individuals with Charcot-Marie-Tooth disease in using medications, including perceived impact of drug-induced adverse effects. Secondarily, it aimed to determine whether individuals with Charcot-Marie-Tooth disease feel adequately supported to make decisions about medication safety. Setting Focus groups and interviews (face-to-face or telephone) of individuals with Charcot-Marie-Tooth disease in Australia. Method A mixed methods qualitative study was conducted between September 2015 and August 2016 using semi-structured interviews. Thematic analysis of interview transcripts was conducted independently by two researchers using inductive coding until concept saturation was achieved. Main outcome measure Perceptions of medicines safety in people with Charcot-Marie-Tooth disease, including barriers to making informed decisions about medication safety. Results Twenty-four adults with Charcot-Marie-Tooth disease participated. Anaesthetics (18%) and pregabalin (15%) were the medications most frequently reported as impacting on Charcot-Marie-Tooth symptoms. Participants sought medication information primarily from general practitioners or neurologists. The main barriers identified by participants were a perceived poor understanding in non-specialist health professionals about Charcot-Marie-Tooth disease and lack of attention to medication safety concerns in people with Charcot-Marie-Tooth disease; this resulted in dissatisfaction about the advice provided. Many individuals who faced uncertainty in obtaining and understanding medicines information turned to internet resources, peer groups, and use of complementary and alternative medicines to self-manage Charcot-Marie-Tooth exacerbations. Conclusion Participants reported drug-related adverse effects and a difficulty in obtaining safety information about medication. This study highlights the need for improved evidence about medication safety in people with Charcot-Marie-Tooth disease. Development of evidence-based resources, increased awareness amongst health professionals about Charcot-Marie-Tooth disease and a team-based care approach could facilitate shared decisions about medication use for people with Charcot-Marie-Tooth disease.
Asunto(s)
Enfermedad de Charcot-Marie-Tooth/complicaciones , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/etiología , Satisfacción del Paciente , Farmacéuticos , Rol Profesional , Acceso a la Información , Adulto , Anciano , Actitud del Personal de Salud , Australia , Enfermedad de Charcot-Marie-Tooth/diagnóstico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/diagnóstico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/prevención & control , Femenino , Grupos Focales , Conocimientos, Actitudes y Práctica en Salud , Humanos , Entrevistas como Asunto , Masculino , Persona de Mediana Edad , Participación del Paciente , Seguridad del Paciente , Relaciones Profesional-Paciente , Investigación Cualitativa , Calidad de Vida , Medición de Riesgo , Factores de Riesgo , AutocuidadoRESUMEN
OBJECTIVE: To explore the feasibility of integrating a residential care pharmacist and describe the activities they subsequently undertake in an established residential aged care facility. METHODS: A residential care pharmacist was integrated part-time (15 hours per week) into a 104-bed residential aged care facility in the Australian Capital Territory, for 6 months. The pharmacist documented all activities performed during the study period. RESULTS: The residential care pharmacist documented 335.3 hours performing 284 activities. The two broad classes of activities were as follows: (1) organisation-oriented, which were system-level interventions to improve medication safety, and (2) resident-oriented, which were clinical interventions conducted at the individual level. The activities most frequently performed were pharmaceutical opinion, quality improvement and comprehensive medication review. The stakeholder and organisational demand for these activities indicated feasibility for the role. CONCLUSION: Pharmacists working collaboratively as part of a multidisciplinary aged care team can perform a range of clinically and operationally beneficial activities.
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Atención a la Salud , Farmacéuticos , Anciano , Australia , Territorio de la Capital Australiana , Humanos , Proyectos PilotoRESUMEN
OBJECTIVES: The feasibility of pharmacist-led influenza vaccination services in residential aged care homes has not previously been studied. The primary objective of this pilot study was to evaluate the feasibility of this service. The secondary objective was to assess the effect of the service on employee vaccination rates. METHODS: An in-house pharmacist-led vaccination service was implemented at a single site in 2017. De-identified employee influenza vaccination records at this site for 2016 and 2017 were compared to assess the change in vaccination rate. RESULTS: The residential care pharmacist administered 37% of all influenza vaccinations to employees (n = 78) in 2017. Between 2016 and 2017, there was a significant improvement in the employee vaccination rate at the site (46.5% vs 69.2%, P < 0.01). CONCLUSIONS: It is feasible for pharmacists to administer influenza vaccinations to employees in residential aged care. The flexibility of an in-house pharmacist improves accessibility and can therefore promote uptake of influenza vaccination by employees.
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Servicios de Salud para Ancianos , Vacunas contra la Influenza/inmunología , Farmacéuticos , Vacunación , Anciano , Humanos , Proyectos Piloto , Vacunación/estadística & datos numéricosRESUMEN
Glutathione transferase kappa (GSTK1-1) is a highly conserved, mitochondrial enzyme potentially involved in redox reactions. GSTK1-1-deficient mice were generated to further study the enzyme's biological role. Reduced and total glutathione levels in liver and kidney were unchanged by GSTK1-1 deficiency and NADPH quinone oxidoreductase 1 expression was not elevated indicating that there is no general underlying oxidative stress in Gstk1(-/-) mice. Electron microscopy of liver and kidney showed no changes in mitochondrial morphology with GSTK1-1 deficiency. The death of a number of Gstk1(-/-) males with urinary tract problems prompted close examination of the kidneys. Electron microscopy revealed glomerular basement membrane changes at 3 months, accompanied by detectable microalbuminuria in male mice (albumin:creatinine ratio of 2.66±0.83 vs 1.13±0.20 mg/mmol for Gstk1(-/-) and wild-type (WT), respectively, P=0.001). This was followed by significant foot process effacement (40-55% vs 10% for Gstk1(-/-) and WT, respectively) at 6 months of age in all Gstk1(-/-) mice examined. Kidney tubules were ultrastructurally normal. Compared with human disease, the Gstk1(-/-) kidneys show changes seen in glomerulopathies causing nephrotic syndrome. Gstk1(-/-) mice may offer insights into the early development of glomerular nephropathies.
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Glomerulonefritis/etiología , Glomerulonefritis/patología , Glutatión Transferasa/deficiencia , Albuminuria/etiología , Animales , Análisis Químico de la Sangre , Western Blotting , Ensayo de Inmunoadsorción Enzimática , Inmunohistoquímica , Riñón/ultraestructura , Hígado/ultraestructura , Masculino , Ratones , Ratones Noqueados , Microscopía Electrónica , Estrés Oxidativo/fisiología , UrinálisisRESUMEN
The level of glutathione transferase Kappa (GSTK1-1) has been correlated with obesity (Liu et.al. 2008 PNAS 105: 18302-7) and a polymorphism in the hGSTK1 promoter has been associated with insulin secretion and fat deposition (Gao et al 2009 Endocr J 56: 487-94). We searched for additional polymorphisms that may influence GSTK1-1 function or expression. Two SNPs were identified in the 5' non-coding region. A SNP at -1308 that occurs in Chinese subjects is predicted to eliminate a FXR/RXR transcription factor-binding site and causes a 55% increase in transcription rate in HepG2 cells and a 59% decrease in HEK293 cells. These data suggest that the impact of this polymorphism is complex and tissue specific. A SNP at -1032 alters a methylation site and represses transcription by 38%. These observations provide the first functional insight into genetic factors that regulate hGSTK1 expression and may directly influence insulin secretion and fat deposition.
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Regulación de la Expresión Génica , Glutatión Transferasa/biosíntesis , Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas , Femenino , Glutatión Transferasa/genética , Células Hep G2 , Humanos , Insulina/genética , Insulina/metabolismo , Secreción de Insulina , Masculino , Obesidad/genética , Obesidad/metabolismoRESUMEN
Mutations in the ganglioside-induced differentiation-associated protein 1 (GDAP1) gene have been linked with Charcot-Marie-Tooth (CMT) disease. This protein, and its paralogue GDAP1L1, appear to be structurally related to the cytosolic glutathione S-transferases (GST) including an N-terminal thioredoxin fold domain with conserved active site residues. The specific function, of GDAP1 remains unknown. To further characterise their structure and function we purified recombinant human GDAP1 and GDAP1L1 proteins using bacterial expression and immobilised metal affinity chromatography. Like other cytosolic GSTs, GDAP1 protein has a dimeric structure. Although the full-length proteins were largely insoluble, the deletion of a proposed C-terminal transmembrane domain allowed the preparation of soluble protein. The purified proteins were assayed for glutathione-dependent activity against a library of 'prototypic' GST substrates. No evidence of glutathione-dependent activity or an ability to bind glutathione immobilised on agarose was found.
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Glutatión Transferasa/fisiología , Proteínas del Tejido Nervioso/fisiología , Secuencia de Aminoácidos , Western Blotting , Línea Celular , Enfermedad de Charcot-Marie-Tooth/genética , Dimerización , Humanos , Datos de Secuencia Molecular , Proteínas del Tejido Nervioso/genética , Proteínas Recombinantes de Fusión/biosíntesis , Proteínas Recombinantes de Fusión/aislamiento & purificación , Alineación de SecuenciaRESUMEN
Styrene-7,8-oxide (SO) is a highly reactive epoxide able to undergo reactions with endogenous nucleophiles, such as DNA. SO is inactivated by glutathione-S-transferase M1 (GSTM1). This detoxification enzyme is absent in approximately one-half of Caucasian (49%) populations. A GSTM1 recombinant human lymphoblastoid cell line (FB7) was generated from a GSTM1 negative parental cell line (WIL2NS). GSTM1 status was determined using RT-PCR and immunochemistry. Cells were challenged with a range of SO doses and subsequent toxicity (population growth in flasks) and genotoxicity (mutations at the HPRT locus) were monitored. FB7 (GSTM1 positive) exhibited greater cell survival after SO exposure relative to the GSTM1 negative parental line. The IC50 following a 1 h exposure to SO was 0.5 mM for WIL2NS, compared to greater than 2.5 mM for FB7. The extrapolated IC50 for FB7 was 5.5 mM. Significantly fewer mutant cells were induced by SO for FB7 than for WIL2NS at equivalent doses of SO. These findings suggest that the sensitivity of cells to styrene-7,8-oxide is influenced by GSTM1 status and that a recombinant GSTM1 positive cell line can efficiently detoxify styrene-7,8-oxide.