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1.
J Am Med Dir Assoc ; 25(6): 104944, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38428832

RESUMEN

OBJECTIVE: We aimed to explore medicines regimens charted for older people living in residential aged care facilities (RACFs). DESIGN: Repeated cross-sectional study using routinely collected data sampled in a cross-sectional manner at 11 time points (day of admission, then at 1, 3, 7, 14, and 30 days, and 3, 6, 12, 18, and 24 months post admission). SETTING AND PARTICIPANTS: The cohort is set in 34 RACFs managed by a single Australasian provider. People aged ≥65 years admitted to permanent care between January 1, 2017, and October 1, 2021, with medicines charted on the date of admission. METHODS: Medicines charted were evaluated for potentially suboptimal prescribing including number of medicines, high-risk prescribing (eg, potentially inappropriate medicines, anticholinergic burden), and potential underprescribing. RESULTS: The 3802 residents in the final cohort had a mean age of 84.9 ± 7.2 years at admission. At least 1 example of suboptimal prescribing was identified in 3479 (92%) residents at admission increasing to 1410 (97%) at 24 months. The number of medicines charted for each resident increased over time from 6.0 ± 3.8 regular and 2.8 ± 2.7 as required medicines at admission to 8.9 ± 4.1 regular and 8.1 ± 3.7 as required medicines at 24 months. Anticholinergic drug burden increased from 1.6 ± 2.4 at admission to 3.0 ± 2.8 at 24 months. Half the residents (2173; 57%) used at least 1 potentially inappropriate medicine at admission, which rose to nearly three-quarters (1060; 73%) at 24 months admission. CONCLUSION AND IMPLICATIONS: The total number of medicines charted for older adults living in RACFs increases with length of stay, with charted as required medicines nearly tripling. Effective interventions to optimize medicines use in this vulnerable population are required.


Asunto(s)
Prescripción Inadecuada , Humanos , Estudios Transversales , Femenino , Masculino , Anciano de 80 o más Años , Anciano , Prescripción Inadecuada/estadística & datos numéricos , Hogares para Ancianos/estadística & datos numéricos , Polifarmacia , Lista de Medicamentos Potencialmente Inapropiados , Australia , Casas de Salud
2.
J Am Med Dir Assoc ; 25(3): 539-544.e2, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38307120

RESUMEN

OBJECTIVES: The structured, clinically supervised withdrawal of medicines, known as deprescribing, is one strategy to address inappropriate polypharmacy. This study aimed to evaluate the costs and consequences of deprescribing in frail older people living in residential aged care facilities (RACFs) in Australia. DESIGN: A within-trial cost-consequence analysis of a deprescribing intervention-Opti-Med. The Opti-Med double-blind randomized controlled trial of deprescribing included 3 groups: blinded control, blinded intervention, and an open intervention group. SETTING AND PARTICIPANTS: Seventeen RACFs in Western Australia and New South Wales. Participants were 303 older people living in participating RACFs from March 2014 to February 2019. METHODS: Analysis was conducted from the health sector perspective. Health economic outcomes assessed include cost saved from deprescribed medicines and the incremental quality-adjusted life-years. Costs were presented in 2022 Australian dollars. RESULTS: The total cost of the Opti-Med intervention was $239.13 per participant. The costs saved through deprescribed medicines over 12 months after adjusting for mortality within the trial period was $328.90 per participant in the blinded intervention group and $164.00 per participant in the open intervention group. On average, the cost of the intervention was more than offset by the cost saved from deprescribed medicines. Extrapolating these findings to the Australian population suggests a potential net cost saving of about $1 to $16 million per annum for the health system nationally. The incremental quality-adjusted life-years were very similar across the 3 groups within the trial period. CONCLUSIONS AND IMPLICATIONS: Deprescribing for frail older people living in RACFs can be a cost-saving intervention without reducing the quality of life. Systemwide implementation of deprescribing across RACFs in Australia has the potential to improve health care delivery through the cost savings, which could be reapplied to further optimize care within RACFs.


Asunto(s)
Deprescripciones , Humanos , Anciano , Australia , Anciano Frágil , Calidad de Vida , Ahorro de Costo , Evaluación de Resultado en la Atención de Salud
3.
J Med Case Rep ; 17(1): 444, 2023 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-37803426

RESUMEN

BACKGROUND: Here we report the only formally documented case in the United Kingdom, to our knowledge, of a cerebral fat embolism secondary to non-iatrogenic trauma through a Tarlov cyst. This case demonstrates the pathology clearly giving an excellent opportunity to demonstrate a rarely seen pathology as well as illustrating the importance of the patient history to guiding further management. CASE PRESENTATION: A middle-aged patient was admitted on the acute medical take complaining of severe headache with photophobia, having just returned after a skiing holiday. Computerised tomography scan of the head showed fat within the anterior horn of both lateral ventricles, and within the subarachnoid space. Re-discussion with the patient and subsequent MRI (Magnetic Resonance Imaging) of the spine identified the pathogenesis of her symptoms: a sacral insufficiency fracture through a Tarlov cyst, causing subarachnoid fat embolism and symptoms of a low-pressure headaches due to a dural leak. Patient was medically managed and discharged with planned follow-up. Due to the Coronavirus pandemic and resolution of the patient's symptoms, they declined further follow up imaging. CONCLUSIONS: The case demonstrates a rarely seen pathology as cause of a common presenting problem, headache. Emphasizing the importance of history taking and appropriate investigations in medical cases that do not conform to the usual diagnosis.


Asunto(s)
Embolia Grasa , Trastornos de Cefalalgia , Fracturas de la Columna Vertebral , Quistes de Tarlov , Persona de Mediana Edad , Femenino , Humanos , Quistes de Tarlov/complicaciones , Quistes de Tarlov/diagnóstico , Fracturas de la Columna Vertebral/complicaciones , Fracturas de la Columna Vertebral/diagnóstico por imagen , Embolia Grasa/diagnóstico por imagen , Embolia Grasa/etiología , Cefalea/etiología
4.
J Prim Health Care ; 15(2): 184-185, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37390025

Asunto(s)
Muerte , Anciano , Humanos
5.
Age Ageing ; 52(5)2023 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-37247404

RESUMEN

BACKGROUND: potentially harmful polypharmacy is very common in older people living in aged care facilities. To date, there have been no double-blind randomised controlled studies of deprescribing multiple medications. METHODS: three-arm (open intervention, blinded intervention and blinded control) randomised controlled trial enrolling people aged over 65 years (n = 303, noting pre-specified recruitment target of n = 954) living in residential aged care facilities. The blinded groups had medications targeted for deprescribing encapsulated while the medicines were deprescribed (blind intervention) or continued (blind control). A third open intervention arm had unblinded deprescribing of targeted medications. RESULTS: participants were 76% female with mean age 85.0 ± 7.5 years. Deprescribing was associated with a significant reduction in the total number of medicines used per participant over 12 months in both intervention groups (blind intervention group -2.7 medicines, 95% CI -3.5, -1.9, and open intervention group -2.3 medicines; 95% CI -3.1, -1.4) compared with the control group (-0.3, 95% CI -1.0, 0.4, P = 0.053). Deprescribing regular medicines was not associated with any significant increase in the number of 'when required' medicines administered. There were no significant differences in mortality in the blind intervention group (HR 0.93, 95% CI 0.50, 1.73, P = 0.83) or the open intervention group (HR 1.47, 95% CI 0.83, 2.61, P = 0.19) compared to the control group. CONCLUSIONS: deprescribing of two to three medicines per person was achieved with protocol-based deprescribing during this study. Pre-specified recruitment targets were not met, so the impact of deprescribing on survival and other clinical outcomes remains uncertain.


Asunto(s)
Deprescripciones , Anciano Frágil , Anciano , Humanos , Femenino , Anciano de 80 o más Años , Masculino , Hogares para Ancianos , Método Doble Ciego , Polifarmacia , Evaluación de Resultado en la Atención de Salud , Ensayos Clínicos Controlados Aleatorios como Asunto
6.
Aust J Gen Pract ; 52(4): 173-180, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-37021442

RESUMEN

BACKGROUND: Deprescribing is an integral part of patient care. The term 'deprescribing' may be new to some, but the concept is not. Deprescribing refers to the planned withdrawal of medicines that are causing harm or not helping an individual. OBJECTIVE: This article collates the latest evidence on deprescribing to guide general practitioners (GPs) and nurse practitioners on how to deprescribe for their elderly patients. DISCUSSION: Deprescribing is a safe and effective method of reducing polypharmacy and high-risk prescribing. The challenge for GPs in deprescribing medicines for older people is to avoid adverse drug withdrawal events. Strategies to deprescribe confidently in partnership with patients include incorporating a 'stop slow, go low' approach and careful consideration of the medicine withdrawal plan.


Asunto(s)
Deprescripciones , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Medicina General , Médicos Generales , Humanos , Anciano
7.
Arch Gerontol Geriatr ; 107: 104910, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36565605

RESUMEN

BACKGROUND: Deprescribing is an intervention to address the high prevalence of inappropriate polypharmacy in older people living in residential aged care facilities (RACFs). Many deprescribing interventions are complex and involve several stages including initial pharmacist recommendation, subsequent acceptance of the recommendations by a prescriber and the patient, and then actual implementation. OBJECTIVES: This study aimed to investigate pharmacist deprescribing recommendations for residents within RACFs, general practitioner (GP) acceptance, and the actual implementation of the accepted recommendations at 12-month. METHODS: The intervention occurred as part of a randomised controlled trial and comprised a pharmacist-led medication review using an evidence-based algorithm, with the focus on identifying medications to potentially deprescribe. Consent to participate was obtained from residents (or surrogate decision-makers), RACF nursing staff and the resident's GP. Deprescribing recommendations were reviewed by GPs before implementation as part of the intervention and control arms of the trial, although control group participants continued to receive their usual medications in a blinded manner. RESULTS: There were 303 participants enrolled in the study, and 77% (941/1222) of deprescribing recommendations suggested by the pharmacists were accepted by GPs. Of the recommendations accepted by GPs, 74% (692/ 941) were successfully implemented at the end of the follow-up visit at 12 months. The most common reason for deprescribing was because medications were no longer needed (42%, 513/ 1231). CONCLUSION: Pharmacist-led deprescribing recommendations arising from an algorithm-based medication review are acceptable to doctors and can have a significant impact on reducing the number of inappropriate medications consumed by older people in RACFs. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12613001204730.


Asunto(s)
Deprescripciones , Médicos Generales , Anciano , Humanos , Farmacéuticos , Australia , Hogares para Ancianos , Polifarmacia
8.
Arch Gerontol Geriatr ; 105: 104849, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36399891

RESUMEN

OBJECTIVE: To describe medicines regimens used by older people living in residential aged care facilities (RACFs). MATERIALS AND METHODS: This cross-sectional study presents baseline data from a randomised controlled trial in seventeen Australian RACFs that recruited residents aged 65 years and older at the participating facilities. The main outcome measures were to evaluation of medicines utilisation, including the number of medicines, medicine regimen complexity, potential under-prescribing and high-risk prescribing (prescribing cascades, anticholinergic or sedative medicines or other potentially inappropriate medicines) with data analysed descriptively. RESULTS: Medicines regimens were analysed for 303 residents (76% female) with a mean age of 85.0 ± 7.5 years, of whom the majority were living with dementia (72%). Residents were prescribed an average of 10.3 ± 4.5 regular medicines daily. Most participants (85%) had highly complex regimens. Most residents (92%) were exposed to polypharmacy (five or more medicines). Nearly all, 302 (98%) residents had at least one marker of potentially suboptimal prescribing. At least one instance of potential under-prescribing was identified in 86% of residents. At least one instance of high-risk prescribing was identified in 81% of residents including 16% of participants with at least one potential prescribing cascade. CONCLUSION(S): Potentially suboptimal prescribing affected almost all residents in this study, and most had highly complex medicines regimens. If generalisable, these findings indicate most older people in RACFs may be at risk of medicines-related harm from suboptimal prescribing, in addition to the burden of administration of complex medicines regimens for facility staff and residents.


Asunto(s)
Estudios Transversales , Femenino , Humanos , Anciano , Anciano de 80 o más Años , Masculino , Australia
9.
Blood Adv ; 6(18): 5494-5504, 2022 09 27.
Artículo en Inglés | MEDLINE | ID: mdl-35640238

RESUMEN

Chronic lymphocytic leukemia (CLL) cells have variably low surface IgM (sIgM) levels/signaling capacity, influenced by chronic antigen engagement at tissue sites. Within these low levels, CLL with relatively high sIgM (CLLhigh) progresses more rapidly than CLL with low sIgM (CLLlow). During ibrutinib therapy, surviving CLL cells redistribute into the peripheral blood and can recover sIgM expression. Return of CLL cells to tissue may eventually recur, where cells with high sIgM could promote tumor growth. We analyzed time to new treatment (TTNT) following ibrutinib in 70 patients with CLL (median follow-up of 66 months) and correlated it with pretreatment sIgM levels and signaling characteristics. Pretreatment sIgM levels correlated with signaling capacity, as measured by intracellular Ca2+ mobilization (iCa2+), in vitro (r = 0.70; P < .0001). High sIgM levels/signaling strongly correlated with short TTNT (P < .05), and 36% of patients with CLLhigh vs 8% of patients with CLLlow progressed to require a new treatment. In vitro, capacity of ibrutinib to inhibit sIgM-mediated signaling inversely correlated with pretherapy sIgM levels (r = -0.68; P = .01) or iCa2+ (r = -0.71; P = .009). In patients, sIgM-mediated iCa2+ and ERK phosphorylation levels were reduced by ibrutinib therapy but not abolished. The residual signaling capacity downstream of BTK was associated with high expression of sIgM, whereas it was minimal when sIgM expression was low (P < .05). These results suggested that high sIgM levels facilitated CLL cell resistance to ibrutinib in patients. The CLL cells, surviving in the periphery with high sIgM expression, include a dangerous fraction that is able to migrate to tissue and receive proliferative stimuli, which may require targeting by combined approaches.


Asunto(s)
Leucemia Linfocítica Crónica de Células B , Adenina/análogos & derivados , Calcio , Humanos , Inmunoglobulina M , Leucemia Linfocítica Crónica de Células B/metabolismo , Piperidinas
11.
Blood Adv ; 5(15): 2935-2944, 2021 08 10.
Artículo en Inglés | MEDLINE | ID: mdl-34323957

RESUMEN

Single-nucleotide polymorphisms (SNPs) have been shown to influence Fcγ receptor (FcγR) affinity and activity, but their effect on treatment response is unclear. We assessed their importance in the efficacy of obinutuzumab or rituximab combined with chemotherapy in untreated advanced follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) in the GALLIUM (www.clinicaltrials.gov #NCT01332968) and GOYA (#NCT01287741) trials, respectively. Genomic DNA was extracted from patients enrolled in GALLIUM (n = 1202) and GOYA (n = 1418). Key germline SNPs, FCGR2A R131H (rs1801274), FCGR3A F158V (rs396991), and FCGR2B I232T (rs1050501), were genotyped and assessed for their impact on investigator-assessed progression-free survival (PFS). In both cohorts there was no prognostic effect of FCGR2A or FCGR3A. In FL, FCGR2B was associated with favorable PFS in univariate and multivariate analyses comparing I232T with I232I, with a more modest association for rituximab-treated (univariate: hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.54-1.14; P = .21) vs obinutuzumab-treated patients (HR, 0.56; 95% CI, 0.34-0.91; P = .02). Comparing T232T with I232I, an association was found for obinutuzumab (univariate: HR, 2.76; 95% CI, 1.02-7.5; P = .0459). Neither observation retained significance after multiple-test adjustment. FCGR2B was associated with poorer PFS in multivariate analyses comparing T232T with I232I in rituximab- but not obinutuzumab-treated patients with DLBCL (HR, 4.40; 95% CI, 1.71-11.32; P = .002; multiple-test-adjusted P = .03); however, this genotype was rare (n = 13). This study shows that FcγR genotype is not associated with response to rituximab/obinutuzumab plus chemotherapy in treatment-naive patients with advanced FL or DLBCL.


Asunto(s)
Linfoma Folicular , Receptores de IgG , Humanos , Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma Folicular/tratamiento farmacológico , Polimorfismo de Nucleótido Simple , Receptores de IgG/genética , Rituximab/uso terapéutico
12.
Blood Adv ; 5(15): 2945-2957, 2021 08 10.
Artículo en Inglés | MEDLINE | ID: mdl-34323958

RESUMEN

Fc γ receptor IIB (FcγRIIB) is an inhibitory molecule capable of reducing antibody immunotherapy efficacy. We hypothesized its expression could confer resistance in patients with diffuse large B-cell lymphoma (DLBCL) treated with anti-CD20 monoclonal antibody (mAb) chemoimmunotherapy, with outcomes varying depending on mAb (rituximab [R]/obinutuzumab [G]) because of different mechanisms of action. We evaluated correlates between FCGR2B messenger RNA and/or FcγRIIB protein expression and outcomes in 3 de novo DLBCL discovery cohorts treated with R plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) reported by Arthur, Schmitz, and Reddy, and R-CHOP/G-CHOP-treated patients in the GOYA trial (NCT01287741). In the discovery cohorts, higher FCGR2B expression was associated with significantly shorter progression-free survival (PFS; Arthur: hazard ratio [HR], 1.09; 95% confidence interval [CI], 1.01-1.19; P = .0360; Schmitz: HR, 1.13; 95% CI, 1.02-1.26; P = .0243). Similar results were observed in GOYA with R-CHOP (HR, 1.26; 95% CI, 1.00-1.58; P = .0455), but not G-CHOP (HR, 0.91; 95% CI, 0.69-1.20; P = .50). A nonsignificant trend that high FCGR2B expression favored G-CHOP over R-CHOP was observed (HR, 0.67; 95% CI, 0.44-1.02; P = .0622); however, low FCGR2B expression favored R-CHOP (HR, 1.58; 95% CI, 1.00-2.50; P = .0503). In Arthur and GOYA, FCGR2B expression was associated with tumor FcγRIIB expression; correlating with shorter PFS for R-CHOP (HR, 2.17; 95% CI, 1.04-4.50; P = .0378), but not G-CHOP (HR, 1.37; 95% CI, 0.66-2.87; P = .3997). This effect was independent of established prognostic biomarkers. High FcγRIIB/FCGR2B expression has prognostic value in R-treated patients with DLBCL and may confer differential responsiveness to R-CHOP/G-CHOP.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma de Células B Grandes Difuso , Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ciclofosfamida/uso terapéutico , Humanos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/genética , Pronóstico , Receptores de IgG/genética , Rituximab/uso terapéutico , Vincristina/uso terapéutico
13.
Res Social Adm Pharm ; 17(4): 707-714, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33722353

RESUMEN

BACKGROUND: Therapeutic decision making, prescribing, administering and managing medications can be difficult for people with dementia. OBJECTIVES: To explore stakeholder roles in medication management for people with dementia, including barriers and enablers to achieving those roles. METHODS: Focus groups were held with stakeholders (consumers, general practitioners, nurses and pharmacists) from both rural and metropolitan communities in two Australian states. Focus groups were audio-recorded, transcribed and thematically analysed using an inductive approach. RESULTS: Nine focus groups were held with 55 participants. Four major themes were identified: supporting the role of the person with dementia, carer roles and challenges, health professional roles, and process and structure barriers to medication management. Stakeholders discussed the importance of advance care planning, and the potential benefits of early implementation of dose administration aids to support patients in self-managing their medication. Carers were seen to have a vital role as patient advocates, but carer burden and changes in the patient-carer roles acted as barriers to this role. General practitioners were perceived as the main care coordinator for a person with dementia, with effective interprofessional collaboration and communication with allied health professionals and specialists further enabling optimisation of medication use. A lack of evidence, guidelines and practitioner training to guide prescribing and deprescribing decisions in people with dementia were mentioned as barriers to medication management. CONCLUSION: Medication management is increasingly challenging for people with dementia and each stakeholder perceives that they have a different role and faces different barriers and enablers. Future research should focus on improving the evidence base to guide prescribing, facilitating stakeholder communication and ensuring early documentation of patient wishes for the future.


Asunto(s)
Demencia , Médicos Generales , Australia , Cuidadores , Demencia/tratamiento farmacológico , Humanos , Administración del Tratamiento Farmacológico , Participación de los Interesados
14.
PLoS One ; 14(2): e0207420, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30730893

RESUMEN

Mycoplasma ovipneumoniae is a globally distributed pathogen that has been associated with pneumonia in both domestic and wild Caprinae. It is closely related to M. hyopneumoniae, a respiratory pathogen of swine that is associated with decreased growth rates of pigs as well as clinical respiratory disease. In order to assess the effects of M. ovipneumoniae on lamb performance, we generated a cohort of lambs free of M. ovipneumoniae by segregation of test negative ewes after lambing, then compared the growth and carcass quality traits of M. ovipneumoniae-free and -colonized lambs from weaning to harvest. Some signs of respiratory disease were observed during the feeding trial in both lamb groups, but the M. ovipneumoniae-exposed group included more affected lambs and higher average disease scores. At harvest, lungs of lambs in both groups showed few grossly visible lesions, although the M. ovipneumoniae-exposed group did exhibit increased microscopic lung lesions (P<0.05). In addition, M. ovipneumoniae exposed lambs produced lower average daily gains (P<0.05), and lower yield grade carcasses (P<0.05) compared to those of non-exposed lambs. The results demonstrated the feasibility of test and segregation for elimination of M. ovipneumoniae from groups of sheep and suggested that this pathogen may impair lamb growth and productivity even in the absence of overt respiratory disease.


Asunto(s)
Mycoplasma ovipneumoniae/patogenicidad , Neumonía por Mycoplasma/microbiología , Neumonía por Mycoplasma/fisiopatología , Oveja Doméstica/crecimiento & desarrollo , Oveja Doméstica/microbiología , Animales , Femenino , Pulmón/microbiología , Pulmón/fisiología , Masculino , Proyectos Piloto , Ovinos , Enfermedades de las Ovejas/microbiología , Enfermedades de las Ovejas/fisiopatología , Oveja Doméstica/fisiología , Porcinos/crecimiento & desarrollo , Porcinos/microbiología
15.
Breast Cancer Res ; 20(1): 19, 2018 03 22.
Artículo en Inglés | MEDLINE | ID: mdl-29566726

RESUMEN

BACKGROUND: Early-onset breast cancer (EOBC) affects about one in 300 women aged 40 years or younger and is associated with worse outcomes than later onset breast cancer. This study explored novel serum proteins as surrogate markers of prognosis in patients with EOBC. METHODS: Serum samples from EOBC patients (stages 1-3) were analysed using agnostic high-precision quantitative proteomics. Patients received anthracycline-based chemotherapy. The discovery cohort (n = 399) either had more than 5-year disease-free survival (DFS) (good outcome group, n = 203) or DFS of less than 2 years (poor outcome group, n = 196). Expressed proteins were assessed for differential expression between the two groups. Bioinformatics pathway and network analysis in combination with literature research were used to determine clinically relevant proteins. ELISA analysis against an independent sample set from the Prospective study of Outcomes in Sporadic versus Hereditary breast cancer (POSH) cohort (n = 181) was used to validate expression levels of the selected target. Linear and generalized linear modelling was applied to determine the effect of target markers, body mass index (BMI), lymph node involvement (LN), oestrogen receptor (ER), progesterone receptor and human epidermal growth factor receptor 2 status on patients' outcome. RESULTS: A total of 5346 unique proteins were analysed (peptide FDR p ≤ 0.05). Of these, 812 were differentially expressed in the good vs poor outcome groups and showed significant enrichment for the insulin signalling (p = 0.01) and the glycolysis/gluconeogenesis (p = 0.01) pathways. These proteins further correlated with interaction networks involving glucose and fatty acid metabolism. A consistent nodal protein to these metabolic networks was resistin (upregulated in the good outcome group, p = 0.009). ELISA validation demonstrated resistin to be upregulated in the good outcome group (p = 0.04), irrespective of BMI and ER status. LN involvement was the only covariate with a significant association with resistin measurements (p = 0.004). An ancillary in-silico observation was the induction of the inflammatory response, leucocyte infiltration, lymphocyte migration and recruitment of phagocytes (p < 0.0001, z-score > 2). Survival analysis showed that resistin overexpression was associated with improved DFS. CONCLUSIONS: Higher circulating resistin correlated with node-negative patients and longer DFS independent of BMI and ER status in women with EOBC. Overexpression of serum resistin in EOBC may be a surrogate indicator of improved prognosis.


Asunto(s)
Proteínas Sanguíneas/genética , Neoplasias de la Mama/sangre , Proteómica , Resistina/sangre , Adulto , Biomarcadores de Tumor/sangre , Índice de Masa Corporal , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Supervivencia sin Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Resistencia a la Insulina , Ganglios Linfáticos/patología , Células Neoplásicas Circulantes/patología , Pronóstico , Receptores de Estrógenos/genética , Receptores de Progesterona/genética
16.
PLoS One ; 13(1): e0192006, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29364974

RESUMEN

[This corrects the article DOI: 10.1371/journal.pone.0178707.].

17.
BMJ Open ; 7(8): e017906, 2017 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-28838905

RESUMEN

OBJECTIVES: The Medication Appropriateness Tool for Comorbid Health conditions in Dementia (MATCH-D) criteria provide expert consensus guidance about medication use for people with dementia. This study aimed to identify enablers and barriers to implementing the criteria in practice. SETTING: Participants came from both rural and metropolitan communities in two Australian states. PARTICIPANTS: Focus groups were held with consumers, general practitioners, nurses and pharmacists. OUTCOMES: data were analysed thematically. RESULTS: Nine focus groups were conducted. Fifty-five participants validated the content of MATCH-D, appraising them as providing patient-centred principles of care. Participants identified potential applications (including the use of MATCH-D as a discussion aid or educational tool for consumers about medicines) and suggested supporting resources. CONCLUSION: Participants provided insights into applying MATCH-D in practice and suggested resources to be included in an accompanying toolkit. These data provide external validation of MATCH-D and an empiric basis for their translation to practice. Following resource development, we plan to evaluate the feasibility and efficacy of implementation in practice.


Asunto(s)
Demencia/tratamiento farmacológico , Administración del Tratamiento Farmacológico/normas , Adulto , Anciano , Anciano de 80 o más Años , Australia , Comorbilidad , Consenso , Femenino , Grupos Focales , Humanos , Entrevistas como Asunto , Masculino , Persona de Mediana Edad , Guías de Práctica Clínica como Asunto , Investigación Cualitativa , Encuestas y Cuestionarios
18.
PLoS One ; 12(6): e0178707, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28591169

RESUMEN

BACKGROUND: Bronchopneumonia is a population limiting disease of bighorn sheep (Ovis canadensis) that has been associated with contact with domestic Caprinae. The disease is polymicrobial but is initiated by Mycoplasma ovipneumoniae, which is commonly carried by both domestic sheep (O. aries) and goats (Capra aegagrus hircus). However, while previous bighorn sheep comingling studies with domestic sheep have resulted in nearly 100% pneumonia mortality, only sporadic occurrence of fatal pneumonia was reported from previous comingling studies with domestic goats. Here, we evaluated the ability of domestic goats of defined M. ovipneumoniae carriage status to induce pneumonia in comingled bighorn sheep. METHODOLOGY/PRINCIPAL FINDINGS: In experiment 1, three bighorn sheep naïve to M. ovipneumoniae developed non-fatal respiratory disease (coughing, nasal discharge) following comingling with three naturally M. ovipneumoniae-colonized domestic goats. Gross and histological lesions of pneumonia, limited to small areas on the ventral and lateral edges of the anterior and middle lung lobes, were observed at necropsies conducted at the end of the experiment. A control group of three bighorn sheep from the same source housed in isolation during experiment 1 remained free of observed respiratory disease. In experiment 2, three bighorn sheep remained free of observed respiratory disease while comingled with three M. ovipneumoniae-free domestic goats. In experiment 3, introduction of a domestic goat-origin strain of M. ovipneumoniae to the same comingled goats and bighorn sheep used in experiment 2 resulted in clinical signs of respiratory disease (coughing, nasal discharge) in both host species. At the end of experiment 3, gross and histological evidence of pneumonia similar to that observed in experiment 1 bighorn sheep was observed in both affected bighorn sheep and domestic goats. CONCLUSIONS/SIGNIFICANCE: M. ovipneumoniae strains carried by domestic goats were transmitted to comingled bighorn sheep, triggering development of pneumonia. However, the severity of the disease was markedly milder than that seen in similar experiments with domestic sheep strains of the bacterium.


Asunto(s)
Animales Domésticos/microbiología , Cabras/microbiología , Mycoplasma ovipneumoniae/fisiología , Neumonía por Mycoplasma/veterinaria , Borrego Cimarrón/microbiología , Animales , Pulmón/microbiología , Pulmón/patología , Neumonía por Mycoplasma/patología
19.
Vet Radiol Ultrasound ; 57(5): 467-74, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27377036

RESUMEN

Tooth resorption is the most common dental disease in cats and can be a source of oral pain. The current clinical gold standard for diagnosis includes a combination of oral exam and dental radiography, however early lesions are not always detected. Computed tomography (CT) of the skull, including the dental arches, is a commonly performed diagnostic procedure, however the appearance of tooth resorption on CT and the diagnostic ability of CT to detect tooth resorption have not been evaluated. The purpose of this prospective, descriptive, diagnostic accuracy study was to characterize the CT appearance of tooth resorption in a sample of affected cats and to evaluate the sensitivity and specificity of CT for tooth resorption compared to the clinical gold standard of oral exam and intraoral dental radiography. Twenty-eight cat cadaver specimens were recruited for inclusion. Each specimen was evaluated using oral exam, intraoral dental radiography, and computed tomography (four different slice thicknesses). Each tooth was evaluated for the presence or absence of tooth resorption. Teeth with lesions and a subset of normal teeth were evaluated with histopathology. On CT, tooth resorption appeared as irregularly marginated hypoattenuating defects in the mineral attenuating tooth components, most commonly involving the root or cementoenamel junction. Sensitivity for CT detection of tooth resorption was fair to poor (42.2-57.7%) and specificity was good to excellent (92.8-96.3%). Findings from this study indicated that CT has high specificity but low sensitivity for detection of tooth resorption in cats.


Asunto(s)
Enfermedades de los Gatos/diagnóstico por imagen , Tomografía Computarizada por Rayos X/veterinaria , Resorción Dentaria/veterinaria , Animales , Enfermedades de los Gatos/etiología , Gatos , Estudios Prospectivos , Sensibilidad y Especificidad , Tomografía Computarizada por Rayos X/métodos , Resorción Dentaria/diagnóstico por imagen
20.
Maturitas ; 91: 115-34, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27451330

RESUMEN

Older people with chronic disease have great potential to benefit from their medications but are also at high risk of harm from their medications. The use of medications is particularly important for symptom control and disease progression in older people. Under-treatment means older people can miss out on the potential benefits of useful medications, while over-treatment (polypharmacy) puts them at increased risk of harm. Deprescribing attempts to balance the potential for benefit and harm by systematically withdrawing inappropriate medications with the goal of managing polypharmacy and improving outcomes. The evidence base for deprescribing in older people is growing. Studies to reduce polypharmacy have used a range of methods. Most evidence for deprescribing relates to the withdrawal of specific medications, and evidence supports attempts to deprescribe potentially inappropriate medicines (such as long-term benzodiazepines). There is also evidence that polypharmacy can be reduced by withdrawing specific medications using individualised interventions. More work is needed to identify the sub-groups of older people who may most benefit from deprescribing and the best approaches to undertaking the deprescribing interventions.


Asunto(s)
Enfermedad Crónica/tratamiento farmacológico , Deprescripciones , Anciano , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Servicios de Salud para Ancianos , Humanos
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