RESUMEN
BACKGROUND: B-cell anomalies play a role in the pathogenesis of membranous nephropathy. B-cell depletion with rituximab may therefore be noninferior to treatment with cyclosporine for inducing and maintaining a complete or partial remission of proteinuria in patients with this condition. METHODS: We randomly assigned patients who had membranous nephropathy, proteinuria of at least 5 g per 24 hours, and a quantified creatinine clearance of at least 40 ml per minute per 1.73 m2 of body-surface area and had been receiving angiotensin-system blockade for at least 3 months to receive intravenous rituximab (two infusions, 1000 mg each, administered 14 days apart; repeated at 6 months in case of partial response) or oral cyclosporine (starting at a dose of 3.5 mg per kilogram of body weight per day for 12 months). Patients were followed for 24 months. The primary outcome was a composite of complete or partial remission of proteinuria at 24 months. Laboratory variables and safety were also assessed. RESULTS: A total of 130 patients underwent randomization. At 12 months, 39 of 65 patients (60%) in the rituximab group and 34 of 65 (52%) in the cyclosporine group had a complete or partial remission (risk difference, 8 percentage points; 95% confidence interval [CI], -9 to 25; P = 0.004 for noninferiority). At 24 months, 39 patients (60%) in the rituximab group and 13 (20%) in the cyclosporine group had a complete or partial remission (risk difference, 40 percentage points; 95% CI, 25 to 55; P<0.001 for both noninferiority and superiority). Among patients in remission who tested positive for anti-phospholipase A2 receptor (PLA2R) antibodies, the decline in autoantibodies to anti-PLA2R was faster and of greater magnitude and duration in the rituximab group than in the cyclosporine group. Serious adverse events occurred in 11 patients (17%) in the rituximab group and in 20 (31%) in the cyclosporine group (P = 0.06). CONCLUSIONS: Rituximab was noninferior to cyclosporine in inducing complete or partial remission of proteinuria at 12 months and was superior in maintaining proteinuria remission up to 24 months. (Funded by Genentech and the Fulk Family Foundation; MENTOR ClinicalTrials.gov number, NCT01180036.).
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Ciclosporina/uso terapéutico , Glomerulonefritis Membranosa/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Rituximab/uso terapéutico , Administración Oral , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Ciclosporina/efectos adversos , Esquema de Medicación , Femenino , Humanos , Factores Inmunológicos/uso terapéutico , Inmunosupresores/efectos adversos , Infusiones Intravenosas , Análisis de Intención de Tratar , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Proteinuria/tratamiento farmacológico , Inducción de Remisión , Rituximab/efectos adversos , Insuficiencia del Tratamiento , Adulto JovenRESUMEN
OBJECTIVES: Screening tools to determine which outpatients with cirrhosis are at highest risk for unplanned hospitalization are lacking. Frailty is a novel prognostic factor but conventional screening for frailty is time consuming. We evaluated the ability of a 1 min bedside screen (Clinical Frailty Scale (CFS)) to predict unplanned hospitalization or death in outpatients with cirrhosis and compared the CFS with two conventional frailty measures (Fried Frailty Criteria (FFC) and Short Physical Performance Battery (SPPB)). METHODS: We prospectively enrolled consecutive outpatients from three tertiary care liver clinics. Frailty was defined by CFS >4. The primary outcome was the composite of unplanned hospitalization or death within 6 months of study entry. RESULTS: A total of 300 outpatients were enrolled (mean age 57 years, 35% female, 81% white, 66% hepatitis C or alcohol-related liver disease, mean Model for End-Stage Liver Disease (MELD) score 12, 28% with ascites). Overall, 54 (18%) outpatients were frail and 91 (30%) patients had an unplanned hospitalization or death within 6 months. CFS >4 was independently associated with increased rates of unplanned hospitalization or death (57% frail vs. 24% not frail, adjusted odds ratio 3.6; 95% confidence interval (CI): 1.7-7.5; P=0.0008) and there was a dose response (adjusted odds ratio 1.9 per 1-unit increase in CFS, 95% CI: 1.4-2.6; P<0.0001). Models including MELD, ascites, and CFS >4 had a greater discrimination (c-statistic=0.84) than models using FFC or SPPB. CONCLUSIONS: Frailty is strongly and independently associated with an increased risk of unplanned hospitalization or death in outpatients with cirrhosis. The CFS is a rapid screen that could be easily adopted in liver clinics to identify those at highest risk of adverse events.
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Anciano Frágil , Hospitalización/estadística & datos numéricos , Cirrosis Hepática/epidemiología , Mortalidad , Lesión Renal Aguda/etiología , Anciano , Causas de Muerte , Femenino , Hemorragia Gastrointestinal/etiología , Encefalopatía Hepática/etiología , Humanos , Infecciones/etiología , Cirrosis Hepática/complicaciones , Cirrosis Hepática/mortalidad , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pacientes Ambulatorios , Pruebas en el Punto de Atención , Estudios Prospectivos , Medición de Riesgo , Desequilibrio Hidroelectrolítico/etiologíaRESUMEN
BACKGROUND: The benefits of the Nurse Practitioner role in acute care are known however, the patient's experience of having an Orthopaedic Nurse Practitioner involved in their joint replacement care is unknown. AIM: This study aimed to explore the experience of patients undergoing a hip or knee joint replacement who had an Orthopaedic Nurse Practitioner involved in their care. METHODS: This study used a qualitative descriptive design using semi-structured interviews with eleven participants. Data were analysed using Braun and Clark's six step reflexive thematic analysis framework. RESULTS: Four themes emerged from the thematic analysis: 1) Information sharing and education; 2) Support throughout the journey; 3) Coordination of care, and 4) Reassurance. CONCLUSION: The role of the Orthopaedic Nurse Practitioner in supporting participants throughout their joint replacement journey provided benefits for the patient's health and recovery.
RESUMEN
PURPOSE: To describe the implementation and evaluation of a hospital-initiated, community-based, digital prehabilitation program (My PreHab Program: MPP) for adults referred for elective joint replacement. METHODS: MPP was implemented July 2022 and comprises a personalised digital health screen that guides the provision of self-management resources. Adults (>18 years) referred and accepted, or already waitlisted, for total knee/hip replacement surgery were eligible. Individuals requiring category 1 (urgent) or emergency surgery and those without a mobile phone were excluded. Implementation and intervention outcome measures (program adoption, equity of reach, fidelity, acceptability, appropriateness, feasibility, engagement, preliminary surgical outcomes) were explored via study-specific measures and hospital records. RESULTS: Of those invited (N = 689), 77.8% participated. Participants and non-participants were similar in key demographic variables except regional invitees were more likely to participate than metropolitan (88.0% vs 75.4%, p = .002) and non-participants tended to be older (median age = 69.0 vs 64.0, p = .005). Participants reported on average four modifiable risk factors: most commonly chronic pain (79.1%), obesity (57.3%), and frailty (40.9%). Most participants (80.4%) reviewed all resources provided and reported action/intention to address issues identified (90.9%). Participants perceived MPP as acceptable (3.2/5), appropriate (3.3/5), and feasible (3.4/5). Early trends for participants progressing to surgery (n = 33) show a reduced length of stay (MPP = 4.3, baseline = 5.3 days). CONCLUSION: MPP demonstrated high adoption, fidelity, and participant engagement. It is acceptable, appropriate and feasible and has the potential to be scaled-up digitally at low-cost. Modifiable risk factors were prevalent and early indications suggest this preoperative intervention may benefit both patients and the healthcare system.
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Artroplastia de Reemplazo de Rodilla , Humanos , Masculino , Femenino , Anciano , Persona de Mediana Edad , Artroplastia de Reemplazo de Cadera , Ejercicio PreoperatorioRESUMEN
BACKGROUND: Depression is associated with substantial morbidity and mortality in cirrhosis, but is underdiagnosed and undertreated. AIMS: Using the Mini International Neuropsychiatric Interview (MINI) as a gold-standard, to determine prevalence, predictors, and outcomes of depression, and to develop a screening nomogram for use in cirrhosis patients. METHODS: Cirrhotic outpatients 18-80 years of age, not on anti-depressants, were consecutively recruited from liver clinics at three tertiary care hospitals. Baseline health-related quality of life (HRQoL) and frailty were determined by the chronic liver disease questionnaire, EQ-VAS, Clinical Frailty Scale and Fried Frailty Criteria. Depression was identified using the MINI and participants were followed up to 6 months to determine unplanned hospitalization/death. RESULTS: Of 305 patients, 62% were male; mean age 55(10) years; mean MELD 12.5(5), 61% Child Pugh B/C. Prevalence of depression 18% by MINI. Patients with depression had lower baseline HRQoL and higher frailty scores. Five independently predictive factors were used to develop a clinical nomogram for the diagnosis of clinical depression. These included three Hospital Anxiety and Depression Screening tool variables: "I have lost interest in my appearance" (adjusted odds ratio [aOR] 2.2, P = 0.006), "I look forward with enjoyment to things" (aOR 2.0, P = 0.02), "I feel cheerful" (aOR 2.8, P = 0.002), and two demographic variables: younger age (aOR 0.92, P = 0.001) and not being married or in a common-law relationship (aOR 0.30, P = 0.008). CONCLUSIONS: Depression is common in patients with cirrhosis. It has a significant impact on HRQoL and functional status. The developed clinical nomogram is promising for the rapid screening of depression in patients with cirrhosis.
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Depresión/diagnóstico , Depresión/epidemiología , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/epidemiología , Tamizaje Masivo/métodos , Nomogramas , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Depresión/psicología , Femenino , Humanos , Cirrosis Hepática/psicología , Masculino , Tamizaje Masivo/psicología , Persona de Mediana Edad , Prevalencia , Estudios Prospectivos , Calidad de Vida/psicología , Encuestas y Cuestionarios , Adulto JovenRESUMEN
OBJECTIVES: Diagnosis and management of osteoporosis in hospitals are poor. Effective medications for reducing fracture risk are often underutilised in hospital settings. Studies have shown that improvements in secondary prevention of osteoporosis can occur with the implementation of clinical pathways and are effective in improving the prescription for osteoporosis medications. We aimed to assess the long-term sustainability of the benefit of the osteoporosis pathway implemented at The Queen Elizabeth Hospital, Adelaide, Australia, in 2003. METHODS: An audit was performed to review the rate of prescription for osteoporosis therapy 5 years after the implementation of a pharmacist-driven osteoporosis pathway in patients presented with a minimal trauma fracture and admitted to the Department of Orthopaedics at The Queen Elizabeth Hospital. KEY FINDINGS: Our review of a 5-year period shows that the rate of prescription for osteoporosis therapy in this patient group is 95%. CONCLUSIONS: The pharmacist-driven osteoporosis pathway at The Queen Elizabeth Hospital has sustained the rate of prescription for osteoporosis therapy over a prolonged period of time.
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Fracturas Óseas/prevención & control , Osteoporosis/tratamiento farmacológico , Farmacéuticos/organización & administración , Servicio de Farmacia en Hospital/organización & administración , Femenino , Fracturas Óseas/etiología , Humanos , Masculino , Auditoría Médica , Persona de Mediana Edad , Osteoporosis/complicaciones , Pautas de la Práctica en Medicina/normas , Australia del Sur , Factores de TiempoRESUMEN
Familial adenomatous polyposis (FAP) is characterized by the presence of hundreds to thousands of adenomas that carpet the entire colon and rectum. Nonsense and frameshift mutations in the adenomatous polyposis coli (APC) gene account for the majority of mutations identified to date and predispose primarily to the typical disease phenotype. Some APC mutations are associated with a milder form of the disease known as attenuated FAP. Virtually all mutations that have been described in the APC gene result in the formation of a premature stop codon and very little is known about missense mutations apart from a common Ashkenazi Jewish mutation (1307 K) and a British E1317Q missense change. The incidence of missense mutations in the APC gene has been underreported since the APC gene lends itself to analysis using an artificial transcription and translation assay known as the Protein Truncation Test (PTT) or the In Vitro Synthetic Protein assay (IVSP).In this report we have used denaturing high performance liquid chromatography to analyse the entire coding sequence of the APC gene to determine if a cohort of patients adhering to the diagnostic criteria of FAP to assess the frequency of missense mutations in the APC gene. Altogether 112 patients were studied and 22 missense mutations were identified. From the total of 22 missense changes, 13 were silent changes and the remaining 9 resulted in amino acid substitutions. One or more of these changes were identified multiple times in 62.5% of the population under study.The results reveal that missense mutations in the APC gene appear not to radically alter protein function but may be associated with more subtle processing of RNA transcripts which in turn could result in the expression of differentially spliced forms of the APC gene which may interfere with the functional activity of the APC protein.