RESUMEN
COVID-19 has put a spotlight on the senior living sector. Transformational change is needed to address the challenges of an institutional model of long-term care. This article makes recommendations applying the Systems Transformation domain of the LEADS leadership capabilities framework to change the way older persons experience the ageing journey by creating a small home model of living. A literature review reinforces the spotlight on the capital investment needed to reinvent the nursing home into a centre for living.
Asunto(s)
COVID-19 , Anciano , Anciano de 80 o más Años , Hospitales , Humanos , Liderazgo , Casas de Salud , SARS-CoV-2RESUMEN
Eldercare is a significant challenge globally. The role of health leaders is foremost as agents of the transformational change needed to address the increasing demands for long-term care. This article applies the System Transformation domain of the LEADS leadership capabilities framework to redesign the delivery of care and housing to the aging demographic. A literature review reveals the radical shifts in how programs and services support person-centred care and quality life.
Asunto(s)
Servicios de Salud para Ancianos , Innovación Organizacional , Anciano , Servicios de Salud Comunitaria/organización & administración , Demencia/terapia , Servicios de Salud para Ancianos/organización & administración , Servicios de Atención de Salud a Domicilio/organización & administración , Humanos , Casas de Salud/organización & administración , Cultura Organizacional , Mejoramiento de la Calidad/organización & administraciónRESUMEN
BACKGROUND: Many individuals do not respond to a three-dose series of hepatitis B vaccine (HBV) and most do not achieve a protective antibody response until after dose 2 or 3. METHODS: Healthy, seronegative 18-28 year old adults were randomly assigned in equal numbers to receive two doses of the experimental vaccine (HBV-ISS without alum) (0, 8 weeks) and placebo (24 weeks) or Engerix-B (0, 8, 24 weeks). Adverse events were collected during the first week and at 4 weeks after each injection. Antibodies were measured 4 weeks after dose 1; before, 1 and 4 weeks after dose 2, and before, 1 and 4 weeks after dose 3 and at 1 year. RESULTS: Ninety-nine participants were enrolled (65% female; mean age 22.6 years). 79% of HBV-ISS and 12% of Engerix-B recipients had a protective antibody response 4 weeks post dose 1 (geometric mean concentration [GMC] 23.0 and 1.87 mIU/mL, respectively). By 1 week post dose 2, 100% of HBV-ISS and 18% Engerix-B recipients had protective levels (GMC 1603 versus 2.40 mIU/mL). Rates of adverse events were low and similar in both groups; headache and fatigue were the most common systemic adverse events in up to 1/3 of both groups. Mild injection-site tenderness was more common after HBV-ISS than Engerix-B after both doses (74-77% compared to 34-58%; pAsunto(s)
Adyuvantes Inmunológicos/administración & dosificación
, Antígenos de Superficie de la Hepatitis B/administración & dosificación
, Vacunas contra Hepatitis B/administración & dosificación
, Oligonucleótidos/administración & dosificación
, Tionucleótidos/administración & dosificación
, Adolescente
, Adulto
, Femenino
, Anticuerpos contra la Hepatitis B/sangre
, Antígenos de Superficie de la Hepatitis B/efectos adversos
, Antígenos de Superficie de la Hepatitis B/inmunología
, Vacunas contra Hepatitis B/efectos adversos
, Vacunas contra Hepatitis B/inmunología
, Humanos
, Masculino
RESUMEN
We assessed the tolerability, safety, pharmacokinetics and dose-limiting toxicity (DLT) of the recombinant humanized IgG4 anti-vascular endothelial growth factor (VEGF) monoclonal antibody, HuMV833, in patients with advanced cancer. Cohorts of patients with progressive solid tumours received escalating doses of HuMV833 as a 1-h intravenous (I.V.) infusion on days 1, 15, 22, and 29. Twenty patients (median Eastern Cooperative Oncology Group (ECOG) score 1) were accrued. HuMV833 infusions were well tolerated and there were no grade III or IV toxicities definitely related to the antibody. Grade I or II toxicities probably related to the antibody included fatigue, dyspnoea and rash. There were two episodes of asymptomatic hypocalcaemia, one at grade III and one grade IV, which were recorded in early follow-up. There were eight grade I episodes of asymptomatic elevation of activated partial thromboplastin time (APTT) and two grade III events; one in a patient receiving 1 mg/kg and the other receiving extended doses of 10 mg/kg. Pharmacokinetic analysis revealed a non-linear kinetic and an elimination half-life of between 8.2 (0.3 mg/kg) and 18.7 (10 mg/kg) days. One patient with ovarian cancer experienced a partial response (PR) of 9 months duration and eight had disease stabilisation (SD) including one patient with colorectal carcinoma whose disease was stable for 14 months. In 13 of the 14 samples taken from 12 patients, the plasma concentration of hepatocyte growth factor (HGF) was reduced 24 h after drug administration. HuMV833 is safe and lacked DLT at doses up to 10 mg/kg on this schedule. Multiple doses were well tolerated, despite occasional asymptomatic elevations in APTT. By combining pharmacokinetic, pharmacodynamic and toxicity data, we can identify doses of 1 and 3mg/kg for further investigation. HuMV833 appears to possess some clinical activity.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Neoplasias/terapia , Adulto , Anciano , Anticuerpos Monoclonales/farmacocinética , Anticuerpos Monoclonales Humanizados , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteínas Recombinantes/farmacocinética , Proteínas Recombinantes/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND: Vascular endothelial growth factor (VEGF) is a potent angiogenic cytokine, and various inhibitory agents, including specific antibodies, have been developed to block VEGF-stimulated angiogenesis. We developed HuMV833, a humanized version of a mouse monoclonal anti-VEGF antibody (MV833) that has antitumor activity against a number of human tumor xenografts, and investigated the distribution and biologic effects of HuMV833 in patients in a phase I trial. METHODS: Twenty patients with progressive solid tumors were treated with various doses of HuMV833 (0.3, 1, 3, or 10 mg/kg). Positron emission tomography with (124)I-HuMV833 was used to measure the antibody distribution in and clearance from tissues. Magnetic resonance imaging was used to measure the vascular permeability surface area product with a first-pass pharmacokinetic model (k(fp)) to determine tumor vascular permeability. RESULTS: The antibody was generally well tolerated, although the incremental dose, phase I study design, and pharmacodynamic endpoints could not identify the optimum biologically active dose. Antibody distribution and clearance were markedly heterogeneous between and within patients and between and within individual tumors. HuMV833 distribution to normal tissues also varied among patients, but the antibody was cleared from these tissues in a homogeneous fashion. Permeability was strongly heterogeneous between and within patients and between and within individual tumors. All tumors showed a reduction in k(fp) 48 hours after the first treatment (median = 44%; range = 4%-91%). CONCLUSIONS: Because of the heterogeneity in tumor biology with respect to antibody uptake and clearance, we suggest that either intrapatient dose escalation approaches or larger, more precisely defined patient cohorts would be preferable to conventional strategies in the design of phase I studies with antiangiogenic compounds like HuMV833.