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Introduction: Kidney supportive care (KSC) integrates kidney and palliative care to improve quality of life for people with chronic kidney disease (CKD). Despite increasing interest and global advocacy to integrate KSC into kidney care, evidence to guide optimal care delivery is limited. Methods: This observational cross-sectional study used an online survey to describe current KSC models in Australia, Aotearoa-New Zealand, and the UK. Results: Between April and December 2022, 114 nephrology units responded (response rate 67%), with 66% having a dedicated KSC service (UK, 74%; Australia, 58%; and New Zealand, 67%). Many different health care professionals worked in KSC services with diversity in clinical resources and activities between units and across countries. Overall, funding for KSC services was low, with a median full time equivalent (FTE) per unit (standardized per 100 people receiving hemodialysis [HD]) of 0.51 (interquartile range [IQR], 0.17-1.05) and 4 units provided a service without allocated funding. The scope of KSC service was wide-ranging and prioritized activities included symptom management, psychological support, complex future treatment planning and discussion, and care coordination. There were no significant differences between countries in terms of location of care provision, frequency of review, referral patterns or discharge rates; however, there was variation described within countries. Conclusion: Models of KSC vary markedly across kidney units and between countries. Despite this variation, there was consistency in terms of clinical priorities which were person-centered and focused on physical and psychosocial well-being. Further research is required to evaluate the effectiveness of KSC provision, alongside improved funding methods to ensure sustainable and equitable KSC delivery.
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A point-of-care (POC) device to measure mouse glucose and lipid profiles is an important unmet need for cost-effective, immediate decision making in research. We compared metabolic analyte profiles obtained using a human clinical POC device with those from a veterinary laboratory chemical analyzer (LCA). Unfasted terminal blood samples were obtained by cardiac puncture from C57Bl/6J mice used in a diet-induced obesity model of type 2 diabetes mellitus; age-matched C57Bl/6J controls; a transgenic mouse model of Alzheimer's disease on a C57BL/6J background (16 wk old); and aged C57BL/6J mice (24 to 60 wk old). Aliquots of the blood were immediately assayed onsite using the POC device. Corresponding serum aliquots were sent analyzed by LCA. Measures from the POC and LCA devices were compared by using the Bland-Altman and Passing-Bablok methods. Of a total of 40 aliquots, LCA results were within reported reference ranges for each model. POC results that fell beyond the device range were excluded from the analyses. The coefficient of determination and Passing-Bablok analysis demonstrated that POC glucose and HDL had the best agreement with LCA. The Bland-Altman analysis found no value-dependent bias in glucose and no significant bias in HDL. The remaining lipid analytes (cholesterol and triglyceride) showed significant bias. Until an improved, validated mouse POC device with lipid profile capability is available, the POC device that we tested appears adequate for screening glucose and HDL in mouse blood. Disadvantages of this clinical POC device are the narrow human ranges relative to ranges found in mice and its limited precision as compared with the LCA. This study demonstrates that when the samples are within the device range limits, this human POC device can accurately track metabolic syndrome and be used to compare patterns in glucose and HDL.
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Enfermedad de Alzheimer , Diabetes Mellitus Tipo 2 , Anciano , Envejecimiento , Animales , Glucosa , Humanos , Lípidos , Ratones , Ratones Endogámicos C57BL , Sistemas de Atención de PuntoRESUMEN
A systematic review of the Bristol-Myers Squibb normal healthy volunteers (NHVs) database identified phase 1 trials that included NHVs administered placebo with the aim of characterizing normal inter- and intraindividual safety parameter variability. Twenty-five single and multiple ascending dose studies, median duration 28 (2 to 63) days, were included in the pooled analysis (355 NHVs). Laboratory evaluations, vital signs, electrocardiograms, and adverse events were assessed. The most commonly occurring adverse event was headache (28 [7.9%] NHVs; 519.5 events/100 person-years). During the dosing period (on placebo), evaluations showed 5.1 events/100 measures of alanine aminotransferase and 7.3 events/100 measures of creatine kinase 1× above the upper limit of normal. Alanine aminotransferase and creatine kinase elevations occurred in 28 (7.9%) and 39 (11.0%) NHVs, respectively; 105 (30.3%) NHVs had low and 46 (13.3%) had high diastolic blood pressure. This analysis may inform future study designs and provide a context for interpretation of safety signals in early phase clinical trials.
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Placebos/efectos adversos , Ensayos Clínicos Fase I como Asunto , Electrocardiografía , Voluntarios Sanos , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Signos VitalesRESUMEN
BACKGROUND: Compare the efficacy and safety of Plasma-Lyte A (PLA) versus 0.9 % sodium chloride (NaCl) intravenous (IV) fluid replacement in children with moderate to severe dehydration secondary to acute gastroenteritis (AGE). METHODS: Prospective, randomized, double-blind study conducted at eight pediatric emergency departments (EDs) in the US and Canada (NCT#01234883). The primary outcome measure was serum bicarbonate level at 4 h. Secondary outcomes included safety and tolerability. The hypothesis was that PLA would be superior to 0.9 % NaCl in improvement of 4-h bicarbonate. Patients (n = 100) aged ≥6 months to <11 years with AGE-induced moderate-to-severe dehydration were enrolled. Patients with a baseline bicarbonate level ≤22 mEq/L formed the modified intent to treat (mITT) group. RESULTS: At baseline, the treatment groups were comparable except that the PLA group was older. At hour 4, the PLA group had greater increases in serum bicarbonate from baseline than did the 0.9 % NaCl group (mean ± SD at 4 h: 18 ± 3.74 vs 18.0 ± 3.67; change from baseline of 1.6 and 0.0, respectively; P = .004). Both treatment groups received similar fluid volumes. The PLA group had less abdominal pain and better dehydration scores at hour 2 (both P = .03) but not at hour 4 (P = 0.15 and 0.08, respectively). No patient experienced clinically relevant worsening of laboratory findings or physical examination, and hospital admission rates were similar. One patient in each treatment group developed hyponatremia. Four patients developed hyperkalemia (PLA:1, 0.9 % NaCl:3). CONCLUSION: In comparison with 0.9 % NaCl, PLA for rehydration in children with AGE was well tolerated and led to more rapid improvement in serum bicarbonate and dehydration score. TRIAL REGISTRATION: NCT#01234883 (Registration Date: November 3, 2010).
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Deshidratación/terapia , Electrólitos/uso terapéutico , Gastroenteritis/complicaciones , Sustitutos del Plasma/uso terapéutico , Soluciones para Rehidratación/uso terapéutico , Cloruro de Sodio/uso terapéutico , Bicarbonatos/sangre , Niño , Preescolar , Deshidratación/sangre , Deshidratación/etiología , Método Doble Ciego , Electrólitos/efectos adversos , Humanos , Lactante , Infusiones Intravenosas , Análisis de Intención de Tratar , Sustitutos del Plasma/efectos adversos , Estudios Prospectivos , Soluciones para Rehidratación/efectos adversos , Cloruro de Sodio/efectos adversosRESUMEN
This pilot study compared otoprotection provided by trans-tympanic formulations and systemic intraperitoneal administration of L-N-acetylcysteine from cisplatin-induced cochlear oxidative stress. Protection was assessed by measures of hearing loss and cochlear glutathione levels. All groups received an equivalent single dose of L-N-acetylcysteine followed by cisplatin. Cisplatin was administered subcutaneously for 3 days (5.5 mg/kg/day). Two hours prior to day 1 cisplatin, L-N-acetylcysteine was administered either intraperitoneally (250 mg/kg), trans-tympanic as 2% L-N-acetylcysteine in gel, or trans-tympanic as L-N-acetylcysteine-loaded nanocapsules in gel. Hearing was assessed prior to and 3 days after cisplatin followed by microdissection of cochlear tissue. The levels of reduced (GSH) and oxidized (GSSG) glutathione in homogenized tissue supernatants were determined via luminometry. Intraperitoneal L-N-acetylcysteine administration preceding cisplatin resulted in less hearing loss and a higher GSH/GSSG ratio than either trans-tympanic formulation. This suggests that for equivalent doses of L-N-acetylcysteine, systemic rather than targeted cochlear delivery provides increased otoprotection from cisplatin ototoxicity.
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Acetilcisteína/administración & dosificación , Cisplatino/efectos adversos , Depuradores de Radicales Libres/administración & dosificación , Pérdida Auditiva/inducido químicamente , Pérdida Auditiva/tratamiento farmacológico , Animales , Femenino , Cobayas , Estrés Oxidativo , Proyectos Piloto , Membrana TimpánicaAsunto(s)
Antineoplásicos/administración & dosificación , Cisplatino/administración & dosificación , Pérdida Auditiva Sensorineural/prevención & control , Antineoplásicos/efectos adversos , Antineoplásicos/sangre , Antineoplásicos/farmacocinética , Niño , Cisplatino/efectos adversos , Cisplatino/sangre , Cisplatino/farmacocinética , Tumor del Seno Endodérmico/complicaciones , Tumor del Seno Endodérmico/tratamiento farmacológico , Semivida , Pérdida Auditiva Sensorineural/inducido químicamente , Humanos , Infusiones Intravenosas , Inyecciones Intravenosas , Neoplasias de Células Germinales y Embrionarias/complicaciones , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Unión Proteica , Estudios RetrospectivosRESUMEN
Autosomal dominant polycystic kidney disease (ADPKD) is a significant familial disorder, crossing multiple ethnicities as well as organ systems. The goal of understanding and, ultimately, curing ADPKD has fostered collaborative efforts among many laboratories, mustered on by the opportunity to probe fundamental cellular biology. Here we review what is known about ADPKD including well-accepted data such as the identification of the causative genes and the fact that PKD1 and PKD2 act in the same pathway, fairly well-accepted concepts such as the "two-hit hypothesis," and somewhat confusing information regarding polycystin-1 and -2 localization and protein interactions. Special attention is paid to the recently discovered role of the cilium in polycystic kidney disease and the model it suggests. Studying ADPKD is important, not only as an evaluation of a multisystem disorder that spans a lifetime, but as a testament to the achievements of modern biology and medicine.
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Proteínas de la Membrana/metabolismo , Enfermedades Renales Poliquísticas/genética , Enfermedades Renales Poliquísticas/metabolismo , Proteínas/metabolismo , Animales , Cilios/patología , Modelos Animales de Enfermedad , Células Epiteliales/metabolismo , Células Epiteliales/patología , Genes Dominantes/genética , Humanos , Túbulos Renales/metabolismo , Túbulos Renales/patología , Túbulos Renales/fisiopatología , Proteínas de la Membrana/genética , Enfermedades Renales Poliquísticas/fisiopatología , Proteínas/genética , Canales Catiónicos TRPPRESUMEN
The interaction of extracellular matrix and receptors plays a role in tissue homeostasis. The thickened strial capillary basement membrane (SCBM) reported in animal models of presbycusis and Alport's syndrome might be secondary to elevated synthesis and/or decreased turnover of specific basement membrane (BM) components. In this study, expression of specific BM proteins, integrin receptors and mediators of matrix turnover in the murine lateral wall were determined using cDNA probes and antibodies. The presence of collagen alpha1 and alpha2(IV) and laminin-8 in the SCBM was verified. The integrin subunits alpha3, alphav and beta1, cell surface receptors for the BM proteins, localized primarily to the SCBM and/or the strial marginal cells as did TIMP-3, a tissue inhibitor of matrix metalloproteinase. The epithelial cell line SV-k1, derived from the lateral wall of the 'immortomouse', showed expression of the same BM proteins as well as demonstrating the presence of markers specific to strial marginal cells, namely Na,K-ATPase alpha1 and beta2 subunits. Thus, the cultured cells are identified as deriving from marginal cells of the stria vascularis. Moreover, these data suggest that a culture system using this marginal cell line will be useful to delineate mechanisms underlying the pathologic accumulation of extracellular matrix in the SCBM.