This study examines the availability and use of neighborhood resources in relation to clinical lower limb osteoarthritis (LLOA) in older participants from six European countries. Of the 2757 participants (65–85 years), 22.7% had LLOA. Participants with LLOA made more use of places to sit (OR=2.50; CI: 1.36–4.60 in the UK), and less use of parks and walking areas (OR=0.30; CI: 0.12–0.75 in Sweden), compared to participants without LLOA, particularly in countries with high availability of resources. The results suggest that specific features of the environment impact the use of neighborhood resources by older adults with LLOA. 相似文献
AimsThe aims were to 1) develop the pharmacokinetics model to describe and predict observed tanezumab concentrations over time, 2) test possible covariate parameter relationships that could influence clearance and distribution and 3) assess the impact of fixed dosing vs. a dosing regimen adjusted by body weight.MethodsIndividual concentration–time data were determined from 1608 patients in four phase 3 studies conducted to assess efficacy and safety of intravenous tanezumab. Patients received two or three intravenous doses (2.5, 5 or 10 mg) every 8 weeks. Blood samples for assessment of tanezumab PK were collected at baseline, 1 h post‐dose and at weeks 4, 8, 16 and 24 (or early termination) in all studies. Blood samples were collected at week 32 in two studies. Plasma samples were analyzed using a sensitive, specific, validated enzyme‐linked immunosorbent assay.ResultsA two compartment model with parallel linear and non‐linear elimination processes adequately described the data. Population estimates for clearance (CL), central volume (V1), peripheral volume (V2), inter‐compartmental clearance, maximum elimination capacity (VM) and concentration at half‐maximum elimination capacity were 0.135 l day–1, 2.71 l, 1.98 l, 0.371 l day–1, 8.03 μg day–1 and 27.7 ng ml–1, respectively. Inter‐individual variability (IIV) was included on CL, V1, V2 and VM. A mixture model accounted for the distribution of residual error. While gender, dose and creatinine clearance were significant covariates, only body weight as a covariate of CL, V1 and V2 significantly reduced IIV.ConclusionsThe small increase in variability associated with fixed dosing is consistent with other monoclonal antibodies and does not change risk : benefit. 相似文献
Trastuzumab, a key treatment for HER2-positive breast cancer, is available in weight-based IV and fixed-dose (600 mg) SC formulations. While the Phase 3 HannaH trial indicated non-inferiority of the SC formulation, there is some concern that the target plasma concentration may not be reached in overweight/obese patients whereas low-body-weight patients may be at risk of toxicity.This scoping review evaluated whether overweight/obese patients are at risk of below-target exposure with fixed-dose SC trastuzumab, whether low-body-weight patients are at risk of increased toxicity, especially cardiotoxicity, and whether IV and SC trastuzumab are equivalent in terms of treatment-emergent adverse events (TEAEs) (e.g. infections). Thirty-seven publications that met the eligibility criteria were included.Body weight is not an important determinant of exposure to trastuzumab at steady state (i.e. pre-dose cycle 8); however, real-world evidence suggests that the target concentration (20 μg/mL) may not be reached with the first SC dose in overweight/obese patients. There is no evidence that low-body-weight patients are at increased risk of cardiotoxicity with SC trastuzumab, although this may be confounded by the higher rate of cardiovascular comorbidities in overweight patients. In Phase 3 trials, SC trastuzumab was associated with higher rates of ISRs, ADAs and SAEs, the latter often requiring hospitalization and occurring during adjuvant treatment when patients are not burdened by chemotherapy.The route of administration of trastuzumab (IV vs SC) in different treatment settings should be discussed with the patient, taking into account the risks and benefits associated with each route. 相似文献
BackgroundProlonged emergency department (ED) wait times could potentially lead to increased morbidity and mortality. While previous work has demonstrated disparities in wait times associated with race, information about the relationship between experiencing homelessness and ED wait times is lacking.ObjectivesThe purpose of this study was to explore the relationship between residence status (undomiciled vs. domiciled) and ED wait times. We hypothesized that being undomiciled would be associated with longer wait times.MethodsWe obtained data from the National Hospital Ambulatory Medical Care Survey from 2014 to 2017. We compared wait times in each triage category using t tests. We used multivariate linear regression to explore associations between residence status and wait times while controlling for other patient- and hospital-level variables.ResultsOn average, undomiciled patients experienced significantly longer mean ED wait times than domiciled patients (53.4 vs. 38.9 min; p < 0.0001). In the multivariate model, undomiciled patients experienced significantly different wait times by 15.5 min (p = 0.0002). Undomiciled patients experienced increasingly longer waits vs. domiciled patients for the emergent and urgent triage categories (+33.5 min, p < 0.0001, and +22.7 min, p < 0.0001, respectively).ConclusionsUndomiciled patients experience longer ED wait times when compared with domiciled patients. This disparity is not explained by undomiciled patients seeking care in the ED for minor illness, because the disparity is more pronounced for urgent and emergent triage categories. 相似文献
ObjectivesThe aim of this study was to examine whether variables related to mothers’ psychological functioning could be associated with mother-child attachment insecurity in children referred to an outpatient mental health clinic.MethodTwenty-nine children (23–71 months) and their mothers participated in this study. According to child age, mother-child attachment was assessed using the Strange Situation or the Separation-Reunion Procedure. Mothers’ symptoms of depression, anxiety and parental stress were assessed using self-report inventories.ResultsAvoidant attachment was marginally related to maternal depression and significantly associated with maternal anxiety. Greater parental stress was related to more disorganized and less secure attachment behaviors. A marginal association was also found between maternal stress and ambivalent attachment behaviors.ConclusionThese results support the importance of pursuing research on possible links between maternal psychological determinants and mother-child attachment in children referred to outpatient mental health clinics. 相似文献
Objectives: To establish the first plasma and cerebrospinal fluid (CSF) oxycodone population pharmacokinetic (PopPK) model after epidural (EPI) and intravenous (IV) oxycodone administration.
Methods: The study was conducted with 30 female subjects undergoing elective gynecological surgery with epidural analgesia. A parallel single dose of EPI oxycodone with IV placebo (EPI group; n = 18) or IV oxycodone with EPI placebo (IV group; n = 12) was administered. An epidural catheter for drug administration was placed at T12/L1 and a spinal catheter for CSF sampling at L3/4. Plasma and CSF for oxycodone analysis were frequently collected. A PopPK model was built using the NONMEM software package.
Results: Plasma and CSF oxycodone concentrations were evaluated using separate central plasma and CSF compartments and separate peripheral plasma and CSF compartments. Epidural space served as a depot compartment with transfer to both the plasma and CSF central compartments. The population parameters for plasma clearance and apparent distribution volumes for central and peripheral compartments for plasma and CSF were 37.4 L/h, 90.2 L, 68.9 L, 0.035 L (fixed based on literature), and 0.039 L, respectively.
Conclusion: A PopPK model was developed and found to precisely and accurately describe oxycodone time-concentration data in plasma and CSF. 相似文献