Disability assessments: Effects of response mode and experience

Purpose.?To what extent response mode and experience affect the assessment of disability was investigated.

Method.?An experiment was conducted in which 34 medical doctors (17 inexperienced and 15 experienced) were required to assess disability of a videotaped client. Participants either gave a probability assessment after each piece of information or only after all information had been processed (step-by-step, SBS, or end-of-sequence, EOS). They were furthermore required to indicate how confident they were of their judgement and which information was most important for their judgement.

Results.?Neither response mode nor experience affected the assessment of disability. Only experienced doctors changed their judgement after seeing the video as compared to their judgement after reading the file. Even though all doctors became more confident after seeing the video, this increase was stronger for experienced than inexperienced doctors. Experienced doctors more often mentioned limitations as the basis for their judgements and, to a lesser degree, client's motivation to return to work than inexperienced doctors.

Conclusions.?The results suggest that assessments of disability are largely based on the initial representation that is formed after reading the file. The main pitfall is that the final representation is based on general beliefs rather than on actual client information. For training and support this would mean that doctors should be made aware of the extent to which their assessment is anchored in the case at hand.     

Myocardial perfusion MRI shows impaired perfusion of the mouse hypertrophic left ventricle

There is growing consensus that myocardial perfusion deficits play a pivotal role in the transition from compensated to overt decompensated hypertrophy. The purpose of this study was to systematically study myocardial perfusion deficits in the highly relevant model of pressure overload induced hypertrophy and heart failure by transverse aortic constriction (TAC), which was not done thus far. Regional left ventricular (LV) myocardial perfusion (mL/min/g) was assessed in healthy mice (n = 6) and mice with TAC (n = 14). A dual-bolus first-pass perfusion MRI technique was employed to longitudinally quantify myocardial perfusion values between 1 and 10 weeks after surgery. LV function and morphology were quantified from cinematographic MRI. Myocardial rest perfusion values in both groups did not change significantly over time, in line with the essentially constant global LV function and mass. Myocardial perfusion was significantly decreased in TAC mice (4.2 ± 0.9 mL/min/g) in comparison to controls (7.6 ± 1.8 mL/min/g) (P = 0.001). No regional differences in perfusion were observed within the LV wall. Importantly, increased LV volumes and mass, and decreased ejection fraction correlated with decreased myocardial perfusion (P < 0.001, in all cases). Total LV blood flow was decreased in TAC mice (0.5 ± 0.1 mL/min, P < 0.001) in comparison to control mice (0.7 ± 0.2 mL/min). Myocardial perfusion in TAC mice was significantly reduced as compared to healthy controls. Perfusion was proportional to LV volume and mass, and related to decreased LV ejection fraction. Furthermore, this study demonstrates the potential of quantitative first-pass contrast-enhanced MRI for the study of perfusion deficits in the diseased mouse heart.     

NT-pro-BNP levels in patients with acute pulmonary embolism are correlated to right but not left ventricular volume and function

N-terminal pro-Brain Natriuretic Peptide (NT-pro-BNP) is primarily secreted by left ventricular (LV) stretch and wall tension. Notably, NT-pro-BNP is a prognostic marker in acute pulmonary embolism (PE), which primarily stresses the right ventricle (RV). We sought to evaluate the relative contribution of the RV to NT-pro-BNP levels during PE. A post-hoc analysis of an observational prospective outcome study in 113 consecutive patients with computed tomography (CT)-proven PE and 226 patients in whom PE was clinically suspected but ruled out by CT. In all patients RV and LV function was established by assessing ECG-triggered-CT measured ventricular end-diastolic-volumes and ejection fraction (EF). NT-pro-BNP was assessed in all patients. The correlation between RV and LV end-diastolic-volumes and systolic function was evaluated by multiple linear regression corrected for known confounders. In the PE cohort increased RVEF (β-coefficient (95% confidence interval [CI]) -0.044 (± -0.011); p<0.001) and higher RV end-diastolic-volume (β-coefficient 0.005 (± 0.001); p<0.001) were significantly correlated to NT-pro-BNP, while no correlation was found with LVEF (β-coefficient 0.005 (± 0.010); p=0.587) and LV end-diastolic-volume (β-coefficient -0.003 (± 0.002); p=0.074). In control patients without PE we found a strong correlation between NT-pro-BNP levels and LVEF (β-coefficient -0.027 (± -0.006); p<0.001) although not LV end-diastolic-volume (β-coefficient 0.001 (± 0.001); p=0.418). RVEF (β-coefficient -0.002 (± -0.006); p=0.802) and RV end-diastolic-volume (β-coefficient <0.001 (± 0.001); p=0.730) were not correlated in patients without PE. In PE patients, lower RVEF and higher RV end-diastolic-volume were significantly correlated to NT-pro-BNP levels as compared to control patients without PE. These observations provide pathophysiological ground for the well-known prognostic value of NT-pro-BNP in acute PE.     

Platelet‐derived growth factor is involved in the differentiation of second heart field‐derived cardiac structures in chicken embryos

For the establishment of a fully functional septated heart, addition of myocardium from second heart field‐derived structures is important. Platelet‐derived growth factors (PDGFs) are known for their role in cardiovascular development. In this study, we aim to elucidate this role of PDGF‐A, PDGF‐C, and their receptor PDGFR‐α. We analyzed the expression patterns of PDGF‐A, ‐C, and their receptor PDGFR‐α during avian heart development. A spatiotemporal pattern of ligands was seen with colocalization of the PDGFR‐α. This was found in second heart field‐derived myocardium as well as the proepicardial organ (PEO) and epicardium. Mechanical inhibition of epicardial outgrowth as well as chemical disturbance of PDGFR‐α support a functional role of the ligands and the receptor in cardiac development. Developmental Dynamics 238:2658–2669, 2009. © 2009 Wiley‐Liss, Inc.     

Chemotherapy in the oldest old: Choices and outcomes

Treatment decision‐making in older patients with cancer is difficult due to a paucity of data evaluating chemotherapy tolerability in this population. We investigated the feasibility of chemotherapy in the oldest old and performed a singl‐centre retrospective analysis of patients aged ≥80 years initiating chemotherapy for one of five common solid malignancies or non‐Hodgkin lymphoma between 2010 and 2016. Treatment plan and course were extracted from medical files. Primary outcome was whether chemotherapy was completed according to plan, defined as a calculated relative dose intensity (RDI) ≥85%. A total of 104 patients receiving 129 chemotherapy lines were included. Median age at diagnosis was 82 years (range 80–94 years). Most patients (64%) received palliative intent chemotherapy. Primary and secondary chemotherapy adaptations were implemented in 63% and 65% of the cases, and hospitalisation occurred in a quarter. 52% of all cases completed chemotherapy according to plan. Almost half of the chemotherapy regimens started in the oldest old were not completed according to plan, despite frequently implemented upfront adaptations. The decision to start chemotherapy in these patients should be carefully considered. To improve decision‐making in current practice, there is a need for the implementation of validated tools assessing chemotherapy feasibility in these patients.     

Altered glycosylation of IgG4 promotes lectin complement pathway activation in anti-PLA2R1–associated membranous nephropathy

Primary membranous nephropathy (pMN) is a leading cause of nephrotic syndrome in adults. In most cases, this autoimmune kidney disease is associated with autoantibodies against the M-type phospholipase A2 receptor (PLA2R1) expressed on kidney podocytes, but the mechanisms leading to glomerular damage remain elusive. Here, we developed a cell culture model using human podocytes and found that anti-PLA2R1–positive pMN patient sera or isolated IgG4, but not IgG4-depleted sera, induced proteolysis of the 2 essential podocyte proteins synaptopodin and NEPH1 in the presence of complement, resulting in perturbations of the podocyte cytoskeleton. Specific blockade of the lectin pathway prevented degradation of synaptopodin and NEPH1. Anti-PLA2R1 IgG4 directly bound mannose-binding lectin in a glycosylation-dependent manner. In a cohort of pMN patients, we identified increased levels of galactose-deficient IgG4, which correlated with anti-PLA2R1 titers and podocyte damage induced by patient sera. Assembly of the terminal C5b-9 complement complex and activation of the complement receptors C3aR1 or C5aR1 were required to induce proteolysis of synaptopodin and NEPH1 by 2 distinct proteolytic pathways mediated by cysteine and aspartic proteinases, respectively. Together, these results demonstrated a mechanism by which aberrantly glycosylated IgG4 activated the lectin pathway and induced podocyte injury in primary membranous nephropathy.     

Predictors of stenosing tenosynovitis in the hand and hand-related activity limitations in patients with rheumatoid arthritis

Ursum J, Horsten NC, Hoeksma AF, Dijkmans BA, Knol DL, van Schaardenburg D, Dekker J, Roorda LD. Predictors of stenosing tenosynovitis in the hand and hand-related activity limitations in patients with rheumatoid arthritis.

Objectives

To identify early predictors of stenosing tenosynovitis in the hand and hand-related activity limitations in patients with rheumatoid arthritis (RA).

Design

A longitudinal study of an inception cohort.

Setting

A large outpatient clinic.

Participants

Consecutive patients who attended the Early Arthritis Clinic for at least 2 years and fulfilled the American College of Rheumatology criteria for RA at baseline and/or at the 1-year follow-up were invited to participate until 200 patients were included.

Interventions

Not applicable.

Main Outcome Measures

Stenosing tenosynovitis, assessed by means of a standardized physical examination. Hand-related activity limitations, assessed with the Disabilities of Arm, Shoulder and Hand questionnaire (DASH). A DASH score above the upper limit of the 95% range of the normative score was defined as abnormal. Prognostic factors: demographic and disease activity–related variables, radiographic damage, the Health Assessment Questionnaire (HAQ) total score and category scores at the 2-year follow-up.

Results

The mean age ± SD of the patients was 59.7±10.7 years (75% female). The mean time ± SD between the 2-year follow-up and the assessment of the dependent variables was 3.9±2.7 years. Stenosing tenosynovitis was present in 33%. The median (interquartile range) DASH score was 26.7 (10.8–42.5); 30% were abnormal. Stenosing tenosynovitis was predicted by the HAQ subscale regarding the use of hands (HAQ-hand) at the 2-year follow-up (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.2–4.2). Hand-related activity limitations were predicted by the Disease Activity Score in 28 joints (OR, 1.8; 95% CI, 1.3–2.4) and HAQ-hand (OR, 2.4; 95% CI, 1.3–5.8) at the 2-year follow-up.

Conclusions

Stenosing tenosynovitis in patients with RA was predicted by HAQ-hand at the 2-year follow-up, and hand-related activity limitations were predicted by disease activity and HAQ-hand at the 2-year follow-up.