Death and the preclinical medical student ii: Attitudes toward telling the terminal patient the prognosis

Abstract

The first and second year students in the Faculty of Medicine were surveyed concerning their attitudes toward informing a person that his or her illness was likely to be terminal if the person in question were the student, a parent, or a member of the general public. Attitudes were overwhelmingly in favor of direct truth telling, especially in the second year group. The possible influence of the first year course in Behavioral Sciences is considered.     

Sculpting of an erodible body by flowing water

Erosion by flowing fluids carves striking landforms on Earth and also provides important clues to the past and present environments of other worlds. In these processes, solid boundaries both influence and are shaped by the surrounding fluid, but the emergence of morphology as a result of this interaction is not well understood. We study the coevolution of shape and flow in the context of erodible bodies molded from clay and immersed in a fast, unidirectional water flow. Although commonly viewed as a smoothing process, we find that erosion sculpts pointed and cornerlike features that persist as the solid shrinks. We explain these observations using flow visualization and a fluid mechanical model in which the surface shear stress dictates the rate of material removal. Experiments and simulations show that this interaction ultimately leads to self-similarly receding boundaries and a unique front surface characterized by nearly uniform shear stress. This tendency toward conformity of stress offers a principle for understanding erosion in more complex geometries and flows, such as those present in nature.     

Estrogen receptor–β activated apoptosis in benign hyperplasia and cancer of the prostate is androgen independent and TNFα mediated

Prostate cancer (PCa) and benign prostatic hyperplasia (BPH) are androgen-dependent diseases commonly treated by inhibiting androgen action. However, androgen ablation or castration fail to target androgen-independent cells implicated in disease etiology and recurrence. Mechanistically different to castration, this study shows beneficial proapoptotic actions of estrogen receptor–β (ERβ) in BPH and PCa. ERβ agonist induces apoptosis in prostatic stromal, luminal and castrate-resistant basal epithelial cells of estrogen-deficient aromatase knock-out mice. This occurs via extrinsic (caspase-8) pathways, without reducing serum hormones, and perturbs the regenerative capacity of the epithelium. TNFα knock-out mice fail to respond to ERβ agonist, demonstrating the requirement for TNFα signaling. In human tissues, ERβ agonist induces apoptosis in stroma and epithelium of xenografted BPH specimens, including in the CD133⁺ enriched putative stem/progenitor cells isolated from BPH-1 cells in vitro. In PCa, ERβ causes apoptosis in Gleason Grade 7 xenografted tissues and androgen-independent cells lines (PC3 and DU145) via caspase-8. These data provide evidence of the beneficial effects of ERβ agonist on epithelium and stroma of BPH, as well as androgen-independent tumor cells implicated in recurrent disease. Our data are indicative of the therapeutic potential of ERβ agonist for treatment of PCa and/or BPH with or without androgen withdrawal.     

Pediatric solid organ transplant recipients: Transition to home and chronic illness care

Pediatric SOT recipients are medically fragile and present with complex care issues requiring high‐level management at home. Parents of hospitalized children have reported inadequate preparation for discharge, resulting in problems transitioning from hospital to home and independently self‐managing their child's complex care needs. The aim of this study was to investigate factors associated with the transition from hospital to home and chronic illness care for parents of heart, kidney, liver, lung, or multivisceral recipients. Fifty‐one parents from five pediatric transplant centers completed questionnaires on the day of hospital discharge and telephone interviews at three wk, three months, and six months following discharge from the hospital. Care coordination (p = 0.02) and quality of discharge teaching (p < 0.01) was significantly associated with parent readiness for discharge. Readiness for hospital discharge was subsequently significantly associated with post‐discharge coping difficulty (p = 0.02) at three wk, adherence with medication administration (p = 0.03) at three months, and post‐discharge coping difficulty (p = 0.04) and family management (p = 0.02) at six months post‐discharge. The results underscore the important aspect of education and care coordination in preparing patients and families to successfully self‐manage after hospital discharge. Assessing parental readiness for hospital discharge is another critical component for identifying risk of difficulties in managing post‐discharge care.     

The influence of lower-limb prostheses technology on Paracanoeing time-trial performance

Within the Paracanoeing discipline, it is important to ensure that appropriate control is achieved by a paddler with a disability. However, this Paralympic Games discipline has seen very little attention to date. The aims of this study were to understand the kinematic impact to a paracanoeist when not utilizing the use of a prosthetic lower-limb. A kayaker with a uni-lateral transfemoral amputation completed several 200?m maximal efforts both with and without their prosthesis. When the prosthetic limb was removed, there were significant differences found in stroke rate, stroke speed, stroke length and overall power output. Sagittal and frontal video analysis demonstrated the residual limb movements when paddling and indicated where support would be required to improve the kayak’s control. It is recommended that those with lower-limb absence wishing to paddle a kayak competitively utilize the use of a prostheses designed for the kayaking environment that supports the residual limb at both the upper and inner thigh and the distal end.

• Implications for rehabilitation

• This paper is the first study to investigate both biomechanical and assistive technology-related issues in the new Paralympic Games sport of Paracanoeing.

• For participants possessing lower-limb absence, a prosthetic limb that is designed specifically for the kayaking environment is recommended when Paracanoeing to maximize efficient propulsion.

• Use of an ergometer and multiple 2D cameras provides practitioners the ability to optimize both the comfort and fit of a prosthetic limb.

• Use of an ergometer and multiple 2D cameras provides both athletes and practitioners the ability to optimize the points of human contact within a kayak to ensure comfort and control.

     

Dynamic changes in injured myocardium,very early after acute myocardial infarction,quantified using T1 mapping cardiovascular magnetic resonance

Background

It has recently been suggested that myocardial oedema follows a bimodal pattern early post ST-segment elevation myocardial infarction (STEMI). Yet, water content, quantified using tissue desiccation, did not return to normal values unlike oedema quantified by cardiovascular magnetic resonance (CMR) imaging. We studied the temporal changes in the extent and intensity of injured myocardium using T1-mapping technique within the first week after STEMI.

Methods

A first group (n?=?31) underwent 3 acute 3?T CMR scans (time-point (TP) <?3?h, 24?h and 6?days), including cine, native shortened modified look-locker inversion recovery T1 mapping, T2* mapping and late gadolinium enhancement (LGE). A second group (n?=?17) had a single scan at 24?h with an additional T2-weighted sequence to assess the difference in the extent of area-at-risk (AAR) compared to T1-mapping.

Results

The mean T1 relaxation time value within the AAR of the first group was reduced after 24?h (P?<?0.001 for TP1 vs.TP2) and subsequently increased at 6?days (P?=?0.041 for TP2 vs.TP3). However, the extent of AAR quantified using T1-mapping did not follow the same course, and no change was detected between TP1&TP2 (P?=?1.0) but was between TP2 &TP3 (P?=?0.019). In the second group, the extent of AAR was significantly larger on T1-mapping compared to T2-weighted (42?±?15% vs. 39?±?15%, P?=?0.025). No change in LGE was detected while microvascular obstruction and intra-myocardial haemorrhage peaked at different time points within the first week of reperfusion.

Conclusion

The intensity of oedema post-STEMI followed a bimodal pattern; while the extent of AAR did not track the same course. This discrepancy has implications for use of CMR in this context and may explain the previously reported disagreement between oedema quantified by imaging and tissue desiccation.

     

Resampling to Address the Winner's Curse in Genetic Association Analysis of Time to Event

The “winner's curse” is a subtle and difficult problem in interpretation of genetic association, in which association estimates from large‐scale gene detection studies are larger in magnitude than those from subsequent replication studies. This is practically important because use of a biased estimate from the original study will yield an underestimate of sample size requirements for replication, leaving the investigators with an underpowered study. Motivated by investigation of the genetics of type 1 diabetes complications in a longitudinal cohort of participants in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Genetics Study, we apply a bootstrap resampling method in analysis of time to nephropathy under a Cox proportional hazards model, examining 1,213 single‐nucleotide polymorphisms (SNPs) in 201 candidate genes custom genotyped in 1,361 white probands. Among 15 top‐ranked SNPs, bias reduction in log hazard ratio estimates ranges from 43.1% to 80.5%. In simulation studies based on the observed DCCT/EDIC genotype data, genome‐wide bootstrap estimates for false‐positive SNPs and for true‐positive SNPs with low‐to‐moderate power are closer to the true values than uncorrected naïve estimates, but tend to overcorrect SNPs with high power. This bias‐reduction technique is generally applicable for complex trait studies including quantitative, binary, and time‐to‐event traits.     

Reasons for Distress Among Burn Survivors at 6, 12, and 24 Months Postdischarge: A Burn Injury Model System Investigation

Objective

To identify important sources of distress among burn survivors at discharge and 6, 12, and 24 months postinjury, and to examine if the distress related to these sources changed over time.