Influence of medication risks and benefits on treatment preferences in older patients with multimorbidity

Multimorbidity is associated with use of multiple medicines, increased risk of adverse events and treatment conflicts. This study aimed to examine how older patients with multimorbidity and clinicians balance the benefits and harms associated with a medication and in the presence of competing health outcomes. Interviews were conducted with 15 participants aged ≥65 years with 2 or more chronic conditions. Three clinical scenarios were presented to understand patient preference to take a medicine according to i) degree of benefit, ii) type of adverse event and impact on daily living and iii) influence of comorbid conditions as competing health outcomes. Semi-structured interviews were also conducted with participants (n=15) and clinicians (n=5) to understand patient preferences and treatment decisions, in the setting of multimorbidity. The median age of participants was 79 years, 55% had 5 or more conditions and 47% took 8 or more medicines daily. When the level of benefit of the medicine ranged from 14% to 70%, 80% of participants chose to take the medicine, but when adverse effects were present, this was reduced to 0-33% depending upon impact on daily activities. In the presence of competing health outcomes, 13%-26% of patients chose to take the medicine. Two-thirds of patients reported that their doctor respects and considers their preferences and discussed medication benefits and harms. Interviews with clinicians showed that their overall approach to treatment decision-making for older individuals with multimorbidity was based upon 2 main factors, the patients' prognosis and their preferences. The degree of benefit gained was not the driver of patients' preference to take a medicine; rather, this decision was influenced by type and severity of adverse effects. Inclusion of patient preferences in the setting of risks and benefits of medicines with consideration and prioritization of competing health outcomes may result in improved health outcomes for people with multimorbidity.Gillian E Caughey, Kirsty Tait, Agnes I Vitry, Sepehr Shaki

Laser Velocimeter Measurements in the Leakage Annulus of a Whirling Shrouded Centrifugal Pump

Previous experiments conducted in the Rotor Force Test Facility at the California Institute of Technology have thoroughly examined the effect of leakage flows on the rotordynamic forces on a centrifugal pump impeller undergoing a prescribed circular whirl. These leakage flows have been shown to contribute substantially to the total fluid induced forces acting on a pump. However, to date nothing is known of the flow field in the leakage annulus of shrouded centrifugal pumps. No attempt has been made to qualitatively or quantitatively examine the velocity field in the leakage annulus. Hence the test objective of this experiment is to acquire fluid velocity data for a geometry representative of the leakage annulus of a shrouded centrifugal pump while the rotor is whirling using laser velocimetry. Tests are performed over a range of whirl ratios and a flowrate typical of Space Shuttle Turbopump designs. In addition to a qualitive study of the flow field, the velocity data can be used to anchor flow models

Synthesis and structural characterization of a mimetic membrane-anchored prion protein

During pathogenesis of transmissible spongiform encephalopathies (TSEs) an abnormal form (PrPSc) of the host encoded prion protein (PrPC) accumulates in insoluble fibrils and plaques. The two forms of PrP appear to have identical covalent structures, but differ in secondary and tertiary structure. Both PrPC and PrPSc have glycosylphospatidylinositol (GPI) anchors through which the protein is tethered to cell membranes. Membrane attachment has been suggested to play a role in the conversion of PrPC to PrPSc, but the majority of in vitro studies of the function, structure, folding and stability of PrP use recombinant protein lacking the GPI anchor. In order to study the effects of membranes on the structure of PrP, we synthesized a GPI anchor mimetic (GPIm), which we have covalently coupled to a genetically engineered cysteine residue at the C-terminus of recombinant PrP. The lipid anchor places the protein at the same distance from the membrane as does the naturally occurring GPI anchor. We demonstrate that PrP coupled to GPIm (PrP-GPIm) inserts into model lipid membranes and that structural information can be obtained from this membrane-anchored PrP. We show that the structure of PrP-GPIm reconstituted in phosphatidylcholine and raft membranes resembles that of PrP, without a GPI anchor, in solution. The results provide experimental evidence in support of previous suggestions that NMR structures of soluble, anchor-free forms of PrP represent the structure of cellular, membrane-anchored PrP. The availability of a lipid-anchored construct of PrP provides a unique model to investigate the effects of different lipid environments on the structure and conversion mechanisms of PrP

Pregnancy Intendedness by Maternal Disability Status and Type in the United States

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154611/1/psrh12130.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154611/2/psrh12130_am.pd

Guideline compliance in chronic heart failure patients with multiple comorbid diseases: evaluation of an individualised multidisciplinary model of care

OBJECTIVE: To assess the impact of individualised, reconciled evidence-based recommendations (IRERs) and multidisciplinary care in patients with chronic heart failure (CHF) on clinical guideline compliance for CHF and common comorbid conditions. DESIGN AND SETTING: A retrospective hospital clinical audit conducted between 1st July 2006 and February 2011. PARTICIPANTS: A total of 255 patients with a diagnosis of CHF who attended the Multidisciplinary Ambulatory Consulting Services (MACS) clinics, at the Royal Adelaide Hospital, were included. MAIN OUTCOME MEASURES: Compliance with Australian clinical guideline recommendations for CHF, atrial fibrillation, diabetes mellitus and ischaemic heart disease. RESULTS: Study participants had a median of eight medical conditions (IQR 6-10) and were on an average of 10 (±4) unique medications. Compliance with clinical guideline recommendations for pharmacological therapy for CHF, comorbid atrial fibrillation, diabetes or ischaemic heart disease was high, ranging from 86% for lipid lowering therapy to 98% anti-platelet agents. For all conditions, compliance with lifestyle recommendations was lower than pharmacological therapy, ranging from no podiatry reviews for CHF patients with comorbid diabetes to 75% for heart failure education. Concordance with many guideline recommendations was significantly associated if the patient had IRERs determined, a greater number of recommendations, more clinic visits or if patients participated in a heart failure program. CONCLUSIONS: Despite the high number of comorbid conditions and resulting complexity of the management, high compliance to clinical guideline recommendations was associated with IRER determination in older patients with CHF. Importantly these recommendations need to be communicated to the patient's general practitioner, regularly monitored and adjusted at clinic visits.Tam H. Ho, Gillian E. Caughey, Sepehr Shaki