Exercise Studies in Patients With Rotary Blood Pumps: Cause,Effects, and Implications for Starling‐Like Control of Changes in Pump Flow

This multicenter study examines in detail the spontaneous increase in pump flow at fixed speed that occurs in exercise. Eight patients implanted with the VentrAssist rotary blood pump were subjected to maximal and submaximal cycle ergometry studies, the latter being completed with patients supine and monitored with right heart catheter and echocardiography. Maximal exercise studies conducted in each patient at three different pump speeds on separate days established initially the magnitude and consistency of increases in pump flow that correlated well with changes in heart rate. However, there was considerable variation, coefficients of variation for mean heart rate and pump flow being 47.9 and 49.3%, respectively. Secondly, these studies indicated that increasing pump flows caused significant improvements in maximal exercise capacity. An increase of 2.1 L/min (35%) in maximum blood flow caused 12 W (16%) further increase in achievable work, 1.26 (9.3%) mL/kg/min in maximal oxygen uptake, and 2.3 (23%) mL/kg/min in anaerobic threshold. Mean increases in lactate were 0.85 mm (24%), but mean B‐type natiuretic peptide fell by 126 mm , (?78%). From submaximal supine exercise studies, multiple linear regression of pump flow on factors thought to underlie the spontaneous increase in pump flow indicated that it was associated with increases in heart rate (P = 0.039), pressure gradient across the left ventricle (P = 0.032), and right atrial pressure (P = 0.003). These changes have implications for the recently reported Starling‐like controller for pump flow based on pump pulsatility values, which emulates the Starling curve relating pump output to left ventricular preload. Unmodified, the controller would not permit the full benefits of this effect to be afforded to patients implanted with rotary blood pumps. A modification to the pump control algorithm is proposed to eliminate this problem     

《英国非酒精性脂肪性肝炎肝移植指南》导读

非酒精性脂肪性肝炎（non—alcoholicsteatohepatitis,NASH）现已成为肝移植愈来愈重要的基础肝病。鉴于晚期NASH患者常并存多种影响肝移植转归的临床问题,而至今尚无针对NASH患者进行肝移植的评估和治疗指南,为此英国移植学会（British Transplant Society,BTS）邀请相关专家制定了指南,以指导肝移植前后NASH患者的处理。     

Extensive Cytoreductive Surgery for Appendiceal Carcinomatosis: Morbidity, Mortality, and Survival

Background

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemoperfusion (HIPEC) are frequently used to treat appendiceal carcinomatosis. Some patients require multivisceral resection because of the volume of disease. It is unclear whether extent of CRS impacts survival in appendiceal carcinomatosis.

Methods

We analyzed 282 patients undergoing attempted CRS/HIPEC for appendiceal carcinomatosis. Patients were defined as having undergone Extensive CRS (n = 60) if they had >3 organ resections or >2 anastomoses; a subgroup of Extreme CRS patients (n = 10) had ≥5 organ resections and ≥3 anastomoses. Kaplan–Meier survival curves and multivariate Cox-regression models were used to identify prognostic factors affecting outcomes.

Results

Relative to the comparison group, patients undergoing Extensive CRS had a higher median peritoneal carcinomatosis index, operative duration, blood loss, and length of stay. No difference in completeness of cytoreduction, severe morbidity, or 60-day mortality was evident. Subgroup analysis of 10 patients undergoing extreme CRS likewise revealed no increase in severe morbidity or mortality. Median progression-free (PFS) and overall survival (OS) were 23.5 and 74 months in the comparison group; 18.5 (p = 0.086) and 51 (p = 0.85) months in the Extensive CRS group; and 40 months and not reached in the Extreme CRS subgroup. In a multivariable analysis, extent of CRS was not independently associated with PFS or OS.

Conclusions

Extensive CRS is associated with greater OR time, blood loss, and length of stay, but is not associated with higher morbidity, mortality, or inferior oncologic outcomes in patients with appendiceal carcinomatosis.     

Effect of Intrathecal Baclofen Concentration on Spasticity Control: Case Series

Background/Objective: Intrathecal baclofen (ITB) has been shown to be an effective treatment for severe spasticity of spinal or cerebral origin. Although most patients respond well to an ITB trial, there are often difficulties in achieving and/or maintaining such effectiveness with ITB pump treatment. There are few published guidelines for dosing efficacy and no studies looking at the effect of concentration of ITB on spasticity management.

Methods: Case series of 3 adults with severe spasticity treated with ITB pump: a 44-year-old man with C7 tetraplegia using a 40-mL Medtronic SynchroMed II pump with 500-μg/mL concentration; a 35-year-old woman with traumatic brain injury with right spastic hemiplegia using a 18-mL Medtronic SynchroMed EL pump with 2,000-μg/mL concentration; and a 43-year-old woman with spastic diplegic cerebral palsy using a 40-mL Medtronic SynchroMed II pump with 2,000-μg/mL concentration.

Results: After reducing ITB concentrations in the pump, either as part of a standard protocol for dye study to assess the integrity of pump and catheter system or secondary to plateau in therapeutic efficacy, patients experienced temporary, significant reduction in spasticity based on range of motion, Modified Ashworth scores, and verbal feedback.

Conclusions: Decreasing the concentration of ITB seems to affect spasticity control. Further research in this area is needed for those patients with refractory spasticity to optimize efficacy of ITB therapy.     

Digital atlas of the zebra finch (Taeniopygia guttata) brain: A high‐resolution photo atlas

We describe a set of new comprehensive, high‐quality, high‐resolution digital images of histological sections from the brain of male zebra finches (Taeniopygia guttata) and make them publicly available through an interactive website ( http://zebrafinch.brainarchitecture.org/ ). These images provide a basis for the production of a dimensionally accurate and detailed digital nonstereotaxic atlas. Nissl‐ and myelin‐stained brain sections are provided in the transverse, sagittal, and horizontal planes, with the transverse plane approximating the more traditional Frankfurt plane. In addition, a separate set of brain sections in this same plane is stained for tyrosine hydroxylase, revealing the distribution of catecholaminergic neurons (dopaminergic, noradrenergic, and adrenergic) in the songbird brain. For a subset of sagittal sections we also prepared a corresponding set of drawings, defining and annotating various nuclei, fields, and fiber tracts that are visible under Nissl and myelin staining. This atlas of the zebra finch brain is expected to become an important tool for birdsong research and comparative studies of brain organization and evolution. J. Comp. Neurol. 521:3702–3715, 2013. © 2013 Wiley Periodicals, Inc.     

Rescheduling Part 2 of the 11+ reduces injury burden and increases compliance in semi‐professional football

Although the 11+ program has been shown to reduce injuries in sub‐elite football, program compliance is typically poor, suggesting that strategies to optimize delivery are necessary. This study investigated the effect of rescheduling Part 2 of the three‐part 11+ program on program effectiveness. Twenty‐five semi‐professional football clubs were randomly allocated to either a Standard‐11+ (n = 398 players) or P2_post group (n = 408 players). Both groups performed the 11+ program at least twice a week throughout the 2017 football season. The Standard‐11+ group performed the entire 11+ program before training activities commenced, whereas the P2_post group performed Parts 1 and 3 of the 11+ program before and Part 2 after training. Injuries, exposure, and individual player 11+ dose were monitored throughout the season. No significant between group difference in injury incidence rate (P2_post vs Standard‐11+ = 11.8 vs 12.3 injuries/1000 h) was observed. Severe time loss injuries > 28 days (33 vs 58 injuries; P < .002) and total days lost to injury (4303 vs 5815 days; P < .001) were lower in the P2_post group. A higher 11+ program dose was observed in the P2_post (29.1 doses; 95% CI 27.9‐30.1) versus Standard‐11+ group (18.9 doses; 95% CI 17.6?20.2; P < .001). In semi‐professional football, rescheduling Part 2 of the 11+ program to the end of training maintained the effectiveness of the original 11+ program to reduce injury incidence. Importantly, rescheduling Part 2 improved player compliance and reduced the number of severe injuries and total injury burden, thereby enhancing effectiveness of the 11+ program.     

A (five-)level playing field for mental health conditions?: exploratory analysis of EQ-5D-5L-derived utility values

Purpose

Economic evaluations of mental health interventions often measure health benefit in terms of utility values derived from the EQ-5D. For the five-level version of the EQ-5D, there are two methods of estimating utility [crosswalk and stated preference (5L-SP)]. This paper explores potential impacts for researchers and decision-makers when comparing utility values derived from either method in the specific context of mental health.

Methods

Baseline EQ-5D-5L data from three large randomised controlled trials of interventions for mental health conditions were analysed. Utility values were generated using each method. Mean utility values were compared using a series of t tests on pooled data and subgroups. Scenario analyses explored potential impacts on cost-effectiveness decisions.

Results

EQ-5D data were available for 1399 participants. The mean utility value for each trial was approximately 0.08 higher when estimated using the 5L-SP approach compared to crosswalk (p?<?0.0001). The difference was greatest among people reporting extreme anxiety/depression (mean utility 5L-SP 0.309, crosswalk 0.084; difference?=?0.225; p?<?0.0001). Identical improvements in health status were associated with higher costs to gain one QALY with the 5L-SP approach; this is more pronounced when improvements are across all domains compared to improvements on the anxiety/depression domain only.

Conclusions

The two approaches produce significantly different utility values in people with mental health conditions. Resulting differences in cost per QALY estimates suggest that thresholds of cost-effectiveness may also need to be reviewed. Researchers and decision-makers should exercise caution when comparing or synthesising data from trials of mental health interventions using different utility estimation approaches.