Capacity to make health care decisions: its importance in clinical practice

Background. Assessment of capacity plays a pivotal role in determining when decisions need to be made on behalf of an individual. It therefore has major clinical management implications for health care professionals and civil liberties implications for the person concerned. In many countries, there is a presumption that adults have the capacity to make health care decisions. However, in persons with a mental disability, capacity may be temporarily or permanently impaired. Methods. A selective review is presented which considers: (i) the broad approaches taken to determining capacity; (ii) the abilities commonly assessed in determining capacity; and (iii) the principles underlying health care decision-making for adults who are without capacity. Results. Capacity is a functional concept, determined by the person's ability to understand, retain, and weigh up information relevant to the decision in order to arrive at a choice, and then to communicate that choice. We have reviewed the studies that examined decision-making abilities in people with dementia, chronic mental illness or intellectual disabilities. Approaches to decision-making in adults who lack capacity include: anticipatory decisions made through advance health care statements or decisions by proxy based on ‘best interests’ or ‘substituted judgement’. Conclusions. The understanding of clinical and legal aspects of capacity is still developing. This paper examines current concepts of capacity and decision-making on behalf of those without capacity. We propose a framework, in line with current ethical and legal guidelines, as an aid to clinicians when they are seeking consent for a health care intervention.published_or_final_versio

Seeing Through the "Science Eyes" of the ExoMars Rover

The ExoMars rover, due to launch in mid 2020, will travel to Mars in search of signs of past or present habitability. The rover will carry the Panoramic Camera, PanCam, a scientific camera system designed to provide crucial remote sensing capabilities as mission scientists search for targets of interest. In preparation for the mission operations, the visual output of PanCam has been simulated and modeled with a three-dimensional rendering system, allowing the team to investigate the capabilities of the camera system and providing insight into how it may be calibrated and used for engineering tasks during the surface mission

The capacity of people with a ‘mental disability’ to make a health care decision

Background. Based on the developing clinical and legal literature, and using the framework adopted in draft legislation, capacity to make a valid decision about a clinically required blood test was investigated in three groups of people with a ‘mental disability’ (i.e. mental illness (chronic schizophrenia), ‘learning disability’ (‘mental retardation’, or intellectual or developmental disability), or, dementia) and a fourth, comparison group. Methods. The three ‘mental disability’ groups (N = 20 in the ‘learning disability’ group, N = 21 in each of the other two groups) were recruited through the relevant local clinical services; and through a phlebotomy clinic for the ‘general population’ comparison group (N = 20). The decision-making task was progressively simplified by presenting the relevant information as separate elements and modifying the assessment of capacity so that responding became gradually less dependent on expressive verbal ability. Results. Compared with the ‘general population’ group, capacity to make the particular decision was significantly more impaired in the ‘learning disability’ and ‘dementia’ groups. Importantly, however, it was not more impaired among the ‘mental illness’ group. All the groups benefited as the decision-making task was simplified, but at different stages. In each of the ‘mental disability’ groups, one participant benefited only when responding did not require any expensive verbal ability. Conclusions. Consistent with current views, capacity reflected an interaction between the decision-maker and the demands of the decision-making task. The findings have implications for the way in which decisions about health care interventions are sought from people with a ‘mental disability’. The methodology may be extended to assess capacity to make other legally-significant decisions.published_or_final_versio

Is the SMART risk prediction model ready for real-world implementation? A validation study in a routine care setting of approximately 380 000 individuals

AIMS: Reliably quantifying event rates in secondary prevention could aid clinical decision-making, including quantifying potential risk reductions of novel, and sometimes expensive, add-on therapies. We aimed to assess whether the SMART risk prediction model performs well in a real-world setting. METHODS AND RESULTS: We conducted a historical open cohort study using UK primary care data from the Clinical Practice Research Datalink (2000-2017) diagnosed with coronary, cerebrovascular, peripheral, and/or aortic atherosclerotic cardiovascular disease (ASCVD). Analyses were undertaken separately for cohorts with established (≥6 months) vs. newly diagnosed ASCVD. The outcome was first post-cohort entry occurrence of myocardial infarction, stroke, or cardiovascular death. Among the cohort with established ASCVD [n = 244 578, 62.1% male, median age 67.3 years, interquartile range (IQR) 59.2-74.0], the calibration and discrimination achieved by the SMART model was not dissimilar to performance at internal validation [Harrell's c-statistic = 0.639, 95% confidence interval (CI) 0.636-0.642, compared with 0.675, 0.642-0.708]. Decision curve analysis indicated that the model outperformed treat all and treat none strategies in the clinically relevant 20-60% predicted risk range. Consistent findings were observed in sensitivity analyses, including complete case analysis (n = 182 482; c = 0.624, 95% CI 0.620-0.627). Among the cohort with newly diagnosed ASCVD (n = 136 445; 61.0% male; median age 66.0 years, IQR 57.7-73.2), model performance was weaker with more exaggerated risk under-prediction and a c-statistic of 0.559, 95% CI 0.556-0.562. CONCLUSIONS: The performance of the SMART model in this validation cohort demonstrates its potential utility in routine healthcare settings in guiding both population and individual-level decision-making for secondary prevention patients

A Systematic Review of Magnesium Sulfate for Perinatal Neuroprotection: What Have We Learnt From the Past Decade?

There is an important unmet need to improve long term outcomes of encephalopathy for preterm and term infants. Meta-analyses of large controlled trials suggest that maternal treatment with magnesium sulfate (MgSO4) is associated with a reduced risk of cerebral palsy and gross motor dysfunction after premature birth. However, to date, follow up to school age has found an apparent lack of long-term clinical benefit. Because of this inconsistency, it remains controversial whether MgSO4 offers sustained neuroprotection. We systematically reviewed preclinical and clinical studies reported from January 1 2010, to January 31 2020 to evaluate the most recent advances and knowledge gaps relating to the efficacy of MgSO4 for the treatment of perinatal brain injury. The outcomes of MgSO4 in preterm and term-equivalent animal models of perinatal encephalopathy were highly inconsistent between studies. None of the perinatal rodent studies that suggested benefit directly controlled body or brain temperature. The majority of the studies did not control for sex, study long term histological and functional outcomes or use pragmatic treatment regimens and many did not report controlling for potential study bias. Finally, most of the recent preterm or term human studies that tested the potential of MgSO4 for perinatal neuroprotection were relatively underpowered, but nevertheless, suggest that any improvements in neurodevelopment were at best modest or absent. On balance, these data suggest that further rigorous testing in translational preclinical models of perinatal encephalopathy is essential to ensure safety and best regimens for optimal preterm neuroprotection, and before further clinical trials of MgSO4 for perinatal encephalopathy at term are undertaken

Deletion of the Polycomb-Group Protein EZH2 Leads to Compromised Self-Renewal and Differentiation Defects in Human Embryonic Stem Cells

Through the histone methyltransferase EZH2, the Polycomb complex PRC2 mediates H3K27me3 and is associated with transcriptional repression. PRC2 regulates cell-fate decisions in model organisms; however, its role in regulating cell differentiation during human embryogenesis is unknown. Here, we report the characterization of $\small \textit{EZH2}$-deficient human embryonic stem cells (hESCs). H3K27me3 was lost upon $\small \textit{EZH2}$ deletion, identifying an essential requirement for EZH2 in methylating H3K27 in hESCs, in contrast to its non-essential role in mouse ESCs. Developmental regulators were derepressed in $\small \textit{EZH2}$-deficient hESCs, and single-cell analysis revealed an unexpected acquisition of lineage-restricted transcriptional programs. $\small \textit{EZH2}$-deficient hESCs show strongly reduced self-renewal and proliferation, thereby identifying a more severe phenotype compared to mouse ESCs. $\small \textit{EZH2}$-deficient hESCs can initiate differentiation toward developmental lineages; however, they cannot fully differentiate into mature specialized tissues. Thus, $\small \textit{EZH2}$ is required for stable ESC self-renewal, regulation of transcriptional programs, and for late-stage differentiation in this model of early human development.Wellcome Trust (Grant ID: WT093736), Biotechnology and Biological Sciences Research Council (Grant ID: BBS/E/B/000C0402), Medical Research Council (DTG Studentships, Grant ID: MR/J003808/1

An Update of Our Understanding of Fetal Heart Rate Patterns in Health and Disease.

UNDERSTANDING FETAL HEART RATE PATTERNS THAT MAY PREDICT ANTENATAL AND INTRAPARTUM NEURAL INJURY: Christopher A. Lear, Jenny A. Westgate, Austin Ugwumadu, Jan G. Nijhuis, Peter R. Stone, Antoniya Georgieva, Tomoaki Ikeda, Guido Wassink , Laura Bennet , Alistair J. Gunn Seminars in Pediatric Neurology Volume 28, December 2018, Pages 3-16 Electronic fetal heart rate (FHR) monitoring is widely used to assess fetal well-being throughout pregnancy and labor. Both antenatal and intrapartum FHR monitoring are associated with a high negative predictive value and a very poor positive predictive value. This in part reflects the physiological resilience of the healthy fetus and the remarkable effectiveness of fetal adaptations to even severe challenges. In this way, the majority of "abnormal" FHR patterns in fact reflect a fetus' appropriate adaptive responses to adverse in utero conditions. Understanding the physiology of these adaptations, how they are reflected in the FHR trace and in what conditions they can fail is therefore critical to appreciating both the potential uses and limitations of electronic FHR monitoring