Summary Sarcopenic obesity (SO) is assuming a prominent role as a risk factor because of the double metabolic burden derived from low muscle mass (sarcopenia) and excess adiposity (obesity). The ...increase in obesity prevalence rates in older subjects is of concern given the associated disease risks and more limited therapeutic options available in this age group. This review has two main objectives. The primary objective is to collate results from studies investigating the effects of SO on physical and cardio-metabolic functions. The secondary objective is to evaluate published studies for consistency in methodology, diagnostic criteria, exposure and outcome selection. Large between-study heterogeneity was observed in the application of diagnostic criteria and choice of body composition components for the assessment of SO, which contributes to the inconsistent associations of SO with cardio-metabolic outcomes. We propose a metabolic load:capacity model of SO given by the ratio between fat mass and fat free mass, and discuss how this could be operationalised. The concept of regional fat distribution could be incorporated into the model and tested in future studies to advance our understanding of SO as a predictor of risk for cardio-metabolic diseases and physical disability.
Type 2 diabetes is rapidly increasing in prevalence worldwide, in concert with epidemics of obesity and sedentary behavior that are themselves tracking economic development. Within this broad ...pattern, susceptibility to diabetes varies substantially in association with ethnicity and nutritional exposures through the life-course. An evolutionary perspective may help understand why humans are so prone to this condition in modern environments, and why this risk is unequally distributed. A simple conceptual model treats diabetes risk as the function of two interacting traits, namely 'metabolic capacity' which promotes glucose homeostasis, and 'metabolic load' which challenges glucose homoeostasis. This conceptual model helps understand how long-term and more recent trends in body composition can be considered to have shaped variability in diabetes risk. Hominin evolution appears to have continued a broader trend evident in primates, towards lower levels of muscularity. In addition, hominins developed higher levels of body fatness, especially in females in relative terms. These traits most likely evolved as part of a broader reorganization of human life history traits in response to growing levels of ecological instability, enabling both survival during tough periods and reproduction during bountiful periods. Since the emergence of Homo sapiens, populations have diverged in body composition in association with geographical setting and local ecological stresses. These long-term trends in both metabolic capacity and adiposity help explain the overall susceptibility of humans to diabetes in ways that are similar to, and exacerbated by, the effects of nutritional exposures during the life-course.
To establish the diagnostic accuracy of the Montreal Cognitive Assessment (MoCA) when screening externally validated cognition in Parkinson disease (PD), by comparison with a PD-focused test (Scales ...for Outcomes in Parkinson disease-Cognition SCOPA-COG) and the standardized Mini-Mental State Examination (S-MMSE) as benchmarks.
A convenience sample of 114 patients with idiopathic PD and 47 healthy controls was examined in a movement disorders center. The 21 patients with dementia (PD-D) were diagnosed using Movement Disorders Society criteria, externally validated by detailed independent functional and neuropsychological tests. The 21 patients with mild cognitive impairment (PD-MCI) scored 1.5 SD or more below normative data in at least 2 measures in 1 of 4 cognitive domains. Other patients had normal cognition (PD-N).
Primary outcomes using receiver operating characteristic (ROC) curve analyses showed that all 3 mental status tests produced excellent discrimination of PD-D from patients without dementia (area under the curve AUC, 87%-91%) and PD-MCI from PD-N patients (AUC, 78%-90%), but the MoCA was generally better suited across both assessments. The optimal MoCA screening cutoffs were <21/30 for PD-D (sensitivity 81%; specificity 95%; negative predictive value NPV 92%) and <26/30 for PD-MCI (sensitivity 90%; specificity 75%; NPV 95%). Further support that the MoCA is at least equivalent to the SCOPA-COG, and superior to the S-MMSE, came from the simultaneous classification of the 3 PD patient groups (volumes under a 3-dimensional ROC surface, chance = 17%: MoCA 79%, confidence interval CI 70%-89%; SCOPA-COG 74%, CI 62%-86%; MMSE-Sevens item 56%, CI 44%-68%; MMSE-World item 62%, CI 50%-73%).
The MoCA is a suitably accurate, brief test when screening all levels of cognition in PD.
Background: Disruption of circadian rhythms has been associated with obesity in children and adolescents, and with hypertension in adults, in industrialized populations. Objective: We examined ...cross-sectional associations between sleep duration or television viewing and obesity and blood pressure in Brazilian adolescents. Design: The sample consisted of 4452 adolescents aged 10-12 years participating in a prospective birth cohort study in Pelotas, Brazil. Sleep duration and television viewing were determined through questionnaires. Obesity was assessed using international cut-offs for body mass index (BMI), and body fatness by skinfold thicknesses. Blood pressure was measured using a validated monitor. Results: Short sleep duration was associated with increased BMI, skinfolds, systolic blood pressure, activity levels and television viewing. Each hour of sleep reduced BMI by 0.16 kg/m2 (s.e. 0.04), and was associated with odds ratio for obesity of 0.86 (s.e. 0.04), both P<0.001. Television viewing was associated with increased BMI and skinfolds, and increased blood pressure. The effects of sleep duration and television viewing on obesity were independent of one another. Their associations with blood pressure were mediated by body fatness. Conclusions: Both short sleep duration and increased television viewing were associated with greater body fatness, obesity and higher blood pressure, independently of physical activity level. These associations were independent of maternal BMI, identified in other studies as the strongest predictor of childhood obesity. Our study shows that behavioural factors associated with metabolic risk in industrialized populations exert similar deleterious effects in a population undergoing nutritional transition and suggest options for public health interventions.
The scientific study of obesity has been dominated throughout the twentieth century by the concept of energy balance. This conceptual approach, based on fundamental thermodynamic principles, states ...that energy cannot be destroyed, and can only be gained, lost or stored by an organism. Its application in obesity research has emphasised excessive appetite (gluttony), or insufficient physical activity (sloth), as the primary determinants of excess weight gain, reflected in current guidelines for obesity prevention and treatment. This model cannot explain why weight accumulates persistently rather than reaching a plateau, and underplays the effect of variability in dietary constituents on energy and intermediary metabolism. An alternative model emphasises the capacity of fructose and fructose-derived sweeteners (sucrose, high-fructose corn syrup) to perturb cellular metabolism via modification of the adenosine monophosphate (AMP)/adenosine triphosphate (ATP) ratio, activation of AMP kinase and compensatory mechanisms, which favour adipose tissue accretion and increased appetite while depressing physical activity. This conceptual model implicates chronic hyperinsulinaemia in the presence of a paradoxical state of 'cellular starvation' as a key driver of the metabolic modifications inducing chronic weight gain. We combine evidence from in vitro and in vivo experiments to formulate a perspective on obesity aetiology that emphasises metabolic flexibility and dietary composition rather than energy balance. Using this model, we question the direction of causation of reported associations between obesity and sleep duration or childhood growth. Our perspective generates new hypotheses, which can be tested to improve our understanding of the current obesity epidemic, and to identify novel strategies for prevention or treatment.
One third of deceased donor kidneys for transplantation in the UK are donated following cardiac death (DCD). Such kidneys have a high rate of delayed graft function (DGF) following transplantation. ...We conducted a multicenter, randomized controlled trial to determine whether kidney preservation using cold, pulsatile machine perfusion (MP) was superior to simple cold storage (CS) for DCD kidneys. One kidney from each DCD donor was randomly allocated to CS, the other to MP. A sequential trial design was used with the primary endpoint being DGF, defined as the necessity for dialysis within the first 7 days following transplant. The trial was stopped when data were available for 45 pairs of kidneys. There was no difference in the incidence of DGF between kidneys assigned to MP or CS (58% vs. 56%, respectively), in the context of an asystolic period of 15 min and median cold ischemic times of 13.9 h for MP and 14.3 h for CS kidneys. Renal function at 3 and 12 months was similar between groups, as was graft and patient survival. For kidneys from controlled DCD donors (with mean cold ischemic times around 14 h), MP offers no advantage over CS, which is cheaper and more straightforward.
Machine perfusion and simple cold storage of DCD kidneys produce equivalent transplant outcome in a UK multicentre randomised controlled trial. See editorial by Irish & Katz on page 1955.
In idiopathic interstitial pneumonia (IIP), the significance of connective tissue disease (CTD) features in the absence of a specific CTD diagnosis remains unclear. We studied the clinical and ...prognostic utility of a diagnosis of undifferentiated CTD (UCTD) in patients with biopsy-proven IIP. IIP patients undergoing surgical lung biopsy (1979-2005) were studied (nonspecific interstitial pneumonia (NSIP), n = 45; idiopathic pulmonary fibrosis, n = 56). UCTD was considered present when serum autoantibodies were present and symptoms or signs suggested CTD. The relationship between UCTD and NSIP histology was evaluated. A clinical algorithm that best predicted NSIP histology was constructed using a priori variables. The prognostic utility of UCTD, and of this algorithm, was evaluated. UCTD was present in 14 (31%) NSIP and seven (13%) IPF patients. UCTD was not associated with a survival benefit. The algorithm predictive of NSIP (OR 10.4, 95% CI 3.21-33.67; p<0.0001) consisted of the absence of typical high-resolution computed tomography (HRCT) features for IPF and 1) a compatible demographic profile (females aged <50 yrs) or 2) Raynaud's phenomenon. In patients with an HRCT scan not typical for IPF, this algorithm predicted improved survival (hazard ratio 0.35, 95% CI 0.14-0.85; p = 0.02) independent of IIP severity. UCTD is associated with NSIP histology. However, the diagnostic and prognostic significance of UCTD in IIP patients remains unclear.
The COVID-19 New Mum Study is recording maternal experiences and infant feeding during the UK lockdown. This report from week 1 of the survey describes and compares the delivery and post-natal ...experiences of women who delivered before (BL) versus during (DL) the lockdown.
Women living in the UK aged ≥18 years with an infant ≤12 months of age completed an anonymous online survey (https://is.gd/covid19newmumstudy). Information/links are shared via websites, social media and existing contacts.
From 27.5.20–3.6.20, 1365 women provided data (94% white, 95% married/with partner, 66% degree/higher qualification, 86% living in house; 1049 (77%) delivered BL and 316 (23%) DL. Delivery mode, skin-to-skin contact and breastfeeding initiation did not differ between groups. DL women had shorter hospital stays (p < 0.001). 39% reported changes to their birth plan. Reflecting younger infant age, 59% of DL infants were exclusively breast-fed/mixed fed versus 39% of BL (p < 0.05). 13% reported a change in feeding; often related to lack of breastfeeding support, especially with practical problems. Important sources of feeding support were the partner (60%), health professional (50%) and online groups (47%). 45% of DL women reported insufficient feeding support. Among BL women, 57% and 69% reported decreased feeding support and childcare, respectively. 40% BL/45% DL women reported insufficient support with their own health, 8%/9% contacted a mental health professional; 11% reported their mental health was affected. 9% highlighted lack of contact/support from family and distress that they had missed seeing the baby.
Lockdown has impacted maternal experiences, resulting in distress for many women. Our findings suggest the need for better infant feeding support, especially ‘face-to-face’ support for practical issues; and recognising and supporting mothers who are struggling with mental health challenges or other aspects of their health. The effectiveness of online versus face-to-face contact is currently uncertain, and requires further evaluation.
Most slope stability analyses have employed limit equilibrium methods (LEMs) or the finite-element method (FEM) as the standard approach. However, slope instability is often accompanied by ...discontinuous failure of the soil, which cannot be modelled by either LEMs or FEM. To overcome this limitation, this paper presents an extension of the smoothed particle hydrodynamics (SPH) method to evaluate the stability of a slope, and to simulate the post-failure behaviour of soil. For the slope stability analysis, the shear strength reduction technique with a modified failure criterion for distinguishing convergent from non-convergent solutions is applied to estimate the safety factor of a slope, and the critical slip surface is determined from a contour plot of accumulated plastic strain. To take the pore water pressure into account, a new SPH formulation for soil motion is developed. It is suggested that this equation can be applied to further developments of SPH for saturated soil. As an application of the proposed method, several smoothed particle slope stability analyses and corresponding slope failure simulations are presented, and compared with other solutions. The results show good agreements with other methods in terms of the safety factor and the critical slip surface. As compared with such traditional methods, however, an advantage of SPH is that it can simulate large deformation and post-failure of soil, and can thereby treat a wide range of applications in computational geomechanics, especially those that include large deformation and failure of geomaterials.
Poorly controlled pain is a global public health issue. The personal, familial and societal costs are immeasurable. Only a minority of European patients have access to a comprehensive specialist pain ...clinic. More commonly the responsibility for chronic pain management and initiating opioid therapy rests with the primary care physician and other non‐specialist opioid prescribers. There is much confusing and conflicting information available to non‐specialist prescribers regarding opioid therapy and a great deal of unjustified fear is generated. Opioid therapy should only be initiated by competent clinicians as part of a multi‐faceted treatment programme in circumstances where more simple measures have failed. Throughout, all patients must be kept under close clinical surveillance. As with any other medical therapy, if the treatment fails to yield the desired results and/or the patient is additionally burdened by an unacceptable level of adverse effects, the overall management strategy must be reviewed and revised. No responsible clinician will wish to pursue a failed treatment strategy or persist with an ineffective and burdensome treatment. In a considered attempt to empower and inform non‐specialist opioid prescribers, EFIC convened a European group of experts, drawn from a diverse range of basic science and relevant clinical disciplines, to prepare a position paper on appropriate opioid use in chronic pain. The expert panel reviewed the available literature and harnessed the experience of many years of clinical practice to produce these series of recommendations. Its success will be judged on the extent to which it contributes to an improved pain management experience for chronic pain patients across Europe.
Significance
This position paper provides expert recommendations for primary care physicians and other non‐ specialist healthcare professionals in Europe, particularly those who do not have ready access to specialists in pain medicine, on the safe and appropriate use of opioid medications as part of a multi‐faceted approach to pain management, in properly selected and supervised patients.
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