Factors Underlying the Early Limb Muscle Weakness in Acute Quadriplegic Myopathy Using an Experimental ICU Porcine Model

The basic mechanisms underlying acquired generalized muscle weakness and paralysis in critically ill patients remain poorly understood and may be related to prolonged mechanical ventilation/immobilization (MV) or to other triggering factors such as sepsis, systemic corticosteroid (CS) treatment and administration of neuromuscular blocking agents (NMBA). The present study aims at exploring the relative importance of these factors by using a unique porcine model. Piglets were all exposed to MV together with different combinations of endotoxin-induced sepsis, CS and NMBA for five days. Peroneal motor nerve conduction velocity and amplitude of the compound muscle action potential (CMAP) as well as biceps femoris muscle biopsy specimens were obtained immediately after anesthesia on the first day and at the end of the 5-day experimental period. Results showed that peroneal nerve motor conduction velocity is unaffected whereas the size of the CMAP decreases independently of the type of intervention, in all groups after 5 days. Otherwise, despite a preserved size, muscle fibre specific force (maximum force normalized to cross-sectional area) decreased dramatically for animals exposed to MV in combination with CS or/and sepsis. These results suggest that the rapid declines in CMAP amplitude and in force generation capacity are triggered by independent mechanisms with significant clinical and therapeutic implications

Nail surface topography and onychochronobiology.

Peer reviewe

Place of death in patients with lung cancer: a retrospective cohort study from 2004-2013

Introduction: Many patients with cancer die in an acute hospital bed, which has been frequently identified as the least preferred location, with psychological and financial implications. This study looks at place and cause of death in patients with lung cancer and identifies which factors are associated with dying in an acute hospital bed versus at home. Methods and Findings: We used the National Lung Cancer Audit linked to Hospital Episode Statistics and Office for National Statistics data to determine cause and place of death in those with lung cancer; both overall and by cancer Network. We used multivariate logistic regression to compare features of those who died in an acute hospital versus those who died at home. Results: Of 143627 patients identified 40% (57678) died in an acute hospital, 29% (41957) died at home and 17% (24108) died in a hospice. Individual factors associated with death in an acute hospital bed compared to home were male sex, increasing age, poor performance status, social deprivation and diagnosis via an emergency route. There was marked variation between cancer Networks in place of death. The proportion of patients dying in an acute hospital ranged from 28% to 48%, with variation most notable in provision of hospice care (9% versus 33%). Cause of death in the majority was lung cancer (86%), with other malignancies, chronic obstructive pulmonary disease (COPD) and ischaemic heart disease (IHD) comprising 9% collectively. Conclusions: A substantial proportion of patients with lung cancer die in acute hospital beds and this is more likely with increasing age, male sex, social deprivation and in those with poor performance status. There is marked variation between Networks, suggesting a need to improve end-of-life planning in those at greatest risk, and to review the allocation of resources to provide more hospice beds, enhanced community support and ensure equal access

Social sciences research in neglected tropical diseases 2: A bibliographic analysis

The official published version of the article can be found at the link below.Background There are strong arguments for social science and interdisciplinary research in the neglected tropical diseases. These diseases represent a rich and dynamic interplay between vector, host, and pathogen which occurs within social, physical and biological contexts. The overwhelming sense, however, is that neglected tropical diseases research is a biomedical endeavour largely excluding the social sciences. The purpose of this review is to provide a baseline for discussing the quantum and nature of the science that is being conducted, and the extent to which the social sciences are a part of that. Methods A bibliographic analysis was conducted of neglected tropical diseases related research papers published over the past 10 years in biomedical and social sciences. The analysis had textual and bibliometric facets, and focussed on chikungunya, dengue, visceral leishmaniasis, and onchocerciasis. Results There is substantial variation in the number of publications associated with each disease. The proportion of the research that is social science based appears remarkably consistent (<4%). A textual analysis, however, reveals a degree of misclassification by the abstracting service where a surprising proportion of the "social sciences" research was pure clinical research. Much of the social sciences research also tends to be "hand maiden" research focused on the implementation of biomedical solutions. Conclusion There is little evidence that scientists pay any attention to the complex social, cultural, biological, and environmental dynamic involved in human pathogenesis. There is little investigator driven social science and a poor presence of interdisciplinary science. The research needs more sophisticated funders and priority setters who are not beguiled by uncritical biomedical promises

Retention on Buprenorphine Is Associated with High Levels of Maximal Viral Suppression among HIV-Infected Opioid Dependent Released Prisoners

HIV-infected prisoners lose viral suppression within the 12 weeks after release to the community. This prospective study evaluates the use of buprenorphine/naloxone (BPN/NLX) as a method to reduce relapse to opioid use and sustain viral suppression among released HIV-infected prisoners meeting criteria for opioid dependence (OD).From 2005-2010, 94 subjects meeting DSM-IV criteria for OD were recruited from a 24-week prospective trial of directly administered antiretroviral therapy (DAART) for released HIV-infected prisoners; 50 (53%) selected BPN/NLX and were eligible to receive it for 6 months; the remaining 44 (47%) selected no BPN/NLX therapy. Maximum viral suppression (MVS), defined as HIV-1 RNA<50 copies/mL, was compared for the BPN/NLX and non-BPN/NLX (N = 44) groups.The two groups were similar, except the BPN/NLX group was significantly more likely to be Hispanic (56.0% v 20.4%), from Hartford (74.4% v 47.7%) and have higher mean global health quality of life indicator scores (54.18 v 51.40). MVS after 24 weeks of being released was statistically correlated with 24-week retention on BPN/NLX [AOR = 5.37 (1.15, 25.1)], having MVS at the time of prison-release [AOR = 10.5 (3.21, 34.1)] and negatively with being Black [AOR = 0.13 (0.03, 0.68)]. Receiving DAART or methadone did not correlate with MVS.In recognition that OD is a chronic relapsing disease, strategies that initiate and retain HIV-infected prisoners with OD on BPN/NLX is an important strategy for improving HIV treatment outcomes as a community transition strategy

Multiple populations in globular clusters. Lessons learned from the Milky Way globular clusters

Recent progress in studies of globular clusters has shown that they are not simple stellar populations, being rather made of multiple generations. Evidence stems both from photometry and spectroscopy. A new paradigm is then arising for the formation of massive star clusters, which includes several episodes of star formation. While this provides an explanation for several features of globular clusters, including the second parameter problem, it also opens new perspectives about the relation between globular clusters and the halo of our Galaxy, and by extension of all populations with a high specific frequency of globular clusters, such as, e.g., giant elliptical galaxies. We review progress in this area, focusing on the most recent studies. Several points remain to be properly understood, in particular those concerning the nature of the polluters producing the abundance pattern in the clusters and the typical timescale, the range of cluster masses where this phenomenon is active, and the relation between globular clusters and other satellites of our Galaxy.Comment: In press (The Astronomy and Astrophysics Review

A case review to describe variation in care following diagnosis of Perthes' disease

Aims Perthes’ disease is a condition which leads to necrosis of the femoral head. It is most commonly reported in children aged four to nine years, with recent statistics suggesting it affects around five per 100,000 children in the UK. Current treatment for the condition aims to maintain the best possible environment for the disease process to run its natural course. Management typically includes physiotherapy with or without surgical intervention. Physiotherapy intervention often will include strengthening/stretching programmes, exercise/activity advice, and, in some centres, will include intervention, such as hydrotherapy. There is significant variation in care with no consensus on which treatment option is best. The importance of work in this area has been demonstrated by the British Society for Children’s Orthopaedic Surgery through the James Lind Alliance’s prioritization of work to determine/identify surgical versus non-surgical management of Perthes’ disease. It was identified as the fourth-highest priority for paediatric lower limb surgery research in 2018. Methods Five UK NHS centres, including those from the NEWS (North, East, West and South Yorkshire) orthopaedic group, contributed to this case review, with each entre providing clinical data from a minimum of five children. Information regarding both orthopaedic and physiotherapeutic management over a two-year post-diagnosis period was reviewed. Results Data were extracted from the clinical records of 32 children diagnosed with Perthes’ disease; seven boys and 25 girls. The mean age of the children at diagnosis was 6.16 years (standard deviation (SD) 3.001). In all, 26 children were referred for physiotherapy. In the two-year period following diagnosis, children were seen a median of 7.5 times (interquartile range (IQR) 4.25 to 11) by an orthopaedic surgeon, and a median of 9.5 times (IQR 8 to 18.25) by a physiotherapist. One centre had operated on all of their children, while another had operated on none. Overall, 17 (53%) of the children were managed conservatively in the two-year follow-up period, and 15 (47%) of the children underwent surgery in the two-year follow-up period. Conclusion The results of this case review demonstrate a variation of care provided to children in the UK with Perthes’ disease. Further national and international understanding of current care is required to underpin the rationale for different treatment options in children with Perthes’ disease

Health status in older hospitalized patients with cancer or non-neoplastic chronic diseases

BACKGROUND: Whether cancer is more disabling than other highly prevalent chronic diseases in the elderly is not well understood, and represents the objective of the present study. METHODS: We used data from the Gruppo Italiano di Farmacovigilanza nell'Anziano (GIFA) study, a large collaborative observational study based in community and university hospitals located throughout Italy. Our series consisted of three groups of patients with non-neoplastic chronic disease (congestive heart failure, CHF, N = 832; diabetes mellitus, N = 939; chronic obstructive pulmonary disease, COPD, N = 399), and three groups of patients with cancer (solid tumors without metastasis, N = 813; solid tumors with metastasis, N = 259; leukemia/lymphoma, N = 326). Functional capabilities were ascertained using the activities of daily living (ADL) scale, and categorical variables for dependency in at least 1 ADL or dependency in 3 or more ADLs were considered in the analysis. Cognitive status was evaluated by the 10-items Hodgkinson Abbreviated Mental Test (AMT). RESULTS: Cognitive impairment was more prevalent in patients with CHF (28.0%) or COPD (25.8%) than in those with cancer (solid tumors = 22.9%; leukemia/lymphoma = 19.6%; metastatic cancer = 22.8%). Dependency in at least 1 ADL was highly prevalent in patients with metastatic cancer (31.3% vs. 24% for patients with CHF and 22.4% for those with non-metastatic solid tumors, p < 0.001). In people aged 80 years or more, metastatic cancer was not associated with increased prevalence of physical disability. In multivariable analysis, metastatic cancer was associated with a greater prevalence of physical (OR 2.09, 95%CI 1.51–2.90) but not cognitive impairment (OR 1.34, 95%CI 0.94–1.91) with respect to CHF patients. Finally, diabetes was significantly associated with cognitive impairment (OR 1.40, 95%CI 1.11–1.78). CONCLUSION: Cancer should not be considered as an ineluctable cause of severe cognitive and physical impairment, at least not more than other chronic conditions highly prevalent in older people, such as CHF and diabetes mellitus