A significant proportion of patients with COVID-19 develop acute respiratory distress syndrome (ARDS) with high risk of death. The efficacy of veno-venous extracorporeal membrane oxygenation ...(VV-ECMO) for COVID-19 on longer-term outcomes, unlike in other viral pneumonias, is unknown. In this study, we aimed to compare the 6 month mortality of patients receiving VV-ECMO support for COVID-19 with a historical viral ARDS cohort. Fifty-three consecutive patients with COVID-19 ARDS admitted for VV-ECMO to the Royal Brompton Hospital between March 17, 2020 and May 30, 2020 were identified. Mortality, patient characteristics, complications, and ECMO parameters were then compared to a historical cohort of patients with non-COVID-19 viral pneumonia. At 6 months survival was significantly higher in the COVID-19 than in the non-COVID-19 viral pneumonia cohort (84.9% vs. 66.0%, p = 0.040). Patients with COVID-19 had an increased Murray score (3.50 vs. 3.25, p = 0.005), a decreased burden of organ dysfunction (sequential organ failure score score 8.76 vs. 10.42, p = 0.004), an increased incidence of pulmonary embolism (69.8% vs. 24.5%, p < 0.001) and in those who survived to decannulation longer ECMO runs (19 vs. 11 days, p = 0.001). Our results suggest that survival in patients supported with EMCO for COVID-19 are at least as good as those treated for non-COVID-19 viral ARDS.
Objective To explore the use of simulated‐patient methods in community pharmacy for non‐prescription medicines.
Methods The databases IPA (International Pharmaceutical s), EMBASE and MEDLINE were ...searched for articles published between 1990 and 2010 outlining studies using simulated‐patient methods.
Key findings Thirty studies from 31 articles were reviewed. The majority used simulated‐patient methods to purely assess counselling behaviour of pharmacy staff, rather than as an opportunity to provide educational feedback to improve counselling behaviour.
Conclusions Few simulated‐patient studies have incorporated performance feedback to encourage behavioural change and improve counselling skills. Studies that incorporated feedback did not provide sufficient detail, and few studies have explored participant perceptions. Additionally, very few studies have employed scenarios involving children's medicines. Future studies should test the feasibility of using the simulated‐patient method, with appropriate performance feedback and describe participant perceptions of the value and acceptability of this training method.
Veno-Venous Extracorporeal Membrane Oxygenation (VV-ECMO) provides a bridge to recovery in patients with acute respiratory failure due to the acute respiratory distress syndrome (ARDS). Survival in ...ARDS has improved over 15 years, and VV-ECMO may rescue even the most severe of these patients. Predictors of survival on ICU are based upon the principles of reversibility of the inciting aetiology, and premorbid 'reserve' - an imprecise term encompassing comorbidities and frailty. ECMO can support failing organs for prolonged periods, thus sometimes masking trajectories of decline, or unmasking irretrievable intrinsic conditions at a later time point in the critical illness. Clinicians are confronted with new on-treatment dilemmas: how long should we continue this high level of care? Will the patient's limited respiratory reserve manage off ECMO? Or are we hastening their demise? How long is it justifiable to keep someone on ECMO, if the predicted survival off is ultimately poor, but they are in a stable state whilst supported? The palliative withdrawal from ECMO is unchartered territory that requires further study. We describe two representative cases and discuss the wide ethical issues surrounding the initiation and withdrawal of ECMO.
Arterial stiffening and cardiac dysfunction are hallmarks of premature aging in Hutchinson-Gilford Progeria Syndrome (HGPS), but the molecular regulators remain unknown. Here, we show that the LaminA
...mouse model of HGPS recapitulates the premature arterial stiffening and early diastolic dysfunction seen in human HGPS. Lysyl oxidase (LOX) is up-regulated in the arteries of these mice, and treatment with the LOX inhibitor, β-aminopropionitrile, improves arterial mechanics and cardiac function. Genome-wide and mechanistic analysis revealed reduced expression of the LOX-regulator, miR-145, in HGPS arteries, and forced expression of miR-145 restores normal LOX gene expression in HGPS smooth muscle cells. LOX abundance is also increased in the carotid arteries of aged wild-type mice, but its spatial expression differs from HGPS and its up-regulation is independent of changes in miR-145 abundance. Our results show that miR-145 is selectively misregulated in HGPS and that the consequent up-regulation of LOX is causal for premature arterial stiffening and cardiac dysfunction.
Veno-Venous Extracorporeal Membrane Oxygenation (VV-ECMO) provides a bridge to recovery in patients with acute respiratory failure due to the acute respiratory distress syndrome (ARDS). Survival in ...ARDS has improved over 15 years, and VV-ECMO may rescue even the most severe of these patients. Predictors of survival on ICU are based upon the principles of reversibility of the inciting aetiology, and premorbid 'reserve' - an imprecise term encompassing comorbidities and frailty. ECMO can support failing organs for prolonged periods, thus sometimes masking trajectories of decline, or unmasking irretrievable intrinsic conditions at a later time point in the critical illness. Clinicians are confronted with new on-treatment dilemmas: how long should we continue this high level of care? Will the patient's limited respiratory reserve manage off ECMO? Or are we hastening their demise? How long is it justifiable to keep someone on ECMO, if the predicted survival off is ultimately poor, but they are in a stable state whilst supported? The palliative withdrawal from ECMO is unchartered territory that requires further study. We describe two representative cases and discuss the wide ethical issues surrounding the initiation and withdrawal of ECMO.
Background
Community pharmacy staff play a crucial role in the management of common childhood ailments. Simulated patient studies have not yet explored the management of children’s cough/cold and ...fever, nor have many previous studies used simulated patient methods with focus on self-assessment as a training tool to shape future counselling behaviour.
Objectives
To assess and shape the counselling behavior of pharmacy staff when dealing with children’s cough/cold and fever; investigate influential factors of counselling behavior; and explore participant perceptions of simulated patient methods as a training tool, with particular emphasis on self-assessment.
Setting
Community pharmacies in the inner city region of metropolitan Sydney.
Method
Six simulated caregivers visited eight community pharmacies. After applying their scenario, the interaction was scored and immediate performance feedback was delivered in the form of self-assessment. Semi-structured interviews followed, focusing on participant perceptions of self-assessment.
Main outcome measures
Scores for each simulated patient interaction, and qualitative interviews responses from participants.
Results
The highest mean percentage score achieved was for the symptom based request for a cough/cold remedy in a five year old (48 ± 14.3 %), while the lowest was the direct product request equivalent (22 ± 8.5 %). Qualitative results showed that simulated patient visits were viewed positively and self-assessment was highly regarded.
Conclusion
Using simulated caregivers in pharmacy to assess and improve children’s cough/cold and fever management is feasible and acceptable. The opportunity to self-assess is particularly beneficial, allowing participants to demonstrate key psychology principles associated with behaviour change.
We consider the \emph{exact} error correction of a noisy Euclidean distance matrix, EDM, where the elements are the squared distances between \(n\) points in \(R^d\). For our problem we are given two ...facts: (i) the embedding dimension, \(d\), (ii) \emph{exactly one} distance in the data is corrupted by \emph{nonzero noise}. But we do \underline{not} know the magnitude nor position of the noise. Thus there is a combinatorial element to the problem. We present three solution techniques. These use three divide and conquer strategies in combination with three versions of facial reduction that use: exposing vectors, facial vectors, and Gale transforms. This sheds light on the connections between the various forms of facial reduction related to Gale transforms. Our highly successful empirics confirm the success of these approaches as we can solve huge problems of the order of \(100,000\) nodes in approximately one minute to machine precision. \\Our algorithm depends on identifying whether a principal submatrix of the \EDM contains the corrupted element. We provide a theorem for doing this that is related to the existing results for identifying \emph{yielding} elements, i.e.,~we provide a characterization for guaranteeing the perturbed EDM remains an EDM with embedding dimension \(d\). The characterization is particularly simple in the \(d=2\) case. \\In addition, we characterize when the intuitive approach of the nearest EDM problem, solves our problem. In fact, we show that this happens if, and only if, the original distance element is \(0\), degenerate, and the perturbation is negative.
Hyaluronan, a widely distributed component of the extracellular matrix,
exists in a high molecular weight (native) form and lower molecular weight
form (HMW- and LMW-HA, respectively). These ...different forms of hyaluronan bind
to CD44 but elicit distinct effects on cellular function. A striking example
is the opposing effects of HMW- and LMW-HA on the proliferation of vascular
smooth muscle cells; the binding of HMW-HA to CD44 inhibits cell cycle
progression, whereas the binding of LMW-HA to CD44 stimulates cell cycle
progression. We now report that cyclin D1 is the primary target of LMW-HA in
human vascular smooth muscle cells, as it is for HMW-HA, and that the opposing
cell cycle effects of these CD44 ligands result from differential regulation
of signaling pathways to cyclin D1. HMW-HA binding to CD44 selectively
inhibits the GTP loading of Rac and Rac-dependent signaling to the cyclin D1
gene, whereas LMW-HA binding to CD44 selectively stimulates ERK activation and
ERK-dependent cyclin D1 gene expression. These data describe a novel mechanism
of growth control in which a ligand-receptor system generates opposing effects
on mitogenesis by differentially regulating signaling pathways to a common
cell cycle target. They also emphasize how a seemingly subtle change in matrix
composition can have a profound effect on cell proliferation.
Stents eluting anti-proliferative drugs limit restenosis, but drugs commonly used to date are relatively non-specific cytostatic agents which inhibit proliferation of intimal endothelial cells as ...well as medial smooth muscle cells and may thereby contribute to the clinical complications associated with angioplasty. In an effort to identify a more specific anti-proliferative agent, we compared the effects of rapamycin to those of cicaprost, a mimetic of the naturally occurring anti-mitogen, PGI
2. Rapamycin and cicaprost were both strongly anti-mitogenic in vascular smooth muscle cells (VSMCs). But unlike rapamycin, cicaprost did not inhibit mitogenesis in aortic endothelial cells even when used at concentrations >10-fold higher than its ED
50 for VSMCs. Similarly, both rapamycin and cicaprost have been reported to regulate levels of the cdk inhibitor, p27
kip1. But rapamycin remained anti-mitogenic in p27
kip1-null VSMCs whereas the anti-mitogenic effect of cicaprost was completely dependent on p27
kip1. We conclude that stable PGI
2 mimetics may be highly specific inhibitors of p27
kip1-dependent VSMC proliferation after vascular injury.
Pneumoperitoneum in the presence of acute abdominal pain is well recognised as an indication for laparotomy. We present a case of acute abdominal pain in the presence of an incidental ...pneumoperitoneum secondary to the rupture of pneumatosis intestinalis. We will discuss the importance of clinical context in the diagnosis and management of pneumoperitoneum and pneumatosis intestinalis.
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