Lipid rescue of massive verapamil overdose: a case report

<p>Abstract</p> <p>Introduction</p> <p>Massive intentional verapamil overdose is a toxic ingestion which can cause multiorgan system failure and has no currently known antidote.</p> <p>Case Presentation</p> <p>The patient is a 41-year-old Caucasian woman who ingested 19.2 g of sustained release verapamil in a suicide attempt. Our patient became hypotensive requiring three high-dose vasopressors to maintain arterial pressure. She also developed acute respiratory failure, bradycardic ventricular rhythm necessitating continuous transvenous pacing, and anuric renal failure. Our patient was treated with intravenous calcium, bicarbonate, hyperinsulinemic euglycemic therapy and continuous venovenous hemodialysis without success. On the fourth day after hospital admission continuous intravenous lipid therapy was initiated. Within three hours of beginning lipid therapy, our patient's vasopressor requirement decreased by half. Within 24 hours, she was on minimal vasopressor support and regained an underlying junctional rhythm. After three days of lipid infusion, she no longer required inotropic agents to maintain blood pressure or pacing to maintain stable hemodynamics.</p> <p>Conclusions</p> <p>Intravenous fat emulsion therapy may be an effective antidote for massive verapamil toxicity.</p

Key components of external facilitation in an acute stroke quality improvement collaborative in the Veterans Health Administration

Background Facilitation is a key component for successful implementation in several implementation frameworks; however, there is a paucity of research specifying this component. As part of a stroke quality improvement intervention in the Veterans Health Administration (VHA), facilitation plus data feedback was compared to data feedback alone in 11 VA medical facilities. The objective of this study was to elucidate upon the facilitation components of the stroke quality improvement. Methods We conducted a secondary evaluation of external facilitation using semi-structured interviews. Five facilitators and two program directors were interviewed. Qualitative analysis was performed on transcribed interviews to gain an understanding of the role and activities of external facilitators during the on-site and telephone facilitation. Quantitative frequencies were calculated from the self-reported time spent in facilitation tasks by facilitators. Results The external facilitators saw their role as empowering the clinical teams to take ownership of the process changes at the clinical sites to improve their performance quality. To fulfill this role, they reported engaging in a number of core tasks during telephone and on-site visits including: assessing the context in which the teams were currently operating, guiding the clinical teams through their planned changes and use of process improvement tools, identifying resources and making referrals, holding teams accountable for plan implementation with on-site visits, and providing support and encouragement to the teams. Time spent in facilitation activities changed across time from guiding change (early) to supporting efforts made by the clinical teams (later). Facilitation activity transitioned to more monitoring, problem solving, and intentional work to hand over the clinical improvement process to the site teams with the coach’s role being increasingly that of a more distant consultant. Overall, this study demonstrated that external facilitation is not an event but rather a process where relationships and responsibilities evolve over time. Conclusions This study shows that external facilitation involves core elements related to communication, relationship building, methods training, monitoring performance over time, and facilitating team-based problem solving. Importantly, this work demonstrates the fluid nature of external facilitation over time, as teams learn, grow, change, and experience changing contexts

Genetically-predicted life-long lowering of low-density lipoprotein cholesterol is associated with decreased frailty: A Mendelian randomization study in UK biobank

BACKGROUND: High circulating low-density lipoprotein cholesterol (LDL-C) is a major risk factor for atherosclerosis and age-associated cardiovascular events. Long-term dyslipidaemia could contribute to the development of frailty in older individuals through its role in determining cardiovascular health and potentially other physiological pathways. METHODS: We conducted Mendelian randomization (MR) analyses using genetic variants to estimate the effects of long-term LDL-C modification on frailty in UK Biobank (n = 378,161). Frailty was derived from health questionnaire and interview responses at baseline when participants were aged 40 to 69 years, and calculated using an accumulation-of-deficits approach, i.e. the frailty index (FI). Several aggregated instrumental variables (IVs) using 50 and 274 genetic variants were constructed from independent single-nucleotide polymorphisms (SNPs) to instrument circulating LDL-C concentrations. Specific sets of variants in or near genes that encode six lipid-lowering drug targets (HMGCR, PCSK9, NPC1L1, APOB, APOC3, and LDLR) were used to index effects of exposure to related drug classes on frailty. SNP-LDL-C effects were available from previously published studies. SNP-FI effects were obtained using adjusted linear regression models. Two-sample MR analyses were performed with the IVs as instruments using inverse-variance weighted, MR-Egger, weighted median, and weighted mode methods. To address the stability of the findings, MR analyses were also performed using i) a modified FI excluding the cardiometabolic deficit items and ii) data from comparatively older individuals (aged ≥60 years) only. Several sensitivity analyses were also conducted. FINDINGS: On average 0.14% to 0.23% and 0.16% to 0.31% decrements in frailty were observed per standard deviation reduction in LDL-C exposure, instrumented by the general IVs consisting of 50 and 274 variants, respectively. Consistent, though less precise, associations were observed in the HMGCR-, APOC3-, NPC1L1-, and LDLR-specific IV analyses. In contrast, results for PCSK9 were in the same direction but more modest, and null for APOB. All sensitivity analyses produced similar findings. INTERPRETATION: A genetically-predicted life-long lowering of LDL-C is associated with decreased frailty in midlife and older age, representing supportive evidence for LDL-C's role in multiple health- and age-related pathways. The use of lipid-lowering therapeutics with varying mechanisms of action may differ by the extent to which they provide overall health benefits

Expressivity of parameterized and data-driven representations in quality diversity search

Algorithms and the Foundations of Software technolog

Olanzapine and pulmonary embolism, a rare association: a case report

Venous thromboembolism is a very common pathological process for which there are many well known (and less well-known) predisposing factors. Likewise, olanzapine is a commonly used anti-psychotic medication

Changes in cephalometric "A" point with maxillary protraction

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Transcriptional activation of endothelial cells by TGFβ coincides with acute microvascular plasticity following focal spinal cord ischaemia/reperfusion injury

Microvascular dysfunction, loss of vascular support, ischaemia and sub-acute vascular instability in surviving blood vessels contribute to secondary injury following SCI (spinal cord injury). Neither the precise temporal profile of the cellular dynamics of spinal microvasculature nor the potential molecular effectors regulating this plasticity are well understood. TGFβ (transforming growth factor β) isoforms have been shown to be rapidly increased in response to SCI and CNS (central nervous system) ischaemia, but no data exist regarding their contribution to microvascular dysfunction following SCI. To examine these issues, in the present study we used a model of focal spinal cord ischaemia/reperfusion SCI to examine the cellular response(s) of affected microvessels from 30 min to 14 days post-ischaemia. Spinal endothelial cells were isolated from affected tissue and subjected to focused microarray analysis of TGFβ-responsive/related mRNAs 6 and 24 h post-SCI. Immunohistochemical analyses of histopathology show neuronal disruption/loss and astroglial regression from spinal microvessels by 3 h post-ischaemia, with complete dissolution of functional endfeet (loss of aquaporin-4) by 12 h post-ischaemia. Coincident with this microvascular plasticity, results from microarray analyses show 9 out of 22 TGFβ-responsive mRNAs significantly up-regulated by 6 h post-ischaemia. Of these, serpine 1/PAI-1 (plasminogen-activator inhibitor 1) demonstrated the greatest increase (>40-fold). Furthermore, uPA (urokinase-type plasminogen activator), another member of the PAS (plasminogen activator system), was also significantly increased (>7.5-fold). These results, along with other select up-regulated mRNAs, were confirmed biochemically or immunohistochemically. Taken together, these results implicate TGFβ as a potential molecular effector of the anatomical and functional plasticity of microvessels following SCI