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Article: Curcumin: a natural substance with potential efficacy in Alzheimer's disease.

Potter, Pamela E

2013 Volume 5, Page(s) 23–31

Abstract: Curcumin is a component of turmeric, a spice used in many types of cooking. Epidemiological evidence suggesting that populations that eat food with a substantial amount of curcumin were at lower risk of Alzheimer's disease (AD) led to the idea that this ... ...

Abstract	Curcumin is a component of turmeric, a spice used in many types of cooking. Epidemiological evidence suggesting that populations that eat food with a substantial amount of curcumin were at lower risk of Alzheimer's disease (AD) led to the idea that this compound might have a neuroprotective effect. Curcumin has substantial antioxidant and anti-inflammatory effects, and is being used as a potential preventative agent or treatment for many types of cancer. There is evidence to suggest that the addition of curcumin to cultured neuronal cells decreases brain inflammation and protects against β-amyloid-induced neurotoxicity. Curcumin also protects against toxicity when β-amyloid is administered to produce animal models of AD. Curcumin decreases β-amyloid formation from amyloid precursor protein, and also inhibits aggregation of β-amyloid into pleated sheets. Studies in transgenic mice with overproduction of β-amyloid demonstrate a neuroprotective effect of curcumin as well. Cognitive function was also improved in these animal models. Clinical trials of curcumin in AD have not been very promising. It is possible that this is due to poor oral bioavailability of curcumin in humans, and thus several approaches are being developed to improve delivery systems or to create analogs that will mimic the neuroprotective effects and easily reach the brain. The lack of efficacy of curcumin in humans with AD may also result from treating for too short a time or starting treatment too late in the course of the disease, where substantial neuronal death has already occurred and cannot be reversed. Curcumin may be beneficial in protecting against development or progression of AD if taken over the long term and started before symptoms of AD become apparent.
Language	English
Publishing date	2013-05-02
Publishing country	New Zealand
Document type	Journal Article ; Review
ZDB-ID	2587465-2
ISSN	1179-1454
ISSN	1179-1454
DOI	10.2147/JEP.S26803
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Article ; Online: Investigational medications for treatment of patients with Alzheimer disease.

Potter, Pamela E

The Journal of the American Osteopathic Association

2010 Volume 110, Issue 9 Suppl 8, Page(s) S27–36

Abstract: Development of effective treatments for patients with Alzheimer disease has been challenging. Currently approved treatments include acetylcholinesterase inhibitors and the N-methyl-D-aspartate receptor antagonist memantine hydrochloride. To investigate ... ...

Abstract	Development of effective treatments for patients with Alzheimer disease has been challenging. Currently approved treatments include acetylcholinesterase inhibitors and the N-methyl-D-aspartate receptor antagonist memantine hydrochloride. To investigate treatments in development for patients with Alzheimer disease, the author conducted a review of the literature. New approaches for treatment or prevention focus on several general areas, including cholinergic receptor agonists, drugs to decrease β-amyloid and tau levels, antiinflammatory agents, drugs to increase nitric oxide and cyclic guanosine monophosphate levels, and substances to reduce cell death or promote cellular regeneration. The author focuses on medications currently in clinical trials. Cholinergic agents include orthostatic and allosteric muscarinic M1 agonists and nicotinic receptor agonists. Investigational agents that target β-amyloid include vaccines, antibodies, and inhibitors of β-amyloid production. Anti-inflammatory agents, including nonsteroidal anti-inflammatory drugs, the natural product curcumin, and the tumor necrosis factor α inhibitor etanercept, have also been studied. Some drugs currently approved for other uses may also show promise for treatment of patients with Alzheimer disease. Results of clinical trials with many of these investigational drugs have been disappointing, perhaps because of their use with patients in advanced stages of Alzheimer disease. Effective treatment may need to begin earlier-before neurodegeneration becomes severe enough for symptoms to appear.
MeSH term(s)	Alzheimer Disease/drug therapy ; Alzheimer Vaccines ; Amyloid Precursor Protein Secretases/antagonists & inhibitors ; Amyloid Precursor Protein Secretases/metabolism ; Amyloid beta-Peptides/drug effects ; Anti-Inflammatory Agents/therapeutic use ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Antibodies, Monoclonal/therapeutic use ; Cholinergic Agents/therapeutic use ; Drugs, Investigational ; Etanercept ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ; Immunoglobulin G/therapeutic use ; Indoles/therapeutic use ; Nicotinic Antagonists/therapeutic use ; Phosphodiesterase 5 Inhibitors/therapeutic use ; Receptors, Tumor Necrosis Factor/therapeutic use ; tau Proteins/drug effects
Chemical Substances	Alzheimer Vaccines ; Amyloid beta-Peptides ; Anti-Inflammatory Agents ; Anti-Inflammatory Agents, Non-Steroidal ; Antibodies, Monoclonal ; Cholinergic Agents ; Drugs, Investigational ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Immunoglobulin G ; Indoles ; Nicotinic Antagonists ; Phosphodiesterase 5 Inhibitors ; Receptors, Tumor Necrosis Factor ; tau Proteins ; Amyloid Precursor Protein Secretases (EC 3.4.-) ; latrepirdine (OD9237K1Z6) ; Etanercept (OP401G7OJC)
Language	English
Publishing date	2010-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	410350-6
ISSN	1945-1997 ; 0003-0287 ; 0098-6151
ISSN (online)	1945-1997
ISSN	0003-0287 ; 0098-6151
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Article ; Online: Presence of Neck or Shoulder Pain Following Sport-Related Concussion Negatively Influences Recovery.

Provance, Aaron J / Howell, David R / Potter, Morgan N / Wilson, Pamela E / D'Lauro, Allison M / Wilson, Julie C

Journal of child neurology

2020 Volume 35, Issue 7, Page(s) 456–462

Abstract: Our objective was to examine the effect of current neck or shoulder pain on concussion outcomes. Variables included symptom resolution and return-to-sport time, symptom severity, amount of school missed, and sleep disturbances. Three hundred twelve ... ...

Abstract	Our objective was to examine the effect of current neck or shoulder pain on concussion outcomes. Variables included symptom resolution and return-to-sport time, symptom severity, amount of school missed, and sleep disturbances. Three hundred twelve patients (37% female; median age = 15.0 years; evaluated median = 9 days postinjury) reported experiencing current neck or shoulder pain at initial evaluation, and 268 did not (31% female; median age = 14.7 years; evaluated median = 8 days postinjury). Neck or shoulder pain was associated with longer symptom resolution time (β = 6.38, 95% confidence interval [CI] = 2.44, 10.31;
MeSH term(s)	Adolescent ; Athletic Injuries/complications ; Brain Concussion/complications ; Female ; Humans ; Male ; Neck Pain/complications ; Prospective Studies ; Return to Sport/statistics & numerical data ; Risk Factors ; Severity of Illness Index ; Shoulder Pain/complications
Language	English
Publishing date	2020-03-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	639288-x
ISSN	1708-8283 ; 0883-0738
ISSN (online)	1708-8283
ISSN	0883-0738
DOI	10.1177/0883073820909046
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Article ; Online: Early physical activity and clinical outcomes following pediatric sport-related concussion.

Wilson, Julie C / Kirkwood, Michael W / Potter, Morgan N / Wilson, Pamela E / Provance, Aaron J / Howell, David R

Journal of clinical and translational research

2020 Volume 5, Issue 4, Page(s) 161–168

Abstract: Objective: The objective of the study was to evaluate the clinical outcomes among patients who did and did not report engaging in early physical activity (PA) following sport-related concussion.: Methods: We evaluated pediatric patients seen within ... ...

Abstract	Objective: The objective of the study was to evaluate the clinical outcomes among patients who did and did not report engaging in early physical activity (PA) following sport-related concussion. Methods: We evaluated pediatric patients seen within 21 days of concussion. The independent variable was early PA engagement (since the injury and before initial clinical evaluation). Dependent variables included demographics, injury details, medical history, Health and Behavior Inventory (HBI) score, and balance, vestibular, and oculomotor function tests. Results: We examined data from 575 pediatric patients: Sixty-nine (12%) reported engaging in early PA (mean age=14.3±2.4 years; 30% female). The no PA group (mean age=14.5±2.4 years; 35% female) had significantly longer symptom resolution times than the early PA group (median= 16 [interquartile range (IQR)=8-24] vs. 10.5 [IQR=4-17] days; p=0.02). When controlling for pre-existing headache history and time from injury-evaluation time, the early PA group demonstrated lower odds of reporting current headache (adjusted odds ratio=0.14; 95% CI=0.07, 0.26), and reported lower symptom frequency ratings than the no PA group (b=-5.58, 95% CI=-8.94, -2.22). Conclusions: Patients who did not engage in early PA had longer symptom duration, greater odds of post-injury headache, and greater symptoms at initial clinical evaluation. We cannot determine if patients engaged in early PA due to the lower symptom burden and higher functioning at the time of assessment, or if early PA positively affected outcomes. However, as early PA was associated with better post-injury outcomes, clinicians may consider supervised and structured early PA programs as a method to improve clinical outcomes following concussion. Relevance for patients: Children and adolescents who were engaged in PA after concussion presented to a clinic with less severe symptoms and had symptoms that resolved sooner compared to those who did not engage in early PA after concussion.
Language	English
Publishing date	2020-04-16
Publishing country	Singapore
Document type	Journal Article
ZDB-ID	3019815-X
ISSN	2424-810X ; 2382-6533
ISSN (online)	2424-810X
ISSN	2382-6533
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Article ; Online: Sleep Problems and Melatonin Prescription After Concussion Among Youth Athletes.

Howell, David R / Potter, Morgan N / Provance, Aaron J / Wilson, Pamela E / Kirkwood, Michael W / Wilson, Julie C

Clinical journal of sport medicine : official journal of the Canadian Academy of Sport Medicine

2020 Volume 31, Issue 6, Page(s) 475–480

Abstract: Objectives: To examine the effect of sleep disturbances on concussion symptom recovery and to examine the effect of melatonin prescription on symptom improvement among concussed adolescents with sleep problems.: Design: Longitudinal test-retest.: ... ...

Abstract	Objectives: To examine the effect of sleep disturbances on concussion symptom recovery and to examine the effect of melatonin prescription on symptom improvement among concussed adolescents with sleep problems. Design: Longitudinal test-retest. Setting: Sports medicine clinic. Participants: Patients aged 8 to 18 years, diagnosed with a concussion, evaluated within 14 days after injury, and evaluated again 15 to 35 days after injury. Independent variables: We grouped patients based on whether they reported sleep disturbances within 14 days of injury. Main outcome measures: Outcome measures included symptom severity, headache severity, melatonin prescription, and the change in symptom severity between visits. Results: Two hundred twenty-five patients were included: 36% who reported sleep problems (44% female; age = 14.4 ± 2.0 years; evaluated 7.3 ± 3.8 and 23.2 ± 5.4 days after injury) and 64% who did not (32% female; age = 14.6 ± 2.3 years; evaluated 7.2 ± 3.4 and 23.0 ± 5.3 days after injury). Those with sleep problems reported higher symptom severity than those without across the 2 visits (22.1 ± 14.3 vs 14.6 ± 12.5; P < 0.001). There was no significant difference in the change in symptom severity between visits among those who received [median = 9-point improvement; interquartile range (IQR) = 1-14] and did not (median = 9, IQR = 2-18) receive a melatonin prescription (P = 0.80). Conclusions: Sleep problems among pediatric patients within 2 weeks of concussion are associated with more severe symptoms. Melatonin prescription was not associated with faster symptom recovery.
MeSH term(s)	Adolescent ; Athletes ; Athletic Injuries/complications ; Athletic Injuries/drug therapy ; Brain Concussion/complications ; Brain Concussion/drug therapy ; Child ; Female ; Humans ; Male ; Melatonin/therapeutic use ; Post-Concussion Syndrome/drug therapy ; Prescriptions ; Sleep Wake Disorders/drug therapy ; Sleep Wake Disorders/etiology
Chemical Substances	Melatonin (JL5DK93RCL)
Language	English
Publishing date	2020-10-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	1062530-6
ISSN	1536-3724 ; 1050-642X
ISSN (online)	1536-3724
ISSN	1050-642X
DOI	10.1097/JSM.0000000000000803
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Article ; Online: Clinical predictors of symptom resolution for children and adolescents with sport-related concussion.

Howell, David R / Potter, Morgan N / Kirkwood, Michael W / Wilson, Pamela E / Provance, Aaron J / Wilson, Julie C

Journal of neurosurgery. Pediatrics

2019 Volume 24, Issue 1, Page(s) 54–61

Abstract: Objective: The goal of this study was to determine which variables assessed during an initial clinical evaluation for concussion are independently associated with time until symptom resolution among pediatric patients.: Methods: Data collected from a ...

Abstract	Objective: The goal of this study was to determine which variables assessed during an initial clinical evaluation for concussion are independently associated with time until symptom resolution among pediatric patients. Methods: Data collected from a prospective clinical registry of pediatric patients with concussion were analyzed. The primary outcome variable was time from injury until symptom resolution. Predictor variables assessed within 10 days after injury included preinjury factors, Health and Behavior Inventory scores, headache severity, and balance, vestibular, and oculomotor test performances. The researchers used univariate Cox proportional models to identify potential predictors of symptom resolution time and constructed a multivariate Cox proportional hazards model in which total duration of concussion symptoms remained the outcome variable. Results: The sample consisted of 351 patients (33% female, mean age 14.6 ± 2.2 years, evaluated 5.6 ± 2.6 days after concussion). Univariate Cox proportional hazards models indicated that several variables were associated with a longer duration of symptoms, including headache severity (hazard ratio [HR] 0.90 [95% CI 0.85-0.96]), headache frequency (HR 0.83 [95% CI 0.71-0.96]), confusion (HR 0.79 [95% CI 0.69-0.92]), forgetfulness (HR 0.79 [95% CI 0.68-0.92]), attention difficulties (HR 0.83 [95% CI 0.72-0.96]), trouble remembering (HR 0.84 [95% CI 0.72-0.98]), getting tired often (HR 0.86 [95% CI 0.76-0.97]), getting tired easily (HR 0.86 [95% CI 0.76-0.98]), dizziness (HR 0.86 [95% CI 0.75-0.99]), and abnormal performance on the Romberg test (HR 0.59 [95% CI 0.40-0.85]). A multivariate Cox proportional hazards model indicated that an abnormal performance on the Romberg test was independently associated with a longer duration of symptoms (HR 0.65 [95% CI 0.44-0.98]; p = 0.038). Conclusions: For children and adolescents evaluated within 10 days after receiving a concussion, abnormal performance on the Romberg test was independently associated with a longer duration of symptoms during recovery. In line with findings of other recent studies investigating predictors of symptom resolution, postural stability tests may provide useful prognostic information for sports medicine clinicians.
MeSH term(s)	Adolescent ; Attention ; Brain Concussion/complications ; Brain Concussion/diagnosis ; Child ; Confusion/etiology ; Dizziness/etiology ; Fatigue/etiology ; Female ; Headache/etiology ; Health Behavior ; Health Status ; Humans ; Male ; Memory Disorders/etiology ; Motor Skills ; Postural Balance ; Proportional Hazards Models ; Recovery of Function ; Registries ; Sensation Disorders ; Symptom Assessment ; Time Factors ; Vestibular Function Tests
Language	English
Publishing date	2019-04-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	2403985-8
ISSN	1933-0715 ; 1933-0707
ISSN (online)	1933-0715
ISSN	1933-0707
DOI	10.3171/2018.11.PEDS18626
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Article ; Online: Enzyme replacement therapy and hematopoietic stem cell transplant: a new paradigm of treatment in Wolman disease.

Orphanet journal of rare diseases

2021 Volume 16, Issue 1, Page(s) 235

Abstract: Background: Wolman disease is a rare, lysosomal storage disorder in which biallelic variants in the LIPA gene result in reduced or complete lack of lysosomal acid lipase. The accumulation of the substrates; cholesterol esters and triglycerides, ... ...

Abstract	Background: Wolman disease is a rare, lysosomal storage disorder in which biallelic variants in the LIPA gene result in reduced or complete lack of lysosomal acid lipase. The accumulation of the substrates; cholesterol esters and triglycerides, significantly impacts cellular function. Untreated patients die within the first 12 months of life. Clinically, patients present severely malnourished, with diarrhoea and hepatosplenomegaly, many have an inflammatory phenotype, including with hemophagocytic lymphohistiocytosis (HLH). Hematopoietic stem cell transplant (HCT) had been historically the only treatment available but has a high procedure-related mortality because of disease progression and disease-associated morbidities. More recently, enzyme replacement therapy (ERT) with dietary substrate reduction (DSR) has significantly improved patient survival. However, ERT is life long, expensive and its utility is limited by anti-drug antibodies (ADA) and the need for central venous access. Results: We describe five Wolman disease patients diagnosed in infancy that were treated at Royal Manchester Children's Hospital receiving ERT with DSR then HCT-multimodal therapy. In 3/5 an initial response to ERT was attenuated by ADA with associated clinical and laboratory features of deterioration. 1/5 developed anaphylaxis to ERT and the other patient died post HCT with ongoing HLH. All patients received allogeneic HCT. 4/5 patients are alive, and both disease phenotype and laboratory parameters are improved compared to when they were on ERT alone. The gastrointestinal symptoms are particularly improved after HCT, with reduced diarrhoea and vomiting. This allows gradual structured normalisation of diet with improved tolerance of dietary fat. Histologically there are reduced cholesterol clefts, fewer foamy macrophages and an improved villous structure. Disease biomarkers also show improvement with ERT, immunotherapy and HCT. Three patients have mixed chimerism after HCT, indicating a likely engraftment-defect in this condition. Conclusion: We describe combined ERT, DSR and HCT, multimodal treatment for Wolman disease. ERT and DSR stabilises the sick infant and reduces the formerly described prohibitively high, transplant-associated mortality in this condition. HCT abrogates the problems of ERT, namely attenuating ADA, the need for continuing venous access, and continuing high cost drug treatment. HCT also brings improved efficacy, particularly evident in improved gastrointestinal function and histology. Multimodal therapy should be considered a new paradigm of treatment for Wolman disease patients where there is an attenuated response to ERT, and for all patients where there is a well-matched transplant donor, in order to improve long term gut function, tolerance of a normal diet and quality of life.
MeSH term(s)	Enzyme Replacement Therapy ; Hematopoietic Stem Cell Transplantation ; Humans ; Infant ; Quality of Life ; Sterol Esterase/therapeutic use ; Wolman Disease/therapy
Chemical Substances	Sterol Esterase (EC 3.1.1.13)
Language	English
Publishing date	2021-05-21
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2225857-7
ISSN	1750-1172 ; 1750-1172
ISSN (online)	1750-1172
ISSN	1750-1172
DOI	10.1186/s13023-021-01849-7
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Article ; Online: Embolization of percutaneous left atrial appendage closure devices: timing, management and clinical outcomes.

Eppinger, Sophie / Piayda, Kerstin / Galea, Roberto / Sandri, Marcus / Maarse, Moniek / Güner, Ahmet / Karabay, Can Y / Pershad, Ashish / Ding, Wern Y / Aminian, Adel / Akin, Ibrahim / Davtyan, Karapet V / Chugunov, Ivan A / Marijon, Eloi / Rosseel, Liesbeth / Schmidt, Thomas Robert / Amabile, Nicolas / Korsholm, Kasper / Lund, Juha /

Guerios, Enio / Amat-Santos, Ignacio J / Boccuzzi, Giacomo / Ellis, Christopher R / Sabbag, Avi / Ebelt, Henning / Clapp, Brian / Assa, Hana Vaknin / Levi, Amos / Ledwoch, Jakob / Lehmann, Sonja / Lee, Oh-Hyun / Mark, George / Schell, Wendy / Della Rocca, Domenico G / Natale, Andrea / de Backer, Ole / Kefer, Joelle / Esteban, Pablo P / Abelson, Mark / Ram, Pradhum / Moceri, Pamela / Galache Osuna, Jose G / Alvarez, Xavier Millán / Cruz-Gonzalez, Ignacio / de Potter, Tom / Ghassan, Moubarak / Osadchiy, Andrey / Chen, Weita / Goyal, Sandeep K / Giannini, Francesco / Rivero-Ayerza, Máximo / Afzal, Shazia / Jung, Christian / Skurk, Carsten / Langel, Martin / Spence, Mark / Merkulov, Evgeny / Lempereur, Mathieu / Shin, Seung Y / Mesnier, Jules / McKinney, Heather L / Schuler, Brian T / Armero, Sebastien / Gheorghe, Livia / Ancona, Marco B M / Santos, Lino / Mansourati, Jacques / Nombela-Franco, Luis / Nappi, Francesco / Kühne, Michael / Gaspardone, Achille / van der Pals, Jesper / Montorfano, Matteo / Fernández-Armenta, Juan / Harvey, James E / Rodés-Cabau, Josep / Klein, Norbert / Sabir, Sajjad A / Kim, Jung-Sun / Cook, Stephane / Kornowski, Ran / Saraste, Antti / Nielsen-Kudsk, Jens E / Gupta, Dhiraj / Boersma, Lucas / Räber, Lorenz / Sievert, Kolja / Sievert, Horst / Bertog, Stefan

Cardiovascular revascularization medicine : including molecular interventions

2024

Abstract: Background: Left atrial appendage (LAA) occluder embolization is an infrequent but serious complication.: Objectives: We aim to describe timing, management and clinical outcomes of device embolization in a multi-center registry.: Methods: Patient ... ...

Abstract	Background: Left atrial appendage (LAA) occluder embolization is an infrequent but serious complication. Objectives: We aim to describe timing, management and clinical outcomes of device embolization in a multi-center registry. Methods: Patient characteristics, imaging findings and procedure and follow-up data were collected retrospectively. Device embolizations were categorized according to 1) timing 2) management and 3) clinical outcomes. Results: Sixty-seven centers contributed data. Device embolization occurred in 108 patients. In 70.4 % of cases, it happened within the first 24 h of the procedure. The device was purposefully left in the LA and the aorta in two (1.9 %) patients, an initial percutaneous retrieval was attempted in 81 (75.0 %) and surgery without prior percutaneous retrieval attempt was performed in 23 (21.3 %) patients. Two patients died before a retrieval attempt could be made. In 28/81 (34.6 %) patients with an initial percutaneous retrieval attempt a second, additional attempt was performed, which was associated with a high mortality (death in patients with one attempt: 2.9 % vs. second attempt: 21.4 %, p < 0.001). The primary outcome (bailout surgery, cardiogenic shock, stroke, TIA, and/or death) occurred in 47 (43.5 %) patients. Other major complications related to device embolization occurred in 21 (19.4 %) patients. Conclusions: The majority of device embolizations after LAA closure occurs early. A percutaneous approach is often the preferred method for a first rescue attempt. Major adverse event rates, including death, are high particularly if the first retrieval attempt was unsuccessful. Condensed abstract: This dedicated multicenter registry examined timing, management, and clinical outcome of device embolization. Early embolization (70.4 %) was most frequent. As a first rescue attempt, percutaneous retrieval was preferred in 75.0 %, followed by surgical removal (21.3 %). In patients with a second retrieval attempt a higher mortality (death first attempt: 2.9 % vs. death second attempt: 24.1 %, p < 0.001) was observed. Mortality (10.2 %) and the major complication rate after device embolization were high.
Language	English
Publishing date	2024-02-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	2212113-4
ISSN	1878-0938 ; 1553-8389
ISSN (online)	1878-0938
ISSN	1553-8389
DOI	10.1016/j.carrev.2024.02.014
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Article ; Online: Enzyme replacement therapy and hematopoietic stem cell transplant

Orphanet Journal of Rare Diseases, Vol 16, Iss 1, Pp 1-

a new paradigm of treatment in Wolman disease

2021 Volume 14

Abstract: Abstract Background Wolman disease is a rare, lysosomal storage disorder in which biallelic variants in the LIPA gene result in reduced or complete lack of lysosomal acid lipase. The accumulation of the substrates; cholesterol esters and triglycerides, ... ...

Abstract	Abstract Background Wolman disease is a rare, lysosomal storage disorder in which biallelic variants in the LIPA gene result in reduced or complete lack of lysosomal acid lipase. The accumulation of the substrates; cholesterol esters and triglycerides, significantly impacts cellular function. Untreated patients die within the first 12 months of life. Clinically, patients present severely malnourished, with diarrhoea and hepatosplenomegaly, many have an inflammatory phenotype, including with hemophagocytic lymphohistiocytosis (HLH). Hematopoietic stem cell transplant (HCT) had been historically the only treatment available but has a high procedure-related mortality because of disease progression and disease-associated morbidities. More recently, enzyme replacement therapy (ERT) with dietary substrate reduction (DSR) has significantly improved patient survival. However, ERT is life long, expensive and its utility is limited by anti-drug antibodies (ADA) and the need for central venous access. Results We describe five Wolman disease patients diagnosed in infancy that were treated at Royal Manchester Children's Hospital receiving ERT with DSR then HCT—multimodal therapy. In 3/5 an initial response to ERT was attenuated by ADA with associated clinical and laboratory features of deterioration. 1/5 developed anaphylaxis to ERT and the other patient died post HCT with ongoing HLH. All patients received allogeneic HCT. 4/5 patients are alive, and both disease phenotype and laboratory parameters are improved compared to when they were on ERT alone. The gastrointestinal symptoms are particularly improved after HCT, with reduced diarrhoea and vomiting. This allows gradual structured normalisation of diet with improved tolerance of dietary fat. Histologically there are reduced cholesterol clefts, fewer foamy macrophages and an improved villous structure. Disease biomarkers also show improvement with ERT, immunotherapy and HCT. Three patients have mixed chimerism after HCT, indicating a likely engraftment-defect in this ...
Keywords	Enzyme replacement therapy (ERT) ; Dietary substrate reduction (DSR) ; Gene therapy ; Hematopoietic stem cell transplant (HCT) ; Hemophagocytic lymphohistiocytosis (HLH) ; Lysosomal storage disorders (LSD) ; Medicine ; R
Subject code	610
Language	English
Publishing date	2021-05-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
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Article: Readiness of nurse executives and leaders to advocate for health information systems supporting nursing.

Oakes, Mary / Frisch, Noreen / Potter, Pamela / Borycki, Elizabeth

Studies in health technology and informatics

2015 Volume 208, Page(s) 296–301

Abstract: Literature suggests that nurses at all levels remain unprepared to make use of full use of technologies required for current practice. Specifically, nurses lack sufficient background to engage with information systems, electronic records, and unit-level ... ...

Abstract	Literature suggests that nurses at all levels remain unprepared to make use of full use of technologies required for current practice. Specifically, nurses lack sufficient background to engage with information systems, electronic records, and unit-level and aggregated data that could support understanding of the contributions of nursing services to care and the development of best practice guidelines. Given that nursing leadership is needed in this area, the authors conducted a review of graduate nursing curricula preparing nurses to take on leadership, management and executive roles. Findings revealed that only 12 out of 36 graduate nursing programs on the west coast of the US and Canada required any content in informatics, and five more offered elective opportunities. Implications for education and practice are discussed.
Language	English
Publishing date	2015
Publishing country	Netherlands
Document type	Journal Article
ISSN	0926-9630
ISSN	0926-9630
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Inter-library loan at ZB MED