Aducanumab: 4 in 10 high dose trial participants experienced brain swelling or bleeding

ObjectiveIGF levels, their binding proteins (IGFBPs) and high-dose statin therapy have been linked to the development of diabetes. We aimed to identify whether atorvastatin caused dose-related changes in IGF proteins.Design and methodsWe measured IGF1, IGF2, IGFBP1 and IGFBP3 concentrations at baseline, 6 and 12 months in Protection Against Nephropathy in Diabetes with Atorvastatin trial participants with type 2 diabetes randomised to 10 mg (n=59) vs 80 mg (n=60) of atorvastatin (n=119; mean (s.d.): age 64 (10) years; 83% male; HbA1c 61 (10) mmol/mol; blood pressure 131/73 mmHg).ResultsAtorvastatin was associated with overall reductions in circulating IGF1, IGF2 and IGFBP3 concentrations (P<0.05 for all changes). The adjusted mean (95% CI) between-group differences that indicate dose-related changes in IGF proteins were not significant for IGF1: −3 (−21 to 14) ng/ml; IGF2: −23 (−65 to 18) ng/ml and IGFBP3: −0.34 (−0.71 to 0.03) μg/ml, negative values indicating numerically greater lowering with high dose. The IGFBP1 concentration did not change with atorvastatin therapy overall but the adjusted mean (95% CI) between-group difference indicating a dose-related change in log IGFBP1 was highly significant −0.41 (−0.69 to 0.13, P=0.004).ConclusionIGF1, IGF2 and IGFBP3 concentrations decreased following atorvastatin therapy. A differential effect of low- vs high-dose atorvastatin on IGFBP1 concentrations was observed with likely implications for IGF bioavailability. The dose-related differential impact of atorvastatin treatment on concentration of IGF proteins merits investigation as a mechanism to explain the worsening of glucose tolerance with statin therapy.

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Abstract 19591: Long-term Renal Function Following Worsening Renal Function Precipitated by Aggressive Diuresis: Insights From the DOSE Trial Limited Dataset

Circulation ◽

10.1161/circ.132.suppl_3.19591 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Jennifer Simon ◽

Isaac E Hall ◽

Chukwuma O Onyebeke ◽

Jennifer Schaub ◽

Meredith A Brisco ◽

...

Keyword(s):

Renal Function ◽

Low Dose ◽

Loop Diuretic ◽

Acute Decompensated Heart Failure ◽

High Dose ◽

Dose Strategy ◽

Renal Outcomes ◽

Worsening Renal Function ◽

Dose Trial

Background: Worsening renal function (WRF) is a common complication of the treatment of acute decompensated heart failure and can be precipitated by aggressive diuresis. The DOSE trial randomized patients to a high vs. low intensity loop diuretic strategy. Notably, the rate of WRF during the 72-hour intervention period was increased with the high dose strategy but post-discharge non-renal outcomes were similar. However, the long term renal outcomes in patients with WRF precipitated by aggressive diuresis have not been described. Objective: To determine the long term renal outcomes of patients with WRF in the high and low dose arms of the DOSE trial. Methods: Participants of the DOSE trial with data on renal function at baseline and 60 days were studied. To maximize the number of events, WRF was defined as any worsening in estimated glomerular filtration rate (eGFR) from randomization to 72 hours. Results: In total, 224 patients (72.7%) in the DOSE trial population had data on renal function available at baseline and 60 days. Of this subset, 102 patients (45.5%) experienced WRF at 72 hours and these patients had an average 16.7 ± 12.0% worsening in eGFR. In patients with WRF that were randomized to the high dose strategy (n=58) eGFR improved from 44.9 ± 22.4 ml/min/1.73m 2 at 72 hours to 53.1 ± 30.0 ml/min/1.73m 2 (p<0.001) at 60 days. Notably, eGFR was not significantly different at 60 days compared to baseline in these patients (p=0.18). However, in patients with WRF randomized to the low dose strategy (n=44), eGFR did not significantly improve from 72 hours to 60 days (46.4 ± 18.1 ml/min/1.73m 2 to 48.8 ± 22.4 ml/min/1.73m 2 , p=0.34) and eGFR at 60 days was significantly worse than baseline (p=0.02). Conclusion: In the DOSE trial, WRF precipitated by an aggressive loop diuretic strategy was transient and not associated with worse eGFR at 60 days whereas WRF in the absence of aggressive diuresis was associated with long term decline in renal function. The mechanism underlying WRF may be important in driving long term renal outcomes.

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Rare case of Hashimoto’s encephalitis mimicking grief reaction

BMJ Case Reports ◽

10.1136/bcr-2018-227190 ◽

2019 ◽

Vol 12 (1) ◽

pp. e227190

Author(s):

Angeliki Giannopoulou ◽

Sajjad Ahmad ◽

Chandranath Sarkar ◽

Atul Kalhan

Keyword(s):

Cerebrospinal Fluid ◽

Antiviral Therapy ◽

Cognitive Functions ◽

Rare Case ◽

High Dose ◽

Brain Swelling ◽

Level Of Consciousness ◽

Clonic Seizures ◽

Global Brain ◽

Rare Diagnosis

A 46-year-old woman was admitted with tonic-clonic seizures. She was noticed to be withdrawn and low in mood for few months. She had reduced level of consciousness with hyper-reflexia and myoclonus. Metabolic, vasculitic, autoimmune, paraneoplastic and septic screen were normal. Lumbar puncture showed raised protein in the cerebrospinal fluid but the cytology, bacterial and viral screens were negative. A CT of the head revealed global brain swelling consistent with encephalitis which was empirically treated with antibiotics and antiviral therapy. Despite this she continued to have altered sensorium. She had moderately raised titres of antithyroid peroxidise antibodies suggestive of an underlying diagnosis of Hashimoto’s encephalitis. She displayed a significant improvement in her cognitive functions with high-dose steroids which was further in keeping with this rare diagnosis.

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Mixed-model analysis of incomplete longitudinal data from a high-dose trial of tacrine (cognex®) in alzheimer's patients

Journal of Biopharmaceutical Statistics ◽

10.1080/10543409608835122 ◽

1996 ◽

Vol 6 (1) ◽

pp. 59-67 ◽

Cited By ~ 10

Author(s):

Fraser Smith

Keyword(s):

Longitudinal Data ◽

Mixed Model ◽

Model Analysis ◽

High Dose ◽

Mixed Model Analysis ◽

Dose Trial

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Arteriovenous Malformation in the Territory of the Occluded Middle Cerebral Artery with Massive Intraoperative Brain Swelling: Case Report

Neurosurgery ◽

10.1227/00006123-198505000-00013 ◽

1985 ◽

Vol 16 (5) ◽

pp. 660-662 ◽

Cited By ~ 13

Author(s):

Nobuhiko Aoki ◽

Hiroshi Mizutani

Keyword(s):

Case Report ◽

Arteriovenous Malformation ◽

Middle Cerebral Artery ◽

Cerebral Artery ◽

Rare Case ◽

High Dose ◽

Brain Swelling ◽

Increased Intracranial Pressure ◽

Main Trunk ◽

Barbiturate Therapy

Abstract We present an extremely rare case of an arteriovenous malformation (AVM) in the territory of the middle cerebral artery, the main trunk of which was occluded asymptomatically. Immediately after an uneventful excision of the entire AVM, massive brain swelling occurred unexpectedly and was treated successfully with high dose barbiturate therapy associated with other standard measures of controlling increased intracranial pressure. The underlying pathophysiological mechanisms leading to the massive intraoperative brain swelling in this case are discussed.

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Electron Beam Damage of Biomolecules Assessed by Energy Loss Spectroscopy

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100069855 ◽

1978 ◽

Vol 36 (3) ◽

pp. 61-69

Author(s):

M. Isaacson ◽

M.L. Collins ◽

M. Listvan

Keyword(s):

Electron Microscopy ◽

Radiation Damage ◽

Structural Integrity ◽

Analytical Electron Microscopy ◽

High Dose ◽

Dose Rates ◽

Special Cases ◽

Analytical Electron ◽

Atom Migration ◽

Beam Damage

Over the past five years it has become evident that radiation damage provides the fundamental limit to the study of blomolecular structure by electron microscopy. In some special cases structural determinations at very low doses can be achieved through superposition techniques to study periodic (Unwin & Henderson, 1975) and nonperiodic (Saxton & Frank, 1977) specimens. In addition, protection methods such as glucose embedding (Unwin & Henderson, 1975) and maintenance of specimen hydration at low temperatures (Taylor & Glaeser, 1976) have also shown promise. Despite these successes, the basic nature of radiation damage in the electron microscope is far from clear. In general we cannot predict exactly how different structures will behave during electron Irradiation at high dose rates. Moreover, with the rapid rise of analytical electron microscopy over the last few years, nvicroscopists are becoming concerned with questions of compositional as well as structural integrity. It is important to measure changes in elemental composition arising from atom migration in or loss from the specimen as a result of electron bombardment.

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Electron-diffraction studies in synthetic polymer materials

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100075579 ◽

1983 ◽

Vol 41 ◽

pp. 362-365

Author(s):

D.T. Grubb

Keyword(s):

Electron Diffraction ◽

Synthetic Polymer ◽

Polymer Materials ◽

Crystallographic Structure ◽

High Dose ◽

Electron Dose ◽

Dose Rates ◽

First Case ◽

Diffraction Patterns ◽

The Many

Diffraction studies in polymeric and other beam sensitive materials may bring to mind the many experiments where diffracted intensity has been used as a measure of the electron dose required to destroy fine structure in the TEM. But this paper is concerned with a range of cases where the diffraction pattern itself contains the important information.In the first case, electron diffraction from paraffins, degraded polyethylene and polyethylene single crystals, all the samples are highly ordered, and their crystallographic structure is well known. The diffraction patterns fade on irradiation and may also change considerably in a-spacing, increasing the unit cell volume on irradiation. The effect is large and continuous far C94H190 paraffin and for PE, while for shorter chains to C 28H58 the change is less, levelling off at high dose, Fig.l. It is also found that the change in a-spacing increases at higher dose rates and at higher irradiation temperatures.

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