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Impact of LDL Cholesterol on Microvascular Versus Macrovascular Disease: A Mendelian Randomization Study.
Emanuelsson, F, Nordestgaard, BG, Tybjærg-Hansen, A, Benn, M
Journal of the American College of Cardiology. 2019;(11):1465-1476
Abstract
BACKGROUND Low-density lipoprotein cholesterol (LDL-C) is causally associated with a high risk of coronary artery disease. Whether this also holds for a spectrum of peripheral vascular diseases is unknown. OBJECTIVES The purpose of this study was to determine whether high LDL-C causally relates to risk of retinopathy, neuropathy, chronic kidney disease (CKD), and peripheral arterial disease (PAD) in the general population. METHODS One-sample Mendelian randomization (MR) of 116,419 Danish individuals, 2-sample MR on summary-level data from the Global Lipid Genetics Consortium (GLGC) (n = 94,595) and the UK Biobank (n = 408,455), and meta-analysis of randomized statin trials (n = 64,134) were performed. RESULTS Observationally, high LDL-C did not associate with high risk of retinopathy or neuropathy. There were stepwise increases in risk of CKD and PAD with higher LDL-C (both p for trend <0.001), with hazard ratios of 1.05 (95% confidence interval [CI]: 0.97 to 1.13) for CKD, and 1.41 (95% CI: 1.23 to 1.62) for PAD in individuals with LDL-C above the 95th percentile versus below the 50th percentile. In genetic, causal analyses in the Copenhagen studies, the risk ratio of disease for a 1 mmol/l higher LDL-C was 1.06 (95% CI: 0.24 to 4.58) for retinopathy, 1.05 (95% CI: 0.64 to 1.72) for neuropathy, 3.83 (95% CI: 2.00 to 7.34) for CKD, and 2.09 (95% CI: 1.30 to 2.38) for PAD. Summary-level data from the GLGC and the UK Biobank for retinopathy, neuropathy, and PAD gave similar results. For CKD, a 1-mmol/l lower LDL-C conferred a higher eGFR of 1.95 ml/min/1.73 m2 (95% CI: 1.88 to 2.02 ml/min/1.73 m2) observationally, 5.92 ml/min/1.73 m2 (95% CI: 4.97 to 6.86 ml/min/1.73 m2) genetically, and 2.69 ml/min/1.73 m2 (95% CI: 1.48 to 3.94 ml/min/1.73 m2) through statin therapy. CONCLUSIONS High LDL-C was not causally associated with risk of retinopathy and neuropathy; however, high LDL-C was observationally and genetically associated with high risks of PAD and CKD, suggesting that LDL-C is causally involved in the pathogenesis of these diseases.
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2.
The drooling reduction intervention trial (DRI): a single blind trial comparing the efficacy of glycopyrronium and hyoscine on drooling in children with neurodisability.
Parr, JR, Weldon, E, Pennington, L, Steen, N, Williams, J, Fairhurst, C, O'Hare, A, Lodh, R, Colver, A
Trials. 2014;:60
Abstract
BACKGROUND Drooling saliva is a common problem in children with neurodevelopmental disorders. The negative consequences of drooling include skin breakdown, dehydration, and damage to clothing and equipment. Children and families often suffer social embarrassment due to drooling. There is no evidence about the relative effectiveness, side effect profiles or patient acceptability of the two medications most commonly used to reduce drooling - glycopyrronium and hyoscine. Consequently, there is no consensus or guideline to aid clinical decisions about which drug to use, and at what dose. METHODS/DESIGN A multi-centre, randomised trial of treatment with glycopyrronium or hyoscine in children with problematic drooling and non-progressive neurodisability. Ninety children aged between 3 and 15 years who have never received medication for drooling will be stratified by severity of drooling and care centre. Randomisation to receive treatment with glycopyrronium or hyoscine will be computer generated from the trial randomisation website. Dose adjustment and side effect monitoring will occur via telephone consultation. Medication arm will be known to participants and clinicians but not the Trial Outcome Assessor.The primary outcome measure is the Drooling Impact Scale score at four weeks, at which time all children will be on the maximum tolerated dose of their medication. Secondary outcome measures include change in Drooling Impact Scale score between baseline, 4, 12 and 52 weeks, change in Drooling Severity and Frequency Scale score and difference between groups in the Treatment Satisfaction Questionnaire for Medication score. A structured interview with children and young people of sufficient age, cognitive and communication ability will explore their perceptions of drooling and the effectiveness and acceptability of the medications. DISCUSSION The primary objective of the study is to identify whether glycopyrronium or hyoscine is more effective in treating drooling in children with non-progressive neurodisability. The study will also determine which medications at what doses are most acceptable and have fewest side effects. This information will be used to develop evidence based guidance to inform the medical treatment of drooling. DRI TRIAL REGISTRATION Current Controlled Trials: ISRCTN75287237.EUDRACT 2013-000863-94.Medicines and Healthcare products Regulatory Agency (MHRA): 17136/0264/001-0003.
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3.
Aluminium exposure from parenteral nutrition in preterm infants and later health outcomes during childhood and adolescence.
Fewtrell, MS, Edmonds, CJ, Isaacs, E, Bishop, NJ, Lucas, A
The Proceedings of the Nutrition Society. 2011;(3):299-304
Abstract
Aluminium is the most common metallic element, but has no known biological role. It accumulates in the body when protective gastrointestinal mechanisms are bypassed, renal function is impaired, or exposure is high - all of which apply frequently to preterm infants. Recognised clinical manifestations of aluminium toxicity include dementia, anaemia and bone disease. Parenteral nutrition (PN) solutions are liable to contamination with aluminium, particularly from acidic solutions in glass vials, notably calcium gluconate. When fed parenterally, infants retain >75% of the aluminium, with high serum, urine and tissue levels. Later health effects of neonatal intravenous aluminium exposure were investigated in a randomised trial comparing standard PN solutions with solutions specially sourced for low aluminium content. Preterm infants exposed for >10 d to standard solutions had impaired neurologic development at 18 months. At 13-15 years, subjects randomised to standard PN had lower lumbar spine bone mass; and, in non-randomised analyses, those with neonatal aluminium intake above the median had lower hip bone mass. Given the sizeable number of infants undergoing intensive care and still exposed to aluminium via PN, these findings have contemporary relevance. Until recently, little progress had been made on reducing aluminium exposure, and meeting Food and Drug Administration recommendations (<5 μg/kg per d) has been impossible in patients <50 kg using available products. Recent advice from the UK Medicines and Healthcare regulatory Authority that calcium gluconate in small volume glass containers should not be used for repeated treatment in children <18 years, including preparation of PN, is an important step towards addressing this problem.
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4.
Analgesic transition after remifentanil-based anesthesia in neurosurgery. A comparison of sufentanil and tramadol.
Cafiero, T, Burrelli, R, Latina, P, Mastronardi, P
Minerva anestesiologica. 2004;(1-2):45-52
Abstract
AIM: Transition from the end of remifentanil infusion and postoperative analgesia must be planned carefully owing to remifentanil's (R) rapid offset. Intraoperative morphine has been used for the transition to postoperative analgesia following remifentanil-based anesthesia. Sufentanil (S) is a very potent opioid with high micro-receptor affinity, a much wider therapeutic index and a lower fractional receptor occupancy. These pharmacological and dynamics features make sufentanil an interesting alternative to morphine for immediate postoperative analgesia. EXPERIMENTAL DESIGN perspective, randomized, single blinded and comparative study. Institution: neurosurgical operating theatre at University. PATIENTS 96 patients, aging from 25 to 67 years, ASA class I-III, undergoing neurosurgical operations, were studied. INTERVENTIONS AND MEASUREMENTS the anesthetic management was: premedication: atropine 0.01 microg kg(-1) + remifentanil 0.20 microg kg(-1) min(-1); induction: propofol 2.0 microg kg(-1) + cisatracurium 0.15 microg kg(-1); maintenance: sevoflurane 0.8% + remifentanil (titrated infusion) cisatracurium. All patients received ketorolac 30 mg i.v. 1 hour before the end of surgery and ketorolac (60-90 mg) + tramadol (200-300 mg) by elastomeric pump; patients were divided into 2 groups: group T receiving tramadol 100 mg and group S receiving a bolus dose of sufentanil 0.10 microg kg(-1), 30 and 15 minutes before the end of surgery respectively. Recovery time, postoperative analgesia evaluated by VAS, cardiocirculatory parameters and side effects like nausea, vomiting, shivering, muscle rigidity, sedation and respiratory depression were recorded. RESULTS VAS was significantly lower in Group S. Recovery time was shorter in Group T than in Group S (8.8 +/- 3.6 vs 11.6 +/- 4.6 min), no statistically significant differences between groups as regards nausea, vomiting and shivering. Short-lasting respiratory depression was detected in 3 cases in Group S. CONCLUSION At the emergence much better control of the transition phase in patients treated with sufentanil: smooth recovery with better tolerability of the endotracheal tube; efficacious analgesia along with cardiocirculatory stability.
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5.
[Neurogenic dysphagia: physiology, physiopathology and rehabilitative treatment].
Patti, F, Emmi, N, Restivo, DA, Liberto, A, Pappalardo, A, Torre, LM, Reggio, A
La Clinica terapeutica. 2002;(6):403-19
Abstract
Swallowing is both a voluntary than a reflex function. It consist in transporting feeding from mouth to the stomach. Swallowing function occurs with very frequency during the day and needs complex neuromuscular coordination. Several neurologic diseases determine swallowing disorders. Dysphagia, is the difficulty in swallowing. In slight disorders, swallowing function is sufficiently compensated, symptoms are few or absent. Sometimes the patient is able to compensate and obtains a safe deglutition. Rehabilitation of swallowing disorders is based on the assessment of all symptoms and troubles causing dysphagia and on the improvement of the specific disabilities. Rehabilitation is aimed to make patient able for a safe oral feeding. We can use classic specific physiotherapy, compensatory movements of head and neck, electrostimulation, and the chemical myotomia by botulinum toxin injection.