ORCID Profile
0000-0002-4732-0859
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Publisher: Wiley
Date: 02-1988
Publisher: Massachusetts Medical Society
Date: 25-12-2008
Publisher: American Diabetes Association
Date: 16-01-2012
DOI: 10.2337/DC11-1109
Abstract: Diabetic patients with moderate renal impairment (estimated glomerular filtration rate [eGFR] 30–59 mL/min/1.73 m2) are at particular cardiovascular risk. Fenofibrate’s safety in these patients is an issue because it may elevate plasma creatinine. Furthermore, guidelines regarding fenofibrate dosing in renal impairment vary internationally. We investigated fenofibrate’s effects on cardiovascular and end-stage renal disease (ESRD) events, according to eGFR, in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study. Type 2 diabetic patients (aged 50–75 years) with eGFR ≥30 mL/min/1.73 m2 were randomly allocated to a fixed dose of fenofibrate (200 mg daily) (n = 4,895) or placebo (n = 4,900) for 5 years. Baseline renal function (Modification of Diet in Renal Disease equation) was grouped by eGFR (30–59, 60–89, and ≥90 mL/min/1.73 m2). The prespecified outcome was total cardiovascular events (composite of cardiovascular death, myocardial infarction, stroke, and coronary/carotid revascularization). Serious adverse events and instances of ESRD (plasma creatinine & μmol/L, dialysis, renal transplant, or renal death) were recorded. Analysis was by intention to treat. Overall, fenofibrate reduced total cardiovascular events, compared with placebo (hazard ratio 0.89 [95% CI 0.80–0.99] P = 0.035). This benefit was not statistically different across eGFR groupings (P = 0.2 for interaction) (eGFR 30–59 mL/min/1.73 m2: 0.68 [0.47–0.97], P = 0.035 eGFR ≥90 mL/min/1.73 m2: 0.85 [0.70–1.02], P = 0.08). ESRD rates were similar between treatment arms, without adverse safety signals of fenofibrate use in renal impairment. Patients with type 2 diabetes and moderate renal impairment benefit from long-term fenofibrate, without excess drug-related safety concerns compared with those with no or mild renal impairment. Fenofibrate treatment should not be contraindicated in moderate renal impairment, suggesting that current guidelines may be too restrictive.
Publisher: Mary Ann Liebert Inc
Date: 02-1998
Abstract: In most trials, at least 50% of patients with Graves' disease treated with antithyroid drugs (ATD) relapse after achieving euthyroidism. At present, there are no definitive prognostic parameters available early in treatment to indicate those likely to achieve long-term remission. Because thyrotropin receptor antibodies (TRAb) are specific for Graves' disease, the possibility that their rate of change early in treatment (0 to 6 months) might be such an indicator was explored. TRAb were measured both as thyrotropin binding inhibitory immunoglobulins (TBII) and as thyroid-stimulating antibodies (TSAb) in 85 patients with untreated Graves' disease at 6-month intervals throughout their ATD treatment. The patients in the study were treated for a minimum period of 12 months and were categorized retrospectively into two groups depending on whether or not they remained in remission after ATD treatment. Remission was deemed as reached in patients who remained euthyroid for a minimum period of 15 months after cessation of ATD. The mean initial TBII and TSAb values in the nonremission group were significantly higher than in the remission group (p < 0.001 for both parameters). The rates of fall in mean TBII levels were similar for each group in the first 6 months of treatment, but while they continued to fall in the remission group over the next 6 to 12 months, mean values for the nonremission group plateaued and failed to fall to control levels within that period. These results indicate that changes in TRAb levels, measured either as TBII or TSAb, occur more rapidly in the second 6 months of treatment in patients who ultimately achieve remission than those who do not. If TBII fall to control levels by 12 months, the patient has at least a 70% chance of ultimately achieving remission with ATD treatment alone.
Publisher: Wiley
Date: 24-01-2022
DOI: 10.5694/MJA2.51385
Publisher: Elsevier BV
Date: 06-1990
DOI: 10.1016/0021-9150(90)90037-J
Abstract: Human plasma lipoproteins or human whole plasma have been incubated in vitro with canine hepatic lipase (HL) and bovine milk lipoprotein lipase (LPL) to determine the effects of lipases on the particle size distribution of HDL. Confirming previous reports, HL preferentially hydrolysed high density lipoprotein (HDL) triacylglycerol while LPL hydrolysed predominantly very low density lipoprotein (VLDL) triacylglycerol however, neither lipase altered HDL particle size unless both VLDL and cholesteryl ester transfer protein (CETP) were present. Under these conditions HL promoted marked reduction in HDL particle size in a process dependent on the concentration of VLDL triacylglycerol while LPL was virtually without effect. When both LPL and HL were included in the same incubation, however, LPL prevented the effects of HL. These results are consistent with a proposition that HL has a direct effect on HDL particle size in a process which is dependent on concurrent lipid transfers between HDL and VLDL and that LPL reduces the effect of HL by reducing the concentration of VLDL triacylglycerol.
Publisher: Ubiquity Press, Ltd.
Date: 2021
DOI: 10.5334/IJIC.5634
Publisher: Wiley
Date: 08-11-2019
Abstract: The Victorian Emergency Minimum Dataset (VEMD) collects administrative and clinical data for all presentations to Victorian public ED. The present study aimed to examine the level of agreement between the VEMD data and the medical record for a s le of patients coded as having acute cardiovascular conditions (acute coronary syndrome, stroke and transient ischaemic attack [TIA]) and unspecified chest pain in the VEMD. Six months of data provided to the VEMD from a large metropolitan hospital was obtained, and a random s le of 10% of cases (n = 310) were selected for review. Data for eight VEMD items were compared for concordance to data recorded in the ED medical record. Complete concordance between the VEMD and medical records for all eight items was observed only for 101 (33%) presentations. Overall, the least concordant variables were those with a high number of coding options: usual type of accommodation (76%), referral pattern (84%) and primary diagnosis (85%). The concordance of the VEMD primary diagnosis varied when examined as in idual codes (range 75%-100%) and when combined (acute coronary syndrome = 94%, stroke or TIA = 85% and chest pain unspecified = 75%). The level of agreement for some items improved when VEMD codings were combined. When compared to the medical record, our data suggest there is likely variation in the accuracy of some VEMD items, and suggests a larger prospective validation of the VEMD is warranted. For researchers using existing VEMD data, combining of some codes may be necessary.
Publisher: Wiley
Date: 11-2013
DOI: 10.1111/IMJ.12275
Abstract: In the week following the onset of the 2009 heatwave in Melbourne, Australia, The Alfred Hospital observed a significant increase in total hospital admissions (adjusted incidence rate ratio (IRR) 1.11, P = 0.046), emergency department presentations (IRR 1.15, P < 0.01) and general medical admissions (IRR 1.81, P < 0.01). Under the general medical unit there was a rise in the number of deaths (IRR 3.9, P < 0.01), and patients with a broad range of disorders, particularly of the endocrine/metabolic (IRR 2.2, P < 0.01), circulatory (IRR 1.9, P < 0.01) and genitourinary (IRR 2.6, P < 0.01) systems.
Publisher: Wiley
Date: 04-2012
DOI: 10.1111/J.1445-5994.2011.02502.X
Abstract: A perceived risk of time-limited emergency department (ED) assessment of patients is inadequate workup leading to inappropriate disposition. The aim of this study was to examine the association of time to disposition plan (TDP) on ED length of stay (LOS) and correlate this to mortality. A retrospective review of data collected from ED information systems at three hospitals was conducted between June 2008 and October 2009. Included patients were admitted to a general medical unit. Patients were excluded if admitted to intensive care, coronary care, a cardiac monitored bed or required surgery in first 24 h or had an expected LOS of <48 h. Multivariate regression analysis was used to identify independent associations with mortality. A total of 10,107 patient episodes was analysed, of which 6768 patients (67.0%) had an ED LOS of ≥8 h. There was significant effect modification by ED LOS in the association of TDP and mortality. In the setting of longer ED LOS, a TDP of <4 h was associated with significantly higher mortality (OR 1.57, 95% CI: 1.28-1.92, P < 0.001), corrected for age, gender and triage category. This association was not significant when ED LOS was <8 h (OR 0.88, 95% CI: 0.60-1.27, P = 0.49). In the setting of prolonged ED LOS, completing ED assessment and management within 4 h of presentation was associated with significantly higher mortality. Further prospective studies are required to understand the relationship between rapid decision making in the ED and patient safety.
Publisher: Wiley
Date: 04-1987
Publisher: Elsevier BV
Date: 02-1992
DOI: 10.1016/0005-2760(92)90125-F
Abstract: The effects of lipid transfers and hepatic lipase (HL) on the concentration, composition, particle size distribution and morphology of high density lipoproteins (HDL) have been investigated. Human plasma supplemented with additional very low density lipoproteins (VLDL), cholesteryl ester transfer protein (CETP) and HL has been incubated at 37 degrees C for up to 8 h. The HDL became depleted of cholesteryl esters and reduced in particle size. Within 2 h of such incubation they had also lost about 30% of their apo A-I. However, with extension of the incubations beyond 2 h, the apo A-I returned progressively to the HDL fraction until, after 8 h, the concentration of apo A-I in HDL was identical to that in non-incubated s les. This return of apo A-I to the HDL density range was accompanied by a progressive appearance in electron micrographs of discoidal HDL particles. Thus, the depletion of the core lipid content and the reduction in particle size of HDL promoted by lipid transfers and HL activity in vitro is accompanied by a shedding of apo A-I which forms the nucleus of new discoidal HDL particles. The potential physiological importance of such a process is considerable.
Publisher: Elsevier BV
Date: 03-1997
DOI: 10.1016/S0140-6736(97)90002-7
Abstract: We investigated the effect of the diameter size of single-walled carbon nanotubes (SWCNTs), on their high-temperature energy storage behavior in an electric double layer capacitor (EDLC) using the ionic liquid triethyl(2-methoxyethyl) phosphonium bis(trifluoromethylsulfonyl)imide (P
Publisher: Elsevier BV
Date: 05-1990
DOI: 10.1016/0005-2760(90)90218-M
Abstract: Studies have been performed to determine the involvement of very-low-density lipoproteins (VLDL), cholesteryl ester transfer protein (CETP) and hepatic lipase (HL) in the formation of very small HDL particles. Human whole plasma has been incubated for 6 h at 37 degrees C in the absence and in the presence of various additions. There was minimal formation of very small HDL in incubations of non-supplemented plasma or in plasma supplemented with either VLDL, CETP or HL alone nor were small HDL prominent after incubating plasma supplemented with mixtures of VLDL plus CETP, VLDL plus HL or CETP plus HL. By contrast, when plasma was supplemented with a mixture containing all three of VLDL, CETP and HL, incubation resulted in an almost total conversion of the HDL fraction into very small particles of radius 3.7 nm. The appearance of these very small HDL was independent of activity of lecithin: cholesterol acyltransferase. It was, however, dependent on both duration of incubation and on the concentrations of the added VLDL, CETP and HL. The effects of these incubations was also assessed in terms of changes to the concentration and distribution of lipid constituents across the lipoprotein spectrum. It was found that not only did lipid transfers and HL exhibit a marked synergism in promoting a reduction in HDL particle size but also that HL, although deficient in intrinsic transfer activity, enhanced the CETP-mediated transfers of cholesteryl esters from HDL to other lipoprotein fractions.
Publisher: Elsevier BV
Date: 06-1990
DOI: 10.1016/0005-2760(90)90206-D
Abstract: Purified human cholesteryl ester transfer protein (CETP) has been found, under certain conditions, to promote changes to the particle size distribution of high-density lipoproteins (HDL) which are comparable to those attributed to a putative HDL conversion factor. When preparations of either the conversion factor or CETP are incubated with HDL3 in the presence of very-low-density lipoproteins (VLDL) or low-density lipoproteins (LDL), the HDL3 are converted to very small particles. The possibility that the conversion factor may be identical to CETP was supported by two observations: (1) CETP was found to be the main protein constituent of preparations of the conversion factor and (2) an antibody to CETP not only abolished the cholesteryl ester transfer activity of the conversion factor preparations but also inhibited changes to HDL particle size. In additional studies, the changes to HDL particle size promoted by purified CETP were inhibited by the presence of fatty-acid-free bovine serum albumin by contrast, albumin had no effect on the cholesteryl ester transfer activity of the CETP. The possibility that albumin may inhibit changes to HDL particle size by removing unesterified fatty acids from either the lipoproteins or CETP was tested by adding exogenous unesterified fatty acids to the incubations. In incubations of HDL with either VLDL or LDL, sodium oleate had no effect on HDL particle size. However, when CETP was also present in the incubation mixtures the capacity of CETP to reduce the particle size of HDL was greatly enhanced by the addition of sodium oleate. It is concluded that the changes in HDL particle size which were previously attributed to an HDL conversion factor can be explained in terms of the interacting effects of CETP and unesterified fatty acids.
Publisher: Elsevier BV
Date: 05-1992
DOI: 10.1016/0005-2760(92)90059-5
Abstract: Previous reports have produced conflicting views of the effects of lipoprotein lipase (LPL) on the particle size distribution of high density lipoproteins (HDL). In this study we have investigated the changes in particle size of HDL promoted by the interaction of LPL, the cholesteryl ester transfer protein (CETP) and very low density lipoproteins (VLDL). When the plasma fraction of d less than 1.21 g/ml (containing all lipoprotein fractions) was incubated for 24 h with bovine milk LPL alone or with CETP alone, there was relatively little change in the particle size distribution of HDL. When both LPL and CETP were added to the lipoprotein mixture, there was a substantial reduction in the particle size of HDL. This reduction in HDL particle size was found to be a direct function of the concentration of CETP. It was also influenced by the concentrations of VLDL and LPL, although in these cases the relationships were complex. When mixtures of the plasma fraction of d = 1.006-1.21 g/ml (this fraction includes low density lipoproteins and HDL but not VLDL) were supplemented with both LPL and CETP and incubated in the presence of varying concentrations of added VLDL, there was a progressive increase in the conversion of HDL into very small HDL particles of radius 3.7 nm as the concentration of VLDL triacylglycerol increased up to about 400 nmol/nml. However, further increases in the concentration of VLDL were accompanied by a progressive reduction in the formation of small HDL particles until, at higher VLDL concentrations, the effect was all but abolished. There was a similar enhancement in the formation of small HDL when LPL was added at low but not at high concentrations. These findings are consistent with the existence of two opposing processes. On the one hand there is likely to be a synergism between CETP and the non-esterified fatty acids (NEFA) released by LPL this will favour a reduction in HDL particle size. On the other hand, the transfer of lipolysis products from VLDL to HDL may mask any such particle size reduction. The fact that the reduction in HDL particle size promoted by LPL, CETP and VLDL was found to be all but abolished by adding fatty acid-poor albumin to the incubation mixture is consistent with the proposition that NEFA are involved in the process. It also suggests, however, that the phenomenon may have little if any physiological significance.
Publisher: AMPCo
Date: 02-2012
DOI: 10.5694/MJA11.10619
Publisher: Elsevier BV
Date: 2006
DOI: 10.1016/J.JDIACOMP.2005.05.007
Abstract: Lignocaine is a cardiac antiarrhythmic agent occasionally used to treat neuropathic pain. This study was designed to examine the effectiveness of intravenous lignocaine in patients with intractable painful diabetic neuropathy. Fifteen patients with painful diabetic peripheral neuropathy, who had appeared to respond to previous lignocaine infusions, completed a double-blind, placebo-controlled crossover trial of two doses of intravenous lignocaine (5 and 7.5 mg/kg) versus saline. Infusions were administered in random order over 4 h at four weekly intervals. The effect of treatment on pain perception was assessed using the McGill Pain Questionnaire (MPQ), a daily pain diary, hours of sleep, fasting blood glucose, and use of other pain-relieving medication. Both doses of lignocaine significantly (P<.05 to P<.001 for the different measures) reduced the severity of pain compared with placebo. This reduction was present at both 14 and 28 days after the infusion. The qualitative nature of the pain was also significantly (P<.05 to P<.01) modified by lignocaine compared with placebo for up to 28 days. The preceding dose 4 weeks earlier significantly (P<.01 and P<.001) affected the response to the next dose. There were no significant effects of treatment on the other measures of response. There were no significant side effects of the treatment. This study shows that intravenous lignocaine ameliorates pain in some diabetic participants with intractable neuropathic pain who have failed to respond to or are intolerant of available conventional therapy.
Publisher: Elsevier BV
Date: 1993
DOI: 10.1016/S0950-351X(05)80271-X
Abstract: Cardiovascular disease remains the major cause of death for postmenopausal women in Western societies. The majority of epidemiological studies indicate that postmenopausal oestrogen replacement therapy is associated with a 50% reduction in the risk of cardiovascular disease, with much of the reduction being mediated by changes in the plasma concentration of cholesterol within high and low density lipoproteins. In addition to favourably influencing the plasma concentration of lipoproteins, oestrogens also influence the complex metabolism of lipoproteins in the arterial wall, helping to impede the formation of the atherosclerotic plaque. Whilst oestrogens alter endothelial function, vascular reactivity and fibrinolysis, these changes are also seen with reduction of LDL cholesterol and may partly reflect the altered concentration of plasma lipoproteins induced by oestrogens. Oral oestrogens have substantially greater favourable effects on LDL and HDL cholesterol than their transdermal counterparts but also result in greater hypertriglyceridaemia. Most progestogens antagonize the beneficial effects of oestrogens on lipoproteins in a dose-dependent manner however, cyclical use of low doses of progestogens with an oral oestrogen generally retains a net beneficial effect. Lipoprotein levels fluctuate during cyclical therapy, the most adverse changes being noted at the end of the progestogen phase. Lipoprotein concentrations are constant during continuous combined regimens which have the potential for more prolonged exposure to an adverse progestational effect. Despite adverse effects on the lipoprotein profile, animal studies suggest that progestogens do not substantially reverse the beneficial effects of oestrogens on the development of atherosclerosis. Finally, oestrogen therapy may be useful in the management of postmenopausal women with hyperlipidaemia, and also in the secondary prevention of clinical sequelae in women with established atherosclerosis.
Publisher: BMJ
Date: 12-04-2011
DOI: 10.1136/BMJQS.2010.049668
Abstract: Insulin is a high-risk medicine which may cause significant patient harm or death when given incorrectly. A 10-fold error in administered insulin dose commonly occurs when the abbreviation 'u' is used for 'units' and subsequently misinterpreted as a 'zero.' A multidisciplinary working party was convened and mapped insulin prescribing, dispensing and administration. All inpatient orders above 25 units for short-acting insulin and 50 units for other insulin require validation by an additional source. Educational strategies to support adherence to the guideline and product-labelling alerts were developed. Implementation occurred in August 2008 across the three hospital sites. In 90 weeks after implementation, there were 150 patients identified in which 200 high doses of insulin were prescribed (>25 units for short-acting insulin and 50 units for other insulin). There were eight instances where high doses of insulin were prescribed in error but were detected and rectified through the new validation process. There were 12 dosing errors that occurred, including two 10-fold dosing errors. In contrast, seven major errors resulting in excessive insulin administration were identified over a 2-year period prior to the introduction of the insulin high-dose validation system. A structured validation process was successful in reducing incorrect prescription and administration of high-dose insulin and has reduced the risk of associated fatalities or significant patient harm. Consideration should be given to adopting this process in any setting where insulin is prescribed and administered.
No related grants have been discovered for Harvey Newnham.