Slade Matthews

Depression, Comorbid Anxiety Disorders, and Heart Rate Variability in Physically Healthy, Unmedicated Patients: Implications for Cardiovascular Risk

Context There is evidence that heart rate variability (HRV) is reduced in major depressive disorder (MDD), although there is debate about whether this effect is caused by medication or the disorder per se. MDD is associated with a two to fourfold increase in the risk of cardiac mortality, and HRV is a robust predictor of cardiac mortality; determining a direct link between HRV and not only MDD, but common comorbid anxiety disorders, will point to psychiatric indicators for cardiovascular risk reduction. Objective To determine in physically healthy, unmedicated patients whether (1) HRV is reduced in MDD relative to controls, and (2) HRV reductions are driven by MDD alone, comorbid generalized anxiety disorder (GAD, characterized by anxious anticipation), or comorbid panic and posttraumatic stress disorders (PD/PTSD, characterized by anxious arousal). Design, Setting, and Patients A case-control study in 2006 and 2007 on 73 MDD patients, including 24 without anxiety comorbidity, 24 with GAD, and 14 with PD/PTSD. Seventy-three MDD and 94 healthy age- and sex-matched control participants were recruited from the general community. Participants had no history of drug addiction, alcoholism, brain injury, loss of consciousness, stroke, neurological disorder, or serious medical conditions. There were no significant differences between the four groups in age, gender, BMI, or alcohol use. Main Outcome Measures HRV was calculated from electrocardiography under a standardized short-term resting state condition. Results HRV was reduced in MDD relative to controls, an effect associated with a medium effect size. MDD participants with comorbid generalized anxiety disorder displayed the greatest reductions in HRV relative to controls, an effect associated with a large effect size. Conclusions Unmedicated, physically healthy MDD patients with and without comorbid anxiety had reduced HRV. Those with comorbid GAD showed the greatest reductions. Implications for cardiovascular risk reduction strategies in otherwise healthy patients with psychiatric illness are discussed.

The impact of frailty on the utilisation of antithrombotic therapy in older patients with atrial fibrillation

OBJECTIVE to investigate the impact of frailty on the utilisation of antithrombotics and on clinical outcomes in older people with atrial fibrillation (AF). DESIGN prospective study of a cohort of 220 acute inpatients aged > or =70 years with AF, admitted to a teaching hospital in Sydney, Australia (April-July 2007), with 207 followed up over 6 months. RESULTS a total of 140 patients (64%) were identified as frail using a validated tool. Frail patients were less likely to receive warfarin than non-frail on hospital admission (P = 0.002) and discharge (P < 0.001). During hospitalisation, the proportion of frail participants prescribed warfarin decreased by 10.7% and that of non-frail increased by 6.3%. Over the 6-month follow-up, 43 major or severe haemorrhages (20.8%), 20 cardioembolic strokes (9.7%) and 40 deaths (19.2%) were reported. Compared to non-frail, frail participants were significantly more likely to experience embolic stroke (RR 3.5, 95% CI 1.0-12.0, P < 0.05), had a small non-significant increase in risk of major haemorrhage (RR 1.5, 95% CI = 0.7-3.0, P = 0.29) and had greater mortality (RR 2.8, 95% CI 1.2-6.5, P = 0.01). CONCLUSION frail older inpatients with AF are significantly less likely to receive warfarin than non-frail and appear more vulnerable to adverse clinical outcomes, with and without antithrombotic therapy.

The assessment of frailty in older people in acute care

Aim:  Develop a measure of frailty for older acute inpatients to be performed by non‐geriatricians.

Hepatotoxicity of therapeutic short‐course paracetamol in hospital inpatients: impact of ageing and frailty

Background:  Paracetamol, a commonly used simple analgesic, can be fatal in overdose. Case reports suggest liver damage may occur at therapeutic doses. In older and particularly frail patients, dose reduction of therapeutic paracetamol is recommended due to concerns of an increased risk of hepatotoxicity.

Gentamicin pharmacokinetics in old age and frailty.

AIMS Frailty, a syndrome of decreased physiological reserve that is prevalent in old age, impacts on clinical pharmacology. The aims of the study were to (1) determine whether frailty affects the pharmacokinetics of gentamicin and (2) assess the accuracy of different estimates of body size and renal clearance as estimates of gentamicin pharmacokinetics in older inpatients. METHODS This was an observational study of gentamicin pharmacokinetics in a cohort of Australian hospital inpatients aged ≥65 years, who were administered prophylactic intravenous gentamicin. RESULTS Of the 31 participants, 14 were frail and 17 non frail on the Reported Edmonton Frail Scale. The mean volume of distribution of gentamicin was 14.8 ± 1.4 l in frail participants and 15.3 ± 2.2 l in non frail (NS). Volume of distribution correlated best with lean bodyweight. Gentamicin clearance was significantly lower in frail participants (46.6 ± 10.7 ml min(-1)) than in non frail (58.2 ± 12.4 ml min(-1), P=0.01). The Cockcroft Gault estimate of creatinine clearance calculated using ideal bodyweight gave the best estimate of gentamicin clearance (mean error -0.15 ml min(-1), 95% CI -2.67, 2.39). The Cockcroft Gault creatinine clearance calculated using actual bodyweight and the estimated glomerular filtration rate from the modified diet in renal disease equation overestimated gentamicin clearance, with mean errors of -10.15 ml min(-1) (95%CI -13.60, -6.71) and -18.86 ml min(-1) (95% CI -22.45, -15.27), respectively. The Cockcroft Gault creatinine clearance calculated using lean bodyweight underestimated gentamicin clearance (mean error 6.54 ml min(-1), 95% CI 4.18, 8.90). CONCLUSIONS Frail older people have significantly lower gentamicin clearance than non frail. The best estimate of gentamicin clearance is obtained from the Cockcroft Gault creatinine clearance calculated using ideal bodyweight.

Gastric banding for the treatment of type 2 diabetes mellitus in morbidly obese.

BACKGROUND To assess the efficacy of the Swedish adjustable gastric band in the treatment of type 2 diabetes mellitus (T2DM), impaired glucose tolerance (IGT), and the metabolic syndrome (MS) in the morbidly obese. METHODS We identified all patients with T2DM, IGT, or the MS at surgery from our database of 905 consecutive patients who had undergone placement of the Swedish adjustable gastric band between January 2001 and April 2007. The patients were followed up by our multidisciplinary team, and their T2DM was managed by their treating primary care physician and/or endocrinologist. RESULTS A total of 682 patients had >6 months of follow-up. Of these, 78 patients had T2DM, 64 had IGT, and 100 had the MS. At a median follow-up of 12.5 months, patients with T2DM had a mean +/- SD excess weight loss of 38% +/- 15%. This was associated with hemoglobin A1c and fasting blood sugar levels decreasing from 8.0% +/- 1.7% to 6.1% +/- 1.0% (P <.0001) and from 9.6 +/- 3.4 mmol/L to 5.7 +/- 1.5 mmol/L (P <.0001), respectively. Remission and/or improvement in patients with T2DM was judged by the complete cessation and/or reduction in medication and normalization of laboratory values. This occurred in 81% of those taking oral hypoglycemic agents. Of the patients taking a combination of oral hypoglycemic agents and insulin, 43% ceased and/or reduced their oral hypoglycemic agents, and 93% ceased and/or reduced their insulin requirements. Of those on insulin only, 75% ceased and/or reduced their insulin. No patient with IGT developed diabetes or progressed to require medications. Remission and/or improvement in the MS occurred in 88% of patients. Remission of T2DM was dependent on both the magnitude of excess weight loss (P = .008) and the duration of the pre-existing T2DM. Using binary logistic regression analysis, a duration of T2DM of <5 years before surgery was 6.5 times more likely to lead to resolution of T2DM after the weight loss (P = .004). CONCLUSION Weight loss after Swedish adjustable gastric band placement is an effective treatment of T2DM in morbidly obese patients, with early intervention offering the greatest chance of remission. It might even prevent the occurrence of T2DM in patients with IGT.

The impact of frailty on pharmacokinetics in older people: using gentamicin population pharmacokinetic modeling to investigate changes in renal drug clearance by glomerular filtration

PurposeFrailty, a multifactorial biological syndrome characterized by a cumulative dysregulation of physiological processes, is associated with changes in pharmacokinetics and pharmacodynamics. The aim of this study was to quantify the effect of frailty on glomerular filtration of drugs, using the probe drug gentamicin.MethodsGentamicin concentrations and clinical data including the Reported Edmonton Frail Scale score were pooled from two prospective observational inpatient studies, one on prophylactic gentamicin for urologic surgery and one on therapeutic gentamicin for the empiric treatment of sepsis. Population pharmacokinetic modeling was performed using non-linear mixed effects modeling (NONMEM program) to determine the impact of frailty on gentamicin clearance.ResultsA one-compartment linear pharmacokinetic model best described the data and the addition of frailty to the model reduced the random variability in gentamicin clearance by 12 % after adjustment for renal function (estimated creatinine clearance using lean body weight) and lean body weight. Frail patients had an approximately 12 % lower (bootstrapping results: 14 % median) gentamicin clearance than non-frail patients (calculated as a fractional effect of frailty).ConclusionsFrailty may independently predict reduced clearance of gentamicin in older patients. Frailty could be considered in the development of dosing guidelines for drugs that undergo significant excretion through glomerular filtration.

Increased total heart rate variability and enhanced cardiac vagal autonomic activity in healthy humans with sinus bradycardia

Sinus bradycardia can be defined as a sinus rhythm with a resting heart rate of 60 beats per minute or less. While it is assumed that increased autonomic parasympathetic activity is associated with sinus bradycardia, such an association has yet to be proven. The aims of this study were to compute a number of heart rate variability (HRV) parameters in healthy individuals with sinus bradycardia and determine whether there was a significant vagal component to sinus bradycardia. Forty-three healthy adults with normal sinus rhythm and 25 healthy adults with sinus bradycardia had an electrocardiogram recorded for 20 minutes, from which HRV indices were calculated. Results showed significant increases in SDNN (standard deviation of NN intervals) (P< 0.05), RMSDD (square root of the mean squared differences of successive NN intervals) (P< 0.05), and DFA32 (detrended fluctuation analysis) (P< 0.05) in bradycardic subjects compared with subjects with normal sinus rhythm. There were no significant differences in sympathetic frequency domain indices between the two groups. In conclusion, there were significant increases in total heart variability and increased parasympathetic drive in subjects with bradycardia. Clinically, bradycardia is likely to be cardioprotective in aging populations based upon these HRV findings.

Validation of the Reactions to Ageing Questionnaire: assessing similarities across several countries.

With the increasing numbers of older adults, factors impacting the effectiveness of provision of health care must be addressed. The literature suggests attitudes, particularly those of nurses, impact health service provision. This article reports the outcome of a multicountry validation study of the Reactions to Ageing Questionnaire (RAQ). The RAQ measures attitudes toward personal aging and has been used in Australia for 5 years. This study was designed to determine whether the psychometric characteristics and norms of the RAQ identified for Australian nurses also apply to nursing samples in Sweden and the United Kingdom. Findings indicate the internal structure of the RAQ extends outside Australia, with similar factors appearing across the three countries. Ranges and standard deviations indicate the instrument is able to discriminate between respondents within each country. Cronbachs alpha coefficients were consistent across countries and fell in the moderately high range. The findings indicate the RAQ has many potential applications in attitude assessment and in providing direction for training designed to address attitudinal factors that may impact the effectiveness of nursing practice for older adults.

Diagnosis of oligodendroglioma: Molecular and classical histological assessment in the twenty‐first century

Advances in molecular genetics are currently challenging the traditional morphological categorization of gliomas. Recurrent molecular and cytogenetic aberrations add prognostic and predictive information over and above that provided by standard histomorphological techniques and may influence decisions to re‐operate or observe, to deliver radiation or not, or to administer chemotherapy to glioma patients. The importance of routine hematoxylin and eosin (H–E pathological stains cannot be underestimated, especially in resource‐poor areas and developing countries where there is likely to be a significant economic opportunity cost for molecular diagnosis services. New research tools for image analyses of histological H–E slides, such as the precise measures of cell area, curvature and nuclear roundness, may provide an increased ability to provide an accurate classification for an inherently subjective process of histological assessment. We discuss the current trends, limitations and impact of molecular classification in this mini review.