Physical activity, obesity, and quality of life among rural Australian cancer survivors: a cross-sectional study.

PURPOSE: We aimed to describe physical activity (PA), obesity, and quality of life (QoL) among rural Australian cancer survivors, assess whether total and item-specific QoL are associated with sufficient PA and obesity, and assess whether PA and obesity interact with respect to QoL. METHODS: In a cross-sectional study, convenience sampling was used to recruit adult cancer survivors via a chemotherapy day unit and allied health professionals at a rural hospital in Baw Baw Shire, Australia. Exclusion criteria were acute malnutrition and end-of-life care. PA and QoL were measured using Godin-Shephard and 7-item Functional Assessment of Cancer Therapy (FACT-G7) questionnaires, respectively. Factors associated with total and item-specific QoL were assessed via linear and logistic regression, respectively. RESULTS: Among 103 rural cancer survivors, the median age was 66 years, 35% were sufficiently physically active, and 41% presented with obesity. Mean/median total QoL scores were 17 on the FACT-G7 scale (0-28; higher scores indicate better QoL). Sufficient PA was associated with better QoL ([Formula: see text]=2.29; 95% confidence interval [CI] = 0.26, 4.33) and more energy (odds ratio [OR] = 4.00, 95% CI = 1.48, 10.78) while obesity was associated with worse QoL ([Formula: see text]=-2.09; 95% CI = -4.17, -0.01) and more pain (OR = 3.88, 95% CI = 1.29, 11.68). The PA-obesity interaction was non-significant (p-value = 0.83). CONCLUSIONS: This is the first known study conducted among rural survivors of any cancer to find sufficient PA and obesity are associated with better and worse QoL, respectively. PA, weight management, and QoL-including energy and pain-should be considered when targeting and tailoring supportive care interventions for rural cancer survivors.

Level and correlates of social support in a community-based sample of Australians who primarily smoke methamphetamine.

Little is known about the level and correlates of social support amongst people who use methamphetamine. We aimed to describe, and determine characteristics associated with, social support amongst a community-recruited cohort of Australians who primarily smoked methamphetamine. A cross-sectional study was conducted with data from the Victorian Methamphetamine Cohort Study (VMAX). Adults (aged ≥18 years) who used methamphetamine were recruited from June 2016 to March 2020 across metropolitan and non-metropolitan areas using convenience, snowball, and respondent-driven sampling. Social support was measured using the seven-item Enhancing Recovery In Coronary Heart Disease (ENRICHD) Social Support Inventory (ESSI). Characteristics independently associated with ESSI quartiles were assessed via multivariable partial proportional odds regression. Overall, 718 participants were included for complete-case analysis. Their mean (standard deviation [SD]) age was 34.7 (9.7) years and 62% were male. The mean (SD) and median (lower quartile-upper quartile) ESSI scores were 22.6 (7.6) and 24 (16-29), respectively, on a scale of 8 to 34 where higher scores denote better self-perceived social support. Characteristics independently associated with lower ESSI included past-year homelessness (adjusted odds ratio [aOR] = 0.49, 95% confidence interval [CI] = 0.36-0.66), moderate/severe depression (aOR = 0.60, 95% CI = 0.42-0.86), increasing age relative to <30 years (aOR[30-39] = 0.61, 95% CI = 0.41-0.91; aOR[≥40] = 0.56, 95% CI = 0.35-0.91) and greater than fortnightly methamphetamine use (aOR = 0.69, 95% CI = 0.52-0.91). Characteristics independently associated with higher ESSI were employment (aOR = 1.51, 95% CI = 1.06-2.14) and female gender (aOR = 1.39, 95% CI = 1.00-1.92). Social support services for people who use methamphetamine could be targeted and tailored to subgroups defined by correlates of social support, such as those who experience homelessness, depression or unemployment.

Long term survival following a medical emergency team call at an Australian regional hospital.

Objective: To investigate the long term survival of medical emergency team (MET) patients at an Australian regional hospital and describe associated patient and MET call characteristics. Design: Retrospective cohort study. Data linkage to the statewide death registry was performed to allow for long term survival analysis, including multivariable Cox proportional hazards regression and production of Kaplan-Meier survival curves. Setting: A large Australian regional hospital. Participants: Adult patients who received a MET call from 1 July 2012 to 3 March 2020. Main outcome measures: Survival to 30, 90 and 180 days; one year; and 5-years after index MET call. Results: The study included 6499 eligible patients. The cohort median age was 71 years, and 52.4% of the patients were female. Surgical (39.6%) and medical (36.9%) patients comprised most of the cohort. Thirty-day survival was 86.5% one-year survival was 66.1%. Among patients aged < 75 years, factors independently associated with significantly higher long term mortality included age (hazard ratio [HR], 3.26 [95% CI, 2.63-4.06]; for patients aged 65-74 v 18-54 years), male sex (HR, 0.71 [95% CI, 0.61-0.83]; for females) and pre-existing limitation of medical therapy (HR, 2.76; 95% CI, 2.28-3.35). Among patients aged ≥ 75 years, factors independently associated with significantly higher long term mortality included age (HR, 1.46 [95% CI, 1.29-1.65]; for patients aged ≥ 85 years), male sex (HR, 0.74 [95% CI, 0.66-0.83]; for females), and altered MET criteria (HR, 1.33; 95% CI, 1.03-1.71). Conclusions: Long term survival probabilities of MET call patients are affected by factors including age, sex, and limitation of medical therapy status. These data may be useful for clinicians conducting end-of-life discussions with patients.

Functional outcomes following an in-hospital cardiac arrest: A retrospective cohort study.

BACKGROUND/PURPOSE: Whilst much is known about the survival outcomes of patients that suffer an in-hospital cardiac arrest (IHCA) in Australia very little is known about the functional outcomes of survivors. This study aimed to describe the functional outcomes of a cohort of patients that suffered an in-hospital cardiac arrest (IHCA) and survived to hospital discharge in a regional Australian hospital. METHODS: This is a single-centre retrospective observational cohort study conducted in a regional Australian hospital. All adult patients that had an IHCA in the study hospital between 1 Jan 2017 and 31 Dec 2019 and survived to hospital discharge were included in the study. Functional outcomes were reported using the Modified Rankin Scale (mRS), a six-point scale for which increasing scores represent increasing disability. Scores were assigned through a retrospective review of medical notes. RESULTS: Overall, 102 adult patients had an IHCA during the study period, of whom 50 survived to hospital discharge. The median age of survivors was 68 years, and a third had a shockable initial arrest rhythm. Of survivors, 47 were able to be assigned both mRS scores. At discharge, 81% of patients achieved a favourable functional outcome (mRS 0-3 or equivalent function at discharge equal to admission). CONCLUSIONS: Most survivors to hospital discharge following an IHCA have a favourable functional outcome and are discharged home. Although these results are promising, larger studies across multiple hospitals are required to further inform what is known about functional outcomes in Australian IHCA survivors.

Factors Associated With Quality of Life Among People Living With a Stoma in Nonmetropolitan Areas.

BACKGROUND: Interruption of gastrointestinal continuity through surgical formation of a stoma can be lifesaving. However, it is also typically associated with reduced quality of life (QoL). Although past research has investigated QoL among people living with a stoma, no known studies have investigated stoma-related QoL, specifically among nonmetropolitan residents who may experience distinct health issues compared with their metropolitan counterparts. OBJECTIVES: The aim of the study was to investigate the level of and factors associated with QoL among people living with a stoma in nonmetropolitan Australia. METHODS: In a cross-sectional survey, 678 adults with colostomy, ileostomy, and/or urostomy and with membership in a regional Victorian stoma association were given the City of Hope Quality of Life Questionnaire for a Patient With an Ostomy (QOL-O). Total QoL score was calculated and described before categorization into quintiles. Patient factors associated with quintiles of QoL were assessed using univariable and multivariable proportional odds ordinal logistic regression, with a 95% confidence interval excluding 1.00 denoting statistical significance. RESULTS: Overall, 311 regional ostomy association members (46%) responded to any QOL-O questions; 285 members responded to >80% of QOL-O questions and contributed data to the study. Their median age was 73 years, and 60% were male. The median total QoL score was 6.9 on a scale of 0-10, where a higher number indicates better QoL. Factors independently associated with better QoL in the multivariable model were working full/part time, no poststoma clothing change, poststoma sexual activity, and older age. Factors independently associated with worse QoL were poststoma depression and a stoma location issue. DISCUSSION: People living with a stoma in nonmetropolitan Australia reported moderate-to-high QoL. Better QoL was identified in those who worked, had no poststoma clothing change, were sexually active poststoma, and were older. Worse QoL was seen in those who had poststoma depression and stoma location issues. Healthcare providers could influence stoma-related QoL by identifying risk factors and tailoring interventions toward individuals in nonmetropolitan settings.

A data visualisation method for assessing exposure misclassification in case-crossover studies: the example of tricyclic antidepressants and the risk of hip fracture in older people.

BACKGROUND: The case-crossover design is suited to medication safety studies but is vulnerable to exposure misclassification. Using the example of tricyclic antidepressants and the risk of hip fracture, we present a data visualisation tool for observing exposure misclassification in case-crossover studies. METHODS: A case-crossover study was conducted using Australian Government Department of Veterans' Affairs claims data. Beneficiaries aged over 65 years who were hospitalised for hip fracture between 2009 and 2012 were included. The case window was defined as 1-50 days pre fracture. Control window one and control window two were defined as 101-150 and 151-200 days pre fracture, respectively. Patients were stratified by whether exposure status changed when control window two was specified instead of control window one. To visualise potential misclassification, each subject's tricyclic antidepressant dispensings were plotted over the 200 days pre fracture. RESULTS: The study population comprised 8828 patients with a median age of 88 years. Of these subjects, 348 contributed data to the analyses with either control window. The data visualisation suggested that 14% of subjects were potentially misclassified with control window one while 45% were misclassified with control window two. The odds ratio for the association between tricyclic antidepressants and hip fracture was 1.18 (95% confidence interval = 0.91-1.52) using control window one, whereas risk was significantly increased (odds ratio = 1.43, 95% confidence interval = 1.11-1.83) using control window two. CONCLUSIONS: Exposure misclassification was less likely to be present with control window one than with an earlier control window, control window two. When specifying different control windows in a case-crossover study, data visualisation can help to assess the extent to which exposure misclassification may contribute to variable results.

The Risk of Hip Fracture Due to Mirtazapine Exposure When Switching Antidepressants or Using Other Antidepressants as Add-On Therapy.

BACKGROUND: Antidepressants are associated with adverse effects such as sedation and hypotension, which can result in falls and fractures. Few studies have assessed the risk of hip fracture due to mirtazapine, and no known studies have assessed whether the risk of hip fracture is higher in patients taking other antidepressant medicines in combination with mirtazapine. OBJECTIVES: This study aimed to examine the risk of hip fracture in older people due to mirtazapine use as well as switching between or concurrently using mirtazapine and other antidepressants. METHOD: A matched case-control study was conducted. Cases were people aged over 65 years who were eligible for Australian Government Department of Veterans' Affairs (DVA) benefits and who sustained a hip fracture between 2009 and 2012. Each case was matched with up to four randomly selected controls of the same gender and age (± 2 years). Multivariable conditional logistic regression was used to estimate associations between antidepressant use and hip fracture. In order to assess whether combined antidepressant effects differed from the sum of individual effects, the relative excess risk due to interaction (RERI) was calculated. RESULTS: The study population comprised 8828 cases and 35,310 controls. The median age of these participants was 88 years and 63% were women. The risk of hip fracture was increased for mirtazapine (continuous use: odds ratio [OR] 1.27, 95% confidence interval [CI] 1.12-1.44). The combinations associated with increased odds of hip fracture were addition of selective serotonin reuptake inhibitors (SSRIs) to mirtazapine (OR 11, 95% CI 2.2-51; RERI 7.7, 95% CI -9.0 to 24), addition of tricyclic antidepressants (TCAs) to mirtazapine (OR 14, 95% CI 1.4-132; RERI 12, 95% CI -19 to 43) and continuous use of both SSRIs and mirtazapine (OR 2.4, 95% CI 1.4-4.2; RERI 0.4, 95% CI -0.9 to 1.7). RERIs indicated that the effect of each antidepressant pair equalled the sum of the effects of individual antidepressant use. There was no evidence of dispensing of lower strength mirtazapine upon introducing TCAs and SSRIs. CONCLUSIONS: Our results show elevated risk of hip fracture following use of mirtazapine alone and in combination with other antidepressants. The overlapping use of antidepressants may reflect the treatment of comorbidities (e.g. anxiety), switching from mirtazapine to other antidepressants, or add-on therapy. Our results highlight the risks of employing add-on therapy or switching antidepressants in older people, providing further evidence to support cautious cross-tapering where switching between antidepressants is required.

Risk of Hip Fracture in Older People Using Selective Serotonin Reuptake Inhibitors and Other Psychoactive Medicines Concurrently: A Matched Case-Control Study in Australia.

BACKGROUND: Few studies have assessed the risk of hip fracture following concurrent use of psychoactive medicines, and none has investigated combinations with selective serotonin reuptake inhibitors. OBJECTIVES: To assess the risk of hip fracture in older people as a result of concurrent use of selective serotonin reuptake inhibitors and other psychoactive medicines. METHODS: A matched case-control design was employed. Cases were Australian Government Department of Veterans' Affairs beneficiaries aged over 65 years who experienced a hip fracture between 2009 and 2012. Each case was matched with up to four randomly selected controls of the same age (±2 years) and sex. Medicine-hip fracture associations were estimated via conditional logistic regression. The relative excess risk due to interaction (RERI) was calculated to determine whether combined effects differed from the sum of individual effects. RESULTS: There were 8828 cases and 35,310 controls. The median age of subjects was 88 years and 63% were women. The risk of hip fracture was elevated for all medicines assessed individually, most notably selective serotonin reuptake inhibitors (initiation: odds ratio [OR] = 2.7, 95% confidence interval [CI] 2.1, 3.6) and opioids (initiation: OR = 2.3, 95% CI 1.9, 2.9). Combinations associated with an increased odds of hip fracture included addition of benzodiazepines to selective serotonin reuptake inhibitor therapy (OR = 3.0, 95% CI 1.9, 4.8; RERI = 0.9, 95% CI -0.5, 2.3), concurrent use of both opioids and selective serotonin reuptake inhibitors (OR = 2.2, 95% CI 1.9, 2.6; RERI = 0.1, 95% CI -0.3, 0.5), addition of opioids to selective serotonin reuptake inhibitor therapy (OR = 3.2, 95% CI 1.8, 5.5; RERI = -0.1, 95% CI -2.0, 1.7), and initiation of both benzodiazepines and selective serotonin reuptake inhibitors (OR = 4.7, 95% CI 1.7, 13; RERI = 1.3, 95% CI -3.8, 6.3). The RERI results suggested that the effect of each of these medicine combinations equalled the sum of the effects of individual medicine use. CONCLUSIONS: In older people, the concurrent use of selective serotonin reuptake inhibitors and other psychoactive medicines increased the risk of hip fracture as much as the sum of the risks owing to individual medicine use. Our results highlight the need for prescribers to consider the sedative burden of medicines in each older patient as well as the potential for an additive risk of hip fracture when initiating additional psychoactive therapy.

Psychoactive medicine use and the risk of hip fracture in older people: a case-crossover study.

PURPOSE: Many factors can increase the risk of hip fracture, including medicines. Traditional observational studies have assessed the risk, but results may be confounded by unmeasured factors. The case-crossover design is an alternative approach that controls for patient-specific, time-invariant confounding factors. This study aimed to assess associations between psychoactive medicines and hip fracture in the elderly using the case-crossover method. METHODS: Data were sourced from the Australian Government Department of Veterans' Affairs healthcare claims database. The study population comprised beneficiaries aged over 65 years who were hospitalised for hip fracture between 2009 and 2012. The case-crossover method was used to compare individuals' medicine exposure immediately before hip fracture (case window) with their exposure at an earlier time (control window). Conditional logistic regression was employed to quantify associations between medicine use and hip fracture. Alternative exposure windows were assessed in sensitivity analyses. RESULTS: Eight thousand eight hundred twenty-eight patients were hospitalised for hip fracture. Their median age was 88 years, and 63% were female. Odds of hip fracture were increased for opioids (odds ratio [OR] = 1.62, 95% confidence interval [CI] = 1.42-1.84), selective serotonin reuptake inhibitors (OR = 1.54, 95% CI = 1.28-1.86) and antipsychotics (OR = 1.47, 95% CI = 1.21-1.80). There was no significant association for tricyclic antidepressants in the primary analysis (OR = 1.18, 95% CI = 0.91-1.52), but there was a significant association in the sensitivity analysis using an alternative, earlier control window (OR = 1.43, 95% CI = 1.11-1.83). CONCLUSIONS: Increased risk of hip fracture in older people was found for opioids, selective serotonin reuptake inhibitors and antipsychotics. The choice of control window influenced the result for tricyclic antidepressants.

Factors associated with quality of life in 7-year survivors of stroke.

BACKGROUND: Little is known about health-related quality of life (HRQoL) in the long term after stroke. AIM: The aim of this study was to assess the level of, and factors associated with, HRQoL at 7 years post-stroke. METHODS: All stroke cases from a prospective community-based stroke incidence study (excluding subarachnoid haemorrhage) were assessed 7 years after stroke. HRQoL was measured with the Assessment of Quality of Life instrument. Proportional odds ordinal logistic regression was used to determine factors associated with HRQoL at 7 years post-stroke. RESULTS: Overall, 1321 stroke cases were recruited. Seven years after stroke, 413 (31.2%) were alive and 328 (79.4%) were assessed. Those assessed were less often current smokers pre-stroke than those not assessed (p<0.01). Seventy-six survivors (23%) had very poor HRQoL (range: -0.038 to 0.100). Factors present at 7 years that were associated with better 7-year HRQoL were independence in instrumental activities of daily living (IADL) (estimated OR=11.2, 95% CI 4.87 to 25.6, p<0.001), independence in basic activities of daily living (BADL) (OR=4.53, 95% CI 2.03 to 10.1, p<0.001), independence in IADL and BADL (OR=9.90, 95% CI 4.51 to 21.7, p<0.001), male gender (OR=1.89, 95% CI 1.21 to 2.96, p=0.005) and lesser handicap (trend: OR=3.47, 95% CI 2.51 to 4.79, p<0.001). Participants' HRQoL scores tended to be lower when HRQoL assessments were completed by proxy (OR=0.13, 95% CI 0.06 to 0.31, p<0.001). CONCLUSION: At 7 years post-stroke, 68.8% had died and a substantial proportion of survivors had poor HRQoL. Factors such as handicap, BADL and IADL could be targeted to improve HRQoL in long-term survivors of stroke.

A novel drug binding site on voltage-gated sodium channels in rat brain.

The effectiveness of several antiepileptic, analgesic, and neuroprotective drugs is attributable to state-dependent inhibition of voltage-gated sodium channels. To help characterize their site and mode of action on sodium channels, a member of the lamotrigine family, R-(-)-2,4-diamino-6-(fluromethyl)-5-(2,3,5-trichlorophenyl)-pyrimidine (BW202W92), was radiolabeled and used as a binding ligand in rat forebrain synaptosomes. Although the level of specific [(3)H]BW202W92 binding in a standard incubation medium was relatively poor, low concentrations of tetrodotoxin (EC(50) = 2-3 nM) greatly enhanced the binding, apparently by increasing the affinity of the binding sites. Tetrodotoxin-dependent binding was stereoselective (the less active enantiomer, S-(-)-2,4-diamino-6-(fluromethyl)-5-(2,3,5-trichlorophenyl)-pyrimidine (BW203W92), was up to 30-fold less potent, depending on conditions) and was extremely sensitive to inhibition by raised K(+) concentration (IC(50) = 5.9 mM), an effect that was ascribed to changes in membrane potential. In addition, the binding was inhibited by sodium channel neurotoxins acting on sites 3 and 4, but it was resistant to batrachotoxin (site 2) and brevetoxin (site 5). Several drugs acting on sodium channels displaced tetrodotoxin-dependent [(3)H]BW202W92 binding, and most of those tested showed different affinities under depolarized (100 mM K(+)) and polarized (1 mM K(+)) conditions. In a subset of compounds for which data were available, binding affinity in depolarized synaptosomes correlated well with apparent affinity for the inactivated state of sodium channels. The [(3)H]BW202W92 binding site is novel and is likely to represent a pharmacologically important site of action of drugs on voltage-gated sodium channels in the brain.

The neuroprotective agent sipatrigine blocks multiple cardiac ion channels and causes triangulation of the ventricular action potential.

Sipatrigine (BW 619C89), a blocker of neuronal Na+ and Ca2+ channels that is structurally related to lamotrigine, has been shown to be neuroprotective in models of cortical ischaemia. Although associated with cardiovascular effects in animal models in vivo, there is no published information concerning the effects of sipatrigine on cardiac ion currents and action potentials (AP). The aim of the present study was to examine the effects of sipatrigine on the delayed rectifier currents (I(Kr) and I(Ks)), the inward rectifier current (I(K1)), the L-type Ca2+ current (I(Ca,L)) and the fast Na+ current (I(Na)), as well as on AP duration at 30% (APD30) and 90% (APD90) repolarization, in guinea-pig isolated ventricular myocytes. Each of the currents was inhibited by sipatrigine, demonstrating the drug to be a relatively broad-spectrum blocker of cation channels in the heart. However, sipatrigine was a comparatively more potent inhibitor of I(Kr) (IC50 = 0.85 micromol/L) and I(Ks) (IC50 = 0.92 micromol/L) than of I(K1) (IC50 = 5.3 micromol/L), I(Ca,L) (IC50 = 6.0 micromol/L) and I(Na) (IC50 = 25.5 micromol/L). Consistent with block of I(Kr), I(Ks) and I(K1), sipatrigine (1-30 micromol/L) produced a concentration-dependent prolongation of APD90. Although lower concentrations of sipatrigine (< or = 3 micromol/L) caused APD(30) prolongation, higher concentrations (> or = 10 micromol/L) shortened APD30, consistent with an involvement of I(Ca,L) blockade. The contrasting effects of sipatrigine on APD30 and APD90 at higher concentrations resulted in a marked concentration-dependent triangulation of the AP. 5. The results of the present study demonstrate that sipatrigine, at concentrations previously shown to be neuroprotective in vitro, modulates cardiac K+, Ca2+ and Na+ currents and repolarization of the cardiac ventricular action potential.