Withholding and withdrawal of ‘futile’ life-sustaining treatment : unilateral medical decision-making in Australia and New Zealand

This article examines the law in Australia and New Zealand that governs the withholding and withdrawal of ‘futile’ life-sustaining treatment. Although doctors have both civil and criminal law duties to treat patients, those general duties do not require the provision of treatment that is deemed to be futile. This is either because futile treatment is not in a patient’s best interests or because stopping such treatment does not breach the criminal law. This means, in the absence of a duty to treat, doctors may unilaterally withdraw or withhold treatment that is futile; consent is not required. The article then examines whether this general position has been altered by statute. It considers a range of suggested possible legislation but concludes it is likely that only Queensland’s adult guardianship legislation imposes a requirement to obtain consent to withhold or withdraw such treatment.

Metal ion levels post unilateral primary Exeter total hip replacement

There has been much discussion and controversy in the media recently regarding metal toxicity following large head metal on metal (MoM) total hip replacement (THR). Patients have been reported as having hugely elevated levels of metal ions with, at times, devastating systemic, neurolgical and/or orthopaedic sequelae. However, no direct correlation between metal ion level and severity of metallosis has yet been defined. Normative levels of metal ions in well functioning, non Cobalt-Chrome hips have also not been defined to date. The Exeter total hip replacement contains no Cobalt-Chrome (Co-Cr) as it is made entirely from stainless steel. However, small levels of these metals may be present in the modular head of the prosthesis, and their effect on metal ion levels in the well functioning patient has not been investigated. We proposed to define the “normal” levels of metal ions detected by blood test in 20 well functioning patients at a minimum 1 year post primary Exeter total hip replacement, where the patient had had only one joint replaced. Presently, accepted normal levels of blood Chromium are 10–100 nmol/L and plasma Cobalt are 0–20 nmol/L. The UK Modern Humanities Research Association (MHRA) has suggested that levels of either Cobalt or Chromium above 7 ppb (equivalent to 135 nmol/L for Chromium and 120 nmol/L for Cobalt) may be significant. Below this level it is indicated that significant soft tissue reaction and tissue damage is less likely and the risk of implant failure is reduced. Hips were a mixture of cemented and hybrid procedures performed by two experienced orthopaedic consultants. Seventy percent were female, with a mixture of head sizes used. In our cohort, there were no cases where the blood Chromium levels were above the normal range, and in more than 70% of cases, levels were below recordable levels. There were also no cases of elevated plasma Cobalt levels, and in 35% of cases, levels were negligible. We conclude that the implantation with an Exeter total hip replacement does not lead to elevation of blood metal ion levels.

Pregnancy loss and psychiatric disorders in young women : an Australian birth cohort study

Background Recent evidence has linked induced abortion with later adverse psychiatric outcomes in young women. Aims To examine whether abortion or miscarriage are associated with subsequent psychiatric and substance use disorders. Method A sample (n=1223) of women from a cohort born between 1981 and 1984 in Australia were assessed at 21 years for psychiatric and substance use disorders and lifetime pregnancy histories. Results Young women reporting a pregnancy loss had nearly three times the odds of experiencing a lifetime illicit drug disorder (excluding cannabis): abortion odds ratio (OR)=3.6 (95% CI 2.0–6.7) and miscarriage OR=2.6 (95% CI 1.2–5.4). Abortion was associated with alcohol use disorder (OR=2.1, 95% CI 1.3–3.5) and 12-month depression (OR=1.9, 95% CI 1.1–3.1). Conclusions These findings add to the growing body of evidence suggesting that pregnancy loss per se, whether abortion or miscarriage, increases the risk of a range of substance use disorders and affective disorders in young women.

Pregnancy loss and mental health

Between 8 and 20 percent of depression in young men and women aged 18-23 is associated with pregnancy loss, according to a recent analysis of the 30 year Mater Hospital longitudinal study of mothers and children. Dr Kaeleen Dingle from the University of Queensland explains the study and discusses the implications for both men and women.

FP01-5 Pregnancy loss and psychiatric disorders in young men and women : results from Australian longitudinal cohort study

Recent evidence has linked induced abortion with later adverse psychiatric outcomes in young women. Little is known about later adverse psychiatric outcomes in young men whose partners have fallen pregnant and either go on to have a child, have an abortion or miscarry. 1223 women and 1159 men, from an Austrailan cohort born between 1981 and 1984, were assessed at 21 years for psychiatric and substance misuse and lifetime pregnancy histories. Young women reporting a pregnancy loss (either miscarriage or abortion) had nearly three times the odds of experiencing a illicit drug disorder (excluding cannabis), and nearly twice the odds of an alcohol misuse compared to never pregnant women. Young men whose partner had an abortion, but not a miscarriage, had nearly twice the odds of cannabis disorder, illicit drug disorder, and mood disorder compared to men that had never fathered a pregnancy. Young women who have lost a pregnancy have an increased risk of developing alcohol or substance abuse in later life. Young men whose partner aborted a pregnancy only had an increased of substance abuse and mood disorder in later life. These findings add to the growing body of evidence suggesting that pregnancy loss per se increases the risk of a range of substance use disorders in young women. The findings for young men are novel and raise the possibility that the associations measured may be due to common unmeasured factors associated with early pregnancy in young people rather than pregnancy loss.

High-resolution loss of heterozygosity screening implicates PTPRJ as a potential tumor suppressor gene that affects susceptibility to non-Hodgkin's Lymphoma

We employed a Hidden-Markov-Model (HMM) algorithm in loss of heterozygosity (LOH) analysis of high-density single nucleotide polymorphism (SNP) array data from Non-Hodgkin’s lymphoma (NHL) entities, follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL). This revealed a high frequency of LOH over the chromosomal region 11p11.2, containing the gene encoding the protein tyrosine phosphatase receptor type J (PTPRJ). Although PTPRJ regulates components of key survival pathways in B-cells (i.e., BCR, MAPK, and PI3K signaling), its role in B-cell development is poorly understood. LOH of PTPRJ has been described in several types of cancer but not in any hematological malignancy. Interestingly, FL cases with LOH exhibited down-regulation of PTPRJ, in contrast no significant variation of expression was shown in DLBCLs. In addition, sequence screening in Exons 5 and 13 of PTPRJ identified the G973A (rs2270993), T1054C (rs2270992), A1182C (rs1566734), and G2971C (rs4752904) coding SNPs (cSNPs). The A1182 allele was significantly more frequent in FLs and in NHLs with LOH. Significant over-representation of the C1054 (rs2270992) and the C2971 (rs4752904) alleles were also observed in LOH cases. A haplotype analysis also revealed a significant lower frequency of haplotype GTCG in NHL cases, but it was only detected in cases with retention. Conversely, haplotype GCAC was over-representated in cases with LOH. Altogether, these results indicate that the inactivation of PTPRJ may be a common lymphomagenic mechanism in these NHL subtypes and that haplotypes in PTPRJ gene may play a role in susceptibility to NHL, by affecting activation of PTPRJ in these B-cell lymphomas.

Functional analysis of missense variants in the TRESK (KCNK18) K+ channel

A loss of function mutation in the TRESK K2P potassium channel (KCNK18), has recently been linked with typical familial migraine with aura. We now report the functional characterisation of additional TRESK channel missense variants identified in unrelated patients. Several variants either had no apparent functional effect, or they caused a reduction in channel activity. However, the C110R variant was found to cause a complete loss of TRESK function, yet is present in both sporadic migraine and control cohorts, and no variation in KCNK18 copy number was found. Thus despite the previously identified association between loss of TRESK channel activity and migraine in a large multigenerational pedigree, this finding indicates that a single non-functional TRESK variant is not alone sufficient to cause typical migraine and highlights the genetic complexity of this disorder. Migraine is a common, disabling neurological disorder with a genetic, environmental and in some cases hormonal component. It is characterized by attacks of severe, usually unilateral and throbbing headache, can be accompanied by nausea, vomiting and photophobia and is clinically divided into two main subtypes, migraine with aura (MA) when a migraine is accompanied by transient and reversible focal neurological symptoms and migraine without aura (MO)1. The multifactorial and clinical heterogeneity of the disorder have considerably hindered the identification of common migraine susceptibility genes and most of our current understanding comes from the studies of familial hemiplegic migraine (FHM), a rare monogenic autosomal dominant form of MA2. So far, the three susceptibility genes that have been convincingly identified in FHM families all encode ion channels or transporters: CACNA1A encoding the α1 subunit of the Cav2.1 calcium channel3, SCN1A encoding the Nav1.1 sodium channel4 and ATP1A2 encoding the α2 subunit of the Na+/K+ pump5. It is believed that mutations in these genes may lead to increased efflux of glutamate and potassium in the synapse and thereby cause migraine by rendering the brain more susceptible to cortical spreading depression (CSD)6 which is thought to play a role in initiating a migraine attack7,8. However, these genes have not to date been implicated in common forms of migraine9. Nevertheless, current opinion suggests that typical migraine, like FHM, is also disorder of neuronal excitability, ion homeostasis and neurotransmitter release10,11,12. Mutations in the SLC4A4 gene encoding the sodium-bicarbonate cotransporter NBCe1, have recently been implicated in several different forms of migraine13, and a variety of genes involved in glutamate homeostasis (PGCP, MTDH14 and LRP115) and a cation channel (TRPM8)15 have also recently been implicated in migraine via genome-wide association studies. Ion channels are therefore highly likely to play an important role in the pathogenesis of typical migraine. TRESK (KCNK18), is a member of the two-pore domain (K2P) family of potassium channels involved in the control of cellular electrical excitability16. Regulation of TRESK activity by the calcium-dependent phosphatase calcineurin17, as well as its expression in dorsal root ganglia (DRG)18 and trigeminal ganglia (TG)19,20 has led to a proposed role for this channel in a variety of pain pathways. In a recent study, a frameshift mutation (F139Wfsx24) in TRESK was identified in a large multigenerational pedigree where it co-segregated perfectly with typical MA and a significant genome-wide linkage LOD score of 3.0. Furthermore, functional analysis revealed that this mutation caused a complete loss of TRESK function and that the truncated subunit was also capable of down regulating wild-type channel function. This therefore highlighted KCNK18 as potentially important candidate gene and suggested that TRESK dysfunction might play a possible role in the pathogenesis of familial migraine with visual aura20. Additional screening for KCNK18 mutations in unrelated sporadic migraine and control cohorts also identified a number of other missense variants; R10G, A34V, C110R, S231P and A233V20. The A233V variant was found only in the control cohort, whilst A34V was identified in a single Australian migraine proband for which family samples were not available, but it was not detected in controls. By contrast, the R10G, C110R, and S231P variants were found in both migraineurs and controls in both cohorts. In this study, we have investigated the functional effect of these variants to further probe the potential association of TRESK dysfunction with typical migraine.

A new method to detect loss of heterozygosity using cohort heterozygosity comparisons

Background Loss of heterozygosity (LOH) is an important marker for one of the 'two-hits' required for tumor suppressor gene inactivation. Traditional methods for mapping LOH regions require the comparison of both tumor and patient-matched normal DNA samples. However, for many archival samples, patient-matched normal DNA is not available leading to the under-utilization of this important resource in LOH studies. Here we describe a new method for LOH analysis that relies on the genome-wide comparison of heterozygosity of single nucleotide polymorphisms (SNPs) between cohorts of cases and un-matched healthy control samples. Regions of LOH are defined by consistent decreases in heterozygosity across a genetic region in the case cohort compared to the control cohort. Methods DNA was collected from 20 Follicular Lymphoma (FL) tumor samples, 20 Diffuse Large B-cell Lymphoma (DLBCL) tumor samples, neoplastic B-cells of 10 B-cell Chronic Lymphocytic Leukemia (B-CLL) patients and Buccal cell samples matched to 4 of these B-CLL patients. The cohort heterozygosity comparison method was developed and validated using LOH derived in a small cohort of B-CLL by traditional comparisons of tumor and normal DNA samples, and compared to the only alternative method for LOH analysis without patient matched controls. LOH candidate regions were then generated for enlarged cohorts of B-CLL, FL and DLBCL samples using our cohort heterozygosity comparison method in order to evaluate potential LOH candidate regions in these non-Hodgkin's lymphoma tumor subtypes. Results Using a small cohort of B-CLL samples with patient-matched normal DNA we have validated the utility of this method and shown that it displays more accuracy and sensitivity in detecting LOH candidate regions compared to the only alternative method, the Hidden Markov Model (HMM) method. Subsequently, using B-CLL, FL and DLBCL tumor samples we have utilised cohort heterozygosity comparisons to localise LOH candidate regions in these subtypes of non-Hodgkin's lymphoma. Detected LOH regions included both previously described regions of LOH as well as novel genomic candidate regions. Conclusions We have proven the efficacy of the use of cohort heterozygosity comparisons for genome-wide mapping of LOH and shown it to be in many ways superior to the HMM method. Additionally, the use of this method to analyse SNP microarray data from 3 common forms of non-Hodgkin's lymphoma yielded interesting tumor suppressor gene candidates, including the ETV3 gene that was highlighted in both B-CLL and FL.

A systematic review of baseline psychosocial characterisation in dietary randomised controlled trials for weight loss

BACKGROUND/OBJECTIVE: To investigate the extent of baseline psychosocial characterisation of subjects in published dietary randomised controlled trials (RCTs) for weight loss. SUBJECTS/METHODS: Systematic review of adequately sized (nX10) RCTs comprising X1 diet-alone arm for weight loss were included for this systematic review. More specifically, trials included overweight (body mass index 425 kg/m2) adults, were of duration X8 weeks and had body weight as the primary outcome. Exclusion criteria included specific psychological intervention (for example, Cognitive Behaviour Therapy (CBT)), use of web-based tools, use of supplements, liquid diets, replacement meals and very-low calorie diets. Physical activity intervention was restricted to general exercise only (not supervised or prescribed, for example, VO2 maximum level). RESULTS: Of 176 weight-loss RCTs published during 2008–2010, 15 met selection criteria and were assessed for reported psychological characterisation of subjects. All studies reported standard characterisation of clinical and biochemical characteristics of subjects. Eleven studies reported no psychological attributes of subjects (three of these did exclude those taking psychoactive medication). Three studies collected data on particular aspects of psychology related to specific research objectives (figure scale rating, satiety and quality-of-life). Only one study provided a comprehensive background on psychological attributes of subjects. CONCLUSION: Better characterisation in behaviour-change interventions will reduce potential confounding and enhance generalisability of such studies.

"Listening, hearing and drawing things together to work on solutions" : NAPCAN Play a Part, Queensland, 2010-2013, Evaluation-Research Report

Responding to the idea of child friendly communities, Play a Part is an innovative program advancing preventative strategies for children and young people to minimise exposure to abuse and neglect. The program was developed ensuing an increase in notifications of suspected child abuse and neglect in 2007. Now completing the second phase, the program is a community engagement strategy that aims to prevent child abuse. Play a Part is described as “a whole of community approach to creating child friendly communities” (NAPCAN, 2012). The Play a Part program was piloted between 2007 and 2010 in five southeast Queensland communities, and is currently operating in parts of Logan City region and the Redlands region. To assess the merit of the second phase of the program the Children and Youth Research Centre at Queensland University of Technology was contracted to undertake an evaluation-research at the beginning of 2013.

A method of extracting switching loss from a high efficiency MOSFET based half bridge converter

The measurement of losses in high efficiency / high power converters is difficult. Measuring the losses directly from the difference between the input and output power results in large errors. Calorimetric methods are usually used to bypass this issue but introduce different problems, such as, long measurement times, limited power loss measurement range and/or large set up cost. In this paper the total losses of a converter are measured directly and switching losses are exacted. The measurements can be taken with only three multimeters and a current probe and a standard bench power supply. After acquiring two or three power loss versus output current sweeps, a series of curve fitting processes are applied and the switching losses extracted.

Depression scores predict adherence in a dietary weight loss intervention trial

Background & aims Depression has a complex association with cardiometabolic risk, both directly as an independent factor and indirectly through mediating effects on other risk factors such as BMI, diet, physical activity, and smoking. Since changes to many cardiometabolic risk factors involve behaviour change, the rise in depression prevalence as a major global health issue may present further challenges to long-term behaviour change to reduce such risk. This study investigated associations between depression scores and participation in a community-based weight management intervention trial. Methods A group of 64 overweight (BMI > 27), otherwise healthy adults, were recruited and randomised to follow either their usual diet, or an isocaloric diet in which saturated fat was replaced with monounsaturated fat (MUFA), to a target of 50% total fat, by adding macadamia nuts to the diet. Subjects were assessed for depressive symptoms at baseline and at ten weeks using the Beck Depression Inventory (BDI-II). Both control and intervention groups received advice on National Guidelines for Physical Activity and adhered to the same protocol for food diary completion and trial consultations. Anthropometric and clinical measurements (cholesterol, inflammatory mediators) also were taken at baseline and 10 weeks. Results During the recruitment phase, pre-existing diagnosed major depression was one of a range of reasons for initial exclusion of volunteers from the trial. Amongst enrolled participants, there was a significant correlation (R = −0.38, p < 0.05) between BDI-II scores at baseline and duration of participation in the trial. Subjects with a baseline BDI ≥10 (moderate to severe depression symptoms) were more likely to dropout of the trial before week 10 (p < 0.001). BDI-II scores in the intervention (MUFA) diet group decreased, but increased in the control group over the 10-week period. Univariate analysis of variance confirmed these observations (adjusted R2 = 0.257, p = 0.01). Body weight remained static over the 10-week period in the intervention group, corresponding to a relative increase in the control group (adjusted R2 = 0.097, p = 0.064). Conclusions Depression symptoms have the potential to affect enrolment in and adherence to dietbased risk reduction interventions, and may consequently influence the generalisability of such trials. Depression scores may therefore be useful for characterising, screening and allocating subjects to appropriate treatment pathways.

Court finds solicitor in breach of fiduciary duty owed to client but loss not caused by the breach

A solicitor owes fiduciary obligations to his or her client including the obligations of loyalty and disclosure. The Court of Appeal in Mantonella Pty Ltd v Thompson (2009) 255 ALR 367; [2009] QCA 80; BC200902311 recently considered when the fiduciary duty owed by a solicitor to a client is breached and the consequent liability of the solicitor...

Characteristics of on-road driving performance of persons with central vision loss who use bioptic telescopes

Purpose. To compare the on-road driving performance of visually impaired drivers using bioptic telescopes with age-matched controls. Methods. Participants included 23 persons (mean age = 33 ± 12 years) with visual acuity of 20/63 to 20/200 who were legally licensed to drive through a state bioptic driving program, and 23 visually normal age-matched controls (mean age = 33 ± 12 years). On-road driving was assessed in an instrumented dual-brake vehicle along 14.6 miles of city, suburban, and controlled-access highways. Two backseat evaluators independently rated driving performance using a standardized scoring system. Vehicle control was assessed through vehicle instrumentation and video recordings used to evaluate head movements, lane-keeping, pedestrian detection, and frequency of bioptic telescope use. Results. Ninety-six percent (22/23) of bioptic drivers and 100% (23/23) of controls were rated as safe to drive by the evaluators. There were no group differences for pedestrian detection, or ratings for scanning, speed, gap judgments, braking, indicator use, or obeying signs/signals. Bioptic drivers received worse ratings than controls for lane position and steering steadiness and had lower rates of correct sign and traffic signal recognition. Bioptic drivers made significantly more right head movements, drove more often over the right-hand lane marking, and exhibited more sudden braking than controls. Conclusions. Drivers with central vision loss who are licensed to drive through a bioptic driving program can display proficient on-road driving skills. This raises questions regarding the validity of denying such drivers a license without the opportunity to train with a bioptic telescope and undergo on-road evaluation.

An instrument to measure adherence to weight loss programs : the Compliance Praxis Survey-Diet (COMPASS-Diet)

Adherence to behavioral weight loss strategies is important for weight loss success. We aimed to examine the reliability and validity of a newly developed compliance praxis-diet (COMPASS-diet) survey with participants in a 10-week dietary intervention program. During the third of five sessions, participants of the “slim-without-diet” weight loss program (n = 253) completed the COMPASS-diet survey and provided data on demographic and clinical characteristics, and general self-efficacy. Group facilitators completed the COMPASS-diet-other scale estimating participants’ likely adherence from their perspective. We calculated internal consistency, convergent validity, and predictive value for objectively measured weight loss. Mean COMPASS-diet-self score was 82.4 (SD 14.2) and COMPASS-diet-other score 80.9 (SD 13.6) (possible range 12–108), with lowest scores in the normative behavior subscale. Cronbach alpha scores of the COMPASS-diet-self and -other scale were good (0.82 and 0.78, respectively). COMPASS-diet-self scores (r = 0.31) correlated more highly with general self-efficacy compared to COMPASS-diet-other scores (r = 0.04) providing evidence for validity. In multivariable analysis adjusted for age and gender, both the COMPASS-diet-self (F = 10.8, p < 0.001, r2 = 0.23) and other (F = 5.5, p < 0.001, r2 = 0.19) scales were significantly associated with weight loss achieved at program conclusion. COMPASS-diet surveys will allow group facilitators or trainers to identify patients who need additional support for optimal weight loss.