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Three cases of research misconduct, none conceded by their appropriate approving IRB/HREC. Without international transparency, nothing can be trusted.
Research Governance in Australia: exposing empirical deception
A case series of three ethical breaches within research institutions
The replacement of genuine moral reflection by procedures and protocols finally paralyses people’s
capacity for moral reflection... Padmasiri De Silva
Geoff Kirwood,
A case series of three ethical breaches within research institutions. The absence of audit for
purposes of Quality Control, so as to curtail undue industry influence or investigator deceit, damages
confidence in the medical evidence base. A history of research misconduct scandals exposed in the
Australian media is unfortunate recourse to redress deceptions, and publicly disparaging to a field of
mostly altruistic and dedicated scientists.
Method. Ethical failures by Victorian researchers, uncovered in the course of Clinical Research
studies, were investigated between 2015 and 2017. No recourse is made to privileged information,
but reliance is wholly upon published incriminatory facts. Three institutional and three government
regulatory governance bodies were tested for integrity per declared responsibilities, in three cases
for concern. Correspondence was sought from authors, their affiliated institution, and then
misconduct allegations escalated to funding bodies and finally, governmental regulators.
Results. A journal publisher declined to comment on a fabricated report; research Sponsors were
satisfied with progress of a study despite nothing having been published two and a half years
subsequent to final data collection; Federal Ministers were unconcerned by misappropriated grants;
and the only Institution conceding prima facie case for misconduct did so under cover of
Confidentiality. This concealment also applies to Australian Research Integrity Committee reporting
of that and all other cases.
Conclusion. Minimal evidence of accountability in Australian research was apparent in six regulatory
bodies’ ethical failures. Published statements as to ‘doing the right thing’ aside, the performance
record of both the institutional ethical governance and the national integrity authorities should be
reported upon. This would forewarn potential whistleblowers of not only career jeopardy, but also
the impossibility of redressing wrongdoing. Further investigation as to the extent of fraudulent,
fabricated or buried study reports is required before policy redress is undertaken.
A well-publicised exposé through national Australian Broadcasting Corporation (ABC) radio and TV
documentary of allegations over two years of ongoing scientific misconduct, fraud and fabricated
studies at University of New South Wales (UNSW) resulted in a finding by Vice-Chancellor Rory
Hume of errors of judgement warranting censure (Van Der Weyden (2004). Charges against Bruce
Hall, who is still a research Professor at UNSW, had been found proven by external inquiry under Sir
Gerard Brennan, onetime High Court Chief Justice. Hume resigned two years into his five year
tenure, and backed independent St James Ethics Centre inquiry’s recommendation (News, 2005) for
a US-style Office of Research Integrity (ORI), so as to remove responsibility for investigating research
misconduct from the funding bodies.
A decade later, again consequent to ABC coverage (Scott, 2013), UNSW’s failure to twice adequately
address allegations against Levon Khachigian of manipulated cancer cell images, caused National
Health & Medical Research Council (NHMRC) to withdraw $AUD8.4m in funding to the team,
pending an investigation. The resultant internal review stopped short of using the descriptor
‘misconduct’, but conceded that their Code of Conduct had been breached albeit apparently
inadvertently. Professor Khachigian was reinstated, and funding resumed, but the whistleblower Dr
Ying Morgan was not re-employed (Scott, 2013; UNSW, 2015; Israel and Drenth, 2016). This followed
UNSW’s confidentially twice dismissing allegations at both a preliminary and a subsequent review by
external panel insisted upon by Dr Morgan. The histology expertise of Prof David Vaux helped to air
the matter, and his subsequent article (Vaux, 2016) considers the spectrum of misconduct from
error through to intentional falsehood - putting not only trial participants at risk but, by inference,
including future iatrogenic harm through a corrupted evidence base. Repercussions of convicted US
felon Scott Reuben’s fabricated trials weren’t redressed by retraction alone, since there’s 21
systematic reviews to amend, and clinical protocols that may never be rewritten (Marret et al.,
The Australian Research Integrity Committee (ARIC) would appear to function as an ORI equal to
those of the US or UK, but lacking statutory powers. Their charter is to “Review the process by which
a nominated institution has managed an allegation of research misconduct
(AustralianResearchCouncil, 2011) and inform the appropriate CEO of either NHMRC or translational
science funding body, the Aust Research Council. ARIC discloses their activity as a paragraph in the
parent body annual report. These past five years consistently report a de-identified finding of:
“…several weaknesses in an institution’s investigative process. The NHMRC CEO subsequently
communicated with the institution on the matter(Brent, 2014). There are no mentions of retraction
or other repercussion.
Methods and Rationale
Testing of institutions is poorly tolerated in academia, making this report novel. Quality
Management in organisations is prescribed by ISO9001, which follows a ‘Plan, Do, Check, Act’ model.
Quality Assurance establishes process frameworks, then Quality Control checks upon their success,
and acts appropriately. However research institutions wholly focus on guidelines as preventative of
ethical failure, and lack precedents for robust methods of detection or remedial action.
The following examples of hitherto unreported misconduct detailed were encountered in the course
of studies at Deakin and Monash Universities. None meet the definition of ‘whistleblow’ in that
privileged information isn’t leaked, rather the allegations are reliant upon facts which are publicly
available. The concern is that there was no forum available to dispute research conduct. The three
exemplified situations involved repeated institutional Human Research Ethics Committee (HREC)
apathy to complaints from this non-faculty member author. These tests of integrity were further
applied to three regulatory authorities.
Allegations of an ethical breach were raised to, first the designated corresponding author (p.o.c) and
Principal Investigator (PI), then second the institutional ethics approvers, and third multiple
independent bodies grant funding and/or government regulators, or journal editors and/or
ethicists at contributing author’s universities.
1. Relationship Between Mental Health and Foot Pain
NHMRC funded a cohort study on obesity and osteoarthritic knee pain (Berry et al., 2010), data from
which and with additional support from Royal Australasian College of Physicians (RACP) resulted in
this offshoot study (Butterworth et al., 2014) published in journal Arthritis Care and Research
(AC&R). The authors comprised rheumatologists, podiatrists, and bariatric physicians. The above title
and Conclusion: “Mental health is associated with changes in foot pain” are at odds with data
presented. Table 1 of the article reveals a non-significant p=0.08 association between chronic pain
non-improvers and poor mental health. However, the significant association of Vitality as measured
by SF-36 with the outcome (p=0.02) is overlooked. Both PI , p.o.c. in Monash School of Public Health
& Preventative Medicine (SPHPM), and her NHMRC rheumatology grants Assigner co-author
declined to acknowledge the complaint, and subsequent NHMRC trial funded by grant 1083664 of a
TriCyclic Antidepressant to treat pain sensitisation in that population concluded in 2018 and awaits
report. This matter was brought to the attention of an ARIC member and onetime NHMRC
Commissioner of Unanswered complaints who co-presented at SPHPM seminar ‘Why very few
patients benefit from the drugs they take and why many are harmed by them, on 6th Feb 2015 and
again on 8th Jun.
NHMRC Director of Grants repeated their response deferring accountability to Monash HREC on 17th
April, stating: To reiterate, we would anticipate that the institution would manage the allegation of
research misconduct in accordance with Part B of the Code [Australian Code for the Responsible
Conduct of Research (NHMRC, 2007a)] … If you are not satisfied with the liaison you have had with
the institution… One option is lodging your complaint with the Commonwealth Ombudsman.
A complaint was made to the Commonwealth Ombudsman, whose reply conceded systemic faults:
“… the NHMRC's response of 12 May 2015 to your complaint, indicated that the NHMRC referred you
to other bodies to pursue your complaint, in particular the researcher's institution. In my view this
was not an unreasonable response. I am aware, however, that your approaches to other bodies,
including the researcher's university, have been unsuccessful to date(Baragry, 2015). The editor of
AC&R was contacted 24th April 2015, as were publishers American College of Rheumatology, but
without reply. SPHPM Research Governance Officer was contacted on 19th May, with this third
instance complaining of ethical breaches within the department, but only the two matters previous
were acknowledged even if not pursued. Monash HREC was then notified on 21st May, and
acknowledged on 29th October 2015, but took no action and stopped corresponding. Complaint
made to Manager of Research at RACP Foundation was answered 4th Aug with “… the College does
no enter into correspondence regarding its decisions(Winne, 2015).
2. PT056 Pharmacological Restoration of Mood In Heart Failure (Pro-Heart): Rationale
And Design(Hare et al., 2014)
PRO-HEART enrolled the first participant in the 6-month trial of anti-depressant escitalopram in Oct
2010, the same year that the manufacturer pleaded guilty to allegations of “off-label promotion of
the drugs and various forms of illegal remuneration for doctors, including cash payments disguised as
grants or consulting fees, preceptorships, speaking fees, expensive meals and lavish entertainment
and other valuable goods and services(Office-PublicAffairs, 2010). The study p.o.c. and PI both
declined to answer a concern raised on 3rd June 2014, and sent again on 9th July 2015, regarding the
worsened risk of hyponatremia in the studied population, an association which was later proven
(Leth-Møller et al., 2016).
A German trial’s finding against the use of escitalopram in heart failure (Angermann et al., 2016)
should have been raised by the team with their Ethics Committee per Section 12.8(e) of NHMRC
guidelines (NHMRC, 2007b), but Austin Health refused a formal Freedom of Information Act request
of 19th July 2017 as to whether this adverse event was envisaged or ever communicated. Their
grounds given being (Stephens, 2017) under Trade Secrets and Information Communicated in
Confidence where “Disclosure may impair our ability to acquire such information in the future”. This
commercial confidentiality was despite funding having come from two public charities.
The sponsors forecast a completion year of 2014 (BeyondBlue, 2007) and final data was collected
Feb 2018. The CEO of BeyondBlue stated on 18th August 2017 that she was satisfied with its
progress, and chair Julia Gillard declined to comment to absence of a report two and a half years
later. Funding partner Heart Foundation’s manager of executive services responded 9th July 2015 on
behalf of the CEO, to advise that “Safe-guarding the rights and welfare of human subjects involved in
research during the tenure of Heart Foundation funded research is the responsibility of the awardee
and of the institution in which the award is held". Another author on the protocol (Hare et al., 2014)
was approached, answering on 4th September 2017 of: Im not involved in this trial. If you have any
problems with this trial please direct your inquiries to Austin Health ethics committee. Austin Health
Research manager ignored the latest challenge to buried results, in July 2020, having declined a 2018
offered right-of-reply to this article’s draft.
3. The Feasibility of Embedding Data Collection into the Routine Service Delivery of a
Multi-Component Program for High-Risk Young People (Knight et al., 2017)
A UNSW Professor was serving on the NHMRC GRANTS committee when $AUD386,771 was awarded
to his brother’s business BackTrack, for a trial proposing to provide cognitive based therapy to
teenage abusers of alcohol (Shakeshaft, 2015). The BackTrack manager’s prior experience was as a
dogcatcher (Meldrum-Hanna, 2011), and there are no skills in delivery of psychotherapy among the
staff. Indeed, operations as documented in an observational PhD includes physical abuse, and the
manager has been caught Driving Under the Influence of alcohol (Pastor, 2015). The published
report (Knight et al., 2017) contains only survey data, and neither the PI, Bernie Shakeshaft, nor
p.o.c. (lead author, qualification being BA and Bach Business) responded to a request for details of
the claimed intervention. BackTrack runs a residential farm, offering inmates free board and
(unaccredited) farm skills training in return for labour to neighbouring properties. Both Indigenous
and white juvenile (14-17yo) miscreants are recruited when presenting at Armidale Magistrates
Court, when custodial sentencing appears to be the only option due to prior record. The first three
principles of the Code’ (NHMRC, 2007a) are violated, being: respect the rights of those affected;
manage conflicts of interest; and adopt methods appropriate for proposal aims.
NHMRC Ethics and Governance memo of 17th May 2017 advised: “Your allegations of misconduct
would need to be addressed by raising your concerns with the research institution through which the
research was conducted. NHMRC has no remit to independently investigate allegations of research
misconduct or breaches of the Code”. Director of Integrity at UNSW had acknowledged the complaint
sent 5th May 2017, and committed to respond to the alleged conflict of interest within three weeks.
A reminder was sent when this lapsed, along with assertion of criminal fraud in that money was
claimed for works not performed. UNSW advised on 29th Jun 2017 that another week was needed
for answering very serious and complex concerns, and two years later on 14th Feb 2019 sent a
Strictly Confidential letter finding a prima facie case of Research Code breach, but not one of
Research Misconduct owing to not being ‘multiple and continuous’.
Australian Federal Police disclaimed jurisdiction: “Under the Australian Government Investigations
Standards, Commonwealth entities have their own anti-fraud or investigative components, and have
the primary responsibility for investigating fraud involving their agencies(Witchard, 2017). Of the
two AFP suggested agencies, the Fraud Section in Dept of Prime Minister & Cabinet didn’t reply, and
the Ombudsman sent a case closure letter (Hill, 2017) stating: ”I suggest that you raise this matter
with the UNSW again. On 13th Aug 2017 a formal Request for Review form was submitted to ARIC,
and four days later notification received that a response should be had within three weeks. A status
request was answered on 19th Oct with an update from the ARIC Chair of “still under investigation
by UNSW (Brent, 2017).
77 American Institutional Research Integrity Officers were interviewed for a report on process,
where it was found that 23% of complaints were lodged by post-doc level or below, and 71% by
Scientist or Professor (Bonito et al., 2012). This could indicate that seniority imbued greater
confidence to break rank, even when given statutory protection. That is one of several factors, along
with institutional supportiveness, mooted as being predictive of complaint effectiveness (Malek,
2010). Risk vs benefit steers the moral compass for most placed in such a dilemma. The Dalai Lama’s
call for moral responsibility despite the presence of dirty business and dirty science is described as
‘muscular compassion’ (Goleman, 2015), and reliant upon an inner strength outside of any
framework’s support.
The US independent ORI is envisaged, on the basis of researcher survey, to handle 2300 cases p.a.,
yet receives at most a hundred allegations (Bonito et al., 2012). The scale of the problem is
perceived as being two dozen times bigger than the effort to expose it. Over the last decade
misconduct findings by ORI have averaged 11 p.a., and twice as many more complaints were not
pursued or lacked evidence (Partin, 2017).
The ARIC and SPHPM member to whom complaint was made of the false mental health and pain
conclusion has opined that whistleblowers are undervalued and lack support, while auditing was
overly costly (Breen, 2016). He’d earlier authored a chapter with mention of the Hall affair: The
Code places an onus on institutions to ensure that researchers are trained in research ethics and
research practices according to the Code, the National Statement on Ethical Conduct in Human
Research and related documents, and places an onus on researchers to make themselves familiar
with these documents. One study of the staff of a large research institute suggested that clinician
researchers were the group least informed about these documents(Breen, 2010), entrusting
guideline compliance to a self-regulatory model and putting blame on clinicians for ignorance (Babl
and Sharwood, 2008). On the one hand organisational stonewalling blocks individuals making an
ethical stance, yet on the other reform is being suggested from the bottom upwards.
A Medical Journal of Australia editorial (Van Der Weyden, 2004) on UNSW’s Prof Hall itemised these
needs: External inquiry upfront; Statutory powers; Panel expertise; Transparency rather than
confidentiality; Universal process; and Prevention rather than detection. Two years later the current
Monash SPHPM Governance Officer and Head of School co-authored a document endorsing their
internal audit process (Poustie et al., 2006), citing the MJA editorial but mentioning neither these six
lessons nor the merit of an ORI.
As of Feb 2017 a substantially revised 2010 ‘NHMRC policy on actions to be taken in response to
misconduct involving NHMRC funding’ came into effect, having grown from 6 to 23 pages (Director,
2016). A major amendment was mandatory notification to NHMRC by the institution of any
investigation exceeding 56 days. Disregard of this timeframe by UNSW demonstrates the weakness
of guidelines alone. A concurrent revision to ‘the Code’ (NHMRC, 2007a), approved in 2018, was
circulated for feedback to both institutions and the largely independent Association of Australian
Medical Research Industries, with the latter submitting that (if adopted) the administrative burden
of “adhering to multiple legislative and policy instruments” would be lessened (Hilton, 2015).
Introduction to part B ‘Breaches of the Code and misconduct in research’ acknowledges calls for
holding of investigations in independent statutory tribunals, but considers the Federal Constitution
to be among the legal obstacles. A further impediment to justice came from Workplace Agreements
in academia (Van Der Weyden, 2004), so a legal Commission of Inquiry could be requisite to
improved conduct.
Integrity means doing the right thing in a reliable way. Much is written about ethics, but the lack of
cohesion between words and actions strengthens the claim made: there is no accountability in these
institutions medical research governance. Three of the universities are members of the Group of
Eight, a coalition of leading Australian research universities in receipt of 60% of the NHMRC
$AUD800m budget, ostensibly robust institutions.
A global review of national Ethics Committees performance would be a merit-worthy study, one
that compared the record of misconduct allegations with investigational outcomes. This report
recorded failures due to stonewalling from four institutional HRECs, and two regulators i.e.
Commonwealth Ombudsman and NHMRC Ethics & Integrity. This consistent result gives confidence
to the declaration that governance in Australian research is not assured, and hence contamination of
the global evidence base is to an indeterminate degree. The prevailing attitude in Australia seems to
be that ‘what happens in the department, stays in the institution’.
Empty suggestions of further templates for best practice, or ongoing research into misconduct’s
roots, both continue the unhealthy situation of unchecked breaches. It’s been postulated that extant
mandatory training, and diligent mentoring are sufficient (Kornfeld and Titus, 2017). But without
international registries for reporting against complaints, it’s impossible to tell if the Australian
context is unique.
Institutional process documents are written on the assumption that a staff member is intending to
whistleblow, yet the three cases were submitted by a postgrad student.
Acknowledgements and Declaration
Thanks to Prof Brian Martin, University of Wollongong, whose assistance through writing critique
was greatly appreciated. The author has no conflicts-of-interest to declare, and is self-funded. This
report does not reuse any material published elsewhere.
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Background: There is little evidence about how to improve outcomes for high-risk young people, of whom Indigenous young people are disproportionately represented, due to few evaluation studies of interventions. One way to increase the evidence is to have researchers and service providers collaborate to embed evaluation into the routine delivery of services, so program delivery and evaluation occur simultaneously. This study aims to demonstrate the feasibility of integrating best-evidence measures into the routine data collection processes of a service for high-risk young people, and identify the number and nature of risk factors experienced by participants. Methods: The youth service is a rural based NGO comprised of multiple program components: (i) engagement activities; (ii) case management; (iii) diversionary activities; (iv) personal development; and (v) learning and skills. A best-evidence assessment tool was developed by staff and researchers and embedded into the service's existing intake procedure. Assessment items were organised into demographic characteristics and four domains of risk: education and employment; health and wellbeing; substance use; and crime. Descriptive data are presented and summary risk variables were created for each domain of risk. A count of these summary variables represented the number of co-occurring risks experienced by each participant. The feasibility of this process was determined by the proportion of participants who completed the intake assessment and provided research consent. Results: This study shows 85% of participants completed the assessment tool demonstrating that data on participant risk factors can feasibly be collected by embedding a best-evidence assessment tool into the routine data collection processes of a service. The most prevalent risk factors were school absence, unemployment, suicide ideation, mental distress, substance use, low levels of physical activity, low health service utilisation, and involvement in crime or with the juvenile justice system. All but one participant experienced at least two co-occurring domains of risk, and the majority of participants (58%) experienced co-occurring risk across four domains. Conclusions: This is the first study to demonstrate that best-evidence measures can feasibly be embedded into the routine data collection processes of a service for high-risk young people. This process allows services to tailor their activities to the most prevalent risks experienced by participants, and monitor these risks over time. Replication of this process in other services would improve the quality of services, facilitate more high quality evaluations of services, and contribute evidence on how to improve outcomes for high-risk young people.
Full-text available
Importance: Depression is frequent in patients with heart failure and is associated with adverse clinical outcomes. Long-term efficacy and safety of selective serotonin reuptake inhibitors in these patients are unknown. Objective: To determine whether 24 months of treatment with escitalopram improves mortality, morbidity, and mood in patients with chronic systolic heart failure and depression. Design, setting, and participants: The Effects of Selective Serotonin Re-Uptake Inhibition on Morbidity, Mortality, and Mood in Depressed Heart Failure Patients (MOOD-HF) study was a double-blind, placebo-controlled randomized clinical trial conducted at 16 tertiary medical centers in Germany. Between March 2009 and February 2014, patients at outpatient clinics with New York Heart Association class II-IV heart failure and reduced left ventricular ejection fraction (<45%) were screened for depression using the 9-item Patient Health Questionnaire. Patients with suspected depression were then invited to undergo a Structured Clinical Interview based on the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) to establish the diagnosis. Interventions: Patients were randomized 1:1 to receive escitalopram (10-20 mg) or matching placebo in addition to optimal heart failure therapy. Study duration was 24 months. Main outcomes and measures: The composite primary outcome was time to all-cause death or hospitalization. Prespecified secondary outcomes included safety and depression severity at 12 weeks of treatment (including the titration period), which were determined using the 10-item Montgomery-Åsberg Depression Rating Scale (total possible score, 0 to 60; higher scores indicate more severe depression). Results: A total of 372 patients (mean age, 62 years; 24% female) were randomized and had taken at least 1 dose of study medication when the data and safety monitoring committee recommended the trial be stopped early. During a median participation time of 18.4 months (n = 185) for the escitalopram group and 18.7 months (n = 187) for the placebo group, the primary outcome of death or hospitalization occurred in 116 (63%) patients and 119 (64%) patients, respectively (hazard ratio, 0.99 [95% CI, 0.76 to 1.27]; P = .92). The mean Montgomery-Åsberg Depression Rating Scale sum score changed from 20.2 at baseline to 11.2 at 12 weeks in the escitalopram group and from 21.4 to 12.5 in the placebo group (between-group difference, -0.9 [95% CI,-2.6 to 0.7]; P = .26). Safety parameters were comparable between groups. Conclusions and relevance: In patients with chronic heart failure with reduced ejection fraction and depression, 18 months of treatment with escitalopram compared with placebo did not significantly reduce all-cause mortality or hospitalization, and there was no significant improvement in depression. These findings do not support the use of escitalopram in patients with chronic systolic heart failure and depression. Trial registration: Identifier: ISRCTN33128015.
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Objective To examine the association between classes of antidepressants and hyponatremia, and between specific antidepressants and hyponatremia. Design Retrospective register-based cohort study using nationwide registers from 1998 to 2012. Setting The North Denmark Region. Participants In total, 638 352 individuals were included. Primary and secondary outcome measures Plasma sodium was obtained from the LABKA database. The primary outcome was hyponatremia defined as plasma sodium (p-sodium) below 135 mmol/L and secondary outcome was severe hyponatremia defined as p-sodium below 130 mmol/L. The association between use of specific antidepressants and hyponatremia was analysed using multivariable Poisson regression models. Results An event of hyponatremia occurred in 72 509 individuals and 11.36% (n=6476) of these events happened during treatment with antidepressants. Incidence rate ratios and CIs for the association with hyponatremia in the first p-sodium measured after initiation of treatment were for citalopram 7.8 (CI 7.42 to 8.20); clomipramine 4.93 (CI 2.72 to 8.94); duloxetine 2.05 (CI 1.44 to 292); venlafaxine 2.90 (CI 2.43 to 3.46); mirtazapine 2.95 (CI 2.71 to 3.21); and mianserin 0.90 (CI 0.71 to 1.14). Conclusions All antidepressants except mianserin are associated with hyponatremia. The association is strongest with citalopram and lowest with duloxetine, venlafaxine and mirtazapine.
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Making an allegation of research misconduct can be stressful for a whistleblower. The Research Integrity Officer (RIO) can play an important role in helping reduce the stress by thoroughly discussing what whistleblowers can expect if they make an allegation. Through interviews with 77 RIOs who had recently handled a research misconduct case, we found that RIOs who addressed more topics as well as specific aspects of the topics were more likely to have used some type of memory aide in their initial contact with whistleblowers, talked with ORI staff or other RIOs about "hypothetical" research misconduct cases, or attended a RIO boot camp training. We believe that RIOs who more fully inform whistleblowers are providing timely preparation and building whistleblowers' confidence so they can make a more informed decision about reporting and experience less stress.
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Obesity is an important risk factor for knee OA. Evidence suggests that fat and muscle have differential effects on the pathogenesis of disease. The aim of this study was to examine the relationship between body composition and knee structure, including knee cartilage volume, defects and bone marrow lesions (BMLs). A total of 153 subjects aged 25-60 years, 81% females, were recruited across a range of BMI (18-55 kg/m2) for a study examining the relationship between obesity and musculoskeletal disease. MRI was performed of the dominant knee. Cartilage volume, defects and BMLs were measured using validated methods. Body composition was measured using dual X-ray absorptiometry. There was an 81 (95% CI: 69, 94) mm3 increase in cartilage volume for every 1 kg increase in skeletal muscle mass. Fat mass was not significantly associated with cartilage volume. Fat mass, but not skeletal muscle mass, was a risk factor for cartilage defects and BMLs. For every 1 kg increase in total body fat there was an increased risk of cartilage defects (OR=1.31, 95% CI: 1.04, 1.64) and BMLs (OR=1.09, 95% CI: 1.01, 1.18). In this relatively healthy population, fat mass was associated with increased cartilage defects and BMLs, which are features of early knee OA. In contrast, skeletal muscle mass was positively associated with cartilage volume, which may be due to coinheritance, a commonality of environmental factors associated with cartilage accrual or a protective effect of increased muscle.
Much published science, especially biomedical science, is not reproducible. While most of this is likely due to sloppy research practices, part of it is due to deliberate falsification or fabrication of data, i.e., research misconduct. Plagiarism is also a form of misconduct, and although it might not cause errors to enter the literature, it undermines trust, creates inefficiencies, and deters honest researchers from careers in science. While a growing number of papers are being retracted, and the biggest reason for retractions is misconduct, it is not clear whether there is an increase in the incidence of misconduct, an increase in awareness, or both. Authors, readers, reviewers, editors, publishers, and institutions all have responsibilities in detecting and managing misconduct and correcting the literature. To improve the situation, the incentives to fabricate need to be reduced, and rewards for authors, readers, reviewers, editors, publishers, and institutions who do the right thing should be increased. Every country needs to establish research integrity bodies to provide advice and oversight, collect data, and improve codes of practice.
The incidence of research misconduct appears to be increasing, drawing attention in the general media and academic literature. Concerns have been expressed about probable under-reporting, harms arising, lack of an agreed international definition, welfare of whistleblowers and the adequacy of the investigation processes and any subsequent sanctions. A fully satisfactory approach to prevention, detection, investigation and adjudication has yet to emerge. While the definition of research misconduct contained in the Australian Code for the Responsible Conduct of Research is comprehensive, universities and other research institutions at times struggle in their task of investigating and adjudicating allegations of research misconduct. A more centralised, independent process of oversight and monitoring of this role played by the universities and institutions would help support those institutions and help maintain community confidence in the research endeavour.
Introduction: More than 20% of chronic heart failure (CHF) patients are depressed and have an increased mortality risk, poor medication adherence and poor quality of life. There is currently no evidence that depressed CHF patients respond to anti-depressant medications. The Pharmacological Restoration of mOod in HEART failure (PRO-HEART) trial ( is an investigator initiated, double- blind, randomized, placebo-controlled, parallel group, multi-centre study run by Austin Health with collaborative funding from the Heart Foundation of Australia and beyondblue. Objectives: The primary aim of PRO-HEART is to assess the efficacy of the selective serotonin re-uptake inhibitor, escitalopram, to reduce depression symptoms in CHF patients using the Hamilton Depression Rating Scale (HAM-D) and the Cardiac Depression Scale (CDS). Secondary aims are to examine the association between change in depression scores and autonomic function, psychosocial functioning, and gene polymorphisms. Methods: Systolic CHF patients receiving optimal heart failure pharmacotherapy, with documented LVEF < 0.40 and screening positive for depression confirmed by psychiatric interview are eligible for enrolment. Power calculations on the primary end-point require randomisation of 124 patients, stratified according to investigational site and depression severity. Escitalopram or matching placebo will be up-titrated from 5mg to 10mg after 1 week, followed by depression-severity guided up-titration to 20mg at 2 months. Patients will receive allocated, blinded treatment for 6 months, followed by a 6 month open label phase for the active treatment group. Results: Treatment efficacy will be evaluated from baseline to 6 months on the CDS and 17-item HAM-D scores for combined Major and Minor Depression using Analysis of Covariance (ANCOVA), with the effects of escitalopram on depression, autonomic and psychosocial functioning adjusted for age, gender and baseline psychological functioning. Hierarchical multiple regression will be used to examine the association between change in depression and change in intermediate cardiac end points, such as autonomic functioning, and social support. Conclusion: PRO-HEART should inform and contribute to international management guidelines for depression in CHF patients.
Objective: Although mental health is related to the persistence of musculoskeletal pain, our understanding of the relationship between mental health and foot pain is limited. Subsequently, we conducted a 3-year longitudinal study to examine the relationship between mental health and foot pain in a community-based population. Methods: Eighty-three community-dwelling participants (mean ± SD body mass index [BMI] 35.3 ± 9.0 kg/m2) who had foot pain at study inception in 2008 and for whom measures of mental health (Short Form 36 [SF-36] health survey mental component summary [MCS]) were available, were invited to take part in this followup study in 2011. Change in foot pain was determined by the difference between the Manchester Foot Pain and Disability Index score at baseline and followup; therefore, a decrease in the score indicated improved foot pain and an increase indicated deterioration in foot pain. Linear regression was used to determine the factors affecting change in foot pain. Results: Of the 62 respondents (75% response rate, 49 women and 13 men), there were 27 (44%) whose foot pain deteriorated. A higher MCS score of the SF-36 health survey at baseline was associated with a slower progression of foot pain (β coefficient −0.29, 95% confidence interval −0.42, −0.01), adjusted for age, sex, BMI, and physical health. Conclusion: Mental health is associated with changes in foot pain. Clinicians dealing with this population should consider the contribution of mental health in their management and treatment of foot pain.