Evidence-based recommendations for the diagnosis of ankylosing spondylitis: Results from the Australian 3E initiative in rheumatology

• As part of the 3E program, we conducted a systematic literature review and gathered consensus from 23 practising Australian rheumatologists to develop guidelines for early identification of ankylosing spondylitis and specialist referral. • In three rounds of break-out sessions followed by discussion and voting, the specialist panel addressed three questions related to diagnosis of ankylosing spondylitis: In individuals with back pain, what are the early clinical features that suggest ankylosing spondylitis? How useful is imaging in identifying early ankylosing spondylitis? Based on which clinical features should a general practitioner refer a patient to a rheumatologist for further evaluation? • The panel agreed on six recommendations related to the three questions: 1a. Early clinical features to suggest ankylosing spondylitis include inflammatory back pain and age at symptom onset < 45 years. 1b. The absence of symptomatic response to an appropriate course of non-steroidal anti-inflammatory drugs makes the diagnosis of ankylosing spondylitis less likely. 1c. Raised inflammatory markers are supportive, but their absence does not rule out the diagnosis of ankylosing spondylitis. 2a. Despite low sensitivity to detect changes of early ankylosing spondylitis, plain radiographs of the pelvis and spine are appropriate initial imaging techniques. 2b. Magnetic resonance imaging is a useful imaging modality for detecting early changes of ankylosing spondylitis. 3. Individuals with inflammatory back pain should be referred to a rheumatologist for further evaluation. • Effective dissemination and implementation of these recommendations are important to standardise the approach to early diagnosis of ankylosing spondylitis.

Medical negligence, causation and 'exceptional cases' under the civil liability legislation

Under the civil liability legislation enacted in most Australian jurisdictions, factual causation will be established if, on the balance of probabilities, the claimant can prove that the defendant's negligence was 'a necessary condition of the occurrence of the [claimant's] harm'. Causation will then be satisfied by showing that the harm would not have occurred 'but for' the defendant's breach of their duty of care. However, in an exceptional or appropriate case, sub-section 2 of the legislation provides that if the 'but for' test is not met, factual causation may instead be determined in accordance with other 'established principles'. In such a case, 'the court is to consider (amongst other relevant things) whether or not and why responsibility for the harm should be imposed' on the negligent party.

Liability and statutory defence in Queensland

Context Increasing client awareness of valuer's duty of care - Webb Resolutions Ltd v E.Surv Ltd [2012] - Provident Capital Limited v John Virtue Pty Ltd (No 2) [2012] - Including disciplinary actions: Valuers Registration Board of Qld v Conroy [2013] QCAT 688 combined with Post-GFC ‘drops’ in value!

What’s law got to do with it?: Medical negligence, causation and the use of policy

In a medical negligence context, and under the causation provisions enacted pursuant to Civil Liability Legislation in most Australian jurisdictions, the normative concept of “scope of liability” requires a consideration of whether or not and why a medical practitioner should be responsible for a patient’s harm. As such, it places a limit on the extent to which practitioners are deemed liable for a breach of the duty of care owed by them, in circumstances where a legal factual connection between that breach and the causation of a patient’s harm has already been shown. It has been said that a determination of causation requires ‘the identification and articulation of an evaluative judgement by reference to “the purposes and policy of the relevant part of the law”’: Wallace v Kam (2013) 297 ALR 383, 388. Accordingly, one of the normative factors falling within scope of liability is an examination of the content and purpose of the rule or duty of care violated – that is, its underlying policy and whether this supports an attribution of legal responsibility upon a practitioner. In this context, and with reference to recent jurisprudence, this paper considers: the policy relevant to a practitioner’s duty of care in each of the areas of diagnosis, treatment and advice; how this has been used to determine an appropriate scope of liability for the purpose of the causation inquiry in medical negligence claims; and whether such an approach is problematic for medical standards or decision-making.

Standard errors and covariance matrices for smoothed rank estimators

A 'pseudo-Bayesian' interpretation of standard errors yields a natural induced smoothing of statistical estimating functions. When applied to rank estimation, the lack of smoothness which prevents standard error estimation is remedied. Efficiency and robustness are preserved, while the smoothed estimation has excellent computational properties. In particular, convergence of the iterative equation for standard error is fast, and standard error calculation becomes asymptotically a one-step procedure. This property also extends to covariance matrix calculation for rank estimates in multi-parameter problems. Examples, and some simple explanations, are given.

Evaluation of growth and changes in body composition following neonatal diagnosis of cystic fibrosis

Early deficits in nutritional status that might require specific treatment and early response to nutritional therapy were studied longitudinally in 25 infants with cystic fibrosis (CF) diagnosed by neonatal screening, using anthropometric and research body composition methodology, and evaluation of pancreatic function. At the time of confirmed diagnosis (mean 5.4 weeks), body mass, length, total body fat (TBF), and total body potassium (TBK) were all significantly reduced. Following diagnosis and commencement of therapy there was a normalization of weight, length, and TBK by 6-12 months of age, indicating catch-up growth. But in some individuals the response was incomplete, and as a group, mean total body fat remained significantly lower than normal at 1 year of age. Seven of 25 (28%) were pancreatic sufficient at diagnosis, and all but one had evidence of declining pancreatic function requiring the institution of pancreatic enzyme therapy during the next 1-9 months. The median age of commencement of enzyme therapy was 10 weeks (range 5 weeks to 11 months). These longitudinal assessments emphasize the dynamic changes occurring in absorptive function, body composition, and nutritional status following neonatal diagnosis of cystic fibrosis and may reflect previously described abnormalities of energy metabolism in this age group. Abnormal body composition is evident in most CF infants following diagnosis by neonatal screening but pancreatic damage may still be evolving. We suggest that early active nutritional therapy and surveillance for changes in pancreatic function are warranted in CF infants diagnosed by neonatal screening.

The impact of inter-fraction set-up errors on the probability of pulmonary and cardiac complication in left-sided breast cancer patients

Purpose This study evaluated the impact of patient set-up errors on the probability of pulmonary and cardiac complications in the irradiation of left-sided breast cancer. Methods and Materials Using the CMS XiO Version 4.6 (CMS Inc., St Louis, MO) radiotherapy planning system's NTCP algorithm and the Lyman -Kutcher-Burman (LKB) model, we calculated the DVH indices for the ipsilateral lung and heart and the resultant normal tissue complication probabilities (NTCP) for radiation-induced pneumonitis and excess cardiac mortality in 12 left-sided breast cancer patients. Results Isocenter shifts in the posterior direction had the greatest effect on the lung V20, heart V25, mean and maximum doses to the lung and the heart. Dose volume histograms (DVH) results show that the ipsilateral lung V20 tolerance was exceeded in 58% of the patients after 1cm posterior shifts. Similarly, the heart V25 tolerance was exceeded after 1cm antero-posterior and left-right isocentric shifts in 70% of the patients. The baseline NTCPs for radiation-induced pneumonitis ranged from 0.73% - 3.4% with a mean value of 1.7%. The maximum reported NTCP for radiation-induced pneumonitis was 5.8% (mean 2.6%) after 1cm posterior isocentric shift. The NTCP for excess cardiac mortality were 0 % in 100% of the patients (n=12) before and after setup error simulations. Conclusions Set-up errors in left sided breast cancer patients have a statistically significant impact on the Lung NTCPs and DVH indices. However, with a central lung distance of 3cm or less (CLD <3cm), and a maximum heart distance of 1.5cm or less (MHD<1.5cm), the treatment plans could tolerate set-up errors of up to 1cm without any change in the NTCP to the heart.

Social audit failure: Legal liability of external auditors

In this chapter, we look at the step beyond reporting, to the external audit or assurance function. The role of any audit engagement is to provide a professional opinion on a set of financial or non-financial assertions reported by an organization's management, based on an agreed evaluative framework. Any such opinion is not a guarantee that the underlying report is free from fraud or misstatement. Where an audit opinion on financial statements is incorrect, this is referred to as an audit failure. Specifically, the textbook definition of audit failure has two components: that the financial statements contain a serious error and that the auditor has failed to detect the error due to the auditor's failure during the audit process.

Moments of flux in intermediary liability for copyright infringement

This chapter provides an overview of a recent shift in regulatory strategies to address copyright infringement toward enlisting the assistance of general purpose Internet Service Providers. In Australia, the High Court held in 2012 that iiNet, a general purpose ISP, had no legal duty to police what its subscribers did with their internet connections. We provide an overview of three recent developments in Australian copyright law since that decision that demonstrate an emerging shift in the way that obligations are imposed on ISPs to govern the actions of their users without relying on secondary liability. The first is a new privately negotiated industry code that introduces a 'graduated response' system that requires ISPs to pass on warnings to subscribers who receive allegations of infringement. The second involves a recent series of Federal Court cases where rightsholders made a partially successful application to require ISPs to hand over the identifying details of subscribers whose households are alleged to have infringed copyright. The third is a new legislative scheme that will require ISPs to block access to foreign websites that 'facilitate' infringement. We argue that these shifts represent a greater sophistication in approaches to enrolling general purpose intermediaries in the regulatory project. We also suggest that these shifts represent a potentially disturbing trend towards enforcement of copyright law in a way that does not provide strong safeguards for the legitimate constitutional due process interests of users. We conclude with a call for greater attention and research to better understand how intermediaries make decisions when governing the conduct of users, how those decisions may be influenced by both state and non-state actors, and how the rights of individuals to due process can be adequately protected.

Duty and Control in Intermediary Copyright Liability: An Australian Perspective

In the internet age, copyright owners are increasingly looking to online intermediaries to take steps to prevent copyright infringement. Sometimes these intermediaries are closely tied to the acts of infringement; sometimes – as in the case of ISPs – they are not. In 2012, the Australian High Court decided the Roadshow Films v iiNet case, in which it held that an Australian ISP was not liable under copyright’s authorization doctrine, which asks whether the intermediary has sanctioned, approved or countenanced the infringement. The Australian Copyright Act 1968 directs a court to consider, in these situations, whether the intermediary had the power to prevent the infringement and whether it took any reasonable steps to prevent or avoid the infringement. It is generally not difficult for a court to find the power to prevent infringement – power to prevent can include an unrefined technical ability to disconnect users from the copyright source, such as an ISP terminating users’ internet accounts. In the iiNet case, the High Court eschewed this broad approach in favor of focusing on a notion of control that was influenced by principles of tort law. In tort, when a plaintiff asserts that a defendant should be liable for failing to act to prevent harm caused to the plaintiff by a third party, there is a heavy burden on the plaintiff to show that the defendant had a duty to act. The duty must be clear and specific, and will often hinge on the degree of control that the defendant was able to exercise over the third party. Control in these circumstances relates directly to control over the third party’s actions in inflicting the harm. Thus, in iiNet’s case, the control would need to be directed to the third party’s infringing use of BitTorrent; control over a person’s ability to access the internet is too imprecise. Further, when considering omissions to act, tort law differentiates between the ability to control and the ability to hinder. The ability to control may establish a duty to act, and the court will then look to small measures taken to prevent the harm to determine whether these satisfy the duty. But the ability to hinder will not suffice to establish liability in the absence of control. This chapter argues that an inquiry grounded in control as defined in tort law would provide a more principled framework for assessing the liability of passive intermediaries in copyright. In particular, it would set a higher, more stable benchmark for determining the copyright liability of passive intermediaries, based on the degree of actual, direct control that the intermediary can exercise over the infringing actions of its users. This approach would provide greater clarity and consistency than has existed to date in this area of copyright law in Australia.

Decision examines wrongdoers and liability

In Ligon Sixty-Three Pty Ltd v ClarkeKann [2015] QSC 153 the court considered an application to join parties as defendants when it was alleged they were concurrent wrongdoers for the purpose of the proportionate liability provisions of the Civil Liability Act 2003 (Qld) (the Act).

Look-alike, sound-alike medication errors: A novel case concerning a Slow-Na, Slow-K prescribing error

A 59-year-old man was mistakenly prescribed Slow-Na instead of Slow-K due to incorrect selection from a drop-down list in the prescribing software. This error was identified by a pharmacist during a home medicine review (HMR) before the patient began taking the supplement. The reported error emphasizes the need for vigilance due to the emergence of novel look-alike, sound-alike (LASA) drug pairings. This case highlights the important role of pharmacists in medication safety.

Latent class and genetic analysis does not support migraine with aura and migraine without aura as separate entities

Latent class and genetic analyses were used to identify subgroups of migraine sufferers in a community sample of 6,265 Australian twins (55% female) aged 25-36 who had completed an interview based on International Headache Society (IHS) criteria. Consistent with prevalence rates from other population-based studies, 703 (20%) female and 250 (9%) male twins satisfied the IHS criteria for migraine without aura (MO), and of these, 432 (13%) female and 166 (6%) male twins satisfied the criteria for migraine with aura (MA) as indicated by visual symptoms. Latent class analysis (LCA) of IHS symptoms identified three major symptomatic classes, representing 1) a mild form of recurrent nonmigrainous headache, 2) a moderately severe form of migraine, typically without visual aura symptoms (although 40% of individuals in this class were positive for aura), and 3) a severe form of migraine typically with visual aura symptoms (although 24% of individuals were negative for aura). Using the LCA classification, many more individuals were considered affected to some degree than when using IHS criteria (35% vs. 13%). Furthermore, genetic model fitting indicated a greater genetic contribution to migraine using the LCA classification (heritability, h(2)=0.40; 95% CI, 0.29-0.46) compared with the IHS classification (h(2)=0.36; 95% CI, 0.22-0.42). Exploratory latent class modeling, fitting up to 10 classes, did not identify classes corresponding to either the IHS MO or MA classification. Our data indicate the existence of a continuum of severity, with MA more severe but not etiologically distinct from MO. In searching for predisposing genes, we should therefore expect to find some genes that may underlie all major recurrent headache subtypes, with modifying genetic or environmental factors that may lead to differential expression of the liability for migraine.

Zygosity diagnosis in the absence of genotypic data: An approach using latent class analysis

For zygosity diagnosis in the absence of genotypic data, or in the recruitment phase of a twin study where only single twins from same-sex pairs are being screened, or to provide a test for sample duplication leading to the false identification of a dizygotic pair as monozygotic, the appropriate analysis of respondents' answers to questions about zygosity is critical. Using data from a young adult Australian twin cohort (N = 2094 complete pairs and 519 singleton twins from same-sex pairs with complete responses to all zygosity items), we show that application of latent class analysis (LCA), fitting a 2-class model, yields results that show good concordance with traditional methods of zygosity diagnosis, but with certain important advantages. These include the ability, in many cases, to assign zygosity with specified probability on the basis of responses of a single informant (advantageous when one zygosity type is being oversampled); and the ability to quantify the probability of misassignment of zygosity, allowing prioritization of cases for genotyping as well as identification of cases of probable laboratory error. Out of 242 twins (from 121 like-sex pairs) where genotypic data were available for zygosity confirmation, only a single case was identified of incorrect zygosity assignment by the latent class algorithm. Zygosity assignment for that single case was identified by the LCA as uncertain (probability of being a monozygotic twin only 76%), and the co-twin's responses clearly identified the pair as dizygotic (probability of being dizygotic 100%). In the absence of genotypic data, or as a safeguard against sample duplication, application of LCA for zygosity assignment or confirmation is strongly recommended.

Small nerve fiber quantification in the diagnosis of diabetic sensorimotor polyneuropathy: Comparing corneal confocal microscopy with intraepidermal nerve fiber density

OBJECTIVE Quantitative assessment of small fiber damage is key to the early diagnosis and assessment of progression or regression of diabetic sensorimotor polyneuropathy (DSPN). Intraepidermal nerve fiber density (IENFD) is the current gold standard, but corneal confocal microscopy (CCM), an in vivo ophthalmic imaging modality, has the potential to be a noninvasive and objective image biomarker for identifying small fiber damage. The purpose of this study was to determine the diagnostic performance of CCM and IENFD by using the current guidelines as the reference standard. RESEARCH DESIGN AND METHODS Eighty-nine subjects (26 control subjects and 63 patients with type 1 diabetes), with and without DSPN, underwent a detailed assessment of neuropathy, including CCM and skin biopsy. RESULTS Manual and automated corneal nerve fiber density (CNFD) (P < 0.0001), branch density (CNBD) (P < 0.0001) and length (CNFL) (P < 0.0001), and IENFD (P < 0.001) were significantly reduced in patients with diabetes with DSPN compared with control subjects. The area under the receiver operating characteristic curve for identifying DSPN was 0.82 for manual CNFD, 0.80 for automated CNFD, and 0.66 for IENFD, which did not differ significantly (P = 0.14). CONCLUSIONS This study shows comparable diagnostic efficiency between CCM and IENFD, providing further support for the clinical utility of CCM as a surrogate end point for DSPN.