A systematic review of N-of-1 trials and single case experimental designs in physiotherapy for musculoskeletal conditions.

BACKGROUND: Single Case Experimental Designs (SCEDs) are especially useful for small heterogeneous samples. Their role in evaluation of physiotherapy interventions for musculoskeletal conditions has not been systematically reviewed. OBJECTIVES: Systematically review use, purpose, and outcomes of SCEDs for physiotherapy interventions for musculoskeletal conditions. DATA SOURCES: Electronic databases and grey literature, searched using pre-defined terms. STUDY SELECTION OR ELIGIBILITY CRITERIA: Studies of human participants enrolled in eligible SCEDs (individual or a series). STUDY APPRAISAL AND SYNTHESIS METHODS: We extracted study characteristics, analytic methods and results, synthesising these descriptively. We used RoBiN-T scale to assess risk of bias. RESULTS: We included 19 SCEDs comprising 92 participants, with wide variability in design, methodology, analysis and in conditions and interventions evaluated. 95% of participants responded favourably to the tested intervention. Overall risk of bias was high, due to poor internal validity, especially regarding randomisation, blinding, inter-rater agreement and measurement of treatment adherence. Visual analysis alone was performed in 55% of studies. Assessment of provider and participant satisfaction was limited. CONCLUSIONS AND IMPLICATIONS: of key findings: SCEDs may be well-suited to evaluation of physiotherapy interventions for musculoskeletal conditions, but the risk of bias in studies to date is high. Following SCED guidelines to minimize the risk of bias and maximise clinical usefulness is recommended.

Personalised treatments for acute whiplash injuries: A pilot study of nested N-of-1 trials in a multiple baseline single-case experimental design.

BACKGROUND: Whiplash associated disorder (WAD), a common and disabling condition, incurs huge burden and costs to Australia. Yet, current treatments for whiplash are not very effective; improved outcomes are urgently needed. Clinical guidelines recommend simple analgesia (paracetamol and non-steroidal anti-inflammatory drugs) but there have been no trials of guideline-recommended drugs. This study will investigate the effectiveness of evidence-based advice (EBA), paracetamol, naproxen, and both paracetamol and naproxen, in reducing daily neck pain and preventing chronic neck pain after whiplash injury. METHODS: This study is a pilot series of multi-cycle, double-blinded, randomised N-of-1 trials, nested in a multiple baseline design. The design will comprise three baselines of 5, 8 or 11 days duration. Post enrolment, participants will be randomly assigned to one of the baselines. Fifteen participants with acute (<2 weeks) Grade II WAD, experiencing at least moderate pain (NRS: ≥ 5/10), and at risk of poor recovery will be recruited from hospitals in Queensland, Australia, and through local physiotherapists. Patients will receive EBA plus a randomised sequence of three cycles of ten day treatment triplets (paracetamol designated as a C phase, naproxen, designated as a D phase, and both paracetamol and naproxen, designated as an E phase). DISCUSSION: We will test the effects of different treatments on the primary outcome of average neck pain intensity collected daily and at 4 and 7 months post-injury. Secondary outcomes, including disability, depression, post-traumatic stress symptoms, pain catastrophizing, and feasibility of study procedures, will also be evaluated. The results of this study will inform a larger trial aiming to strengthen the evidence on EBA and simple analgesics for WAD. TRIAL REGISTRATION: Clinical Trials Primary Registry: Australian and New Zealand Clinical Trials Registry. CLINICAL TRIAL REGISTRATION NUMBER: ACTRN12618001291279. DATE OF REGISTRATION: 31/07/2018. PRIMARY TRIAL SPONSOR: The University of Queensland, Brisbane QLD 4072 Australia. FUNDING: The University of Queensland.

Protocol: Using N-of-1 tests to identify responders to melatonin for sleep disturbance in Parkinson's disease.

BACKGROUND: 40% of Parkinson's Disease (PD) sufferers experience insomnia, impacting health and quality of life for patients and family members, especially carers. There is little evidence that current treatments are effective. OBJECTIVES: To determine the effectiveness of melatonin in reducing insomnia in 44 individuals with PD using N-of-1 trials. To aggregate group data to arrive at population estimates of effectiveness (measured by improvements in PDSS-2) and safety (measured by adverse events) of melatonin in improving insomnia in PD. To assess the feasibility of offering N-of-1 trials for insomnia in PD. METHODOLOGY: Participants will receive either immediate-release melatonin or placebo in random order in 3 paired two-week treatment periods (12 weeks total). Based on their response in a two-week run-in period on 3 mg daily, they will trial either 3 mg or 6 mg. Patients will keep daily sleep diaries and wear a MotionWatch throughout. After the trial patients will discuss their individual report with their doctor, which provides direct feedback about effectiveness and safety of melatonin for them. STATISTICAL METHODS: We will analyse N-of-1 tests 1) individually: effects of melatonin on PDSS-2 and safety will be reported; and 2) aggregated across individual N-of-1 studies, combined using a Bayesian multilevel random effects model, which will account for repeated measures on individuals over time, and will return posterior estimates of overall treatment effect, and effect in each individual. CLINICAL TRIAL REGISTRATION NUMBER: ACTRN12617001103358.

Pregabalin versus placebo in targeting pro-nociceptive mechanisms to prevent chronic pain after whiplash injury in at-risk individuals - a feasibility study for a randomised controlled trial.

BACKGROUND: Whiplash-associated disorders (WAD) are an enormous and costly burden to Australian society. Up to 50% of people who experience a whiplash injury will never fully recover. Whiplash is resistant to treatment and no early management approach has yet been shown to prevent chronic pain. The early presence of central sensitization is associated with poor recovery. Pregabalin's effects on central sensitization indicate the potential to prevent or modulate these processes after whiplash injury and to improve health outcomes, but this has not been investigated. This paper describes the protocol for a feasibility study for a randomised controlled trial of pregabalin plus evidence-based advice compared to placebo plus evidence-based advice for individuals with acute whiplash injury who are at risk of poor recovery. METHODS: This double blind, placebo-controlled randomised feasibility study will examine the feasibility and potential effectiveness of pregabalin and evidence-based advice (intervention) compared to placebo and evidence-based advice (control) for individuals with acute whiplash injury at risk of poor recovery. Thirty participants (15 per group) aged 18-65 years with Grade II WAD, within 48 hours of injury and currently experiencing at least moderate pain (NRS: ≥ 5/10) will be recruited from Emergency Departments of public hospitals in Queensland, Australia. Pregabalin will be commenced at 75 mg bd and titrated up to 300 mg bd as tolerated for 4 weeks followed by 1 week of weaning. RESULTS: The feasibility of trial procedures will be tested, as well as the potential effect of the intervention on the outcomes. The primary outcome of neck pain intensity at 3 months from randomisation will be compared between the treatment groups using standard analysis of variance techniques. DISCUSSION: Feasibility and potential effectiveness data will inform an appropriately powered full trial, which if successful, will provide an effective and cost-effective intervention for a costly and treatment resistant condition. It will also have implications for the early management of other traumatic conditions beyond whiplash. TRIAL REGISTRATION: Clinical Trials Primary Registry: Australian and New Zealand Clinical Trials Registry. CLINICAL TRIAL REGISTRATION NUMBER: ACTRN12617000059369 . Date of Registration: 11/01/2017. Primary Trial Sponsor: The University of Queensland, Brisbane QLD 4072 Australia.

Prioritising drugs for single patient (n-of-1) trials in palliative care.

Many of the drugs prescribed commonly to palliative care patients have potentially significant side-effects and are of unproven benefit. The acquisition of evidence to support the prescribing of these drugs has been very slow. Single patient trials (SPTs) (also known as n-of-1 trials) offer a potential means of obtaining the evidence necessary to support or refute the use of several of the drugs and interventions whose use is currently based on physician experience or anecdote alone. A list of SPTs considered "most urgent", for commonly employed treatments and for the most common and most troublesome symptoms in palliative care is presented. These are drugs for which the gap between evidence and practice is greatest, where the evidence of efficacy is most lacking, where significant side effects potentially lead to the greatest morbidity, or where cost is a major patient burden. Although not all the drugs used in palliative care are suitable, SPTs provide a potential alternative method of gathering evidence in palliative care.

Bias influencing maternal reports of child behaviour and emotional state.

BACKGROUND: Previous research has indicated that there may be only a modest degree of agreement between different reporters of a child's behaviour (mental health). This raises the possibility that some descriptions of the child's behaviour may reflect the personal characteristics of the respondent. We examine two potential sources of bias that may influence reports of a child's behaviour/mental health. The first is the mental or emotional impairment of the respondent; the second concerns gender-related expectations of children. METHODS: Mothers (and their children after the birth) were assessed at first clinic visit, 3-5 days after the birth, then 6 months, 5 years and 14 years after the birth. Some 70% of respondents giving birth remained in the study at the 14-year follow-up, leaving some 5277 cases for this analysis. At the 14-year follow-up, child behaviour (mental health) was assessed using the Child Behaviour Check List and the Youth Self Report. Maternal mental health was determined using the anxiety and depression subscales of the Delusions-Symptoms-States Inventory. RESULTS: Mothers who were not emotionally impaired reported fewer child behaviour problems than did the children themselves. As the mother's current emotional impairment increased, so her reports of the child's behaviour problems increased, when compared with the child's own reports. Further, mothers attributed more internalising symptoms to female respondents, and more externalising symptoms to male respondents, than did the child respondents themselves. CONCLUSIONS: Mothers differ systematically from their children when they are reporting their child's behaviour (mental health). The more emotionally impaired the mother, the greater the degree to which she imputes the child to have behaviour problems. Further, female children are attributed to have more internalising behaviours and male children externalising behaviours.

Mothers' mental illness and child behavior problems: cause-effect association or observation bias?

OBJECTIVE: A number of studies have consistently found that a mother's mental health (particularly her level of depression) is a strong predictor of mental health problems experienced by her child(ren). However, the validity of this finding is in doubt because the majority of these studies have relied on maternal reports as indicators of children's behavior. METHOD: This prospective, longitudinal study examines data on the mental health of the mother from prior to the birth of her child to when the child reaches 14 years of age. Child behavior is measured at 14 years of age using reports from mother and child. Mother and child responses are compared to provide an indication of the possible magnitude of maternal observation bias in the reporting of child behavior problems. RESULTS: Anxious and/or depressed mothers tend to report more cases of child behavior problems than do their mentally healthy counterparts or children themselves. Differences between mothers and youths in reporting behavior problems appear to be related to the mothers' mental health. CONCLUSIONS: Current maternal mental health impairment appears to have a substantial effect on the reporting of child behavior problems by the mother, thereby raising questions about the validity of reports of child behavior by persons who are currently emotionally distressed.

[A new multidirectional sigmoid sinus retractor]. / Nouveau rétracteur du sinus sigmoïde à grande variabilité de positionnement.

Retraction of the sigmoid sinus requires a strong instrument. The instruments currently available allow only a limited degree of freedom due to their lack of mobility and versatility. A new sigmoid sinus retractor (MICRO-FRANCE/INSTRUMENTARIUM) was constructed to facilitate the surgeon's task by offering the following advantages: Three-dimensional mobility of the blade: lateral, rotatory and longitudinal, Safe positioning of the retractor by three sets of sharp teeth, Fixation of blade by a single screw, Strong retraction without giving-way.