Sebastian Straube

Evidence in chronic pain--establishing best practice in the reporting of systematic reviews.

‘‘Evidence” in chronic pain – establishing best practice in the reporting of systematic reviews R. Andrew Moore *, Christopher Eccleston , Sheena Derry , Phillip Wiffen , Rae F. Bell , Sebastian Straube , Henry McQuay , for the ACTINPAIN writing group of the IASP Special Interest Group (SIG) on Systematic Reviews in Pain Relief and the Cochrane Pain, Palliative and Supportive Care Systematic Review Group editors

Pain measures and cut-offs – ‘no worse than mild pain’ as a simple, universal outcome

Now admittedly the patient in question had undergone a life-saving operation in a brand new hospital staffed by some wonderful and talented people. However, a pain score of 6/10 is not mild, but borderline between moderate and severe, and the patient did need something for that. Was the nurse ignorant of what pain scores meant, or was it just that caring professionals typically underestimate patients’ pain [1]? Both these questions are deserving of research, but for this patient, the only point is that the system failed him, and for him the reasons behind the failure were of little interest. He had pain that was borderline severe, and it was not treated. This is not uncommon. A fairly recent survey of Italian hospital wards came to the hardly original conclusion that those wards in which less analgesic was prescribed had higher rates of patients experiencing severe pain than those where more analgesics were prescribed [2]; Fig. 1 shows the clear inverse relationship between the presence of severe pain and the percentage of patients treated for their pain. There is a wealth of evidence that pain is poorly treated, and that significant proportions of patients suffer from moderate or severe pain, whether it is acute pain in hospital [3] or chronic pain in the community [4, 5]. Barriers to progress are many and varied, but one particular and important barrier is a degree of confusion about pain scoring systems and what they mean. How does a simple categorical verbal rating system (no pain, mild, moderate, severe) relate to a 100-mm visual analogue scale (VAS) or an 11-point numerical rating scale (NRS)? Does it matter what the anchors are at each end? Where are the boundaries for moderate or severe pain? What is the minimal clinically significant difference? Does it matter whether the scale has been ‘validated’ in Welsh, or Farsi, or Urdu? All of which makes for terrific grist for

The Costs and Consequences of Adequately Managed Chronic Non-Cancer Pain and Chronic Neuropathic Pain

Chronic pain is distressing for patients and a burden on healthcare systems and society. Recent research demonstrates different aspects of the negative impact of chronic pain and the positive impact of successful treatment, making an overview of the costs and consequences of chronic pain appropriate.

Fibromyalgia: Moderate and substantial pain intensity reduction predicts improvement in other outcomes and substantial quality of life gain

&NA; Chronic pain is associated with a range of other problems, including disturbed sleep, depression, anxiety, fatigue, reduced quality of life, and an inability to work or socialise. We investigated whether good symptom control of pain (using definitions of moderate and substantial benefit) is associated with improvement in other symptoms. Individual patient data from four randomised trials in fibromyalgia (2575 patients) lasting 8–14 weeks were used to calculate percentage pain reduction for each completing patient (1858), divided into one of five groups according to pain reduction, irrespective of treatment: substantial benefit – ≥50% pain reduction; moderate – 30% to <50%; minimal – 15% to <30%; marginal – 0% to <15%; worse – <0% (increased pain intensity). We then calculated change from baseline to end of trial for measures of fatigue, function, sleep, depression, anxiety, ability to work, general health status, and quality‐adjusted life year (QALY) gain over a 12‐month period. Substantial and moderate pain intensity reductions were associated with statistically significant reduction from baseline by end of trial in all measures, with values by trial end at or approaching normative values. Substantial pain intensity reduction resulted in 0.11 QALYs gained, and moderate pain intensity reduction in 0.07 QALYs gained over a 12‐month period. Substantial and moderate pain intensity reduction predicts broad beneficial outcomes and improved quality of life that do not occur without pain relief. Pain intensity reduction is a simple and effective predictor of which patients should continue treatment, and which should discontinue and try an alternative therapy.

Estimate at your peril: imputation methods for patient withdrawal can bias efficacy outcomes in chronic pain trials using responder analyses.

a Pain Research and Nuffield Division of Anaesthetics, Department of Clinical Neurosciences, University of Oxford, The Churchill Hospital, Oxford, UK b Department of Occupational, Social and Environmental Medicine, University Medical Center Göttingen, Göttingen, Germany c Centre for Pain Research, The University of Bath, Bath, UK d The UK Cochrane Centre, NHS R&D Programme, Summertown Pavilion, Middle Way, Oxford, UK e Pain Clinic/Regional Centre of Excellence in Palliative Care, Haukeland University Hospital, Bergen, Norway f Pain Clinic, Department of Anaesthesiology and Intensive Care Medicine, Helsinki University Central Hospital, Meilahti Hospital, Helsinki, Finland g College of Human and Health Sciences, Swansea University, Swansea, Wales, UK

Minimum efficacy criteria for comparisons between treatments using individual patient meta-analysis of acute pain trials: Examples of etoricoxib, paracetamol, ibuprofen, and ibuprofen/paracetamol combinations after third molar extraction

&NA; We defined response in acute pain trials according to percentage of maximum possible efficacy. Minimum efficacy criteria (MEC) of 0%, or at least 15%, 30%, 50%, and 70% pain relief were used to examine stability over time using total pain relief and summed pain intensity difference (SPID), sex differences, and sensitivity. We used individual patient data from placebo‐controlled third molar extraction trials: 4 with single‐dose oral etoricoxib 120 mg, and 2 with paracetamol, ibuprofen, and ibuprofen plus paracetamol combinations. With etoricoxib, numbers needed to treat (NNTs) were stable between response levels of at least 15% (MEC15) and 50% pain relief (MEC50), and similar for total pain relief and SPID. NNTs were higher (worse) at extremes of MEC, especially with SPID. Results for women and men were similar. NNTs of lower efficacy treatments (paracetamol 500 and 1000 mg) rose rapidly at higher MEC. NNTs of high efficacy treatments (ibuprofen plus paracetamol combinations) showed greater separation at higher MEC. The highest degree of discrimination between treatments was with MEC50 and MEC70. Etoricoxib 120 mg (NNT for ⩾50% maximum 6‐hour pain relief 1.7) and ibuprofen 200/400 mg plus paracetamol 500/1000 mg (NNTs 1.5 and 1.6, respectively) produced the lowest (best) NNTs in the dental pain model. Timing of patient request for additional analgesia is an alternative analgesic efficacy outcome measure. Individual patient analyses demonstrate that the choice of minimum efficacy criteria influences numbers needed to treat and that higher minimum efficacy criteria produce greater discrimination between treatments.

Effect of preoperative Cox-II-selective NSAIDs (coxibs) on postoperative outcomes: A systematic review of randomized studies

Background:  Preoperative use of coxibs has been claimed to reduce postoperative pain and analgesic consumption, and to affect other postoperative outcomes.

Vitamin D and chronic pain.

A number of studies have suggested a link between low levels of vitamin D and higher incidence of chronic pain [4,7,22]. There is a well-established link between low vitamin D and pain due to osteomalacia. There is no clear biological mechanism of how low vitamin D might be causally related to other types of chronic pain, though vitamin D is thought to be involved in regulating inflammatory cytokine synthesis [17], and might be implicated in some chronic pain conditions. Associations of pain with latitude and season of the year offer circumstantial evidence that vitamin D may be involved. These associations have been suggested for such diverse types of pain as headache, abdominal pain, knee pain and back pain; but the evidence is far from convincing [24,29,34]. This paper undertakes an assessment of the relationship between vitamin D and chronic pain. Before vitamin D supplementation can be advocated for chronic pain, evidence for health benefits and adverse effects needs to be assessed rigorously. Vitamin D and its roles in health and disease have been of interest in the scientific community [17] and the general media [20]. Many tissues express vitamin D receptors, and it is not surprising that a physiological role beyond the skeleton has been proposed. Vitamin D deficiency has been implicated in conditions like autoimmune and cardiovascular diseases, cancers, and chronic pain [17]. A recent meta-analysis even suggested reduced all-causemortality with vitamin D supplementation [5]. This contrasts with antioxidant vitamins A and E, where a review suggested a possible increase in mortality rates [8]. Some experts advocate limited and sensible sun exposure and vitamin D supplementation [17] in order to ensure adequate blood levels. Excessive dietary supplementation can lead to vitamin D intoxication [1], and excessive sun exposure increases the risk of skin cancers, already a substantial health problem. Although cases of vitamin D intoxication have been reported infrequently, they could become more common with widespread use of vitamin D supplements. If there is a link between vitamin D deficiency and chronic pain, a systematic review of the evidence would be expected to uncover two things: firstly, an inverse association between pain and 25-OH

Mortality with upper gastrointestinal bleeding and perforation: effects of time and NSAID use.

BackgroundSome people who suffer an upper gastrointestinal bleed or perforation die. The mortality rate was estimated at 12% in studies published before 1997, but a systematic survey of more recent data is needed. Better treatment is likely to have reduced mortality. An estimate of mortality is helpful in explaining to patients the risks of therapy, especially with NSAIDs.MethodsA systematic review of studies published before 1997, and between 1997 and 2008. Any study architecture was acceptable if it reported on cases who died from any cause of upper gastrointestinal bleed or perforation. Analyses were conducted separately for all cases, and those prescribed NSAID or aspirin.ResultsInformation was available for 61,067 cases (81% published since 1997) of whom 5,001 died. The mortality rate in all cases fell significantly, from 11.6% (95% confidence interval, 11.0 to 12.2) in pre-1997 studies to 7.4% (7.2 to 7.6) in those published since 1997. In 5,526 patients taking NSAID or aspirin, mortality increased, from 14.7% (13.6 to 15.8) before 1997 to 20.9% (18.8 to 22.9) since 1997.ConclusionUpper gastrointestinal bleed or perforation still carries a finite risk of death. Differences in study architecture, population characteristics, risk factors, definition of mortality, and reporting of outcomes impose limitations on interpreting effect size. Data published since 1997 suggest that mortality in patients suffering from an upper gastrointestinal bleed or perforation has fallen to 1 in 13 overall, but remains higher at about 1 in 5 in those exposed to NSAID or aspirin.

Pregabalin in fibromyalgia: meta-analysis of efficacy and safety from company clinical trial reports

OBJECTIVES Meta-analysis of pregabalin trials in FM using company trial reports, which provide more detailed information about trials than published papers. FM is a common condition with a significant impact on quality of life. METHODS Reports of five high-quality randomized trials (3808 patients) of pregabalin in FM were obtained from Pfizer. Four trials (2754 patients) were of classical trial design and one was an enriched enrolment randomized withdrawal design. Outcomes for meta-analysis from the four trials with classical design were pooled in an intention-to-treat analysis. RESULTS Significant benefit of pregabalin over placebo was seen for a variety of outcomes including mean pain and sleep scores, the proportion of patients achieving at least 50% pain relief and most of the individual domains of short-form 36. Only a minority of patients achieve moderate or substantial pain relief. The proportions of patients with any adverse event, somnolence or dizziness were also significantly greater with pregabalin than with placebo. There was no difference with regard to serious adverse events. A dose-response relationship was apparent for at least 50% pain relief and for adverse event outcomes. CONCLUSIONS Pregabalin is effective in treating FM and is relatively safe. The size of therapeutic effect is similar to that with other recent interventions such as duloxetine and the combination of tramadol and paracetamol. Enriched enrolment randomized withdrawal design gives similar results to classical trial designs in FM.