Estimating the number needed to treat from continuous outcomes in randomised controlled trials: methodological challenges and worked example using data from the UK Back Pain Exercise and Manipulation (BEAM) trial

Background Reporting numbers needed to treat (NNT) improves interpretability of trial results. It is unusual that continuous outcomes are converted to numbers of individual responders to treatment (i.e., those who reach a particular threshold of change); and deteriorations prevented are only rarely considered. We consider how numbers needed to treat can be derived from continuous outcomes; illustrated with a worked example showing the methods and challenges. Methods We used data from the UK BEAM trial (n = 1, 334) of physical treatments for back pain; originally reported as showing, at best, small to moderate benefits. Participants were randomised to receive 'best care' in general practice, the comparator treatment, or one of three manual and/or exercise treatments: 'best care' plus manipulation, exercise, or manipulation followed by exercise. We used established consensus thresholds for improvement in Roland-Morris disability questionnaire scores at three and twelve months to derive NNTs for improvements and for benefits (improvements gained+deteriorations prevented). Results At three months, NNT estimates ranged from 5.1 (95% CI 3.4 to 10.7) to 9.0 (5.0 to 45.5) for exercise, 5.0 (3.4 to 9.8) to 5.4 (3.8 to 9.9) for manipulation, and 3.3 (2.5 to 4.9) to 4.8 (3.5 to 7.8) for manipulation followed by exercise. Corresponding between-group mean differences in the Roland-Morris disability questionnaire were 1.6 (0.8 to 2.3), 1.4 (0.6 to 2.1), and 1.9 (1.2 to 2.6) points. Conclusion In contrast to small mean differences originally reported, NNTs were small and could be attractive to clinicians, patients, and purchasers. NNTs can aid the interpretation of results of trials using continuous outcomes. Where possible, these should be reported alongside mean differences. Challenges remain in calculating NNTs for some continuous outcomes

Low back pain in general practice: cost-effectiveness of a minimal psychosocial intervention versus usual care

An intervention that can prevent low back pain (LBP) becoming chronic, may not only prevent great discomfort for patients, but also save substantial costs for the society. Psychosocial factors appear to be of importance in the transition of acute to chronic LBP. The aim of this study was to compare the cost-effectiveness of an intervention aimed at psychosocial factors to usual care in patients with (sub)acute LBP. The study design was an economic evaluation alongside a cluster-randomized controlled trial, conducted from a societal perspective with a follow-up of 1 year. Sixty general practitioners in 41 general practices recruited 314 patients with non-specific LBP of less than 12 weeks’ duration. General practitioners in the minimal intervention strategy (MIS) group explored and discussed psychosocial prognostic factors. Usual care (UC) was not protocolized. Clinical outcomes were functional disability (Roland–Morris Disability Questionnaire), perceived recovery and health-related quality of life (EuroQol). Cost data consisted of direct and indirect costs and were measured by patient cost diaries and general practitioner registration forms. Complete cost data were available for 80% of the patients. Differences in clinical outcomes between both the groups were small and not statistically significant. Differences in cost data were in favor of MIS. However, the complete case analysis and the sensitivity analyses with imputed cost data were inconsistent with regard to the statistical significance of this difference in cost data. This study presents conflicting points of view regarding the cost-effectiveness of MIS. We conclude that (Dutch) general practitioners, as yet, should not replace their usual care by this new intervention

Controls on gut phosphatisation : the trilobites from the Weeks Formation Lagerstätte (Cambrian; Utah)

Despite being internal organs, digestive structures are frequently preserved in Cambrian Lagerstätten. However, the reasons for their fossilisation and their biological implications remain to be thoroughly explored. This is particularly true with arthropods--typically the most diverse fossilised organisms in Cambrian ecosystems--where digestive structures represent an as-yet underexploited alternative to appendage morphology for inferences on their biology. Here we describe the phosphatised digestive structures of three trilobite species from the Cambrian Weeks Formation Lagerstätte (Utah). Their exquisite, three-dimensional preservation reveals unique details on trilobite internal anatomy, such as the position of the mouth and the absence of a differentiated crop. In addition, the presence of paired pygidial organs of an unknown function is reported for the first time. This exceptional material enables exploration of the relationships between gut phosphatisation and the biology of organisms. Indeed, soft-tissue preservation is unusual in these fossils as it is restricted to the digestive structures, which indicates that the gut played a central role in its own phosphatisation. We hypothesize that the gut provided a microenvironment where special conditions could develop and harboured a source of phosphorus. The fact that gut phosphatization has almost exclusively been observed in arthropods could be explained by their uncommon ability to store ions (including phosphorous) in their digestive tissues. However, in some specimens from the Weeks Formation, the phosphatisation extends to the entire digestive system, suggesting that trilobites might have had some biological particularities not observed in modern arthropods. We speculate that one of them might have been an increased capacity for ion storage in the gut tissues, related to the moulting of their heavily-mineralised carapace

Multilab Direct Replication of Flavell, Beach, and Chinsky (1966): Spontaneous Verbal Rehearsal in a Memory Task as a Function of Age

Work by Flavell, Beach, and Chinsky indicated a change in the spontaneous production of overt verbalization behaviors when comparing young children (age 5) with older children (age 10). Despite the critical role that this evidence of a change in verbalization behaviors plays in modern theories of cognitive development and working memory, there has been only one other published near replication of this work. In this Registered Replication Report, we relied on researchers from 17 labs who contributed their results to a larger and more comprehensive sample of children. We assessed memory performance and the presence or absence of verbalization behaviors of young children at different ages and determined that the original pattern of findings was largely upheld: Older children were more likely to verbalize, and their memory spans improved. We confirmed that 5- and 6-year-old children who verbalized recalled more than children who did not verbalize. However, unlike Flavell et al., substantial proportions of our 5- and 6-year-old samples overtly verbalized at least sometimes during the picture memory task. In addition, continuous increase in overt verbalization from 7 to 10 years old was not consistently evident in our samples. These robust findings should be weighed when considering theories of cognitive development, particularly theories concerning when verbal rehearsal emerges and relations between speech and memory

An updated overview of clinical guidelines for the management of non-specific low back pain in primary care

The aim of this study was to present and compare the content of (inter)national clinical guidelines for the management of low back pain. To rationalise the management of low back pain, evidence-based clinical guidelines have been issued in many countries. Given that the available scientific evidence is the same, irrespective of the country, one would expect these guidelines to include more or less similar recommendations regarding diagnosis and treatment. We updated a previous review that included clinical guidelines published up to and including the year 2000. Guidelines were included that met the following criteria: the target group consisted mainly of primary health care professionals, and the guideline was published in English, German, Finnish, Spanish, Norwegian, or Dutch. Only one guideline per country was included: the one most recently published. This updated review includes national clinical guidelines from 13 countries and 2 international clinical guidelines from Europe published from 2000 until 2008. The content of the guidelines appeared to be quite similar regarding the diagnostic classification (diagnostic triage) and the use of diagnostic and therapeutic interventions. Consistent features for acute low back pain were the early and gradual activation of patients, the discouragement of prescribed bed rest and the recognition of psychosocial factors as risk factors for chronicity. For chronic low back pain, consistent features included supervised exercises, cognitive behavioural therapy and multidisciplinary treatment. However, there are some discrepancies for recommendations regarding spinal manipulation and drug treatment for acute and chronic low back pain. The comparison of international clinical guidelines for the management of low back pain showed that diagnostic and therapeutic recommendations are generally similar. There are also some differences which may be due to a lack of strong evidence regarding these topics or due to differences in local health care systems. The implementation of these clinical guidelines remains a challenge for clinical practice and research

Cost-effectiveness of general practice care for low back pain: a systematic review

Care from a general practitioner (GP) is one of the most frequently utilised healthcare services for people with low back pain and only a small proportion of those with low back pain who seek care from a GP are referred to other services. The aim of this systematic review was to evaluate the evidence on cost-effectiveness of GP care in non-specific low back pain. We searched clinical and economic electronic databases, and the reference list of relevant systematic reviews and included studies to June 2010. Economic evaluations conducted alongside randomised controlled trials with at least one GP care arm were eligible for inclusion. Two reviewers independently screened search results and extracted data. Eleven studies were included; the majority of which conducted a cost-effectiveness or cost-utility analysis. Most studies investigated the cost-effectiveness of usual GP care. Adding advice, education and exercise, or exercise and behavioural counselling, to usual GP care was more cost-effective than usual GP care alone. Clinical rehabilitation and/or occupational intervention, and acupuncture were more cost-effective than usual GP care. One study investigated the cost-effectiveness of guideline-based GP care, and found that adding exercise and/or spinal manipulation was more cost-effective than guideline-based GP care alone. In conclusion, GP care alone did not appear to be the most cost-effective treatment option for low back pain. GPs can improve the cost-effectiveness of their treatment by referring their patients for additional services, such as advice and exercise, or by providing the services themselves

Minimum detectable and minimal clinically important changes for pain in patients with nonspecific neck pain

<p>Abstract</p> <p>Background</p> <p>The minimal detectable change (MDC) and the minimal clinically important changes (MCIC) have been explored for nonspecific low back pain patients and are similar across different cultural settings. No data on MDC and MCIC for pain severity are available for neck pain patients. The objectives of this study were to estimate MDC and MCIC for pain severity in subacute and chronic neck pain (NP) patients, to assess if MDC and MCIC values are influenced by baseline values and to explore if they are different in the subset of patients reporting referred pain, and in subacute versus chronic patients.</p> <p>Methods</p> <p>Subacute and chronic patients treated in routine clinical practice of the Spanish National Health Service for neck pain, with or without pain referred to the arm, and a pain severity ≥ 3 points on a pain intensity number rating scale (PI-NRS), were included in this study. Patients' own "global perceived effect" over a 3 month period was used as the external criterion. The minimal detectable change (MDC) was estimated by means of the standard error of measurement in patients who self-assess as unchanged. MCIC were estimated by the mean value of change score in patients who self-assess as improved (mean change score, MCS), and by the optimal cutoff point in receiver operating characteristics curves (ROC). The effect on MDC and MCIC of initial scores, duration of pain, and existence of referred pain were assessed.</p> <p>Results</p> <p>658 patients were included, 487 of them with referred pain. MDC was 4.0 PI-NRS points for neck pain in the entire sample, 4.2 for neck pain in patients who also had referred pain, and 6.2 for referred pain. MCS was 4.1 and ROC was 1.5 for referred and for neck pain, both in the entire sample and in patients who also complained of referred pain. ROC was lower (0.5 PI-NRS points) for subacute than for chronic patients (1.5 points). MCS was higher for patients with more intense baseline pain, ranging from 2.4 to 4.9 PI-NRS for neck pain and from 2.4 to 5.3 for referred pain.</p> <p>Conclusion</p> <p>In general, improvements ≤ 1.5 PI-NRS points could be seen as irrelevant. Above that value, the cutoff point for clinical relevance depends on the methods used to estimate MCIC and on the patient's baseline severity of pain. MDC and MCIC values in neck pain patients are similar to those for low back pain and other painful conditions.</p

Cost-effectiveness of guideline-endorsed treatments for low back pain: a systematic review

Healthcare costs for low back pain (LBP) are increasing rapidly. Hence, it is important to provide treatments that are effective and cost-effective. The purpose of this systematic review was to investigate the cost-effectiveness of guideline-endorsed treatments for LBP. We searched nine clinical and economic electronic databases and the reference list of relevant systematic reviews and included studies for eligible studies. Economic evaluations conducted alongside randomised controlled trials investigating treatments for LBP endorsed by the guideline of the American College of Physicians and the American Pain Society were included. Two independent reviewers screened search results and extracted data. Data extracted included the type and perspective of the economic evaluation, the treatment comparators, and the relative cost-effectiveness of the treatment comparators. Twenty-six studies were included. Most studies found that interdisciplinary rehabilitation, exercise, acupuncture, spinal manipulation or cognitive-behavioural therapy were cost-effective in people with sub-acute or chronic LBP. Massage alone was unlikely to be cost-effective. There were inconsistent results on the cost-effectiveness of advice, insufficient evidence on spinal manipulation for people with acute LBP, and no evidence on the cost-effectiveness of medications, yoga or relaxation. This review found evidence supporting the cost-effectiveness of the guideline-endorsed treatments of interdisciplinary rehabilitation, exercise, acupuncture, spinal manipulation and cognitive-behavioural therapy for sub-acute or chronic LBP. There is little or inconsistent evidence for other treatments endorsed in the guideline

"Dreaming in colour’: disabled higher education students’ perspectives on improving design practices that would enable them to benefit from their use of technologies"

The focus of this paper is the design of technology products and services for disabled students in higher education. It analyses the perspectives of disabled students studying in the US, the UK, Germany, Israel and Canada, regarding their experiences of using technologies to support their learning. The students shared how the functionality of the technologies supported them to study and enabled them to achieve their academic potential. Despite these positive outcomes, the students also reported difficulties associated with: i) the design of the technologies, ii) a lack of technology know-how and iii) a lack of social capital. When identifying potential solutions to these difficulties the disabled students imagined both preferable and possible futures where faculty, higher education institutions, researchers and technology companies are challenged to push the boundaries of their current design practices

Metal stressors consistently modulate bacterial conjugal plasmid uptake potential in a phylogenetically conserved manner.

Published onlineJOURNAL ARTICLEThe environmental stimulants and inhibitors of conjugal plasmid transfer in microbial communities are poorly understood. Specifically, it is not known whether exposure to stressors may cause a community to alter its plasmid uptake ability. We assessed whether metals (Cu, Cd, Ni, Zn) and one metalloid (As), at concentrations causing partial growth inhibition, modulate community permissiveness (that is, uptake ability) against a broad-host-range IncP-type plasmid (pKJK5). Cells were extracted from an agricultural soil as recipient community and a cultivation-minimal filter mating assay was conducted with an exogenous E. coli donor strain. The donor hosted a gfp-tagged pKJK5 derivative from which conjugation events could be microscopically quantified and transconjugants isolated and phylogenetically described at high resolution via FACS and 16S rRNA amplicon sequencing. Metal stress consistently decreased plasmid transfer frequencies to the community, while the transconjugal pool richness remained unaffected with OTUs belonging to 12 bacterial phyla. The taxonomic composition of the transconjugal pools was distinct from their respective recipient communities and clustered dependent on the stress type and dose. However, for certain OTUs, stress increased or decreased permissiveness by more than 1000-fold and this response was typically correlated across different metals and doses. The response to some stresses was, in addition, phylogenetically conserved. This is the first demonstration that community permissiveness is sensitive to metal(loid) stress in a manner that is both partially consistent across stressors and phylogenetically conserved.The ISME Journal advance online publication, 2 August 2016; doi:10.1038/ismej.2016.98.We thank J Magid for access to the CRUCIAL field plot, LK Jensen for technical assistance in the laboratory and SM Milani for assistance in FACS sorting. This work was funded by the Villum Kann Rasmussen Foundation Center of Excellence CREAM (Center for Environmental and Agricultural Microbiology). UK is currently supported through an MRC/BBSRC grant (MR/N007174/1)