Sensory hyperalgesia is characteristic of nonspecific arm pain: A comparison with cervical radiculopathy and pain-free controls

Objectives: Nonspecific arm pain (NSAP) is a common clinical entity, the pathophysiological mechanisms of which are poorly understood. The purpose of this study was to investigate sensory profiles in individuals with nonspecific arm pain compared with cervical radiculopathy and pain-free controls. Methods: Forty office workers with NSAP, 17 people with cervical radiculopathy, and 40 pain-free controls were assessed by means of quantitative sensory testing (thermal and vibration detection thresholds; thermal and pressure pain thresholds), tests for neural tissue sensitivity, and questionnaires. Between-group comparisons were conducted using Kruskal-Wallis tests. An exploratory factor analysis was used to determine characteristic features in NSAP. Results: Both patient groups demonstrated cold and pressure pain sensitivity (P<0.003; P<0.05) and neural tissue sensitivity (P<0.001). The NSAP group also demonstrated heat pain sensitivity (P<0.001). Both patient groups demonstrated hypoaesthesia to vibration thresholds (P<0.05), whereas thermal hypoaesthesia was only evident in the cervical radiculopathy group (P<0.05). Exploratory factor analysis revealed pressure and thermal pain sensitivity as the key characteristics of this NSAP group. Discussion: Sensory profiles in NSAP and cervical radiculopathy differ. NSAP is characterized by widespread sensitivity to thermal and pressure pain in the absence of thermal hypoaesthesia, whereas cervical radiculopathy is characterized by the presence of thermal and vibratory hypoaesthesia as well as more localized cold and pressure pain sensitivity. The identification of widespread sensory hypersensitivity in NSAP has important implications for clinical decision making

Mechanisms-based classifications of musculoskeletal pain: Part 1 of 3: Symptoms and signs of central sensitisation in patients with low back (AEleg) pain

a b s t r a c t As a mechanisms-based classification of pain &apos;central sensitisation pain&apos; (CSP) refers to pain arising from a dominance of neurophysiological dysfunction within the central nervous system. Symptoms and signs associated with an assumed dominance of CSP in patients attending for physiotherapy have not been extensively studied. The purpose of this study was to identify symptoms and signs associated with a clinical classification of CSP in patients with low back (AEleg) pain. Using a cross-sectional, between-subjects design; four hundred and sixty-four patients with low back (AEleg) pain were assessed using a standardised assessment protocol. Patients&apos; pain was assigned a mechanisms-based classification based on experienced clinical judgement. Clinicians then completed a clinical criteria checklist specifying the presence or absence of various clinical criteria. A binary logistic regression analysis with Bayesian model averaging identified a cluster of three symptoms and one sign predictive of CSP, including: &apos;Disproportionate, non-mechanical, unpredictable pattern of pain provocation in response to multiple/non-specific aggravating/easing factors&apos;, &apos;Pain disproportionate to the nature and extent of injury or pathology&apos;, &apos;Strong association with maladaptive psychosocial factors (e.g. negative emotions, poor self-efficacy, maladaptive beliefs and pain behaviours)&apos; and &apos;Diffuse/nonanatomic areas of pain/tenderness on palpation&apos;. This cluster was found to have high levels of classification accuracy (sensitivity 91.8%, 95% confidence interval (CI): 84.5e96.4; specificity 97.7%, 95% CI: 95.6e99.0). Pattern recognition of this empirically-derived cluster of symptoms and signs may help clinicians identify an assumed dominance of CSP in patients with low back pain disorders in a way that might usefully inform their management

Developing Data Literacy for Data Enabled Student Success

Tapping in to the potential benefits of learning analytics requires staff and students in higher education to be proficient in data literacy. This poster reports on a project to review and identify professional development needs for learning analytics, with an emphasis on the effective use of learning data to promote student success. We report on the development of an evidence based strategy and implementation plan that addresses the skills gaps and professional development requirements of students and higher education staff who teach or lead teaching and learning enhancement. The outputs will enable upskilling of staff and also facilitate students to be more aware, and make greater use of, their own data ‘footprint’. This facilitates the development of important life skills such as self-regulation and self actualisation. In the broader institutional context, this should have the resulting impact of more widespread adoption of evidence based decisions that support student success initiatives

The clinical utility of pain classification in non-specific arm pain

Mechanisms-based pain classification has received considerable attention recently for its potential use in clinical decision making. A number of algorithms for pain classification have been proposed. Non-specific arm pain (NSAP) is a poorly defined condition, which could benefit from classification according to pain mechanisms to improve treatment selection. This study used three published classification algorithms (hereafter called NeuPSIG, Smart, Schafer) to investigate the frequency of different pain classifications in NSAP and the clinical utility of these systems in assessing NSAP. Forty people with NSAP underwent a clinical examination and quantitative sensory testing. Findings were used to classify participants according to three classification algorithms. Frequency of pain classification including number unclassified was analysed using descriptive statistics. Inter-rater agreement was analysed using kappa coefficients. NSAP was primarily classified as ‘unlikely neuropathic pain’ using NeuPSIG criteria, ‘peripheral neuropathic pain’ using the Smart classification and ‘peripheral nerve sensitisation’ using the Schafer algorithm. Two of the three algorithms allowed classification of all but one participant; up to 45% of participants (n = 18) were categorised as mixed by the Smart classification. Inter-rater agreement was good for the Schafer algorithm (к = 0.78) and moderate for the Smart classification (к = 0.40). A kappa value was unattainable for the NeuPSIG algorithm but agreement was high. Pain classification was achievable with high inter-rater agreement for two of the three algorithms assessed. The Smart classification may be useful but requires further direction regarding the use of clinical criteria included. The impact of adding a pain classification to clinical assessment on patient outcomes needs to be evaluated

Effect of diabetes on caregiver burden in an observational study of individuals with Alzheimer’s disease

Background The burden on caregivers of patients with Alzheimer’s disease (AD) is associated with the patient’s functional status and may also be influenced by chronic comorbid medical conditions, such as diabetes. This post-hoc exploratory analysis assessed whether comorbid diabetes in patients with AD affects caregiver burden, and whether caregivers with diabetes experience greater burden than caregivers without diabetes. Caregiver and patient healthcare resource use (HCRU) were also assessed. Methods Baseline data from the GERAS observational study of patients with AD and their caregivers (both n = 1495) in France, Germany and the UK were analyzed. Caregiver burden was assessed using the Zarit Burden Interview (ZBI). Caregiver time on activities of daily living (ADL: basic ADL; instrumental ADL, iADL) and supervision (hours/month), and caregiver and patient HCRU (outpatient visits, emergency room visits, nights hospitalized) were assessed using the Resource Utilization in Dementia instrument for the month before the baseline visit. Regression analyses were adjusted for relevant covariates. Time on supervision and basic ADL was analyzed using zero-inflated negative binomial regression. Results Caregivers of patients with diabetes (n = 188) were younger and more likely to be female (both p < 0.05), compared with caregivers of patients without diabetes (n = 1307). Analyses showed caregivers of patients with diabetes spent significantly more time on iADL (+16 %; p = 0.03; increases were also observed for basic ADL and total caregiver time but did not reach statistical significance) and had a trend towards increased ZBI score. Patients with diabetes had a 63 % increase in the odds of requiring supervision versus those without diabetes (p = 0.01). Caregiver and patient HCRU did not differ according to patient diabetes. Caregivers with diabetes (n = 127) did not differ from those without diabetes (n = 1367) regarding burden/time, but caregivers with diabetes had a 91 % increase in the odds of having outpatient visits (p = 0.01). Conclusions This cross-sectional analysis found caregiver time on iADL and supervision was higher for caregivers of patients with AD and diabetes versus without diabetes, while HCRU was unaffected by patient diabetes. Longitudinal analyses assessing change in caregiver burden over time by patient diabetes status may help clarify the cumulative impact of diabetes and AD dementia on caregiver burden

Risk of Early-Onset Neonatal Group B Streptococcal Disease With Maternal Colonization Worldwide: Systematic Review and Meta-analyses.

Background: Early-onset group B streptococcal disease (EOGBS) occurs in neonates (days 0-6) born to pregnant women who are rectovaginally colonized with group B Streptococcus (GBS), but the risk of EOGBS from vertical transmission has not been systematically reviewed. This article, the seventh in a series on the burden of GBS disease, aims to estimate this risk and how it varies with coverage of intrapartum antibiotic prophylaxis (IAP), used to reduce the incidence of EOGBS. Methods: We conducted systematic reviews (Pubmed/Medline, Embase, Latin American and Caribbean Health Sciences Literature (LILACS), World Health Organization Library Information System [WHOLIS], and Scopus) and sought unpublished data from investigator groups on maternal GBS colonization and neonatal outcomes. We included articles with ≥200 GBS colonized pregnant women that reported IAP coverage. We did meta-analyses to determine pooled estimates of risk of EOGBS, and examined the association in risk of EOGBS with IAP coverage. Results: We identified 30 articles including 20328 GBS-colonized pregnant women for inclusion. The risk of EOGBS in settings without an IAP policy was 1.1% (95% confidence interval [CI], .6%-1.5%). As IAP increased, the risk of EOGBS decreased, with a linear association. Based on linear regression, the risk of EOGBS in settings with 80% IAP coverage was predicted to be 0.3% (95% CI, 0-.9). Conclusions: The risk of EOGBS among GBS-colonized pregnant women, from this first systematic review, is consistent with previous estimates from single studies (1%-2%). Increasing IAP coverage was linearly associated with decreased risk of EOGBS disease

Strain-Dependent Differences in Bone Development, Myeloid Hyperplasia, Morbidity and Mortality in Ptpn2-Deficient Mice

Single nucleotide polymorphisms in the gene encoding the protein tyrosine phosphatase TCPTP (encoded by PTPN2) have been linked with the development of autoimmunity. Here we have used Cre/LoxP recombination to generate Ptpn2ex2−/ex2− mice with a global deficiency in TCPTP on a C57BL/6 background and compared the phenotype of these mice to Ptpn2−/− mice (BALB/c-129SJ) generated previously by homologous recombination and backcrossed onto the BALB/c background. Ptpn2ex2−/ex2− mice exhibited growth retardation and a median survival of 32 days, as compared to 21 days for Ptpn2−/− (BALB/c) mice, but the overt signs of morbidity (hunched posture, piloerection, decreased mobility and diarrhoea) evident in Ptpn2−/− (BALB/c) mice were not detected in Ptpn2ex2−/ex2− mice. At 14 days of age, bone development was delayed in Ptpn2−/− (BALB/c) mice. This was associated with increased trabecular bone mass and decreased bone remodeling, a phenotype that was not evident in Ptpn2ex2−/ex2− mice. Ptpn2ex2−/ex2− mice had defects in erythropoiesis and B cell development as evident in Ptpn2−/− (BALB/c) mice, but not splenomegaly and did not exhibit an accumulation of myeloid cells in the spleen as seen in Ptpn2−/− (BALB/c) mice. Moreover, thymic atrophy, another feature of Ptpn2−/− (BALB/c) mice, was delayed in Ptpn2ex2−/ex2− mice and preceded by an increase in thymocyte positive selection and a concomitant increase in lymph node T cells. Backcrossing Ptpn2−/− (BALB/c) mice onto the C57BL/6 background largely recapitulated the phenotype of Ptpn2ex2−/ex2− mice. Taken together these results reaffirm TCPTP's important role in lymphocyte development and indicate that the effects on morbidity, mortality, bone development and the myeloid compartment are strain-dependent

Nonchromosomal birth defects and risk of childhood acute leukemia : An assessment in 15 000 leukemia cases and 46 000 controls from the Childhood Cancer and Leukemia International Consortium

Although recent studies have demonstrated associations between nonchromosomal birth defects and several pediatric cancers, less is known about their role on childhood leukemia susceptibility. Using data from the Childhood Cancer and Leukemia International Consortium, we evaluated associations between nonchromosomal birth defects and childhood leukemia. Pooling consortium data from 18 questionnaire-based and three registry-based case-control studies across 13 countries, we used multivariable logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between a spectrum of birth defects and leukemia. Our analyses included acute lymphoblastic leukemia (ALL, n = 13 115) and acute myeloid leukemia (AML, n = 2120) cases, along with 46 172 controls. We used the false discovery rate to account for multiple comparisons. In the questionnaire-based studies, the prevalence of birth defects was 5% among cases vs 4% in controls, whereas, in the registry-based studies, the prevalence was 11% among cases vs 7% in controls. In pooled adjusted analyses, there were several notable associations, including (1) digestive system defects and ALL (OR = 2.70, 95% CI: 1.46-4.98); (2) congenital anomalies of the heart and circulatory system and AML (OR = 2.86, 95% CI: 1.81-4.52) and (3) nervous system defects and AML (OR = 4.23, 95% CI: 1.50-11.89). Effect sizes were generally larger in registry-based studies. Overall, our results could point to novel genetic and environmental factors associated with birth defects that could also increase leukemia susceptibility. Additionally, differences between questionnaire- and registry-based studies point to the importance of complementary sources of birth defect phenotype data when exploring these associations

Parental Tobacco Smoking and Acute Myeloid Leukemia : The Childhood Leukemia International Consortium

The association between tobacco smoke and acute myeloid leukemia (AML) is well established in adults but not in children. Individual-level data on parental cigarette smoking were obtained from 12 case-control studies from the Childhood Leukemia International Consortium (CLIC, 1974-2012), including 1,330 AML cases diagnosed at age <15 years and 13,169 controls. We conducted pooled analyses of CLIC studies, as well as meta-analyses of CLIC and non-CLIC studies. Overall, maternal smoking before, during, or after pregnancy was not associated with childhood AML; there was a suggestion, however, that smoking during pregnancy was associated with an increased risk in Hispanics (odds ratio = 2.08, 95% confidence interval (CI): 1.20, 3.61) but not in other ethnic groups. By contrast, the odds ratios for paternal lifetime smoking were 1.34 (95% CI: 1.11, 1.62) and 1.18 (95% CI: 0.92, 1.51) in pooled and meta-analyses, respectively. Overall, increased risks from 1.2- to 1.3-fold were observed for pre- and postnatal smoking (P < 0.05), with higher risks reported for heavy smokers. Associations with paternal smoking varied by histological type. Our analyses suggest an association between paternal smoking and childhood AML. The association with maternal smoking appears limited to Hispanic children, raising questions about ethnic differences in tobacco-related exposures and biological mechanisms, as well as study-specific biases

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder