142 research outputs found

    Burden of Illness Associated with Peripheral and Central Neuropathic Pain among Adults Seeking Treatment in the U nited S tates: A Patient‐Centered Evaluation

    Full text link
    Objective The aim of this study was to evaluate patient‐reported burden associated with peripheral and central neuropathic pain ( NeP ) by pain severity and NeP condition. Design Six hundred twenty‐four subjects with one of six NeP conditions were recruited during routine office visits. Subjects consented to retrospective chart review and completed a one‐time questionnaire (including E uro Q ol‐5 dimensions, 12‐item S hort‐ F orm H ealth S urvey, B rief P ain I nventory‐ S hort F orm, M edical O utcomes S tudy S leep S cale, H ospital A nxiety and D epression S cale, and demographic and clinical characteristics). Pain severity scores were used to stratify subjects by mild, moderate, and severe pain. Summary statistics and frequency distributions were calculated. Differences by severity level were compared using K ruskal– W allis (continuous variables) and chi‐square or F isher's exact test (categorical variables). Effect size was computed with C ohen's d (mild vs severe). Results Subjects' mean age was 55.5. The majority (80.8%) had moderate or severe pain. Patient‐reported outcomes (health status, physical and mental health, pain interference with function, sleep, anxiety, and depression) were significantly worse among subjects with greater pain severity (all P  0.95) for all others. The observed burden was most substantial among chronic low back pain‐ NeP , although the pattern of disease burden was similar across the six NeP conditions. Conclusions Subjects across NeP conditions exhibited high pain levels, which were significantly associated with poor function, compromised health status and sleep, and increased anxiety and depression. Results indicate substantial patient burden across broad NeP , particularly among subjects with severe pain.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109996/1/pme12502.pd

    Variation in renal responses to exercise in the heat with progressive acclimatisation

    Get PDF
    Objectives To investigate changes in renal status from exercise in the heat with acclimatisation and to evaluate surrogates markers of Acute Kidney Injury. Design Prospective observational cohort study. Methods 20 male volunteers performed 60 min standardised exercise in the heat, at baseline and on four subsequent occasions during a 23-day acclimatisation regimen. Blood was sampled before and after exercise for serum creatinine, copeptin, interleukin-6, normetanephrine and cortisol. Fractional excretion of sodium was calculated for corresponding urine samples. Ratings of Perceived Exertion were reported every 5 min during exercise. Acute Kidney Injury was defined as serum creatinine rise ≄26.5 Όmol L−1 or fall in estimated glomerular filtration rate >25%. Predictive values of each candidate marker for developing Acute Kidney Injury were determined by ROC analysis. Results From baseline to Day 23, serum creatinine did not vary at rest, but showed a significant (P < 0.05) reduction post-exercise (120 [102, 139] versus 102 [91, 112] ÎŒmol L−1). Acute Kidney Injury was common (26/100 exposures) and occurred most frequently in the unacclimatised state. Log-normalised fractional excretion of sodium showed a significant interaction (exercise by acclimatization day), with post-exercise values tending to rise with acclimatisation. Ratings of Perceived Exertion predicted AKI (AUC 0.76, 95% confidence interval 0.65–0.88), performing at least as well as biochemical markers. Conclusions Heat acclimatization is associated with reduced markers of renal stress and AKI incidence, perhaps due to improved regional perfusion. Acclimatisation and monitoring Ratings of Perceived Exertion are practical, non-invasive measures that could help to reduce renal injury from exercise in the heat

    Relative changes in brain and kidney biomarkers with Exertional Heat Illness during a cool weather marathon

    Get PDF
    BACKGROUND: Medical personnel may find it challenging to distinguish severe Exertional Heat Illness (EHI), with attendant risks of organ-injury and longer-term sequalae, from lesser forms of incapacity associated with strenuous physical exertion. Early evidence for injury at point-of-incapacity could aid the development and application of targeted interventions to improve outcomes. We aimed to investigate whether biomarker surrogates for end-organ damage sampled at point-of-care (POC) could discriminate EHI versus successful marathon performance. METHODS: Eight runners diagnosed as EHI cases upon reception to medical treatment facilities and 30 successful finishers of the same cool weather marathon (ambient temperature 8 rising to 12 ÂșC) were recruited. Emerging clinical markers associated with injury affecting the brain (neuron specific enolase, NSE; S100 calcium-binding protein B, S100ÎČ) and renal system (cystatin C, cysC; kidney-injury molecule-1, KIM-1; neutrophil gelatinase-associated lipocalin, NGAL), plus copeptin as a surrogate for fluid-regulatory stress, were sampled in blood upon marathon collapse/completion, as well as beforehand at rest (successful finishers only). RESULTS: Versus successful finishers, EHI showed significantly higher NSE (10.33 [6.37, 20.00] vs. 3.17 [2.71, 3.92] ug.L-1, P<0.0001), cysC (1.48 [1.10, 1.67] vs. 1.10 [0.95, 1.21] mg.L-1, P = 0.0092) and copeptin (339.4 [77.0, 943] vs. 18.7 [7.1, 67.9] pmol.L-1, P = 0.0050). Discrimination of EHI by ROC (Area-Under-the-Curve) showed performance that was outstanding for NSE (0.97, P<0.0001) and excellent for copeptin (AUC = 0.83, P = 0.0066). CONCLUSIONS: As novel biomarker candidates for EHI outcomes in cool-weather endurance exercise, early elevations in NSE and copeptin provided sufficient discrimination to suggest utility at point-of-incapacity. Further investigation is warranted in patients exposed to greater thermal insult, followed up over a more extended period

    Resource utilization and costs before and after total joint arthroplasty

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>The purpose of this study was to compare pre- and post-surgical healthcare costs in commercially insured total joint arthroplasty (TJA) patients with osteoarthritis (OA) in the United States (U.S.).</p> <p>Methods</p> <p>Using a large healthcare claims database, we identified patients over age 39 with hip or knee OA who underwent unilateral primary TJA (hip or knee) between 1/1/2006 and 9/30/2007. Utilization of healthcare services and costs were aggregated into three periods: 12 months "pre-surgery," 91 days "peri-operative," and 3 to 15 month "follow-up," Mean total pre-surgery costs were compared with follow-up costs using Wilcoxon signed-rank test.</p> <p>Results</p> <p>14,912 patients met inclusion criteria for the study. The mean total number of outpatient visits declined from pre-surgery to follow-up (18.0 visits vs 17.1), while the percentage of patients hospitalized increased (from 7.5% to 9.8%) (both <it>p </it>< 0.01). Mean total costs during the follow-up period were 18% higher than during pre-surgery (11,043vs.11,043 vs. 9,632, <it>p </it>< 0.01), largely due to an increase in the costs of inpatient care associated with hospital readmissions (3,300vs.3,300 vs. 1,817, p < 0.01). Pharmacotherapy costs were similar for both periods (2013[follow−up]vs.2013 [follow-up] vs. 1922 [pre-surgery], p = 0.33); outpatient care costs were slightly lower in the follow-up period (4338vs.4338 vs. 4571, <it>p </it>< 0.01). Mean total costs for the peri-operative period were $36,553.</p> <p>Conclusions</p> <p>Mean total utilization of outpatient healthcare services declined slightly in the first year following TJA (exclusive of the peri-operative period), while mean total healthcare costs increased during the same time period, largely due to increased costs associated with hospital readmissions. Further study is necessary to determine whether healthcare costs decrease in subsequent years.</p

    Evaluation of the current knowledge limitations in breast cancer research: a gap analysis

    Get PDF
    BACKGROUND A gap analysis was conducted to determine which areas of breast cancer research, if targeted by researchers and funding bodies, could produce the greatest impact on patients. METHODS Fifty-six Breast Cancer Campaign grant holders and prominent UK breast cancer researchers participated in a gap analysis of current breast cancer research. Before, during and following the meeting, groups in seven key research areas participated in cycles of presentation, literature review and discussion. Summary papers were prepared by each group and collated into this position paper highlighting the research gaps, with recommendations for action. RESULTS Gaps were identified in all seven themes. General barriers to progress were lack of financial and practical resources, and poor collaboration between disciplines. Critical gaps in each theme included: (1) genetics (knowledge of genetic changes, their effects and interactions); (2) initiation of breast cancer (how developmental signalling pathways cause ductal elongation and branching at the cellular level and influence stem cell dynamics, and how their disruption initiates tumour formation); (3) progression of breast cancer (deciphering the intracellular and extracellular regulators of early progression, tumour growth, angiogenesis and metastasis); (4) therapies and targets (understanding who develops advanced disease); (5) disease markers (incorporating intelligent trial design into all studies to ensure new treatments are tested in patient groups stratified using biomarkers); (6) prevention (strategies to prevent oestrogen-receptor negative tumours and the long-term effects of chemoprevention for oestrogen-receptor positive tumours); (7) psychosocial aspects of cancer (the use of appropriate psychosocial interventions, and the personal impact of all stages of the disease among patients from a range of ethnic and demographic backgrounds). CONCLUSION Through recommendations to address these gaps with future research, the long-term benefits to patients will include: better estimation of risk in families with breast cancer and strategies to reduce risk; better prediction of drug response and patient prognosis; improved tailoring of treatments to patient subgroups and development of new therapeutic approaches; earlier initiation of treatment; more effective use of resources for screening populations; and an enhanced experience for people with or at risk of breast cancer and their families. The challenge to funding bodies and researchers in all disciplines is to focus on these gaps and to drive advances in knowledge into improvements in patient care

    IL-13 is a driver of COVID-19 severity

    Get PDF
    Immune dysregulation is characteristic of the more severe stages of SARS-CoV-2 infection. Understanding the mechanisms by which the immune system contributes to COVID-19 severity may open new avenues to treatment. Here, we report that elevated IL-13 was associated with the need for mechanical ventilation in 2 independent patient cohorts. In addition, patients who acquired COVID-19 while prescribed Dupilumab, a mAb that blocks IL-13 and IL-4 signaling, had less severe disease. In SARS-CoV-2–infected mice, IL-13 neutralization reduced death and disease severity without affecting viral load, demonstrating an immunopathogenic role for this cytokine. Following anti–IL-13 treatment in infected mice, hyaluronan synthase 1 (Has1) was the most downregulated gene, and accumulation of the hyaluronan (HA) polysaccharide was decreased in the lung. In patients with COVID-19, HA was increased in the lungs and plasma. Blockade of the HA receptor, CD44, reduced mortality in infected mice, supporting the importance of HA as a pathogenic mediator. Finally, HA was directly induced in the lungs of mice by administration of IL-13, indicating a new role for IL-13 in lung disease. Understanding the role of IL-13 and HA has important implications for therapy of COVID-19 and, potentially, other pulmonary diseases. IL-13 levels were elevated in patients with severe COVID-19. In a mouse model of the disease, IL-13 neutralization reduced the disease and decreased lung HA deposition. Administration of IL-13–induced HA in the lung. Blockade of the HA receptor CD44 prevented mortality, highlighting a potentially novel mechanism for IL-13–mediated HA synthesis in pulmonary pathology

    Operationalizing marketable blue carbon

    Get PDF
    The global carbon sequestration and avoided emissions potentially achieved via blue carbon is high (∌3% of annual global greenhouse gas emissions); however, it is limited by multidisciplinary and interacting uncertainties spanning the social, governance, financial, and technological dimensions. We compiled a transdisciplinary team of experts to elucidate these challenges and identify a way forward. Key actions to enhance blue carbon as a natural climate solution include improving policy and legal arrangements to ensure equitable sharing of benefits; improving stewardship by incorporating indigenous knowledge and values; clarifying property rights; improving financial approaches and accounting tools to incorporate co-benefits; developing technological solutions for measuring blue carbon sequestration at low cost; and resolving knowledge gaps regarding blue carbon cycles. Implementing these actions and operationalizing blue carbon will achieve measurable changes to atmospheric greenhouse gas concentrations, provide multiple co-benefits, and address national obligations associated with international agreements

    The state of the Martian climate

    Get PDF
    60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes
    • 

    corecore