A descriptive study of older adults with persistent pain: Use and perceived effectiveness of pain management strategies [ISRCTN11899548]

BACKGROUND: Persistent pain is a common, often debilitating, problem in older adults; however, few studies have focused on the experiences of older adults in managing their pain. The objective of this study was to describe the use and perceived effectiveness of pain management strategies in a sample of older adults and to explore the associations of these variables with demographic and psychosocial characteristics. METHODS: Adults ≥ 65 years old and living in retirement facilities who reported persistent pain (N = 235, mean age = 82 years, 84% female, 94% white) completed measures of demographics, pain, depression, self-efficacy for managing pain, and a Pain Management Strategies Survey. Participants identified current and previous-year use of 42 pain management strategies and rated helpfulness of each on a 5-point scale. RESULTS: Acetaminophen, regular exercise, prayer, and heat and cold were the most frequently used pain management strategies (61%, 58%, 53%, and 48%, respectively). Strategies used by >25% of the sample that were rated moderately or more helpful (i.e., >2 on a 0 to 4 scale) were prayer [mean (SD) = 2.9 (0.9)], opioids [2.6 (0.8)], regular exercise [2.5 (1.0)], heat/cold [2.5 (1.0)], nonsteroidal anti-inflammatory drugs [2.4 (1.0)], and acetaminophen [2.3 (1.0)]. Young-old (65–74 years) study participants reported use of more strategies than did old-old (85+ years) participants (p = .03). Perceived helpfulness of strategy use was significantly associated with pain intensity (r = -.14, p < .0001), self-efficacy (r = .28, p < .0001), and depression (r = -.20, p = .003). CONCLUSION: On average, older adults view the strategies they use for persistent pain as only moderately helpful. The associations between perceived helpfulness and self-efficacy and depression suggest avenues of pain management that are focused less on specific treatments and more on how persons with persistent pain think about their pain

Urocortin-1 within the Centrally-Projecting Edinger-Westphal Nucleus Is Critical for Ethanol Preference

Converging lines of evidence point to the involvement of neurons of the centrally projecting Edinger-Westphal nucleus (EWcp) containing the neuropeptide Urocortin-1 (Ucn1) in excessive ethanol (EtOH) intake and EtOH sensitivity. Here, we expanded these previous findings by using a continuous-access, two-bottle choice drinking paradigm (3%, 6%, and 10% EtOH vs. tap water) to compare EtOH intake and EtOH preference in Ucn1 genetic knockout (KO) and wild-type (WT) mice. Based on previous studies demonstrating that electrolytic lesion of the EWcp attenuated EtOH intake and preference in high-drinking C57BL/6J mice, we also set out to determine whether EWcp lesion would differentially alter EtOH consumption in Ucn1 KO and WT mice. Finally, we implemented well-established place conditioning procedures in KO and WT mice to determine whether Ucn1 and the corticotropin-releasing factor type-2 receptor (CRF-R2) were involved in the rewarding and aversive effects of EtOH (2 g/kg, i.p.). Results from these studies revealed that (1) genetic deletion of Ucn1 dampened EtOH preference only in mice with an intact EWcp, but not in mice that received lesion of the EWcp, (2) lesion of the EWcp dampened EtOH intake in Ucn1 KO and WT mice, but dampened EtOH preference only in WT mice expressing Ucn1, and (3) genetic deletion of Ucn1 or CRF-R2 abolished the conditioned rewarding effects of EtOH, but deletion of Ucn1 had no effect on the conditioned aversive effects of EtOH. The current findings provide strong support for the hypothesis that EWcp-Ucn1 neurons play an important role in EtOH intake, preference, and reward

Variations in corticosteroid/anesthetic injections for painful shoulder conditions: comparisons among orthopaedic surgeons, rheumatologists, and physical medicine and primary-care physicians

<p>Abstract</p> <p>Background</p> <p>Variations in corticosteroid/anesthetic doses for injecting shoulder conditions were examined among orthopaedic surgeons, rheumatologists, and primary-care sports medicine (PCSMs) and physical medicine and rehabilitation (PMRs) physicians to provide data needed for documenting inter-group differences for establishing uniform injection guidelines.</p> <p>Methods</p> <p>264 surveys, sent to these physicians in our tri-state area of the western United States, addressed corticosteroid/anesthetic doses and types used for subacromial impingement, degenerative glenohumeral and acromioclavicular arthritis, biceps tendinitis, and peri-scapular trigger points. They were asked about preferences regarding: 1) fluorinated vs. non-fluorinated corticosteroids, 2) acetate vs. phosphate types, 3) patient age, and 4) adjustments for special considerations including young athletes and diabetics.</p> <p>Results</p> <p>169 (64% response rate, RR) surveys were returned: 105/163 orthopaedic surgeons (64%RR), 44/77 PCSMs/PMRs (57%RR), 20/24 rheumatologists (83%RR). Although corticosteroid doses do not differ significantly between specialties (p > 0.3), anesthetic volumes show broad variations, with surgeons using larger volumes. Although 29% of PCSMs/PMRs, 44% rheumatologists, and 41% surgeons exceed "recommended" doses for the acromioclavicular joint, >98% were within recommendations for the subacromial bursa and glenohumeral joint. Depo-Medrol^®(methylprednisolone acetate) and Kenalog^®(triamcinolone acetonide) are most commonly used. More rheumatologists (80%) were aware that there are acetate and phosphate types of corticosteroids as compared to PCSMs/PMRs (76%) and orthopaedists (60%). However, relatively fewer rheumatologists (25%) than PCSMs/PMRs (32%) or orthopaedists (32%) knew that phosphate types are more soluble. Fluorinated corticosteroids, which can be deleterious to soft tissues, were used with these frequencies for the biceps sheath: 17% rheumatologists, 8% PCSMs/PMRs, 37% orthopaedists. Nearly 85% use the same non-fluorinated corticosteroid for all injections; <10% make adjustments for diabetic patients.</p> <p>Conclusion</p> <p>Variations between specialists in anesthetic doses suggest that surgeons (who use significantly larger volumes) emphasize determining the percentage of pain attributable to the injected region. Alternatively, this might reflect a more profound knowledge that non-surgeons specialists have of the potentially adverse cardiovascular effects of these agents. Variations between these specialists in corticosteroid/anesthetic doses and/or types, and their use in some special situations (e.g., diabetics), bespeak the need for additional investigations aimed at establishing uniform injection guidelines, and for identifying knowledge deficiencies that warrant advanced education.</p

Melatonin the "light of night" in human biology and adolescent idiopathic scoliosis

Melatonin "the light of night" is secreted from the pineal gland principally at night. The hormone is involved in sleep regulation, as well as in a number of other cyclical bodily activities and circadian rhythm in humans. Melatonin is exclusively involved in signalling the 'time of day' and 'time of year' (hence considered to help both clock and calendar functions) to all tissues and is thus considered to be the body's chronological pacemaker or 'Zeitgeber'. The last decades melatonin has been used as a therapeutic chemical in a large spectrum of diseases, mainly in sleep disturbances and tumours and may play a role in the biologic regulation of mood, affective disorders, cardiovascular system, reproduction and aging. There are few papers regarding melatonin and its role in adolescent idiopathic scoliosis (AIS). Melatonin may play a role in the pathogenesis of scoliosis (neuroendocrine hypothesis) but at present, the data available cannot clearly support this hypothesis. Uncertainties and doubts still surround the role of melatonin in human physiology and pathophysiology and future research is needed

Canine cancer immunotherapy studies: linking mouse and human

Despite recent major clinical breakthroughs in human cancer immunotherapy including the use of checkpoint inhibitors and engineered T cells, important challenges remain, including determining the sub-populations of patients who will respond and who will experience at times significant toxicities. Although advances in cancer immunotherapy depend on preclinical testing, the majority of in-vivo testing currently relies on genetically identical inbred mouse models which, while offering critical insights regarding efficacy and mechanism of action, also vastly underrepresent the heterogeneity and complex interplay of human immune cells and cancers. Additionally, laboratory mice uncommonly develop spontaneous tumors, are housed under specific-pathogen free conditions which markedly impacts immune development, and incompletely model key aspects of the tumor/immune microenvironment. The canine model represents a powerful tool in cancer immunotherapy research as an important link between murine models and human clinical studies. Dogs represent an attractive outbred combination of companion animals that experience spontaneous cancer development in the setting of an intact immune system. This allows for study of complex immune interactions during the course of treatment while also directly addressing long-term efficacy and toxicity of cancer immunotherapies. However, immune dissection requires access to robust and validated immune assays and reagents as well as appropriate numbers for statistical evaluation. Canine studies will need further optimization of these important mechanistic tools for this model to fulfill its promise as a model for immunotherapy. This review aims to discuss the canine model in the context of existing preclinical cancer immunotherapy models to evaluate both its advantages and limitations, as well as highlighting its growth as a powerful tool in the burgeoning field of both human and veterinary immunotherapy

Genetic determinants of risk in pulmonary arterial hypertension: international genome-wide association studies and meta-analysis

Background Rare genetic variants cause pulmonary arterial hypertension, but the contribution of common genetic variation to disease risk and natural history is poorly characterised. We tested for genome-wide association for pulmonary arterial hypertension in large international cohorts and assessed the contribution of associated regions to outcomes. Methods We did two separate genome-wide association studies (GWAS) and a meta-analysis of pulmonary arterial hypertension. These GWAS used data from four international case-control studies across 11744 individuals with European ancestry (including 2085 patients). One GWAS used genotypes from 5895 whole-genome sequences and the other GWAS used genotyping array data from an additional 5849 individuals. Cross-validation of loci reaching genome-wide significance was sought by meta-analysis. Conditional analysis corrected for the most significant variants at each locus was used to resolve signals for multiple associations. We functionally annotated associated variants and tested associations with duration of survival. All-cause mortality was the primary endpoint in survival analyses. Findings A locus near SOX17 (rs10103692, odds ratio 1·80 [95% CI 1·55–2·08], p=5·13×10– ¹⁵) and a second locus in HLA-DPA1 and HLA-DPB1 (collectively referred to as HLA-DPA1/DPB1 here; rs2856830, 1·56 [1·42–1·71], p=7·65×10– ²⁰) within the class II MHC region were associated with pulmonary arterial hypertension. The SOX17 locus had two independent signals associated with pulmonary arterial hypertension (rs13266183, 1·36 [1·25–1·48], p=1·69×10– ¹²; and rs10103692). Functional and epigenomic data indicate that the risk variants near SOX17 alter gene regulation via an enhancer active in endothelial cells. Pulmonary arterial hypertension risk variants determined haplotype-specific enhancer activity, and CRISPR-mediated inhibition of the enhancer reduced SOX17 expression. The HLA-DPA1/DPB1 rs2856830 genotype was strongly associated with survival. Median survival from diagnosis in patients with pulmonary arterial hypertension with the C/C homozygous genotype was double (13·50 years [95% CI 12·07 to >13·50]) that of those with the T/T genotype (6·97 years [6·02–8·05]), despite similar baseline disease severity. Interpretation This is the first study to report that common genetic variation at loci in an enhancer near SOX17 and in HLA-DPA1/DPB1 is associated with pulmonary arterial hypertension. Impairment of SOX17 function might be more common in pulmonary arterial hypertension than suggested by rare mutations in SOX17. Further studies are needed to confirm the association between HLA typing or rs2856830 genotyping and survival, and to determine whether HLA typing or rs2856830 genotyping improves risk stratification in clinical practice or trials. Funding UK NIHR, BHF, UK MRC, Dinosaur Trust, NIH/NHLBI, ERS, EMBO, Wellcome Trust, EU, AHA, ACClinPharm, Netherlands CVRI, Dutch Heart Foundation, Dutch Federation of UMC, Netherlands OHRD and RNAS, German DFG, German BMBF, APH Paris, INSERM, Université Paris-Sud, and French ANR