Genome-wide enriched pathway analysis of acute post-radiotherapy pain in breast cancer patients: a prospective cohort study.
Ontology highlight
ABSTRACT:
SUBMITTER: Lee E
PROVIDER: S-EPMC6567461 | biostudies-literature | 2019 Jun
REPOSITORIES: biostudies-literature
Publications
Genome-wide enriched pathway analysis of acute post-radiotherapy pain in breast cancer patients: a prospective cohort study.
Lee Eunkyung E Takita Cristiane C Wright Jean L JL Slifer Susan H SH Martin Eden R ER Urbanic James J JJ Langefeld Carl D CD Lesser Glenn J GJ Shaw Edward G EG Hu Jennifer J JJ
Human genomics 20190613 1
<h4>Background</h4>Adjuvant radiotherapy (RT) can increase the risk of developing pain; however, the molecular mechanisms of RT-related pain remain unclear. The current study aimed to identify susceptibility loci and enriched pathways for clinically relevant acute post-RT pain, defined as having moderate to severe pain (pain score ≥ 4) at the completion of RT.<h4>Methods</h4>We conducted a genome-wide association study (GWAS) with 1,344,832 single-nucleotide polymorphisms (SNPs), a gene-based an ...[more]
Similar Datasets
Project description:Background:Although cesarean delivery is one of the most commonly performed surgical procedures, robust data regarding post-cesarean pain is still lacking. Recent studies showed an association between pain upon local anesthetic (LA) injection for spinal anesthesia, or the use of a "three simple questions", and acute post-cesarean pain. Nevertheless, these assessments have yet to be validated further, despite their relative ease of use. We aimed to assess the association between pain score upon LA injection with acute post-cesarean pain after 24 hours at rest (primary outcome) and sub-acute post-cesarean pain lasting for 4 weeks or more (secondary outcome). Methods:Women undergoing cesarean delivery under spinal anesthesia were given pre-operative questionnaires on pain and psychological vulnerability. We also assessed the pain score upon LA injection and mechanical temporal summation. Univariate and multivariable logistic regressions were performed. Results:The incidence of moderate-to-severe acute post-cesarean pain at 24 hours was 21.0% (95% CI=16.6-27.6%) (48 of 217 patients). Pain score upon LA injection was not significantly associated with acute post-cesarean pain after 24 hours at rest (unadjusted OR=1.10, 95% CI=0.95-1.27, P=0.21). However, pain score upon LA injection was significantly associated with sub-acute post-cesarean pain (adjusted OR=1.29, 95% CI=1.07-1.55, P=0.0089) with significant covariate of increased pre-operative central sensitization inventory (CSI) scores (adjusted OR=1.05, 95% CI=1.01-1.09, P=0.0111; area under the curve (AUC)=0.691). Conclusion:There was no association between increased pain score upon LA injection and acute post-cesarean pain, but it was associated with sub-acute post-cesarean pain. Further work is needed to define pain score upon LA injection as a convenient pragmatic measure of risk stratifying patients predisposed to sub-acute post-cesarean pain.
| S-EPMC7509311 | biostudies-literature
Project description:ObjectivesPain is common after craniotomy. Its incidence and predictors in developing nations are not adequately studied. We aimed to assess the incidence, predictors, and impact of acute post-operative pain after intracranial neurosurgeries.Materials and methodsThis prospective observational study was conducted in adult patients undergoing intracranial neurosurgeries. After patient consent, ethics committee approval, and study registration, we assessed the incidence of post-operative pain using numerical rating scale (NRS) score. Predictors and impact of pain on patient outcomes were also evaluated.ResultsA total of 497 patients were recruited during 10-month study period. Significant (4-10 NRS score) post-operative pain at any time-point during the first 3 days after intracranial neurosurgery was reported by 65.5% (307/469) of patients. Incidence of significant pain during the 1st post-operative h, on the 1st, 2nd, and 3rd post-operative days was 20% (78/391), 50% (209/418), 38% (152/401), and 24% (86/360), respectively. Higher pre-operative NRS score and pain during the 1st h post-operatively, predicted the occurrence of pain during the first 3 days after surgery, P = 0.003 and P < 0.001, respectively. Pain was significantly associated with poor sleep quality on the first 2 post-operative nights (P < 0.001). Patient satisfaction score was higher in patients with post-operative pain, P = 0.002.ConclusionEvery two in three patients undergoing elective intracranial neurosurgery report significant pain at some point during the first 3 postoperative days. Pre-operative pain and pain during 1st post-operative h predict the occurrence of significant post-operative pain.
| S-EPMC10696338 | biostudies-literature
Project description:IntroductionOpioid analgesics are often used to treat moderate-to-severe acute non-cancer pain; however, there is little high-quality evidence to guide clinician prescribing. An essential element to developing evidence-based guidelines is a better understanding of pain management and pain control among individuals experiencing acute pain for various common diagnoses.Methods and analysisThis multicentre prospective observational study will recruit 1550 opioid-naïve participants with acute pain seen in diverse clinical settings including primary/urgent care, emergency departments and dental clinics. Participants will be followed for 6 months with the aid of a patient-centred health data aggregating platform that consolidates data from study questionnaires, electronic health record data on healthcare services received, prescription fill data from pharmacies, and activity and sleep data from a Fitbit activity tracker. Participants will be enrolled to represent diverse races and ethnicities and pain conditions, as well as geographical diversity. Data analysis will focus on assessing patients' patterns of pain and opioid analgesic use, along with other pain treatments; associations between patient and condition characteristics and patient-centred outcomes including resolution of pain, satisfaction with care and long-term use of opioid analgesics; and descriptive analyses of patient management of leftover opioids.Ethics and disseminationThis study has received approval from IRBs at each site. Results will be made available to participants, funders, the research community and the public.Trial registration numberNCT04509115.
| S-EPMC9258513 | biostudies-literature
Project description:AimsTesting a relatively small genomic region with a few hundred SNPs provides limited information. Genome-wide association studies (GWAS) provide an opportunity to overcome the limitation of candidate gene association studies. Here, we report the results of a GWAS for the responses to an NSAID analgesic.Materials & methodsEuropean Americans (60 females and 52 males) undergoing oral surgery were genotyped with Affymetrix 500K SNP assay. Additional SNP genotyping was performed from the gene in linkage disequilibrium with the candidate SNP revealed by the GWAS.ResultsGWAS revealed a candidate SNP (rs2562456) associated with analgesic onset, which is in linkage disequilibrium with a gene encoding a zinc finger protein. Additional SNP genotyping of ZNF429 confirmed the association with analgesic onset in humans (p = 1.8 x 10(-10), degrees of freedom = 103, F = 28.3). We also found candidate loci for the maximum post-operative pain rating (rs17122021, p = 6.9 x 10(-7)) and post-operative pain onset time (rs6693882, p = 2.1 x 10(-6)), however, correcting for multiple comparisons did not sustain these genetic associations.ConclusionGWAS for acute clinical pain followed by additional SNP genotyping of a neighboring gene suggests that genetic variations in or near the loci encoding DNA binding proteins play a role in the individual variations in responses to analgesic drugs.
| S-EPMC2696643 | biostudies-literature
Project description:BackgroundPost-surgery adjuvant radiotherapy (RT) significantly improves clinical outcomes in breast cancer patients; however, some patients develop cancer or treatment-related pain that negatively impacts quality of life. This study examined an inflammatory biomarker, C-reactive protein (CRP), in RT-related pain in breast cancer.MethodsDuring 2008 and 2014, breast cancer patients who underwent RT were prospectively evaluated for pre- and post-RT pain. Pre- and post-RT plasma CRP levels were measured using a highly sensitive CRP ELISA kit. Pain score was assessed as the mean of four pain severity items (i.e., pain at its worst, least, average, and now) from the Brief Pain Inventory. Pain scores of 4-10 were classified as clinically relevant pain. Multivariable logistic regression analyses were applied to ascertain the associations between CRP and RT-related pain.ResultsIn 366 breast cancer patients (235 Hispanic whites, 73 black/African Americans, and 58 non-Hispanic whites), 17% and 30% of patients reported pre- and post-RT pain, while 23% of patients had RT-related pain. Both pre- and post-RT pain scores differed significantly by race/ethnicity. In multivariable logistic regression analysis, RT-related pain was significantly associated with elevated pre-RT CRP (≥ 10 mg/L) alone (odds ratio (OR) = 2.44; 95% confidence interval (CI) = 1.02, 5.85); or combined with obesity (OR = 4.73; 95% CI = 1.41, 15.81) after adjustment for age and race/ethnicity.ConclusionsThis is the first pilot study of CRP in RT-related pain, particularly in obese breast cancer patients. Future larger studies are warranted to validate our findings and help guide RT decision-making processes and targeted interventions.
| S-EPMC6537305 | biostudies-literature
Project description:BackgroundLow back pain (LBP) has a lifetime prevalence of 70-80%. Access to timely and personalized, evidence-based care is key to prevent chronic progression. Digital solutions may ease accessibility to treatment while reducing healthcare-related costs.PurposeWe aim to report the results of a fully remote digital care program (DCP) for acute LBP.Patients and methodsThis was an interventional, single-arm, cohort study of patients with acute LBP who received a DCP. Primary outcome was the mean change in disability (Oswestry Disability Index - ODI) after 12 weeks. Secondary outcomes included change in pain (NPRS), analgesic consumption, surgery likelihood, depression (PHQ-9), anxiety (GAD-7), fear-avoidance beliefs (FABQ-PA), work productivity (WPAI) and engagement.ResultsA total of 406 patients were enrolled in the program and of those, 332 (81.8%) completed the intervention. A significant disability reduction of 55.1% (14.93, 95% CI 13.95; 15.91) was observed, corresponding to a 76.1% responder rate (30% cut-off). Disability reduction was accompanied by significant improvements in pain (61.0%), depression (55.4%), anxiety (59.5%), productivity (65.6%), fear-avoidance beliefs (46.3%), intent to pursue surgery (59.1%), and analgesic consumption (from 35.7% at baseline to 10.8% at program end). DCP-related patient satisfaction score was 8.7/10.0 (SD 1.4).ConclusionThis study demonstrated the utility of a multimodal DCP for patients with acute LBP. Very high adherence rates and patient satisfaction were observed, alongside significant reductions in all assessed outcomes, consistent with the growing body of evidence supporting the management of acute LBP with DCPs.
| S-EPMC9261956 | biostudies-literature
Project description:PurposeThe characteristics and natural history of the paclitaxel-acute pain syndrome (P-APS) and paclitaxel's more chronic neuropathy have not been well delineated.MethodsPatients receiving weekly paclitaxel (70 to 90 mg/m(2)) completed daily questionnaires and weekly European Organisation for Research and Treatment of Cancer (EORTC) Chemotherapy-Induced Peripheral Neuropathy (CIPN) -20 instruments during the entire course of therapy.ResultsP-APS symptoms peaked 3 days after chemotherapy. Twenty percent of patients had pain scores of 5 to 10 of 10 with the first dose of paclitaxel. Sensory neuropathy symptoms were more prominent than were motor or autonomic neuropathy symptoms. Of the sensory neuropathy symptoms, numbness and tingling were more prominent than was shooting or burning pain. Patients with higher P-APS pain scores with the first dose of paclitaxel appeared to have more chronic neuropathy.ConclusionThese data support that the P-APS is related to nerve pathology as opposed to being arthralgias and/or myalgias. Numbness and tingling are more prominent chronic neuropathic symptoms than is shooting or burning pain.
| S-EPMC3082985 | biostudies-literature
Project description:Pain is the leading cause of disability in the developed world but remains a poorly treated condition. Specifically, post-surgical pain continues to be a frequent and undermanaged condition. Here, we investigate the analgesic potential of pharmacological NaV1.7 inhibition in a mouse model of acute post-surgical pain, based on incision of the plantar skin and underlying muscle of the hind paw. We demonstrate that local and systemic treatment with the selective NaV1.7 inhibitor μ-theraphotoxin-Pn3a is effectively anti-allodynic in this model and completely reverses mechanical hypersensitivity in the absence of motor adverse effects. In addition, the selective NaV1.7 inhibitors ProTx-II and PF-04856264 as well as the clinical candidate CNV1014802 also reduced mechanical allodynia. Interestingly, co-administration of the opioid receptor antagonist naloxone completely reversed analgesic effects of Pn3a, indicating an involvement of endogenous opioids in the analgesic activity of Pn3a. Additionally, we found super-additive antinociceptive effects of sub-therapeutic Pn3a doses not only with the opioid oxycodone but also with the GABAB receptor agonist baclofen. Transcriptomic analysis of gene expression changes in dorsal root ganglia of mice post-surgery revealed decreased expression of several pro-nociceptive genes including N- and P/Q-type voltage-gated calcium channels important for neurotransmitter release, which suggest a reactive compensatory mechanism to reduce excessive pain similar to the endogenous opioid system. In summary, these findings suggest that pain after surgery can be successfully treated with NaV1.7 inhibitors alone or in combination with baclofen or opioids, which may present a novel and safe treatment strategy for this frequent and poorly managed condition.
2019-05-01 | GSE125076 | GEO
Project description:BackgroundLarge-scale trials have shown that hypofractionated adjuvant breast radiotherapy was as effective in terms of survival and local control as conventional fractionated radiotherapy, and acute toxicity was reduced with hypofractionated radiotherapy. However, there is a lack of data about the toxicity of breast with regional nodal irradiation (RNI). The aim of this study was to assess the effect of fractionation on radiation-related acute skin toxicity in patients receiving RNI in addition to whole-breast or chest wall irradiation, using real-life data.MethodsWe conducted a prospective, multicenter cohort study with systematic computerized data collection integrated into Mosaiq®. Three comprehensive cancer centers used a standardized form to prospectively collect patient characteristics, treatment characteristics and toxicity.ResultsBetween November 2016 and January 2022, 1727 patients were assessed; 1419 (82.2%) and 308 (17.8%) patients respectively received conventional fractionated and hypofractionated radiation therapy. Overall, the incidence of acute grade 2 or higher dermatitis was 28.4% (490 patients). Incidence was lower with hypofractionated than with conventional fractioned radiation therapy (odds ratio (OR) 0.34 [0.29;0.41]). Two prognostic factors were found to increase the risk of acute dermatitis, namely 3D (vs IMRT) and breast irradiation (vs chest wall).ConclusionUsing real-life data from unselected patients with regional nodal irradiation, our findings confirm the decreased risk of dermatitis previously reported with hypofractionated radiation therapy in clinical trials. Expansion of systematic data collection systems to include additional centers as well as dosimetric data is warranted to further evaluate the short- and long-term effects of fractionation in real life.
| S-EPMC9755801 | biostudies-literature
Project description:ObjectivesInadequate acute pain management can reduce the quality of life, cause unnecessary suffering and can often lead to the development of chronic pain. Using group-based trajectory modelling, we previously identified six distinct pain intensity trajectories for the first 14-day postemergency department (ED) discharge; two linear ones with moderate or severe pain during follow-up (~40% of the patients) and four cubic polynomial order trajectories with mild or no pain at the end of the 14 days (low final pain trajectories). We assessed if previously described acute pain intensity trajectories over 14 days after ED discharge are predictive of chronic pain 3 months later.DesignProspective cohort study.SettingTertiary care trauma centre academic hospital.ParticipantsThis study included 18 years and older ED patients who consulted for acute (≤2 weeks) pain conditions that were discharged with an opioid prescription. Patients completed a 14-day diary in which they listed their daily pain intensity (0-10 numeric rating scale).OutcomesThree months after ED visit, participants were questioned by phone about their current pain intensity (0-10 numeric rating scale). Chronic pain was defined as patients with current pain intensity ≥4 at 3 months.ResultsA total of 305 participants remained in the study at 3 months, 49% were women and a mean age of 55±15 years. Twelve per cent (11.9; 95% CI 8.2 to 15.4) of patients had chronic pain at the 3-month follow-up. Controlling for age, sex and pain condition, patients with moderate or severe pain trajectories and those with only a severe pain trajectory were respectively 5.1 (95% CI 2.2 to 11.8) and 8.2 (95% CI 3.4 to 20.0) times more likely to develop chronic pain 3 months later compared with patients in the low final pain trajectories.ConclusionSpecific acute pain trajectories following an ED visit are closely related to the development of chronic pain 3 months later.Trial registration numberNCT02799004; Results.
| S-EPMC7722811 | biostudies-literature