Project description:BackgroundPrevious studies of prognosis for women with Fibromyalgia (FM) or chronic widespread pain (CWP) show contradictory results. However, some women appear to improve in pain and other core symptoms over time. There is limited knowledge about predictors of substantial improvement in pain intensity over a longer period of time. The primary objective of this study was to investigate the natural course of pain intensity and distribution of pain over 10 to 12 years in a cohort of 166 women with FM or CWP. Secondarily we wanted to investigate predictors of substantial improvement (≥50%) in pain intensity after 10 to 12 years.MethodsThe study is a longitudinal prospective cohort study. 166 women with FM or CWP were followed up after 10 to 12 years. 126 women (76%) participated in the follow-up and completed a battery of questionnaires concerning pain intensity, pain distribution and other physical and mental aspects of health. Differences in symptoms within the cohort over 10 to 12 years and predictors of substantial improvement (≥50%) in pain intensity were calculated.ResultsPain had improved at the 10 to 12 year follow-up (p < 0.001) with a mean change of - 9.2 mm (SD 23.3, 95% CI: - 13.3; - 5.0) for pain intensity and - 2.0 sites (SD 4.2, 95% CI: - 2.7; - 1.2) for pain distribution. Nine percent of the 126 women showed an individual moderate improvement in pain intensity while 16% showed a substantial improvement at the follow-up as compared to baseline. Lower symptoms of stress and higher pain intensity at baseline predicted higher probability of reporting at least 50% less pain intensity after 10 to 12 years as compared to baseline.ConclusionsA majority of women with FM and CWP appear to have a positive course of pain over time, which should be communicated to these patients in health care. Reducing stress levels might contribute to better chances of improvement over time.Trial registrationClinicaltrials.gov NCT02872129, registered 06/30/2016.
Project description:This SuperSeries is composed of the SubSeries listed below. Gene expression profiling of continuous or intermittent energy restriction in women at increased risk of breast cancer
Project description:BackgroundChronic pelvic pain persists in some women with endometriosis even after lesion removal and optimized hormonal treatment.ObjectiveCharacterize the presence and distribution of pain, myofascial dysfunction and sensitisation beyond the pelvis in women with endometriosis-associated chronic pelvic pain.MethodsCross-sectional study of 30 women prior to participation in a clinical trial. Evaluation included pain-focused abdominopelvic gynaecologic examination with the identification of pelvic floor muscle spasm. Neuro-musculoskeletal examination assessed paraspinal allodynia and hyperalgesia bilaterally and myofascial trigger points in 13 paired muscles. Pressure-pain thresholds were measured over interspinous ligaments and trigger points. Women completed the body territories element of the Body Pain Index.ResultsAll women had a pelvic floor muscle spasm that they self-identified as a major focus of pain. Twenty of 30 women described their pelvic pain as focal. However, all demonstrated widespread myofascial dysfunction with low pressure-pain thresholds and trigger points in over two-thirds of 26 assessed regions. Widespread spinal segmental sensitisation was present in 17/30, thoracic in 21/30 and lumbosacral/pelvic in 18/30. Cervical sensitisation manifested as low pressure-pain thresholds with 23/30 also reporting recurrent, severe headaches and 21/30 experiencing orofacial pain. Those reporting diffuse pelvic pain were more likely to have widespread (p = .024) and lumbosacral/pelvic (p = .036) sensitisation and report over 10 painful body areas (p = .009).ConclusionsWomen with endometriosis-associated chronic pelvic pain often have myofascial dysfunction and sensitisation beyond the pelvic region that may be initiated or maintained by on-going pelvic floor spasm. These myofascial and nervous system manifestations warrant consideration when managing pain in this population. Clinicaltrials.gov identifier: NCT01553201.SignificanceWomen with endometriosis often have pelvic pain persisting after surgery despite hormonal therapies and these women have regional pelvic sensitisation and myofascial dysfunction. Pelvic floor muscle spasm is a major pain focus in this population. Sensitisation and myofascial dysfunction are widespread, beyond the pelvic region. On-going pelvic floor spasm may initiate or maintain sensitisation. Myofascial/sensitisation manifestations warrant consideration when managing pain in this population.
Project description:Current pain management protocols involving many anesthetic and analgesic drugs reportedly provide adequate analgesia after TKA. However, control of emetic events associated with the drugs used in current multimodal pain management remains challenging.We determined (1) whether ramosetron prophylaxis reduces postoperative emetic events; and (2) whether it influences pain levels and opioid consumption in patients managed with a current multimodal pain management protocol after TKA.We randomized 119 patients undergoing TKA to receive either ramosetron (experimental group, n = 60) or no prophylaxis (control group, n = 59). All patients received regional anesthesia, preemptive analgesic medication, continuous femoral nerve block, periarticular injection, and fentanyl-based intravenous patient-controlled analgesia. We recorded the incidence of emetic events, rescue antiemetic requirements, complete response, pain level, and opioid consumption during three periods (0-6, 6-24, and 24-48 hours postoperatively). The severity of nausea was evaluated using a 0 to 10 VAS.The ramosetron group tended to have a lower incidence of nausea with a higher complete response and tended to have less severe nausea and fewer rescue antiemetic requirements during the 6- to 24-hour period. However, the overall incidences of emetic events, rescue antiemetic requirements, and complete response were similar in both groups. We found no differences in pain level or opioid consumption between the two groups.Ramosetron reduced postoperative emetic events only during the 6- to 24-hour postoperative period and did not affect pain relief. More efficient measures to reduce emetic events after TKA should be explored.Level I, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.
Project description:PurposeManufacturers of total knee arthroplasty (TKA) have introduced narrower femurs to improve bone-implant fit. However, few studies have reported the clinical consequences of mediolateral oversizing. Our hypothesis was that component oversizing negatively influences the results after TKA.MethodsOne hundred and twelve prospectively followed patients with 114 consecutive TKA (64 females and 50 males) were retrospectively assessed. The mean age of the patients was 72 years (range, 56 to 85 years). The dimensions of the femur and tibia were measured on a preoperative CT-scan and were compared with those of the implanted TKA. The influence of size variation on the clinical outcomes 1 year after surgery was assessed.ResultsMediolateral overhang was observed in at least one area in 66 % of the femurs (84 % in females and 54 % in males) and 61 % of the tibia (81 % in females and 40 % in males). Twenty-two patients presented no overhang in any area and 16 had overhang in all studied zones. The increase in the Pain and KOOS scores were 43 ± 21 and 36 ± 18 in the patients without overhang and 31 ± 19 and 25 ± 13 in patients with overhang (p = 0.033; p = 0.032). Knee flexion was 127° ± 7 and 121° ± 11, respectively. Regression and latent class analysis showed a significant negative correlation between overall oversizing and overall outcome.ConclusionsThis study confirms that oversizing may lead to worse clinical results in TKA. The clinical consequences are that surgeons should pay attention not to oversize implants during implantation nd that oversizing should be ruled out in case of so called unexplained pain.Level of evidenceIV.
Project description:Lymphocyte and breast tissue samples from overweight woman at increased risk of breast cancer before and after 1 month of intermittant energy restriction Introduction Observational studies indicate that weight loss and energy restriction reduce breast cancer risk. Intermittent energy restriction (IER) reduces weight as well as, or more than continuous energy restriction (CER), but its effect on the breast and systemic metabolism as indicators of breast cancer risk are not known. Methods We assessed the effect of IER ( 2 days of 65% energy restriction) for one menstrual cycle on the breast (breast gene expression and fat cell size) and systemic metabolism (insulin resistance, lipids, serum and urine metabolites) in 23 overweight premenopausal women at high risk of breast cancer. Unsupervised hierarchical analysis selected 100 genes with the highest variance between pre and post IER biopsies in 20 subjects, whilst mass spectrometry was used to assess corresponding changes in serum (LCMS) and urine metabolites (GCMS) in 23 subjects in the restricted and unrestricted days of the IER. Results Women lost on average 4.8% (± 2.0) of body weight and 8.0% (± 5.0) of body fat. Insulin resistance (HOMA) was reduced by 29.8% (±17.8) on the restricted days and by 11%(±34) on the unrestricted days of the IER. Over 250 serum and urine metabolites significantly increased or decreased during the two restricted days and most returned to normal after the subsequent five day period . In the breast tissue, approximately half (In 11) of the subjects displayed down regulation of several metabolic pathways including lipid synthesis, growth factors and hormones, whilst epithelial genes including milk proteins, secretoglobulins and mucins were up-regulated and several metabolic pathways down-regulated including lipid synthesis, growth factors and hormones. In the other nine subjects there was no appreciable effect of IER on the breast. CorrespondingThe gene changes were not seen in peripheral blood lymphocytes, and there was no reduction in breast fat cell size. The two groups defined by change in gene expression or lack of it did not differ in the degree of weight or fat loss, other systemic metabolic markers, or histological assessment of the biopsies. Conclusion We conclude that breasts vary in response to short-term IER, the mechanism of which requires further investigation. Trial registration ISRCTN77916487
Project description:Objectives: Although generalized muscle pain, tiredness, anxiety, and depression are commonly present among chronic widespread pain (CWP) patients, the molecular mechanisms behind CWP are not fully elucidated. Moreover, the lack of biomarkers often makes diagnosis and treatment problematic. In this study, we investigated the correlation between pain intensity, psychological distress, and plasma proteins among CWP patients and controls (CON). Methods: The plasma proteome of CWP (n = 15) and CON (n = 23) was analyzed using two-dimensional gel electrophoresis. Orthogonal Partial Least Square analysis (OPLS) was used to determine proteins associated with pain intensity (numeric rating scale) in CWP and psychological distress (Hospital and Depression Scale, HADS) in CWP and CON. Significant proteins were identified by MALDI-TOF and tandem MS. Results: In CWP, pain intensity was associated with plasma proteins mostly involved in metabolic and immunity processes (e.g., kininogen-1, fibrinogen gamma chain, and ceruloplasmin), and psychological distress was associated with plasma proteins related to immunity response, iron ion, and lipid metabolism (e.g., complement factor B, complement C1r subcomponent, hemopexin, and clusterin). Discussion: This study suggests that different plasma protein patterns are associated with different pain intensity and psychological distress in CWP. Proteins belonging to the coagulation cascade and immunity processes showed strong associations to each clinical outcome. Using the plasma proteome profile of CWP to study potential biomarker candidates provides a snapshot of ongoing systemic mechanisms in CWP.
Project description:BACKGROUND:There is a remarkable lack of detailed knowledge on pain areas in axial spondyloarthritis (axSpA), and their clinical relevance is largely unknown. Pain area may reflect local disease processes, but amplification of nervous system signalling may alter this relationship. Also, gender differences in pain area may exist in axSpA, possibly confounding disease activity outcomes. Therefore, we firstly detailed pain locations in axSpA and evaluated gender differences. Secondly, we explored the relationship of regional pain definitions with clinical outcomes. Finally, we explored the role of pain area in the assessment of disease activity. METHODS:Body charts informed on the presence of axial, peripheral articular and non-articular pain in 170 patients (108 men, 62 women) with axSpA. Multivariate Odds Ratios (ORs) were used to compare genders. General linear models were used to explore clinical differences in disease activity (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]), activity limitations (Bath Ankylosing Spondylitis Functional Index [BASFI]), fear of movement (Tampa Scale for Kinesiophobia 11-item version [TSK-11]), anxiety (Hospital Anxiety and Depression Scale subscale anxiety [HADS-A]) and depression (HADS subscale depression [HADS-D]) between four subgroups classified by widespread non-articular pain (WNAP+/-) and physician global assessment of disease activity (PGDA+/-) (p?<?.05). Principal Component Analysis (PCA) was performed to explore gender differences in the structure of disease activity. RESULTS:Axial thoracic pain was least prevalent (lumbar, 74.4%; cervical, 47.6%; cervicothoracic, 47.6%; thoracic, 32.4%), but it was about three times more likely in women (OR, 2.92; p?=?.009). Axial cervicothoracic junction pain spread more diffusely in women (OR, 2.48; p?=?.018). Women exhibited a two- to threefold increased likelihood of widespread axial (OR, 3.33; p?=?.007) and peripheral articular (OR, 2.34; p?=?.023) pain. A subgroup of WNAP+/PGDA- combined with low PGDA (27% of all patients) was associated with worse BASFI, BASDAI, HADS-A and HADS-D in men and worse TSK-11 and HADS-A in women (p?<?.05). Disease activity outcomes showed a two-factor structure in women but not in men. CONCLUSIONS:In patients with axSpA, the location and spread of pain was different between genders and was related to worse clinical status. On the basis of pain area and PGDA, clinical subgroups exhibiting a remarkably distinct health status were identified. Outcome instruments such as BASDAI should acknowledge gender differences to ensure structural validity.
Project description:Dietary energy restriction (DER) reduces risk of spontaneous mammary cancer in rodents. In humans, DER in premenopausal years seems to reduce risk of postmenopausal breast cancer. Markers of DER are required to develop acceptable DER regimens for breast cancer prevention. We therefore examined markers of DER in the breast, adipose tissue, and serum. Nineteen overweight or obese women at moderately increased risk of breast cancer (lifetime risk, 1 in 6 to 1 in 3) ages between 35 and 45 were randomly allocated to DER [liquid diet, 3,656 kJ/d (864 kcal/d); n = 10] or asked to continue their normal eating patterns (n = 9) for one menstrual cycle. Biopsies of the breast and abdominal fat were taken before and after the intervention. RNA was extracted from whole tissues and breast epithelium (by laser capture microdissection) and hybridized to Affymetrix GeneChips. Longitudinal plasma and urine samples were collected before and after intervention, and metabolic profiles were generated using gas chromatography-mass spectrometry. DER was associated with significant reductions in weight [-7.0 (+/-2.3) kg] and in alterations of serum biomarkers of breast cancer risk (insulin, leptin, total and low-density lipoprotein cholesterol, and triglycerides). In both abdominal and breast tissues, as well as isolated breast epithelial cells, genes involved in glycolytic and lipid synthesis pathways (including stearoyl-CoA desaturase, fatty acid desaturase, and aldolase C) were significantly down-regulated. We conclude that reduced expressions of genes in the lipid metabolism and glycolytic pathways are detectable in breast tissue following DER, and these may represent targets for DER mimetics as effective chemoprophylactic agents Transcriptomic and Metabolomic intervention study of continuous energy restriction in 19 participants
Project description:Epithelial ovarian cancer is a fatal disease of largely unknown etiology. Higher parity is associated with reduced risk of ovarian cancer. However, among parous women, the impact of pregnancy-related factors on risk is not well understood. This population-based case-control study included all parous women with epithelial ovarian cancer in Denmark, Finland, Norway and Sweden during 1967-2013 (n = 10,957) and up to 10 matched controls (n = 107,864). We used conditional logistic regression to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for pregnancy-related factors and ovarian cancer risk by histological subtype. Preterm delivery was associated with an increased risk [pregnancy length (last pregnancy) ≤30 vs. 39-41 weeks, OR 1.33 (95% CI 1.06-1.67), adjusted for number of births]; the OR increased as pregnancy length decreased (p for trend < 0.001). Older age at first and last birth was associated with a decreased risk [first birth: 30-39 vs. <25 years: adjusted OR 0.76 (95% CI 0.70-0.83); last birth 30-39 vs. <25 years: adjusted OR 0.76 (95% CI 0.71-0.82)]. Increasing number of births was protective [≥4 births vs. 1; OR 0.63 (95% CI 0.59-0.68)] for all subtypes, most pronounced for clear-cell tumors [OR 0.30, (95% CI 0.21-0.44), pheterogeneity < 0.001]. No associations were observed for multiple pregnancies, preeclampsia or offspring size. In conclusion, in addition to high parity, full-term pregnancies and pregnancies at older ages were associated with decreased risk of ovarian cancer. Our findings favor the cell clearance hypothesis, i.e. a recent pregnancy provides protection by clearing of precancerous cells from the epithelium of the ovary/fallopian tubes, mediated by placental or ovarian hormones.