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Endometriosis is a systemic and chronic condition in women of childbearing age, yet a highly enigmatic disease with unresolved questions: there are no known biomarkers, nor established clinical stages. We here investigate the use of patient-generated health data and data-driven phenotyping to characterize endometriosis patient subtypes, based on their reported signs and symptoms. We aim at unsupervised learning of endometriosis phenotypes using self-tracking data from personal smartphones. We leverage data from an observational research study of over 4000 women with endometriosis that track their condition over more than 2 years. We extend a classical mixed-membership model to accommodate the idiosyncrasies of the data at hand, i.e., the multimodality and uncertainty of the self-tracked variables. The proposed method, by jointly modeling a wide range of observations (i.e., participant symptoms, quality of life, treatments), identifies clinically relevant endometriosis subtypes. Experiments show that our method is robust to different hyperparameter choices and the biases of self-tracking data (e.g., the wide variations in tracking frequency among participants). With this work, we show the promise of unsupervised learning of endometriosis subtypes from self-tracked data, as learned phenotypes align well with what is already known about the disease, but also suggest new clinically actionable findings. More generally, we argue that a continued research effort on unsupervised phenotyping methods with patient-generated health data via new mobile and digital technologies will have significant impact on the study of enigmatic diseases in particular, and health in general.
Sex differences in pain sensitivity have been well documented, such that women often report greater sensitivity than men. However, clinical reports highlighting sex differences often equate gender and sex. This is a particularly critical oversight for those whose gender identity is different than their genetic sex.
In the United States (US), long-term opioid therapy has been commonly prescribed for chronic pain. Since recognition of the opioid overdose epidemic, clinical practice guidelines have recommended tapering long-term opioids to reduced doses or discontinuation. The Effects of Prescription Opioid Changes for veterans (EPOCH) study is a national population-based prospective observational study of US Veterans Health Administration primary care patients designed to assess effects of evolving opioid prescribing practice on patients treated with long-term opioids for chronic pain. A stratified random sampling design was used to identify a survey sample from the target population of patients treated with opioid analgesics for ≥ 6 months. Demographic, diagnostic, visit, and pharmacy dispensing data were extracted from existing datasets. A 2016 mixed-mode mail and telephone survey collected patient-reported data, including the main patient-reported outcomes of pain-related function (Brief Pain Inventory interference; BPI-I scores 0-10, higher scores = worse) and health-related quality of life. Data on survey participants and non-participants were analyzed to assess potential nonresponse bias. Weights were used to account for design. Linear regression models were used to assess cross-sectional associations of opioid treatment with patient-reported measures. Of 14,160 patients contacted, 9253 (65.4%) completed the survey. Participants were older than non-participants (63.9 ± 10.6 vs. 59.6 ± 13.0 years). The mean number of bothersome pain locations was 6.8 (SE 0.04). Effectiveness of pain treatment and quality of pain care were rated fair or poor by 56.1% and 45.3%, respectively. The opioid daily dosage range was 1.6 to 1038.2 mg, with mean = 50.6 mg (SE 1.1) and median = 30.9 mg (IQR 40.7). Among the 73.2% of patients who did not receive long-acting opioids, the mean daily dosage was 30.4 mg (SE 0.6) and mean BPI-I was 6.4 (SE 00.4). Among patients who received long-acting opioids, the mean daily dosage was 106.2 mg (SE 2.8) and mean BPI-I was 6.8 (SE 0.07). Higher daily dosage was associated with worse pain-related function and quality of life among patients without long-acting opioids, but not among patients with long-acting opioids. Future analyses will use follow-up data to examine effects of opioid dose reduction and discontinuation on patient outcomes.
Non-specific low back pain (NSLBP) is the most prevalent musculoskeletal condition in western countries and is associated with persistent disability and high consumption of health care resources. NSLBP patients first seek primary health care services but the outcomes are often uncertain. This study aimed to examine the clinical course of the outcomes and to identify prognostic indicators for poor outcomes in NSLBP patients who consulted primary care.
Neuromyelitis optica (NMO) is a disease characterised by severe relapses of optic neuritis and longitudinally extensive transverse myelitis and it has a strong female predilection. Pain is one of the most typical symptom in NMO. However, few studies have been conducted to examine the neuropathic pain mechanism of NMO patients or gender-specific effects using magnetic resonance imaging technique. A total of 38 female patients with NMO, 28 with pain (NMOWP) and 10 without pain (NMOWoP), were classified using the Brief Pain Inventory (BPI); 22 healthy females were also recruited. We used the FSL Image Registration and Segmentation Toolbox (FIRST) for subcortical region volumes quantifications, and voxel-based morphometry analysis for cortical gray matter (GM) volume, to examine the brain morphology in NMOWP patients. In addition, correlation test between structural measurements of NMO patients and clinical indexes was also performed. The results showed: 1) no significant differences in cortical GM density between the NMOWP and NMOWoP groups; 2) significantly smaller hippocampus and pallidum volumes in the NMOWP group compared with the NMOWoP group; 3) significant negative correlation between the average BPI and volumes of the accumbens nucleus and thalamus in NMO patients. These results revealed that structural abnormality exists in NMO female patients who have pain, with significant implications for our understanding of the brain morphology in NMO patients with pain.
A child maltreatment history is reported more frequently among adults with chronic pain compared to the general population; unfortunately, studies have primarily relied upon retrospective maltreatment reports by adults with chronic pain. This prospective study assessed pain symptoms in a cohort of young adult women with a documented history of child maltreatment, compared with a matched cohort of women who did not experience childhood maltreatment. Young women (N = 477) were recruited between ages 14-17 years and followed annually to age 19. Of these women, 57% experienced maltreatment (i.e., physical, sexual, or emotional abuse, neglect; n = 273) substantiated by child welfare record. Maltreated women were demographically-matched to non-maltreated women, also confirmed by child welfare record. In adolescence, post-traumatic stress was assessed. Women were contacted as young adults (Mage = 24.76; n = 383) and surveyed about their pain experiences, including the presence of pain in the past week, pain severity (0-10), and number of body areas with pain. Mediation path analyses examining the impact of maltreatment and adolescent post-traumatic stress on young adult pain were estimated via structural equation modeling. As adults, women who had experienced child maltreatment reported higher pain intensity, a greater number of pain locations, and were more likely to experience pain in the previous week than non-maltreated women. Adolescent post-traumatic stress partially explained the effects of maltreatment on pain. Young adult women who experienced child maltreatment are at higher risk for pain, particularly when they also experienced post-traumatic stress as adolescents.
It is often assumed that there are two types of pain patients: those who respond well to efficacious pain therapies and those who do not respond at all, with few people in the middle. This assumption is based on research that claims that changes in pain intensity have a bimodal distribution. The claim of bimodality has led to calls for a change in how pain clinical trials are designed and analyzed, for example, performing "responder" analyses instead of comparing group means to evaluate the treatment effect. We analyzed data from four clinical trials, two each of duloxetine and pregabalin, for chronic musculoskeletal and neuropathic pain conditions to critically examine the claim of bimodality of the distribution of change in pain intensity. We found that the improper construction of histograms, using unequal bin widths, was the principal flaw leading to the bimodality claim, along with the use of the oft-criticized baseline observation carried forward (BOCF) method for imputing missing data also serving as a contributing factor. Properly constructed histograms of absolute change in pain intensity using equal bin widths, combined with more principled methods for handling missing data, resulted in distributions that had a more unimodal appearance. While our findings neither support nor refute the hypothesis that distinct populations of "responders" and "non-responders" to pain interventions exist, the analyses presented in earlier work do not provide support for this hypothesis, nor for the recommendation that pain clinical trials prioritize "responder" analyses, a less efficient analysis strategy.
Multiple risk factors predict temporomandibular disorders (TMD) onset, but temporal changes in risk factors and their contribution to risk of TMD have not been evaluated. The study aims were to (1) describe changes occurring in premorbid TMD risk factors when re-measured at TMD onset and six months later; and (2) determine if measures of change improve accuracy in predicting TMD incidence compared to premorbid measures alone.
Interdisciplinary pain rehabilitation programs are an evidence-based biopsychosocial treatment approach for chronic pain. The purpose of the current study is to assess outcomes for a 10-week interdisciplinary, Acceptance and Commitment Therapy (ACT)-based, outpatient treatment model and to evaluate the relationship between psychological process variables (i.e., pain catastrophizing, pain acceptance, pain self-efficacy) and treatment outcomes.
To determine preliminary outcomes of a treatment for refractory pediatric migraine that integrates outpatient dihydroergotamine (DHE) infusion with interdisciplinary adjunctive care.