Obstetrical outcomes of women with new-onset isolated proteinuria diagnosed after 24 weeks' gestation.

PURPOSE: To assess a possible association between marked proteinuria and the risk of preeclampsia with severe features, as defined by the American College of Obstetricians and Gynecologists. METHODS: This retrospective study included data recorded at a tertiary university-affiliated hospital between 2017 and 2022. Women at or beyond 24 weeks of gestation with proteinuria (protein levels > 300 mg in a 24 h urine collection) and normal blood pressure during the initial 48 h of admission were included. Obstetrical and neonatal outcomes were compared between women with mild proteinuria (300-1000 mg/24 h) and marked proteinuria (≥ 1000 mg/24 h). RESULTS: Among the women with marked proteinuria (n = 48) compared to those with mild proteinuria (n = 108), the incidences were higher of preeclampsia (50.0% vs. 22.2%, p = 0.001) and of preeclampsia with severe features (18.8% vs. 2.8%, p < 0.001). In multivariate analysis that adjusted for maternal age, primiparity, multiple pregnancy, uric acid level > 6 mg/dL and aspirin treatment, marked proteinuria was a risk factor for preeclampsia with severe features (adjusted odds ratio [aOR] = 10.2, confidence interval [CI] 95% 1.9-54.0, p = 0.007) and for small-for-gestational-age infants (aOR = 2.4, 95% CI 1.02-5.6, p = 0.001). Among women with marked compared to mild proteinuria, rates were also higher of labor induction (58.3% vs. 25.9%, p < 0.001), indicated preterm delivery (41.7% vs. 25.0%, p = 0.04) and admission to the neonatal intensive care unit (44.1% vs. 25.8%, p = 0.017). CONCLUSIONS: Women with marked compared to mild isolated proteinuria showed higher risk of developing preeclampsia with severe features and of delivering small-for-gestational-age neonates.

"Nociplastic Pain": A Challenge to Nosology and to Nociception.

The construct of "nociplastic pain" has met with divergent receptions. On the one hand it has been enthusiastically embraced, to the extent of conflation with central sensitization of nociception and the International Classification of Diseases 11th Revision (ICD-11) entity of "primary" pain, and the promulgation of "nociplastic pain syndromes." On the other hand, it has been rejected by those whose skepticism derives from the absence, by definition, of underlying activation of nociceptors. This article seeks to dissect these divergent views and search for reconciliation between them. One line of argument is that "nociplastic" pain, "primary" pain, and "central sensitisation of nociception" reflect different domains of inquiry and should not be conflated. "Nociplastic" pain emerges as a hypothesis that confers clinical legitimacy and utility; while that hypothesis needs a minor but important modification and continues to require testing, discipline in its usage is necessary. The other line of argument discovers an unexpected impasse: the construct of "nociplastic pain" describes a phenomenon that accords with the International Association for the Study of Pain definition of pain but occurs in the absence of nociception-as-currently-defined, thus challenging the definitional link between pain and tissue damage. The article offers a resolution of this impasse by suggesting that nociception-as-currently-defined be replaced by the resurrected concept of a nociceptive apparatus, activation of which is necessary but not sufficient for the experience of pain. One consequence would be to allow the assertions underpinning "nociplastic" to be tested empirically; another would be to relate the phenomenon of pain to a more biologically plausible basis than "actual" or "resemblance to" tissue damage. PERSPECTIVE: This article explores the major challenges posed by "nociplastic pain" to nosology and to nociception. While discipline in the clinical use of the construct is required, it also emerges that the main issue is the International Association for the Study of Pain definition of nociception. A reconceptualization of nociception is proposed for logical, biological, and clinical coherence.

Clarifying "chronic primary musculoskeletal pain"? The waters remain murky.

Commentary on: Fitzcharles M-A, Cohen SP, Clauw DJ, Littlejohn G, Usui C, Häuser W. Chronic primary musculoskeletal pain: a new concept of non-structural regional pain. PAIN Reports 2022;7:e1024. See also: Treede R-D. Chronic musculoskeletal pain: traps and pitfalls in classification and management of a major global disease burden. PAIN Reports 2022;7:e1023.

Pain is Not a "thing": How That Error Affects Language and Logic in Pain Medicine.

Effectiveness in academic and clinical communication depends upon agreement on what words and concepts denote and on the consequent ability to argue logically and accurately. In the pain medicine literature there are many examples of imprecision and confusion in this respect, including misnomers and fallacies in reasoning. This article firstly critically examines some of these misnomers. Identified themes include pain being conceptualised as a "thing," conflation between nociception and pain, and confusion between stimulus and response and between the perspectives of the experiencer and the observer of "pain." Secondly, fallacies in reasoning are identified that contribute to imprecision and confusion. These include reification of pain, attributing to the brain functions that belong to whole organisms, and the illusory truth effect. Thirdly, these themes are identified also in constructs that are shown to be based more on speculation than on fact. Taken together, these observations reveal a need to review and, where necessary, modify terminology and concepts used in Pain Medicine. PERSPECTIVE: This article examines a number of words and constructs commonly found in the pain literature from the perspective of accuracy in terms of their consistency of usage, concordance with fact, degree of speculation and logical argument. A common major theme is the error of considering pain as a "thing" that has agentive properties. A need to clarify much of the language used in Pain Medicine is identified.

Use of pharmacological and nonpharmacological treatments for chronic noncancer pain among people using opioids: a longitudinal cohort study.

ABSTRACT: Although multimodal management of chronic noncancer pain (CNCP) is recommended, long-term treatment utilization patterns among people using opioids are not well known. The Pain and Opioids IN Treatment study recruited Australian adults receiving opioids for CNCP for more than 6 weeks from community pharmacies. Pharmacological (opioid and nonopioid analgesics and psychotropic medicines) and nonpharmacological (physical, mental health, and specialized) treatments used in the previous 12 months and 30 days were collected annually over 4 years (2015-2018). Associations were explored between 30-day treatment use and sociodemographic characteristics and pain measures. Overall, 1334 participants completed at least one annual follow-up. The median pain severity (5.0, interquartile range [IQR] 3.8 to 6.3) and pain interference scores (5.7, IQR 3.9-7.3) indicated moderate pain throughout the study period, despite most participants reporting the use of nonopioid pharmacological (12 month: 97.6% and 30 day: 96.8%) and nonpharmacological treatments (12 month: 91.8% and 30 day: 66.1%). Some treatment use was inconsistent with guidelines: ongoing nonsteroidal anti-inflammatory drugs and sedative-hypnotic use were common, whereas fewer people engaged with pain management programs (12 month: 22.3%). Private health insurance was associated with using physical (adjusted odds ratio 1.61, 99.5% confidence intervals 1.15-2.24) and specialized nonpharmacological treatments (adjusted odds ratio 1.47, 99.5% confidence intervals 1.14-1.91). This study demonstrates that many Australians taking opioids long-term for CNCP also use nonopioid pharmacological and nonpharmacological treatments. The use of pharmacological treatments including nonsteroidal anti-inflammatory drugs, psychotropic medicines, and gabapentinoids, outside guidelines, warrants review. Furthermore, despite Australia's universal healthcare scheme subsidising some nonpharmacological treatments, overall use of these treatments was associated with having private health insurance, highlighting a need for more equitable service provision.

Pharmaceutical Opioid Use Patterns and Indicators of Extramedical Use and Harm in Adults With Chronic Noncancer Pain, 2012-2018.

Importance: Despite concern about harms related to long-term prescribed opioid use among individuals with chronic noncancer pain (CNCP), no study has examined whether the same patients engage in a risky pattern of use consistently for the long term. Objective: To examine the prevalence, incidence, persistence, and cessation of a range of opioid behaviors, indicators of extramedical use, and harm among individuals who are prescribed opioids. Design, Setting, and Participants: This 5-year prospective cohort study in communities across Australia included 1514 adults who were prescribed opioids for CNCP. Data collection took place from August 2012 to December 2018, and data analysis took place from February to November 2020. Exposure: Prescription opioid use. Main Outcomes and Measures: High-dose opioid use (≥200 oral morphine equivalent [OME] mg/d); requesting an increase in opioid dose; requesting an early prescription renewal; tampering with opioid medication; diversion of medication to others; and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision opioid dependence. Cessation of opioid use was also assessed. Results: Of the 1514 participants, 672 (44.39%) were men, the mean (SD) age was 58 (19) years, and 737 (48.68%) were unemployed. At each annual interview, approximately 1 in 8 people (10.98% [95% CI, 10.33%-11.63%] to 14.73% [95% CI, 13.98%-15.48%] at any given interview) were taking more than 200 OME mg/d; comparatively more had requested an increased dosage in the previous 3 months (8.46% [95% CI, 7.89%-9.03%] to 23.77% [95% CI, 22.82%-24.73%]); and fewer asked for an early prescription renewal (4.61% [95% CI, 4.19%-5.03%] to 13.97% [95% CI, 13.24%-14.70%]). In any given interview, between 3.06% (95% CI, 2.72%-3.40%) and 7.86% (95% CI, 7.31%-8.41%) of respondents reported tampering and between 0.47% (95% CI, 0.33%-0.60%) and 1.39% (95% CI, 1.16%-1.62%) reported diversion to others. Between 8.28% (95% CI, 7.71%-8.84%) and 13.06% (95% CI, 12.35%-13.77%) met criteria for opioid dependence at each interview. Opioid cessation increased across interviews, from year 1 (9.15% [95% CI, 8.55%-9.74%]) to year 5 (20.02% [19.14%-20.89%]). There was considerable incidence and cessation in all behaviors from 1 interview to the next: most who engaged in any of these behaviors only did so at only 1 interview. For pharmaceutical opioid dependence, between 55.26% (95% CI, 53.81%-56.71%) and 64.44% (95% CI, 62.87%-66.00%) of cases in 1 interview did not meet dependence criteria in the following interview. Conclusions and Relevance: These findings suggest considerable fluidity in opioid use, extramedical behaviors, and opioid dependence among people with CNCP. This reinforces the need for reassessment of the effectiveness and safety of prescription opioid use over time.

Classification algorithm for the International Classification of Diseases-11 chronic pain classification: development and results from a preliminary pilot evaluation.

ABSTRACT: The International Classification of Diseases-11 (ICD-11) chronic pain classification includes about 100 chronic pain diagnoses on different diagnostic levels. Each of these diagnoses requires specific operationalized diagnostic criteria to be present. The classification comprises more than 200 diagnostic criteria. The aim of the Classification Algorithm for Chronic Pain in ICD-11 (CAL-CP) is to facilitate the use of the classification by guiding users through these diagnostic criteria. The diagnostic criteria were ordered hierarchically and visualized in accordance with the standards defined by the Society for Medical Decision Making Committee on Standardization of Clinical Algorithms. The resulting linear decision tree underwent several rounds of iterative checks and feedback by its developers, as well as other pain experts. A preliminary pilot evaluation was conducted in the context of an ecological implementation field study of the classification itself. The resulting algorithm consists of a linear decision tree, an introduction form, and an appendix. The initial decision trunk can be used as a standalone algorithm in primary care. Each diagnostic criterion is represented in a decision box. The user needs to decide for each criterion whether it is present or not, and then follow the respective yes or no arrows to arrive at the corresponding ICD-11 diagnosis. The results of the pilot evaluation showed good clinical utility of the algorithm. The CAL-CP can contribute to reliable diagnoses by structuring a way through the classification and by increasing adherence to the criteria. Future studies need to evaluate its utility further and analyze its impact on the accuracy of the assigned diagnoses.

Clinical correlates and outcomes associated with pregabalin use among people prescribed opioids for chronic non-cancer pain: A five-year prospective cohort study.

AIMS: Pregabalin has become widely used as an alternative to opioids in treating certain types of chronic non-cancer pain, but few studies have examined its clinical efficacy outside trials. We address this gap by examining the utilization, correlates and clinical outcomes of pregabalin use among an Australian community-based cohort of people prescribed opioids for chronic non-cancer pain. METHODS: Through a five-year prospective cohort study (n = 1514) we examined associations between pregabalin use and pain severity and interference, mental health, opioid dose and past month use of ambulance and emergency department services. We used fixed-effects regression models to examine within-participant differences, and random-effects regression models to examine within- and between-participant differences in clinical outcomes. RESULTS: In an analysis of cases with complete data over five-years (n = 896), the prevalence of pregabalin use ranged from 16% at cohort entry to 29% at 36- and 48-months, and 46% reported pregabalin use at any time during the five years. Pregabalin use was associated with greater pain severity and interference and greater use of high-risk opioid doses (>90 oral morphine equivalents/day). Pregabalin use was not associated with changes in mental health symptoms, ambulance or emergency department attendance in the fixed or random effects models. CONCLUSIONS: Pregabalin use was common, but for most people use was not associated with clinically meaningful improvements in pain or functioning.

Risk factors for indicators of opioid-related harms amongst people living with chronic non-cancer pain: Findings from a 5-year prospective cohort study.

BACKGROUND: The literature suggests patient characteristics and higher opioid doses and long-term duration are associated with problematic opioid behaviours but no one study has examined the role of all these factors simultaneously in a long-term prospective cohort study. METHODS: Five-year, community-based, prospective cohort of people prescribed opioids for chronic non-cancer pain (CNCP). Logistic mixed effect models with multiple imputation were used to address missing data. Oral morphine equivalent (OME) mg per day was categorised as: 0 mg OME/day, 1-49 mg OME/day (reference), 50-89 mg OME/day, 90-199 mg OME/day and 200mg+ OME/day. Patient risk factors included: age, gender, substance use, mental health history and pain-related factors. Main outcomes included: Prescribed Opioids Difficulties Scale (PODS), Opioid-Related Behaviours In Treatment (ORBIT) scale, and ICD-10 opioid dependence. Multiple confounders for problematic opioid behaviours were assessed. FINDINGS: Of 1,514 participants 44.4% were male (95%CI 41.9-46.9) and their mean age was 58 years (IQR 48-67). Participants had a mean duration of pain of 10 years (IQR 4.5-20.0) and had been taking strong opioids for a median of four years (IQR 1.0-10.0). At baseline, median OME/day was 73 (IQR 35-148). At 5-years, 85% were still taking strong opioids. PODS moderate-high scores reduced from 59.9% (95%CI 58.8-61.0) at baseline to 51.5% (95%CI 50.0-53.0) at 5-years. Around 9% met criteria for ICD-10 opioid dependence at each wave. In adjusted mixed effect models, the risk factors most consistently associated with problematic opioid use were: younger age, substance dependence, mental health histories and higher opioid doses. INTERPRETATION: Both patient risk factors and opioid dose are associated with problematic opioid use behaviours.

The revised International Association for the Study of Pain definition of pain: concepts, challenges, and compromises.

ABSTRACT: The current International Association for the Study of Pain (IASP) definition of pain as "An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage" was recommended by the Subcommittee on Taxonomy and adopted by the IASP Council in 1979. This definition has become accepted widely by health care professionals and researchers in the pain field and adopted by several professional, governmental, and nongovernmental organizations, including the World Health Organization. In recent years, some in the field have reasoned that advances in our understanding of pain warrant a reevaluation of the definition and have proposed modifications. Therefore, in 2018, the IASP formed a 14-member, multinational Presidential Task Force comprising individuals with broad expertise in clinical and basic science related to pain, to evaluate the current definition and accompanying note and recommend whether they should be retained or changed. This review provides a synopsis of the critical concepts, the analysis of comments from the IASP membership and public, and the committee's final recommendations for revisions to the definition and notes, which were discussed over a 2-year period. The task force ultimately recommended that the definition of pain be revised to "An unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage," and that the accompanying notes be updated to a bulleted list that included the etymology. The revised definition and notes were unanimously accepted by the IASP Council early this year.

Experimental shoulder pain models do not validly replicate the clinical experience of shoulder pain.

Background and aims People with shoulder pain often present with abnormal shoulder muscle function. It is not known whether shoulder pain causes or is the result of muscle dysfunction. If pain leads to muscle dysfunction, therapeutic interventions that produce shoulder pain may be contraindicated. Experimentally induced nociception can be used to investigate a causal relationship between shoulder pain and muscle dysfunction. However, the validity of current experimental shoulder pain protocols has not been established. The aim of this study was to determine whether current experimental shoulder pain protocols validly replicate the clinical experience of shoulder pain with respect to pain distribution, quality and behaviour. Methods Nine pain free participants received two injections of hypertonic saline, one into the subacromial space and one into supraspinatus, in random order, at least 1 week apart. Investigators blind to the injection site assessed pain distribution, pain response to clinical tests which provoke shoulder pain and pain quality assessed using the McGill Pain Questionnaire. Results Following hypertonic saline injection into both the subacromial space and supraspinatus: pain was most commonly reported in the deltoid region and did not extend beyond the elbow; the most common response to clinical tests which provoke shoulder pain was a decrease in pain; and the highest rating of pain quality was in the sensory domain with very few responses in the affective domain. Conclusions Experimental shoulder pain induced by injection of hypertonic saline into either the subacromial space or supraspinatus produced a pain distribution similar to that observed in clinical shoulder pain, but neither experimental pain protocol could reproduce the increases in pain intensity following shoulder provocation tests or the emotional distress commonly observed in people with clinical shoulder pain. Implications Pain induced by local shoulder nociception produced by hypertonic saline injection into shoulder structures has significant limitations as a model of clinical shoulder pain. While it is perhaps unsurprising that short duration, chemically-induced experimental pain does not replicate the quality of the clinical experience of shoulder pain, the validity of experimental shoulder pain models which produce the opposite response to provocation testing to clinical shoulder pain must be questioned.