Effects of proactive healthcare on pain, physical and activities of daily living functioning in vulnerable older adults with chronic pain: a pragmatic clinical trial with one- and two-year follow-up.

PURPOSE: To investigate the changes in pain, physical and activities of daily living (ADL) functioning in vulnerable older adults with chronic pain after proactive primary care intervention. METHODS: This study was embedded in a prospective, pragmatic, matched-control multicenter trial at 19 primary care practices in Sweden, with proactive medical and social care (Intervention Group, IG, n = 134) in comparison with usual care (Control Group, CG, n = 121). Patients with chronic pain, defined as pain experienced longer than 3 months, were included in this subgroup analysis. Data on pain aspects, physical and ADL functioning were collected in the questionnaires at baseline, one- and two-year follow-up (FU-1 and FU-2). Data on prescribed pain medications was collected by local health authorities. RESULTS: Mean age was 83.0 ± 4.7 years with almost equal representation of both genders. From baseline until FU-2, there were no significant within-group or between-group changes in pain intensity. Small adjustments of pain medication prescriptions were made in both groups. Compared to FU-1, the functional changes were more measurable at FU-2 as fewer participants had impaired physical functioning in IG (48.4%) in comparison to CG (62.6%, p = 0.027, Effect Size φ = 0.14). Higher scores of ADL-staircase (more dependent) were found in both groups (p < 0.01, Effect Size r = 0.24 in CG and r = 0.16 in IG). CONCLUSION: Vulnerable older adults with chronic pain seemed to remain physical and ADL functioning after proactive primary care intervention, but they may need tailored strategies of pain management to improve therapeutic effects. TRIAL REGISTRATION: ClinicalTrials.gov 170608, ID: NCT03180606.

Eating habits and the desire to eat healthier among patients with chronic pain: a registry-based study.

Healthcare professionals often meet pain patients with a poor nutritional status such as obesity, unhealthy dietary behaviors, and a suboptimal dietary intake. A poor nutritional status may play a significant role in the occurrence, development, and prognosis of chronic pain. This study investigated eating habits in a specialized pain rehabilitation center using data (N = 2152) from the Swedish quality registry for pain rehabilitation during the period 2016-2021. Patients answered a lifestyle questionnaire regarding their eating habits and desire to modify their lifestyle. The mean (SD) patient age was 46.1 (14.6) years, with 24.8% classified as obese. Suboptimal eating habits included irregular mealtimes (27.2%), weekly consumption of fast-food (20.3%) and nearly daily consumption of confectionery (33.3%). Approximately 20% (n = 426) reported a desire to eat healthier. Frequent confectionery intake (Odds ratio [OR] 1.23, 95% Confidence Interval (CI) 1.04-1.47) and fast-food consumption (OR 1.58, 95% CI 1.24-2.02) increased the likelihood to desire healthier eating. Younger patients (18-29 years), those classified as obese, and those with more extended spatial pain were more likely to express a desire to eat healthier. Eating habits should be addressed in pain management and interdisciplinary pain rehabilitation teams are encouraged to provide nutritional care tailored to the patient's needs.

Catastrophizing and acceptance are mediators between insomnia and pain intensity-an SQRP study of more than 6,400 patients with non-malignant chronic pain conditions.

Background: Sleep problems (insomnia) and chronic pain are associated. Chronic pain and insomnia/insufficient sleep quality share similar symptoms and features. Although they have a bidirectional relationship, more research is needed to understand how they interact via mediators and how moderators influence this relationship. Aims: In this large clinical registry-based cohort study (N = 6,497), we investigate important mediators between insomnia and pain intensity in a cross-sectional sample of chronic pain patients using advanced path analysis. In addition, we investigate whether some background variables were moderators of the identified important paths or not and the correlation patterns between insomnia and pain intensity in relation to the mediators. Methods: This study includes a cohort of adult patients with chronic non-cancer pain from the Swedish Quality Registry for Pain Rehabilitation (SQRP) with data on patient-reported outcome measures (PROMs) (2008-2016). The PROMs cover the background, pain aspects, psychological distress, pain-related cognitions, activity/participation, and health-related quality of life variables of the patients. Partial least squares structural equation modeling was used to explore the direct and indirect (via mediators) relationships between insomnia and pain intensity at baseline. Results: In this cohort study, insomnia was prevalent at 62.3%, and both direct and indirect mediating paths were present for the insomnia-pain intensity relationship. All of the mediating effects combined were weaker than the direct effect between insomnia and pain intensity. The mediating effects via catastrophizing and acceptance showed the strongest and equal mediating paths, and mediating effects via fear avoidance were the second strongest. Insomnia showed stronger direct significant correlations with psychological distress, catastrophizing, and acceptance compared with those of pain intensity. Sex, age, education level, spatial extent of pain, or body mass index did not moderate the mediating paths. Discussion and conclusion: This study confirms the existence of significant direct and mediating paths between reported insomnia and pain intensity. Future studies should focus on illuminating how sleep interventions influence pain intensity and other important key factors that contribute to the distress of chronic pain patients.

Lifestyle changes are burdensome with my body broken by pain and obesity: patients' perspectives after pain rehabilitation.

BACKGROUND: Despite the existing evidence regarding the interrelated relationship between pain and obesity, knowledge about patients' perspectives of this relationship is scarce, especially from patients with chronic pain and obesity after completing Interdisciplinary Pain Rehabilitation Program (IPRP). AIMS: This qualitative study expands the understanding of patients' perspectives on how chronic pain and obesity influence each other and how the two conditions affect the ability to make lifestyle changes. METHOD: A purposive sample of patients with Body Mass Index (BMI) ≥ 30 kg/m2 and who had completed an IPRP were recruited for individual semi-structured interviews. The transcribed interviews were analysed using latent content analysis and a pattern of theme and categories was constructed based on the participants' perspectives. RESULTS: Sixteen patients (aged 28-63 years, 11 female, BMI 30-43 kg/m2) shared their experiences of chronic pain, obesity and lifestyle changes after IPRP. The analysis revealed one overall theme (lifestyle changes are burdensome with a body broken by both pain and obesity) and four categories (pain disturbing days and nights worsens weight control, pain-related stress makes lifestyle changes harder, a painful and obese body intertwined with negative emotions and the overlooked impact of obesity on chronic pain). Most participants perceived that their pain negatively impacted their obesity, but they were uncertain whether their obesity negatively impacted their pain. Nevertheless, the participants desired and struggled to make lifestyle changes. CONCLUSION: After IPRP, patients with chronic pain and obesity perceived difficulties with self-management and struggles with lifestyle changes. They experienced a combined burden of the two conditions. Their perspective on the unilateral relationship between pain and obesity differed from the existing evidence. Future tailored IPRPs should integrate nutritional interventions and address the knowledge gaps as well.

Teaching the biopsychosocial model of chronic pain: Whom are we talking to?

The biopsychosocial (BPS) model of chronic pain can be illustrated in many ways. Our aim is to adapt three illustrations of the BPS approach selected from the literature to target different groups: patients, health professionals and clinical trainees. In clinician-patient consultations, we use an illustration which shows the interactions among the BPS domains in the creation of suffering and pain behaviours in a "vicious spiral". Moreover, we help our patients understand chronic pain often does not entail remaining tissue damage. In clinical practice, we communicate to other health professionals that the relative contribution of each BPS domain varies from patient to patient. This disproportional contribution may also change dynamically over the time. In teaching clinical trainees, we combine thoroughness (i.e., focus on "details") with an understanding of the "dynamics" of pain chronification/chronic pain, i.e., focus on helping the trainee identify the mutual and joint interactions between different parts of the BPS framework. CONCLUSION: The three illustrations can be used as pedagogical tools for better-informed BPS perspectives in different settings. PRACTICE IMPLICATIONS: Clinicians need to be keen observers and adapt their communication depending on whom they are talking to.

Semi-Synthesis of Flavonoid Glycosides and Their Anti-Inflammatory and Antitumor Activities towards Triple Negative Breast Cancer.

BACKGROUND: Flavonoid glycosides are known to possess diverse bioactivities including antitumor and anti-inflammatory properties. Hesperetin is abundant in nature and can be used to synthesize bioactive flavonoids. This has the advantages of low cost, short synthetic steps, simple operation, and good yields. OBJECTIVE: In this study, we aimed to synthesize bioactive flavonoids and flavonoid glycosides from hesperetin and evaluate the antitumor and anti-inflammatory activities of these compounds. METHODS: A series of flavonoids and their derivatives were synthesized by methoxylation, oxidative dehydrogenation, benzylation, debenzylation, and deacetylation as well as using a modified peroxyacetone method and a glycoside condensation reaction. Their anti-inflammatory activities were evaluated for their inhibitory effects on nitric oxide (NO), tumor necrosis factor (TNF-α), and interleukin-6 (IL-6) production in LPS-induced RAW264.7 mouse macrophages. Their structures were characterized by HRMS, 1 H-NMR, and 13 C-NMR, and their cytotoxicity on the human triple-negative breast cancer cell (TNBC) line, SUM 149, was tested by using the MST assay. RESULTS: Most of the compounds markedly reduced NO production in LPS-stimulated murine macrophages at the tested concentrations in a dose-dependent manner. Among these, compounds 1, 7, 9, and 17 showed significant anti-inflammatory activities against NO production in LPS-induced RAW264.7 mouse macrophages. In addition, they could also reduce the release of TNF-α and IL-6 in a concentration-dependent manner. Most of the tested compounds showed remarkable anti-human TNBC activities. Compounds 1b-1m, 1, and 3 showed a certain degree of growth inhibition effect on the human TNBC cell lines and their IC50 values were all below 16.61 µM. In addition, compound 1l was the most cytotoxic with IC50 values of 1.38±0.31 µM, while the other compounds were inactive with inhibition rates <50 % at the highest concentration tested (20 µM). CONCLUSIONS: A novel series of flavonoids were synthesized from the natural flavonoid, hesperetin, including 17 new compounds. Screening tests indicated that most of these compounds reduced NO production in LPS-stimulated murine macrophages at concentrations of 15 to 60 µM, and the inhibition generally increased in a dose-dependent manner. Some compounds showed different degrees of cytotoxicity on the human TBNC cell lines, SUM 149.

Fibromyalgia in women: association of inflammatory plasma proteins, muscle blood flow, and metabolism with body mass index and pain characteristics.

Introduction: Obesity is a common comorbidity in fibromyalgia (FM). Both FM and obesity have been connected to low-grade inflammation, although it is possible that previously reported inflammatory alterations in FM primarily may be linked to increased body mass index (BMI). Objective: This study aimed to investigate whether the inflammatory plasma protein profile, muscle blood flow, and metabolism and pain characteristics (clinical parameters and patient-reported outcome measurements) differed between female patients with FM with and without obesity. Methods: Patients with FM underwent clinical examinations, physical tests, and answered questionnaires. They were dichotomized according to BMI (<30 kg/m2 [n = 14]; ≥30 kg/m2 [n = 13]). Blood samples were collected and analyzed using a panel of 71 inflammatory plasma proteins. Results: There were significant (P < 0.05) differences in blood pressure, pulse, max VO2, pain intensity, physical capacity, and Fibromyalgia Impact Questionnaire between the groups; the obese group had higher blood pressure, pulse, pain intensity, and Fibromyalgia Impact Questionnaire. There were 14 proteins that contributed to the group belonging. The 4 most important proteins for the group discrimination were MIP1ß, MCP4, IL1RA, and IL6, which showed higher concentrations in obese patients with FM. Significantly decreased blood flow and increased concentration of pyruvate were detected in obese patients compared with nonobese patients. There was significant correlation between inflammatory proteins and sedentary behavior and health status in obese patients with FM. Conclusions: These findings suggest that metabolism and inflammation interact in female patients with FM with obesity and might cause chronic low-grade inflammation. Screening for obesity and monitoring of BMI changes should be considered in the treatment of patients with FM.

The Importance of Nutrition as a Lifestyle Factor in Chronic Pain Management: A Narrative Review.

In everyday clinical practice, healthcare professionals often meet chronic pain patients with a poor nutritional status. A poor nutritional status such as malnutrition, unhealthy dietary behaviors, and a suboptimal dietary intake can play a significant role in the occurrence, development, and prognosis of chronic pain. The relationship between nutrition and chronic pain is complex and may involve many underlying mechanisms such as oxidative stress, inflammation, and glucose metabolism. As such, pain management requires a comprehensive and interdisciplinary approach that includes nutrition. Nutrition is the top modifiable lifestyle factor for chronic non-communicable diseases including chronic pain. Optimizing one's dietary intake and behavior needs to be considered in pain management. Thus, this narrative review reports and summarizes the existing evidence regarding (1) the nutrition-related health of people experiencing pain (2) the underlying potential mechanisms that explain the interaction between nutrition and chronic pain, and (3) the role of nutrition screening, assessment and evaluation for people experiencing pain and the scope of nutrition practice in pain management. Future directions in the nutrition and chronic pain field are also discussed.

Reported Outcomes in Interdisciplinary Pain Treatment: An Overview of Systematic Reviews and Meta-Analyses of Randomised Controlled Trials.

Background: There is considerable diversity of outcome selections and methodologies for handling the multiple outcomes across all systematic reviews (SRs) of Interdisciplinary Pain Treatment (IPT) due to the complexity. This diversity presents difficulties for healthcare decision makers. Better recommendations about how to select outcomes in SRs (with or without meta-analysis) are needed to explicitly demonstrate the effectiveness of IPT. Objective: This overview systematically collates the reported outcomes and measurements of IPT across published SRs and identifies the methodological characteristics. Additionally, we provide some suggestions on framing the selection of outcomes and on conducting SRs of IPT. Methods: Three electronic databases (PubMed, Cochrane Library, and Epistemonikos) and the PROSPERO registry for ongoing SR were supplemented with hand-searching ending on 30 September 2021. Results: We included 18 SRs with data on 49007 people from 356 primary randomised controlled trials (RCTs); eight were followed by meta-analysis and ten used narrative syntheses of data. For all the SRs, pain was the most common reported outcome (72%), followed by disability/functional status (61%) and working status (61%). Psychological well-being and quality of life were also reported in half of the included SR (50%). The core outcome domains according to VAPAIN, IMMPACT, and PROMIS were seldom met. The methodological quality varied from critically low to moderate according to AMSTAR2. The AMSTAR2 rating was negatively correlated to the number of outcome domains in PROMIS, and VAPAIN was positively correlated with IMMPACT and PROMIS, indicating the intercorrelations between the reported outcomes. Conclusion: This systematic overview showed wide-ranging disparity in reported outcomes and applied outcome domains in SRs evaluating IPT interventions for chronic pain conditions. The intercorrelations between the reported outcomes should be appropriately handled in future research. Some approaches are discussed as well.

Prevalence and clinical characteristics of septicemia in children with Mycoplasma pneumoniae pneumonia.

BACKGROUND: Mycoplasma pneumoniae (MP) pneumonia in children can be challenging to treat, and the impact of MP blood infection is unclear. The present study aims to determine the prevalence and clinical characteristics of MP septicemia among pediatric patients. METHODS: Children hospitalized at our center for MP pneumonia between October 2017 and June 2018 were included. Healthy controls visiting our outpatient clinic for regular physical examinations were also enrolled. MP was detected by real-time polymerase chain reaction (qPCR) analysis of plasma and peripheral blood mononuclear cell (PBMC) samples. RESULTS: Sixty-one children with MP pneumonia and 30 healthy children were included. Among children with MP infection, 31 (50.8%) were positive for MP by qPCR (19 in plasma samples, 8 in PBMC samples, and 4 in both). All healthy controls were negative for MP by qPCR. CONCLUSIONS: The prevalence of MP septicemia in children with MP pneumonia is moderate. However, detection of MP in blood samples may have limited clinical value for guiding treatment.

Lose Pain, Lose Weight, and Lose Both: A Cohort Study of Patients with Chronic Pain and Obesity Using a National Quality Registry.

BACKGROUND: It is known that chronic pain makes it difficult to lose weight, but it is unknown whether obese patients (body mass index ≥30 kg/m2) who experience significant pain relief after interdisciplinary multimodal pain rehabilitation (IMMPR) lose weight. OBJECTIVE: This study investigated whether obese patients with chronic pain lost weight after completing IMMPR in specialist pain units. The association of pain relief and weight change over time was also examined. METHODS: Data from obese patients included in the Swedish Quality Registry for Pain Rehabilitation for specialized pain units were used (N=224), including baseline and 12-month follow-up after IMMPR from 2016 to 2018. Patients reported body weight and height, pain aspects (eg, pain intensity), physical activity behaviours, psychological distress, and health-related quality of life (HRQoL). A reduction of at least 5% of initial weight indicates clinically significant weight loss. Patients were classified into three groups based on the pain relief levels after IMMPR: pain relief of clinical significance (30% or more reduction of pain intensity); pain relief without clinical significance (less than 30% reduction of pain intensity); and no pain relief. Linear mixed regression models were used to examine the weight changes among the groups with different pain relief levels. RESULTS: A significant reduction of pain intensity was found after IMMPR (p < 0.01, effect size Cohen's d = 0.34). A similar proportion of patients in the three groups with different pain relief levels had clinically significant weight loss (20.2%~24.3%, p = 0.47). Significant improvements were reported regarding physical activity behaviour, psychological distress, and HRQoL, but weight change was not associated with changes of pain intensity. CONCLUSION: About one-fifth of obese patients achieved significant weight reduction after IMMPR. Obese patients need a tailored pain rehabilitation program incorporating a targeted approach for weight management.

Association between Participation Activities, Pain Severity, and Psychological Distress in Old Age: A Population-Based Study of Swedish Older Adults.

Although chronic pain is common in old age, previous studies on participation activities in old age seldom consider pain aspects and its related consequences. This study analyses associations between participation activities, pain severity, and psychological distress in an aging population of Swedish older adults (N = 6611). We examined older adults' participation in five common leisure activities using the Multidimensional Pain Inventory (MPI), sociodemographic factors, pain severity, weight status, comorbidities, and pain-related psychological distress (anxiety, depression, insomnia severity, and pain catastrophising). We found that gender, body mass index (BMI) levels, and psychological distress factors significantly affected older adults' participation in leisure activities. Pain severity and multimorbidity were not significantly associated with older adults' participation in leisure activities nor with gender stratification in generalised linear regression models. The potentially modifiable factors, such as high levels of BMI and psychological distress, affected activity participation in men and women differently. Health professionals and social workers should consider gender and target potentially modifiable factors such as weight status and psychological distress to increase older adults' participation in leisure activities.

Pain Characteristics and Quality of Life in Older People at High Risk of Future Hospitalization.

This study deals with how pain characteristics in conjunction with other factors affect quality of life (QoL) in a vulnerable primary care population. We recruited vulnerable older people (75+, n = 825) living in south-eastern Sweden. A postal questionnaire included pain aspects, QoL (EQ-5D-3L, RAND-36 physical functioning, attitudes toward own aging, and life satisfaction), functional status, social networks, and basic demographic information. Pain extent and localization was obtained by digitalization of pain drawings reported on standard body charts. Most respondents were experiencing pain longer than 3 months (88.8%). Pain frequency varied mostly between occasionally (33.8%) and every day (34.8%). A minority reported high pain intensity (13.6%). The lower back and lower legs were the most frequently reported pain locations (>25%). Multiple linear regression model revealed three characteristics of pain (intensity, frequency, and extent) remained inversely associated with the EQ-5D-3L index score (R2 = 0.57). Individually, each of these pain characteristics showed a negative impact on the other three dimensions of QoL (R2 = 0.23-0.59). Different features of pain had impact on different dimensions of QoL in this aging population. A global pain assessment is useful to facilitate individual treatment and rehabilitation strategies in primary care.

Facing obesity in pain rehabilitation clinics: Profiles of physical activity in patients with chronic pain and obesity-A study from the Swedish Quality Registry for Pain Rehabilitation (SQRP).

BACKGROUND: The obesity epidemic has influenced pain rehabilitation clinics. To date, little is known about baseline level of physical activity (PA) in patients referred to pain rehabilitation clinics. We aimed to investigate the PA levels of patients referred to pain rehabilitation clinics and to evaluate the effect of excess weight on PA level. METHODS AND FINDINGS: Data were obtained from the Swedish Quality Registry for Pain Rehabilitation between 2016 and 2017. These data included PA time (everyday PA and physical exercise per week), Body Mass Index (BMI), sociodemographic factors, chronic pain and psychological aspects (e.g., pain intensity, depressive and anxiety symptoms and insomnia problems). Insufficient PA was defined as less than 150 minutes per week. We performed logistic regressions as well as orthogonal partial least square regression to estimate the effects of excess weight on PA. Over one-fourth of the patients were classified as obese (BMI ≥30 kg/m2, 871/3110, 25.3%) and nearly one-third of these patients were classified as severely obese (BMI ≥35 kg/m2, 242/871, 27.8%). Time estimations for physical exercise varied among the BMI groups, but patients in the higher BMI category were more likely to spend less time on everyday PA. Compared to normal weight, mild obesity [odds ratio (OR) 0.65, 95% confidence interval (CI) 0.53-0.81] and severe obesity (OR 0.56, 95% CI 0.42-0.74) were associated with less PA. Mild obese patients had an elevated risk of 65% and severe obese patients had an elevated risk of 96% for insufficient PA. Increased pain intensity was positively related to insufficient PA (OR 1.17, 95% CI 1.06-1.29) among the obese patients. CONCLUSION: Having low PA is very common for patients referred to pain rehabilitation clinics, especially for those with comorbid obesity. As a first step to increase PA, obese patients need to be encouraged to increase the intensity and amount of less painful daily PA.

Lanostane-type triterpenoids from Ganoderma applanatum and their inhibitory activities on NO production in LPS-induced BV-2 cells.

Five previously undescribed lanostane-type triterpenoids, including two triterpenoids with a rearranged side chain (applanoic acids E and F), one C21 nortriterpenoid (16,17-dehydroapplanone E), as well as two highly oxygenated lanostane triterpenoids (methyl applaniate B and applanoic acid G), were isolated from the fruiting bodies of Ganoderma applanatum (Pers.) Pat. Their structures were elucidated on the basis of spectroscopic analysis, X-ray crystallography and ECD data. Applanoic acid E, 16,17-dehydroapplanone E, and methyl applaniate B showed inhibitory effects on the release of NO by LPS-induced BV-2 cells.

Pain Catastrophizing in Older Adults with Chronic Pain: The Mediator Effect of Mood Using a Path Analysis Approach.

Cognitive models of pain propose that catastrophic thinking is negatively associated with chronic pain. However, pain catastrophizing is a complex phenomenon requiring a multivariate examination. This study estimates the effects of mood variables (anxiety and depression) on pain catastrophizing in older adults with chronic pain. A postal survey addressing pain aspects was sent to 6611 people ≥ 65 years old living in south-eastern Sweden. Pain catastrophizing was measured using the pain catastrophizing scale. Anxiety and depression were assessed using two subscales of the general well-being schedule. Data were analysed using a path analysis approach. A total of 2790 respondents (76.2 ± 7.4 years old) reported chronic pain (≥three months). The mediation model accounted for 16.3% of anxiety, 17.1% of depression, and 30.9% of pain catastrophizing variances. Pain intensity, insomnia, number of comorbidities, and lifestyle factors (smoking, alcohol consumption, and weight) significantly affected both pain catastrophizing and mood. Anxiety (standardized path coefficient (bstd) = 0.324, p < 0.001) in comparison to depression (bstd = 0.125, p < 0.001) had a greater effect on pain catastrophizing. Mood mediated the relationship between pain catastrophizing and pain-related factors accounting for lifestyle and sociodemographic factors.

ASS1 Overexpression: A Hallmark of Sonic Hedgehog Hepatocellular Adenomas; Recommendations for Clinical Practice.

Until recently, 10% of hepatocellular adenomas (HCAs) remained unclassified (UHCA). Among the UHCAs, the sonic hedgehog HCA (shHCA) was defined by focal deletions that fuse the promoter of Inhibin beta E chain with GLI1. Prostaglandin D2 synthase was proposed as immunomarker. In parallel, our previous work using proteomic analysis showed that most UHCAs constitute a homogeneous subtype associated with overexpression of argininosuccinate synthase (ASS1). To clarify the use of ASS1 in the HCA classification and avoid misinterpretations of the immunohistochemical staining, the aims of this work were to study (1) the link between shHCA and ASS1 overexpression and (2) the clinical relevance of ASS1 overexpression for diagnosis. Molecular, proteomic, and immunohistochemical analyses were performed in UHCA cases of the Bordeaux series. The clinico-pathological features, including ASS1 immunohistochemical labeling, were analyzed on a large international series of 67 cases. ASS1 overexpression and the shHCA subgroup were superimposed in 15 cases studied by molecular analysis, establishing ASS1 overexpression as a hallmark of shHCA. Moreover, the ASS1 immunomarker was better than prostaglandin D2 synthase and only found positive in 7 of 22 shHCAs. Of the 67 UHCA cases, 58 (85.3%) overexpressed ASS1, four cases were ASS1 negative, and in five cases ASS1 was noncontributory. Proteomic analysis performed in the case of doubtful interpretation of ASS1 overexpression, especially on biopsies, can be a support to interpret such cases. ASS1 overexpression is a specific hallmark of shHCA known to be at high risk of bleeding. Therefore, ASS1 is an additional tool for HCA classification and clinical diagnosis.

Reported Outcomes in Published Systematic Reviews of Interdisciplinary Pain Treatment: Protocol for a Systematic Overview.

BACKGROUND: Interdisciplinary pain treatment (IPT) is a complex intervention; its outcomes are very diverse, as are the methodologies for handling those outcomes. This diversity may hamper evidence-based decision making. Presently, there is no gold standard recommendation of how to select reported outcomes in published systematic reviews and meta-analyses to explicitly demonstrate the effectiveness of IPT. OBJECTIVE: In this systematic overview, we aim to evaluate the reported outcome domains and measurements across published systematic reviews and meta-analyses and to identify any methods, considerations, and discussion regarding the handling of the chosen outcome domains and measurements. METHODS: This article describes the protocol for a systematic overview of the outcomes reported in published systematic reviews and meta-analyses of randomized control trials for the effectiveness of IPT versus any control. To this end, we searched the PubMed, Cochrane Library, and Epistemonikos databases from inception to December 2019. Two independent investigators screened the titles, the abstracts of the identified records, and the full texts of the potentially eligible systematic reviews and meta-analyses, performed data extraction according to predefined forms, and rated the quality of the included systematic reviews and meta-analyses. The quality of the included systematic reviews and meta-analyses will be rated with AMSTAR (A MeaSurement Tool to Assess systematic Reviews) 2. Data will be analyzed descriptively and stratified by AMSTAR 2. RESULTS: We introduced the rationale and design of a systematic overview to summarize and map the chosen IPT outcome domains and the methods of handling these outcomes reported in published systematic reviews and meta-analyses. As of December 2019, we collected 5229 systematic reviews, of which 147 (2.81%) were examined in-depth for eligibility. Topline results are anticipated by September 2020. CONCLUSIONS: The results of this study will be published as soon as they are available. Our results will fill a gap in the related literature and will be used to inform the development of a set of recommendations that can be applied in systematic reviews and hopefully serve as a gold standard. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/17795.

Clinically useful prediction of hospital admissions in an older population.

BACKGROUND: The healthcare for older adults is insufficient in many countries, not designed to meet their needs and is often described as disorganized and reactive. Prediction of older persons at risk of admission to hospital may be one important way for the future healthcare system to act proactively when meeting increasing needs for care. Therefore, we wanted to develop and test a clinically useful model for predicting hospital admissions of older persons based on routine healthcare data. METHODS: We used the healthcare data on 40,728 persons, 75-109 years of age to predict hospital in-ward care in a prospective cohort. Multivariable logistic regression was used to identify significant factors predictive of unplanned hospital admission. Model fitting was accomplished using forward selection. The accuracy of the prediction model was expressed as area under the receiver operating characteristic (ROC) curve, AUC. RESULTS: The prediction model consisting of 38 variables exhibited a good discriminative accuracy for unplanned hospital admissions over the following 12 months (AUC 0.69 [95% confidence interval, CI 0.68-0.70]) and was validated on external datasets. Clinically relevant proportions of predicted cases of 40 or 45% resulted in sensitivities of 62 and 66%, respectively. The corresponding positive predicted values (PPV) was 31 and 29%, respectively. CONCLUSION: A prediction model based on routine administrative healthcare data from older persons can be used to find patients at risk of admission to hospital. Identifying the risk population can enable proactive intervention for older patients with as-yet unknown needs for healthcare.

Factors Associated with Life Satisfaction in Older Adults with Chronic Pain (PainS65+).

BACKGROUND: Chronic pain in later life is a worldwide problem. In younger patients, chronic pain affects life satisfaction negatively; however, it is unknown whether this outcome will extend into old age. OBJECTIVE: This study examines which factors determine life satisfaction in older adults who suffer from chronic pain with respect to socio-demographics, lifestyle behaviors, pain, and comorbidities. METHODS: This cross-sectional study recruited a random sample of people ≥65 years old living in south-eastern Sweden (N= 6611). A postal survey addressed pain aspects and health experiences. Three domains from the Life Satisfaction Questionnaire (LiSat-11) were used to capture the individual's estimations of overall satisfaction (LiSat-life), somatic health (LiSat-somhealth), and psychological health (LiSat-psychhealth). RESULTS: Respondents with chronic pain (2790, 76.2±7.4 years old) rated lower on life satisfaction than those without chronic pain, with medium effect size (ES) on LiSat-somhealth (r = 0.38, P < 0.001) and small ES on the other two domains (r < 0.3). Among the respondents with chronic pain, severe pain (OR 0.29-0.59) and pain spreading (OR 0.87-0.95) were inversely associated with all three domains of the LiSat-11. Current smoking, alcohol overconsumption, and obesity negatively affected one or more domains of the LiSat-11. Most comorbidities were negatively related to LiSat-somhealth, and some comorbidities affected the other two domains. For example, having tumour or cancer negatively affected both LiSat-life (OR 0.62, 95% CI 0.44-0.88) and LiSat-somhealth (OR 0.42, 95% CI 0.24-0.74). Anxiety or depression disorders had a negative relationship both for LiSat-life (OR 0.54, 95% CI 0.38-0.78) and LiSat-psychhealth (OR 0.10, 95% CI 0.06-0.14). CONCLUSION: Older adults with chronic pain reported lower life satisfaction but the difference from their peers without chronic pain was trivial, except for satisfaction with somatic health. Pain management in old age needs to consider comorbidities and severe pain to improve patients' life satisfaction.