Is pain associated with premature mortality in patients with psoriatic arthritis? A nested case-control study using the DANBIO Register.

OBJECTIVES: It has been hypothesized that the presence of chronic pain causes excess mortality. Since chronic pain is prevalent among patients with PsA this potential association should be explored. We aimed to investigate whether higher cumulative pain intensity is associated with an excess mortality risk in patients with PsA. METHODS: A nested case-control study using data from the nationwide DANBIO Register (Danish Database for Biological Therapies in Rheumatology) Register and Danish healthcare registers. Cases were patients who died and corresponding to the date of death, matched on sex, year of birth and calendar period at the time of death with up to five controls. Exposure of interest was mean pain intensity reported during the time followed in routine rheumatology practice. Pain intensity was measured using a visual analogue scale from 0 to 100 and conditional logistic regression was used to calculate odds of mortality per 5 unit increase in pain while adjusting for confounders. RESULTS: The cohort consisted of 8019 patients. A total of 276 cases were identified and matched with 1187 controls. Higher mean pain intensity was associated with increased odds of mortality [odds ratio 1.06 (95% CI 1.02, 1.10)] in the crude model, but there was no association [odds ratio 0.99 (95% CI 0.95, 1.03)] when adjusting for additional confounders. Factors shown to increase the odds of mortality were recent glucocorticoid use, concomitant chronic obstructive pulmonary disease, diabetes mellitus, cancer and cardiovascular disease. CONCLUSION: These results indicate that experienced pain in itself is not associated with premature mortality in patients with PsA. However, recent glucocorticoid use and concurrent comorbidities were.

Activation of GPR37 in macrophages confers protection against infection-induced sepsis and pain-like behaviour in mice.

GPR37 was discovered more than two decades ago, but its biological functions remain poorly understood. Here we report a protective role of GPR37 in multiple models of infection and sepsis. Mice lacking Gpr37 exhibited increased death and/or hypothermia following challenge by lipopolysaccharide (LPS), Listeria bacteria, and the mouse malaria parasite Plasmodium berghei. Sepsis induced by LPS and Listeria in wild-type mice is protected by artesunate (ARU) and neuroprotectin D1 (NPD1), but the protective actions of these agents are lost in Gpr37-/- mice. Notably, we found that ARU binds to GPR37 in macrophages and promotes phagocytosis and clearance of pathogens. Moreover, ablation of macrophages potentiated infection, sepsis, and their sequelae, whereas adoptive transfer of NPD1- or ARU-primed macrophages reduced infection, sepsis, and pain-like behaviors. Our findings reveal physiological actions of ARU in host cells by activating macrophages and suggest that GPR37 agonists may help to treat sepsis, bacterial infections, and malaria.

Intraarticular triamcinolone hexacetonide, stanozolol, Hylan G-F 20 and platelet concentrate in a naturally occurring canine osteoarthritis model.

Osteoarthritis (OA) is a disease transversal to all mammals, a source of chronic pain and disability, a huge burden to societies, with a significant toll in healthcare cost, while reducing productivity and quality of life. The dog is considered a useful model for the translational study of the disease, closely matching human OA, with the advantage of a faster disease progression while maintaining the same life stages. In a prospective, longitudinal, double-blinded, negative controlled study, one hundred (N = 100) hip joints were selected and randomly assigned to five groups: control group (CG, n = 20, receiving a saline injection), triamcinolone hexacetonide group (THG, n = 20), platelet concentrate group (PCG, n = 20), stanozolol group (SG, n = 20) and hylan G-F 20 group (HG). Evaluations were conducted on days 0 (T0, treatment day), 8, 15, 30, 60, 90, 120, 150 and 180 days post-treatment, consisting of weight distribution analysis and data from four Clinical Metrology Instruments (CMI). Kaplan-Meier estimators were generated and compared with the Breslow test. Cox proportional hazard regression analysis was used to investigate the influence of variables of interest on treatment survival. All results were analyzed with IBM SPSS Statistics version 20 and a significance level of p < 0.05 was set. Sample included joints of 100 pelvic limbs (of patients with a mean age of 6.5 ± 2.4 years and body weight of 26.7 ± 5.2 kg. Joints were graded as mild (n = 70), moderate (n = 20) and severe (n = 10) OA. No differences were found between groups at T0. Kaplan-Meier analysis showed that all treatments produced longer periods with better results in the various evaluations compared to CG. Patients in HG and PCG took longer to return to baseline values and scores. A higher impact on pain interference was observed in THG, with a 95% improvement over CG. PCG and HG experienced 57-81% improvements in functional evaluation and impairments due to OA, and may be a better options for these cases. This study documented the efficacy of several approaches to relieve OA clinical signs. These approaches varied in intensity and duration. HG and PCG where the groups were more significant improvements were observed throughout the follow-up periods, with lower variation in results.

Greater Pain Severity Is Associated with Worse Outcomes in Patients with Heart Failure.

We examined the relationship between pain severity and outcomes in patients with heart failure with reduced ejection fraction (HFrEF) in the HF-ACTION randomized controlled trial. Trends of health-related quality of life (HRQoL) measures grouped by patients' self-reported baseline bodily pain severity were compared using correlation tests, and the association between pain severity and clinical outcomes (including a primary composite endpoint of all-cause mortality and all-cause hospitalization) was assessed using multivariable adjusted analyses. Of the 2310 patients, 22.9% reported no pain, 45.8% very mild/mild, 24.9% moderate, and 6.4% severe/very severe. Greater pain severity was associated with worse HRQoL measures (EuroQoL-5D-3L and Kansas City Cardiomyopathy Questionnaire; both p < 0.0001). Compared to those reporting no pain, patients reporting severe/very severe pain had greater risk for the primary endpoint (adjusted hazard ratio 1.42, 95% confidence interval 1.11-1.83, p = 0.01). In patients with HFrEF, greater pain severity was associated with worse HRQoL and clinical outcomes. Trial Registration: NCT00047437.

Radiofrequency Ablation for the Palliative Treatment of Bone Metastases: Outcomes from the Multicenter OsteoCool Tumor Ablation Post-Market Study (OPuS One Study) in 100 Patients.

PURPOSE: To evaluate the effectiveness of radiofrequency (RF) ablation as measured by change in worst pain score from baseline to 3 mo after RF ablation for the palliative treatment of painful bone metastases. MATERIALS AND METHODS: One hundred patients (mean age, 64.6 y) underwent RF ablation for metastatic bone disease and were followed up to 6 mo. Subjects' pain and quality of life were measured before RF ablation and postoperatively by using the Brief Pain Index and European Quality of Life questionnaires. Opioid agent use and device-, procedure-, and/or therapy-related adverse events (AEs) were collected. RESULTS: Eighty-seven patients were treated for tumors involving the thoracolumbar spine and 13 for tumors located in the pelvis and/or sacrum. All ablations were technically successful, and 97% were followed by cementoplasty. Mean worst pain score decreased from 8.2 ± 1.7 at baseline to 3.5 ± 3.2 at 6 mo (n = 22; P < 0.0001 for all visits). Subjects experienced significant improvement for all visits in average pain (P < .0001), pain interference (P < .0001), and quality of life (P < .003). Four AEs were reported, of which 2 resulted in hospitalization for pneumonia and respiratory failure. All 30 deaths reported during the study were attributed to the underlying malignancy and not related to the study procedure. CONCLUSIONS: Results from this study show rapid (within 3 d) and statistically significant pain improvement with sustained long-term relief through 6 mo in patients treated with RF ablation for metastatic bone disease.

Effectiveness of Radiofrequency Ablation in the Treatment of Painful Osseous Metastases: A Correlation Meta-Analysis with Machine Learning Cluster Identification.

A systematic review and meta-analysis of pain response after radiofrequency (RF) ablation over time for osseous metastases was conducted in 2019. Analysis used a random-effects model with GOSH plots and meta-regression. Fourteen studies comprising 426 patients, most with recalcitrant pain, were identified. Median pain reduction after RF ablation was 67% over median follow-up of 24 weeks (R2 = -.66, 95% confidence interval -0.76 to -0.55, I2 = 71.24%, fail-safe N = 875) with 44% pain reduction within 1 week. A low-heterogeneity subgroup was identified with median pain reduction after RF ablation of 70% over 12 weeks (R2 = -.75, 95% confidence interval -0.80 to -0.70, I2 = 2.66%, fail-safe N = 910). Addition of cementoplasty after RF ablation did not significantly affect pain scores. Primary tumor type and tumor size did not significantly affect pain scores. A particular, positive association between pain after RF ablation and axial tumors was identified, implying possible increased palliative effects for RF ablation on axial over appendicular lesions. RF ablation is a useful palliative therapy for osseous metastases, particularly in patients with recalcitrant pain.

Perioperative Outcomes of Lower Extremity Revascularization for Rest Pain and Tissue Loss.

BACKGROUND: Critical limb ischemia (CLI) is the clinical manifestation of severe peripheral artery disease presenting as rest pain (RP) and tissue loss (TL). Most studies compare CLI as a homogenous group with claudication with limited database studies specifically studying these differences. We hypothesize that CLI should be stratified into RP and TL because of significant differences in disease severity, comorbidities, and outcomes. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database from 2012 to 2016 was reviewed. All patients with a postoperative diagnosis of CLI undergoing femoral to popliteal bypass (FPB) with vein or graft were identified. Patients were stratified into cohorts based on International Classification of Disease (ICD)-9 or ICD-10 codes for RP or TL (gangrene or ulcer). Univariate and multivariate analyses were performed to examine 30-day mortality, morbidity, major amputation, and readmission adjusting for demographics, comorbidities, and procedural details. RESULTS: There were 5,304 patients. Compared to RP, patients with TL were older (P < 0.0001) and more likely to be dependent (P < 0.0001). TL patients were also more likely to have diabetes (P < 0.0001), congestive heart failure (P < 0.0001), renal failure (P = 0.004), dialysis (P < 0.0001), history of wound infection (P < 0.0001), and sepsis (P < 0.0001). TL patients had higher American Society of Anesthesiologists class (P < 0.0001), were less likely to be transferred from home (P < 0.0001), and more likely to receive an FPB with vein (P = 0.03). Patients with TL had worse perioperative outcomes compared with RP in terms of pneumonia (P = 0.004), unplanned intubation (P = 0.009), cardiac arrest requiring cardiopulmonary resuscitation (P = 0.003), bleeding requiring transfusions (P < 0.0001), sepsis (P < 0.0001), septic shock (P = 0.02), and reoperation (P < 0.0001). TL was associated with significantly higher 30-day morbidity (P < 0.0001), 30-day mortality (P < 0.0001), major amputation (P = 0.0004), and readmission rates (P = 0.005). Patients with TL compared with those with RP also had longer hospital stays (P < 0.0001) and days between operation to discharge (P < 0.0001). TL was independently associated with increased 30-day morbidity (OR: 1.16 [1.00-1.35]) and major amputation (OR: 2.48 [1.29-4.76]) compared with RP. CONCLUSIONS: Patients with RP and TL have drastic differences that impact perioperative mortality and readmissions. TL is an independent predictor of 30-day morbidity and major amputation. The stratification of CLI into RP and TL can provide insight into variations in outcomes and provide a means to quantify the risks associated with the 2 manifestations of the disease.

Association of periprocedural intravenous morphine use on clinical outcomes in ST-elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention: Systematic review and meta-analysis.

OBJECTIVES: To conduct a systematic review and meta-analysis of studies examining the impact of periprocedural intravenous morphine on clinical outcomes in patients undergoing primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI). BACKGROUND: Morphine analgesia may reduce the absorption of co-prescribed P2Y12 antagonists attenuating platelet inhibition. The impact of periprocedural intravenous morphine on clinical outcomes in patients undergoing PCI for STEMI is not well defined. METHODS: Analysis of the electronic databases of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, Web of Science and ClinicalTrials.gov for association of peri-PCI intravenous morphine use with in-hospital or 30-day myocardial infarction (MI) (primary outcome) and in-hospital or 30-day mortality. RESULTS: A total of 11 studies were included for systematic review. One study was a randomized controlled trial, 10 were observational studies. Five studies including 3,748 patients were included in meta-analysis of in-hospital or 30-day MI. Within this group, patients were treated concurrently with ticagrelor (n = 2,239), clopidogrel (n = 1,256) and prasugrel (n = 253). There was no significant association of in-hospital or 30-day MI with intravenous morphine (odds ratio 1.88; 95% confidence interval [CI] 0.87-4.09; I2 0%). Across seven studies and 5,800 patients, no increased risk of mortality at the same composite time endpoint was evident (odds ratio 0.70; 95% CI 0.40-1.23; I2 19%). CONCLUSIONS: Periprocedural intravenous morphine administration was not associated with adverse short-term clinical outcomes in patients undergoing primary PCI for STEMI. Further randomized trial data are needed to evaluate the pharmacologic interaction between morphine and P2Y12 antagonists with clinical outcomes.

Quality of life trajectories in survivors of acute myocardial infarction: a national longitudinal study.

AIM: To define trajectories of perceived health-related quality of life (HRQoL) among survivors of acute myocardial infarction (AMI) and identify factors associated with trajectories. METHODS: Data on HRQoL among 9566 survivors of AMI were collected from 77 National Health Service hospitals in England between 1 November 2011 and 24 June 2015. Longitudinal HRQoL was collected using the EuroQol five-dimension questionnaire measured at hospitalisation, 1, 6 and 12 months post-AMI. Trajectories of perceived HRQoL post-MI were determined using multilevel regression analysis and latent class growth analysis (LCGA). RESULTS: One or more percieved health problems in mobility, self-care, usual activities, pain/discomfort and anxiety/depression was reported by 69.1% (6607/9566) at hospitalisation and 59.7% (3011/5047) at 12 months. Reduced HRQoL was associated with women (-4.07, 95% CI -4.88 to -3.25), diabetes (-2.87, 95% CI -3.87 to -1.88), previous AMI (-1.60, 95% CI -2.72 to -0.48), previous angina (-1.72, 95% CI -2.77 to -0.67), chronic renal failure (-2.96, 95% CI -5.08 to -0.84; -3.10, 95% CI -5.72 to -0.49), chronic obstructive pulmonary disease (-3.89, 95% CI -5.07 to -2.72) and cerebrovascular disease (-2.60, 95% CI -4.24 to -0.96). LCGA identified three subgroups of HRQoL which we labelled: improvers (68.1%), non-improvers (22.1%) and dis-improvers (9.8%). Non-improvers and dis-improvers were more likely to be women, non-ST-elevation myocardial infarction (NSTEMI) and have long-term health conditions, compared with improvers. CONCLUSIONS: Quality of life improves for the majority of survivors of AMI but is significantly worse and more likely to decline for women, NSTEMI and those with long-term health conditions. Assessing HRQoL both in hospital and postdischarge may be important in determining which patients could benefit from tailored interventions. TRIAL REGISTRATION: NCT01808027 and NCT01819103.

Association of Opioid Use in the Week Before Death Among Patients With Advanced Lung Cancer Having Sepsis.

Opioid use can induce immunosuppression; however, it is unclear whether opioid use increases infections in patients with advanced cancers. This study assessed the association between opioid use in the week before death and mortality among patients with advanced lung cancer having sepsis. Data on opioid usage in the week before death, general information, and clinical information of the patients were collected retrospectively. The primary outcome was the association between opioid use in the week before death and mortality after sepsis. The study included 980 patients who died of advanced lung cancer between January 2003 and June 2017 (sepsis related: 413, unrelated to sepsis: 567). The average morphine equivalent daily dose in the final week was higher in the sepsis group (313.5 ± 510.5 mg) than in the nonsepsis group (125.2 ± 246.9 mg, P < .001). A significant association was found between the average morphine equivalent daily dose in the final week and mortality due to sepsis (odds ratio: 1.02, 95% confidence interval: 1.01-1.02, P < .001). This was especially evident when the dose was increased by 10 mg in the final week. Furthermore, older age, male sex, and a lower body mass index were associated with an increased risk of mortality after developing sepsis. Opioid use in the week before death may be associated with mortality for patients with advanced lung cancer having sepsis.

End of life care for people with alcohol and drug problems: Findings from a Rapid Evidence Assessment.

People who use alcohol and other drugs(hereafter "substances") and who are over the age of 40 are now more likely to die of a non-drug related cause than people who use substances under the age of 40. This population will therefore potentially need greater access to palliative and end of life care services. Initially, the purpose of this rapid evidence assessment (REA), conducted August 2016-August 2017, was to explore the peer-reviewed evidence base in relation to end of life care for people with problematic substance use. The following databases were searched using date parameters of 1 January 2004-1 August 2016: Amed, Psycharticles, Ovid, Ageinfo, Medline, Ebscohost, ASSIA, Social Care Online, Web of Knowledge, Web of Science, SSCI, Samsha, NIAAA. Data were extracted using a predefined protocol incorporating inclusion and exclusion criteria. Given the dearth of evidence emerging on interventions and practice responses to problematic substance use, the inclusion criteria were broadened to include any peer-reviewed literature focussing on substance use specifically and end of life care. There were 60 papers that met the inclusion criteria. These were quality assessed. Using a textual thematic approach to categorise findings, papers fell into three broad groups (a) pain management, (b) homeless and marginalised groups, and (c) alcohol-related papers. In general, this small and diverse literature lacked depth and quality. The papers suggest there are challenges for health and social care professionals in meeting the end of life needs of people who use substances. Addressing issues like safe prescribing for pain management becomes more challenging in the presence of substance use and requires flexible service provision from both alcohol/drug services and end of life care providers. Work is needed to develop models of good practice in working with co-existing substance use and end of life conditions as well as prevalence studies to provide a wider context for policy development.

Opioid-related deaths and previous care for drug use and pain relief in Sweden.

AIM: In 2006-2014, the rate of drug-related deaths, typically opioid poisonings, more than doubled in Sweden. Opioid prescriptions for pain control or opioid agonist therapy also increased. In this retrospective study, we compared death rates between individuals whose first recorded contact with prescribed opioids was for pain control and individuals that had received substance use disorder (SUD) treatment before their first recorded opioid prescription. METHODS: We included 2834 forensically examined individuals (ages 15-64 years) that died of poisoning in Sweden in 2006-2014. For each death we acquired data on previous opioid prescriptions and SUD treatments. We compared three study groups: pain control (n = 788); a SUD treatment group (n = 1629); and a group with no prescription for pain control or SUD treatment (n = 417). RESULTS: Overall fatal poisonings increased from 2.77 to 7.79 (per 100,000 individuals) from 2006 to 2014 (relative 181% increase). Fatal poisoning increased from 2006 to 2014 by 269% in the pain control group (0.64 to 2.36 per 100,000) and by 238% in the SUD treatment group (1.35 to 4.57 per 100,000). Heroin-related deaths remained constant; consequently, the increase was likely attributable to prescription opioids. CONCLUSION: A rapid increase in deaths attributable mainly to prescription opioids for pain control, was reported previously in the United States. Our study indicated that increased access to prescription opioids might contribute to higher death rates also in Sweden among patients seeking pain control and individuals with an established SUD; however, deaths related to prescription opioids mainly occurred among those with SUDs.

Pain and Lethality Induced by Insect Stings: An Exploratory and Correlational Study.

Pain is a natural bioassay for detecting and quantifying biological activities of venoms. The painfulness of stings delivered by ants, wasps, and bees can be easily measured in the field or lab using the stinging insect pain scale that rates the pain intensity from 1 to 4, with 1 being minor pain, and 4 being extreme, debilitating, excruciating pain. The painfulness of stings of 96 species of stinging insects and the lethalities of the venoms of 90 species was determined and utilized for pinpointing future directions for investigating venoms having pharmaceutically active principles that could benefit humanity. The findings suggest several under- or unexplored insect venoms worthy of future investigations, including: those that have exceedingly painful venoms, yet with extremely low lethality-tarantula hawk wasps (Pepsis) and velvet ants (Mutillidae); those that have extremely lethal venoms, yet induce very little pain-the ants, Daceton and Tetraponera; and those that have venomous stings and are both painful and lethal-the ants Pogonomyrmex, Paraponera, Myrmecia, Neoponera, and the social wasps Synoeca, Agelaia, and Brachygastra. Taken together, and separately, sting pain and venom lethality point to promising directions for mining of pharmaceutically active components derived from insect venoms.

Effect of Age on Opioid Prescribing, Overdose, and Mortality in Massachusetts, 2011 to 2015.

OBJECTIVES: To examine the effect of age on the likelihood of PIP of opioids and the effect of PIP on adverse outcomes. DESIGN: Retrospective cohort study. SETTING: Data from multiple state agencies in Massachusetts from 2011 to 2015. PARTICIPANTS: Adult Massachusetts residents (N=3,078,163) who received at least one prescription opioid during the study period; approximately half (1,589,365) aged 50 and older. MEASUREMENTS: We measured exposure to 5 types of PIP: high-dose opioids, coprescription with benzodiazepines, multiple opioid prescribers, multiple opioid pharmacies, and continuous opioid therapy without a pain diagnosis. We examined 3 adverse outcomes: nonfatal opioid overdose, fatal opioid overdose, and all-cause mortality. RESULTS: The rate of any PIP increased with age, from 2% of individuals age 18 to 29 to 14% of those aged 50 and older. Older adults also had higher rates of exposure to 2 or more different types of PIP (40-49, 2.5%; 50-69, 5%; ≥70, 4%). Of covariates assessed, older age was the greatest predictor of PIP. In analyses stratified according to age, any PIP and specific types of PIP were associated with nonfatal overdose, fatal overdose, and all-cause mortality in younger and older adults. CONCLUSION: Older adults are more likely to be exposed to PIP, which increases their risk of adverse events. Strategies to reduce exposure to PIP and to improve outcomes in those already exposed will be instrumental to addressing the opioid crisis in older adults. J Am Geriatr Soc 67:128-132, 2019.

Methadone: Maximizing Safety and Efficacy for Pain Control in Patients with Cancer.

Methadone is a valuable opioid in the management of patients who have cancer with pain. Methadone is a mu-, kappa-, and delta-opioid agonist, and an N-methyl-D-aspartate receptor antagonist. These mechanisms of action make methadone an attractive option for complex pain syndromes. It is critically important that providers consider a patient's risk status before beginning methadone. Careful consideration must be given to dosing methadone in both opioid-naïve and opioid-tolerant patients, with vigilant monitoring for therapeutic effectiveness and potential toxicity until the patient achieves steady state.

Pain and mortality: mechanisms for a relationship.

Moderate to severe chronic pain affects 1 in 5 adults and its impact increases with age. People with chronic pain that interferes with their lives have an increased risk of mortality. Identifying how interfering chronic pain can lead to mortality may highlight potential intervention strategies. This study uses a novel approach to test whether lifestyle, health, social, and psychological factors mediate the relationship between pain and mortality. Survival analyses (Cox's proportional hazard modelling and a technique to assess mediation within survival models) were conducted on a large population study of adults aged 50 years or older from the English Longitudinal Study of Ageing (n = 6324). Data collected at wave 2 (2004) were used as baseline and follow-up was until 2012. The relationship between being "often troubled with pain" and mortality was examined. Lifestyle, health, social, and psychological factors were tested as potential mediators. The strongest mediating factors for the relationship between troubling pain and mortality were functional limitation (hazard ratio 1.31; 95% confidence interval 1.20-1.39), symptoms preventing walking quarter of a mile (1.45 [1.35-1.58]), physical inactivity (1.14 [1.10-1.20]), and poor self-rated health (1.32 [1.23-1.41]). Mediators of the relationship between troubling pain and mortality provide targets for preventive health programmes. Interventions to improve general health, activity, and function could improve long-term survival in patients with this clinical problem.

Pain and Mortality in Older Adults: The Influence of Pain Phenotype.

OBJECTIVE: Moderate to severe chronic pain affects 1 in 5 adults. Pain may increase the risk of mortality, but the relationship is unclear. This study investigated whether mortality risk was influenced by pain phenotype, characterized by pain extent or pain impact on daily life. METHODS: The study population was drawn from 2 large population cohorts of adults ages ≥50 years, the English Longitudinal Study of Ageing (n = 6,324) and the North Staffordshire Osteoarthritis Project (n = 10,985). Survival analyses (Cox's proportional hazard models) estimated the risk of mortality in participants reporting any pain and then separately according to the extent of pain (total number of pain sites, widespread pain according to the American College of Rheumatology [ACR] criteria, and widespread pain according to Manchester criteria) and pain impact on daily life (pain interference and often troubled with pain). Models were cumulatively adjusted for age, sex, education, and wealth/adequacy of income. RESULTS: After adjustments, the report of any pain (mortality rate ratio [MRR] 1.06 [95% confidence interval (95% CI) 0.95-1.19]) or having widespread pain (ACR 1.07 [95% CI 0.92-1.23] or Manchester 1.16 [95% CI 0.99-1.36]) was not associated with an increased risk of mortality. Participants who were often troubled with pain (MRR 1.29 [95% CI 1.12-1.49]) and those who reported quite a bit of pain interference (MRR 1.38 [95% CI 1.20-1.59]) and extreme pain interference (MRR 1.88 [1.54-2.29]) had an increased risk of all-cause mortality. CONCLUSION: Pain that interferes with daily life, rather than pain per se, was associated with an increased risk of mortality. Future studies should investigate the mechanisms through which pain increases mortality risk.

Prognostic significance of non-chest pain symptoms in patients with non-ST-segment elevation myocardial infarction.

BACKGROUND/AIMS: Chest pain is an essential symptom in the diagnosis of acute coronary syndrome (ACS). One-third of patients with ACS present atypically, which can influence their receiving timely lifesaving therapy. METHODS: A total of 617 NSTEMI patients from the Korea Acute MI Registry (KAMIR) and the Korea Working Group on MI (KorMI) databases were analyzed. The study population was divided into two groups by symptoms at presentation (typical symptoms group, 128; atypical symptoms groups, 128). RESULTS: In this study population, 23% of patients presented without chest pain. After propensity score matching, the contact-to-device time (2,618 ± 381 minutes vs. 1,739 ± 241 minutes, p = 0.050), the symptoms-to-balloon time (3,426 ± 389 minutes vs. 2,366 ± 255 minutes, p = 0.024), and the door-to-balloon time (2,339 ± 380 minutes vs. 1,544 ± 244 minutes, p = 0.002) were significantly higher in the patients with atypical symptoms than in those with typical symptoms, respectively. Atypical symptoms were an independent predictor for 1-year mortality (hazard ratio, 2.820; 95% confidence interval, 1.058 to 7.515; p = 0.038). The Kaplan-Meier estimates showed higher risk for 12-month mortality in patients with atypical symptoms (p = 0.048) and no significant difference for 12-month major adverse cardiac events (p = 0.487). CONCLUSION: Acute myocardial infarction patients with atypical symptoms were not rare in clinical practice and showed a high risk of delayed reperfusion therapy. After imbalance between the groups was minimized by use of propensity score matching, patients who presented atypically had a high mortality rate.

Explaining recent mortality trends among younger and middle-aged White Americans.

Background: Recent research has suggested that increases in mortality among middle-aged US Whites are being driven by suicides and poisonings from alcohol and drug use. Increases in these 'despair' deaths have been argued to reflect a cohort-based epidemic of pain and distress among middle-aged US Whites. Methods: We examine trends in all-cause and cause-specific mortality rates among younger and middle-aged US White men and women between 1980 and 2014, using official US mortality data. We estimate trends in cause-specific mortality from suicides, alcohol-related deaths, drug-related deaths, 'metabolic diseases' (i.e. deaths from heart diseases, diabetes, obesity and/or hypertension), and residual deaths from extrinsic causes (i.e. causes external to the body). We examine variation in mortality trends by gender, age and cause of death, and decompose trends into period- and cohort-based variation. Results: Trends in middle-aged US White mortality vary considerably by cause and gender. The relative contribution to overall mortality rates from drug-related deaths has increased dramatically since the early 1990s, but the contributions from suicide and alcohol-related deaths have remained stable. Rising mortality from drug-related deaths exhibit strong period-based patterns. Declines in deaths from metabolic diseases have slowed for middle-aged White men and have stalled for middle-aged White women, and exhibit strong cohort-based patterns. Conclusions: We find little empirical support for the pain- and distress-based explanations for rising mortality in the US White population. Instead, recent mortality increases among younger and middle-aged US White men and women have likely been shaped by the US opiate epidemic and an expanding obesogenic environment.