All-cause mortality in patients with long-term opioid therapy compared with non-opioid analgesics for chronic non-cancer pain: a database study.

BACKGROUND: Hitherto only studies with selected populations have found an increased all-cause mortality of some selected opioids compared to selected non-opioids for chronic non-cancer pain (CNCP). We have examined the all-cause mortality for CNCP associated with all established opioids compared to non-opioid analgesic therapy (anticonvulsants, antidepressants, dipyrone, non-steroidal agents). METHODS: The study used the InGef (Institute for Applied Health Research Berlin) database which is an anonymized healthcare claims database including 4,711,668 insured persons who were covered by 61 German statutory health insurances between 2013 and 2017.The health insurance companies are the owners of the database. All-cause mortality was determined from death certificates. Adjusted hazard ratios (HRs) including age, gender, comorbidity index, and propensity score as covariates and risk differences (RD) in incidence of death between patients with long-term opioid therapy (LTOT) and control-drug therapy were calculated. RESULTS: The mean age of participants was 66 years; 55% were women. There were 554 deaths during 10,435 person-years for the LTOT patients, whereas there were 340 deaths during 11,342 person-years in the control group. The HR for all-cause mortality was 1.59 (95% CI, 1.38-1.82) with a risk difference of 148 excess deaths (95% CI 99-198) per 10,000 person-years. The elevated risk of death for LTOT was confined to the out-of-hospital deaths: LTOT patients had 288 out-of-hospital deaths during 10,435 person-years (276 per 10,000 person-years) whereas there were 110 deaths during 11,342 person-years (97 per 10,000 person-years) in the control group. HR was 2.29 (95% CI 1.86, 2.83). Although our propensity score matching model indicated a good classification, residual confounding cannot be fully excluded. The opioid group had a higher prevalence of heart failure and a higher use of anti-thrombotic and antiplatelet agents and of psycholeptics. CONCLUSIONS: LTOT for CNCP compared to non-opioid analgesics was associated with an increased risk for all-cause mortality. When considering treatment options for patients with CNCP, the relevant risk of increased all-cause mortality with opioids should be discussed. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03778450, Registered on 7 December 2018.

Mortality among immigrant patients 20-45 years of age with chronic back pain in primary care in Sweden: A 15-year follow-up cohort study.

BACKGROUND: Mortality rates among immigrant patients undergoing rehabilitation for musculoskeletal backache are unknown. OBJECTIVE: To study the association between marital status, severe psychosocial strain, receiving long-term time-limited sickness allowance (TLSA) and all-cause mortality (ACM) in a cohort of immigrants aged 20-45 years with long-standing backache in Sweden. METHODS: We studied 318 patients (92% foreign-born, 76% non-European) of known marital status on sick-leave for musculoskeletal backache. They were followed up for ACM until 2015. Socio-demographic data, TLSA and psychosocial strain, including major depression, severe psychosocial stressors and pessimistic thoughts, were analysed using multiple-imputation Cox regression. RESULTS: Over a mean (standard deviation) follow-up time of 15 (5.0) years, 11 (3.5%) participants died. At baseline, 34% were unmarried, 19% were receiving TLSA, and 71% had ⩾ 1 psychosocial strain component (38% depression; 47% severe stressors; 35% pessimistic thoughts). After concomitant risk factors were adjusted for, being unmarried and receiving TLSA were associated with higher mortality by factors of 6.2 (p= 0.005) and 5.8 (p= 0.006), respectively. Psychosocial strain was only significantly associated with higher mortality in the unadjusted analyses. CONCLUSIONS: Being unmarried and receiving TLSA were associated with significantly higher ACM in this highly marginalized group of immigrant patients.

Characteristics and circumstances of heroin and pharmaceutical opioid overdose deaths: Comparison across opioids.

BACKGROUND: Although much is known about the correlates of heroin overdose, less is known about pharmaceutical opioid (PO) overdose. This study aimed to examine correlates of opioid overdose deaths by opioid and compare correlates between opioids. METHODS: Analysis of opioid overdose deaths in Australia between 2000-2015, extracted from the National Coronial Information System (NCIS). The NCIS is an online database of deaths reportable to the coroner, and contains coroner's findings, autopsy and toxicology reports. Deaths were categorized into mutually exclusive groups: 1) Heroin deaths; and 2) PO deaths (excluding heroin). PO deaths were examined by individual opioid. RESULTS: There were 10,795 opioid overdose deaths over the study period. Relative to deaths occurring in major cities, deaths in regional/remote areas had 15.2 (95 % CI: 11.5-20.2) times the risk of being attributed to pharmaceutical fentanyl than heroin. Relative to deaths among people without a recorded history of chronic pain, deaths among people with a recorded history of chronic pain had a 1.9-10.7-fold increased risk of the death being attributed to POs than heroin. Deaths among people with a recorded history of substance use problems where the opioid was injected prior to death had 7.2 and 1.7 times the risk of being attributed to methadone and pharmaceutical fentanyl (respectively) than heroin. CONCLUSIONS: Findings suggest the need to: educate PO consumers about the risks of overdose at the time of prescribing; increase coverage and engagement in opioid dependence treatment (particularly in regional/remote areas); and increase uptake of take-home naloxone to reduce opioid overdose mortality.

Trends in chronic opioid use and association with five-year survival in South Korea: a population-based cohort study.

BACKGROUND: The Korean National Health Insurance Service (NHIS) was developed to provide population data for medical research. The aim of this study was to estimate trends in prescription opioid use in South Korea, and to determine the association between chronic opioid use and 5-yr mortality in cancer and non-cancer patients. METHODS: A population-based cohort study was conducted amongst the South Korean adult population using data from the NHIS. Those prescribed a continuous supply of opioids for ≥90 days were defined as chronic opioid users. Multivariable Cox regression analysis was used to assess the association between chronic opioid use and 5-yr mortality. RESULTS: The proportion of chronic weak opioid users increased from 1.03% in 2002 to 9.62% in 2015. The proportion of chronic strong opioid users increased from 0.04% in 2002 to 0.24% in 2015. In the 2010 cohort (n=822 214), compared with non-users, chronic weak opioid users had a significantly lower 5-yr mortality (hazard ratio [HR]: 0.93; 95% confidence interval [CI]: 0.89-0.96; P<0.001), and chronic strong opioid users had a significantly higher 5-yr mortality (HR: 1.45; 95% CI: 1.28-1.63; P<0.001). Similar results were observed in non-cancer patients, but chronic weak opioid users were not significantly associated with 5-yr mortality in cancer patients (P=0.063). CONCLUSIONS: In South Korea, chronic opioid use has increased since 2002. Chronic strong opioid use was associated with a higher 5-yr mortality, and chronic weak opioid use was associated with a slightly lower 5-yr mortality. However, the findings regarding chronic weak opioid users should be interpreted carefully because there might be residual confounders in this study. Further study is needed to confirm these retrospective findings.

Mortality After Discontinuation of Primary Care-Based Chronic Opioid Therapy for Pain: a Retrospective Cohort Study.

BACKGROUND: Despite known risks of using chronic opioid therapy (COT) for pain, the risks of discontinuation of COT are largely uncharacterized. OBJECTIVE: To evaluate mortality, prescription opioid use, and primary care utilization of patients discontinued from COT, compared with patients maintained on opioids. DESIGN: Retrospective cohort study of patients with chronic pain enrolled in an opioid registry as of May 2010. PARTICIPANTS: Patients with chronic pain enrolled in the opioid registry of a primary care clinic at an urban safety-net hospital in Seattle, WA. MAIN OUTCOMES AND MEASURES: Discontinuation from the opioid registry was the exposure of interest. Pre-specified main outcomes included mortality, prescription and primary care utilization data, and reasons for discontinuation. Data was collected through March 2015. KEY RESULTS: The study cohort comprised 572 patients with a mean age of 54.9 ± 10.1 years. COT was discontinued in 344 patients (60.1%); 254 (73.8%) discontinued patients subsequently filled at least one opioid prescription in Washington State, and 187 (54.4%) continued to visit the clinic. During the study period, 119 (20.8%) registry patients died, and 21 (3.7%) died of definite or possible overdose: 17 (4.9%) discontinued patients died of overdose, whereas 4 (1.75%) retained patients died of overdose. Most patients had at least one provider-initiated reason for COT discontinuation. Discontinuation of COT was associated with a hazard ratio for death of 1.35 (95% CI, 0.92 to 1.98, p = 0.122) and for overdose death of 2.94 (1.01-8.61, p = 0.049), after adjusting for age and race. CONCLUSIONS: In this cohort of patients prescribed COT for chronic pain, mortality was high. Discontinuation of COT did not reduce risk of death and was associated with increased risk of overdose death. Improved clinical strategies, including multimodal pain management and treatment of opioid use disorder, may be needed for this high-risk group.

The silent epidemic of chronic pain in older adults.

Chronic pain is highly prevalent among older adults where it is associated with significant suffering, disability, social isolation, and greater costs and burden to health care systems. Pharmaceutical treatment of chronic pain in older adults is usually only partially effective and is often limited by side effects including urinary retention, constipation, sedation, cognitive impairment, and increased risk of falls. Since older adults are underrepresented in clinical trials testing treatments for chronic pain, the potential impacts of polypharmacy and frailty on reported outcomes and side effect profiles are largely unknown. Thus, for current treatments, providers and patients must balance anticipated benefits of pain reduction with the known and unknown risks of treatment. Chronic pain is also a risk factor for premature death as well as accelerated cognitive decline, suggesting potential shared mechanisms between persistent pain (or its treatment) and dementia. Cognitive decline and dementia may also impact pain perception and the ability to report pain, complicating treatment decisions. Associations between persistent pain and the risks of premature death and accelerated cognitive decline make estimates for chronic pain in these populations particularly challenging. Future research is needed to improve estimates for chronic pain in older adults, to elucidate underlying mechanisms of pain with aging, and to develop and advance safer, more effective treatment options for chronic pain in older adults.

Widespread pain is a risk factor for cardiovascular mortality: results from the Framingham Heart Study.

AIMS: With the introduction of widespread pain (WSP) as a separate diagnostic code in the ICD-11, WSP has now become an own clinical diagnosis independent of the underlying pathophysiology. Research has reported aetiological associations of WSP and cardiovascular diseases. However, studies on mortality risk in individuals with WSP have reported inconsistent results. This study investigates whether there is increased mortality in WSP individuals and establish potential determinants of mortality risk. Therefore, we evaluates the population-based prospective cohort of the Framingham Heart Study (FHS). METHODS AND RESULTS: The FHS is a longitudinal multi-generational study. Pain status was assessed uniquely between 1990 and 1994. Cox proportional hazards modelling was used to estimate hazard ratios (HRs) of WSP on all-cause mortality controlling for sex and age, cardiovascular risk factors, cancer history, lifestyle factors and current medication. WSP examination was carried out in 4746 participants of the FHS (60.3 ± 13.5 years, 55.1% women). A total of 678 (14.5%) subjects fulfilled the criteria for WSP, whereas 4011 (85.5%) subjects did not. The follow-up time was 15 years, during which 202 persons died in the WSP group and 1144 in the no-WSP group. When adjusting for age and sex, all-cause mortality was increased by about 16% in WSP subjects. Individuals with WSP had an increased HR particularly for cardiovascular cause of death (HR adjusted by age and sex = 1.46, 95% confidence interval 1.10-1.94). CONCLUSION: Our data show that in a large population-based cohort, WSP is associated with increased HR for cardiovascular cause of death, underlining the need for pain assessments in cardiovascular practice.

Chronic pain is underestimated and undertreated in dialysis patients: A retrospective case study.

Significant chronic pain is highly prevalent in chronic kidney disease patients and is associated with morbidity and mortality. In this study, we retrospectively evaluated the incidence and treatment of pain in the dialysis unit of our tertiary referral center. The cohort included 147 patients. Over 66% reported significant (VAS >40) chronic pain during the preceding 3 months, most often characterized as stabbing (38%) and with concurrent itching (44%). Only 33% of patients received chronic pain medications, while 55.6% of patients with severe pain and 45.9% with pain characterized as the worst imaginable did not receive any analgesics. Pregabalin or weak opioids were the most frequently used. In conclusion, chronic pain is highly prevalent and markedly undertreated in dialysis patients, despite its significant adverse impact.

Cause-specific mortality of patients with severe chronic pain referred to a multidisciplinary pain clinic: a cohort register-linkage study.

Background and aims Almost 20% of the adult population suffers from chronic pain. Chronic pain may be linked to an elevated mortality; however, results from previous studies are inconsistent. Some studies find similar mortality levels in chronic pain patients and pain-free controls while other studies show elevated mortality levels among chronic pain patients, primarily with respect to cancer, diseases of the circulatory and respiratory systems, and suicide. These conflicting results are potentially due to different population samples and different operational definitions of chronic pain. Further research on overall and cause-specific mortality in patients with severe chronic pain is needed to inform clinical practice. The objective of this register-linkage study was to investigate whether patients with severe chronic pain referred to multidisciplinary pain treatment have higher cause-specific mortality rates than the general population. Methods In this register-linkage cohort study, data from 6,142 chronic pain patients (female: n=3,941, male: n=2,201, mean age: 48.2±14.2; range: 16-97 years) attending an interdisciplinary Pain Center in Odense, Denmark from 2005 to 2014 were linked to the Danish Register of Causes of Death. Age and gender standardized mortality ratios (SMRs) with their 95% confidence intervals (CI) were calculated and compared with those of the general population. Data from the general population was extracted from the Danish Register of Causes of Death, and Causes of death were classified according to national Classification of Disease (ICD-10). Results In all, 276 deaths (women: n=152, men: n=124) were observed among the chronic pain patients, and a six-fold higher overall mortality rate was found [SMR: 6.2 (95% CI: 5.5-7.0)] compared with the general population. Elevated cause-specific mortality rates were noted for chronic patients with respect to cancer and neoplasms [4.7 (95% CI: 3.7-5.9)], diseases of the circulatory system [5.7 (95% CI: 4.3-7.3)], diseases of the respiratory system [8.7 (95% CI: 6.2-11.9)], and suicide [7.3 (95% CI: 2.7-15.9)]. Conclusions The overall mortality rate of patients with severe chronic pain in this study was six-fold higher than the rate of the general population in this region. This was reflected in select specific causes of death (cancer and neoplasms, diseases of the circulatory system, diseases of the respiratory system, and suicide). The results are in agreement with previous studies and emphasize the need to understand which factors causally affect this increased mortality allowing for targeted interventions in similar chronic pain populations. Implications Potential reasons for the excess mortality should be adequately addressed by future studies in order to better target this in the management of these patients. The chronic pain population included in this study may have several comorbidities contributing to the increased mortality. To better address these aspects, complete medical profiles are needed in future studies. In addition, implementation of management strategies towards potential risk factors such as poor diet, low levels of physical activity, smoking, and high BMI as well as sleep deprivation and morphine use previously shown associated with having pain may reduce the excess mortality ratio.

Opioid Prescription, Morbidity, and Mortality in US Transplant Recipients.

BACKGROUND: Centers for Disease Control and Prevention guidelines recommend caution in prescribing opioids for chronic pain. The characteristics of opioid prescription (OpRx) among kidney transplant (KTx) recipients have not been described in a national population. METHODS: We assessed OpRx prevalence among prevalent KTx recipients, and associated duration (long-term, defined as ≥90 days in a year) and dosing (in morphine milligram equivalents per day of <50, 50-89, and ≥90) with outcomes, death and graft loss, among incident KTx recipients using 2006-2010 US Renal Data System files, including Medicare Part D for medication ascertainment. Cox models controlled for recipient factors. RESULTS: Of 36,486 KTx recipients in the 2010 prevalent cohort, approximately 14.6% had long-term OpRx. The strongest association with long-term OpRx after KTx was long-term OpRx before KTx (64%; adjusted odds ratio, 95% confidence interval, 95.2, 74.2-122.1). Incident KTx recipients with long-term OpRx had increased risk of mortality and graft loss compared with those without OpRx or short-term OpRx after KTx. This risk was highest among recipients with long-term OpRx doses of ≥90 morphine milligram equivalents or higher per day (adjusted hazard ratio, 95% confidence interval, 1.61, 1.24-2.10 for death, and 1.33, 1.05-1.67 for graft loss, respectively). CONCLUSIONS: In contrast to either no or short-term OpRx, long-term, and especially long-term high-dose OpRx, is associated with increased risk of death and graft loss in US KTx recipients. Causal relationships cannot be inferred, and OpRx may be an illness marker. Nevertheless, efforts to treat pain effectively in KTx recipients with less toxic interventions and decrease OpRx deserve consideration.

Pattern and severity of multimorbidity among patients attending primary care settings in Odisha, India.

Multimorbidity is increasingly the primary concern of healthcare systems globally with substantial implications for patient outcomes and resource cost. A critical knowledge gap exists as to the magnitude of multimorbidity in primary care practice in low and middle income countries with available information limited to prevalence. In India, primary care forms the bulk of the health care delivery being provided through both public (community health center) and private general practice setting. We undertook a study to identify multimorbidity patterns and relate these patterns to severity among primary care attendees in Odisha state of India. A total of 1649 patients attending 40 primary care facilities were interviewed using a structured multimorbidity assessment questionnaire. Multimorbidity patterns (dyad and triad) were identified for 21 chronic conditions, functional limitation was assessed as a proxy measure of severity and the mean severity score for each pattern, was determined after adjusting for age. The leading dyads in younger age group i.e. 18-29 years were acid peptic disease with arthritis/ chronic back ache/tuberculosis /chronic lung disease, while older age groups had more frequent combinations of hypertension + arthritis/ chronic lung disease/vision difficulty, and arthritis + chronic back ache. The triad of acid peptic disease + arthritis + chronic backache was common in men in all age groups. Tuberculosis and lung diseases were associated with significantly higher age-adjusted mean severity score (poorer functional ability). Among men, arthritis, chronic backache, chronic lung disease and vision impairment were observed to have highest severity) whereas women reported higher severity for combinations of hypertension, chronic back ache and arthritis. Given the paucity of studies on multimorbidity patterns in low and middle income countries, future studies should seek to assess the reproducibility of our findings in other populations and settings. Another task is the potential implications of different multimorbidity clusters for designing care protocols, as currently the protocols are disease specific, hardly taking comorbidity into account.

Persons with chronic widespread pain experience excess mortality: longitudinal results from UK Biobank and meta-analysis.

OBJECTIVE: It is uncertain whether persons with chronic widespread pain (CWP) experience premature mortality. Using the largest study conducted, we determine whether such a relationship exists, estimate its magnitude and establish what factors mediate any relationship. METHODS: UK Biobank, a cohort study of 0.5 million people aged 40-69 years, recruited throughout Great Britain in 2006-2010. Participants reporting 'pain all over the body' for >3 months were compared with persons without chronic pain. Information on death (with cause) was available until mid-2015. We incorporated these results in a meta-analysis with other published reports to calculate a pooled estimate of excess risk. RESULTS: 7130 participants reported CWP and they experienced excess mortality (mortality risk ratio 2.43, 95%CI 2.17 to 2.72). Specific causes of death in excess were cancer (1.73adjusted age and sex, 95% CI 1.46 to 2.05), cardiovascular (3.24adjusted age and sex, 95% CI 2.55 to 4.11), respiratory (5.66adjusted age and sex, 95% CI 4.00 to 8.03) and other disease-related causes (4.04adjusted age and sex, 95% CI 3.05 to 5.34). Excess risk was substantially reduced after adjustment for low levels of physical activity, high body mass index, poor quality diet and smoking. In meta-analysis, all studies showed significant excess all-cause (combined estimate 1.59 (95% CI 1.05 to 2.42)), cardiovascular and cancer mortality. CONCLUSIONS: Evidence is now clear that persons with CWP experience excess mortality. UK Biobank results considerably reduce uncertainty around the magnitude of excess risk and are consistent with the excess being explained by adverse lifestyle factors, which could be targeted in the management of such patients.

Physical activity and exercise for chronic pain in adults: an overview of Cochrane Reviews.

BACKGROUND: Chronic pain is defined as pain lasting beyond normal tissue healing time, generally taken to be 12 weeks. It contributes to disability, anxiety, depression, sleep disturbances, poor quality of life, and healthcare costs. Chronic pain has a weighted mean prevalence in adults of 20%.For many years, the treatment choice for chronic pain included recommendations for rest and inactivity. However, exercise may have specific benefits in reducing the severity of chronic pain, as well as more general benefits associated with improved overall physical and mental health, and physical functioning.Physical activity and exercise programmes are increasingly being promoted and offered in various healthcare systems, and for a variety of chronic pain conditions. It is therefore important at this stage to establish the efficacy and safety of these programmes, and furthermore to address the critical factors that determine their success or failure. OBJECTIVES: To provide an overview of Cochrane Reviews of adults with chronic pain to determine (1) the effectiveness of different physical activity and exercise interventions in reducing pain severity and its impact on function, quality of life, and healthcare use; and (2) the evidence for any adverse effects or harm associated with physical activity and exercise interventions. METHODS: We searched theCochrane Database of Systematic Reviews (CDSR) on the Cochrane Library (CDSR 2016, Issue 1) for systematic reviews of randomised controlled trials (RCTs), after which we tracked any included reviews for updates, and tracked protocols in case of full review publication until an arbitrary cut-off date of 21 March 2016 (CDSR 2016, Issue 3). We assessed the methodological quality of the reviews using the AMSTAR tool, and also planned to analyse data for each painful condition based on quality of the evidence.We extracted data for (1) self-reported pain severity, (2) physical function (objectively or subjectively measured), (3) psychological function, (4) quality of life, (5) adherence to the prescribed intervention, (6) healthcare use/attendance, (7) adverse events, and (8) death.Due to the limited data available, we were unable to directly compare and analyse interventions, and have instead reported the evidence qualitatively. MAIN RESULTS: We included 21 reviews with 381 included studies and 37,143 participants. Of these, 264 studies (19,642 participants) examined exercise versus no exercise/minimal intervention in adults with chronic pain and were used in the qualitative analysis.Pain conditions included rheumatoid arthritis, osteoarthritis, fibromyalgia, low back pain, intermittent claudication, dysmenorrhoea, mechanical neck disorder, spinal cord injury, postpolio syndrome, and patellofemoral pain. None of the reviews assessed 'chronic pain' or 'chronic widespread pain' as a general term or specific condition. Interventions included aerobic, strength, flexibility, range of motion, and core or balance training programmes, as well as yoga, Pilates, and tai chi.Reviews were well performed and reported (based on AMSTAR), and included studies had acceptable risk of bias (with inadequate reporting of attrition and reporting biases). However the quality of evidence was low due to participant numbers (most included studies had fewer than 50 participants in total), length of intervention and follow-up (rarely assessed beyond three to six months). We pooled the results from relevant reviews where appropriate, though results should be interpreted with caution due to the low quality evidence. Pain severity: several reviews noted favourable results from exercise: only three reviews that reported pain severity found no statistically significant changes in usual or mean pain from any intervention. However, results were inconsistent across interventions and follow-up, as exercise did not consistently bring about a change (positive or negative) in self-reported pain scores at any single point. Physical function: was the most commonly reported outcome measure. Physical function was significantly improved as a result of the intervention in 14 reviews, though even these statistically significant results had only small-to-moderate effect sizes (only one review reported large effect sizes). Psychological function and quality of life: had variable results: results were either favourable to exercise (generally small and moderate effect size, with two reviews reporting significant, large effect sizes for quality of life), or showed no difference between groups. There were no negative effects. Adherence to the prescribed intervention: could not be assessed in any review. However, risk of withdrawal/dropout was slightly higher in the exercising group (82.8/1000 participants versus 81/1000 participants), though the group difference was non-significant. Healthcare use/attendance: was not reported in any review. Adverse events, potential harm, and death: only 25% of included studies (across 18 reviews) actively reported adverse events. Based on the available evidence, most adverse events were increased soreness or muscle pain, which reportedly subsided after a few weeks of the intervention. Only one review reported death separately to other adverse events: the intervention was protective against death (based on the available evidence), though did not reach statistical significance. AUTHORS' CONCLUSIONS: The quality of the evidence examining physical activity and exercise for chronic pain is low. This is largely due to small sample sizes and potentially underpowered studies. A number of studies had adequately long interventions, but planned follow-up was limited to less than one year in all but six reviews.There were some favourable effects in reduction in pain severity and improved physical function, though these were mostly of small-to-moderate effect, and were not consistent across the reviews. There were variable effects for psychological function and quality of life.The available evidence suggests physical activity and exercise is an intervention with few adverse events that may improve pain severity and physical function, and consequent quality of life. However, further research is required and should focus on increasing participant numbers, including participants with a broader spectrum of pain severity, and lengthening both the intervention itself, and the follow-up period.

Prescripción de opioides de acción prolongada y mortalidad en pacientes con dolor crónico no oncológico / Prescribing long-acting opioids and mortality in patients with chronic noncancer pain

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The Mortality Associated With Chronic Widespread Musculoskeletal Complaints: A Systematic Review of the Literature.

BACKGROUND: Chronic widespread musculoskeletal complaints (CWMSC) are a prevalent condition with a large impact on quality of life and with a large burden on society. Studies investigating the relationship between CWMSC and mortality have yielded inconsistent results. The present study aimed to clarify this relationship through a systematic review of the existing literature, including meta-analyses, to estimate pooled results and heterogeneity. METHODS: The MEDLINE, EMBASE and Science Citation Index Expanded databases were searched in February 2016. Broad search terms were used to identify as many observational studies as possible that investigated the association between CWMSC and mortality. The identified studies were evaluated according to predetermined inclusion criteria. RESULTS: Six studies fulfilled the inclusion criteria. In pooled unadjusted analyses of three studies evaluating CWMSC, a non-significant tendency of increased overall mortality was found [mortality risk ratio (MRR) 1.69, 95% confidence interval (CI) 0.91-3.14]. However, in pooled analyses of all six studies reporting adjusted results, the non-significant tendency for higher mortality rates in those with CWMSC was nearly eliminated (MRR 1.13, 95% CI 0.95-1.34). Heterogeneity between studies was moderate to high, particularly regarding the use of confounding factors. CONCLUSIONS: In this systematic review, based on a limited number of studies, pooled data gave no evidence of a higher mortality rate among individuals with CWMSC. The non-significant tendency for a higher mortality rate in unadjusted pooled analyses was nearly eliminated in the adjusted pooled analyses, considering lifestyle factors such as physical activity smoking. In population-based studies evaluating the relationship between CWMSC and mortality rates, we recommend that both unadjusted and adjusted analyses should be presented. Copyright © 2016 John Wiley & Sons, Ltd.

Spinal Cord Stimulation (SCS)-The Implantable Systems Performance Registry (ISPR).

OBJECTIVES: The Implantable Systems Performance Registry (ISPR) was created to monitor the product performance of Medtronic Spinal Cord Stimulation (SCS) and implanted intrathecal drug infusion systems available in the United States. MATERIALS AND METHODS: Data were collected on 2605 patients from 44 centers from various geographic regions across the United States implanting and following patients with SCS systems between June 25, 2004 and January 31, 2014. Actuarial life table methods are used to estimate device performance over time. Of the 2605 patients, 1490 (57.2%) were female, 1098 (42.1%) were male and 17 (0.7%) did not provide gender data. The average age at enrollment was 56.3 years (range: 4-97, SD = 14.3) and average follow-up time was 20.1 months (SD = 22.5). RESULTS: Currently the estimates of device survival from neurostimulator-related events exceed 97% for all neurostimulator models across the applicable follow-up time points and all applicable extension models had greater than 95% survival from extension events. The majority of product performance events were lead-related. At 5 years of follow-up, all applicable lead families, with the exception of the Pisces-Quad LZ family, had greater than 75% survival from lead events. CONCLUSIONS: The ISPR is designed to serve as an ongoing source of system and device-related information with a focus on "real-world" safety and product performance. ISPR data continue to be used to guide future product development efforts aimed at improving product reliability and quality.

Prescription of Long-Acting Opioids and Mortality in Patients With Chronic Noncancer Pain.

IMPORTANCE: Long-acting opioids increase the risk of unintentional overdose deaths but also may increase mortality from cardiorespiratory and other causes. OBJECTIVE: To compare all-cause mortality for patients with chronic noncancer pain who were prescribed either long-acting opioids or alternative medications for moderate to severe chronic pain. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study between 1999 and 2012 of Tennessee Medicaid patients with chronic noncancer pain and no evidence of palliative or end-of-life care. EXPOSURES: Propensity score-matched new episodes of prescribed therapy for long-acting opioids or either analgesic anticonvulsants or low-dose cyclic antidepressants (control medications). MAIN OUTCOMES AND MEASURES: Total and cause-specific mortality as determined from death certificates. Adjusted hazard ratios (HRs) and risk differences (difference in incidence of death) were calculated for long-acting opioid therapy vs control medication. RESULTS: There were 22,912 new episodes of prescribed therapy for both long-acting opioids and control medications (mean [SD] age, 48 [11] years; 60% women). The long-acting opioid group was followed up for a mean 176 days and had 185 deaths and the control treatment group was followed up for a mean 128 days and had 87 deaths. The HR for total mortality was 1.64 (95% CI, 1.26-2.12) with a risk difference of 68.5 excess deaths (95% CI, 28.2-120.7) per 10,000 person-years. Increased risk was due to out-of-hospital deaths (154 long-acting opioid, 60 control deaths; HR, 1.90; 95% CI, 1.40-2.58; risk difference, 67.1; 95% CI, 30.1-117.3) excess deaths per 10,000 person-years. For out-of-hospital deaths other than unintentional overdose (120 long-acting opioid, 53 control deaths), the HR was 1.72 (95% CI, 1.24-2.39) with a risk difference of 47.4 excess deaths (95% CI, 15.7-91.4) per 10,000 person-years. The HR for cardiovascular deaths (79 long-acting opioid, 36 control deaths) was 1.65 (95% CI, 1.10-2.46) with a risk difference of 28.9 excess deaths (95% CI, 4.6-65.3) per 10,000 person-years. The HR during the first 30 days of therapy (53 long-acting opioid, 13 control deaths) was 4.16 (95% CI, 2.27-7.63) with a risk difference of 200 excess deaths (95% CI, 80-420) per 10,000 person-years. CONCLUSIONS AND RELEVANCE: Prescription of long-acting opioids for chronic noncancer pain, compared with anticonvulsants or cyclic antidepressants, was associated with a significantly increased risk of all-cause mortality, including deaths from causes other than overdose, with a modest absolute risk difference. These findings should be considered when evaluating harms and benefits of treatment.