Increased cancer incidence and mortality among people with opioid use-related disorders: A nation-wide cohort study.

BACKGROUND AND AIMS: Studies on cancer incidence and mortality among people with opioid use-related disorders are lacking. We aimed to measure cancer-specific incidence, mortality and survival among people diagnosed with opioid use-related disorders in Norway during 2010-18. DESIGN AND SETTING: This was a cohort study conducted in Norway during 2010-18. PARTICIPANTS: Individuals (n = 20 710) diagnosed with opioid use-related disorders. MEASUREMENTS: We conducted a cohort study utilizing a data-linkage of national health and population registers. Information on opioid use-related disorders was extracted from specialized healthcare, malignancies from the Cancer Registry of Norway and deaths from Cause of Death Registry. Cancer incidence and mortality were compared with the general population by calculating sex-specific age-standardized incidence (SIR) and mortality (SMR) ratios. One-year survival rates were computed. FINDINGS: Compared with the general population, people with opioid use-related disorders were at an increased risk of developing cancer overall [SIR = 1.2, 95% confidence interval (CI) = 1.1-1.3] with a higher than twofold cancer mortality rate (SMR = 2.3, 95% CI = 2.0-2.7). Excess risk was observed for liver (12.6, 95% CI = 9.1-17.0), larynx (4.7, 95% CI = 1.7-10.2), lung (3.5, 95% CI = 2.8-4.3) and pancreas cancer (2.6, 95% CI = 1.6-4.0), whereas reduced risk was found for melanoma (0.5, 95% CI = 0.3-0.9), breast (0.6, 95% CI = 0.4-0.9) and prostate cancers (0.3, 95% CI = 0.1-0.4). Site-specific SMRs were significantly elevated for liver (12.3, 95% CI = 8.5-17.2), lung (3.9, 95% CI = 3.0-5.0), pancreas (3.0, 95% CI = 1.7-4.8) and colon cancers (1.9, 95% CI = 1.1-3.1). The average 1-year survival rate after a cancer diagnosis was low in liver, pancreas and colon cancer, ranging from 10 to 15% less than that of the general population. CONCLUSIONS: In Norway, cancer incidence and cancer-related mortality appear to be elevated among individuals with opioid use-related disorders.

Psykiske lidelser og plager ved vedvarende opioidbruk for langvarige ikke-kreftrelaterte smerter ­ en registerstudie.

Background: Knowledge of mental disorders among patients with persistent opioid use for the treatment of chronic non-cancer pain is essential, as mental disorders and symptoms can exacerbate or perpetuate pain and impact on the ability of patients to manage their illness. We have studied the prevalence of mental disorders and symptoms, including substance use disorders, in patients with persistent opioid use in 2019. Material and method: Persons ≥ 18 years with persistent opioid use and persons ≥ 18 years with at least one registered mental disorder in the specialist healthcare service in 2019 were included. Data were retrieved from national health registries in Norway. Patients who received opioids reimbursed for the treatment of chronic pain were compared with those who received opioids without reimbursement. Results: The prevalence of mental disorders and symptoms was 34 % among 14 403 persons who received reimbursed opioids, and 42 % among 38 001 persons who received opioids without reimbursement. This is equivalent to a two to threefold increase in prevalence compared to the general population. There was a particularly higher prevalence of anxiety disorders and substance use disorders. The prevalence of mental disorders and symptoms was highest in the age group 18-44 years (49-55 %). Interpretation: Among patients with persistent opioid use, a large proportion had mental disorders and symptoms, which are known risk factors for developing problematic opioid use and opioid use disorder.

Cohort Description: Preventing an Opioid Epidemic in Norway - Focusing on Treatment of Chronic Pain (POINT) - A National Registry-Based Study.

Aim: The POINT project aims to provide evidence to optimise chronic pain management, prevent adverse consequences of opioids, and improve chronic pain patients' pain relief, functional capacity, and quality of life. We describe the outline of the project and its work packages. More specifically, we describe a cohort of persons with chronic pain and a cohort of long-term opioid users identified from a national registry linkage. Data Sources: The project utilises data from nationwide healthcare and population registers in Norway. Using the Norwegian Prescription Database, we identified a cohort of persons who have been dispensed drugs reimbursed for chronic pain and a cohort of persons who used opioids long term from 2010 to 2019. Data from the Norwegian Registry for Primary Health Care and the Norwegian Patient Registry (2008-2019), Cancer Registry (1990-2018) Cause of Death Registry (2010-2019) and demographic and socioeconomic registers from Statistics Norway (2010-2019) were linked to the cohorts. Study Population: There were 568,869 participants with chronic pain. Sixty-three percent of the cohort was women, and the mean age was 57.1 years. There were 336,712 long-term opioid users (58.6% women; 60.9 years). In chronic pain and long-term opioid user cohorts, the most frequent musculoskeletal diagnosis was back pain diagnosed in primary care (27.6% and 30.7%). Psychiatric diagnoses were also common. Main Variables: Upcoming studies will utilise psychiatric and somatic diagnoses from the patient registers, drug use from the prescription register, causes of death, demographics, and socioeconomic status (eg, education, income, workability, immigrant status) as exposures or outcomes. Conclusion and Future Plans: The two cohorts have numerous pain-related diagnoses, especially in the musculoskeletal system, and noticeably frequent somatic and psychiatric morbidity. The POINT project also includes later work packages that explore prescriber and patient perspectives around safe and effective treatment of chronic pain.

Individuals Dying of Overdoses Related to Pharmaceutical Opioids Differ from Individuals Dying of Overdoses Related to Other Substances: A Population-Based Register Study.

BACKGROUND: Pharmaceutical opioid (PO) overdose deaths have increased in many Western countries. There are indications that those dying from a PO overdose differ from those dying from other types of overdoses. These differences might pose a challenge as the majority of current preventive measures are tailored toward those with the characteristics of "conventional" overdose deaths. OBJECTIVE: We investigated differences in the characteristics of persons who died from PO overdoses compared to all other overdoses. MATERIAL AND METHODS: Using the Norwegian Cause of Death Registry, we retrieved information on overdoses classified according to ICD-10 and identified PO overdoses (T40.2; T40.4) and all other overdoses (T40.X; T43.6) in 2010-2019. By linking data from nationwide registers, we analyzed data on opioid dispensations and the history of mental and behavioral disorders. 1,224 persons were registered with PO overdoses and 1,432 persons with other overdoses. RESULTS: Persons in the PO overdose group were older and were more frequently women (35.0% vs. 20.5%) than persons with other overdoses. They had a higher prevalence of chronic pain (35.8% vs. 13.2%), history of cancer (8.1% vs. 1.8%), filled prescriptions of analgetic opioids more frequently the month before death (38.8% vs. 12.0%), and used threefold higher doses of prescribed opioids compared to individuals in all other overdose group (66 vs. 26 oral morphine equivalents/day). In the PO overdose group, oxycodone and fentanyl were more frequently dispensed, while codeine was more frequently dispensed in the other overdose groups. A lower proportion of those in the PO overdose group had recorded diagnoses of substance use disorders, schizophrenia, and hyperkinetic disorder compared to the other overdose groups. CONCLUSION: Persons dying from overdoses on POs often differ from the population targeted by existing prevention strategies, as they are more frequently older women with chronic pain and using high doses of prescription opioids.

Filled prescriptions for opioids among children and adolescents - A nationwide study from 2010 to 2018.

BACKGROUND: Prescribing opioids for children and adolescents should be reserved for advanced life-limiting diseases and moderate-to-severe acute pain. Pediatric codeine use is discouraged by several authorities, but the effects of these recommendations are not fully known. We investigated opioid utilization trends among 0-18-year-olds and characterized those who filled ≥1 opioid prescriptions, with emphasis on those who did so >3 times within a year. METHODS: The prevalence of filled opioid prescriptions among 0-18-year-old Norwegians in 2010-2018 (N = 77,942) was measured from nationwide healthcare registries. Characteristics, healthcare utilization, and other drug use of those who newly filled 1, 2-3, or >3 opioid prescriptions in 2011-2014 were compared to 2015-2018, excluding persons with cancer. RESULTS: From 2010 to 2018, the prevalence of opioid use decreased from 9.0 to 7.0 per 1000 persons. The largest decrease was among children <12 years, from 4.1 to 0.4 per 1000 persons, mainly due to decreasing codeine use. The proportion of those who filled >3 opioid prescriptions was 2.1% in 2011-2014 and 3.1% in 2015-2018. Those with >3 dispensations had a median of 4 contacts/year with secondary healthcare (interquartile range 2-7); the most frequent diagnoses indicated post-surgery follow-up. Most commonly dispensed other drugs were non-steroidal anti-inflammatory drugs. CONCLUSIONS: Opioid dispensations for the young have declined in recent years. Multiple opioid dispensations were rare and associated with frequent healthcare utilization. Reducing codeine is in line with recommendations, but the effects of decreased opioid use on the quality of pain management remain unknown.

Medication Management in Frail Older People: Consensus Principles for Clinical Practice, Research, and Education.

Frailty is a geriatric condition associated with increased vulnerability to adverse drug events and medication-related harm. Existing clinical practice guidelines rarely provide medication management recommendations specific to frail older people. This report presents international consensus principles, generated by the Optimizing Geriatric Pharmacotherapy through Pharmacoepidemiology Network, related to medication management in frail older people. This consensus comprises 7 principles for clinical practice, 6 principles for research, and 4 principles for education. Principles for clinical practice include (1) perform medication reconciliation and maintain an up-to-date medication list; (2) assess and plan based on individual's capacity to self-manage medications; (3) ensure appropriate prescribing and deprescribing; (4) simplify medication regimens when appropriate to reduce unnecessary burden; (5) be alert to the contribution of medications to geriatric syndromes; (6) regularly review medication regimens to align with changing goals of care; and (7) facilitate multidisciplinary communication among patients, caregivers, and healthcare teams. Principles for research include (1) include frail older people in randomized controlled trials; (2) consider frailty status as an effect modifier; (3) ensure collection and reporting of outcome measures important in frailty; (4) assess impact of frailty on pharmacokinetics and pharmacodynamics; (5) encourage frailty research in under-researched settings; and (6) utilize routinely collected linked health data. Principles for education include (1) provide undergraduate and postgraduate education on frailty; (2) minimize low-value care related to medication management; (3) improve health and medication literacy; and (4) incorporate evidence in relation to frailty into clinical practice guidelines. These principles for clinical practice, research and education highlight different considerations for optimizing medication management in frail older people. These principles can be used in conjunction with existing best practice guidelines to help achieve optimal health outcomes for this vulnerable population. Implementation of the principles will require multidisciplinary collaboration between healthcare professionals, researchers, educators, organizational leaders, and policymakers.

Hospital-Treated Pneumonia Associated with Opioid Use Among Community Dwellers with Alzheimer's Disease.

BACKGROUND: Pneumonia is a common cause for hospitalization and excess mortality among persons with Alzheimer's disease (AD), but little research exists evaluating drug use as its risk factor. OBJECTIVE: We investigated the association between opioid use and hospital-treated pneumonia among community dwellers with AD. METHODS: This study was part of the Medication use and Alzheimer's Disease (MEDALZ) cohort. We included all community dwellers newly diagnosed with AD during 2010-2011 in Finland with incident prescription opioid use (n = 5,623) and age-, sex-, and time since AD diagnosis-matched nonusers (n = 5,623). Opioid use data, modelled from pharmacy dispensing data, and hospital-treated pneumonia were retrieved from nationwide registers. Patients with active cancer treatment were excluded. Hazard models compared opioid users to nonusers, adjusting for comorbidities, socioeconomic position. and other drug use. RESULTS: Incident opioid use was associated with an increased risk of hospital-treated pneumonia compared to nonuse (adjusted HR, aHR 1.34, 95% CI 1.14-1.57). Highest risk was observed during the first two months of use (aHR 2.58, 95% CI 1.87-3.55). Compared to weak opioids, buprenorphine was not associated with a higher risk of pneumonia (aHR 1.20, 95% CI 0.83-1.76), but strong opioids were (aHR 1.84, 95% CI 1.15-2.97). The risk was higher for those using ≥50 morphine milligram equivalents (MME)/day (aHR 2.03, 95% CI 1.24-3.31), compared to using <50 MME/day. CONCLUSIONS: Opioid use was associated with a risk of hospital-treated pneumonia in a dose-dependent manner among persons with AD. Risk-minimization strategies should be considered if opioid therapy is needed.

Long-term use of opioids for nonmalignant pain among community-dwelling persons with and without Alzheimer disease in Finland: a nationwide register-based study.

Persons with Alzheimer disease (AD) commonly present with chronic nonmalignant pain, but long-term use of opioids among this population has not been studied previously. Our aim was to investigate the prevalence of long-term (≥180 days) use of opioids for nonmalignant pain and associated factors among community-dwelling persons with AD and to compare the prevalence with a matched cohort without AD. The Medication use and Alzheimer's disease (MEDALZ) cohort was used for this study, comprising all community-dwelling persons diagnosed with AD in Finland during 2005 to 2011 and their matched comparison persons without AD. After exclusion of persons with active cancer treatment, 62,074 persons with and 62,074 persons without AD were included in this study. Data were collected from nationwide registers. Opioids were used by 13,111 persons with and by 16,659 without AD. Overall long-term opioid use was more common among persons without AD (8.7%) than among persons with AD (7.2%, P < 0.0001). However, among opioid users, prevalence of long-term opioid use was slightly higher among persons with AD than among those without AD (34.2% vs 32.3%, respectively, P = 0.0004). Long-term use of transdermal opioids was more than 2-fold among opioid users with AD (13.2%) compared with users without AD (5.5%). Factors associated with long-term opioid use included AD, age ≥80 years, female sex, rheumatoid arthritis, osteoporosis, low socioeconomic position, history of substance abuse, and long-term benzodiazepine use. Prevalence of long-term opioid use was somewhat similar among both groups. Among persons with AD, long-term opioid use was strongly associated with transdermal opioids.