Trajectories of Opioid Use Before and After Cancer Diagnosis: A Population-Based Cohort Study.

BACKGROUND: Opioid use prior to cancer diagnosis increases the likelihood of long-term use during survivorship, however, patterns of use before and after diagnosis are not understood. METHODS: We used population-based dispensing data linked with cancer and death notifications to identify two cohorts of adults residing in New South Wales initiating opioids within 24 months prior to a first cancer diagnosed between 2014 and 2016: 'survivors' (alive 24 months following diagnosis) and 'decedents' (died within 24 months). We used group-based trajectory modelling to identify trajectories of monthly opioid dispensings and dispensed oral morphine equivalent milligrams (OMEmg) during the 24 months before/after cancer diagnosis. RESULTS: There were 21,843 survivors with four prediagnosis opioid dispensing trajectories: infrequent (58% of the cohort), late increasing (26%), moderate (10%), and sustained dispensing (6%). We observed an overall increase in dispensed OMEmg of 83 OMEmg (95% CI: 76-91) during the month of diagnosis, with strong opioid formulations comprising most treatment postdiagnosis. Within each prediagnosis opioid trajectory group, we observed five to six postdiagnosis trajectory groups, including no opioid dispensing. Moderate and sustained prediagnosis groups had large proportions of people continuing or increasing opioid dispensing after diagnosis, while small proportions discontinued opioid treatment. We observed similar trajectories in the decedent cohort. CONCLUSIONS: There is considerable heterogeneity in opioid use before and after cancer diagnosis. Our findings suggest noncancer factors drive a significant proportion of postdiagnosis opioid use, but use increased significantly from the month of cancer diagnosis and never returned to prediagnosis levels.

Oxycodone initiation in Australia (2014-2018): Sociodemographic factors and preceding health service use.

AIMS: Oxycodone is the most commonly prescribed strong opioid in Australia. This study describes health service antecedents and sociodemographic factors associated with oxycodone initiation. METHODS: Population-based new user cohort study linking medicine dispensings, hospitalizations, emergency department visits, medical services and cancer notifications from New South Wales (NSW) for 2014-2018. New users had no dispensings of any opioid in the preceding year. We analysed health service use in the 5 days preceding initiation and proportion of people on treatment over 1 year and fitted an area-based, multivariable initiation model with sociodemographic covariates. RESULTS: Oxycodone accounted for 30% of opioid initiations. Annually, 3% of the NSW population initiated oxycodone, and 5-6% were prevalent users; the new user cohort comprised 830 963 people. Discharge from hospital (39.3%), therapeutic procedures (21.4%) and emergency department visits (19.7%) were common; a hospital admission for injury (6.0%) or a past-year history of cancer (7.2%) were less common. At 1 year after initiation, 4.6% of people were using oxycodone. In the multivariable model, new use of oxycodone increased with age and was higher for people outside major cities, for example, an incidence rate ratio of 1.43 (95% confidence interval 1.36-1.51) for inner regional areas relative to major cities; there was no evidence of variation in rates of new use by social disadvantage. CONCLUSION: About half of new oxycodone use in NSW was preceded by a recent episode of hospital care or a therapeutic procedure. Higher rates of oxycodone initiation in rural and regional areas were not explained by sociodemographic factors.

The association of dietary antioxidants and the inflammatory potential of the diet with poor physical function and disability in older Australian men: the Concord Health and Ageing in Men Project.

Our objective was to evaluate the association of antioxidant intake and the inflammatory potential of the diet with functional decline in older men. A diet history questionnaire was used to collect dietary intake data from men aged ≥ 75 years (n 794) participating in the Concord Health and Aging in Men Project cohort study. Intake of vitamins A, C, E and Zn were compared with the Australian Nutrient Reference Values to determine adequacy. The Energy-adjusted Dietary Inflammatory Index (E-DIITM) was used to assess the inflammatory potential of the diet. Physical performance data were collected via handgrip strength and walking speed tests, and activities of daily living (ADL) and instrumental activities of daily living (IADL) questionnaires, at baseline and 3-year follow-up (n 616). Logistic regression analysis was used to identify associations between diet and incident poor physical function and disability. Both poor antioxidant intake and high E-DII scores at baseline were significantly associated with poor grip strength and ADL disability at 3-year follow-up. No significant associations with walking speed or IADL disability were observed. Individual micronutrient analysis revealed a significant association between the lowest two quartiles of vitamin C intake and poor grip strength. The lowest quartiles of intake for vitamins A, C, E and Zn were significantly associated with incident ADL disability. The study observed that poor antioxidant and anti-inflammatory food intake were associated with odds of developing disability and declining muscle strength in older men. Further interventional research is necessary to clarify the causality of these associations.

Pain and its interference with daily living in relation to cancer: a comparative population-based study of 16,053 cancer survivors and 106,345 people without cancer.

BACKGROUND: Pain is a common, debilitating, and feared symptom, including among cancer survivors. However, large-scale population-based evidence on pain and its impact in cancer survivors is limited. We quantified the prevalence of pain in community-dwelling people with and without cancer, and its relation to physical functioning, psychological distress, and quality of life (QoL). METHODS: Questionnaire data from participants in the 45 and Up Study (Wave 2, n = 122,398, 2012-2015, mean age = 60.8 years), an Australian population-based cohort study, were linked to cancer registration data to ascertain prior cancer diagnoses. Modified Poisson regression estimated age- and sex-adjusted prevalence ratios (PRs) for bodily pain and pain sufficient to interfere with daily activities (high-impact pain) in people with versus without cancer, for 13 cancer types, overall and according to clinical, personal, and health characteristics. The relation of high-impact pain to physical and mental health outcomes was quantified in people with and without cancer. RESULTS: Overall, 34.9% (5,436/15,570) of cancer survivors and 31.3% (32,471/103,604) of participants without cancer reported bodily pain (PR = 1.07 [95% CI = 1.05-1.10]), and 15.9% (2,468/15,550) versus 13.1% (13,573/103,623), respectively, reported high-impact pain (PR = 1.13 [1.09-1.18]). Pain was greater with more recent cancer diagnosis, more advanced disease, and recent cancer treatment. High-impact pain varied by cancer type; compared to cancer-free participants, PRs were: 2.23 (1.71-2.90) for multiple myeloma; 1.87 (1.53-2.29) for lung cancer; 1.06 (0.98-1.16) for breast cancer; 1.05 (0.94-1.17) for colorectal cancer; 1.04 (0.96-1.13) for prostate cancer; and 1.02 (0.92-1.12) for melanoma. Regardless of cancer diagnosis, high-impact pain was strongly related to impaired physical functioning, psychological distress, and reduced QoL. CONCLUSIONS: Pain is common, interfering with daily life in around one-in-eight older community-dwelling participants. Pain was elevated overall in cancer survivors, particularly for certain cancer types, around diagnosis and treatment, and with advanced disease. However, pain was comparable to population levels for many common cancers, including breast, prostate and colorectal cancer, and melanoma.

Five-Year Trajectories of Prescription Opioid Use.

Importance: There are known risks of using opioids for extended periods. However, less is known about the long-term trajectories of opioid use following initiation. Objective: To identify 5-year trajectories of prescription opioid use, and to examine the characteristics of each trajectory group. Design, Setting, and Participants: This population-based cohort study conducted in New South Wales, Australia, linked national pharmaceutical claims data to 10 national and state data sets to determine sociodemographic characteristics, clinical characteristics, drug use, and health services use. The cohort included adult residents (aged ≥18 years) of New South Wales who initiated a prescription opioid between July 1, 2003, and December 31, 2018. Statistical analyses were conducted from February to September 2022. Exposure: Dispensing of a prescription opioid, with no evidence of opioid dispensing in the preceding 365 days, identified from pharmaceutical claims data. Main Outcomes and Measures: The main outcome was the trajectories of monthly opioid use over 60 months from opioid initiation. Group-based trajectory modeling was used to classify these trajectories. Linked health care data sets were used to examine characteristics of individuals in different trajectory groups. Results: Among 3 474 490 individuals who initiated a prescription opioid (1 831 230 females [52.7%]; mean [SD] age, 49.7 [19.3] years), 5 trajectories of long-term opioid use were identified: very low use (75.4%), low use (16.6%), moderate decreasing to low use (2.6%), low increasing to moderate use (2.6%), and sustained use (2.8%). Compared with individuals in the very low use trajectory group, those in the sustained use trajectory group were older (age ≥65 years: 22.0% vs 58.4%); had more comorbidities, including cancer (4.1% vs 22.2%); had increased health services contact, including hospital admissions (36.9% vs 51.6%); had higher use of psychotropic (16.4% vs 42.4%) and other analgesic drugs (22.9% vs 47.3%) prior to opioid initiation, and were initiated on stronger opioids (20.0% vs 50.2%). Conclusions and relevance: Results of this cohort study suggest that most individuals commencing treatment with prescription opioids had relatively low and time-limited exposure to opioids over a 5-year period. The small proportion of individuals with sustained or increasing use was older with more comorbidities and use of psychotropic and other analgesic drugs, likely reflecting a higher prevalence of pain and treatment needs in these individuals.

Clinical practice guideline for deprescribing opioid analgesics: summary of recommendations.

INTRODUCTION: Long term opioids are commonly prescribed to manage pain. Dose reduction or discontinuation (deprescribing) can be challenging, even when the potential harms of continuation outweigh the perceived benefits. The Evidence-based clinical practice guideline for deprescribing opioid analgesics was developed using robust guideline development processes and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology, and contains deprescribing recommendations for adults prescribed opioids for pain. MAIN RECOMMENDATIONS: Eleven recommendations provide advice about when, how and for whom opioid deprescribing should be considered, while noting the need to consider each person's goals, values and preferences. The recommendations aim to achieve: implementation of a deprescribing plan at the point of opioid initiation; initiation of opioid deprescribing for persons with chronic non-cancer or chronic cancer-survivor pain if there is a lack of overall and clinically meaningful improvement in function, quality of life or pain, a lack of progress towards meeting agreed therapeutic goals, or the person is experiencing serious or intolerable opioid-related adverse effects; gradual and individualised deprescribing, with regular monitoring and review; consideration of opioid deprescribing for individuals at high risk of opioid-related harms; avoidance of opioid deprescribing for persons nearing the end of life unless clinically indicated; avoidance of opioid deprescribing for persons with a severe opioid use disorder, with the initiation of evidence-based care, such as medication-assisted treatment of opioid use disorder; and use of evidence-based co-interventions to facilitate deprescribing, including interdisciplinary, multidisciplinary or multimodal care. CHANGES IN MANAGEMENT AS A RESULT OF THESE GUIDELINES: To our knowledge, these are the first evidence-based guidelines for opioid deprescribing. The recommendations intend to facilitate safe and effective deprescribing to improve the quality of care for persons taking opioids for pain.

Cohort profile: POPPY II - a population-based cohort examining the patterns and outcomes of prescription opioid use in New South Wales, Australia.

PURPOSE: The POPPY II cohort is an Australian state-based cohort linking data for a population of individuals prescribed opioid medicines, constructed to allow a robust examination of the long-term patterns and outcomes of prescription opioid use. PARTICIPANTS: The cohort includes 3 569 433 adult New South Wales residents who initiated a subsidised prescription opioid medicine between 2003 and 2018, identified through pharmacy dispensing data (Australian Pharmaceutical Benefits Scheme) and linked to 10 national and state datasets and registries including rich sociodemographic and medical services data. FINDINGS TO DATE: Of the 3.57 million individuals included in the cohort, 52.7% were female and 1 in 4 people were aged ≥65 years at the time of cohort entry. Approximately 6% had evidence of cancer in the year prior to cohort entry. In the 3 months prior to cohort entry, 26.9% used a non-opioid analgesic and 20.5% used a psychotropic medicine. Overall, 1 in 5 individuals were initiated on a strong opioid (20.9%). The most commonly initiated opioid was paracetamol/codeine (61.3%), followed by oxycodone (16.3%). FUTURE PLANS: The POPPY II cohort will be updated periodically, both extending the follow-up duration of the existing cohort, and including new individuals initiating opioids. The POPPY II cohort will allow a range of aspects of opioid utilisation to be studied, including long-term trajectories of opioid use, development of a data-informed method to assess time-varying opioid exposure, and a range of outcomes including mortality, transition to opioid dependence, suicide and falls. The duration of the study period will allow examination of population-level impacts of changes to opioid monitoring and access, while the size of the cohort will also allow examination of important subpopulations such as people with cancer, musculoskeletal conditions or opioid use disorder.

Opioid prescribing patterns among medical practitioners in New South Wales, Australia.

INTRODUCTION: Prescriber behaviour is important for understanding opioid use patterns. We described variations in practitioner-level opioid prescribing in New South Wales, Australia (2013-2018). METHODS: We quantified opioid prescribing patterns among medical practitioners using population-level dispensing claims data, and used partitioning around medoids to identify clusters of practitioners who prescribe opioids based on prescribing patterns and patient characteristics identified from linked dispensing claims, hospitalisations and mortality data. RESULTS: The number of opioid prescribers ranged from 20,179 in 2013 to 23,408 in 2018. The top 1% of practitioners prescribed 15% of all oral morphine equivalent (OME) milligrams dispensed annually, with a median of 1382 OME grams (interquartile range [IQR], 1234-1654) per practitioner; the bottom 50% prescribed 1% of OMEs dispensed, with a median of 0.9 OME grams (IQR 0.2-2.6). Based on 63.6% of practitioners with ≥10 patients filling opioid prescriptions in 2018, we identified four distinct practitioner clusters. The largest cluster prescribed multiple analgesic medicines for older patients (23.7% of practitioners) accounted for 76.7% of all OMEs dispensed and comprised 93.0% of the top 1% of practitioners by opioid volume dispensed. The cluster prescribing analgesics for younger patients with high rates of surgery (18.7% of practitioners) prescribed only 1.6% of OMEs. The remaining two clusters comprised 21.2% of prescribers and 20.9% of OMEs dispensed. DISCUSSION AND CONCLUSION: We observed substantial variation in opioid prescribing among practitioners, clustered around four general patterns. We did not assess appropriateness but some prescribing patterns are concerning. Our findings provide insights for targeted interventions to curb potentially harmful practices.

Towards Optimizing Hospitalized Older adults' MEdications (TO HOME): Multi-centre study of medication use and outcomes in routine care.

AIMS: Comprehensively investigate prescribing in usual care of hospitalized older people with respect to polypharmacy; potentially inappropriate medications (PIMs) according to Beers criteria; and cumulative anticholinergic and sedative medication exposure calculated with Drug Burden Index (DBI). Specifically, to quantify exposure to these measures on admission, changes between admission and discharge, associations with adverse outcomes and medication costs. METHODS: Established new retrospective inpatient cohort of 2000 adults aged ≥75 years, consecutively admitted to 6 hospitals in Sydney, Australia, with detailed information on medications, clinical characteristics and outcomes. Conducted cross-sectional analyses of index admission data from cohort. RESULTS: Cohort had mean (standard deviation) age 86.0 (5.8) years, 59% female, 21% from residential aged care. On admission, prevalence of polypharmacy was 77%, PIMs 34% and DBI > 0 in 53%. From admission to discharge, mean difference (95% confidence interval) in total number of medications increased 1.05 (0.92, 1.18); while prevalence of exposure to PIMs (-3.8% [-5.4, -2.1]) and mean DBI score (-0.02 [-0.04, -0.01]) decreased. PIMs and DBI score were associated with increased risks (adjusted odds ratio [95% confidence interval]) of falls (PIMs 1.63 [1.28, 2.08]; DBI score 1.21[1.00, 1.46]) and delirium (PIMs 1.76 [1.38, 1.46]; DBI score 1.42 [1.19, 1.71]). Each measure was associated with increased risk of adverse drug reactions (polypharmacy 1.42 [1.19, 1.71]; PIMs 1.87 [1.40, 2.49]; DBI score 1.90 [1.55, 2.15]). Cost (AU$/patient/hospital day) of medications contributing to PIMs and DBI was low ($0.29 and $0.88). CONCLUSION: In this large cohort of older inpatients, usual hospital care results in an increase in number of medications and small reductions in PIMs and DBI, with variable associations with adverse outcomes.

The association between multimorbidity and osteoporosis investigation and treatment in high-risk fracture patients in Australia: A prospective cohort study.

BACKGROUND: Multimorbidity is common among fracture patients. However, its association with osteoporosis investigation and treatment to prevent future fractures is unclear. This limited knowledge impedes optimal patient care. This study investigated the association between multimorbidity and osteoporosis investigation and treatment in persons at high risk following an osteoporotic fracture. METHODS AND FINDINGS: The Sax Institute's 45 and Up Study is a prospective population-based cohort of 267,153 people in New South Wales, Australia, recruited between 2005 and 2009. This analysis followed up participants until 2017 for a median of 6 years (IQR: 4 to 8). Questionnaire data were linked to hospital admissions (Admitted Patients Data Collection (APDC)), emergency presentations (Emergency Department Data Collection (EDDC)), Pharmaceutical Benefits Scheme (PBS), and Medicare Benefits Schedule (MBS). Data were linked by the Centre for Health Record Linkage and stored in a secured computing environment. Fractures were identified from APDC and EDDC, Charlson Comorbidity Index (CCI) from APDC, Dual-energy X-ray absorptiometry (DXA) investigation from MBS, and osteoporosis treatment from PBS. Out of 25,280 persons with index fracture, 10,540 were classified as high-risk based on 10-year Garvan Fracture Risk (age, sex, weight, prior fracture and falls) threshold ≥20%. The association of CCI with likelihood of investigation and treatment initiation was determined by logistic regression adjusted for education, socioeconomic and lifestyle factors). The high-risk females and males averaged 77 ± 10 and 86 ± 5 years, respectively; >40% had a CCI ≥2. Only 17% of females and 7% of males received a DXA referral, and 22% of females and 14% males received osteoporosis medication following fracture. A higher CCI was associated with a lower probability of being investigated [adjusted OR, females: 0.73 (95% CI, 0.61 to 0.87) and 0.43 (95% CI, 0.30 to 0.62); males: 0.47 (95% CI, 0.33 to 0.68) and 0.52 (0.31 to 0.85) for CCI: 2 to 3, and ≥4 versus 0 to 1, respectively] and of receiving osteoporosis medication [adjusted OR, females: 0.85 (95% CI, 0.74 to 0.98) and 0.78 (95% CI, 0.61 to 0.99); males: 0.75 (95% CI, 0.59 to 0.94) and 0.37 (95% CI, 0.23 to 0.53) for CCI: 2 to 3, and ≥4 versus 0 to 1, respectively]. The cohort is relatively healthy; therefore, the impact of multimorbidity on osteoporosis management may have been underestimated. CONCLUSIONS: Multimorbidity contributed significantly to osteoporosis treatment gap. This suggests that fracture risk is either underestimated or underprioritized in the context of multimorbidity and highlights the need for extra vigilance and improved fracture care in this setting.

Antiresorptive Medication Use Is not Associated With Acute Cardiovascular Risk: An Observational Study.

CONTEXT: Bisphosphonates have been reported to be cardioprotective in some, but not all, studies. It is unknown whether denosumab (Dmab) use protects against cardiovascular events (CVEs). OBJECTIVE: To determine whether oral bisphosphonate (oBP) or Dmab use is associated with CVEs in persons with incident fracture. METHODS: Participants with an incident minimal trauma fracture from the Sax Institute's 45 and Up Study, a population-based cohort from NSW, Australia, were followed between 2005/2009 and 2017. Questionnaire data were linked to hospital admissions (Admitted Patients Data Collection [APDC]) by the Centre for Health Record Linkage). Medicare Benefit Schedule (MBS) and Pharmaceutical Benefits Scheme (PBS) data sets were provided by Services Australia. Data was stored in a secure computing environment (Secure Unified Research Environment). Fractures, CVEs, and comorbidities were identified from the APDC and oBP and Dmab medication from the PBS. oBP and Dmab users were matched to never users (NoRx) by propensity scores. The main outcome measures were association between oBP and Dmab with CVE (acute myocardial infarction, unstable angina, cerebrovascular accident, and transient ischemic attack) and were determined using a stratified Cox's proportional hazards model. RESULTS: There were 880 pairs of oBP and NoRx (616 women) and 770 pairs of Dmab and NoRx (615 women) followed for ∼4.3 years. CVE risk was similar for oBP and NoRx Hazard Ratios (HR) women, 0.88 [95% CI 0.65-1.18]; men, 1.07 [95% CI 0.72-1.57]). Similar findings were obtained for Dmab (Hazard Ratios (HR) women, 1.08 [95% CI 0.78-1.50]; men, 1.55 [95% CI 0.96-2.48]). CONCLUSION: oBP and Dmab use was not associated with CVEs.

Opioid deprescribing: Qualitative perspectives from those with chronic non-cancer pain.

AIM: Deprescribing is the systematic process of discontinuing medications when the harms outweigh the benefits. This study aimed to identify barriers and facilitators in people with chronic non-cancer pain when deprescribing opioid analgesics, and their views on resources that assist with deprescribing. METHODS: A purposive sampling strategy was used to recruit 19 adults with chronic non-cancer pain from the community who were, or had been, on long-term opioid therapy. Recruitment continued until thematic saturation was achieved. Semi-structured telephone interviews were conducted. A five-step framework and thematic analysis method identified themes for each study aim. RESULTS: Themes identifying barriers to opioid deprescribing raised challenges of a lack of available alternatives, managing opioid dependency and withdrawal symptoms or inability to function without opioids when in extreme pain. Facilitating themes described the value of support networks, including a trusting doctor-patient relationship and finding individual coping strategies to address deprescribing barriers. We explored a variety of resources from electronic forms such as websites and apps to paper-based or face to face. Participants expressed that whatever the form, resources need to be educational but also simple and engaging. CONCLUSIONS: Most people suffering from chronic non-cancer pain expressed dissatisfaction with being on opioids but most were still unwilling to deprescribe due to insufficient alternatives, a lack of support from their doctors and lack of information about the deprescribing process. Deprescribing can be facilitated by improving supportive networks and strategies and providing simple and positive educational resources.

Health and service needs, priorities and initiatives of primary health networks related to chronic pain.

BACKGROUND: Chronic pain is a major and growing public health issue. Multidisciplinary tertiary pain services cannot meet patient demand and greater involvement of primary care is needed. The aims of this study were to understand the needs and priorities of Australian primary health networks (PHNs) related to the management and secondary prevention of chronic pain; map current PHN chronic pain initiatives and identify gaps; highlight key enablers to implementation; and highlight solutions identified by PHNs to increase capacity to commission initiatives. METHODS: Mixed methods were used, including: a review of PHN needs assessments; and consultation with PHN executive-level staff and program managers from 27 out of the 28 PHNs, and the WA Primary Health Alliance (WAPHA - a state alliance between three Western Australian PHNs) via telephone interviews, online surveys, a workshop, a deliberative dialogue and email consultation. RESULTS: Chronic pain was identified as a health and/or service need by approximately half of PHNs. Barriers for PHNs to identifying chronic pain as a need or priority are highlighted. Gaps identified by the mapping included: initiatives related to the secondary prevention of chronic pain (post-surgery or post-injury), digitally enabled consumer and health professional chronic pain initiatives, and chronic pain initiatives for specific populations groups such as Aboriginal and Torres Strait Islander people. Among existing PHN practice, two exemplar evidence-based initiatives suitable for scale-up across PHNs in Australia were identified: multidisciplinary community-based pain programs, and an online health professional capacity-building initiative, Project ECHO (chronic pain). Solutions identified by PHNs to increase capacity to commission initiatives included: co-funding initiatives across different PHN funding streams, collaborative initiatives between PHNs, and co-commissioning with government and non-government partners. CONCLUSIONS: Chronic pain has been classified as a disease in itself through the World Health Organization. PHNs recognising chronic pain as a distinct condition in PHN needs analysis and data collection would lead to more dedicated funding. PHNs could do more to improve the secondary prevention and management of chronic pain. A self-identified need for greater collaboration across PHNs and co-commissioning with local and state governments and non-government partners would help to build PHN capacity.

Disability burden due to musculoskeletal conditions and low back pain in Australia: findings from GBD 2019.

BACKGROUND: To report the national prevalence, years lived with disability (YLDs) and attributable risk factors for all musculoskeletal conditions and separately for low back pain (LBP), as well as compare the disability burden related to musculoskeletal with other health conditions in Australia in 2019. METHODS: Global Burden of Disease (GBD) 2019 study meta-data on all musculoskeletal conditions and LBP specifically were accessed and aggregated. Counts and age-standardised rates, for both sexes and across all ages, for prevalence, YLDs and attributable risk factors are reported. RESULTS: In 2019, musculoskeletal conditions were estimated to be the leading cause of YLDs in Australia (20.1%). There were 7,219,894.5 (95% UI: 6,847,113-7,616,567) prevalent cases of musculoskeletal conditions and 685,363 (95% UI: 487,722-921,471) YLDs due to musculoskeletal conditions. There were 2,676,192 (95% UI: 2,339,327-3,061,066) prevalent cases of LBP and 298,624 (95% UI: 209,364-402,395) YLDs due to LBP. LBP was attributed to 44% of YLDs due to musculoskeletal conditions. In 2019, 22.3% and 39.8% of YLDs due to musculoskeletal conditions and LBP, respectively, were attributed to modifiable GBD risk factors. CONCLUSIONS: The ongoing high burden due to musculoskeletal conditions impacts Australians across the life course, and in particular females and older Australians. Strategies for integrative and organisational interventions in the Australian healthcare system should support high-value care and address key modifiable risk factors for disability such as smoking, occupational ergonomic factors and obesity.

Efficacy of interventions to reduce long term opioid treatment for chronic non-cancer pain: systematic review and meta-analysis.

OBJECTIVE: To review interventions to reduce long term opioid treatment in people with chronic non-cancer pain, considering efficacy on dose reduction and discontinuation, pain, function, quality of life, withdrawal symptoms, substance use, and adverse events. DESIGN: Systematic review and meta-analysis of randomised controlled trials and non-randomised studies of interventions. DATA SOURCES: Medline, Embase, PsycINFO, CINAHL, and the Cochrane Library searched from inception to July 2021. Reference lists and previous reviews were also searched and experts were contacted. ELIGIBILITY CRITERIA FOR STUDY SELECTION: Original research in English. Case reports and cross sectional studies were excluded. DATA EXTRACTION AND SYNTHESIS: Two authors independently selected studies, extracted data, and used the Cochrane risk-of-bias tools for randomised and non-randomised studies (RoB 2 and ROBINS-I). Authors grouped interventions into five categories (pain self-management, complementary and alternative medicine, pharmacological and biomedical devices and interventions, opioid replacement treatment, and deprescription methods), estimated pooled effects using random effects meta-analytical models, and appraised the certainty of evidence using GRADE (grading of recommendations, assessment, development, and evaluation). RESULTS: Of 166 studies meeting inclusion criteria, 130 (78%) were considered at critical risk of bias and were excluded from the evidence synthesis. Of the 36 included studies, few had comparable treatment arms and sample sizes were generally small. Consequently, the certainty of the evidence was low or very low for more than 90% (41/44) of GRADE outcomes, including for all non-opioid patient outcomes. Despite these limitations, evidence of moderate certainty indicated that interventions to support prescribers' adherence to guidelines increased the likelihood of patients discontinuing opioid treatment (adjusted odds ratio 1.5, 95% confidence interval 1.0 to 2.1), and that these prescriber interventions as well as pain self-management programmes reduced opioid dose more than controls (intervention v control, mean difference -6.8 mg (standard error 1.6) daily oral morphine equivalent, P<0.001; pain programme v control, -14.31 mg daily oral morphine equivalent, 95% confidence interval -21.57 to -7.05). CONCLUSIONS: Evidence on the reduction of long term opioid treatment for chronic pain continues to be constrained by poor study methodology. Of particular concern is the lack of evidence relating to possible harms. Agreed standards for designing and reporting studies on the reduction of opioid treatment are urgently needed. REVIEW REGISTRATION: PROSPERO CRD42020140943.

Changes in Dietary Total and Nonheme Iron Intake Is Associated With Incident Frailty in Older Men: The Concord Health and Aging in Men Project.

BACKGROUND: Nutritional intake could influence the development of frailty. The aim was to evaluate the associations between dietary iron intakes and changes in dietary iron intakes with frailty. METHODS: Cross-sectional analyses involved 785 men with Fried frailty phenotype (FP) and 758 men with Rockwood frailty index (FI) data aged 75 years and older at nutrition assessment from the Concord Health and Ageing in Men Project prospective cohort study. Of these, 563 men who were FP robust or prefrail, and 432 men who were FI nonfrail were included in the longitudinal analyses for more than 3 years. Dietary intake was assessed at both timepoints using a validated diet history questionnaire. The dietary calculation was used to derive heme iron and nonheme iron intakes from total iron intakes. The associations were evaluated through binary logistic regression. RESULTS: Incidence of FP frailty was 15.3% (n = 86). In longitudinal analyses, maintaining total iron intakes (medium tertile -2.61-0.81 mg/d), increases in total iron and nonheme iron intakes (high tertiles ≥0.82 mg/d and ≥0.80 mg/d), and changes in nonheme iron intake (1 mg increment) were associated with reduced risks of incident FP frailty (OR: 0.47 [95% confindence interval (CI): 0.24, 0.93, p = .031], OR 0.48 [95% CI: 0.23, 0.99, p = .048], OR 0.41 [95% CI: 0.20, 0.88, p = .022], and OR 0.89 [95% CI: 0.82, 0.98, p = .017]). CONCLUSION: Maintaining or increases in total dietary iron and increases or changes in dietary nonheme iron intakes more than 3 years were associated with reduced incidence of FP frailty in older men.

Comparing Effects of Polypharmacy on Inflammatory Profiles in Older Adults and Mice: Implications for Translational Aging Research.

Aging and multimorbidity are associated with inflammation. Polypharmacy is common in older people with multimorbidity. Given the potential for interactions between polypharmacy and inflammation, the relationship between inflammation and polypharmacy were studied in older adults with multimorbidity and in healthy aging mice. A cross-sectional analysis of data from the 5-year wave of the Concord Health and Ageing in Men Project, a population-based study of community-dwelling men aged ≥70 years. Serum concentrations of 27 cytokines were measured using a multiplex immunoassay. Associations between polypharmacy (≥5 medications) and cytokines were evaluated using multivariable linear regression adjusting for age, frailty, comorbidities, and individual drug classes. Interaction between polypharmacy and Drug Burden Index (DBI-drugs with anticholinergic and sedative effects) was analyzed. Effects of polypharmacy and DBI on serum levels of 23 cytokines were determined in aging male mice treated with chronic polypharmacy or control. Compared to the nonpolypharmacy group (n = 495), CHAMP participants with polypharmacy (n = 409) had significantly higher concentrations of IL-8, IL-6, CCL3, Eotaxin, IL-1ra, IL-1ß, IP-10, and lower concentrations of anti-inflammatory cytokine IL-4. In fully-adjusted multivariable models, polypharmacy was positively associated with concentrations of IL-8 and CCL3. There were no significant differences in inflammatory profiles between control and polypharmacy-treated mice. The relationship was not influenced by DBI in men or in mice. Inflammatory markers associated with polypharmacy in older adults were not seen in healthy aged mice administered polypharmacy, and may be related to underlying diseases. The polypharmacy mouse model provides opportunities for mechanistic investigations in translational research.

Community-based pain programs commissioned by primary health networks: key findings from an online survey and consultation with program managers.

OBJECTIVE: There is an increasing demand for tertiary pain services, with long waiting times compounded by limited reach to regional and remote areas. Community-based pain programs are a feasible evidence-based model of care to improve access to multidisciplinary care. Australian primary health networks (PHNs) are well placed to commission pain programs to reduce the growing burden of chronic pain. The aim of this study was to support PHN decision-making by: (1) describing current PHN community-based pain programs; (2) assessing their alignment to key elements and implementation enablers of pain programs identified by an expert consensus process; and (3) describing PHN pain program adaptations during the COVID-19 pandemic. METHODS: PHN program managers of community-based pain programs (n = 9) were invited to participate in an online survey and follow-up email consultation about their pain program. Six PHN program managers (representing South Eastern NSW PHN, Nepean Blue Mountains PHN, North Western Melbourne PHN, Gold Coast PHN, Adelaide PHN and the WA Primary Health Alliance) participated in the study with three PHNs commissioning two different types of pain programs. RESULTS: PHN community-based pain programs are multidisciplinary programs underpinned by a biopsychosocial model of pain, and focus on self-management (e.g. exercise, psychological strategies) and pain education. Most PHN pain programs are group-based programs that target adults with chronic non-cancer pain, provide individual allied health referrals as required and are evaluated as part of the electronic Persistent Pain Outcomes Collaboration. Gaps include pain programs for Aboriginal and Torres Strait Islander people, and people from culturally and linguistically diverse backgrounds, with one notable exception of a PHN pain program for people from culturally and linguistically diverse and refugee backgrounds co-designed with consumers and relevant services. Programs targeting subacute pain to prevent progression to chronic pain are, with one exception, another gap area. PHN pain programs demonstrated a high level of alignment with expert-agreed key elements and implementation enablers. The COVID-19 pandemic precipitated the rapid adaptation of PHN pain programs using available methods for the delivery of digitally enabled care. CONCLUSIONS: The findings provide a greater understanding for researchers and PHN decision-makers of the key features of PHN community-based pain programs, their alignment with expert-agreed key elements and implementation enablers, the target-population gaps, and the types of program adaptations during the COVID-19 pandemic. The findings also illustrate the potential for using digitally enabled delivery methods to increase accessibility to pain programs with further research warranted.

Associations between dietary intake of total protein and sources of protein (plant vs. animal) and risk of all-cause and cause-specific mortality in older Australian men: The Concord Health and Ageing in Men Project.

BACKGROUND: The association between dietary protein intake and the risk of mortality is still controversial. The present study aimed to examine the associations between dietary total, animal and plant protein intake and all-cause and cause-specific mortality. METHODS: Community-dwelling men aged ≥ 70 years were recruited from local government areas surrounding Concord Hospital in Sydney, New South Wales for the Concord Health and Ageing in Men Project (CHAMP). The research dietitian administered a standardised validated diet history questionnaire to capture baseline dietary intake. In total, 794 men participated in a detailed diet history interview at the third wave. Adequacy of protein intake was assessed by comparing participant intake with the Nutrient Reference Values. Total protein intake was categorised into quintiles. Sources of protein were also captured. Mortality was ascertained through the New South Wales death registry. Cox proportional hazard models were used to assess the association between dietary total, animal and plant protein intake and risk of mortality. RESULTS: The mean age of the CHAMP men was 81 years. In total, 162 men died during a median follow-up of 3.7 years. Of these, 54 (33.3%) and 49 (30.2%) men died due to cancer and cardiovascular disease, respectively. There were U-shaped associations between protein intake and all-cause and cancer mortality. In multiple adjusted analysis, the second (hazard ratio [HR] = 0.38; 95% confidence interval [CI] = 0.18-0.82) and third (HR = 0.36; 95% CI = 0.16-0.82) quintiles of protein intakes were significantly associated with reduced risk of all-cause and only second quintile (HR = 0.47; 95% CI = 0.10-0.93) of protein intake was significantly associated with cancer mortality. Each serve increase in animal protein was significantly associated with 12% (HR = 1.12; 95% CI = 1.00-1.26) and 23% (HR = 1.23; 95% CI = 1.02-1.49) increased risk of all-cause mortality and cancer mortality respectively. Conversely, each serve increase in plant protein intake was significantly associated with 25% (HR = 0.75; 95% CI 0.61-0.92) and 28% (HR = 0.72; 95% CI = 0.53-0.97) reduced risk of all-cause and cancer mortality, respectively. No such associations were observed for cardiovascular disease mortality. CONCLUSIONS: Both second and third quintiles of total protein intake were associated with reduced all-cause and cancer mortality. Plant protein was inversely associated with all-cause and cancer mortality, whereas animal protein intake was positively associated with mortality.

Dietary and supplemental antioxidant intake and risk of major adverse cardiovascular events in older men: The concord health and ageing in men project.

BACKGROUND AND AIMS: The role of antioxidant intake in cardiovascular disease remains inconclusive. This study evaluates the association between antioxidant intake and the risk of major adverse cardiovascular events (MACE) among older Australian men. METHODS AND RESULTS: 794 men aged ≥75 years participated in the 3rd wave of the Concord Health and Ageing in Men Project. Dietary adequacy of antioxidant intake was assessed by comparing participants' intake of vitamins A, E, C and zinc to the Nutrient Reference Values (NRV) for Australia. Attainment of NRVs of antioxidants was categorised into a dichotomised variable 'inadequate' (meeting≤2 of 4 antioxidants) or 'adequate' (meeting≥3 of 4 antioxidants). The usage of antioxidant supplements was assessed. The outcome measure was MACE. The composite MACE endpoint was defined as having one of the following: death, myocardial infarction, ischemic stroke, congestive cardiac failure (CCF), and revascularization during the period of observation. There was no significant association between dietary (HR: 1.03, 95% CI: 0.71, 1.48) or supplemental antioxidant intake (HR: 1.10, 95% CI: 0.75, 1.63) and overall MACE. However, a significant association was observed between inadequate antioxidant intake and CCF (HR: 1.32; 95% CI: 1.16, 1.50). The lowest quartile of zinc intake (<11.00 mg/d) was significantly associated with CCF (HR 2.36; 95% CI: 1.04, 5.34). None of the other antioxidants were significantly associated with CCF or other MACE components. CONCLUSION: Inadequate dietary antioxidant intake, particularly zinc, is associated with increased risk of CCF in older Australian men but not associated with overall MACE.