Reducing potentially inappropriate polypharmacy at a national and international level: the impact of deprescribing networks.

INTRODUCTION: Over the past decade, polypharmacy has increased dramatically. Measurable harms include falls, fractures, cognitive impairment, and death. The associated costs are massive and contribute substantially to low-value health care. Deprescribing is a promising solution, but there are barriers. Establishing a network to address polypharmacy can help overcome barriers by connecting individuals with an interest and expertise in deprescribing and can act as an important source of motivation and resources. AREAS COVERED: Over the past decade, several deprescribing networks were launched to help tackle polypharmacy, with evidence of individual and collective impact. A network approach has several advantages; it can spark interest, ideas and enthusiasm through information sharing, meetings and conversations with the public, providers, and other key stakeholders. In this special report, the details of how four deprescribing networks were established across the globe are detailed. EXPERT OPINION: Networks create links between people who lead existing and/or budding deprescribing practices and policy initiatives, can influence people with a shared passion for deprescribing, and facilitate sharing of intellectual capital and tools to take initiatives further and strengthen impact.This report should inspire others to establish their own deprescribing networks, a critical step in accelerating a global deprescribing movement.

Developing an Adolescent and Young Adult Oncology Program in a Medium-Sized Canadian Centre: Lessons Learned.

The Adolescent and Young Adult (AYA) Program at CancerCare Manitoba (CCMB) has experienced tremendous growth since its inception. This report provides an overview of how the AYA program at CCMB was established and the crucial factors that led to its early accomplishments and continued expansion. These factors included actions and decisions made at the individual and organizational level that helped lay a strong foundation for the program's sustained success. We hope that some of these lessons learned can be adapted and implemented by other oncology agencies to improve the care outcomes and experiences of AYAs living with cancer.

Risk factors predicting hospital-acquired pressure injury in adult patients: An overview of reviews.

BACKGROUND: Hospital-acquired pressure injuries remain a significant patient safety threat. Current well-known pressure injury risk assessment tools have many limitations and therefore do not accurately predict the risk of pressure injury development over diverse populations. A contemporary understanding of the risk factors predicting pressure injury in adult hospitalised patients will inform pressure injury prevention and future researchers considering risk assessment tool development may benefit from our summary and synthesis of risk factors. OBJECTIVE: To summarise and synthesise systematic reviews that identify risk factors for hospital-acquired pressure injury development in adult patients. DESIGN: An overview of systematic reviews. METHODS: Cochrane and the Joanna Briggs Institute methodologies guided this overview. The Cochrane library, CINAHL, MEDLINE, and Embase databases were searched for relevant articles published in English from January 2008 to September 2022. Two researchers independently screened articles against the predefined inclusion and exclusion criteria, extracted data and assessed the quality of the included reviews using "a measurement tool to assess systematic reviews" (AMSTAR version 2). Data were categorised using an inductive approach and synthesised according to the recent pressure injury conceptual frameworks. RESULTS: From 11 eligible reviews, 37 risk factors were categorised inductively into 14 groups of risk factors. From these, six groups were classified into two domains: four to mechanical boundary conditions and two to susceptibility and tolerance of the individual. The remaining eight groups were evident across both domains. Four main risk factors, including diabetes, length of surgery or intensive care unit stay, vasopressor use, and low haemoglobin level were synthesised. The overall quality of the included reviews was low in five studies (45 %) and critically low in six studies (55 %). CONCLUSIONS: Our findings highlighted the limitations in the methodological quality of the included reviews that may have influenced our results regarding risk factors. Current risk assessment tools and conceptual frameworks do not fully explain the complex and changing interactions amongst risk factors. This may warrant the need for more high-quality research, such as cohort studies, focussing on predicting hospital-acquired pressure injury in adult patients, to reconsider these risk factors we synthesised. REGISTRATION: This overview was registered with the PROSPERO (CRD42022362218) on 27 September 2022.

Analgesic prescribing in patients with inflammatory arthritis in England: observational studies in the Clinical Practice Research Datalink.

OBJECTIVES: Despite little evidence that analgesics are effective in inflammatory arthritis (IA), studies report substantial opioid prescribing. The extent this applies to other analgesics is uncertain. We undertook a comprehensive evaluation of analgesic prescribing in patients with IA in the Clinical Practice Research Datalink Aurum to evaluate this. METHODS: From 2004 to 2020, cross-sectional analyses evaluated analgesic prescription annual prevalence in RA, PsA and axial spondyloarthritis (axSpA), stratified by age, sex, ethnicity, deprivation and geography. Joinpoint regression evaluated temporal prescribing trends. Cohort studies determined prognostic factors at diagnosis for chronic analgesic prescriptions using Cox proportional hazards models. RESULTS: Analgesic prescribing declined over time but remained common: 2004 and 2020 IA prescription prevalence was 84.2/100 person-years (PY) (95% CI 83.9, 84.5) and 64.5/100 PY (64.2, 64.8), respectively. In 2004, NSAIDs were most prescribed (56.1/100 PY; 55.8, 56.5), falling over time. Opioids were most prescribed in 2020 (39.0/100 PY; 38.7, 39.2). Gabapentinoid prescribing increased: 2004 prevalence 1.1/100 PY (1.0, 1.2); 2020 prevalence 9.9/100 PY (9.7, 10.0). Most opioid prescriptions were chronic (2020 prevalence 23.4/100 PY [23.2, 23.6]). Non-NSAID analgesic prescribing was commoner in RA, older people, females and deprived areas/northern England. Conversely, NSAID prescribing was commoner in axSpA/males, varying little by deprivation/geography. Peri-diagnosis was high-risk for starting chronic opioid/NSAID prescriptions. Prognostic factors for chronic opioid/gabapentinoid and NSAID prescriptions differed, with NSAIDs having no consistently significant association with deprivation (unlike opioids/gabapentinoids). CONCLUSION: IA analgesic prescribing of all classes is widespread. This is neither evidence-based nor in line with guidelines. Peri-diagnosis is an opportune moment to reduce chronic analgesic prescribing.

Changes in comprehensiveness of services delivered by Canadian family physicians: Analysis of population-based linked data in 4 provinces.

OBJECTIVE: To describe changes in the comprehensiveness of services delivered by family physicians across service settings and service areas in 4 Canadian provinces, to identify which settings and areas have changed the most, and to compare the magnitude of changes by physician characteristics. DESIGN: Descriptive analysis of province-wide, population-based billing data linked to population and physician registries. SETTING: British Columbia, Manitoba, Ontario, and Nova Scotia. PARTICIPANTS: Family physicians registered to practise in the 1999-2000 and 2017-2018 fiscal years. MAIN OUTCOME MEASURES: Comprehensiveness was measured across 7 service settings (home care, long-term care, emergency departments, hospitals, obstetric care, surgical assistance, anesthesiology) and in 7 service areas consistent with office-based practice (prenatal and postnatal care, Papanicolaou testing, mental health, substance use, cancer care, minor surgery, palliative home visits). The proportion of physicians with activity in each setting and area are reported and the average number of service settings and areas by physician characteristics is described (years in practice, sex, urban or rural practice setting, and location of medical degree training). RESULTS: Declines in comprehensiveness were observed across all provinces studied. Declines were greater for comprehensiveness of settings than for areas consistent with office-based practice. Changes were observed across all physician characteristics. On average across provinces, declines in the number of service settings and service areas were highest among physicians in practice 20 years or longer, male physicians, and physicians practising in urban areas. CONCLUSION: Declining comprehensiveness was observed across all physician characteristics, pointing to changes in the practice and policy contexts in which all family physicians work.

Oxidised IL-33 drives COPD epithelial pathogenesis via ST2-independent RAGE/EGFR signalling complex.

BACKGROUND: Epithelial damage, repair and remodelling are critical features of chronic airway diseases including chronic obstructive pulmonary disease (COPD). Interleukin (IL)-33 released from damaged airway epithelia causes inflammation via its receptor, serum stimulation-2 (ST2). Oxidation of IL-33 to a non-ST2-binding form (IL-33ox) is thought to limit its activity. We investigated whether IL-33ox has functional activities that are independent of ST2 in the airway epithelium. METHODS: In vitro epithelial damage assays and three-dimensional, air-liquid interface (ALI) cell culture models of healthy and COPD epithelia were used to elucidate the functional role of IL-33ox. Transcriptomic changes occurring in healthy ALI cultures treated with IL-33ox and COPD ALI cultures treated with an IL-33-neutralising antibody were assessed with bulk and single-cell RNA sequencing analysis. RESULTS: We demonstrate that IL-33ox forms a complex with receptor for advanced glycation end products (RAGE) and epidermal growth factor receptor (EGFR) expressed on airway epithelium. Activation of this alternative, ST2-independent pathway impaired epithelial wound closure and induced airway epithelial remodelling in vitro. IL-33ox increased the proportion of mucus-producing cells and reduced epithelial defence functions, mimicking pathogenic traits of COPD. Neutralisation of the IL-33ox pathway reversed these deleterious traits in COPD epithelia. Gene signatures defining the pathogenic effects of IL-33ox were enriched in airway epithelia from patients with severe COPD. CONCLUSIONS: Our study reveals for the first time that IL-33, RAGE and EGFR act together in an ST2-independent pathway in the airway epithelium and govern abnormal epithelial remodelling and muco-obstructive features in COPD.

Tozorakimab (MEDI3506): an anti-IL-33 antibody that inhibits IL-33 signalling via ST2 and RAGE/EGFR to reduce inflammation and epithelial dysfunction.

Interleukin (IL)-33 is a broad-acting alarmin cytokine that can drive inflammatory responses following tissue damage or infection and is a promising target for treatment of inflammatory disease. Here, we describe the identification of tozorakimab (MEDI3506), a potent, human anti-IL-33 monoclonal antibody, which can inhibit reduced IL-33 (IL-33red) and oxidized IL-33 (IL-33ox) activities through distinct serum-stimulated 2 (ST2) and receptor for advanced glycation end products/epidermal growth factor receptor (RAGE/EGFR complex) signalling pathways. We hypothesized that a therapeutic antibody would require an affinity higher than that of ST2 for IL-33, with an association rate greater than 107 M-1 s-1, to effectively neutralize IL-33 following rapid release from damaged tissue. An innovative antibody generation campaign identified tozorakimab, an antibody with a femtomolar affinity for IL-33red and a fast association rate (8.5 × 107 M-1 s-1), which was comparable to soluble ST2. Tozorakimab potently inhibited ST2-dependent inflammatory responses driven by IL-33 in primary human cells and in a murine model of lung epithelial injury. Additionally, tozorakimab prevented the oxidation of IL-33 and its activity via the RAGE/EGFR signalling pathway, thus increasing in vitro epithelial cell migration and repair. Tozorakimab is a novel therapeutic agent with a dual mechanism of action that blocks IL-33red and IL-33ox signalling, offering potential to reduce inflammation and epithelial dysfunction in human disease.

Feasibility and Acceptability of a Virtual "Coping with Brain Fog" Intervention for Improving Cognitive Functioning in Young Adults with Cancer.

Purpose: Cancer-related cognitive deficits (CRCDs) are common among young adults (YAs) (ages: 18-39) with cancer and can be debilitating. We aimed to determine the feasibility and acceptability of a virtual Coping with Brain Fog intervention among YAs with cancer. Our secondary aims were to explore the intervention's effect on cognitive functioning and psychological distress. Methods: This prospective feasibility study involved eight weekly, 90-minute virtual group sessions. Sessions focused on psychoeducation on CRCD, memory skills, task management, and psychological well-being. The primary outcomes were feasibility and acceptability of the intervention evaluated through attendance (>60% not missing >2 consecutive sessions) and satisfaction (Client Satisfaction Questionnaire [CSQ] score >20). Secondary outcomes included the following: cognitive functioning (Functional Assessment of Cancer Therapy-Cognitive Function [FACT-Cog] Scale) and symptoms of distress (Patient-Reported Outcomes Measurement Information System [PROMIS] Short Form-Anxiety/Depression/Fatigue) and participants' experiences using semistructured interviews. Paired t-tests and summative content analysis were used for quantitative and qualitative data analyses. Results: Twelve participants (five male, mean age = 33 years) were enrolled. All but one participant met feasibility criteria of not missing >2 consecutive sessions (11/12 = 92%). The mean CSQ score was 28.1 (standard deviation 2.5). Significant improvement in cognitive function as measured by FACT-Cog Scale was observed postintervention (p < 0.05). Ten participants adopted strategies from the program to combat CRCD, and eight reported CRCD symptom improvement. Conclusion: A virtual Coping with Brain Fog intervention is feasible and acceptable for the symptoms of CRCD among YAs with cancer. The exploratory data indicate subjective improvement in cognitive function, and will inform the design and implementation of a future clinical trial. ClinicalTrials.gov Registration: NCT05115422.

Investigating the effects of arginine methylation inhibitors on microdissected brain tumour biopsies maintained in a miniaturised perfusion system.

Arginine methylation is a post-translational modification that consists of the transfer of one or two methyl (CH3) groups to arginine residues in proteins. Several types of arginine methylation occur, namely monomethylation, symmetric dimethylation and asymmetric dimethylation, which are catalysed by different protein arginine methyltransferases (PRMTs). Inhibitors of PRMTs have recently entered clinical trials to target several types of cancer, including gliomas (NCT04089449). People with glioblastoma (GBM), the most aggressive form of brain tumour, are among those with the poorest quality of life and likelihood of survival of anyone diagnosed with cancer. There is currently a lack of (pre)clinical research on the possible application of PRMT inhibitors to target brain tumours. Here, we set out to investigate the effects of clinically-relevant PRMT inhibitors on GBM biopsies. We present a new, low-cost, easy to fabricate perfusion device that can maintain GBM tissue in a viable condition for at least eight days post-surgical resection. The miniaturised perfusion device enables the treatment of GBM tissue with PRMT inhibitors ex vivo, and we observed a two-fold increase in apoptosis in treated samples compared to parallel control experiments. Mechanistically, we show thousands of differentially expressed genes after treatment, and changes in the type of arginine methylation of the RNA binding protein FUS that are consistent with hundreds of differential gene splicing events. This is the first time that cross-talk between different types of arginine methylation has been observed in clinical samples after treatment with PRMT inhibitors.

Declining Comprehensiveness of Services Delivered by Canadian Family Physicians Is Not Driven by Early-Career Physicians.

We describe changes in the comprehensiveness of services delivered by family physicians in 4 Canadian provinces (British Columbia, Manitoba, Ontario, Nova Scotia) during the periods 1999-2000 and 2017-2018 and explore if changes differ by years in practice. We measured comprehensiveness using province-wide billing data across 7 settings (home, long-term care, emergency department, hospital, obstetrics, surgical assistance, anesthesiology) and 7 service areas (pre/postnatal care, Papanicolaou [Pap] testing, mental health, substance use, cancer care, minor surgery, palliative home visits). Comprehensiveness declined in all provinces, with greater changes in number of service settings than service areas. Decreases were no greater among new-to-practice physicians.

Optimizing biomarkers for accurate ependymoma diagnosis, prognostication, and stratification within International Clinical Trials: A BIOMECA study.

BACKGROUND: Accurate identification of brain tumor molecular subgroups is increasingly important. We aimed to establish the most accurate and reproducible ependymoma subgroup biomarker detection techniques, across 147 cases from International Society of Pediatric Oncology (SIOP) Ependymoma II trial participants, enrolled in the pan-European "Biomarkers of Ependymoma in Children and Adolescents (BIOMECA)" study. METHODS: Across 6 European BIOMECA laboratories, we evaluated epigenetic profiling (DNA methylation array); immunohistochemistry (IHC) for nuclear p65-RELA, H3K27me3, and Tenascin-C; copy number analysis via fluorescent in situ hybridization (FISH) and MLPA (1q, CDKN2A), and MIP and DNA methylation array (genome-wide copy number evaluation); analysis of ZFTA- and YAP1-fusions by RT-PCR and sequencing, Nanostring and break-apart FISH. RESULTS: DNA Methylation profiling classified 65.3% (n = 96/147) of cases as EPN-PFA and 15% (n = 22/147) as ST-ZFTA fusion-positive. Immunohistochemical loss of H3K27me3 was a reproducible and accurate surrogate marker for EPN-PFA (sensitivity 99%-100% across 3 centers). IHC for p65-RELA, FISH, and RNA-based analyses effectively identified ZFTA- and YAP-fused supratentorial ependymomas. Detection of 1q gain using FISH exhibited only 57% inter-center concordance and low sensitivity and specificity while MIP, MLPA, and DNA methylation-based approaches demonstrated greater accuracy. CONCLUSIONS: We confirm, in a prospective trial cohort, that H3K27me3 immunohistochemistry is a robust EPN-PFA biomarker. Tenascin-C should be abandoned as a PFA marker. DNA methylation and MIP arrays are effective tools for copy number analysis of 1q gain, 6q, and CDKN2A loss while FISH is inadequate. Fusion detection was successful, but rare novel fusions need more extensive technologies. Finally, we propose test sets to guide future diagnostic approaches.

Digital exclusion as a potential cause of inequalities in access to care: a survey in people with inflammatory rheumatic diseases.

Objectives: COVID-19 led to rapid uptake of digital health care. We sought to examine digital access, health and digital literacy, and impact on confidence and satisfaction with remote consultations in people with inflammatory rheumatic diseases (IRDs). Methods: People with IRDs (n = 2024) were identified from their electronic health record and invited to participate in a cross-sectional survey, using short message service (SMS) and postal approaches. Data were collected on demographics, self-reported diagnosis, access to and use of internet-enabled devices, health and digital literacy, together with confidence and satisfaction with remote consultations. Ethical approval was obtained (Ref 21/PR/0867). Results: Six hundred and thirty-nine (639) people completed the survey [mean (s.d.) age 64.5 (13.1) years, 384 (60.1%) female]. Two hundred and eighty-seven (44.9%) completed it online. One hundred and twenty-six (19.7%) people reported not having access to an internet-enabled device. Ninety-three (14.6%) reported never accessing the internet; this proportion was highest (23%) in people with RA. One hundred and seventeen (18%) reported limited health literacy. Even in those reporting internet use, digital literacy was only moderate. People with limited health or digital literacy or without internet access were less likely to report confidence or satisfaction with remote consultations. Conclusion: Limited health and digital literacy, lack of digital access and low reported internet use were common, especially in older people with RA. People with limited health literacy or limited digital access reported lower confidence and satisfaction with remote consultations. Digital implementation roll-out needs to take account of people requiring extra support to enable them to access care digitally or risks exacerbating health inequalities.

Experiences of adolescent and young adult cancer survivors during the COVID-19 pandemic.

PURPOSE: This study aimed to evaluate the impact of the COVID-19 pandemic on adolescent and young adult (AYA) cancer survivors. METHODS: We conducted a cross-sectional survey of AYAs aged 18-49 with cancer in Canada between January and February 2021. Data from survivors, defined as AYAs more than one year off cancer treatment, were analysed. Multiple logistic regression was used to identify factors associated with psychological distress, loneliness and insomnia. RESULTS: The analysis included 384 survivors. Moderate-to-severe psychological distress was reported by 257 (68.9%) survivors and was associated with an income ≥ $60,000 (adjusted odds ratio [AOR] 2.15, 95% CI 1.11-4.17) and the presence of a pre-existing chronic physical health condition (AOR 2.05, 95% CI 1.18-3.56). Loneliness was reported by 204 (54.0%) survivors and was associated with being unemployed (AOR 2.26 95%CI 1.18-4.31), pandemic causing finances to be worse (AOR 1.82, 95%CI 1.08-3.06) and the presence of a pre-pandemic mental health condition (AOR 1.88, 95% CI 1.03-3.42). Clinical insomnia was reported by 74 (19.5%) survivors and was associated with employment status as a student (AOR 3.00, 95% CI 1.08-8.29) or unemployed (AOR 3.97, 95% CI 1.46-10.83), earning $60,000 or more in the year 2020 (AOR 4.36, 95% CI 1.43-13.32), having haematologic cancer (AOR 2.21, 95% CI 1.05-4.70) and being single (AOR 2.52, 95% CI 1.08-5.91). Pandemic negatively affected employment, finances, physical activity, cancer care and substance use for 73.9%, 66.5%, 32.5%, 21.8% and 19.2% of survivors, respectively. Worries about finances, contracting COVID-19, cancer treatment increasing the risk of COVID-19 infection, and having poor health outcomes from contracting COVID-19 were reported by 46.0%, 45.6%, 55.0% and 47.3% of survivors, respectively. CONCLUSIONS: The COVID-19 pandemic has had a significant impact on AYA cancer survivors, and these individuals report high levels of psychological distress, insomnia and loneliness. IMPLICATIONS FOR CANCER SURVIVORS: Cancer survivors are at risk for worsening mental and physical health outcomes during the COVID-19 pandemic. Targeted interventions and support programs are urgently needed to support the mental health of AYA cancer survivors and optimize their health outcomes.

Rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis epidemiology in England from 2004 to 2020: An observational study using primary care electronic health record data.

Background: Contemporary data on rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritits (SpA) epidemiology in England are lacking. This knowledge is crucial to planning healthcare services. We updated algorithms defining patients with diagnoses of RA, PsA, and axial SpA in primary care and applied them to describe their incidence and prevalence in the Clinical Practice Research Datalink Aurum, an electronic health record (EHR) database covering ∼20% of England. Methods: Algorithms for ascertaining patients with RA, axial SpA, and PsA diagnoses validated in primary care EHR databases using Read codes were updated (to account for the English NHS change to SNOMED CT diagnosis coding) and applied. Updated diagnosis and synthetic disease-modifying anti-rheumatic drug code lists were devised by rheumatologists and general practitioners. Annual incidence/point-prevalence of RA, PsA, and axial SpA diagnoses were calculated from 2004 to 2020 and stratified by age/sex. Findings: Point-prevalence of RA/PsA diagnoses increased annually, peaking in 2019 (RA 0·779% [95% confidence interval (CI) 0·773, 0·784]; PsA 0·287% [95% CI 0·284, 0·291]) then falling slightly. Point-prevalence of axial SpA diagnoses increased annually (except in 2018/2019), peaking in 2020 (0·113% [95% CI 0·111, 0·115]). RA diagnosis annual incidence was higher between 2013-2019 (after inclusion in the Quality and Outcomes Framework, range 49·1 [95% CI 47·7, 50·5] to 52·1 [95% CI 50·6, 53·6]/100,000 person-years) than 2004-2012 (range 34·5 [95% CI 33·2, 35·7] to 40·0 [95% CI 38·6, 41·4]/100,000 person-years). Increases in the annual incidence of PsA/axial SpA diagnosis occurred following new classification criteria publication. Annual incidence of RA, PsA and axial SpA diagnoses fell by 40·1%, 67·4%, and 38·1%, respectively between 2019 and 2020, likely reflecting the COVID-19 pandemic's impact on their diagnosis. Interpretation: Recorded RA, PsA, and axial SpA diagnoses are increasingly prevalent in England, underlining the importance of organising healthcare services to provide timely, treat-to-target care to optimise the health of >1% of adults in England. Funding: National Institute for Health and Care Research (NIHR300826).

Prevalence and factors associated with insomnia symptoms in adolescents and young adults with cancer during the COVID-19 pandemic.

OBJECTIVE: The COVID-19 pandemic has been particularly distressing for adolescents and young adults (AYAs) diagnosed with cancer. High levels of distress are associated with sleep disturbances. This study examined the prevalence of insomnia symptoms in AYAs during the COVID-19 pandemic and identified factors related to greater insomnia severity. DESIGN, SETTING, AND PARTICIPANTS: An online survey was administered to Canadian AYAs (N = 805) diagnosed with cancer between 15 and 39 years from January to February 2021. MEASUREMENTS: The primary measure was the Insomnia Severity Index (ISI). Univariable and multivariable binomial logistic regression examined demographic, clinical, and psychological factors associated with significant insomnia symptoms (ISI score ≥12). RESULTS: Three hundred twelve (38.8%) participants reported insomnia symptoms. In the multivariable model, severe psychological distress (ie, depression and anxiety; adjusted odds ratio (AOR) = 28.75, p ≤.001), having a pre-existing mental health condition (AOR = 1.92, p = .03), worsened mental health during the pandemic (AOR = 1.73, p = .02), finished cancer treatment ≥1 year ago (AOR = 1.72, p = .03), and experiencing no changes to schooling during the COVID-19 pandemic (AOR = 2.18, p = .004) were associated with significant insomnia symptoms. Standardized coefficients also indicated that worrying about possible disruptions to cancer care and being a homemaker/caretaker contributed to insomnia symptoms. CONCLUSIONS: Nearly 40% of AYAs with cancer reported insomnia symptoms during the COVID-19 pandemic. Insomnia was associated with potentially modifiable factors such as psychological distress, highlighting possible targets for intervention.

Scoping Review of Studies Evaluating Frailty and Its Association with Medication Harm.

INTRODUCTION: Frailty is associated with an increased risk of death and morbid events. Frail individuals are known to have multiple comorbidities which are often associated with polypharmacy. Whilst a relationship between polypharmacy and frailty has been demonstrated, it is not clear if there is an independent relationship between frailty and medication harm. AIMS: This scoping review aimed to identify and critically appraise studies evaluating medication harm in patients with frailty. METHODS: PubMed, EMBASE, CINAHL and Cochrane databases were searched from inception until 1 February 2021 using key search terms that are synonymous with frailty (such as frail and frail elderly) and medication harm (such as adverse drug events and adverse drug reactions). To be included, studies must have identified medication harm as a primary or secondary outcome measure, and used a frailty assessment tool to determine frailty, or clearly defined how frailty was assessed. Data were narratively synthesised and presented in tables. The checklist from the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies from the National Heart, Lung, and Blood Institute was used to assess the quality and risk of bias of studies that met the inclusion criteria. RESULTS: Of 2685 retrieved abstracts, 24 underwent full-text review and nine studies met the inclusion criteria. Three studies were retrospective cohort studies, and six were prospective observational studies. Six studies comprised two distinct groups of frail and non-frail individuals, and the remaining three studies evaluated medication harm in an entirely frail population. Seven studies used validated frailty tools such as the Clinical Frailty Scale, Fried Frailty Index, and Fried Frailty Phenotype. Two studies measured frailty using self-defined criteria. Overall, frail individuals were at risk of medication harm with rates ranging between 18.7 and 77% across the nine studies. However, whether frailty is an independent predictor of medication harm remains uncertain, as this was only evaluated in one study. The risk of bias assessment identified limitations in methods and reporting with all nine studies. CONCLUSION: This scoping review identified nine studies evaluating medication harm in frail patients. However, all were limited by the methodological quality and inadequate reporting of study factors. There are few high-quality studies that described a relationship between medication harm and frailty. More robust studies are required that examine the independent relationship between frailty and medication harm, after adjusting for all possible confounders and in particular polypharmacy.

Psychological distress and experiences of Adolescents and Young Adults with cancer during the COVID-19 pandemic: A cross-sectional survey.

BACKGROUND: This study investigated prevalence of psychological distress, factors associated with distress, and experiences of Adolescents and Young Adults (AYAs) with cancer during the COVID-19 pandemic. It also compared distress in this group to previously surveyed Canadian AYAs with cancer in 2018 by the Young Adults with Cancer in their Prime (YACPRIME) study. METHODS: A cross-sectional, online, self-administered survey of AYAs diagnosed with cancer between 15 and 39 years of age was conducted. Psychological distress was measured by the Kessler Psychological Distress Scale (K10). Associations between variables and high psychological distress (K10 ≥ 25), and comparison of prevalence of psychological distress with the YACPRIME study were done using multivariable logistic regression. Summative qualitative content analysis analyzed participant experiences during this pandemic. RESULTS: We included 805 participants. High psychological distress was present in over two-thirds of the group (68.0%; 95% CI, 64.7%-71.2%). Employment impact during pandemic (AOR (adjusted odds ratio), 2.16; 95% CI, 1.41-3.31) and hematologic malignancy (AOR, 1.76; 95% CI 1.08-2.97) were associated with higher psychological distress, while older age [AOR, 0.95; 95% CI, 0.92-0.99] and personal income < $40,000 (AOR, 0.38; 95% CI, 0.24-0.58) were associated with lower distress. Adjusted odds of experiencing psychological distress among AYAs with cancer during pandemic compared to pre-pandemic years was 1.85 (95% CI: 1.36-2.53). Overarching themes of pandemic experiences included: inferior quality of life, impairment of cancer care, COVID-19 related concerns and extreme social isolation. CONCLUSION: AYAs diagnosed with cancer are experiencing high psychological distress during this pandemic. Distress screening and evidence-based interventions to alleviate distress are essential.

Analgesic prescribing in patients with inflammatory arthritis in England: an observational study using electronic healthcare record data.

OBJECTIVES: International data suggest inflammatory arthritis (IA) pain management frequently involves opioid prescribing, despite little evidence of efficacy, and potential harms. We evaluated analgesic prescribing in English National Health Service-managed patients with IA. METHODS: Repeated cross-sectional analyses in the Consultations in Primary Care Archive (primary care consultation and prescription data in nine general practices from 2000 to 2015) evaluated the annual prevalence of analgesic prescriptions in: (i) IA cases (RA, PsA or axial spondyloarthritis [SpA]), and (ii) up to five age-, sex- and practice-matched controls. Analgesic prescriptions were classified into basic, opioids, gabapentinoids and oral NSAIDs, and sub-classified into chronic and intermittent (≥3 and 1-2 prescriptions per calendar year, respectively). RESULTS: In 2000, there were 594 cases and 2652 controls, rising to 1080 cases and 4703 controls in 2015. In all years, most (65.3-78.5%) cases received analgesics, compared with fewer (37.5-41.1%) controls. Opioid prescribing in cases fell between 2000 and 2015 but remained common with 45.4% (95% CI: 42.4%, 48.4%) and 32.9% (95% CI: 29.8%, 36.0%) receiving at least 1 and ≥3 opioid prescriptions, respectively, in 2015. Gabapentinoid prescription prevalence in cases increased from 0% in 2000 to 9.5% (95% CI: 7.9%, 11.4%) in 2015, and oral NSAID prescription prevalence fell from 53.7% (95% CI: 49.6%, 57.8%) in 2000 to 25.0% (95% CI: 22.4%, 27.7%) in 2015. Across years, analgesic prescribing was commoner in RA than PsA/axial SpA, and 1.7-2.0 times higher in cases than controls. CONCLUSIONS: Analgesic prescribing in IA is common. This is at variance with existing evidence of analgesic efficacy and risks, and guidelines. Interventions are needed to improve analgesic prescribing in this population.

COVID-19-Related Information Sources, Behavioral Changes, and Adherence to Social Distancing Among Adolescents and Young Adults with Cancer.

Purpose: This study aimed to assess the sources of COVID-19 information used, behavioral changes in response to the pandemic, and factors associated with adherence to social distancing guidelines among adolescents and young adults (AYAs) with cancer during the COVID-19 pandemic. Methods: We conducted a self-administered online survey of AYAs with cancer (aged 18-39 years) diagnosed between ages 15 and 39 and living in Canada during January and February 2021. Data were summarized using descriptive statistics. Multiple logistic regression was used to identify the factors associated with adherence to the social distancing guidelines. Results: In total, 805 AYAs were included. Participants were most likely to obtain COVID-19-related information from social media (60.5%), news reports (51.6%), and medical professionals (46.5%). The preferred modes of receiving information were websites of cancer organizations (47.9%), social media (44.8%), and medical professionals (40.2%). The common behavioral changes in response to the COVID-19 pandemic included wearing a protective mask (60.2%), avoiding crowded and public places (56.9%), and abiding by social distancing rules (49.4%). On multivariable analysis, participants were more likely to adhere to social distancing rules if they were women, unemployed or collecting disability/unemployment benefits, or had a personal income of <$40,000 in year 2020 (p < 0.05). Conclusion: Social media and websites of cancer organizations are the preferred modes of COVID-19 information. Since many AYAs are nonadherent to preventative health measures, cancer organizations should help develop and disseminate digital resources that provide tailored information to AYAs with cancer during this pandemic.

Loneliness among adolescents and young adults with cancer during the COVID-19 pandemic: a cross-sectional survey.

BACKGROUND: Adolescents and young adults (AYAs) diagnosed with cancer are at an increased risk of experiencing social isolation and loneliness secondary to their cancer and its treatment. The physical distancing measures implemented during the COVID-19 pandemic may have further increased loneliness among this group. This study examined the prevalence of loneliness and factors associated with loneliness among AYAs with cancer during this pandemic. METHODS: We conducted a self-administered, online, cross-sectional survey of Canadian AYAs diagnosed with cancer between 15 and 39 between January and February 2021. Loneliness was measured using the 3-item UCLA Loneliness Scale. Factors associated with higher levels of loneliness were identified using multiple logistic regression. RESULTS: The analysis included 805 AYAs. The prevalence of loneliness was 52.2% [N = 419, 95% CI (confidence interval) 48.7 to 55.6%]. Individuals who were 18-25 years old [AOR (adjusted odds ratio)1.60, CI 1.03-2.47, p = 0.035], currently undergoing cancer therapy (AOR 1.46, 95% CI 1.03-2.07, p = 0.035), who self-disclosed the presence of a pre-pandemic mental health condition (AOR 2.09, 95% CI = 1.22-3.58, p = 0.007), or were not in a relationship (AOR 2.22, 95% CI 1.57-3.14, p < 0.001) were more likely to report loneliness than others. Participants that lived in rural or remote locations were less likely to experience loneliness (AOR 0.59, 95%CI 0.40-0.87, p = 0.008). CONCLUSION: One in two AYAs with cancer are feeling lonely during the COVID-19 pandemic. Future studies for developing interventions to target loneliness, particularly for those at greater risk, are necessary to improve the health and quality of life of AYAs with cancer.