Potentially modifiable factors associated with health-related quality of life among people with chronic kidney disease: baseline findings from the National Unified Renal Translational Research Enterprise CKD (NURTuRE-CKD) cohort.

Background: Many non-modifiable factors are associated with poorer health-related quality of life (HRQoL) experienced by people with chronic kidney disease (CKD). We hypothesize that potentially modifiable factors for poor HRQoL can be identified among CKD patients, providing potential targets for intervention. Method: The National Unified Renal Translational Research Enterprise Chronic Kidney Disease (NURTuRE-CKD) cohort study recruited 2996 participants from nephrology centres with all stages of non-dialysis-dependent CKD. Baseline data collection for sociodemographic, anthropometric, biochemical and clinical information, including Integrated Palliative care Outcome Scale renal, Hospital Anxiety and Depression score (HADS) and the 5-level EuroQol-5D (EQ-5D-5L) as HRQoL measure, took place between 2017 and 2019. EQ-5D-5L dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) were mapped to an EQ-5D-3L value set to derive index value. Multivariable mixed effects regression models, adjusted for known factors affecting HRQoL with recruitment region as a random effect, were fit to assess potentially modifiable factors associated with index value (linear) and within each dimension (logistic). Results: Among the 2958/2996 (98.7%) participants with complete EQ-5D data, 2201 (74.4%) reported problems in at least one EQ-5D-5L dimension. Multivariable linear regression identified independent associations between poorer HRQoL (EQ-5D-3L index value) and obesity (body mass index ≥30.0 kg/m2, ß -0.037, 95% CI -0.058 to -0.016, P = .001), HADS depression score ≥8 (ß -0.159, -0.182 to -0.137, P < .001), anxiety score ≥8 (ß -0.090, -0.110 to -0.069, P < .001), taking ≥10 medications (ß -0.065, -0.085 to -0.046, P < .001), sarcopenia (ß -0.062, -0.080 to -0.043, P < .001) haemoglobin <100 g/L (ß -0.047, -0.085 to -0.010, P = .012) and pain (ß -0.134, -0.152 to -0.117, P < .001). Smoking and prescription of prednisolone independently associated with problems in self-care and usual activities respectively. Renin-angiotensin system inhibitor (RASi) prescription associated with fewer problems with mobility and usual activities. Conclusion: Potentially modifiable factors including obesity, pain, depression, anxiety, anaemia, polypharmacy, smoking, steroid use and sarcopenia associated with poorer HRQoL in this cohort, whilst RASi use was associated with better HRQoL in two dimensions.

Primary and secondary care service use and costs associated with frailty in an ageing population: longitudinal analysis of an English primary care cohort of adults aged 50 and over, 2006-2017.

BACKGROUND: Frailty becomes more prevalent and healthcare needs increase with age. Information on the impact of frailty on population level use of health services and associated costs is needed to plan for ageing populations. AIM: To describe primary and secondary care service use and associated costs by electronic Frailty Index (eFI) category. DESIGN AND SETTING: Retrospective cohort using electronic health records. Participants aged ≥50 registered in primary care practices contributing to the Oxford Royal College of General Practitioners Research and Surveillance Centre, 2006-2017. METHODS: Primary and secondary care use (totals and means) were stratified by eFI category and age group. Standardised 2017 costs were used to calculate primary, secondary and overall costs. Generalised linear models explored associations between frailty, sociodemographic characteristics. Adjusted mean costs and cost ratios were produced. RESULTS: Individual mean annual use of primary and secondary care services increased with increasing frailty severity. Overall cohort care costs for were highest in mild frailty in all 12 years, followed by moderate and severe, although the proportion of the population with severe frailty can be expected to increase over time. After adjusting for sociodemographic factors, compared to the fit category, individual annual costs doubled in mild frailty, tripled in moderate and quadrupled in severe. CONCLUSIONS: Increasing levels of frailty are associated with an additional burden of individual service use. However, individuals with mild and moderate frailty contribute to higher overall costs. Earlier intervention may have the most potential to reduce service use and costs at population level.

Management of spontaneous dissection and rupture of common iliac artery in vascular Ehlers-Danlos syndrome (VEDS).

A 28-year-old male with history of vascular Ehlers-Danlos syndrome (VEDS) presented with left lower extremity acute limb ischemia. Computed tomography angiography demonstrated spontaneous dissection of the left common iliac artery with occlusion and associated contained rupture . Successful stent placement without associated complications was achieved with the following principles: (1) open arterial exposure for endovascular intervention; (2) no touch technique vessel dissection; (3) circumferential proximal arterial felt cuff reinforcement to reduce systolic pulse wave stretch on sutures, and in case of emergent ligation; and (4) pledgetted "preclose U" stitch monofilament suture prior to access.

A conceptual framework for characterising lifecourse determinants of multiple long-term condition multimorbidity.

Objective: Social, biological and environmental factors in early-life, defined as the period from preconception until age 18, play a role in shaping the risk of multiple long-term condition multimorbidity. However, there is a need to conceptualise these early-life factors, how they relate to each other, and provide conceptual framing for future research on aetiology and modelling prevention scenarios of multimorbidity. We develop a conceptual framework to characterise the population-level domains of early-life determinants of future multimorbidity. Method: This work was conducted as part of the Multidisciplinary Ecosystem to study Lifecourse Determinants and Prevention of Early-onset Burdensome Multimorbidity (MELD-B) study. The conceptualisation of multimorbidity lifecourse determinant domains was shaped by a review of existing research evidence and policy, and co-produced with public involvement via two workshops. Results: Early-life risk factors incorporate personal, social, economic, behavioural and environmental factors, and the key domains discussed in research evidence, policy, and with public contributors included adverse childhood experiences, socioeconomics, the social and physical environment, and education. Policy recommendations more often focused on individual-level factors as opposed to the wider determinants of health discussed within the research evidence. Some domains highlighted through our co-production process with public contributors, such as religion and spirituality, health screening and check-ups, and diet, were not adequately considered within the research evidence or policy. Conclusions: This co-produced conceptualisation can inform research directions using primary and secondary data to investigate the early-life characteristics of population groups at risk of future multimorbidity, as well as policy directions to target public health prevention scenarios of early-onset multimorbidity.

What makes a multidisciplinary medication review and deprescribing intervention for older people work well in primary care? A realist review and synthesis.

BACKGROUND: A third of older people take five or more regular medications (polypharmacy). Conducting medication reviews in primary care is key to identify and reduce/ stop inappropriate medications (deprescribing). Recent recommendations for effective deprescribing include shared-decision making and a multidisciplinary approach. Our aim was to understand when, why, and how interventions for medication review and deprescribing in primary care involving multidisciplinary teams (MDTs) work (or do not work) for older people. METHODS: A realist synthesis following the Realist And Meta-narrative Evidence Syntheses: Evolving Standards guidelines was completed. A scoping literature review informed the generation of an initial programme theory. Systematic searches of different databases were conducted, and documents screened for eligibility, with data extracted based on a Context, Mechanisms, Outcome (CMO) configuration to develop further our programme theory. Documents were appraised based on assessments of relevance and rigour. A Stakeholder consultation with 26 primary care health care professionals (HCPs), 10 patients and three informal carers was conducted to test and refine the programme theory. Data synthesis was underpinned by Normalisation Process Theory to identify key mechanisms to enhance the implementation of MDT medication review and deprescribing in primary care. FINDINGS: A total of 2821 abstracts and 175 full-text documents were assessed for eligibility, with 28 included. Analysis of documents alongside stakeholder consultation outlined 33 CMO configurations categorised under four themes: 1) HCPs roles, responsibilities and relationships; 2) HCPs training and education; 3) the format and process of the medication review 4) involvement and education of patients and informal carers. A number of key mechanisms were identified including clearly defined roles and good communication between MDT members, integration of pharmacists in the team, simulation-based training or team building training, targeting high-risk patients, using deprescribing tools and drawing on expertise of other HCPs (e.g., nurses and frailty practitioners), involving patents and carers in the process, starting with 'quick wins', offering deprescribing as 'drug holidays', and ensuring appropriate and tailored follow-up plans that allow continuity of care and management. CONCLUSION: We identified key mechanisms that could inform the design of future interventions and services that successfully embed deprescribing in primary care.

Multidisciplinary ecosystem to study lifecourse determinants and prevention of early-onset burdensome multimorbidity (MELD-B) - protocol for a research collaboration.

Background: Most people living with multiple long-term condition multimorbidity (MLTC-M) are under 65 (defined as 'early onset'). Earlier and greater accrual of long-term conditions (LTCs) may be influenced by the timing and nature of exposure to key risk factors, wider determinants or other LTCs at different life stages. We have established a research collaboration titled 'MELD-B' to understand how wider determinants, sentinel conditions (the first LTC in the lifecourse) and LTC accrual sequence affect risk of early-onset, burdensome MLTC-M, and to inform prevention interventions. Aim: Our aim is to identify critical periods in the lifecourse for prevention of early-onset, burdensome MLTC-M, identified through the analysis of birth cohorts and electronic health records, including artificial intelligence (AI)-enhanced analyses. Design: We will develop deeper understanding of 'burdensomeness' and 'complexity' through a qualitative evidence synthesis and a consensus study. Using safe data environments for analyses across large, representative routine healthcare datasets and birth cohorts, we will apply AI methods to identify early-onset, burdensome MLTC-M clusters and sentinel conditions, develop semi-supervised learning to match individuals across datasets, identify determinants of burdensome clusters, and model trajectories of LTC and burden accrual. We will characterise early-life (under 18 years) risk factors for early-onset, burdensome MLTC-M and sentinel conditions. Finally, using AI and causal inference modelling, we will model potential 'preventable moments', defined as time periods in the life course where there is an opportunity for intervention on risk factors and early determinants to prevent the development of MLTC-M. Patient and public involvement is integrated throughout.

Treatment burden in multiple long-term conditions: a mixed-methods study protocol.

BACKGROUND: Treatment burden represents the work patients undertake because of their health care, and the impact of that effort on the patient. Most research has focused on older adults (aged >65 years) with multiple long-term conditions (multimorbidity) (MLTC-M), but there are now more younger adults (aged 18-65 years) living with MLTC-M and they may experience treatment burden differently. Understanding experiences of treatment burden, and identifying those most at risk of high treatment burden, are important for designing primary care services to meet their needs. AIM: To understand the treatment burden associated with MLTC-M, for people aged 18-65 years, and how primary care services affect this burden. DESIGN & SETTING: Mixed-methods study in up to 33 primary care practices in two UK regions. METHOD: The following two approaches will be used: (i) in-depth qualitative interviews with adults living with MLTC-M (approximately 40 participants) to understand their experiences of treatment burden and the impact of primary care, with a think-aloud aspect to explore face validity of a novel short treatment burden questionnaire (STBQ) for routine clinical use in the initial 15 interviews; (ii) cross-sectional patient survey (approximately 1000 participants), with linked routine medical record data to examine the factors associated with treatment burden for people living with MLTC-M, and to test the validity of STBQ. CONCLUSION: This study will generate in-depth understanding of the treatment burden experienced by people aged 18-65 years living with MLTC-M, and how primary care services affect this burden. This will inform further development and testing of interventions to reduce treatment burden, and potentially influence MLTC-M trajectories and improve health outcomes.

Associations with age and glomerular filtration rate in a referred population with chronic kidney disease: methods and baseline data from a UK multicentre cohort study (NURTuRE-CKD).

BACKGROUND: Chronic kidney disease (CKD) is common but heterogenous and is associated with multiple adverse outcomes. The National Unified Renal Translational Research Enterprise (NURTuRE)-CKD cohort was established to investigate risk factors for clinically important outcomes in persons with CKD referred to secondary care. METHODS: Eligible participants with CKD stages G3-4 or stages G1-2 plus albuminuria >30 mg/mmol were enrolled from 16 nephrology centres in England, Scotland and Wales from 2017 to 2019. Baseline assessment included demographic data, routine laboratory data and research samples. Clinical outcomes are being collected over 15 years by the UK Renal Registry using established data linkage. Baseline data are presented with subgroup analysis by age, sex and estimated glomerular filtration rate (eGFR). RESULTS: A total of 2996 participants was enrolled. Median (interquartile range) age was 66 (54-74) years, eGFR 33.8 (24.0-46.6) mL/min/1.73 m2 and urine albumin to creatinine ratio 209 (33-926) mg/g; 58.5% were male. Of these participants, 1883 (69.1%) were in high-risk CKD categories. Primary renal diagnosis was CKD of unknown cause in 32.3%, glomerular disease in 23.4% and diabetic kidney disease in 11.5%. Older participants and those with lower eGFR had higher systolic blood pressure and were less likely to be treated with renin-angiotensin system inhibitors (RASi) but were more likely to receive a statin. Female participants were less likely to receive a RASi or statin. CONCLUSIONS: NURTuRE-CKD is a prospective cohort of persons who are at relatively high risk of adverse outcomes. Long-term follow-up and a large biorepository create opportunities for research to improve risk prediction and to investigate underlying mechanisms to inform new treatment development.

The impact of non-alcoholic fatty liver disease and liver fibrosis on adverse clinical outcomes and mortality in patients with chronic kidney disease: a prospective cohort study using the UK Biobank.

BACKGROUND: Chronic kidney disease (CKD) and non-alcoholic fatty liver disease (NAFLD) frequently co-exist. We assess the impact of having NAFLD on adverse clinical outcomes and all-cause mortality for people with CKD. METHODS: A total of 18,073 UK Biobank participants identified to have CKD (eGFR < 60 ml/min/1.73 m2 or albuminuria > 3 mg/mmol) were prospectively followed up by electronic linkage to hospital and death records. Cox-regression estimated the hazard ratios (HR) associated with having NAFLD (elevated hepatic steatosis index or ICD-code) and NAFLD fibrosis (elevated fibrosis-4 (FIB-4) score or NAFLD fibrosis score (NFS)) on cardiovascular events (CVE), progression to end-stage renal disease (ESRD) and all-cause mortality. RESULTS: 56.2% of individuals with CKD had NAFLD at baseline, and 3.0% and 7.7% had NAFLD fibrosis according to a FIB-4 > 2.67 and NFS ≥ 0.676, respectively. The median follow-up was 13 years. In univariate analysis, NAFLD was associated with an increased risk of CVE (HR 1.49 [1.38-1.60]), all-cause mortality (HR 1.22 [1.14-1.31]) and ESRD (HR 1.26 [1.02-1.54]). Following multivariable adjustment, NAFLD remained an independent risk factor for CVE overall (HR 1.20 [1.11-1.30], p < 0.0001), but not ACM or ESRD. In univariate analysis, elevated NFS and FIB-4 scores were associated with increased risk of CVE (HR 2.42 [2.09-2.80] and 1.64 [1.30-2.08]) and all-cause mortality (HR 2.82 [2.48-3.21] and 1.82 [1.47-2.24]); the NFS score was also associated with ESRD (HR 5.15 [3.52-7.52]). Following full adjustment, the NFS remained associated with an increased incidence of CVE (HR 1.19 [1.01-1.40]) and all-cause mortality (HR 1.31 [1.13-1.52]). CONCLUSIONS: In people with CKD, NAFLD is associated with an increased risk of CVE, and the NAFLD fibrosis score is associated with an elevated risk of CVE and worse survival.

Frailty transitions and prevalence in an ageing population: longitudinal analysis of primary care data from an open cohort of adults aged 50 and over in England, 2006-2017.

INTRODUCTION: frailty is common in older adults and is associated with increased health and social care use. Longitudinal information is needed on population-level incidence, prevalence and frailty progression to plan services to meet future population needs. METHODS: retrospective open cohort study using electronic health records of adults aged ≥50 from primary care in England, 2006-2017. Frailty was calculated annually using the electronic Frailty Index (eFI). Multistate models estimated transition rates between each frailty category, adjusting for sociodemographic characteristics. Prevalence overall for each eFI category (fit, mild, moderate and severe) was calculated. RESULTS: the cohort included 2,171,497 patients and 15,514,734 person-years. Frailty prevalence increased from 26.5 (2006) to 38.9% (2017). The average age of frailty onset was 69; however, 10.8% of people aged 50-64 were already frail in 2006. Estimated transitions from fit to any level of frailty were 48/1,000 person-years aged 50-64, 130/1,000 person-years aged 65-74, 214/1,000 person-years aged 75-84 and 380/1,000 person-years aged ≥ 85. Transitions were independently associated with older age, higher deprivation, female sex, Asian ethnicity and urban dwelling. Mean time spent in each frailty category decreased with age, with the longest period spent in severe frailty at all ages. CONCLUSIONS: frailty is prevalent in adults aged ≥50 and time spent in successive frailty states is longer as frailty progresses, resulting in extended healthcare burden. Larger population numbers and fewer transitions in adults aged 50-64 present an opportunity for earlier identification and intervention. A large increase in frailty over 12 years highlights the urgency of informed service planning in ageing populations.

Modern treatment of a Klippel-Trenaunay syndrome patient with Palma procedure.

Klippel-Trenaunay syndrome is a rare congenital anomaly that is associated with abnormalities in the deep venous system. Operative intervention is often used only when patients fail conservative management for chronic venous insufficiency. We present a case of a deep venous abnormality requiring a saphenous vein crossover Palma procedure, in combination with a left femoral arteriovenous PTFE fistula to manage a non-healing wound from chronic venous insufficiency in a 22-year-old man. This case highlights updates for modern treatment tips for technical and medical management decisions to avoid early graft thrombosis.

What are the modifiable factors of treatment burden and capacity among people with Parkinson's disease and their caregivers: A qualitative study.

BACKGROUND: People with long-term conditions must complete many healthcare tasks such as take medications, attend appointments, and change their lifestyle. This treatment burden and ability to manage it (capacity) is not well-researched in Parkinson's disease. OBJECTIVE: To explore and identify potentially modifiable factors contributing to treatment burden and capacity in people with Parkinson's disease and caregivers. METHODS: Semi-structured interviews with nine people with Parkinson's disease and eight caregivers recruited from Parkinson's disease clinics in England (ages 59-84 years, duration of Parkinson's disease diagnosis 1-17 years, Hoehn and Yahr (severity of Parkinson's disease) stages 1-4) were conducted. Interviews were recorded and analyzed thematically. RESULTS: Four themes of treatment burden with modifiable factors were identified: 1) Challenges with appointments and healthcare access: organizing appointments, seeking help and advice, interactions with healthcare professionals, and caregiver role during appointments; 2) Issues obtaining satisfactory information: sourcing and understanding information, and satisfaction with information provision; 3) Managing medications: getting prescriptions right, organizing polypharmacy, and autonomy to adjust treatments; and 4) Lifestyle changes: exercise, dietary changes, and financial expenses. Aspects of capacity included access to car and technology, health literacy, financial capacity, physical and mental ability, personal attributes and life circumstances, and support from social networks. CONCLUSIONS: There are potentially modifiable factors of treatment burden including addressing the frequency of appointments, improving healthcare interactions and continuity of care, improving health literacy and information provision, and reducing polypharmacy. Some changes could be implemented at individual and system levels to reduce treatment burden for people with Parkinson's and their caregivers. Recognition of these by healthcare professionals and adopting a patient-centered approach may improve health outcomes in Parkinson's disease.

Role of foetal kidney size on kidney function in childhood: the born in bradford cohort renal study.

BACKGROUND: Foetal and early childhood development contributes to the risk of adult non-communicable diseases such as hypertension and cardiovascular disease. We aimed to investigate whether kidney size at birth is associated with markers of kidney function at 7-11 years. METHODS: Foetal kidney dimensions were measured using ultrasound scans at 34 weeks gestation and used to derive kidney volume (cm3) in 1802 participants in the Born in Bradford (BiB) birth cohort. Blood and urine samples were taken from those who participated in the BiB follow-up at 7-11 years (n = 630) and analysed for serum creatinine, cystatin C, urea, and urinary albumin to creatinine ratio (ACR), protein to creatinine ratio (PCR) and retinol binding protein (RBP). Estimated glomerular filtration rate (eGFR) was calculated using Schwartz creatinine only and combined with cystatin C, and cystatin C only Zappitelli and Filler equations. Linear regression was used to examine the association between foetal kidney volume and eGFR, ACR, PCR and blood pressure, unadjusted and adjusted for confounders. RESULTS: Kidney volume was positively associated in adjusted models with eGFR calculated using Schwartz combined (0.64 ml/min diff per unit increase in volume, 95% CI 0.25 to 1.02), Zappitelli (0.79, 95% CI 0.38 to 1.20) and Filler (2.84, 95% CI 1.40 to 4.28). There was an association with the presence of albuminuria but not with its level, or with other urinary markers or with blood pressure. CONCLUSION: Foetal kidney volume was associated with small increases in eGFR in mid-childhood. Longitudinal follow-up to investigate the relationship between kidney volume and markers of kidney function as children go through puberty is required.

Extra-Anatomic Bypass and Excision is Superior to Graft Salvage Attempts with Antibiotic Beads to Treat Vascular Graft Infections in the Groin.

BACKGROUND: This study aimed to determine if conventional extra-anatomic bypass and graft removal versus aggressive attempts at graft preservation have better survival and limb salvage in patients with localized groin wound infections of vascular grafts. METHODS: We conducted a retrospective review of 53 consecutive patients with vascular graft infections presenting in the groin. Treatment groups consisted of group 1 (extra-anatomic bypass and graft excision, n = 22) and group 2 (initial graft preservation attempts with utilization of antibiotic beads, n = 31). In group 2, patients underwent serial debridement and placement of antibiotic beads until culture-negative wounds were achieved. Significantly more patients underwent muscle flap coverage in group 2 (27/31) compared with group 1 (7/22; P < 0.001). Data collected included demographics, comorbidities, intraoperative details, and outcomes, including patency, limb salvage, mortality, and number of procedures. Continuous variables were examined with Student's t-test, and dichotomous variables were examined with chi-squared test. Linear and logistic regressions were used to analyze factors associated with outcomes, in addition to Kaplan-Meier analysis with log rank for actuarial analysis. RESULTS: Both groups were similar with respect to demographics. The overall Kaplan-Meier 1- and 3-year survival rates were 66.2% and 34.1%, with no statistically significant difference between groups. The Kaplan-Meier 1- and 3-year limb salvage rates were 68.8% and 36.6% for group 1 vs. 58.5% and 38.7% for group 2 (P = not significant [NS]). The 1- and 3-year primary patency rates were 71% and 71% in traditional group 1 vs. 72% and 56% in group 2 (P = NS). One-year and 3-year secondary patency rates in traditional group 1 were 83% and 71% vs. 85% and 61% in group 2 (P = NS). Patients in group 1 underwent fewer total procedures when compared with group 2 (2.3 ± 0.2 vs. 5.1 ± 0.7, P = 0.03). The late reinfection rate was significantly less in group 1 (4.5%) compared with group 2 (26%; P = 0.04). Freedom from reinfection at 1 and 3 years were 94% and 94% in traditional group 1 vs. 74% and 62% in group 2 (P = 0.03). Multivariable analysis showed a higher incidence of amputation in patients who suffered reinfection (n = 13, P = 0.049). There was a higher mortality in patients with septic shock (n = 10, P = 0.007) and reinfection (n = 13, P = 0.036). Reinfection was associated with the highest mortality (P = 0.03). CONCLUSIONS: Conventional graft excision with extra-anatomic bypass resulted in similar mortality when compared with aggressive attempts at graft preservation and trended toward improved limb salvage and patency. However, attempts at graft preservation with antibiotic beads resulted in a significantly higher reinfection rate and greater number of procedures, and therefore, this approach should be used very selectively.

Planetary health and sustainability teaching in UK medical education: A review of medical school curricula.

BACKGROUND: The doctors of the future need to be empowered to deliver healthcare sustainably while protecting their patients' health in the context of a degrading environment. This study aimed to objectively review the extent and nature of the teaching of planetary health and sustainability topics in UK medical education. METHODS: A multi-centre national review of the timetabled teaching sessions in medical courses in the UK during the academic year 2020/2021 against the General Medical Council's adopted 'Educating for Sustainable Healthcare - Priority Learning Outcomes'. Medical students were recruited and reviewed the entirety of their own institution's online teaching materials associated with core teaching sessions using a standardised data collection tool. Learning outcome coverage and estimated teaching time were calculated and used to rank participating medical schools. RESULTS: 45% of eligible UK medical schools were included in the study. The extent of teaching varied considerably amongst courses. Mean coverage of the 13 learning outcomes was 9.9 (SD:2.5) with a mean estimated teaching time of 140 min (SD:139). Courses with dedicated planetary health and sustainability sessions ranked best. CONCLUSION: There is large disparity in the education that medical students receive on these topics. Teaching may not adequately prioritise sustainability or reflect advances in planetary health knowledge.[Box: see text].

Influence of health-system change on treatment burden: a systematic review.

BACKGROUND: Treatment burden is a patient-centred concept describing the effort required of people to look after their health and the impact this has on their functioning and wellbeing. High treatment burden is more likely for people with multiple long-term conditions (LTCs). Validated treatment burden measures exist, but have not been widely used in practice or as research outcomes. AIM: To establish whether changes in organisation and delivery of health systems and services improve aspects contributing to treatment burden for people with multiple LTCs. DESIGN AND SETTING: Systematic review of randomised controlled trials (RCTs) investigating the impact of system-level interventions on at least one outcome relevant to previously defined treatment burden domains among adults with ≥2 LTCs. METHOD: The Embase, Ovid MEDLINE, and Web of Science electronic databases were searched for terms related to multimorbidity, system-level change, and treatment burden published between January 2010 and July 2021. Treatment burden domains were derived from validated measures and qualitative literature. Synthesis without meta-analysis (SWiM) methodology was used to synthesise results and study quality was assessed using the Cochrane risk-of-bias (version 2) tool. RESULTS: The searches identified 1881 articles, 18 of which met the review inclusion criteria. Outcomes were grouped into seven domains. There was some evidence for the effect of system-level interventions on some domains, but the studies exhibited substantial heterogeneity, limiting the synthesis of results. Some concern over bias gave low confidence in study results. CONCLUSION: System-level interventions may affect some treatment burden domains. However, adoption of a standardised outcome set, incorporating validated treatment burden measures, and the development of standard definitions for care processes in future research would aid study comparability.

Impact of the COVID-19 pandemic on prescription refills for immune-mediated inflammatory disorders: a time series analysis (January 2019 to January 2021) using the English Prescribing Dataset.

OBJECTIVE: To investigate monthly prescription refills for common immunosuppressive/immunomodulatory therapy (sulfasalazine, hydroxychloroquine, azathioprine, methotrexate, leflunomide) prescriptions in England during the complete first wave of the COVID-19 pandemic. Secondary analysis examined unit cost analysis and regional use. DESIGN AND SETTING: A national cohort of community-based, primary care patients who anonymously contribute data to the English Prescribing Dataset, dispensed in the community in England, were included. Descriptive statistics and interrupted time series analysis over 25 months (14 months before, 11 months after first lockdown) were evaluated (January 2019 to January 2021, with March 2020 as the cut-off point). OUTCOME MEASURES: Prescription reimbursement variance in period before the pandemic as compared with after the first lockdown. RESULTS: Fluctuation in monthly medicines use is noted in March 2020: a jump is observed for hydroxychloroquine (Mann-Whitney, SE 14.652, standardised test statistic 1.911, p value=0.059) over the study period. After the first lockdown, medicines use fluctuated, with wide confidence intervals. Unit-cost prices changed substantially: sulfasalazine 33% increase, hydroxychloroquine 98% increase, azathioprine 41% increase, methotrexate 41% increase, leflunomide 20% decrease. London showed the least quantity variance, suggesting more homogeneous prescribing and patient access compared with Midlands and East of England, suggesting that some patients may have received medication over/under requirement, representing potential resource misallocation and a proxy for adherence rates. Changepoint detection revealed four out of the five medicines' use patterns changed with a strong signal only for sulfasalazine in March/April 2020. CONCLUSIONS: Findings potentially present lower rates of adherence because of the pandemic, suggesting barriers to care access. Unit price increases are likely to have severe budget impacts in the UK and potentially globally. Timely prescription refills for patients taking immunosuppressive/immunomodulatory therapies are recommended. Healthcare professionals should identify patients on these medicines and assess their prescription-day coverage, with planned actions to flag and follow-up adherence concerns in patients.