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.

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.

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.

Early-onset burdensome multimorbidity: an exploratory analysis of sentinel conditions, condition accrual sequence and duration of three long-term conditions using the 1970 British Cohort Study.

OBJECTIVES: The prevalence of multiple long-term condition (LTC) multimorbidity is increasing with younger onset among socioeconomically deprived populations. Research on life course trajectories towards multimorbidity is limited and early-onset multimorbidity poorly characterised. Understanding sentinel conditions (the first LTC occurring in the life course), the sequence of LTC accrual and the permanency of the reporting of LTCs may help identify time points for prevention efforts. We used a longitudinal birth cohort to estimate the prevalence of a common three-condition early-onset multimorbidity (multiple long-term condition multimorbidity (MLTC-M)) group at midlife, describe the frequency of sentinel conditions, the sequence of LTC accrual and explore the permanency of one of these conditions: psychological distress. SETTING: 1970 British Cohort Study (BCS70). PARTICIPANTS: 17 196 cohort members born in 1970. OUTCOME MEASURES: Prevalence of the most common three-condition multimorbidity group at age 46. The nature and timing of sentinel conditions, the sequencing patterns of subsequent LTC accrual and the permanency of the reporting of psychological distress. RESULTS: At age 46 high blood pressure, psychological distress and back pain were the most common three-condition MLTC-M group, (4.3%, n=370). A subgroup of 164 (44.3%) people provided complete information on LTC across all time points. Psychological distress measured by the Malaise Index was the most common sentinel condition, occurring in 25.0% (n=41), followed by back pain (22%, n=36). At age 26, 45.1% (75/164) reported their sentinel condition. The most common sequence of LTC accrual was the co-reporting of psychological distress and back pain followed by high blood pressure. Almost one-third (30.5%, n=50) reported a variation of psychological distress across the adult life course. CONCLUSION: In these exploratory analyses, psychological distress and back pain were the most common sentinel conditions, and along with high blood pressure these three conditions represented the most common three-condition MLTC-M group. These analyses suggest that birth cohorts, like the BCS70, may usefully inform life course-multimorbidity research.

Change in treatment burden among people with multimorbidity: a follow-up survey.

BACKGROUND: Treatment burden is the effort required of patients to look after their health and the impact this has on their functioning and wellbeing. Little is known about change in treatment burden over time for people with multimorbidity. AIM: To quantify change in treatment burden, determine factors associated with this change, and evaluate a revised single-item measure for high treatment burden in older adults with multimorbidity. DESIGN AND SETTING: A 2.5-year follow-up of a cross-sectional postal survey via six general practices in Dorset, England. METHOD: GP practices identified participants of the baseline survey. Data on treatment burden (measured using the Multimorbidity Treatment Burden Questionnaire; MTBQ), sociodemographics, clinical variables, health literacy, and financial resource were collected. Change in treatment burden was described, and associations assessed using regression models. Diagnostic test performance metrics evaluated the revised single-item measure relative to the MTBQ. RESULTS: In total, 300 participants were recruited (77.3% response rate). Overall, there was a mean increase of 2.6 (standard deviation 11.2) points in treatment burden global score. Ninety-eight (32.7%) and 53 (17.7%) participants experienced an increase and decrease, respectively, in treatment burden category. An increase in treatment burden was associated with having >5 long-term conditions (adjusted ß 8.26, 95% confidence interval [CI] = 4.20 to 12.32) and living >10 minutes (versus ≤10 minutes) from the GP (adjusted ß 3.88, 95% CI = 1.32 to 6.43), particularly for participants with limited health literacy (mean difference: adjusted ß 9.59, 95% CI = 2.17 to 17.00). The single-item measure performed moderately (sensitivity 55.7%; specificity 92.4%. CONCLUSION: Treatment burden changes over time. Improving access to primary care, particularly for those living further away from services, and enhancing health literacy may mitigate increases in burden.

A pilot trial investigating the feasibility of a future randomised controlled trial of Individualised Placement and Support for people unemployed with chronic pain recruiting in primary care.

BACKGROUND: We investigated the feasibility of recruiting patients unemployed for more than 3 months with chronic pain using a range of methods in primary care in order to conduct a pilot trial of Individual Placement and Support (IPS) to improve quality of life outcomes for people with chronic pain. METHODS: This research was informed by people with chronic pain. We assessed the feasibility of identification and recruitment of unemployed patients; the training and support needs of employment support workers to integrate with pain services; acceptability of randomisation, retention through follow-up and appropriate outcome measures for a definitive trial. Participants randomised to IPS received integrated support from an employment support worker and a pain occupational therapist to prepare for, and take up, a work placement. Those randomised to Treatment as Usual (TAU) received a bespoke workbook, delivered at an appointment with a research nurse not trained in vocational rehabilitation. RESULTS: Using a range of approaches, recruitment through primary care was difficult and resource-intensive (1028 approached to recruit 37 eligible participants). Supplementing recruitment through pain services, another 13 people were recruited (total n = 50). Randomisation to both arms was acceptable: 22 were allocated to IPS and 28 to TAU. Recruited participants were generally not 'work ready', particularly if recruited through pain services. CONCLUSION: A definitive randomised controlled trial is not currently feasible for recruiting through primary care in the UK. Although a trial recruiting through pain services might be possible, participants could be unrepresentative in levels of disability and associated health complexities. Retention of participants over 12 months proved challenging, and methods for reducing attrition are required. The intervention has been manualised.

Persistently normal blood tests in patients taking methotrexate for RA or azathioprine for IBD: a retrospective cohort study.

BACKGROUND: Disease-modifying anti-rheumatic drugs (DMARDs), including methotrexate and azathioprine, are commonly used to treat rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). Blood-test safety monitoring is mainly undertaken in primary care. Normal blood results are common. AIM: To determine the frequency and associations of persistently normal blood tests in patients with RA prescribed methotrexate, and patients with IBD prescribed azathioprine. DESIGN AND SETTING: Two-year retrospective study of a cohort taken from an electronic pseudonymised primary care/laboratory database covering >1.4 million patients across Hampshire, UK. METHOD: Patients with RA and IBD, and associated methotrexate and azathioprine prescriptions, respectively, were identified. Tests and test thresholds recommended by the National Institute for Health and Care Excellence were applied. Persistent normality was defined as no abnormalities of any tests nor alanine aminotransferase (ALT), white blood count (WBC), neutrophils, and estimated glomerular filtration rate (eGFR) individually. Logistic regression was used to identify associations with test normality. RESULTS: Of 702 265 adults, 7102 had RA and 8597 had IBD. In total, 3001 (42.3%) patients with RA were prescribed methotrexate and 1162 (13.5%) patients with IBD were prescribed azathioprine; persistently normal tests occurred in 1585 (52.8%) and 657 (56.5%) of the populations, respectively. In patients with RA on methotrexate, 585 (19.5%) had eGFR, 219 (7.3%) ALT, 217 (7.2%) WBC, and 202 (6.7%) neutrophil abnormalities. In patients with IBD on azathioprine, 138 (11.9%) had WBC, 88 (7.6%) eGFR, 72 (6.2%) ALT, and 65 (5.6%) neutrophil abnormalities. Those least likely to have persistent test normality were older and/or had comorbidities. CONCLUSION: Persistent test normality is common when monitoring these DMARDs, with few hepatic or haematological abnormalities. More stratified monitoring approaches should be explored.

Change in glomerular filtration rate over time in the Oxford Renal Cohort Study: observational study.

BACKGROUND: Decline in kidney function can result in adverse health outcomes. The Oxford Renal Cohort Study has detailed baseline assessments from 884 participants ≥60 years of age. AIM: To determine the proportion of participants with a decline in estimated glomerular filtration rate (eGFR), identify determinants of decline, and determine proportions with chronic kidney disease (CKD) remission. DESIGN AND SETTING: Observational cohort study in UK primary care. METHOD: Data were used from baseline and annual follow-up assessments to monitor change in kidney function. Rapid eGFR decline was defined as eGFR decrease >5 ml/min/1.73 m2/year, improvement as eGFR increase >5 ml/min/1.73 m2/year, and remission in those with CKD at baseline and eGFR >60 ml/min/1.73 m2 during follow-up. Cox proportional hazard models were used to identify factors associated with eGFR decline. RESULTS: There was a net decline in eGFR in the 884 participants over 5 years of follow-up. In 686 participants with >2 eGFR tests with a median follow-up of 2.1 years, 164 (24%) evidenced rapid GFR decline, 185 (27%) experienced eGFR improvement, and 82 of 394 (21%) meeting CKD stage 1-4 at baseline experienced remission. In the multivariable analysis, smoking status, higher systolic blood pressure, and being known to have CKD at cohort entry were associated with rapid GFR decline. Those with CKD stage 3 at baseline were less likely to exhibit GFR decline compared with normal kidney function. CONCLUSION: This study established that 24% of people evidenced rapid GFR decline whereas 21% evidenced remission of CKD. People at risk of rapid GFR decline may benefit from closer monitoring and appropriate treatment to minimise risks of adverse outcomes, although only a small proportion meet the National Institute for Health and Care Excellence criteria for referral to secondary care.

Price versus clinical guidelines in primary care statin prescribing: a retrospective cohort study and cost simulation model.

OBJECTIVE: To investigate the relative impact of generic entry and National Institute for Health and Care Excellence clinical guidelines on prescribing using statins as an exemplar. DESIGN: Retrospective analysis of statin prescribing in primary care and cost simulation model. SETTING: Royal College of General Practitioners Research and Surveillance Centre (RCGP R&SC) database and Prescription Cost Analysis (PCA) database. PARTICIPANTS: New patients prescribed statins for the first time between July 2003 and September 2018. MAIN OUTCOME MEASURES: Shares of new patients prescribed one of the five statins available in the British National Formulary, and cost of prescribing statins to new and existing patients in primary care in England. RESULTS: General trends of statin' prescriptions were largely driven by a decrease in acquisition costs triggered by patent expiration, preceding NICE guidelines which themselves did not seem to affect prescription trends. Significant heterogeneity is observed in the prescription of the most cost-effective statin acrossGPs. A cost simulation shows that, between 2004 and 2018, the NHS could have saved £2.8bn (around 40% of the £6.3bn spent on statins during this time) if all GP practices had prescribed only the most cost-effective treatment. CONCLUSIONS: There is potential for large savings for the NHS if new and, whenever possible, ongoing patients are promptly switched to the first medicine that becomes available as generic within a therapeutic class as long as it has similar efficacy to still-patented medicines.

Characterising risk of non-steroidal anti-inflammatory drug-related acute kidney injury: a retrospective cohort study.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed for pain and inflammation. NSAID complications include acute kidney injury (AKI), causing burden to patients and health services through increased morbidity, mortality, and hospital admissions. AIM: To measure the extent of NSAID prescribing in an adult population, the degree to which patients with potential higher risk of AKI were exposed to NSAIDs, and to quantify their risk of AKI. DESIGN & SETTING: Retrospective 2-year closed-cohort study. METHOD: A retrospective cohort of adults was identified from a pseudonymised electronic primary care database in Hampshire, UK. The cohort had clinical information, prescribing data, and complete GP- and hospital-ordered biochemistry data. NSAID exposure (minimum one prescription in a 2-month period) was categorised as never, intermittent, and continuous, and first AKI using the national AKI e-alert algorithm. Descriptive statistics and logistic regression were used to explore NSAID prescribing patterns and AKI risk. RESULTS: The baseline population was 702 265. NSAID prescription fell from 19 364 (2.8%) to 16 251 (2.4%) over 2 years. NSAID prescribing was positively associated with older age, female sex, greater socioeconomic deprivation, and certain comorbidities (diabetes, hypertension, osteoarthritis, and rheumatoid arthritis) and negatively with cardiovascular disease (CVD) and heart failure. Among those prescribed NSAIDs, AKI was associated with older age, greater deprivation, chronic kidney disease (CKD), CVD, heart failure, diabetes, and hypertension. CONCLUSION: Despite generally good prescribing practice, NSAID prescribing was identified in some people at higher risk of AKI (for example, patients with CKD and older) for whom medication review and NSAID deprescribing should be considered.

Integrating primary care and social services for older adults with multimorbidity: a qualitative study.

BACKGROUND: Growing demand from an increasingly ageing population with multimorbidity has resulted in complex health and social care needs requiring more integrated services. Integrating primary care with social services could utilise resources more efficiently, and improve experiences for patients, their families, and carers. There is limited evidence on progress including key barriers to and drivers of integration to inform large-scale national change. AIM: To elicit stakeholder views on drivers and barriers of integrated primary care and social services, and highlight opportunities for successful implementation. DESIGN AND SETTING: A qualitative interview study. METHOD: Semi-structured interviews with maximum variation sampling to capture stakeholder views across services and professions. RESULTS: Thirty-seven interviews were conducted across England with people including GPs, nurses, social care staff, commissioners, local government officials, voluntary and private sector workers, patients, and carers. Drivers of integration included groups of like-minded individuals supported by good leadership, expanded interface roles to bridge gaps between systems, and co-location of services. Barriers included structural and interdisciplinary tension between professions, organisational self-interest, and challenges in record sharing. CONCLUSION: Drivers and barriers to integration identified in other contexts are also present in primary care and social services. Benefits of integration are unlikely to be realised if these are not addressed in the design and execution of new initiatives. Efforts should go beyond local- and professional-level change to include wider systems- and policy-level initiatives. This will support a more systems-wide approach to integrated care reform, which is necessary to meet the complex and growing needs of an ageing multimorbid population.

Treatment burden for patients with multimorbidity: cross-sectional study with exploration of a single-item measure.

BACKGROUND: Treatment burden is the effort required of patients to look after their health, and the impact this has on their wellbeing. Quantitative data on treatment burden for patients with multimorbidity are sparse, and no single-item treatment burden measure exists. AIM: To determine the extent of, and associations with, high treatment burden among older adults with multimorbidity, and to explore the performance of a novel single-item treatment burden measure. DESIGN AND SETTING: Cross-sectional postal survey via general practices in Dorset, UK. METHOD: Patients ≥55 years, living at home, with three or more long-term conditions (LTCs) were identified by practices. Treatment burden was measured using the Multimorbidity Treatment Burden Questionnaire. Data collected were sociodemographics, LTCs, medications, and characteristics including health literacy and financial resource. Associations with high treatment burden were investigated via logistic regression. Performance of a novel single-item measure of treatment burden was also evaluated. RESULTS: A total of 835 responses were received (response rate 42%) across eight practices. Patients' mean age was 75 years, 55% were female (n = 453), and 99% were white (n = 822). Notably, 39% of patients self-reported fewer than three LTCs (n = 325). Almost one-fifth (18%) of responders reported high treatment burden (n = 150); making lifestyle changes and arranging appointments were particular sources of difficulty. After adjustment, limited health literacy and financial difficulty displayed strong associations with high treatment burden; more LTCs and more prescribed regular medications were also independently associated. The single-item measure discriminated moderately between high and non-high burden with a sensitivity of 89%, but a specificity of 58%. CONCLUSION: High treatment burden was relatively common, underlining the importance of minimising avoidable burden. More vulnerable patients, with less capacity to manage, are at greater risk of being overburdened. Further development of a single-item treatment burden measure is required.

Patients' and kidney care team's perspectives of treatment burden and capacity in older people with chronic kidney disease: a qualitative study.

OBJECTIVE: Chronic kidney disease (CKD) is often a multimorbid condition and progression to more severe disease is commonly associated with increased management requirements, including lifestyle change, more medication and greater clinician involvement. This study explored patients' and kidney care team's perspectives of the nature and extent of this workload (treatment burden) and factors that support capacity (the ability to manage health) for older individuals with CKD. DESIGN: Qualitative semistructured interview and focus group study. SETTING AND PARTICIPANTS: Adults (aged 60+) with predialysis CKD stages G3-5 (identified in two general practitioner surgeries and two renal clinics) and a multiprofessional secondary kidney care team in the UK. RESULTS: 29 individuals and 10 kidney team members were recruited. Treatment burden themes were: (1) understanding CKD, its treatment and consequences, (2) adhering to treatments and management and (3) interacting with others (eg, clinicians) in the management of CKD. Capacity themes were: (1) personal attributes (eg, optimism, pragmatism), (2) support network (family/friends, service providers), (3) financial capacity, environment (eg, geographical distance to unit) and life responsibilities (eg, caring for others). Patients reported poor provision of CKD information and lack of choice in treatment, whereas kidney care team members discussed health literacy issues. Patients reported having to withdraw from social activities and loss of employment due to CKD, which further impacted their capacity. CONCLUSION: Improved understanding of and measures to reduce the treatment burden (eg, clear information, simplified medication, joined up care, free parking) associated with CKD in individuals as well as assessment of their capacity and interventions to improve capacity (social care, psychological support) will likely improve patient experience and their engagement with kidney care services.

Health-related quality of life, functional impairment and comorbidity in people with mild-to-moderate chronic kidney disease: a cross-sectional study.

OBJECTIVES: To determine the associations between comorbidities, health-related quality of life (HRQoL) and functional impairment in people with mild-to-moderate chronic kidney disease (CKD) in primary care. DESIGN: Cross-sectional analysis at 5-year follow-up in a prospective cohort study. SETTING: Thirty-two general practitioner surgeries in England. PARTICIPANTS: 1008 participants with CKD stage 3 (of 1741 people recruited at baseline in the Renal Risk in Derby study) who survived to 5 years and had complete follow-up data for HRQoL and functional status (FS). PRIMARY AND SECONDARY OUTCOME MEASURES: HRQoL assessed using the 5-level EQ-5D version (EQ-5D-5L, with domains of mobility, self-care, usual activities, pain/discomfort and anxiety/depression and index value using utility scores calculated from the English general population), and FS using the Karnofsky Performance Status scale (functional impairment defined as Karnofksy score ≤70). Comorbidity was defined by self-reported or doctor-diagnosed condition, disease-specific medication or blood result. RESULTS: Mean age was 75.8 years. The numbers reporting some problems in EQ-5D-5L domains were: 582 (57.7%) for mobility, 166 (16.5%) for self-care, 466 (46.2%) for usual activities, 712 (70.6%) for pain/discomfort and 319 (31.6%) for anxiety/depression. Only 191 (18.9%) reported no problems in any domain. HRQoL index values showed greater variation among those with lower FS (eg, for those with Karnofsky score of 60, the median (IQR) EQ-5D index value was 0.45 (0.24 to 0.68) compared with 0.94 (0.86 to 1) for those with Karnofsky score of 90). Overall, 234 (23.2%) had functional impairment.In multivariable logistic regression models, functional impairment was independently associated with experiencing problems for all EQ-5D-5L domains (mobility: OR 16.87 (95% CI 8.70 to 32.79, p<0.001, self-care: OR 13.08 (95% CI 8.46 to 20.22), p<0.001, usual activities: OR 8.27 (95% CI 5.43 to 12.58), p<0.001, pain/discomfort: OR 2.94 (95% CI 1.86 to 4.67), p<0.001, anxiety/depression: 3.08 (95% CI 2.23 to 4.27), p<0.001). Higher comorbidity count and obesity were independently associated with problems in mobility, self-care, usual activities and pain/discomfort: for three or more comorbidities versus none: (mobility: OR 2.10 (95% CI 1.08 to 4.10, p for trend 0.002), self-care: OR 2.64 (95% CI 0.72 to 9.67, p for trend 0.05), usual activities: OR 4.20 (95% CI 2.02 to 8.74, p for trend <0.001), pain/discomfort: OR 3.06 (95% CI 1.63 to 5.73, p for trend <0.001)), and for obese (body mass index (BMI) ≥30 kg/m2) versus BMI <25 kg/m2: (mobility: OR 2.44 (95% CI 1.61 to 3.69, p for trend <0.001), self-care: OR 1.98 (95% CI 1.06 to 3.71, p for trend 0.003), usual activities: OR 1.82 (95% CI 1.19 to 2.76, p for trend 0.019), pain/discomfort: OR 2.37 (95% CI 1.58 to 3.55, p for trend <0.001)). Female sex, lower FS and lower educational attainment were independently associated with anxiety/depression (ORs 1.60 (95% CI 1.18 to 2.16, p 0.002), 3.08 (95% CI 2.23 to 4.27, p<0.001) and 1.67 (95% CI 1.10 to 2.52, p 0.009), respectively). Older age, higher comorbidity count, albuminuria (≥30 mg/mmol vs <3 mg/mmol), lower educational attainment (no formal qualifications vs degree level) and obesity were independently associated with functional impairment (ORs 1.07 (95% CI 1.04 to 1.09, p<0.001), 2.18 (95% CI 0.80 to 5.96, p for trend <0.001), 1.74 (95% CI 0.82 to 3.68, p for trend 0.005), 2.08 (95% CI 1.26 to 3.41, p for trend <0.001) and 4.23 (95% CI 2.48 to 7.20), respectively). CONCLUSIONS: The majority of persons with mild-to-moderate CKD reported reductions in at least one HRQoL domain, which were independently associated with comorbidities, obesity and functional impairment. TRIAL REGISTRATION NUMBER: National Institute for Health Research Clinical Research Portfolio Study Number 6632.

Chronic kidney disease: identification and management in primary care.

Chronic kidney disease (CKD) is an important and common noncommunicable condition globally. In national and international guidelines, CKD is defined and staged according to measures of kidney function that allow for a degree of risk stratification using commonly available markers. It is often asymptomatic in its early stages, and early detection is important to reduce future risk. The risk of cardiovascular outcomes is greater than the risk of progression to end-stage kidney disease for most people with CKD. CKD also predisposes to acute kidney injury - a major cause of morbidity and mortality worldwide. Although only a small proportion of people with CKD progress to end-stage kidney disease, renal replacement therapy (dialysis or transplantation) represents major costs for health care systems and burden for patients. Efforts in primary care to reduce the risks of cardiovascular disease, acute kidney injury, and progression are therefore required. Monitoring renal function is an important task, and primary care clinicians are well placed to oversee this aspect of care along with the management of modifiable risk factors, particularly blood pressure and proteinuria. Good primary care judgment is also essential in making decisions about referral for specialist nephrology opinion. As CKD commonly occurs alongside other conditions, consideration of comorbidities and patient wishes is important, and primary care clinicians have a key role in coordinating care while adopting a holistic, patient-centered approach and providing continuity. This review aims to summarize the vital role that primary care plays in predialysis CKD care and to outline the main considerations in its identification, monitoring, and clinical management in this context.

Perspectives on differing health outcomes by city: accounting for Glasgow's excess mortality.

Several health outcomes (including mortality) and health-related behaviors are known to be worse in Scotland than in comparable areas of Europe and the United Kingdom. Within Scotland, Greater Glasgow (in West Central Scotland) experiences disproportionately poorer outcomes independent of measurable variation in socioeconomic status and other important determinants. Many reasons for this have been proposed, particularly related to deprivation, inequalities, and variation in health behaviors. The use of models (such as the application of Bradford Hill's viewpoints on causality to the different hypotheses) has provided useful insights on potentially causal mechanisms, with health behaviors and inequalities likely to represent the strongest individual candidates. This review describes the evolution of our understanding of Glasgow's excess mortality, summarizes some of the key work in this area, and provides some suggestions for future areas of exploration. In the context of demographic change, the experience in Glasgow is an important example of the complexity that frequently lies behind observed variations in health outcomes within and between populations. A comprehensive explanation of Glasgow's excess mortality may continue to remain elusive, but is likely to lie in a complex and difficult-to-measure interplay of health determinants acting at different levels in society throughout the life course. Lessons learned from the detailed examination of different potentially causative determinants in Scotland may provide useful methodological insights that may be applied in other settings. Ongoing efforts to unravel the causal mechanisms are needed to inform public health efforts to reduce health inequalities and improve outcomes in Scotland.