Vitamin D metabolism in critically ill patients with acute kidney injury: a prospective observational study.

BACKGROUND: Vitamin D deficiency in critically ill patients is associated with poor outcomes, and vitamin D supplementation is recommended for patients with chronic kidney disease. Whether acute kidney injury (AKI) is associated with altered Vitamin D metabolism is unknown. We aimed to compare the longitudinal profiles of serum 25(OH)D and 1,25(OH)2D concentrations in critically ill patients with and without moderate to severe AKI and explore the impact of renal recovery and parathyroid hormone (PTH). METHODS: In this prospective, observational study in two centres in the UK, critically ill patients with and without AKI underwent serial measurement of serum 25(OH)D and 1,25(OH)2D and plasma PTH concentrations for 5 days. Linear mixed model analysis and sensitivity analyses were performed. RESULTS: Serial data of 137 patients were analysed. Seventy-one patients had AKI stage II/III of whom 23 recovered kidney function during the 5-day study period; 66 patients did not have AKI at enrolment of whom 14 developed new AKI. On day of enrolment, patients' serum 25(OH)D concentrations were low (median 18 nmol/L) but there was no significant difference between patients with and without AKI. Median serum 1,25(OH)2D levels were significantly lower in patients with AKI II/III (41 pmol/L [IQR 26, 58]) compared to similarly unwell patients without AKI (54 pmol/L [IQR 33, 69]) during the 5-day period. Recovery of kidney function in patients with AKI was associated with a rise in 1,25(OH)2D concentrations. Plasma PTH results were impacted by serum calcium and magnesium levels but not associated with 1,25(OH)2D levels. CONCLUSIONS: Critically ill patients with moderate-to-severe AKI have significantly lower serum 1,25(OH)2D concentrations than similarly sick patients without AKI but there was no difference in serum 25(OH)D concentrations. Recovery of AKI was associated with a rise in serum 1,25(OH)2D concentrations. More research is needed to investigate the health benefits and safety of supplementation with active vitamin D in critically ill patients with moderate-to-severe AKI. Trial registration Clinicaltrials.gov (NCT02869919), registered on 16 May 2016.

Costs of UK community care for individuals with recessive dystrophic epidermolysis bullosa: Findings of the Prospective Epidermolysis Bullosa Longitudinal Evaluation Study.

Background: Recessive dystrophic epidermolysis bullosa (RDEB) is a rare inherited skin fragility disorder requiring multidisciplinary management. Information regarding costs of current standard treatment is scant. Objectives: As part of a longitudinal natural history study, we explored the community care costs of UK patients with different forms of RDEB. Methods: Fifty-nine individuals with RDEB provided detailed information on multiple facets of RDEB including disease severity scores (iscorEB, BEBS) and patient reported outcomes (quality of life evaluation in epidermolysis bullosa, iscorEB patient questionnaire). Costs data included time spent doing dressings, frequency of dressing changes, details of materials used, and paid and unpaid care. Results: Overall costs of dressing materials and associated care were high in RDEB. Median annual costs across all subtypes for those using dressings (n = 51) were over £26 000. For severe RDEB (RDEB-S), median costs were almost £90 000 per annum, with a median of 18 h per week spent on dressing changes. Half of working-age adults with RDEB were unemployed and 39% of carers were unable to take on full-time or part-time paid employment, adding to indirect costs and the financial burden from RDEB on families and society. Conclusions: The findings demonstrate the high costs of care of RDEB, particularly for RDEB-S. The current expense supports the drive to develop new therapies which accelerate wound healing and diminish total wound burden, thereby reducing costs of dressings and care. While costly to bring to market, these might ultimately reduce the overall cost of treatment and also the impact on individuals living with this rare disease. The data also highlight the need for adequate reimbursement for EB care which can place significant financial strain on families.

Hypertension prevalence, coding and control in an urban primary care setting in the UK between 2014 and 2021.

OBJECTIVE: Hypertension is a leading preventable cause of mortality, yet high rates of undiagnosed and uncontrolled hypertension continue. The burden falls most heavily on some ethnic minorities and the socially deprived, with the COVID-19 pandemic having further widened inequalities. We sought to determine the prevalence and predictors of unmeasured blood pressure (BP), uncoded elevated BP and uncontrolled hypertension in primary care across 2014-2021. METHODS: A population-based cohort study using data from all 41 general practices in a socioeconomically diverse inner-city borough. BP measurements, sociodemographic, lifestyle and clinical factors were extracted from anonymized primary care data. Hypertension and BP control were defined using NICE guidelines. Associations between patient characteristics and hypertension outcomes were identified using logistical regression modelling. RESULTS: Of 549 082 patients, 39.5% had unmeasured BP; predictors included male sex [AOR 2.40, 95% confidence interval (95% CI) 2.26-2.43] and registration in the pandemic years. Of 71 970 adults with elevated BP, 36.0% were uncoded; predictors included obesity (AOR 2.51, 95% CI 2.42-2.60) and increasing age. Of 44 648 adults on the hypertension register, 46.8% had uncontrolled hypertension; predictors included black ethnicity compared to white (AOR 1.54, 95% CI 1.41-1.68) and cardiovascular co-morbidities (AOR 1.23, 95% CI 1.21-1.25). Social deprivation was only weakly or not significantly associated with hypertension outcomes. CONCLUSION: The burden of uncoded elevated BP and uncontrolled hypertension is high. Obesity and male sex were associated with uncoded elevated BP and uncontrolled hypertension. Black ethnicity was associated with uncontrolled hypertension. Initiatives are needed to optimize hypertension coding and control, with an emphasis on specific population subgroups.

Itch in recessive dystrophic epidermolysis bullosa: findings of PEBLES, a prospective register study.

BACKGROUND: Itch is common and distressing in epidermolysis bullosa (EB) but has not previously been studied in depth in different recessive dystrophic EB (RDEB) subtypes. OBJECTIVES: As part of a prospective register study of the natural history of RDEB we explored features of itch, medications used, and correlation with disease severity and quality of life. METHODS: Fifty individuals with RDEB aged 8 years and above completed the Leuven Itch Scale (LIS) (total 243 reviews over a 7-year period). Data included itch frequency, severity, duration, distress, circumstances, consequences, itch surface area and medications for itch. The iscorEB disease severity score and the validated EB quality of life tool, QOLEB, were compared to LIS domains and analysed by RDEB subtype. RESULTS: Itch was frequent, present in the preceding month in 93% of reviews. Itch severity and distress were significantly greater in severe (RDEB-S) and pruriginosa (RDEB-Pru) subtypes compared to intermediate RDEB (RDEB-I). Itch medications were reported in just over half of reviews including emollients, topical corticosteroids and antihistamines; the proportion of participants not using medication despite frequent pruritus suggests limited efficacy. In inversa RDEB (RDEB-Inv) and RDEB-I, LIS domains correlated with iscorEB and QOLEB. In contrast to previous studies, correlations were lacking in RDEB-S suggesting that global disease burden relatively reduces the contribution of itch. CONCLUSIONS: This comprehensive study of RDEB-associated itch highlights differences between RDEB subtypes, suggests an unmet need for effective treatments and could serve as control data for future clinical trials incorporating itch as an endpoint.

Self-start HIV postexposure prophylaxis (PEPSE), to reduce time to first dose and increase efficacy.

BACKGROUND: Effectiveness of HIV postexposure prophylaxis (PEPSE) correlates with speed of uptake following HIV exposure. Time to first dose has not improved in the UK for over 10 years. On-demand pre-exposure prophylaxis (PrEP) has shown that people can self-start medication for HIV prevention.We hypothesised that advanced provision of PEPSE (HOME PEPSE) for men who have sex with men (MSM) to self- initiate would reduce time to first dose following HIV exposure. METHODS: Phase IV, randomised, prospective, 48-week, open-label study was carried out. MSM at medium risk of acquiring HIV were randomised (1:1) to immediate or deferred standard of care (SOC) HOME PEPSE. Every 12 weeks, participants self-completed mental health/risk behaviour surveys and had HIV/sexually transmitted infection (STI) testing.HOME PEPSE comprised a 5-day pack of emtricitabine/tenofovir disoproxil fumarate/maraviroc 600 mg once daily initiated following potential exposure to HIV. If taken, participants completed a risk survey; PEPSE continuation was physician directed. Primary outcome was time from potential exposure to HIV to first PEPSE dose. FINDINGS: 139 participants randomised 1:1; 69 to immediate HOME PEPSE and 70 to deferred HOME PEPSE. Median age 30 years (IQR 26-39), 75% white, 55% UK born and 72% university educated. 31 in HOME PEPSE and 15 in SOC arm initiated PEPSE. Uptake of HOME PEPSE was appropriate in 27/31 cases (87%, 95% CI: 71% to 95%). Median time from exposure to first dose was 7.3 hours (3.0, 20.9) for HOME PEPSE and 28.5 hours (17.3, 34.0) for SOC (p<0.01). HOME PEPSE was well tolerated with no discontinuations.No significant differences in missed opportunities for PEPSE uptake, sexual behaviour or bacterial STI infections between treatment arms. INTERPRETATION: HOME PEPSE reduced the time from exposure to first-dose PEPSE by 21+ hours, with no impact on safety. This significantly improves the efficacy of PEPSE and provides an option for people declining PrEP.

Inequalities in developing multimorbidity over time: A population-based cohort study from an urban, multi-ethnic borough in the United Kingdom.

BACKGROUND: Social and material deprivation accelerate the development of multimorbidity, yet the mechanisms which drive multimorbidity pathways and trajectories remain unclear. We aimed to examine the association between health inequality, risk factors and accumulation or resolution of LTCs, taking disease sequences into consideration. METHODS: We conducted a retrospective cohort of adults aged 18 years and over, registered between April 2005 and May 2020 in general practices in one inner London borough (n = 826,936). Thirty-two long term conditions (LTCs) were selected using a consensus process, based on a definition adapted to the demographic characteristics of the local population. sThe development and resolution of these LTCs were examined according to sociodemographic and clinical risk factors (hypertension; moderate obesity (BMI 30·0-39·9 kg/m2), high cholesterol (total cholesterol > 5 mmol/L), smoking, high alcohol consumption (>14 units per week), and psychoactive substance use), through the application of multistate Markov chain models. FINDINGS: Participants were followed up for a median of 4.2 years (IQR = 1·8 - 8·4); 631,760 (76%) entered the study with no LTCs, 121,424 (15%) with 1 LTC, 41,720 (5%) with 2 LTCs, and 31,966 (4%) with three or more LTCs. At the end of follow-up, 194,777 (24%) gained one or more LTCs, while 45,017 (5%) had resolved LTCs and 27,021 (3%) died. In multistate models, deprivation (hazard ratio [HR] between 1·30 to 1·64), female sex (HR 1·13 to 1·20), and Black ethnicity (HR 1·20 to 1·30; vs White) were independently associated with increased risk of transition from one to two LTCs, and shorter time spent in a healthy state. Substance use was the strongest risk factor for multimorbidity with an 85% probability of gaining LTCs over the next year. First order Markov chains identified consistent disease sequences including: chronic pain or osteoarthritis followed by anxiety and depression; alcohol and substance dependency followed by HIV, viral hepatitis, and liver disease; and morbid obesity followed by diabetes, hypertension, and chronic pain. INTERPRETATION: We examined the relations among 32 LTCs, taking the order of disease occurrence into consideration. Distinctive patterns for the development and accumulation of multimorbidity have emerged, with increased risk of transitioning from no conditions to multimorbidity and mortality related to ethnicity, deprivation and gender. Musculoskeletal disorders, morbid obesity and substance abuse represent common entry points to multimorbidity trajectories.

Applying resolved and remission codes reduced prevalence of multimorbidity in an urban multi-ethnic population.

OBJECTIVE: To estimate the prevalence and determinants of multimorbidity in an urban, multi-ethnic area over 15-years and investigate the effect of applying resolved/remission codes on prevalence estimates. STUDY DESIGN AND SETTING: This is a population-based retrospective cross-sectional study using electronic health records of adults registered between 2005 -2020 in general practices in one inner London borough (n = 826,936). Classification of resolved/remission was based on clinical coding defined by the patient's general practitioner. RESULTS: The crude and age-adjusted prevalence of multimorbidity over the study period were 21.2% (95% CI: 21.1 -21.3) and 30.8% (30.6 -31.0), respectively. Applying resolved/remission codes decreased the crude and age-adjusted prevalence estimates to 18.0% (95% CI: 17.9 -18.1) and 27.5% (27.4 -27.7). Asthma (53.2%) and depression (20.2%) were responsible for most resolved and remission codes. Substance use (Adjusted Odds Ratio 10.62 [95% CI: 10.30 -10.95]), high cholesterol (2.48 [2.44 -2.53]), and moderate obesity (2.19 [2.15 -2.23]) were the strongest risk factor determinants of multimorbidity outside of advanced age. CONCLUSION: Our study highlights the importance of applying resolved/remission codes to obtain an accurate prevalence and the increased burden of multimorbidity in a young, urban, and multi-ethnic population. Understanding modifiable risk factors for multimorbidity can assist policymakers in designing effective interventions to reduce progression to multimorbidity.

Identifying longitudinal clusters of multimorbidity in an urban setting: A population-based cross-sectional study.

BACKGROUND: Globally, there is increasing research on clusters of multimorbidity, but few studies have investigated multimorbidity in urban contexts characterised by a young, multi-ethnic, deprived populations. This study identified clusters of associative multimorbidity in an urban setting. METHODS: This is a population-based retrospective cross-sectional study using electronic health records of all adults aged 18 years and over, registered between April 2005 to May 2020 in general practices in one inner London borough. Multiple correspondence analysis and cluster analysis was used to identify groups of multimorbidity from 32 long-term conditions (LTCs). RESULTS: The population included 41 general practices with 826,936 patients registered between 2005 and 2020, with mean age 40 (SD15·6) years. The prevalence of multimorbidity was 21% (n = 174,881), with the median number of conditions being three and increasing with age. Analysis identified five consistent LTC clusters: 1) anxiety and depression (Ratio of within- to between- sum of squares (WSS/BSS <0·01 to <0·01); 2) heart failure, atrial fibrillation, chronic kidney disease (CKD), chronic heart disease (CHD), stroke/transient ischaemic attack (TIA), peripheral arterial disease (PAD), dementia and osteoporosis (WSS/BSS 0·09 to 0·12); 3) osteoarthritis, cancer, chronic pain, hypertension and diabetes (0·05 to 0·06); 4) chronic liver disease and viral hepatitis (WSS/BSS 0·02 to 0·03); 5) substance dependency, alcohol dependency and HIV (WSS/BSS 0·37 to 0·55). INTERPRETATION: Mental health problems, pain, and at-risk behaviours leading to cardiovascular diseases are the important clusters identified in this young, urban population. FUNDING: Impact on Urban Health, United Kingdom.