Attainment of NICE blood pressure targets among older people with newly diagnosed hypertension: nationwide linked electronic health records cohort study.

BACKGROUND: it is not known if clinical practice reflects guideline recommendations for the management of hypertension in older people and whether guideline adherence varies according to overall health status. AIMS: to describe the proportion of older people attaining National Institute for Health and Care Excellence (NICE) guideline blood pressure targets within 1 year of hypertension diagnosis and determine predictors of target attainment. METHODS: a nationwide cohort study of Welsh primary care data from the Secure Anonymised Information Linkage databank including patients aged ≥65 years newly diagnosed with hypertension between 1st June 2011 and 1st June 2016. The primary outcome was attainment of NICE guideline blood pressure targets as measured by the latest blood pressure recording up to 1 year after diagnosis. Predictors of target attainment were investigated using logistic regression. RESULTS: there were 26,392 patients (55% women, median age 71 [IQR 68-77] years) included, of which 13,939 (52.8%) attained a target blood pressure within a median follow-up of 9 months. Success in attaining target blood pressure was associated with a history of atrial fibrillation (OR 1.26, 95% CI 1.11, 1.43), heart failure (OR 1.25, 95% CI 1.06, 1.49) and myocardial infarction (OR 1.20, 95% CI 1.10, 1.32), all compared to no history of each, respectively. Care home residence, the severity of frailty, and increasing co-morbidity were not associated with target attainment following adjustment for confounder variables. CONCLUSIONS: blood pressure remains insufficiently controlled 1 year after diagnosis in nearly half of older people with newly diagnosed hypertension, but target attainment appears unrelated to baseline frailty, multi-morbidity or care home residence.

Physical multimorbidity, depressive symptoms, and social participation in adults over 50 years of age: findings from the English Longitudinal Study of Ageing.

OBJECTIVES: The aim of the current study was to identify specific patterns of physical multimorbidity and examine how these patterns associated with changes in social participation over time. METHODS: We used latent class analysis to identify clusters of physical multimorbidity in 11,391 older adults. Mixed effects regression models were used to assess associations between physical multimorbidity clusters and changes in social participation over 15 years. RESULTS: Four clusters of physical multimorbidity were identified. All physical multimorbidity clusters were associated with a reduction in cultural engagement (e.g. visits to theatre, cinema, museums) over time, with the strongest association seen in the complex/multisystem cluster (ß = -0.26, 95% CI = -0.38 to -0.15). Similar results emerged for leisure activities. Adjusting for depressive symptoms fully attenuated some associations. All physical multimorbidity clusters were associated with an increase in civic participation over time. CONCLUSIONS: Physical multimorbidity reduced some aspects of social participation over time, with specific combinations of conditions having increased risk of reductions.Supplemental data for this article is available online at http://dx.doi.org/10.1080/13607863.2021.2017847.

Multimorbidity clusters among people with serious mental illness: a representative primary and secondary data linkage cohort study.

BACKGROUND: People with serious mental illness (SMI) experience higher mortality partially attributable to higher long-term condition (LTC) prevalence. However, little is known about multiple LTCs (MLTCs) clustering in this population. METHODS: People from South London with SMI and two or more existing LTCs aged 18+ at diagnosis were included using linked primary and mental healthcare records, 2012-2020. Latent class analysis (LCA) determined MLTC classes and multinominal logistic regression examined associations between demographic/clinical characteristics and latent class membership. RESULTS: The sample included 1924 patients (mean (s.d.) age 48.2 (17.3) years). Five latent classes were identified: 'substance related' (24.9%), 'atopic' (24.2%), 'pure affective' (30.4%), 'cardiovascular' (14.1%), and 'complex multimorbidity' (6.4%). Patients had on average 7-9 LTCs in each cluster. Males were at increased odds of MLTCs in all four clusters, compared to the 'pure affective'. Compared to the largest cluster ('pure affective'), the 'substance related' and the 'atopic' clusters were younger [odds ratios (OR) per year increase 0.99 (95% CI 0.98-1.00) and 0.96 (0.95-0.97) respectively], and the 'cardiovascular' and 'complex multimorbidity' clusters were older (ORs 1.09 (1.07-1.10) and 1.16 (1.14-1.18) respectively). The 'substance related' cluster was more likely to be White, the 'cardiovascular' cluster more likely to be Black (compared to White; OR 1.75, 95% CI 1.10-2.79), and both more likely to have schizophrenia, compared to other clusters. CONCLUSION: The current study identified five latent class MLTC clusters among patients with SMI. An integrated care model for treating MLTCs in this population is recommended to improve multimorbidity care.

Quality of acute myocardial infarction care in England and Wales during the COVID-19 pandemic: linked nationwide cohort study.

BACKGROUND AND OBJECTIVE: The impact of the COVID-19 pandemic on the quality of care for patients with acute myocardial infarction (AMI) is uncertain. We aimed to compare quality of AMI care in England and Wales during and before the COVID-19 pandemic using the 2020 European Society of Cardiology Association for Acute Cardiovascular Care quality indicators (QIs) for AMI. METHODS: Cohort study of linked data from the AMI and the percutaneous coronary intervention registries in England and Wales between 1 January 2017 and 27 May 2020 (representing 236 743 patients from 186 hospitals). At the patient level, the likelihood of attainment for each QI compared with pre COVID-19 was calculated using logistic regression. The date of the first national lockdown in England and Wales (23 March 2020) was chosen for time series comparisons. RESULTS: There were 10 749 admissions with AMI after 23 March 2020. Compared with before the lockdown, patients admitted with AMI during the first wave had similar age (mean 68.0 vs 69.0 years), with no major differences in baseline characteristics (history of diabetes (25% vs 26%), renal failure (6.4% vs 6.9%), heart failure (5.8% vs 6.4%) and previous myocardial infarction (22.9% vs 23.7%)), and less frequently had high Global Registry of Acute Coronary Events risk scores (43.6% vs 48.6%). There was an improvement in attainment for 10 (62.5%) of the 16 measured QIs including a composite QI (43.8% to 45.2%, OR 1.06, 95% CI 1.02 to 1.10) during, compared with before, the lockdown. CONCLUSION: During the first wave of the COVID-19 pandemic in England and Wales, quality of care for AMI as measured against international standards did not worsen, but improved modestly.

Changes in Serum Thyroid Function Predict Cognitive Decline in the Very Old: Longitudinal Findings from the Newcastle 85+ Study.

Background: Low serum thyrotropin (TSH) has been associated with an increased risk of cognitive impairment in observational studies of older individuals, but the mechanism underlying this is unclear. We investigated the association between changes in thyroid status and cognitive impairment in very old adults, using prospective data from the Newcastle 85+ study. Method: A cohort of 85-year-old individuals was assessed for health status and thyroid function. Complete data from a comprehensive multidimensional measure of health and repeat thyroid function were available for 642 participants with normal free thyroid hormones and TSH levels ranging between 0.1 and 10 mU/L. Cognitive performance, assessed using Mini-Mental State Examination (MMSE) and Cognitive Drug Research battery was examined by using linear mixed, logistic regression, and Cox proportional hazard models in relation to baseline and 3-year changes in serum TSH, free thyroxine (fT4), and free triiodothyronine (fT3). Results: Over 3 years, declining serum TSH was associated with reductions in fT4 and fT3, and an increased risk of incident cognitive impairment by 5 years (odds ratio1.77 [95% confidence interval: 1.19-2.61]; p = 0.004). A greater reduction in MMSE score was associated with larger TSH decline, at 3 (p = 0.001) and 5 years (p < 0.001), respectively. Steady fT4 concentrations were found in participants with rising TSH. Conclusions: In contrast to physiological expectation, in this group of 85-year-olds, a declining serum TSH was associated with reductions in free thyroid hormones over time. A decreasing serum TSH trajectory over time anticipated cognitive decline in later life. Declining TSH concentrations are a biomarker for cognitive impairment in later life.

Atrial fibrillation and oral anticoagulation in older people with frailty: a nationwide primary care electronic health records cohort study.

BACKGROUND: Atrial fibrillation (AF) is common in older people and is associated with increased stroke risk that may be reduced by oral anticoagulation (OAC). Frailty also increases with increasing age, yet the extent of OAC prescription in older people according to extent of frailty in people with AF is insufficiently described. METHODS: An electronic health records study of 536,955 patients aged ≥65 years from ResearchOne in England (384 General Practices), over 15.4 months, last follow-up 11th April 2017. OAC prescription for AF with CHA2DS2-Vasc ≥2, adjusted (demographic and treatments) risk of all-cause mortality, and subsequent cerebrovascular disease, bleeding and falls were estimated by electronic frailty index (eFI) category of fit, mild, moderate and severe frailty. RESULTS: AF prevalence and mean CHA2DS2-Vasc for those with AF increased with increasing eFI category (fit 2.9%, 2.2; mild 11.2%, 3.2; moderate 22.2%, 4.0; and severe 31.5%, 5.0). For AF with CHA2DS2-Vasc ≥2, OAC prescription was higher for mild (53.2%), moderate (55.6%) and severe (53.4%) eFI categories than fit (41.7%). In those with AF and eligible for OAC, frailty was associated with increased risk of death (HR for severe frailty compared with fit 4.09, 95% confidence interval 3.43-4.89), gastrointestinal bleeding (2.17, 1.45-3.25), falls (8.03, 4.60-14.03) and, among women, stroke (3.63, 1.10-12.02). CONCLUSION: Among older people in England, AF and stroke risk increased with increasing degree of frailty; however, OAC prescription approximated 50%. Given competing demands of mortality, morbidity and stroke prevention, greater attention to stratified stroke prevention is needed for this group of the population.

Association of treatments for acute myocardial infarction and survival for seven common comorbidity states: a nationwide cohort study.

BACKGROUND: Comorbidity is common and has a substantial negative impact on the prognosis of patients with acute myocardial infarction (AMI). Whilst receipt of guideline-indicated treatment for AMI is associated with improved prognosis, the extent to which comorbidities influence treatment provision its efficacy is unknown. Therefore, we investigated the association between treatment provision for AMI and survival for seven common comorbidities. METHODS: We used data of 693,388 AMI patients recorded in the Myocardial Ischaemia National Audit Project (MINAP), 2003-2013. We investigated the association between comorbidities and receipt of optimal care for AMI (receipt of all eligible guideline-indicated treatments), and the effect of receipt of optimal care for comorbid AMI patients on long-term survival using flexible parametric survival models. RESULTS: A total of 412,809 [59.5%] patients with AMI had at least one comorbidity, including hypertension (302,388 [48.7%]), diabetes (122,228 [19.4%]), chronic obstructive pulmonary disease (COPD, 89,221 [14.9%]), cerebrovascular disease (51,883 [8.6%]), chronic heart failure (33,813 [5.6%]), chronic renal failure (31,029 [5.0%]) and peripheral vascular disease (27,627 [4.6%]). Receipt of optimal care was associated with greatest survival benefit for patients without comorbidities (HR 0.53, 95% CI 0.51-0.56) followed by patients with hypertension (HR 0.60, 95% CI 0.58-0.62), diabetes (HR 0.83, 95% CI 0.80-0.87), peripheral vascular disease (HR 0.85, 95% CI 0.79-0.91), renal failure (HR 0.89, 95% CI 0.84-0.94) and COPD (HR 0.90, 95% CI 0.87-0.94). For patients with heart failure and cerebrovascular disease, optimal care for AMI was not associated with improved survival. CONCLUSIONS: Overall, guideline-indicated care was associated with improved long-term survival. However, this was not the case in AMI patients with concomitant heart failure or cerebrovascular disease. There is therefore a need for novel treatments to improve outcomes for AMI patients with pre-existing heart failure or cerebrovascular disease.

Prospective Clinical Study of Keratoconus Progression in Patients Awaiting Corneal Cross-linking.

PURPOSE: Keratoconus progression should be treated with corneal cross-linking (CXL) in a timely manner. This study aimed to investigate patient factors associated with keratoconus progression between time of listing and at time of CXL. METHODS: Prospective observational study at a tertiary center. Ninety-six eyes of 96 patients with keratoconus. Demographic, clinical, and tomographic parameters were analyzed to determine the risk factors for keratoconus progression. Analyzed tomographic indices included steepest keratometry, average keratometry, cornea thinnest point, index of surface variance, index of vertical asymmetry, keratoconus index, center keratoconus index, index of height asymmetry, and index of height decentration. RESULTS: A total of 38 eyes (39.6%) were found to have keratoconus progression during an average waiting time of 153 ± 101 days. There were significant differences in preoperative tomographic parameters such as index of surface variance (111.3 ± 36.6 vs. 88.3 ± 31.8; P = 0.002), index of vertical asymmetry (1.1 ± 0.4 vs. 0.9 ± 0.4; P = 0.005), keratoconus index (1.31 ± 0.12 vs. 1.22 ± 0.11; P < 0.001), and index of height decentration (0.16 ± 0.07 vs. 0.11 ± 0.06; P = 0.015) between eyes that progressed and those that remained stable. There were no significant differences in steepest keratometry, average keratometry, cornea thinnest point, and center keratoconus index. Multivariate analysis did not reveal age, presence of atopy/atopic keratoconjunctivitis, eye rubbing, or waiting time to be a significant risk factor for progression; however, Maori ethnicity was a risk factor (odds ratio = 3.89; P = 0.02). CONCLUSIONS: A significant proportion of eyes were found to be progressing while waiting for CXL. A risk stratification score for patients awaiting CXL may reduce the risk of progression.

A nationwide causal mediation analysis of survival following ST-elevation myocardial infarction.

OBJECTIVE: International studies report a decline in mortality following ST-elevation myocardial infarction (STEMI). The extent to which the observed improvements in STEMI survival are explained by temporal changes in patient characteristics and utilisation of treatments is unknown. METHODS: Cohort study using national registry data from the Myocardial Ischaemia National Audit Project between first January 2004 and 30th June 2013. 232 353 survivors of hospitalisation with STEMI as recorded in 247 hospitals in England and Wales. Flexible parametric survival modelling and causal mediation analysis were used to estimate the relative contribution of temporal changes in treatments and patient characteristics on improved STEMI survival. RESULTS: Over the study period, unadjusted survival at 6 months and 1 year improved by 0.9% and 1.0% on average per year (HR: 0.991, 95% CI: 0.988 to 0.994 and HR: 0.990, 95% CI: 0.987 to 0.993, respectively). The uptake of primary percutaneous coronary intervention (PCI) (HR: 1.025, 95% CI: 1.021 to 1.028) and increased prescription of P2Y12 inhibitors (HR: 1.035, 95% CI: 1.031 to 1.039) were significantly associated with improvements in 1-year survival. Primary PCI explained 16.8% (95% CI: 10.8% to 31.6%) and 13.2% (9.2% to 21.9%) of the temporal survival improvements at 6 months and 1 year, respectively, whereas P2Y12 inhibitor prescription explained 5.3% (3.6% to 8.8%) of the temporal improvements at 6 months but not at 1 year. CONCLUSIONS: For STEMI in England and Wales, improvements in survival between 2004 and 2013 were significantly explained by the uptake of primary PCI and increased use of P2Y12 inhibitors at 6 months and primary PCI only at 1 year. TRIAL REGISTRATION NUMBER: NCT03749694.

Serum Thyroid Function, Mortality and Disability in Advanced Old Age: The Newcastle 85+ Study.

CONTEXT: Perturbations in thyroid function are common in older individuals but their significance in the very old is not fully understood. OBJECTIVE: This study sought to determine whether thyroid hormone status and variation of thyroid hormones within the reference range correlated with mortality and disability in a cohort of 85-year-olds. DESIGN: A cohort of 85-year-old individuals were assessed in their own homes (community or institutional care) for health status and thyroid function, and followed for mortality and disability for up to 9 years. SETTING AND PARTICIPANTS: Six hundred and forty-three 85-year-olds registered with participating general practices in Newcastle and North Tyneside, United Kingdom. MAIN OUTCOMES: All-cause mortality, cardiovascular mortality, and disability according to thyroid disease status and baseline thyroid hormone parameters (serum TSH, FT4, FT3, and rT3). Models were adjusted for age, sex, education, body mass index, smoking, and disease count. RESULTS: After adjustment for age and sex, all-cause mortality was associated with baseline serum rT3 and FT3 (both P < .001), but not FT4 or TSH. After additional adjustment for potential confounders, only rT3 remained significantly associated with mortality (P = .001). Baseline serum TSH and rT3 predicted future disability trajectories in men and women, respectively. CONCLUSIONS: Our study is reassuring that individuals age 85 y with both subclinical hypothyroidism and subclinical hyperthyroidism do not have a significantly worse survival over 9 years than their euthyroid peers. However, thyroid function tests did predict disability, with higher serum TSH levels predicting better outcomes. These data strengthen the argument for routine use of age-specific thyroid function reference ranges.

Deconstructing Complex Multimorbidity in the Very Old: Findings from the Newcastle 85+ Study.

OBJECTIVES: To examine the extent and complexity of the morbidity burden in 85-year-olds; identify patterns within multimorbidity; and explore associations with medication and healthcare use. Participants. 710 men and women; mean (SD) age 85.5 (0.4) years. METHODS: Data on 20 chronic conditions (diseases and geriatric conditions) ascertained from general practice records and participant assessment. Cluster analysis within the multimorbid sample identified subgroups sharing morbidity profiles. Clusters were compared on medication and healthcare use. RESULTS: 92.7% (658/710) of participants had multimorbidity; median number of conditions: 4 (IQR 3-6). Cluster analysis (multimorbid sample) identified five subgroups sharing similar morbidity profiles; 60.0% (395/658) of participants belonged to one of two high morbidity clusters, with only 4.9% (32/658) in the healthiest cluster. Healthcare use was high, with polypharmacy (≥5 medications) in 69.8% (459/658). Between-cluster differences were found in medication count (p = 0.0001); hospital admissions (p = 0.022); and general practitioner (p = 0.034) and practice nurse consultations (p = 0.011). Morbidity load was related to medication burden and use of some, but not all, healthcare services. CONCLUSIONS: The majority of 85-year-olds had extensive and complex morbidity. Elaborating participant clusters sharing similar morbidity profiles will help inform future healthcare provision and the identification of common underlying biological mechanisms.

Respiratory health and disease in a U.K. population-based cohort of 85†year olds: The Newcastle 85+ Study.

BACKGROUND: People aged 85 years and older are the fastest growing age group worldwide. This study assessed respiratory health, prevalence of respiratory disease and use of spirometry in respiratory diagnosis in a population-based cohort of 85 year olds to better understand respiratory health and disease in this sector of society. METHODS: A single year birth-cohort of 85 year olds participated in a respiratory assessment at their home or residential institution including self-reporting of symptoms and measurement of spirometry. General practice medical records were reviewed for respiratory diagnoses and treatments. FINDINGS: In the 845 participants, a substantial burden of respiratory disease was seen with a prevalence of COPD in medical records of 16.6% (n=140). A large proportion of the cohort had environmental exposures through past or current smoking (64.2%, n=539) and occupational risk factors (33.6%, n=269). Spirometry meeting reliability criteria was performed in 87% (n=737) of participants. In the subgroup with a diagnosis of COPD (n=123), only 75.6% (n=93) satisfied Global Initiative in Obstructive Lung Disease (GOLD) criteria for airflow obstruction, and in a healthy subgroup without respiratory symptoms or diagnoses (n=151), 44.4% (n=67) reached GOLD criteria for airflow obstruction and 43.3% (n=29) National Institute of Health and Care Excellence criteria for at least moderate COPD. INTERPRETATION: Spirometry can be successfully performed in the very old, aged 85 years, and may help identify respiratory diseases such as COPD. However interpretation in this age group using current definitions of COPD based on spirometry indices may be difficult and lead to overdiagnosis in a healthy group with transient symptoms.

CMV seropositivity and T-cell senescence predict increased cardiovascular mortality in octogenarians: results from the Newcastle 85+ study.

Although chronic infection with cytomegalovirus (CMV) is known to drive T lymphocytes toward a senescent phenotype, it remains controversial whether and how CMV can cause coronary heart disease (CHD). To explore whether CMV seropositivity or T-cell populations associated with immunosenescence were informative for adverse cardiovascular outcome in the very old, we prospectively analyzed peripheral blood samples from 751 octogenarians (38% males) from the Newcastle 85+ study for their power to predict survival during a 65-month follow-up (47.3% survival rate). CMV-seropositive participants showed a higher prevalence of CHD (37.7% vs. 26.7%, P = 0.030) compared to CMV-seronegative participants together with lower CD4/CD8 ratio (1.7 vs. 4.1, P < 0.0001) and higher frequencies of senescence-like CD4 memory cells (41.1% vs. 4.5%, P < 0.001) and senescence-like CD8 memory cells (TEMRA, 28.1% vs. 6.7%, P < 0.001). CMV seropositivity was also associated with increased six-year cardiovascular mortality (HR 1.75 [1.09-2.82], P = 0.021) or death from myocardial infarction and stroke (HR 1.89 [107-3.36], P = 0.029). Gender-adjusted multivariate Cox regression analysis revealed that low percentages of senescence-like CD4 T cells (HR 0.48 [0.32-0.72], P < 0.001) and near-senescent (CD27 negative) CD8 T cells (HR 0.60 [0.41-0.88], P = 0.029) reduced the risk of cardiovascular death. For senescence-like CD4, but not near-senescent CD8 T cells, these associations remained robust after additional adjustment for CMV status, comorbidities, and inflammation markers. We conclude that CMV seropositivity is linked to a higher incidence of CHD in octogenarians and that senescence in both the CD4 and CD8 T-cell compartments is a predictor of overall cardiovascular mortality as well as death from myocardial infarction and stroke.

Gender and telomere length: systematic review and meta-analysis.

BACKGROUND: It is widely believed that females have longer telomeres than males, although results from studies have been contradictory. METHODS: We carried out a systematic review and meta-analyses to test the hypothesis that in humans, females have longer telomeres than males and that this association becomes stronger with increasing age. Searches were conducted in EMBASE and MEDLINE (by November 2009) and additional datasets were obtained from study investigators. Eligible observational studies measured telomeres for both females and males of any age, had a minimum sample size of 100 and included participants not part of a diseased group. We calculated summary estimates using random-effects meta-analyses. Heterogeneity between studies was investigated using sub-group analysis and meta-regression. RESULTS: Meta-analyses from 36 cohorts (36,230 participants) showed that on average females had longer telomeres than males (standardised difference in telomere length between females and males 0.090, 95% CI 0.015, 0.166; age-adjusted). There was little evidence that these associations varied by age group (p=1.00) or cell type (p=0.29). However, the size of this difference did vary by measurement methods, with only Southern blot but neither real-time PCR nor Flow-FISH showing a significant difference. This difference was not associated with random measurement error. CONCLUSIONS: Telomere length is longer in females than males, although this difference was not universally found in studies that did not use Southern blot methods. Further research on explanations for the methodological differences is required.

Deep sclerectomy versus trabeculectomy: a morphological study with anterior segment optical coherence tomography.

PURPOSE: To investigate the intraocular pressure (IOP) lowering mechanisms of deep sclerectomy (DS) with anterior segment optical coherence tomography (AS-OCT). METHODS: In a prospective cross-sectional study, AS-OCT parameters were compared between DS, trabeculectomy and control cases. Association with IOP and success (IOP≤16 mm Hg without medication) was investigated. RESULTS: 18 DS (15 patients), 17 trabeculectomy (16 patients) and 15 controls (15 patients) were examined. Successful had a taller intrascleral lake (IL) and thicker conjunctival/Tenon's layer (CTL) than non-successful cases (513.3 vs 361.1 µm, p=0.027 and 586.7 vs 251.1 µm, p<0.001, respectively). CTL thickness correlated with IOP (r=-0.6407, p=0.004). CTL thickness was significantly different between controls, DS and trabeculectomy (mean (SD): 203.3 (62.6) vs 418.9 (261.9) vs 604.1 (220.7) µm, p<0.0001). Successful trabeculectomy cases had a taller bleb cavity (BC) than non-successful cases (607.5 vs 176.7 µm, p=0.041). CTL microcysts were detected in 50% of DS and 52.9% of trabeculectomy cases (p=1). CONCLUSIONS: Trans-conjunctival aqueous percolation was identified as a novel DS drainage route. DS had a fluid reservoir below the scleral flap, the IL, in analogy to the trabeculectomy BC. A postoperative tall IL and a thick CTL were associated with good outcome.