The association between restricted activity and patient outcomes in older adults: systematic literature review and meta-analysis.

BACKGROUND: Restricted activity is a potential early marker of declining health in older adults. Previous studies of this association with patient outcomes have been inconclusive. This review aimed to evaluate the extent to which restricted activity is associated with decline in health. METHODS: A search was conducted for studies including people over 65 years old which investigated the association between measures of restricted activity and hospitalisation, cognitive decline, and mortality. Following data extraction by two reviewers, eligible studies were summarised using Inverse Variance Heterogeneity meta-analysis. RESULTS: The search identified 8,434 unique publications, with 11 eligible studies. Three measures of restricted activity were identified: bed rest, restricted movement, and dependency for activities of daily living (ADL). Three studies looked at hospitalisations, with two finding a significant association with bed rest or restricted movement and one showing no evidence of an association. Restricted activity was associated with a significant increase in mortality across all three measures (bed rest odds ratio [OR] 6.34, 95%CI 2.51-16.02, I2 = 76%; restricted movement OR 5.38 95%CI 2.60-11.13, I2 = 69%; general ADL dependency OR 4.65 95%CI 2.25-9.26, I2 = 84%). The significant heterogeneity observed could not be explained by restricting the analysis by length of follow-up, or measure of restricted activity. No meta-analysis was conducted on the limited evidence for cognitive decline outcomes. CONCLUSIONS: Limited studies have considered the prognostic value of restricted activity in terms of predicting future declining health. Current evidence suggests restricted activity is associated with hospitalisation and mortality, and therefore could identify a group for whom early intervention might be possible.

The diagnostic accuracy of cardiac ultrasound for acute myocardial ischemia in the emergency department: a systematic review and meta-analysis.

BACKGROUND: Chest pain is responsible for millions of visits to the emergency department (ED) annually. Cardiac ultrasound can detect ischemic changes, but varying accuracy estimates have been reported in previous studies. We synthetized the available evidence to yield more precise estimates of the accuracy of cardiac ultrasound for acute myocardial ischemia in patients with chest pain in the ED and to assess the effect of different clinical characteristics on test accuracy. METHODS: A systematic search for studies assessing the diagnostic accuracy of cardiac ultrasound for myocardial ischemia in the ED was conducted in MEDLINE, EMBASE, CENTRAL, CINAHL, LILACS, Web of Science, two trial registries and supplementary methods, from inception to December 6th, 2022. Prospective cohort, cross-sectional, case-control studies and randomized controlled trials (RCTs) that included data on diagnostic accuracy were included. Risk of bias was assessed with the QUADAS-2 tool and a bivariate hierarchical model was used for meta-analysis with paired Forest and SROC plots used to present the results. Subgroup analyses was conducted on clinically relevant factors. RESULTS: Twenty-nine studies were included, with 5043 patients. The overall summary sensitivity was 79.3% (95%CI 69.0-86.8%) and specificity was 87.3% (95%CI 79.9-92.2%), with substantial heterogeneity. Subgroup analyses showed increased sensitivity in studies where ultrasound was conducted at ED admission and increased specificity in studies that excluded patients with previous heart disease, when the target condition was acute coronary syndrome, or when final chart review was used as the reference standard. There was very low certainty in the results based on serious risk of bias and indirectness in most studies. CONCLUSIONS: Cardiac ultrasound may have a potential role in the diagnostic pathway of myocardial ischemia in the ED; however, a pooled accuracy must be interpreted cautiously given substantial heterogeneity and that important patient and test characteristics affect its diagnostic performance. PROTOCOL REGISTRATION: PROSPERO (CRD42023392058).

'Legacy publication of a 2009 validation of the Riester Big Ben Square Desk aneroid device for blood pressure measurement according to the European Society of Hypertension International Protocol for validation of blood pressure measuring devices in adults (2002)'.

OBJECTIVE: To report a validation of the Riester Big Ben Square Desk Aneroid Sphygmomanometer according to the international protocol developed by the Working Group on Blood Pressure Monitoring of the European Society of Hypertension 2002 (ESH-IP 2002) in the interest of transparency. This legacy publication is intended to assure users that the device satisfied the requirements in place at that time. METHODS: Performance of the device was assessed by participants' age, sex, arm circumference and entry SBP/DBP. Validation was performed in 33 participants. The sphygmomanometer was assessed according to the ESH-IP, which defines zones of accuracy compared to the mercury standard as ≤5, ≤10, ≤15 mmHg or more. RESULTS: The mean (± SD) age was 50.5 ±â€…13.0 years, range 29-71 years, entry SBP 142.6 ±â€…23.7 mmHg, entry DBP 89.0 ±â€…17.8 mmHg. The device passed all the requirements listed and the validation protocol. The Riester Big Ben Square Desk aneroid sphygmomanometer slightly underestimated the observer-measured SBP, yet slightly overestimated DBP. The observer-device disagreement was -0.8 ±â€…6.4 mmHg SBP and +0.6 ±â€…4.0 mmHg DBP. CONCLUSION: These data show that the Riester Big Ben Square Desk aneroid sphygmomanometer fulfilled the ESH-IP 2002 requirements for the validation of BP monitors. It was on this basis that the British and Irish Hypertension Society recommended it for clinical use in the adult population.

Strategies for Identifying Patients for Deprescribing of Blood Pressure Medications in Routine Practice: An Evidence Review.

PURPOSE OF REVIEW: To summarise the evidence regarding which patients might benefit from deprescribing antihypertensive medications. RECENT FINDINGS: Older patients with frailty, multi-morbidity and subsequent polypharmacy are at higher risk of adverse events from antihypertensive treatment, and therefore may benefit from antihypertensive deprescribing. It is possible to examine an individual's risk of these adverse events, and use this to identify those people where the benefits of treatment may be outweighed by the harms. While such patients might be considered for deprescribing, the long-term effects of this treatment strategy remain unclear. Evidence now exists to support identification of those who are at risk of adverse events from antihypertensive treatment. These patients could be targeted for deprescribing interventions, although the long-term benefits and harms of this approach are unclear. PERSPECTIVES: Randomised controlled trials are still needed to examine the long-term effects of deprescribing in high-risk patients with frailty and multi-morbidity.

Effectiveness of Hypertension Management Strategies in SPRINT-Eligible US Adults: A Simulation Study.

BACKGROUND: Despite reducing cardiovascular disease (CVD) events and death in SPRINT (Systolic Blood Pressure Intervention Trial), intensive systolic blood pressure goals have not been adopted in the United States. This study aimed to simulate the potential long-term impact of 4 hypertension management strategies in SPRINT-eligible US adults. METHODS AND RESULTS: The validated Blood Pressure Control-Cardiovascular Disease Policy Model, a discrete event simulation of hypertension care processes (ie, visit frequency, blood pressure [BP] measurement accuracy, medication intensification, and medication adherence) and CVD outcomes, was populated with 25 000 SPRINT-eligible US adults. Four hypertension management strategies were simulated: (1) usual care targeting BP <140/90 mm Hg (Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure usual care), (2) intensive care per the SPRINT protocol targeting BP <120/90 mm Hg (SPRINT intensive), (3) usual care targeting guideline-recommended BP <130/80 mm Hg (American College of Cardiology/American Heart Association usual care), and (4) team-based care added to usual care and targeting BP <130/80 mm Hg. Relative to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure usual care, among the 18.1 million SPRINT-eligible US adults, an estimated 138 100 total CVD events could be prevented per year with SPRINT intensive, 33 900 with American College of Cardiology/American Heart Association usual care, and 89 100 with team-based care. Compared with the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure usual care, SPRINT intensive care was projected to increase treatment-related serious adverse events by 77 600 per year, American College of Cardiology/American Heart Association usual care by 33 300, and team-based care by 27 200. CONCLUSIONS: As BP control has declined in recent years, health systems must prioritize hypertension management and invest in effective strategies. Adding team-based care to usual care may be a pragmatic way to manage risk in this high-CVD-risk population.

Deintensification of potentially inappropriate medications amongst older frail people with type 2 diabetes: Protocol for a cluster randomised controlled trial (D-MED study).

AIMS: Amongst elderly people with type 2 diabetes (T2D) over prescribing can result in emergency ambulance call-outs, falls and fractures and increased mortality, particularly in frail patients. Current clinical guidelines, however, remain focused on medication intensification rather than deintensification where appropriate. This study aims to evaluate the effectiveness of an electronic decision-support system and training for the deintensification of potentially inappropriate medications amongst older frail people with T2D, when compared to 'usual' care at 12-months. METHODS: This study is an open-label, multi-site, two-armed pragmatic cluster-randomised trial. GP practices randomised to the 'enhanced care' group have an electronic decision support system installed and receive training on the tool and de-intensification of diabetes medications. The system flags eligible patients for possible deintensification of diabetes medications, linking the health care professional to a clinical algorithm. The primary outcome will be the number of patients at 12-months who have had potentially inappropriate diabetes medications de-intensified. RESULTS: Study recruitment commenced in June 2022. Data collection commenced in January 2023. Baseline data have been extracted from 40 practices (3145 patients). CONCLUSIONS: Digital technology, involving computer decision systems, may have the potential to reduce inappropriate medications and aid the process of de-intensification. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number: ISRCTN53221378. Available at: https://www.isrctn.com/ISRCTN53221378.

Outcome Following Intramedullary Nailing of Tibial Diaphyseal Fractures: Suprapatellar Nail Insertion Results in Superior Radiographic Parameters But No Difference in Mid-Term Function.

BACKGROUND: The primary aim of this study was to compare the radiographic parameters (nail insertion-point accuracy [NIPA] and fracture malalignment) of patients who had undergone tibial intramedullary nailing via the suprapatellar (SP) and infrapatellar (IP) approaches. The secondary aims were to compare clinical outcomes and patient-reported outcomes (PROs) between these approaches. METHODS: All adult patients with an acute tibial diaphyseal fracture who underwent intramedullary nailing at a single level-I trauma center over a 4-year period (2017 to 2020) were retrospectively identified. The nailing approach (SP or IP) was at the treating surgeon's discretion. Intraoperative and immediate postoperative radiographs were reviewed to assess NIPA (mean distance from the optimal insertion point) and malalignment (≥5°). Medical records and radiographs were reviewed to evaluate the rates of malunion, nonunion, and other postoperative complications. The Oxford and Lysholm Knee Scores (OKS and LKS) and patient satisfaction (0 = completely dissatisfied, 100 = completely satisfied) were obtained via a postal survey at a minimum of 1 year postoperatively. RESULTS: The cohort consisted of 219 consecutive patients (mean age, 48 years [range, 16 to 90 years], 51% [112] male). There were 61 patients (27.9%) in the SP group and 158 (72.1%) in the IP group. The groups did not differ in baseline demographic or injury-related variables. SP nailing was associated with superior coronal NIPA (p < 0.001; 95% confidence interval [CI] for IP versus SP, 1.17 to 3.60 mm) and sagittal NIPA (p < 0.001; 95% CI, 0.23 to 0.97 mm) and with a reduced rate of malalignment (3% [2 of 61] versus 11% [18 of 158] for IP; p = 0.030). PROs were available for 118 of 211 patients (56%; 32 of 58 in the SP group and 86 of 153 in the IP group) at a mean of 3 years (range, 1.2 to 6.5 years). There was no difference between the SP and IP groups in mean OKS (36.5 versus 39.6; p = 0.246), LKS (71.2 versus 73.5; p = 0.696), or satisfaction scores (81.4 versus 79.9; p = 0.725). CONCLUSIONS: Compared with IP nailing, SP nailing of tibial shaft fractures was associated with superior NIPA and a reduced rate of intraoperative malalignment but not of malunion at healing. However, the superior NIPA may not be clinically important. Furthermore, there were no differences in PROs at mid-term follow-up. LEVEL OF EVIDENCE: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

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.

Development of a modified Cambridge Multimorbidity Score for use with SNOMED CT: an observational English primary care sentinel network study.

BACKGROUND: People with multiple health conditions are more likely to have poorer health outcomes and greater care and service needs; a reliable measure of multimorbidity would inform management strategies and resource allocation. AIM: To develop and validate a modified version of the Cambridge Multimorbidity Score in an extended age range, using clinical terms that are routinely used in electronic health records across the world (Systematized Nomenclature of Medicine - Clinical Terms, SNOMED CT). DESIGN AND SETTING: Observational study using diagnosis and prescriptions data from an English primary care sentinel surveillance network between 2014 and 2019. METHOD: In this study new variables describing 37 health conditions were curated and the associations modelled between these and 1-year mortality risk using the Cox proportional hazard model in a development dataset (n = 300 000). Two simplified models were then developed - a 20-condition model as per the original Cambridge Multimorbidity Score and a variable reduction model using backward elimination with Akaike information criterion as the stopping criterion. The results were compared and validated for 1-year mortality in a synchronous validation dataset (n = 150 000), and for 1-year and 5-year mortality in an asynchronous validation dataset (n = 150 000). RESULTS: The final variable reduction model retained 21 conditions, and the conditions mostly overlapped with those in the 20-condition model. The model performed similarly to the 37- and 20-condition models, showing high discrimination and good calibration following recalibration. CONCLUSION: This modified version of the Cambridge Multimorbidity Score allows reliable estimation using clinical terms that can be applied internationally across multiple healthcare settings.

Predicting the risk of acute kidney injury in primary care: derivation and validation of STRATIFY-AKI.

BACKGROUND: Antihypertensives reduce the risk of cardiovascular disease but are also associated with harms including acute kidney injury (AKI). Few data exist to guide clinical decision making regarding these risks. AIM: To develop a prediction model estimating the risk of AKI in people potentially indicated for antihypertensive treatment. DESIGN AND SETTING: Observational cohort study using routine primary care data from the Clinical Practice Research Datalink (CPRD) in England. METHOD: People aged ≥40 years, with at least one blood pressure measurement between 130 mmHg and 179 mmHg were included. Outcomes were admission to hospital or death with AKI within 1, 5, and 10 years. The model was derived with data from CPRD GOLD (n = 1 772 618), using a Fine-Gray competing risks approach, with subsequent recalibration using pseudo-values. External validation used data from CPRD Aurum (n = 3 805 322). RESULTS: The mean age of participants was 59.4 years and 52% were female. The final model consisted of 27 predictors and showed good discrimination at 1, 5, and 10 years (C-statistic for 10-year risk 0.821, 95% confidence interval [CI] = 0.818 to 0.823). There was some overprediction at the highest predicted probabilities (ratio of observed to expected event probability for 10-year risk 0.633, 95% CI = 0.621 to 0.645), affecting patients with the highest risk. Most patients (>95%) had a low 1- to 5-year risk of AKI, and at 10 years only 0.1% of the population had a high AKI and low CVD risk. CONCLUSION: This clinical prediction model enables GPs to accurately identify patients at high risk of AKI, which will aid treatment decisions. As the vast majority of patients were at low risk, such a model may provide useful reassurance that most antihypertensive treatment is safe and appropriate while flagging the few for whom this is not the case.

The association between antihypertensive treatment and serious adverse events by age and frailty: A cohort study.

BACKGROUND: Antihypertensives are effective at reducing the risk of cardiovascular disease, but limited data exist quantifying their association with serious adverse events, particularly in older people with frailty. This study aimed to examine this association using nationally representative electronic health record data. METHODS AND FINDINGS: This was a retrospective cohort study utilising linked data from 1,256 general practices across England held within the Clinical Practice Research Datalink between 1998 and 2018. Included patients were aged 40+ years, with a systolic blood pressure reading between 130 and 179 mm Hg, and not previously prescribed antihypertensive treatment. The main exposure was defined as a first prescription of antihypertensive treatment. The primary outcome was hospitalisation or death within 10 years from falls. Secondary outcomes were hypotension, syncope, fractures, acute kidney injury, electrolyte abnormalities, and primary care attendance with gout. The association between treatment and these serious adverse events was examined by Cox regression adjusted for propensity score. This propensity score was generated from a multivariable logistic regression model with patient characteristics, medical history and medication prescriptions as covariates, and new antihypertensive treatment as the outcome. Subgroup analyses were undertaken by age and frailty. Of 3,834,056 patients followed for a median of 7.1 years, 484,187 (12.6%) were prescribed new antihypertensive treatment in the 12 months before the index date (baseline). Antihypertensives were associated with an increased risk of hospitalisation or death from falls (adjusted hazard ratio [aHR] 1.23, 95% confidence interval (CI) 1.21 to 1.26), hypotension (aHR 1.32, 95% CI 1.29 to 1.35), syncope (aHR 1.20, 95% CI 1.17 to 1.22), acute kidney injury (aHR 1.44, 95% CI 1.41 to 1.47), electrolyte abnormalities (aHR 1.45, 95% CI 1.43 to 1.48), and primary care attendance with gout (aHR 1.35, 95% CI 1.32 to 1.37). The absolute risk of serious adverse events with treatment was very low, with 6 fall events per 10,000 patients treated per year. In older patients (80 to 89 years) and those with severe frailty, this absolute risk was increased, with 61 and 84 fall events per 10,000 patients treated per year (respectively). Findings were consistent in sensitivity analyses using different approaches to address confounding and taking into account the competing risk of death. A strength of this analysis is that it provides evidence regarding the association between antihypertensive treatment and serious adverse events, in a population of patients more representative than those enrolled in previous randomised controlled trials. Although treatment effect estimates fell within the 95% CIs of those from such trials, these analyses were observational in nature and so bias from unmeasured confounding cannot be ruled out. CONCLUSIONS: Antihypertensive treatment was associated with serious adverse events. Overall, the absolute risk of this harm was low, with the exception of older patients and those with moderate to severe frailty, where the risks were similar to the likelihood of benefit from treatment. In these populations, physicians may want to consider alternative approaches to management of blood pressure and refrain from prescribing new treatment.

Medical Telemonitoring for the Management of Hypertension in Older Patients in Japan.

Hypertension is the most frequent modifiable risk factor associated with cardiovascular disease (CVD) morbidity and mortality. Even in older people, strict blood pressure (BP) control has been recommended to reduce CVD event risks. However, caution should be exercised since older hypertensive patients have increased physical vulnerability due to frailty and multimorbidity, and older patients eligible for clinical trials may not represent the general population. Medical telemonitoring systems, which enable us to monitor a patient's medical condition remotely through digital communication, have become much more prevalent since the coronavirus pandemic. Among various physiological parameters, BP monitoring is well-suited to the use of such systems, which enable healthcare providers to deliver accurate and safe BP management, even in the presence of frailty and/or living in geographically remote areas. Furthermore, medical telemonitoring systems could help reduce nonadherence to antihypertensive medications and clinical inertia, and also enable multi-professional team-based management of hypertension. However, the implementation of medical telemonitoring systems in clinical practice is not easy, and substantial barriers, including the development of user-friendly devices, integration with existing clinical systems, data security, and cost of implementation and maintenance, need to be overcome. In this review, we focus on the potential of medical telemonitoring for the management of hypertension in older people in Japan.

Trends in direct oral anticoagulant (DOAC) prescribing in English primary care (2014-2019).

BACKGROUND: In England, most prescribing of direct-acting oral anticoagulants for atrial fibrillation (AF) is in primary care. However, there remain gaps in our understanding of dosage and disparities in use. We aimed to describe trends in direct oral anticoagulant (DOAC) prescribing, including dose reduction in people with renal impairment and other criteria, and adherence. METHODS: Using English primary care sentinel network data from 2014 to 2019, we assessed appropriate DOAC dose adjustment with creatinine clearance (CrCl). Our primary care sentinel cohort was a subset of 722 general practices, with 6.46 million currently registered patients at the time of this study. RESULTS: Of 6 464 129 people in the cohort, 2.3% were aged ≥18 years with a diagnosis of AF, and 30.8% of these were prescribed vitamin K antagonist and 69.1% DOACs. Appropriate DOAC prescribing following CrCl measures improved between 2014 and 2019; dabigatran from 21.3% (95% CI 15.1% to 28.8%) to 48.7% (95% CI 45.0% to 52.4%); rivaroxaban from 22.1% (95% CI 16.7% to 28.4%) to 49.9% (95% CI 48.5% to 53.3%); edoxaban from 10.0% (95% CI 0.3% to 44.5%) in 2016 to 57.6% (95% CI 54.5% to 60.7%) in 2019; apixaban from 30.8% (95% CI 9.1% to 61.4%) in 2015 to 60.5% (95% CI 57.8% to 63.2%) in 2019.Adherence was highest for factor Xa inhibitors, increasing from 50.1% (95% CI 47.7% to 52.4%) in 2014 to 57.8% (95% CI 57.4% to 58.2%) in 2019. Asian and black/mixed ethnicity was associated with non-adherence (OR 1.81, 95% CI 1.56 to 2.09) as was male gender (OR 1.19, 95% CI 1.15 to 1.22), higher socioeconomic status (OR 1.60, 95% CI 1.52 to 1.68), being an ex-smoker (OR 1.12, 95% CI 1.06 to 1.19) and hypertension (OR 1.07, 95% CI 1.03 to 1.17). CONCLUSIONS: The volume and quality of DOAC prescribing has increased yearly. Future interventions to augment quality of anticoagulant management should target disparities in adherence.

Conserved plant transcriptional responses to microgravity from two consecutive spaceflight experiments.

Introduction: Understanding how plants adapt to the space environment is essential, as plants will be a valuable component of long duration space missions. Several spaceflight experiments have focused on transcriptional profiling as a means of understanding plant adaptation to microgravity. However, there is limited overlap between results from different experiments. Differences in experimental conditions and hardware make it difficult to find a consistent response across experiments and to distinguish the primary effects of microgravity from other spaceflight effects. Methods: Plant Signaling (PS) and Plant RNA Regulation (PRR) were two separate spaceflight experiments conducted on the International Space Station utilizing the European Modular Cultivation System (EMCS). The EMCS provided a lighted environment for plant growth with centrifugal capabilities providing an onboard 1 g control. Results and discussion: An RNA-Seq analysis of shoot samples from PS and PRR revealed a significant overlap of genes differentially expressed in microgravity between the two experiments. Relative to onboard 1 g controls, genes involved in transcriptional regulation, shoot development, and response to auxin and light were upregulated in microgravity in both experiments. Conversely, genes involved in defense response, abiotic stress, Ca++ signaling, and cell wall modification were commonly downregulated in both datasets. The downregulation of stress responses in microgravity in these two experiments is interesting as these pathways have been previously observed as upregulated in spaceflight compared to ground controls. Similarly, we have observed many stress response genes to be upregulated in the 1 g onboard control compared to ground reference controls; however these genes were specifically downregulated in microgravity. In addition, we analyzed the sRNA landscape of the 1 g and microgravity (µ g) shoot samples from PRR. We identified three miRNAs (miR319c, miR398b, and miR8683) which were upregulated in microgravity, while several of their corresponding target genes were found to be downregulated in microgravity. Interestingly, the downregulated target genes are enriched in those encoding chloroplast-localized enzymes and proteins. These results uncover microgravity unique transcriptional changes and highlight the validity and importance of an onboard 1 g control.

Development and external validation of a risk prediction model for falls in patients with an indication for antihypertensive treatment: retrospective cohort study.

OBJECTIVE: To develop and externally validate the STRAtifying Treatments In the multi-morbid Frail elderlY (STRATIFY)-Falls clinical prediction model to identify the risk of hospital admission or death from a fall in patients with an indication for antihypertensive treatment. DESIGN: Retrospective cohort study. SETTING: Primary care data from electronic health records contained within the UK Clinical Practice Research Datalink (CPRD). PARTICIPANTS: Patients aged 40 years or older with at least one blood pressure measurement between 130 mm Hg and 179 mm Hg. MAIN OUTCOME MEASURE: First serious fall, defined as hospital admission or death with a primary diagnosis of a fall within 10 years of the index date (12 months after cohort entry). Model development was conducted using a Fine-Gray approach in data from CPRD GOLD, accounting for the competing risk of death from other causes, with subsequent recalibration at one, five, and 10 years using pseudo values. External validation was conducted using data from CPRD Aurum, with performance assessed through calibration curves and the observed to expected ratio, C statistic, and D statistic, pooled across general practices, and clinical utility using decision curve analysis at thresholds around 10%. RESULTS: Analysis included 1 772 600 patients (experiencing 62 691 serious falls) from CPRD GOLD used in model development, and 3 805 366 (experiencing 206 956 serious falls) from CPRD Aurum in the external validation. The final model consisted of 24 predictors, including age, sex, ethnicity, alcohol consumption, living in an area of high social deprivation, a history of falls, multiple sclerosis, and prescriptions of antihypertensives, antidepressants, hypnotics, and anxiolytics. Upon external validation, the recalibrated model showed good discrimination, with pooled C statistics of 0.833 (95% confidence interval 0.831 to 0.835) and 0.843 (0.841 to 0.844) at five and 10 years, respectively. Original model calibration was poor on visual inspection and although this was improved with recalibration, under-prediction of risk remained (observed to expected ratio at 10 years 1.839, 95% confidence interval 1.811 to 1.865). Nevertheless, decision curve analysis suggests potential clinical utility, with net benefit larger than other strategies. CONCLUSIONS: This prediction model uses commonly recorded clinical characteristics and distinguishes well between patients at high and low risk of falls in the next 1-10 years. Although miscalibration was evident on external validation, the model still had potential clinical utility around risk thresholds of 10% and so could be useful in routine clinical practice to help identify those at high risk of falls who might benefit from closer monitoring or early intervention to prevent future falls. Further studies are needed to explore the appropriate thresholds that maximise the model's clinical utility and cost effectiveness.

Antihypertensive Deprescribing in Older Adults: a Practical Guide.

PURPOSE OF REVIEW: To summarise evidence on both appropriate and inappropriate antihypertensive drug withdrawal. RECENT FINDINGS: Deprescribing should be attempted in the following steps: (1) identify patients with several comorbidities and significant functional decline, i.e. people at higher risk for negative outcomes related to polypharmacy and lower blood pressure; (2) check blood pressure; (3) identify candidate drugs for deprescribing; (4) withdraw medications at 4-week intervals; (5) monitor blood pressure and check for adverse events. Although evidence is accumulating regarding short-term outcomes of antihypertensive deprescribing, long-term effects remain unclear. The limited evidence for antihypertensive deprescribing means that it should not be routinely attempted, unless in response to specific adverse events or following discussions between physicians and patients about the uncertain benefits and harms of the treatment. PERSPECTIVES: Clinical controlled trials are needed to examine the long-term effects of deprescribing in older subjects, especially in those with comorbidities, and significant functional decline.

Predictors and determinants of albuminuria in people with prediabetes and diabetes based on smoking status: A cross-sectional study using the UK Biobank data.

Background: Smoking is attributed to both micro- and macrovascular complications at any stage of metabolic deregulation including prediabetes. Current global diabetes prevention programmes appear to be glucocentric, and do not fully acknowledge the ramifications of cardiorenal risk factors in smokers and ex-smokers. A more holistic approach is needed to prevent vascular complications in people with prediabetes and diabetes before and after quitting. Methods: A cross-sectional study was carried out on participants who agreed to take part in the UK Biobank dataset at the time of their first attendances between March 01, 2006, and December 31, 2010. Those who had their urinary albumin concentration (UAC) data available were included, and those who did not have this data, were excluded. A logistic regression model was fitted to explore the relationship between cardiorenal risk factors and albuminuria in people with prediabetes and diabetes, based on smoking status. Findings: A total of 502,490 participants were included in the UK Biobank dataset. Of them, 30.4% (n=152,896) had their UAC level recorded. Compared with non-smokers, the odds of albuminuria in smokers with prediabetes and diabetes were 1.21 (95% CI 1.05 - 1.39, p=0.009), and 1.26 (95% CI 1.10 - 1.44, p=0.001), respectively. The odds declined after quitting in both groups, but it was not statistically significant (p>0.05). Each unit increase in HbA1c was associated with equivalent increased odds of albuminuria in current and ex-smokers, OR 1.035 (95% CI 1.030 - 1.039, p<0.001), and 1.026 (95% CI 1.023 - 1.028, p <0.001), respectively. Compared to females, male ex-smokers were at 15% increased odds of albuminuria. In ex-smokers, each unit increase in waist circumference was associated with 1% increased risk of albuminuria. Compared with the least deprived quintiles, the odds of albuminuria in the most deprived quintiles, in current and ex-smokers were identical, OR 1.18 (95% CI 1.04-1.324, p=0.010), and 1.19 (95% CI 1.11 - 1.27, p<0.001), respectively. Interpretation: Male smokers are at a higher risk of albuminuria after smoking cessation. Monitoring waist circumference in quitters may identify those who are at a higher risk of albuminuria. Combining smoking cessation intervention in smokers with prediabetes in the current diabetes prevention programmes may offset post-cessation weight gain and reduce the risk of albuminuria. Funding: University of Sheffield.

Cost-Effectiveness of Masked Hypertension Screening and Treatment in US Adults With Suspected Masked Hypertension: A Simulation Study.

BACKGROUND: Recent US blood pressure (BP) guidelines recommend using ambulatory BP monitoring (ABPM) or home BP monitoring (HBPM) to screen adults for masked hypertension. However, limited evidence exists of the expected long-term effects of screening for and treating masked hypertension. METHODS: We estimated the lifetime health and economic outcomes of screening for and treating masked hypertension using the Cardiovascular Disease (CVD) Policy Model, a validated microsimulation model. We simulated a cohort of 100,000 US adults aged ≥20 years with suspected masked hypertension (i.e., office BP 120-129/<80 mm Hg, not taking antihypertensive medications, without CVD history). We compared usual care only (i.e., no screening), usual care plus ABPM, and usual care plus HBPM. We projected total direct healthcare costs (2021 USD), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios. Future costs and QALYs were discounted 3% annually. Secondary outcomes included CVD events and serious adverse events. RESULTS: Relative to usual care, adding masked hypertension screening and treatment with ABPM and HBPM was projected to prevent 14.3 and 20.5 CVD events per 100,000 person-years, increase the proportion experiencing any treatment-related serious adverse events by 2.7 and 5.1 percentage points, and increase mean total costs by $1,076 and $1,046, respectively. Compared with usual care, adding ABPM was estimated to cost $85,164/QALY gained. HBPM resulted in lower QALYs than usual care due to increased treatment-related adverse events and pill-taking disutility. CONCLUSIONS: The results from our simulation study suggest screening with ABPM and treating masked hypertension is cost-effective in US adults with suspected masked hypertension.

Cost-Effectiveness of Antihypertensive Deprescribing in Primary Care: a Markov Modelling Study Using Data From the OPTiMISE Trial.

BACKGROUND: Deprescribing of antihypertensive medications for older patients with normal blood pressure is recommended by some clinical guidelines, where the potential harms of treatment may outweigh the benefits. This study aimed to assess the cost-effectiveness of this approach. METHODS: A Markov patient-level simulation was undertaken to model the effect of withdrawing one antihypertensive compared with usual care, over a life-time horizon. Model population characteristics were estimated using data from the OPTiMISE antihypertensive deprescribing trial, and the effects of blood pressure changes on outcomes were derived from the literature. Health-related quality of life was modeled in Quality-Adjusted Life Years (QALYs) and presented as costs per QALY gained. RESULTS: In the base-case analysis, medication reduction resulted in lower costs than usual care (mean difference £185), but also lower QALYs (mean difference 0.062) per patient over a life-time horizon. Usual care was cost-effective at £2975 per QALY gained (more costly, but more effective). Medication reduction resulted more heart failure and stroke/TIA events but fewer adverse events. Medication reduction may be the preferred strategy at a willingness-to-pay of £20 000/QALY, where the baseline absolute risk of serious drug-related adverse events was ≥7.7% a year (compared with 1.7% in the base-case). CONCLUSIONS: Although there was uncertainty around many of the assumptions underpinning this model, these findings suggest that antihypertensive medication reduction should not be attempted in many older patients with controlled systolic blood pressure. For populations at high risk of adverse effects, deprescribing may be beneficial, but a targeted approach would be required in routine practice.