Natural history of depression up to 18 years after stroke: a population-based South London Stroke Register study.

Background: Current evidence on the long-term natural history of post-stroke depression (PSD) is limited. We aim to determine the prevalence, incidence, duration and recurrence rates of depression to 18-years after stroke and assess differences by onset-time and depression severity. Methods: Data were from the South London Stroke Register (1995-2019, N = 6641 at registration). Depression was defined using the Hospital Anxiety and Depression scale (scores > 7 = depression) at 3-months, then annually to 18-years after stroke. We compared early- (3-months post-stroke) vs late-onset depression (1-year) and initial mild (HADS scores > 7) vs severe depression (scores > 10). Findings: 3864 patients were assessed for depression at any time-points during the follow-up (male:55.4% (2141), median age: 68.0 (20.4)), with the number ranging from 2293 at 1-year to 145 at 18-years after stroke. Prevalence of PSD ranged from 31.3% (28.9-33.8) to 41.5% (33.6-49.3). The cumulative incidence of depression was 59.4% (95% CI 57.8-60.9), of which 87.9% (86.5-89.2) occurred within 5-years after stroke. Of patients with incident PSD at 3-months after stroke, 46.6% (42.1-51.2) recovered after 1 year. Among those recovered, 66.7% (58.0-74.5) experienced recurrent depression and 94.4% (87.5-98.2) of recurrences occurred within 5-years since recovery. Similar estimates were observed in patients with PSD at 1-year. 34.3% (27.9-41.1) of patients with severe depression had recovered at the next time-point, compared to 56.7% (50.5-62.8) with mild depression. Recurrence rate at 1-year after recovery was higher in patients with severe depression (52.9% (35.1-70.2)) compared to mild depression (23.5% (14.1-35.4)) (difference: 29.4% (7.6-51.2), p = 0.003). Interpretation: Long-term depressive status may be established by 5-years post-onset. Early- and late-onset depression presented similar natural history, while severe depression had a longer duration and quicker recurrence than mild depression. These estimates were limited to alive patients completing the depression assessment, who tended to have less severe stroke than excluded patients, so may be underestimated and not generalizable to all stroke survivors. Funding: National Institute for Health and Care Research (NIHR202339).

Barriers and facilitators to early mobilisation and weight-bearing as tolerated after hip fracture surgery among older adults in Saudi Arabia: a qualitative study.

OBJECTIVE: To explore the practice of prescribing and implementing early mobilisation and weight-bearing as tolerated after hip fracture surgery in older adults and identify barriers and facilitators to their implementation. METHODS: Semi-structured interviews were conducted with 20 healthcare providers (10 orthopaedic surgeons and 10 physiotherapists) from Saudi Arabian government hospitals. Data were analysed using inductive thematic analysis. RESULTS: While early mobilisation and weight-bearing as tolerated were viewed as important by most participants, they highlighted barriers to the implementation of these practices. Most participants advocated for mobility within 48 h of surgery, aligning with international guidance; however, the implementation of weight-bearing as tolerated was varied. Some participants stressed the type of surgery undertaken as a key factor in weight-bearing prescription. For others, local protocols or clinician preference was seen as most important, the latter partially influenced by where they were trained. Interdisciplinary collaboration between orthopaedic surgeons and physiotherapists was seen as a crucial part of postoperative care and weight-bearing. Patient and family member buy-in was also noted as a key factor, as fear of further injury can impact a patient's adherence to weight-bearing prescriptions. Participants noted a lack of standardised postoperative protocols and the need for routine patient audits to better understand current practices and outcomes. CONCLUSION: This study contributes to national and global discussions on the prescription of early mobilisation and weight-bearing as tolerated. It highlights the necessity for a harmonised approach, incorporating standardised, evidence-based protocols with patient-specific care, robust healthcare governance and routine audits and monitoring for quality assurance and better patient outcomes.

Improving Palivizumab Administration to High-Risk Infants with Heart Disease via a Communication-Based Quality Improvement Initiative.

To improve palivizumab administration in high-risk infants with congenital heart disease to 80% over 2 years at an academic children's heart center. A multidisciplinary team at our institution implemented a series of interventions over a 2-year prior. Pediatric cardiac patients were identified for palivizumab eligibility, and a baseline rate of administration was obtained. A series of communication and documentation-based interventions were implemented over the course of the next 2 years. Palivizumab eligible infants (n = 114) were determined based on guidelines after review of diagnosis code, oxygen saturation, and medications. Doses of palivizumab were tracked via the electronic health record. The primary outcome measures were the rate of monthly palivizumab doses administered per the number of eligible months and the percentage of infants who received at least 80% of eligible doses during the respiratory syncytial virus season. The rate of monthly palivizumab doses increased from 57.6% during the baseline period to 78.4% during the final year of the project (p = 0.02). The percentage of infants who received 80% of eligible doses increased from 42.1 to 60% but was not statistically significant (p = 0.20). Interventions focused on properly identifying and tracking infants eligible for palivizumab treatment significantly increased the rates of administration.

Trajectories of depressive symptoms 10 years after stroke and associated risk factors: a prospective cohort study.

BACKGROUND: Previous studies have investigated the risk factors for post-stroke depression at only one timepoint, neglecting its dynamic nature. We aimed to identify trajectories of post-stroke depression from multiple assessments and explore their risk factors. METHODS: We did a population-based cohort study with the South London Stroke Register (1995-2019). All stroke patients with three or more measurements of the Hospital Anxiety and Depression Scale were included. We identified trajectories of post-stroke depression over a 10-year follow-up using group-based trajectory modelling. We determined the optimal number and shape of trajectories based on the lowest Bayesian information criterion, average posterior probability of assignment of each group over 0·70, and inclusion of at least 5% of participants within each group. We used multinomial logistic regression adjusted for age, sex, ethnicity, comorbidity, physical disability, stroke severity, history of depression and cognitive impairment to explore associations with different trajectories. FINDINGS: The analysis comprised 1968 participants (mean age 64·9 years [SD 13·8], 56·6% male and 43·4% female, 65·1% white ethnicity, 30·7% severe disability and 32·7% severe stroke). We identified four patterns of symptoms: no depressive symptoms (14·1%, n=277), low symptoms (41·7%, n=820), moderate symptoms and symptoms worsening early and then improving (34·6%, n=681), and high and increasing symptoms (9·7%, n=190). Compared with no depressive symptom trajectory, patients with severe disability, severe stroke, pre-stroke depression, and cognitive impairment were more likely to be in the moderate and high symptom groups (adjusted odds ratios [ORs] 2·26 [95% CI 1·56-3·28], 1·75 [1·19-2·57], 2·20 [1·02-4·74], and 2·04 [1·25-3·32], respectively). Female sex was associated with high depression (OR 1·65 [1·13-2·41]), while older age (≥65 years) was associated with moderate depression (OR 1·82 [1·36-2·45]). In men, the ORs for patients with severe disability, severe stroke, pre-stroke depression, and cognitive impairment being in the high depression group were 1·91 (1·01-3·60), 2·41 (1·26-4·60), 2·57 (0·84-7·88), and 2·68 (1·28-5·60), respectively. In women, the ORs were 1·08 (0·52-2·23), 1·30 (0·60-2·79), 19·2 (2·35-156·05), and 3·80 (1·44-10·01), respectively. INTERPRETATION: Female sex and older age were associated with distinct courses of depressive symptoms. In men, high depressive symptom trajectory was associated with severe stroke and severe disability, which was not the case in women. These findings were limited to patients with three or more assessments, who tended to have less severe disabilities than excluded patients and might not generalise to all stroke survivors. FUNDING: National Institute for Health and Care Research (NIHR).

The role of depression in the association between physiotherapy frequency and duration and outcomes after hip fracture surgery: secondary analysis of the physiotherapy hip fracture sprint audit.

PURPOSE: It is not known whether the association between the frequency and duration of physiotherapy and patient outcomes varies for those with and without depression. This study aims to evaluate whether the associations between the frequency and duration of physiotherapy after hip fracture surgery and discharge home, surviving at 30 days post-admission, and being readmitted 30 days post discharge vary by depression diagnosis. METHODS: Data were from 5005 adults aged 60 and over included in the UK Physiotherapy Hip Fracture Sprint Audit who had undergone surgery for a nonpathological first hip fracture. Logistic regression models were used to estimate the unadjusted and adjusted odds ratios and their 95% confidence intervals for the associations between physiotherapy frequency and duration and outcomes. RESULTS: Physiotherapy frequency and duration were comparable between patients with and without depression (42.1% and 44.6%). The average adjusted odds for a 30-min increase in physiotherapy duration for those with and without depression for discharge home were 1.05 (95% CI 0.85-1.29) vs 1.16 (95% CI 1.05-1.28, interaction p = 0.36), for 30-day survival were 1.26 (95% CI 1.06-1.50) vs 1.11 (95% CI 1.05-1.17, interaction p = 0.45) and for readmission were 0.89 (95% CI 0.81-0.98) vs 0.97 (95% CI 0.93-1.00, interaction p = 0.09). None of the interaction tests reached formal significance, but the readmission models were close (p = 0.09). CONCLUSION: Results suggest physiotherapy duration may be negatively associated with readmission in those with depression but not those without depression, while no clear difference in the other outcomes was noted.

Cohort profile: The South London Stroke Register - a population-based register measuring the incidence and outcomes of stroke.

PURPOSE: The South London Stroke Register (SLSR) is a population-based cohort study, which was established in 1995 to study the causes, incidence, and outcomes of stroke. The SLSR aims to estimate incidence, and acute and long term needs in a multi-ethnic inner-city population, with follow-up durations for some participants exceeding 20 years. PARTICIPANTS: The SLSR aims to recruit residents of a defined area within Lambeth and Southwark who experience a first stroke. More than 7700 people have been registered since inception, and >2750 people continue to be followed up. At the 2011 census, the source population was 357,308. FINDINGS TO DATE: The SLSR was instrumental in highlighting the inequalities in risk and outcomes in the UK, and demonstrating the dramatic improvements in care quality and outcomes in recent decades. Data from the SLSR informed the UK National Audit Office in its 2005 report criticising the poor state of stroke care in England. For people living in the SLSR area the likelihood of being treated in a stroke unit increased from 19% in 1995-7 to 75% in 2007-9. The SLSR has investigated health inequalities in stroke incidence and outcome. SLSR analyses have demonstrated that lower socioeconomic status was associated with poorer outcome, and that Black people and younger people have not experienced the same improvements in stroke incidence as other groups. FUTURE PLANS: As part of an NIHR Programme Grant for Applied Research, from April 2022 the SLSR has expanded to recruit ICD-11 defined stroke (including those with <24 h symptoms where there are neuroimaging findings), and have expanded the follow up interviews to collect more detailed information on quality of life, cognition, and care needs. Additional data items will be added over the Programme based on feedback from patients and other stakeholders.

Prevalence and natural history of depression after stroke: A systematic review and meta-analysis of observational studies.

BACKGROUND: Depression is the most frequent psychiatric condition after stroke and is associated with negative health outcomes. We aim to undertake a systematic review and meta-analysis of the prevalence and natural history of depression after stroke. METHODS AND FINDINGS: Studies published up to 4 November 2022 on Medline, Embase, PsycINFO, and Web of Science Core Collection were searched. We included studies of adults with stroke, where depression was assessed at a prespecified time point. Studies excluding people with aphasia and history of depression are excluded. Critical Appraisal Skills Programme(CASP) cohort study tool was used to assess risk of bias. A total of 77 studies were included in the pooled estimates of the prevalence of poststroke depression (PSD). The overall prevalence of depression was 27% (95% CI 25 to 30). Prevalence of depression was 24% (95% CI 21 to 28) by clinical interview and 29% (95% CI 25 to 32) by rating scales. Twenty-four studies with more than one assessment time point reported the natural history of PSD. Among people who were depressed within 3 months of stroke, 53% (95% CI 47 to 59) experienced persistent depression, while 44% (95% CI 38 to 50) recovered. The incidence of later depression (3 to 12 months after stroke) was 9% (95% CI 7 to 12). The cumulative incidence during 1 year after stroke was 38% (95% CI 33 to 43), and the majority (71% (95% CI 65 to 76)) of depression had onset within 3 months after stroke. The main limitation of the present study is that excluding people in source studies with severe impairments may produce imprecise estimates of the prevalence of PSD. CONCLUSIONS: In this study, we observed that stroke survivors with early-onset depression (within 3 months after stroke) are at high risks for remaining depressed and make up two-thirds of the incident cases during 1 year after stroke. This highlights the need for ongoing clinical monitoring of patients depressed shortly after stroke. TRIAL REGISTRATION: PROSPERO CRD42022314146.

Major variation in hepatocellular carcinoma treatment and outcomes in England: a retrospective cohort study.

Objective: Hepatocellular carcinoma (HCC) is increasingly incident in England, while survival remains poor with regional disparities. We aimed to explore the differences in HCC treatment across different geographical regions and to examine the impact on cancer survival. Methods: Incident HCC cases and treatment were identified from the English Hospital Episode Statistics (2016-2017) and then a subset by National Health Service (NHS) regions. Treatment was grouped into curative, palliative and untreated. Median survival was estimated to date of death in the national statistics. Results: The median observed survival was 8.6 months (95% CI 7.5 to 9.9) across all 2160 HCC cases, 52.1 months (CI 50.5, not reached) in 449 (20.8%) treated with curative intent, 21.0 months (CI 18.5 to 24.5) after other cancer-specific treatment in 449 (20.8%), and 2.3 months (CI 2.1 to 2.6) in 1262 (58.4%) untreated. Across NHS regions, <50% of cases received treatment (30.4%-49.6%), while between 14.2% and 27.7% had curative treatment. The 3-year survival was similar (23.5%-29.7%), except in the London region (40.0%). Conclusion: Majority of HCC cases in England are untreated and survival remains low, with variation in outcomes in regions with similar incident rates. A deeper exploration of regional treatments and screening practice is required to improve early detection and survival.

Using Conditional Inference Forests to Examine Predictive Ability for Future Falls and Syncope in Older Adults: Results from The Irish Longitudinal Study on Ageing.

BACKGROUND: The extent to which gait and mobility measures predict falls relative to other risk factors is unclear. This study examined the predictive accuracy of over 70 baseline risk factors, including gait and mobility, for future falls and syncope using conditional inference forest models. METHODS: Data from 3 waves of The Irish Longitudinal Study on Ageing (TILDA), a population-based study of community-dwelling adults aged ≥50 years were used (n = 4 706). Outcome variables were recurrent falls, injurious falls, unexplained falls, and syncope occurring over 4-year follow-up. The predictive accuracy was calculated using 5-fold cross-validation; as there was a class imbalance, the algorithm was trained using undersampling of the larger class. Classification rate, the area under the receiver operating characteristic curve (AUROC), and area under the precision recall curve (PRAUC) assessed predictive accuracy. RESULTS: Highest overall accuracy was 69.7% for recurrent falls in 50-64-year olds. AUROC and PRAUC were ≤0.69 and ≤0.39, respectively, for all outcomes indicating low predictive accuracy. History of falls, unsteadiness while walking, fear of falling, mobility, medications, mental health, and cardiovascular health and function were the most important predictors for most outcomes. CONCLUSIONS: Conditional inference forest models using over 70 risk factors resulted in low predictive accuracy for future recurrent, injurious and unexplained falls, and syncope in community-dwelling adults. Gait and mobility impairments were important predictors of most outcomes but did not discriminate well between fallers and non-fallers. Results highlight the importance of multifactorial risk assessment and intervention and validate key modifiable risk factors for future falls and syncope.

Trajectories of Depressive Symptoms Among Older Adults and in Adults With Hip Fracture: Analysis From the English Longitudinal Study of Ageing.

BACKGROUND: This study aimed to determine trajectories of depressive symptoms among older adults in England, overall and for those with hip fracture. The study aimed to explore the differential characteristics of each trajectory identified. METHODS: Analysis of adults aged 60 years or more (n = 7 050), including a hip fracture subgroup (n = 384), from the English Longitudinal Study of Ageing. Latent class growth mixture modeling was completed. Depressive symptom prevalence was estimated at baseline. Chi-square tests were completed to compare baseline characteristics across trajectories. RESULTS: Three trajectories of depressive symptoms (no, mild, and moderate-severe) were identified overall and for those with hip fracture. The moderate-severe trajectory comprised 13.7% and 7% of participants for overall and hip fracture populations, respectively. The proportion of participants with depressive symptoms in the moderate-severe trajectory was 65.4% and 85.2% for overall and hip fracture populations, respectively. Depressive symptoms were stable over time, with a weak trend toward increasing severity for the moderate-severe symptom trajectory. Participants in the moderate-severe symptom trajectory were older, more likely to be female, live alone, and had worse health measures than other trajectories (p < .001). CONCLUSIONS: Older adults, and those with hip fracture, follow one of the 3 trajectories of depressive symptoms that are broadly stable over time. Depressive symptoms' prevalence was higher for those with hip fracture and, when present, the symptoms were more severe than the overall population. Results suggest a role of factors including age, gender, and marital status in depressive symptom trajectories.

Stroke Outcomes in Women: A Population-Based Cohort Study.

BACKGROUND: Limited data are available on sex-related disparities in long-term outcomes after stroke. We estimated sex differences in various stroke long-term outcomes among survivors after stroke in a prospective 25-year follow-up study. METHODS: Individuals recruited to the South London Stroke Register, an ongoing multi-ethnic urban-based population stroke register, from 1995 onward were included in the analyses (n=6687). The outcomes were death, subsequent stroke, activity of daily living, instrumental activity of daily living, cognitive impairment, depression, anxiety, and health-related quality of life. Kaplan-Meier curves were generated for mortality, stroke recurrence, and recurrence-free survival by sex and Cox proportional hazards model used to model sex differences up to 25 years. Generalized estimating equation were used to model sex differences in risk of self-reported stroke outcomes over 10 years poststroke outcomes, adjusting for age, preexisting activity of daily living, case-mix, stroke subtypes, and other potential confounding risk factors. RESULTS: There were 49% women (mean age, 72 years; SD, 15.6) and 51% men (mean age, 67 years; SD, 14.3) in 6687 participants. Compared with men, women had 9% (95% CI, 3%-15%) lower covariate-adjusted risk of death and 6% (0%-13%) lower risk of stroke recurrence or death. Generally, women had significantly poorer outcomes in activity of daily living and anxiety than men, and the sex differences persisted to up to 5 years after stroke. Women also had poorer health-related quality of life in physical (ß=-2.06 [95% CI, -3.01 to -1.10]) and mental domains (ß=-1.48 [95% CI, -2.44 to -0.52]). Although not significant, there was a suggestive trend for poorer outcomes in cognitive impairment and depression in women. No significant difference in stroke recurrence were found between men and women. CONCLUSIONS: Female patients with stroke tended to have better covariate-adjusted survival but poorer outcomes among survivors than male patients, with deficits persisting to up to 5 years poststroke.

Prolonged Neuromuscular Blockade From Continuous Vecuronium in an Infant With Renal Failure Being Treated With Dialysis.

Neuromuscular blockade may be required in critically ill pediatric patients to facilitate ventilator synchrony or maintain safety during high-risk procedures. Vecuronium is one neuromuscular blocking agent used for this purpose; however, there are limited data regarding its use in pediatric patients with renal failure. Although predominantly considered to be metabolized by the liver, there are numerous adult cases and 1 pediatric case report that have described extended paralysis from vecuronium due to renal failure. The proposed mechanism is accumulation of renally cleared active metabolites. This case report describes an infant with vecuronium exposure during continuous renal replacement therapy who experienced prolonged neuromuscular blockade for several days after the agent was stopped. This highlights the importance of considering renal function when selecting neuromuscular blocking agent.

Do changes in outcomes following primary and revision hip replacement differ and relate to markers of socioeconomic status? A 1-year population-based cohort study.

BACKGROUND AND PURPOSE: There is little evidence on improvement after revision total hip replacement (THR). Moreover, improvements may be associated with socioeconomic status (SES). We investigated whether changes in Harris Hip Score (HHS) differ among patients undergoing primary and revision THR, and their association with markers of SES. PATIENTS AND METHODS: We conducted a populationbased cohort study on 16,932 patients undergoing primary and/or revision THR from 1995 to 2018 due to hip osteoarthritis. The patients were identified in the Danish Hip Arthroplasty Registry. Outcome was defined as mean change in HHS (0-100) from baseline to 1-year follow-up, and its association with SES markers (education, cohabiting, and wealth) was analyzed using multiple linear regression adjusting for sex, age, comorbidities, and baseline HHS. RESULTS: At 1-year follow-up, HHS improved clinically relevant for patients undergoing both primary THR: mean 43 (95% CI 43-43) and revision THR: mean 31 (CI 29-33); however, the increase was 12 points (CI 10-14) higher for primary THR. For primary THR, improvements were 0.9 points (CI 0.4-1.5) higher for patients with high educational level compared with low educational level, 0.4 points (CI 0.0-0.8) higher for patients cohabiting compared with living alone, and 2.6 points higher (CI 2.1-3.0) for patients with high wealth compared with low wealth. INTERPRETATION: Patients undergoing primary THR achieve higher improvements on HHS than patients undergoing revision THR, and the improvements are negatively related to markers of low SES. Health professionals should be aware of these characteristics and be able to identify patients who may benefit from extra rehabilitation to improve outcomes after THR to ensure equality in health.

Real-world comparison of healthcare resource utilization and costs of [177Lu]Lu-DOTA-TATE in patients with progressive neuroendocrine tumors in England: a matched cohort analysis using data from the hospital episode statistics dataset.

OBJECTIVE: To explore the healthcare resource utilization (HCRU) and costs for patients with progressive gastroenteropancreatic neuroendocrine tumors (GEP-NETs) treated with [177Lu]Lu-DOTA-TATE and matched patients treated with somatostatin analogs (SSAs), chemotherapy, or targeted therapies. METHODS: Hospital Episode Statistics (HES) dataset 2016-2018 was used to compare HCRU and costs between the two cohorts. The [177Lu]Lu-DOTA-TATE cohort included patients assigned with a diagnosis code relevant to GEP-NET, a procedure code for imaging or SSAs, and a subsequent code for radionuclide therapy. The non-[177Lu]Lu-DOTA-TATE cohort included patients assigned with a diagnosis code relevant to GEP-NET who had an increased frequency of SSAs or switched from SSAs to chemotherapy or targeted therapies. Cohorts were matched on propensity scores with sex, age at disease progression, and Charlson Comorbidity Index as parameters. Healthcare Resource Group codes were used for costing. RESULTS: A total of 199 matched patients were included. The [177Lu]Lu-DOTA-TATE cohort had lower overall costs (£1,882,028 vs. £3,016,321; p < .0001), non-elective inpatient spells (289 vs. 611 days) and costs (£849,569 vs. £1,707,109; p < .0001 for both), Accident & Emergency costs (£41,978 vs. £62,480; p = .0013), and average length of stay for overall inpatient spells (14.2 vs. 23.3 days; p = .1092) compared with the non-[177Lu]Lu-DOTA-TATE cohort. CONCLUSIONS: These analyses indicate significantly lower overall costs and HCRU for progressive GEP-NET patients treated with [177Lu]Lu-DOTA-TATE. Current research reveals that future real-world analyses would further benefit from using additional databases linked to the HES dataset such as the Clinical Practice Research Datalink and/or National Cancer Registration and Analysis Service database.

Neuroendocrine neoplasms (NENs) are uncommon cancers involving the body's neuroendocrine cells. One type of NEN that is less aggressive with more favorable characteristics and prognosis is known as neuroendocrine tumor (NET). Somatostatin receptors (SSTR) are expressed by most NETs and are important treatment targets. Two-thirds of NETs originate in the body's gastroenteropancreatic system (GEP-NETs). GEP-NET is typically treated in the first instance with somatostatin analogs (SSAs), while other treatments such as chemotherapy, biologic targeted therapy, or Radio Ligand Therapy (RLT), can be offered to patients who have progressed. [¹⁷⁷Lu]Lu-DOTA-TATE is a form of RLT that has recently been approved for use in England, Wales, and Scotland.The purpose of this study is to analyze the utilization of healthcare resources and the costs associated with the management of GEP-NETs patients who have progressed on SSAs. This study is based on hospital data from England as available in the Hospital Episode Statistics dataset 2016­2018.The utilization and costs of healthcare resources were compared between two groups of patients. Following progression, one group received [¹⁷⁷Lu]Lu-DOTA-TATE, while the other group received other therapies (chemotherapy, biologic targeted therapy, or SSA with escalated or more frequent dosing). Statistical techniques were applied to enhance the comparability of analyzed groups of patients.The results revealed that the [¹⁷⁷Lu]Lu-DOTA-TATE group had lower inpatient admissions, outpatient appointments, and Accident & Emergency attendances compared with the non-[¹⁷⁷Lu]Lu-DOTA-TATE group. Furthermore, the overall costs in the [¹⁷⁷Lu]Lu-DOTA-TATE group were lower by 37.6%. This study indicated that patients and hospitals in England and other parts of the United Kingdom may benefit from the use of [¹⁷⁷Lu]Lu-DOTA-TATE. Further research is foreseen involving additional and linked databases, including further clinical outcomes as well.

Impaired Stabilization of Orthostatic Cerebral Oxygenation Is Associated With Slower Gait Speed: Evidence From The Irish Longitudinal Study on Ageing.

BACKGROUND: Cerebral autoregulation (CAR) systems maintain blood flow to the brain across a wide range of blood pressures. Deficits in CAR have been linked to gait speed (GS) but previous studies had small sample sizes and used specialized equipment which impede clinical translation. The purpose of this work was to assess the association between GS and orthostatic cerebral oxygenation in a large, community-dwelling sample of older adults. METHOD: Data for this study came from the Irish Longitudinal Study on Ageing. A near-infrared spectroscopy (NIRS) device attached to the forehead of each participant (n = 2 708) was used to track tissue saturation index (TSI; the ratio of oxygenated to total hemoglobin) during standing. GS was assessed using a portable walkway. RESULTS: Recovery was impaired in slower GS participants with a TSI value at 20 seconds (after standing) of -0.55% (95% CI: -0.67, -0.42) below baseline in the slowest GS quartile versus -0.14% (95% CI: -0.25, -0.04) in the fastest quartile. Slower GS predicted a lower TSI throughout the 3-minute monitoring period. Results were not substantially altered by adjusting for orthostatic hypotension. Adjustment for clinical and demographic covariates attenuated the association between but differences remained between GS quartiles from 20 seconds to 3 minutes after standing. CONCLUSION: This study reported evidence for impaired recovery of orthostatic cerebral oxygenation depending on GS in community-dwelling older adults. Future work assessing NIRS as a clinical tool for monitoring the relationship between GS and cerebral regulation is warranted.

Diabetes As an Independent Risk Factor for Stroke Recurrence in Ischemic Stroke Patients: An Updated Meta-Analysis.

INTRODUCTION: Stroke and its recurrence and diabetes will increase in incidence as the population ages globally. This study explores the relationship between diabetes and stroke recurrence to understand if diabetes is an independent predictor for stroke recurrence in ischemic stroke (IS) patients. METHODS: We conducted a systematic review and meta-analysis of studies on the effect of diabetes on stroke recurrence among patients with IS. We searched population-based studies published before 15th February 2021 in PubMed and EMBASE following PRISMA guidelines. Random-effects estimates of the pooled hazard ratio (HR) and 95% confidence intervals (CIs) of each study were generated. A funnel plot and an Egger test were performed to evaluate publication bias. All statistical analyses were conducted in the R software 4.0.1 and Stata 16.0. RESULTS: The search identified 3,121 citations, of which 27 studies met inclusion criteria. Diabetes was associated with a significant risk of stroke recurrence in all IS patients (pooled HR, 1.50; 95% CI: 1.36-1.65; I2 = 61.0%). Similar results were found in lacunar stroke patients with diabetes (pooled HR, 1.65; 95% CI: 1.41-1.92; I2 = 22.0%). Moreover, we found that the risk of recurrent IS among patients of IS with diabetes was higher than that in those without diabetes (pooled HR, 1.53; 95% CI: 1.30-1.81; I2 = 74.0%). CONCLUSION: Diabetes is an independent risk factor for stroke recurrence among patients with IS.

Doxycycline promotes proteasome fitness in the central nervous system.

Several studies reported that mitochondrial stress induces cytosolic proteostasis in yeast and C. elegans. Notably, inhibition of mitochondrial translation with doxcycyline decreases the toxicity of ß-amyloid aggregates, in a C. elegans. However, how mitochondrial stress activates cytosolic proteostasis remains unclear. Further whether doxycycline has this effect in mammals and in disease relevant tissues also remains unclear. We show here that doxycycline treatment in mice drastically reduces the accumulation of proteins destined for degradation by the proteasome in a CNS region-specific manner. This effect is associated with the activation of the ERα axis of the mitochondrial unfolded protein response (UPRmt), in both males and females. However, sexually dimorphic mechanisms of proteasome activation were observed. Doxycycline also activates the proteasome in fission yeast, where ERα is not expressed. Rather, the ancient ERα-coactivator Mms19 regulates this response in yeast. Our results suggest that the UPRmt initiates a conserved mitochondria-to-cytosol stress signal, resulting in proteasome activation, and that this signal has adapted during evolution, in a sex and tissue specific-manner. Therefore, while our results support the use of doxycycline in the prevention of proteopathic diseases, they also indicate that sex is an important variable to consider in the design of future clinical trials using doxycycline.

A retrospective cohort study comparing clinical outcomes and healthcare resource utilisation in patients undergoing surgery for osteomyelitis in England: a case for reorganising orthopaedic infection services.

Aims: An investigation of the impact of a multidisciplinary bone infection unit (BIU) undertaking osteomyelitis surgery with a single-stage protocol on clinical outcomes and healthcare utilisation compared to national outcomes in England. Patients and Methods: A tertiary referral multidisciplinary BIU was compared to the rest of England (ROE) and a subset of the 10 next busiest centres based on osteomyelitis treatment episode volume (Top Ten), using the Hospital Episodes Statistics database (HES). A total of 25 006 patients undergoing osteomyelitis surgery between April 2013 and March 2017 were included. Data on secondary healthcare resource utilisation and clinical indicators were extracted for 24 months before and after surgery. Results: Patients treated at the BIU had higher orthopaedic healthcare utilisation in the 2 years prior to their index procedure, with more admissions ( p <  0.001) and a mean length of stay (LOS) over 4 times longer than other groups (10.99 d, compared to 2.79 d for Top Ten and 2.46 d for the ROE, p <  0.001). During the index inpatient period, the BIU had fewer mean theatre visits (1.25) compared to the TT (1.98, p <  0.001) and the ROE (1.64, p =  0.001). The index inpatient period was shorter in the BIU (11.84 d), 33.6 % less than the Top Ten (17.83 d, p <  0.001) and 29.9 % shorter than the ROE (16.88 d, p <  0.001). During follow-up, BIU patients underwent fewer osteomyelitis-related reoperations than Top Ten centres ( p =  0.0139) and the ROE ( p =  0.0137). Mortality was lower (4.71 %) compared to the Top Ten (20.06 %, p <  0.001) and the ROE (22.63 %, p <  0.001). The cumulative BIU total amputation rate was lower (6.47 %) compared to the Top Ten (15.96 %, p <  0.001) and the ROE (12.71 %, p <  0.001). Overall healthcare utilisation was lower in the BIU for all inpatient admissions, LOS, and Accident and Emergency (A&E) attendances. Conclusion: The benefits of managing osteomyelitis in a multi-disciplinary team (MDT) specialist setting included reduced hospital stays, lower reoperation rates for infection recurrence, improved survival, lower amputation rates, and lower overall healthcare utilisation. These results support the establishment of centrally funded multidisciplinary bone infection units that will improve patient outcomes and reduce healthcare utilisation.

Is orthostatic hypotension and co-existing supine and seated hypertension associated with future falls in community-dwelling older adults? Results from The Irish Longitudinal Study on Ageing (TILDA).

Orthostatic hypotension (OH) often co-exists with hypertension. As increasing age affects baroreflex sensitivity, it loses its ability to reduce blood pressure when lying down. Therefore, supine hypertension may be an important indicator of baroreflex function. This study examines (i) the association between OH and future falls in community-dwelling older adults and (ii) if these associations persist in those with co-existing OH and baseline hypertension, measured supine and seated. Data from 1500 community-dwelling adults aged ≥65 years from The Irish Longitudinal Study on Ageing (TILDA) were used. Continuous beat-to-beat blood pressure was measured using digital photoplethysmography during an active stand procedure with OH defined as a drop in systolic blood pressure (SBP) ≥20 mmHg and/or ≥10 mm Hg in diastolic blood pressure (DBP) within 3 minutes of standing. OH at 40 seconds (OH40) was used as a marker of impaired early stabilisation and OH sustained over the second minute (sustained OH) was used to indicate a more persistent deficit, similar to traditional OH definitions. Seated and supine hypertension were defined as SBP ≥140 mm Hg or DBP ≥90 mm Hg. Modified Poisson models were used to estimate relative risk of falls (recurrent, injurious, unexplained) and syncope occurring over four year follow-up. OH40 was independently associated with recurrent (RR = 1.30, 95% CI = 1.02,1.65), injurious (RR = 1.43, 95% CI = 1.13,1.79) and unexplained falls (RR = 1.55, 95% CI = 1.13,2.13). Sustained OH was associated with injurious (RR = 1.55, 95% CI = 1.18,2.05) and unexplained falls (RR = 1.63, 95% CI = 1.06,2.50). OH and co-existing hypertension was associated with all falls outcomes but effect sizes were consistently larger with seated versus supine hypertension. OH, particularly when co-existing with hypertension, was independently associated with increased risk of future falls. Stronger effect sizes were observed with seated versus supine hypertension. This supports previous findings and highlights the importance of assessing orthostatic blood pressure behaviour in older adults at risk of falls and with hypertension. Observed associations may reflect underlying comorbidities, reduced cerebral perfusion or presence of white matter hyperintensities.

Online and telephone access to general practice: a cross-sectional patient survey.

BACKGROUND: Improving access to primary health care in the UK has focused on the use of telephone and online access, but little is known about how awareness of and use varies between different patient groups. AIM: To determine how patients are interacting with telephone and online channels for accessing general practice services and information, and to analyse how this varies according to patient characteristics and health status. DESIGN & SETTING: A cross-sectional self-administered survey of adult patients in general practices across the West Midlands, UK. METHOD: Descriptive statistics were used to show participants' awareness of and interaction with online information sources and remote access. Multivariable logistic regression was used to model the relationships between demographic and health characteristics, and awareness and use of online services and alternatives to face-to-face consultations (for example, telephone). RESULTS: A total of 2789 patients (19.0% response rate) from 43 general practices participated. The study found 60.8% (n = 1651/2715) of participants were aware of online services and 30.3% (n = 811/2674) reported having used one. Daily internet usage and frequently visiting the GP showed the strongest associations with knowledge and use of online services. CONCLUSION: The study shows that there is the potential for inequitable awareness and use of telephone and online services in general practice populations. Given that their use has greatly increased owing to the COVID-19 pandemic, future service design will need to ensure equity is taken into account.