The usability and reliability of a smartphone application for monitoring future dementia risk in ageing UK adults.

BACKGROUND: The rising number of dementia diagnoses and imminent adoption of disease-modifying treatments necessitate innovative approaches to identify individuals at risk, monitor disease course and intervene non-pharmacologically earlier in the disease course. Digital assessments of dementia risk and cognitive function have the potential to outperform traditional in-person assessments in terms of their affordability, accuracy and longitudinal tracking abilities. However, their accessibility and reliability in older adults is unclear. AIMS: To evaluate the usability and reliability of a smartphone assessment of lifestyle and cognitive factors relevant to dementia risk in a group of UK-based older adults. METHOD: Cognitively healthy adults (n = 756) recruited through the Dementias Platform UK Great Minds volunteer register completed three assessments of cognitive function and dementia risk over a 3-month period and provided usability feedback on the Five Lives smartphone application (app). We evaluated cognitive test scores for age, gender and higher education effects, normality distributions, test-retest reliability and their relationship with participants' lifestyle dementia risk factors. RESULTS: Participants found the app 'easy to use', 'quick to complete' and 'enjoyable'. The cognitive tests showed normal or near-to-normal distributions, variable test-retest reliabilities and age-related effects. Only tests of verbal ability showed gender and education effects. The cognitive tests did not correlate with lifestyle dementia risk scores. CONCLUSIONS: The Five Lives assessment demonstrates high usability and reliability among older adults. These findings highlight the potential of digital assessments in dementia research and clinical practice, enabling improved accessibility and better monitoring of cognitive health on a larger scale than traditional in-person assessments.

Exploring the Collateral Damage of the COVID-19 Pandemic on Stroke Care: A Statewide Analysis.

[Figure: see text].

A Therapeutic International Normalized Ratio Results in Smaller Infarcts and Better Outcomes for Patients with Ischemic Stroke.

BACKGROUND: Prior studies have shown that warfarin is effective for both primary and secondary stroke prevention in individuals with atrial fibrillation. It is also known that those on warfarin with atrial fibrillation often have poorer long-term poststroke outcomes, possibly because cardioembolic strokes tend to be larger and more severe. Less is known regarding the direct effect of the international normalized ratio (INR) value at the time of stroke on severity or long-term functional status. METHODS: We prospectively followed a consecutive series of 112 patients presenting to our institution with acute ischemic stroke between 2013 and 2018 who were on warfarin. Along with INR on admission, data were collected regarding patient demographics, vascular risk factors, stroke characteristics, and functional outcomes. Patients were stratified by INR into "therapeutic" and "subtherapeutic" groups. Stroke severity (NIH Stroke Scale), infarct volume, and outcome (modified Rankin Scale) were assessed on admission, discharge, and follow-up (3 months poststroke). Differences were calculated using Student's t-tests and regression analyses. RESULTS: The average INR on admission was 1.6 for the entire cohort. Seventy six percent were subtherapeutic on admission (INR < 2.0). Therapeutic patients had lower National Institutes of Health Stroke Scale scores on admission (5.9 versus 9.5, P = .033), significantly smaller stroke volumes (19.5 cc versus 49.2 cc, P = .036), and were more likely to show more than 1 digit improvement on follow-up mRS than subtherapeutic patients. CONCLUSIONS: Stroke size and severity is significantly reduced in patients with ischemic strokes who present therapeutic on warfarin. The greater volume of brain saved may ultimately lead to better functional recovery.

Predicting symptomatic intracerebral hemorrhage versus lacunar disease in patients with longstanding hypertension.

BACKGROUND AND PURPOSE: Hypertension results in a spectrum of subcortical cerebrovascular disease. It is unclear why some individuals develop ischemia and others develop hemorrhage. Risk factors may differ for each population. We identify factors that predispose an individual to subcortical symptomatic intracerebral hemorrhage (sICH) compared with ischemia. METHODS: Demographic and laboratory data were prospectively collected for hypertensive patients presenting with ischemic stroke or sICH during an 8.5-year period. Neuroimaging was retrospectively reviewed for acute (subcortical lacunes [<2.0 cm] versus subcortical sICH) and chronic (periventricular white matter disease and cerebral microbleeds) findings. We evaluated the impact of age, race, sex, serum creatinine, erythrocyte sedimentation rate, low-density lipoprotein, presence of periventricular white matter disease or cerebral microbleeds, and other factors on the risk of sICH versus acute lacune using multivariate logistic regression. RESULTS: Five hundred seventy-one patients had subcortical pathology. The presence of cerebral microbleeds (adjusted odds ratio [OR], 3.39; confidence interval [CI], 2.09-5.50) was a strong predictor of sICH, whereas severe periventricular white matter disease predicted ischemia (OR, 0.56 risk of sICH; CI, 0.32-0.98). This association was strengthened when the number of microbleeds was evaluated; subjects with >5 microbleeds had an increased risk of sICH (OR, 4.11; CI, 1.96-8.59). It remained significant when individuals with only cortical microbleeds were removed (OR, 1.77, CI, 1.13-2.76). An elevated erythrocyte sedimentation rate (OR, 1.19 per 10 mm/h increase; CI, 1.06-1.34) was significantly associated with sICH, whereas low-density lipoprotein was associated with ischemic infarct (OR, 0.93 risk of sICH per 10 mg/dL increase; CI, 0.86-0.99). CONCLUSIONS: Subclinical pathology is the strongest predictor of the nature of subsequent symptomatic event. Low-density lipoprotein and erythrocyte sedimentation rate may also have a role in risk stratification.

Scrambler therapy for treatment of poststroke pain.

OBJECTIVE: Strokes involving sensory pathways can result in contralesional pain syndromes often refractory to pharmacologic interventions. Scrambler therapy (ST) is a noninvasive electroanalgesia device used to treat pain caused by peripheral neuropathy; however, data are scarce regarding its use in conditions secondary to central nervous system pathology. We evaluate the efficacy of ST to treat poststroke pain. METHODS: Twenty patients with a history of prior stroke resulting in contralesional pain were randomized to receive ST or Sham as an adjunct to their stable medication regimen. Participants underwent 5 consecutive daily 40-min sessions. The study was blinded to patient and assessor. Pain scores (0-10) were recorded at baseline, pre- and postsession, and 4 weeks after final treatment. Student's t-tests compared differences in the mean change in pain score between groups immediately post-treatment #5, and at 4-weeks. The chi-squared analysis compared the proportion of patients in each group with >50% pain reduction. RESULTS: Participants randomized to ST had a mean change in pain score of -3.73 (SD 2.85) postintervention and -2.57 (SD 2.07) at 4 weeks, while the Sham group had a mean change in score of -0.94 (SD 1.36) and -0.25 (SD 0.84) (p between groups = 0.012, 0.004, respectively). Significantly more participants treated with ST reported a >50% reduction in pain immediately postintervention compared to Sham (70% vs. 10%, p = 0.006), but not at follow-up (30% vs. 10%, p = ns). INTERPRETATION: ST may effectively decrease poststroke pain compared to Sham. Larger studies are needed to evaluate confounders such as stroke location, time from stroke, and concomitant treatment with medications.

Self-directed digital interventions for the improvement of emotion regulation-effectiveness for mental health and functioning in adolescents: protocol for a systematic review.

INTRODUCTION: Research suggests that problems with emotion regulation, that is, how a person manages and responds to an emotional experience, are related to a range of psychological disorders (eg, bipolar disorder, anxiety and depression). Interventions targeting emotion regulation have been shown to improve mental health in adults, but evidence on related interventions for adolescents is still emerging. Increasingly, self-directed digital interventions (eg, mobile apps) are being developed to target emotion regulation in this population, but questions remain about their effectiveness. This systematic review aimed to synthesise evidence on current self-directed digital interventions available to adolescents (aged 11-18 years) and their effectiveness in addressing emotion regulation, psychopathology and functioning (eg, academic achievement). METHODS AND ANALYSIS: Several electronic databases will be searched (eg, MEDLINE, PsycINFO, ACM Digital Library) to identify all studies published any time after January 2010 examining self-directed digital interventions for adolescents, which include an emotion regulation component. This search will be updated periodically to identify any new relevant research from the selected databases. Data on the study characteristics (eg, author(s)) and methodology, participant characteristics (eg, age) and the digital interventions used to address emotion (dys-)regulation (eg, name, focus) will be extracted. A narrative synthesis of all studies will be presented. If feasible, the effectiveness data will be synthesised using appropriate statistical techniques. The methodological quality of the included studies will be assessed with the Effective Public Health Practice Project quality assessment tool. ETHICS AND DISSEMINATION: Ethical approval is not required for this study. Findings will be disseminated widely via peer-reviewed publications and presentations at conferences related to this field. REGISTRATION DETAILS: PROSPERO CRD42022385547.

Understanding psychosis complexity through a syndemic framework: A systematic review.

Psychotic conditions pose significant challenges due to their complex aetiology and impact on individuals and communities. Syndemic theory offers a promising framework to understand the interconnectedness of various health and social problems in the context of psychosis. This systematic review aims to examine existing literature on testing whether psychosis is better understood as a component of a syndemic. We conducted a systematic search of 7 databases, resulting in the inclusion of five original articles. Findings from these studies indicate a syndemic characterized by the coexistence of various health and social conditions, are associated with a greater risk of psychosis, adverse health outcomes, and disparities, especially among ethnic minorities and deprived populations. This review underscores the compelling need for a new paradigm and datasets that can investigate how psychosis emerges in the context of a syndemic, ultimately guiding more effective preventive and care interventions as well as policies to improve the health of marginalised communities living in precarity.

Barriers to brain health behaviours: results from the Five Lives Brain Health Ireland Survey.

Modifiable risk factors for dementia remain prevalent in Ireland. A detailed examination of barriers to risk reduction behaviours in an Irish context has heretofore been lacking. Many existing studies examining barriers to brain health behaviours fail to examine how they might vary across different modifiable risk factors. This study undertook a detailed assessment of barriers to individual risk reduction behaviours. As existing research suggests that barriers may vary across sociodemographic factors, we sought to investigate the distribution of barriers across age, gender, educational status, and household income. The Five Lives Brain Health Ireland Survey is a cross-sectional survey that was distributed online amongst a non-patient population. The survey captured the following: (1) Sociodemographic factors; (2) Barriers to brain health behaviours; (3) Exposure to, and knowledge of, modifiable risk factors for dementia, namely diet, social interaction, exercise, hypertension, sleep, current low mood/depression, current smoking, alcohol consumption, cognitive stimulation, hearing impairment, diabetes, air pollution, and head injury; (4) Participants' perceptions regarding potential for dementia prevention, and risk reduction. Lack of motivation was the most prevalent barrier to consuming a healthy diet (64%, n = 213), physical activity (77.7%, n = 167), smoking cessation (68%, n = 85), and moderation of alcohol intake (56.3%, n = 67). Practical factors were the most prevalent barriers to addressing low mood (56.5%, n = 87), air pollution (30.1%, n = 58), hearing impairment (63.8%, n = 44), diabetes (11.1%, n = 5), and head injury (80%, n = 8). Emotional factors were the most prevalent barriers to engaging in mentally stimulating activity (56.9%, n = 66), social activity (54.9%, n = 302), and good sleep (70.1%, n = 129). Lack of knowledge was the most prevalent barrier to hypertension control (14.4%, n = 29). Distribution of barriers varied across age, gender, educational status, and household income. This study investigated barriers to lifestyle change to improve brain health in an Irish sample of adults aged 50 and above. Detailed subtyping of barriers, as well as examination of differences according to age, gender, education, and income were undertaken. The heterogeneity of barriers to brain health behaviours revealed in this study highlights the necessity to tailor public health interventions to their target population, taking into account the gender, age, educational status, and income of recipients.

Modifiable risk factors for dementia, and awareness of brain health behaviors: Results from the Five Lives Brain Health Ireland Survey (FLBHIS).

Up to 40% of dementias globally are attributable to modifiable risk factors. Many existing studies examining attitudes to brain health are limited by a failure to consider a range of pertinent risk factors and associated barriers to protective behaviors. In Ireland, self-reported knowledge of dementia is poor compared to other conditions. In this context, the current study aimed to explore exposure to and awareness of specific modifiable risk factors for dementia. We also aimed to investigate whether exposure to these risk factors is associated with demographic and socioeconomic factors. A cross-sectional survey was administered to 555 voluntary participants in February 2022. The survey captured the following information: (1) Sociodemographic factors; (2) Exposure to, as well as knowledge of modifiable risk factors for dementia, namely diet, social interaction, exercise, hypertension, sleep, depression, smoking, alcohol consumption, cognitive stimulation, hearing impairment, diabetes, air pollution, and head injury. The study population comprised 551 participants (50.3% male; 49.6% female). Mean age was 59.7 years. Modifiable risk factors for dementia were prevalent. Relative to females, male gender was significantly associated with multiple risk factors. Whilst 65.6% of participants believed that lifestyle improvements can decrease a person's risk of developing dementia, only 31.4% believed that dementia could be prevented. Head injury (90.9%, n = 500), low mental stimulation (85.3%, n = 469), and alcohol consumption (77.8%, n = 428) were the three most commonly recognized risk factors. Awareness was significantly greater in both university groups (undergraduate and postgraduate) for multiple risk factors. Our findings demonstrate that the distribution of exposure to modifiable risk factors for dementia is unequal across gender and age groups, and that awareness levels vary across risk factors. These findings highlight that focus surrounding dementia prevention should shift toward individual risk profiling and should be tailored toward an individual's specific needs.

Mental well-being interventions in the military: The ten key principles.

Organisations including the United Kingdom Armed Forces should seek to implement mental health interventions to increase the psychological well-being of their workforce. This editorial briefly presents ten key principles that military forces should consider before implementing such interventions. These include job-focused training; evaluating interventions; the use of internal versus external training providers; the role of leaders; unit cohesion, single versus multiple session psychological interventions; not overgeneralising the applicability of interventions; the need for repeated skills practice; raising awareness and the fallibility of screening.

Myelodysplasia Syndrome, Clonal Hematopoiesis and Cardiovascular Disease.

The development of myelodysplasia syndromes (MDS) is multiphasic and can be driven by a plethora of genetic mutations and/or abnormalities. MDS is characterized by a hematopoietic differentiation block, evidenced by increased immature hematopoietic cells, termed blast cells and decreased mature circulating leukocytes in at least one lineage (i.e., cytopenia). Clonal hematopoiesis of indeterminate potential (CHIP) is a recently described phenomenon preceding MDS development that is driven by somatic mutations in hemopoietic stem cells (HSCs). These mutant HSCs have a competitive advantage over healthy cells, resulting in an expansion of these clonal mutated leukocytes. In this review, we discuss the multiphasic development of MDS, the common mutations found in both MDS and CHIP, how a loss-of-function in these CHIP-related genes can alter HSC function and leukocyte development and the potential disease outcomes that can occur with dysfunctional HSCs. In particular, we discuss the novel connections between MDS development and cardiovascular disease.

The Maryland Acute Stroke Emergency Medical Services Routing Pilot: Expediting Access to Thrombectomy for Stroke.

Background: Mechanical thrombectomy (MT) is the standard of care for acute ischemic stroke caused by large vessel occlusion, but is not available at all stroke centers. Transfers between hospitals lead to treatment delays. Transport directly to a facility capable of MT based on a prehospital stroke severity scale score has been recommended, if transportation time is less than 30 min. Aims: We hypothesized that an Emergency Medical Services (EMS) routing algorithm for stroke, using the Los Angeles Motor Scale (LAMS) in the field, would improve time from last known well to MT, without causing patients to miss the IV Thrombolysis (IVT) window. Methods: An EMS algorithm in the Baltimore metro area using the LAMS was implemented. Patients suspected of having an acute stroke were assessed by EMS using the LAMS. Patients scoring 4 or higher and within 20 h from last known well, were transported directly to a Thrombectomy Center, if transport could be completed within 30 min. The algorithm was evaluated retrospectively with prospectively collected data at the Thrombectomy Centers. The primary outcome variables were proportion of patients with suspected stroke rerouted by EMS, proportion of rerouted ischemic stroke patients receiving MT, time to treatment, and whether the IVT window was missed. Results: A total of 303 patients were rerouted out of 2459 suspected stroke patients over a period of 6 months. Of diverted patients, 47% had acute ischemic stroke. Of these, 48% received an acute stroke treatment: 16.8% IVT, 17.5% MT, and 14% MT+IVT. Thrombectomy occurred 119 min earlier in diverted patients compared to patients transferred from other hospitals (P = 0.006). 55.3% of diverted patients undergoing MT and 38.2% of patients transferred from hospital to hospital were independent at 90 days (modified Rankin score 0-2) (P = 0.148). No patient missed the time window for IVT due to the extra travel time. Conclusions: In this retrospective analysis of prospectively acquired data, implementation of a pre-hospital clinical screening score to detect patients with suspected acute ischemic stroke due to large vessel occlusion was feasible. Rerouting patients directly to a Thrombectomy Center, based on the EMS algorithm, led to a shorter time to thrombectomy.

Streamlining the Process for Intravenous Tissue Plasminogen Activator.

BACKGROUND: For ischemic stroke, the chance of improved recovery is directly impacted by length of time from symptom onset to administration of intravenous tissue plasminogen activator (IV tPA). Despite the importance of rapid treatment, stroke centers struggle with achieving consistent door-to-needle times of less than 60 minutes. METHODS: We implemented a change in our response to the acute stroke patient by adding a dedicated stroke nurse and a nursing flow sheet focused on critical benchmarks before treatment. We collected data on patients treated with IV tPA preintervention and postintervention to determine whether our process increased the number of patients receiving tPA in less than 60 minutes. One hundred thirty-eight patients (n = 78 pre and 60 post) treated between 2009 and 2013 were included. Student t tests and χ tests were used to compare door-to-needle times preintervention and postintervention. RESULTS: By implementing this new approach, the mean time to treatment decreased from 82 to 78 minutes (P = .583). The percentage of patients successfully treated within 60 minutes of arrival improved from 28% to 52% (P = .005). Stroke severity and need for additional imaging were associated with increased time to treatment. CONCLUSION: The use of a stroke nurse and a nursing flow sheet as part of the acute stroke assessment significantly increases the proportion of patients treated with IV tPA within 60 minutes from hospital arrival.

Pre-stroke employment results in better patient-reported outcomes after minor stroke: Short title: Functional outcomes after minor stroke.

OBJECTIVE: Individuals with "minor stroke" lack a dense hemiparesis or aphasia; however, commonly endorse persistent cognitive and motor problems despite low NIHSS scores. They also report problems with mood, energy, and the ability to think clearly that are less well characterized. Socioeconomic factors and stroke severity can influence patient-reported outcomes. In this study we explore patient-reported outcomes and the influence of these factors after minor stroke. PATIENTS AND METHODS: Patients returning to clinic post-stroke with an NIHSS of ≤ 4 were administered a scale to quantify problems with daily activities and resulting functional burden, along with measures of fatigue and depression. T-tests, chi square analysis, and linear regression were used to compare functional outcomes of patients to controls (TIA or stroke mimic (n = 40)), and evaluate the association between patient-reported outcomes, stroke characteristics, and socioeconomic factors. RESULTS: 151 stroke patients were seen a mean 83.6 days post-infarct. Patients reported more problems (11.7 versus 6.9, p = 0.02), resulting in higher functional burden (26.5 versus 12.3, p = 0.01), increased depression (p = 0.07), and greater fatigue (p = 0.02) compared to controls. There was no relationship between stroke characteristics (other than NIHSS), baseline education, income, marital status, or living situation and perception of recovery; however, those actively working prior to their stroke reported better outcomes across all categories (p for each <0.02), and differences persisted in multivariable regression models. CONCLUSION: Prior occupational status may represent an important prognostic indicator for patients with minor stroke. Individuals working at the time of their infarct report better functional outcomes irrespective of age or stroke severity.

The NIH Stroke Scale Has Limited Utility in Accurate Daily Monitoring of Neurologic Status.

BACKGROUND AND PURPOSE: The National Institute of Health Stroke Scale (NIHSS) is rapid and reproducible, a seemingly attractive metric for the documentation of clinical progress in patients presenting with ischemic stroke. Many institutions have adopted it into daily clinical practice. Unfortunately, the scale may not adequately capture all forms of functional change. We evaluate its utility as a measure of recovery in patients treated with intravenous tissue plasminogen activator (IV tPA) for ischemic stroke. METHODS: We prospectively evaluated the difference in the rate of improvement based on NIHSS (a ≥4 point change based on previous trials) versus physician-documented subjective and objective measures in 41 patients' status post IV tPA treatment. The NIHSS 24 hours posttreatment, on discharge, and at follow-up were compared to NIHSS on admission using tests of proportions and McNemar tests of paired data. Secondary analyses were performed defining significant improvement as NIHSS changes of 1 to 3 points. RESULTS: The mean NIHSS improved from 9 to 6, 24 hours post-tPA. Of the 41 patients, 29 improved by physician documentation, although only 11 of the 29 met the NIHSS criteria (P < .001; McNemar P < .001). On discharge, 20 of the 41 patients met the NIHSS criteria; however, the proportion "better" by physician documentation (71%) remained significantly higher (P = .04; McNemar P = .004). The mean postdischarge follow-up NIHSS was 2. Twenty of the 21 patients improved by documentation versus 16 of the 21 by NIHSS (P = .08, McNemar P = .125). Using NIHSS changes of 1 to 3 increased sensitivity for detecting improvement but remained lower than physician documentation. CONCLUSION: The NIHSS has many advantages; however, it may miss functional changes when used in place of a comprehensive neurological examination to measure improvement poststroke.

Predicting Hemorrhagic Transformation of Acute Ischemic Stroke: Prospective Validation of the HeRS Score.

Hemorrhagic transformation (HT) increases the morbidity and mortality of ischemic stroke. Anticoagulation is often indicated in patients with atrial fibrillation, low ejection fraction, or mechanical valves who are hospitalized with acute stroke, but increases the risk of HT. Risk quantification would be useful. Prior studies have investigated risk of systemic hemorrhage in anticoagulated patients, but none looked specifically at HT. In our previously published work, age, infarct volume, and estimated glomerular filtration rate (eGFR) significantly predicted HT. We created the hemorrhage risk stratification (HeRS) score based on regression coefficients in multivariable modeling and now determine its validity in a prospectively followed inpatient cohort.A total of 241 consecutive patients presenting to 2 academic stroke centers with acute ischemic stroke and an indication for anticoagulation over a 2.75-year period were included. Neuroimaging was evaluated for infarct volume and HT. Hemorrhages were classified as symptomatic versus asymptomatic, and by severity. HeRS scores were calculated for each patient and compared to actual hemorrhage status using receiver operating curve analysis.Area under the curve (AUC) comparing predicted odds of hemorrhage (HeRS score) to actual hemorrhage status was 0.701. Serum glucose (P < 0.001), white blood cell count (P < 0.001), and warfarin use prior to admission (P = 0.002) were also associated with HT in the validation cohort. With these variables, AUC improved to 0.854. Anticoagulation did not significantly increase HT; but with higher intensity anticoagulation, hemorrhages were more likely to be symptomatic and more severe.The HeRS score is a valid predictor of HT in patients with ischemic stroke and indication for anticoagulation.

Identification of Stem Cell Units in the Terminal End Bud and Duct of the Mouse Mammary Gland.

The mouse mammary gland may undergo cycles of proliferation, terminal differentiation, tissue remodeling, and more importantly malignant transformation.Mammary epithelial stem cells and their progeny participate in these processes.Mammary epithelial stem cells are multipotent, exhibit properties of self renewal (up to 7 divisions)and may exist either as long-lived nondividing cells or as proliferating-differentiating cells. The focus of this study was to locate stem cells by identifying them as long-lived, label-retaining mammary epithelial cells (LRCs)in growth active (developing)or growth static (aged)mammary ducts. Initially, primary epithelial cells were pulse labeled with either fluorescent tracker dye and/or BrdU. Cells were then transplanted into cleared juvenile syngeneic mammary fat pads and held for 5 weeks or 8 weeks. In this study, we demonstrate that LRCs are stem cells and their progeny (transitional cells)are arranged as transitional units (TUs). Additionally, TUs are located every 250 +/- 75 &mgr;m in ducts or in the terminal end bud 200-600 &mgr;m in diameter. Molecules expressed in TUs were Zonula Occludens-1 and alpha-catenin proteins which were significantly detected in 75%-91% (P <0.001)of the LRCs cells that make up the TU. These data suggest that transitional units may be a group of label-retaining stem cells and maybe involved in the developmental or cancer process.