GGC expansions in NOTCH2NLC contribute to Parkinson disease and dopaminergic neuron degeneration.

BACKGROUND AND PURPOSE: The role of GGC repeat expansions within NOTCH2NLC in Parkinson's disease (PD) and the substantia nigra (SN) dopaminergic neuron remains unclear. Here, we profile the NOTCH2NLC GGC repeat expansions in a large cohort of patients with PD. We also investigate the role of GGC repeat expansions within NOTCH2NLC in the dopaminergic neurodegeneration of SN. METHODS: A total of 2,522 patients diagnosed with PD and 1,085 health controls were analyzed for the repeat expansions of NOTCH2NLC by repeat-primed PCR and GC-rich PCR assay. Furthermore, the effects of GGC repeat expansions in NOTCH2NLC on dopaminergic neurons were investigated by using recombinant adeno-associated virus (AAV)-mediated overexpression of NOTCH2NLC with 98 GGC repeats in the SN of mice by stereotactic injection. RESULTS: Four PD pedigrees (4/333, 1.2%) and three sporadic PD patients (3/2189, 0.14%) were identified with pathogenic GGC repeat expansions (larger than 60 GGC repeats) in the NOTCH2NLC gene, while eight PD patients and one healthy control were identified with intermediate GGC repeat expansions ranging from 41 to 60 repeats. No significant difference was observed in the distribution of intermediate NOTCH2NLC GGC repeat expansions between PD cases and controls (Fisher's exact test p-value = 0.29). Skin biopsy showed P62-positive intranuclear NOTCH2NLC-polyGlycine (polyG) inclusions in the skin nerve fibers of patient. Expanded GGC repeats in NOTCH2NLC produced widespread intranuclear and perinuclear polyG inclusions, which led to a severe loss of dopaminergic neurons in the SN. Consistently, polyG inclusions were presented in the SN of EIIa-NOTCH2NLC-(GGC)98 transgenic mice and also led to dopaminergic neuron loss in the SN. CONCLUSIONS: Overall, our findings provide strong evidence that GGC repeat expansions within NOTCH2NLC contribute to the pathogenesis of PD and cause degeneration of nigral dopaminergic neurons.

Etiologies, mechanisms, and risk factors of ischemic stroke in a young Asian adult cohort.

OBJECTIVES: Risk factors and causes of acute ischemic stroke (AIS) are more diverse in young adults, and traditional stroke classifications may be inadequate. Precise characterisation of AIS is important for guiding management and prognostication. We describe stroke subtypes, risk factors and etiologies for AIS in a young Asian adult population. MATERIALS AND METHODS: Young AIS patients aged 18-50 years admitted to two comprehensive stroke centres from 2020-2022 were included. Stroke etiologies and risk factors were adjudicated using Trial of Org 10172 in Acute Stroke Treatment (TOAST) and International Pediatric Stroke Study (IPSS) risk factors. Potential embolic sources (PES) were identified in a subgroup with embolic stroke of undetermined source (ESUS). These were compared across sex, ethnicities and age groups (18-39 years versus 40-50 years). RESULTS: A total of 276 AIS patients were included, with mean age 43±5.7 years and 70.3% male. Median duration of follow-up was 5 months (IQR: 3-10). The most common TOAST subtypes were small-vessel disease (32.6%) and undetermined etiology (24.6%). IPSS risk factors were identified in 95% of all patients and 90% with undetermined etiology. IPSS risk factors included atherosclerosis (59.5%), cardiac disorders (18.7%), prothrombotic states (12.4%) and arteriopathy (7.7%). In this cohort, 20.3% had ESUS, of which 73.2% had at least one PES, which increased to 84.2% in those <40 years old. CONCLUSIONS: Young adults have diverse risk factors and causes of AIS. IPSS risk factors and ESUS-PES construct are comprehensive classification systems that may better reflect heterogeneous risk factors and etiologies in young stroke patients.

Tissue chondrification and ossification in keloids with primary report of five cases.

Keloid is commonly regarded as a benign skin tumour. Some keloids clinically exhibit hard tissue texture similar to that of cartilage or bone. We hypothesized that the keloid pathological niche environment is likely to induce keloid MSCs towards chondrogenic or osteogenic differentiation and leads to cartilage or bone-like tissue formation. The differences in tissue ossification, histology, mechanical properties, abnormal extracellular matrices and chondrogenic/osteogenic gene expression among sclerous keloids (SKs), regular keloids (RKs) and normal skins (NKs) were carefully examined. The sporadic ossified islets existed in SK group whereas no ossified/chondrified islet was found in other groups by micro-CT reconstruction. H&E, Masson trichrome and safranin O staining revealed lacuna-like structures in SKs, which were featured as bone/cartilage histology. Immunohistochemical staining showed overproduction of osteoprotegerin, type I and III collagen in SK group but similar production level of aggrecan among three groups. The biomechanical analysis demonstrated the weakest compliance of SK tissues. In addition, SK fibroblasts exhibited a relatively slower proliferation rate but higher expression levels of osteogenic and chondrogenic genes among all three groups. These cell populations also showed the strongest potential for lineage transformation. In conclusion, we first reported the presence of ossified and chondrified matrices in some extremely hard keloids in the present study.

Impaired collagen fibril assembly in keloids with enhanced expression of lumican and collagen V.

Keloids are characterized by fibroblast activation and altered architecture of extracellular matrix (ECM). Excessive deposition of ECM molecules and irregular organization of collagen fibers have been observed in keloids. However, the ultrastructural alteration of collagen has not been fully investigated. In this study, the differences in tissue structure, collagen ultrastructure, matrix components, mechanical properties and collagen assembling molecules between keloids and their extra-lesional skins (ELSs) were explored using histology, transmission electron microscope (TEM), qPCR, Western blot, immunohistochemistry and bioinformatics. Histological evaluation showed thinner fibers in keloids with increased contents of collagen III and proteoglycans, which were supported by TEM findings of thinner collagen fibrils and less developed D-band periodicity in keloids than in ELSs (p < 0.05). In addition, total collagen and water contents were significantly increased (p < 0.05) along with richer proteoglycan production in keloids vs ELSs, which also led to increased stiffness and decreased maximal load in keloids compared with ELSs. Mechanism study showed that multiple molecules related to matrix assembly were significantly upregulated in keloids (p < 0.05). In particular, lumican and collagen V showed high degrees in co-expression analysis and their upregulation levels were revealed from microarray data, which were also verified in keloids at both gene and protein levels (p < 0.05). Nevertheless, siRNA knockdown of lumican failed to affect in vitro collagen assembly, but caused upregulated collagen V expression along with the upregulation of focal adhesion kinase, TGF-ß1, TGF-ß3 and PDGF, among which some are known for capable of enhancing collagen V expression. In conclusion, this study demonstrates impaired collagen assembly along with enhanced expression of lumican and collagen V, both are known for interfering with collagen fibril assembly.

Outcomes in young adults with acute ischemic stroke undergoing endovascular thrombectomy: A real-world multicenter experience.

Endovascular thrombectomy (EVT) is the standard of care for anterior circulation acute ischemic stroke (AIS) with large vessel occlusion (LVO). Young patients with AIS-LVO have distinctly different underlying stroke mechanisms and etiologies. Much is unknown about the safety and efficacy of EVT in this population of young AIS-LVO patients. All consecutive AIS-LVO patients aged 50 years and below were included in this multicenter cohort study. The primary outcome measured was functional recovery at 90 days, with modified Rankin Scale of 0-2 deemed as good functional outcome. A total of 275 AIS-LVO patients that underwent EVT from 10 tertiary centers in Germany, Sweden, Singapore, and Taiwan were included. Successful reperfusion was achieved in 85.1% (234/275). Good functional outcomes were achieved in 66.0% (182/275). Arterial dissection was the most prevalent stroke etiology (42/195, 21.5%). National Institutes of Health Stroke Scale (NIHSS) score at presentation was inversely related to good functional outcomes (aOR: 0.92, 95% CI: 0.88-0.96 per point increase, p < 0.001). Successful reperfusion (aOR: 3.22, 95% CI: 1.44-7.21, p = 0.005), higher ASPECTS (aOR: 1.21, 95% CI: 1.01-1.44, p = 0.036), and bridging intravenous thrombolysis (aOR: 2.37, 95% CI: 1.29-4.34, p = 0.005) independently predicted good functional outcomes. Successful reperfusion was inversely associated with in-hospital mortality (aOR: 0.14, 95% CI: 0.03-0.57, p = 0.006). History of hypertension strongly predicted in-hospital mortality (aOR: 4.59, 95% CI: 1.10-19.13, p = 0.036). While differences in functional outcomes exist across varying stroke aetiologies, high rates of successful reperfusion and good outcomes are generally achieved in young AIS-LVO patients undergoing EVT.

Burden of informal care in stroke survivors and its determinants: a prospective observational study in an Asian setting.

BACKGROUND: Informal caregiving is an integral part of post-stroke recovery with strenuous caregiving demands often resulting in caregiving burden, threatening sustainability of caregiving and potentially impacting stroke survivor's outcomes. Our study aimed to examine and quantify objective and subjective informal care burden after stroke; and to explore the factors associated with informal care burden in Singapore. METHODS: Stroke patients and their informal caregivers were recruited from all five tertiary hospitals in Singapore from December 2010 to September 2013. Informal care comprised of assistance provided by informal caregivers with any of the activities of daily living. Informal care burden was measured by patients' likelihood of requiring informal care, hours of informal care required, and informal caregivers' Zarit's Burden Score. We examined informal care burden at 3-months and 12-months post-stroke. Generalized linear regressions were applied with control variables including patients' and informal caregivers' demographic characteristics, arrangement of informal care, and patients' health status including stroke severity (measured using National Institute of Health Stroke Scale), functional status (measured using Modified Rankin Scale), self-reported depression, and common comorbidities. RESULTS: Three hundred and five patients and 263 patients were examined at 3-months and 12-months. Around 35% were female and 60% were Chinese. Sixty three percent and 49% of the patients required informal care at 3-months and 12-months point, respectively. Among those who required informal care, average hours required per week were 64.3 h at 3-months and 76.6 h at 12-months point. Patients with higher functional dependency were more likely to require informal care at both time points, and required more hours of informal care at 3-months point. Female informal caregivers and those caring for patients with higher functional dependency reported higher Zarit's Burden. While informal caregivers who worked full-time reported higher burden, those caring for married stroke patients reported lower burden at 3-months point. Informal caregivers who co-cared with foreign domestic workers, i.e.: stay-in migrant female waged domestic workers, reported lower burden. CONCLUSIONS: Informal care burden remains high up to 12-months post-stroke. Factors such as functional dependency, stroke severity, informal caregiver gender and co-caring with foreign domestic workers were associated with informal care burden.

Role of caregiver factors in outpatient medical follow-up post-stroke: observational study in Singapore.

BACKGROUND: Outpatient medical follow-up post-stroke is not only crucial for secondary prevention but is also associated with a reduced risk of rehospitalization. However, being voluntary and non-urgent, it is potentially determined by both healthcare needs and the socio-demographic context of stroke survivor-caregiver dyads. Therefore, we aimed to examine the role of caregiver factors in outpatient medical follow-up (primary care (PC) and specialist outpatient care (SOC)) post-stroke. METHOD: Stroke survivors and caregivers from the Singapore Stroke Study, a prospective, yearlong, observational study, contributed to the study sample. Participants were interviewed 3-monthly for data collection. Counts of PC and SOC visits were extracted from the National Claims Database. Poisson modelling was used to explore the association of caregiver (and patient) factors with PC/SOC visits over 0-3 months (early) and 4-12 months (late) post-stroke. RESULTS: For the current analysis, 256 stroke survivors and caregivers were included. While caregiver-reported memory problems of a stroke survivor (IRR: 0.954; 95% CI: 0.919, 0.990) and caregiver burden (IRR: 0.976; 95% CI: 0.959, 0.993) were significantly associated with lower early post-stroke PC visits, co-residing caregiver (IRR: 1.576; 95% CI: 1.040, 2.389) and negative care management strategies (IRR: 1.033; 95% CI: 1.005, 1.061) were significantly associated with higher late post-stroke SOC visits. CONCLUSION: We demonstrated that the association of caregiver factors with outpatient medical follow-up varied by the type of service (i.e., PC versus SOC) and temporally. Our results support family-centred care provision by family physicians viewing caregivers not only as facilitators of care in the community but also as active members of the care team and as clients requiring care and regular assessments.

External validation of stroke mimic prediction scales in the emergency department.

BACKGROUND: Acute ischemic stroke is a time-sensitive emergency where accurate diagnosis is required promptly. Due to time pressures, stroke mimics who present with similar signs and symptoms as acute ischemic stroke, pose a diagnostic challenge to the emergency physician. With limited access to investigative tools, clinical prediction, tools based only on clinical features, may be useful to identify stroke mimics. We aim to externally validate the performance of 4 stroke mimic prediction scales, and derive a novel decision tree, to improve identification of stroke mimics. METHODS: We performed a retrospective cross-sectional study at a primary stroke centre, served by a telestroke hub. We included consecutive patients who were administered intravenous thrombolysis for suspected acute ischemic stroke from January 2015 to October 2017. Four stroke mimic prediction tools (FABS, simplified FABS, Telestroke Mimic Score and Khan Score) were rated simultaneously, using only clinical information prior to administration of thrombolysis. The final diagnosis was ascertained by an independent stroke neurologist. Area under receiver operating curve (AUROC) analysis was performed. A classification tree analysis was also conducted using variables which were found to be significant in the univariate analysis. RESULTS: Telestroke Mimic Score had the highest discrimination for stroke mimics among the 4 scores tested (AUROC = 0.75, 95% CI = 0.63-0.87). However, all 4 scores performed similarly (DeLong p > 0.05). Telestroke Mimic Score had the highest sensitivity (91.3%), while Khan score had the highest specificity (88.2%). All 4 scores had high positive predictive value (88.1 to 97.5%) and low negative predictive values (4.7 to 32.3%). A novel decision tree, using only age, presence of migraine and psychiatric history, had a higher prediction performance (AUROC = 0.80). CONCLUSION: Four tested stroke mimic prediction scales performed similarly to identify stroke mimics in the emergency setting. A novel decision tree may improve the identification of stroke mimics.

Comparing the efficacy and safety of direct oral anticoagulants with vitamin K antagonist in cerebral venous thrombosis.

Cerebral venous thrombosis (CVT) causes significant disability and mortality. Current guidelines for CVT management support the initial use of unfractionated heparin or low molecular weight heparin followed by longer-term oral vitamin K antagonist (VKA). There has been increasing, albeit limited, evidence for the use of direct oral anticoagulants (DOAC) as an alternative to VKA. We performed a systematic review and meta-analysis of studies that compared the safety and efficacy of DOACs to VKA in treating CVT. A comprehensive literature search was carried out in Medline, Embase and Cochrane Stroke Group Trials Register using a suitable keyword/MeSH term search strategy. All studies published in English comparing outcomes of patients with CVT treated with DOAC or VKA were included. In total, 6 studies (5 observational studies and 1 randomized clinical trial) comprising 412 patients (age range 16-83 years) were analyzed. DOAC was used in 151 patients, while 261 received VKA. The follow-up period was 3-11 months. The efficacy of DOACs was comparable with VKA in terms of partial or full thrombus recanalization (RR 1.02, 95% CI 0.89-1.16) and excellent functional recovery with modified Rankin scale < 2 (RR 1.02, 95% CI 0.93-1.13). Patients treated with DOAC developed lower major bleeding events when compared to VKA, although this did not reach statistical significance (RR 0.44, 95% CI 0.12-1.59). We provide preliminary evidence to support DOAC as effective and safe alternatives to VKA in CVT treatment. We await the results of upcoming randomized trials to further support our results and validate the use of DOAC.

COVID-19 and ischemic stroke: a systematic review and meta-summary of the literature.

Acute ischemic stroke (AIS) is a life-threatening complication of coronavirus disease 2019 (COVID-19) infection. Increasing reports suggest an association between COVID-19 and AIS, although the underlying mechanism remains uncertain. We performed a systematic review to characterize the clinical characteristics, neuroimaging findings, and outcomes of AIS in COVID-19 patients. A literature search was performed in PubMed and Embase using a suitable keyword search strategy from 1st December 2019 to 29th May 2020. All studies reporting AIS occurrence in COVID-19 patients were included. A total of 39 studies comprising 135 patients were studied. The pooled incidence of AIS in COVID-19 patients from observational studies was 1.2% (54/4466) with a mean age of 63.4 ± 13.1 years. The mean duration of AIS from COVID-19 symptoms onset was 10 ± 8 days, and the mean NIHSS score was 19 ± 8. Laboratory investigations revealed an elevated mean D-dimer (9.2 ± 14.8 mg/L) and fibrinogen (5.8 ± 2.0 g/L). Antiphospholipid antibodies were detected in a significant number of cases. The majority of AIS neuroimaging patterns observed was large vessel thrombosis, embolism or stenosis (62.1%, 64/103), followed by multiple vascular territory (26.2%, 27/103). A high mortality rate was reported (38.0%, 49/129). We report the pooled incidence of AIS in COVID-19 patients to be 1.2%, with a high mortality rate. Elevated D-dimer, fibrinogen and the presence of antiphospholipid antibodies appear to be prominent in COVID-19 patients with concomitant AIS, but further mechanistic studies are required to elucidate their role in pathogenesis.

Cerebral Venous Thrombosis in Patients with COVID-19 Infection: a Case Series and Systematic Review.

BACKGROUND: There has been increasing reports associating the coronavirus disease 2019 (COVID-19) with thromboembolic phenomenon including ischemic strokes and venous thromboembolism. Cerebral venous thrombosis (CVT) is a rare neurovascular emergency that has been observed in some COVID-19 patients, yet much remains to be learnt of its underlying pathophysiology. OBJECTIVE: We present a case series of local patients with concomitant COVID-19 infection and CVT; and aim to perform a systematic review of known cases in the current literature. METHODS: We describe two patients with concomitant COVID-19 infection and CVT from a nationwide registry in Singapore. We then conducted a literature search in PubMed and Embase using a suitable keyword search strategy from 1st December 2019 to 11th June 2020. All studies reporting CVT in COVID-19 patients were included. RESULTS: Nine studies and 14 COVID-19 patients with CVT were studied. The median age was 43 years (IQR=36-58) and majority had no significant past medical conditions (60.0%). The time taken from onset of COVID-19 symptoms to CVT diagnosis was a median of 7 days (IQR=6-14). CVT was commonly seen in the transverse (75.0%) and sigmoid sinus (50.0%); 33.3% had involvement of the deep venous sinus system. A significant proportion of patients had raised D-dimer (75.0%) and CRP levels (50.0%). Two patients reported presence of antiphospholipid antibodies. Most patients received anticoagulation (91.7%) while overall mortality rate was 45.5%. CONCLUSIONS: The high mortality rate of CVT in COVID-19 infection warrants a high index of suspicion from physicians, and early treatment with anticoagulation should be initiated.

TRPM4-specific blocking antibody attenuates reperfusion injury in a rat model of stroke.

Reperfusion therapy is currently the gold standard treatment for acute ischemic stroke. However, reperfusion injuries such as oedema and haemorrhagic transformation largely limit the use of this potent treatment to a narrow time window. Recently, transient receptor potential melastatin 4 (TRPM4) channel has emerged as a potential target for vascular protection in stroke management. Non-specificity and side effects are major concerns for current TRPM4 blockers. The present study was undertaken to develop a novel TRPM4 blocker for stroke management. We report the generation of a TRPM4-specific antibody M4P which binds to a region close to the channel pore. M4P could inhibit TRPM4 current and downregulate TRPM4 surface expression, therefore prevent hypoxia-induced cell swelling. In the rat model of 3-h stroke reperfusion, application of M4P at 2 h after occlusion ameliorated reperfusion injury by improving blood-brain barrier integrity, and enhanced functional recovery. Our results demonstrate that TRPM4 blockade could attenuate reperfusion injury in stroke recanalization. When applied together with reperfusion treatments, TRPM4 blocking antibody has the potential to extend the therapeutic time window for acute ischemic stroke.

Dyadic approach to post-stroke hospitalizations: role of caregiver and patient characteristics.

AIM: To study the association of caregiver factors and stroke patient factors with rehospitalizations over the first 3 months and subsequent 3-12 months post-stroke in Singapore. METHODS: Patients with stroke and their caregivers were recruited in the Singapore Stroke Study, a prospective yearlong cohort. While caregiver and patient variables were taken from this study, hospitalization data were extracted from the national claims database. We used Poisson modelling to perform bivariate and multivariable analysis with counts of hospitalization as the outcome. RESULTS: Two hundred and fifty-six patient with stroke and caregiver dyads (N = 512) were analysed, with patients having spouse (60%), child (29%), sibling (4%) and other (7%) as their caregivers. Among all participants, 89% of index strokes were ischemic, 57% were mild in severity and more than half (59%) of the patients had moderate or severe disability post-stroke as measured on the Modified Rankin Scale. Having social support in the form of a foreign domestic worker for general help of caregiver reduced the hospitalization rate over 3 months post-stroke by 66% (IRR: 0.342; 95% CI: 0.180, 0.651). Compared to having a spousal caregiver, those with a child caregiver had an almost three times greater rate of hospitalizations over 3-12 months post-stroke (IRR: 2.896; 95% CI: 1.399, 5.992). Higher reported caregiving burden at the 3-month point was associated with the higher subsequent rate of hospitalization. CONCLUSION: Recommendations include the adoption of a dyadic or holistic approach to post-stroke care provision by healthcare practitioners, giving due importance to both patients with stroke and their caregivers, integrating caregivers in the healthcare system to extend the care continuum to include informal care in the community and provision of timely support for caregivers.

Pregnancy Promotes Maternal Hippocampal Neurogenesis in Guinea Pigs.

Adult neurogenesis in the hippocampal dentate gyrus (DG) modulates cognition and behavior in mammals, while motherhood is associated with cognitive and behavioral changes essential for the care of the young. In mice and rats, hippocampal neurogenesis is reported to be reduced or unchanged during pregnancy, with few data available from other species. In guinea pigs, pregnancy lasts ~9 weeks; we set to explore if hippocampal neurogenesis is altered in these animals, relative to gestational stages. Time-pregnant primigravidas (3-5 months old) and age-matched nonpregnant females were examined, with neurogenic potential evaluated via immunolabeling of Ki67, Sp8, doublecortin (DCX), and neuron-specific nuclear antigen (NeuN) combined with bromodeoxyuridine (BrdU) birth-dating. Relative to control, subgranular Ki67, Sp8, and DCX-immunoreactive (+) cells tended to increase from early gestation to postpartum and peaked at the late gestational stage. In BrdU pulse-chasing experiments in nonpregnant females surviving for different time points (2-120 days), BrdU+ cells in the DG colocalized with DCX partially from 2 to 42 days (most frequently at 14-30 days) and with NeuN increasingly from 14 to 120 days. In pregnant females that received BrdU at early, middle, and late gestational stages and survived for 42 days, the density of BrdU+ cells in the DG was mostly high in the late gestational group. The rates of BrdU/DCX and BrdU/NeuN colocalization were similar among these groups and comparable to those among the corresponding control group. Together, the findings suggest that pregnancy promotes maternal hippocampal neurogenesis in guinea pigs, at least among primigravidas.

Can acute clinical outcomes predict health-related quality of life after stroke: a one-year prospective study of stroke survivors.

BACKGROUND: Health-related quality of life (HRQoL) is a key metric to understand the impact of stroke from patients' perspective. Yet HRQoL is not readily measured in clinical practice. This study aims to investigate the extent to which clinical outcomes during admission predict HRQoL at 3 months and 1 year post-stroke. METHODS: Stroke patients admitted to five tertiary hospitals in Singapore were assessed with Shah-modified Barthel Index (Shah-mBI), National Institute of Health Stroke Scale (NIHSS), Modified Rankin Scale (mRS), Mini-Mental State Examination (MMSE), and Frontal Assessment Battery (FAB) before discharge, and the EQ-5D questionnaire at 3 months and 12 months post-stroke. Association of clinical measures with the EQ index at both time points was examined using multiple linear regression models. Forward stepwise selection was applied and consistently significant clinical measures were analyzed for their association with individual dimensions of EQ-5D in multiple logistic regressions. RESULTS: All five clinical measures at baseline were significant predictors of the EQ index at 3 months and 12 months, except that MMSE was not significantly associated with the EQ index at 12 months. NIHSS (3-month standardized ß = - 0.111; 12-month standardized ß = - 0.109) and mRS (3-month standardized ß = - 0.122; 12-month standardized ß = - 0.080) were shown to have a larger effect size than other measures. The contribution of NIHSS and mRS as significant predictors of HRQoL was mostly explained by their association with the mobility, self-care, and usual activities dimensions of EQ-5D. CONCLUSIONS: HRQoL at 3 months and 12 months post-stroke can be predicted by clinical outcomes in the acute phase. NIHSS and mRS are better predictors than BI, MMSE, and FAB.

Healthcare utilization and cost trajectories post-stroke: role of caregiver and stroke factors.

BACKGROUND: It is essential to study post-stroke healthcare utilization trajectories from a stroke patient caregiver dyadic perspective to improve healthcare delivery, practices and eventually improve long-term outcomes for stroke patients. However, literature addressing this area is currently limited. Addressing this gap, our study described the trajectory of healthcare service utilization by stroke patients and associated costs over 1-year post-stroke and examined the association with caregiver identity and clinical stroke factors. METHODS: Patient and caregiver variables were obtained from a prospective cohort, while healthcare data was obtained from the national claims database. Generalized estimating equation approach was used to get the population average estimates of healthcare utilization and cost trend across 4 quarters post-stroke. RESULTS: Five hundred ninety-two stroke patient and caregiver dyads were available for current analysis. The highest utilization occurred in the first quarter post-stroke across all service types and decreased with time. The incidence rate ratio (IRR) of hospitalization decreased by 51, 40, 11 and 1% for patients having spouse, sibling, child and others as caregivers respectively when compared with not having a caregiver (p = 0.017). Disability level modified the specialist outpatient clinic usage trajectory with increasing difference between mildly and severely disabled sub-groups across quarters. Stroke type and severity modified the primary care cost trajectory with expected cost estimates differing across second to fourth quarters for moderately-severe ischemic (IRR: 1.67, 1.74, 1.64; p = 0.003), moderately-severe non-ischemic (IRR: 1.61, 3.15, 2.44; p = 0.001) and severe non-ischemic (IRR: 2.18, 4.92, 4.77; p = 0.032) subgroups respectively, compared to first quarter. CONCLUSION: Highlighting the quarterly variations, we reported distinct utilization trajectories across subgroups based on clinical characteristics. Caregiver availability reducing hospitalization supports revisiting caregiver's role as potential hidden workforce, incentivizing their efforts by designing socially inclusive bundled payment models for post-acute stroke care and adopting family-centered clinical care practices.

Can caregivers report their care recipients' post-stroke hospitalizations and outpatient visits accurately? Findings of an Asian prospective stroke cohort.

BACKGROUND: Health services research aimed at understanding service use and improving resource allocation often relies on collecting subjectively reported or proxy-reported healthcare service utilization (HSU) data. It is important to know the discrepancies in such self or proxy reports, as they have significant financial and policy implications. In high-dependency populations, such as stroke survivors, with varying levels of cognitive impairment and dysphasia, caregivers are often potential sources of stroke survivors' HSU information. Most of the work conducted on agreement analysis to date has focused on validating different sources of self-reported data, with few studies exploring the validity of caregiver-reported data. Addressing this gap, our study aimed to quantify the agreement across the caregiver-reported and national claims-based HSU of stroke patients. METHODS: A prospective study comprising multi-ethnic stroke patient and caregiver dyads (N = 485) in Singapore was the basis of the current analysis, which used linked national claims records. Caregiver-reported health services data were collected via face-to-face and telephone interviews, and similar health services data were extracted from the national claims records. The main outcome variable was the modified intraclass correlation coefficient (ICC), which provided the level of agreement across both data sources. We further identified the amount of over- or under-reporting by caregivers across different service types. RESULTS: We observed variations in agreement for different health services, with agreement across caregiver reports and national claims records being the highest for outpatient visits (specialist and primary care), followed by hospitalizations and emergency department visits. Interestingly, caregivers over-reported hospitalizations by approximately 49% and under-reported specialist and primary care visits by approximately 20 to 30%. CONCLUSIONS: The accuracy of the caregiver-reported HSU of stroke patients varies across different service types. Relatively more objective data sources, such as national claims records, should be considered as a first choice for quantifying health care usage before considering caregiver-reported usage. Caregiver-reported outpatient service use was relatively more accurate than inpatient service use over shorter recall periods. Therefore, in situations where objective data sources are limited, caregiver-reported outpatient information can be considered for low volumes of healthcare consumption, using an appropriate correction to account for potential under-reporting.