ObjectiveVarious guidelines recommend offering germline genetic testing to all patients diagnosed with epithelial ovarian cancer, as it helps guide treatment decisions, identify cancer risks in other organs, and empowers patients to notify families for timely screening and risk-reducing surgery. Our study aimed to explore the awareness and uptake rate of germline genetic testing among Chinese women with epithelial ovarian cancer, and to analyze the determinants influencing their decision.MethodsA cross sectional study was conducted at Obstetrics and Gynecology Hospital of Fudan University between November 2023 to September 2024. A questionnaire was used to assess patients’ awareness of germline genetic testing. Disease-related data were extracted from electronic medical records. Binary logistic regression analysis was performed to identify factors associated with uptake of germline genetic testing.ResultsOf the total 154 patients included, 100 underwent germline genetic testing, with an uptake rate of 64.94%. Among included patients, 62.99% demonstrated low awareness of germline genetic testing and 37.01% exhibited a high level of awareness. Logistic regression analysis showed that higher monthly per-capita household income (OR = 3.30, 95 % CI 1.24-8.75, P = 0.017), a family history of BRCA-related cancers (OR = 6.30, 95% CI 1.16-34.12, P = 0.033), and high awareness of germline genetic testing (OR = 8.81, 95 % CI 2.58-30.12, P = 0.001) were associated with a significantly increased likelihood of undergoing testing. Additionally, 19.6% of the tested patients carried a pathogenic variant.ConclusionAmong Chinese patients with epithelial ovarian cancer, awareness of germline genetic testing is generally low, with critical deficiencies in knowledge that directly inform clinical decision-making and familial risk management. Nearly two-thirds of patients diagnosed with epithelial ovarian cancer had undergone germline genetic testing. Socioeconomic status, family history of associated cancer, and patients’ awareness of genetic testing are the principal determinants of germline genetic testing utilization in this population.

Family-specific variant genetic testing is crucial for cancer risk management among at-risk relatives of individuals with hereditary gynecological cancer. However, the uptake of such testing remains suboptimal, and the factors influencing uptake have not been fully elucidated. This study aimed to investigate the uptake of family-specific variant genetic testing among at-risk relatives of probands with hereditary gynecological cancers and to identify factors associated with testing uptake. A cross-sectional study was conducted between August 2023 and September 2024 at the Obstetrics and Gynecology Hospital of Fudan University. Seventy probands with confirmed pathogenic or likely pathogenic (P/LP) germline variants in hereditary gynecological cancer susceptibility genes, along with their 307 at-risk relatives, were enrolled. Self-designed questionnaires were used to collect characteristics of probands and their at-risk relatives, as well as the features of their relationships. Multivariate binary logistic regression analysis was performed to identify factors associated with testing uptake. Among the 70 probands, isolated ovarian cancer accounted for the highest proportion of personal malignancies (60.00

Introduction:Ethylmalonic encephalopathy (EE) is an often-severe inborn error of metabolism caused by biallelic variants in the ETHE1 gene leading to impaired detoxification of hydrogen sulfide (H2S). H2S is produced both exogenously by anerobic intestinal bacteria as well as by the endogenous catabolism of the sulfur-containing amino acids methionine and cysteine. Existing therapies including metronidazole, N-acetylcysteine (NAC), and orthotopic liver transplantation (OLT) have been pursued with the objective of reducing or detoxifying exogenously produced H2S. However, strategies to reduce endogenously produced H2S using a methionine and cysteine restricted diet are an understudied therapeutic avenue. Methods:We performed an open-label, single-arm study to evaluate the effects of dietary intervention with a methionine and cysteine restricted diet (20-30 mg/kg/day) on biochemical parameters and overall clinical trajectory in three patients with molecularly confirmed ethylmalonic encephalopathy (two with attenuated phenotypes, one classically affected). All three patients were receiving a combination of medical therapy with metronidazole and NAC and were status-post OLT at the time of diet initiation. Plasma butyrylcarnitine (C4) levels were measured at diagnosis, serially following initiation of medical therapy and OLT, and at regular follow-up visits in a metabolic clinic after diet initiation. Additionally, we obtained untargeted metabolomics studies and directly evaluated ethylmalonate, butyrylcarnitine, isobutyrylcarnitine, isovalerylcarnitine, 2-methylbutyrylcarnitine, glutarylcarnitine, and methylsuccinate levels in the pre- OLT/medical therapy, post- OLT/medical therapy, and post- sulfur-restricted diet states. Results:We observed a 20-38 % reduction in plasma C4 levels in all three patients following OLT and combination medical therapy with NAC and metronidazole. An 8-10 % reduction in C4 was observed following the introduction of dietary therapy in the two patients with attenuated phenotypes and an 82 % increase in C4 was seen in the patient with the classical phenotype. The metabolic profile as assessed by untargeted metabolomics analysis was largely unchanged in the pre-OLT/medical therapy, post-OLT/medical therapy, and post-diet states. Conclusions:The modest biochemical response to a sulfur-restricted diet observed in our cohort likely reflects the relatively minor contribution of endogenous sulfur-containing amino acid catabolism to overall H2S production. Further work is needed to study the impact of dietary intervention on the natural history of EE including diet only trials in the animal model as well as in the pre-OLT period in human participants.

Designing ionic polymer electrolytes (IPEs) for high-voltage and fast-charging lithium batteries involves searching in a highly complex and discrete chemical space. Traditional material discovery processes struggle with this complexity due to high costs and long evaluation time. A kernel-based Bayesian optimization is described to complete the multi-objective optimization by considering ionic conductivity, electrochemical stability, and discharge capacity simultaneously. According to a recommender based on a union set of acquisition functions, promising IPEs through three iterations with only 2.8% of the chemical space is targeted. The achieved lithium metal batteries exhibit promising performance with ultrahigh cutoff voltage with NCM811 (LiNi0.8Co0.1Mn0.1O2, 4.8 V) and LNMO (LiNi0.5Mn1.5O4, 4.92 V). To further extend the versatility of IPEs and diminish the high cost associated with the glove-box environment, an aqueous and high-voltage lithium-ion battery is developed by introducing water molecules in IPEs coupled with Li4Ti5O12||LiMn2O4, a strong hydrogen bonding network formed between the rigid-rod polyelectrolyte and the embedded water molecules, which effectively suppresses the water reactivity, meanwhile boosting the ionic conductivity. This work reveals an innovative multi-objective optimization that effectively handles multi-targets and discontinuous parameter space, offering critical insights to address complex challenges in material discovery and property optimization for advanced and versatile lithium batteries.

BACKGROUND: The frequency and prognostic significance of subacute neurological improvement (SNI) on 90-day outcomes after acute intracerebral hemorrhage are unknown. METHODS: Secondary analyses of participant data from the INTERACT2 trial (second Intensive Blood Pressure Reduction in Acute Intracerebral Hemorrhage Trial). SNI included any, moderate, significant, and substantial neurological improvement defined as ≥1, ≥2, ≥3, and ≥4 points decrease, respectively, on the National Institutes of Health Stroke Scale from 24 hours to 7 days after intracerebral hemorrhage. Logistic regression models were used to assess associations of SNI and death or major disability (modified Rankin Scale score of 3–6), major disability (modified Rankin Scale scores, 3–5), and death alone at 90 days. Data are reported as odds ratios and 95% CIs. RESULTS: Of 2571 patients included in analyses, 1492 (58.0%), 1057 (41.1%), 731 (28.4%), and 490 (19.1%) patients experienced any, moderate, significant, and substantial SNI (24 hours to 7 days) after intracerebral hemorrhage, respectively. After adjustment for key confounders, any SNI was associated with 49%, 25%, and 65% reduced odds of death or major disability (odds ratio, 0.51 [95% CI, 0.42–0.63]), major disability alone (odds ratio, 0.75 [95% CI, 0.63–0.90]), and death (odds ratio, 0.35 [95% CI, 0.24–0.50]), respectively. Moderate, significant, and substantial SNI were also significantly associated with decreased odds of death or major disability at 90 days. The relationship between any SNI and study outcomes was consistent in most subgroups, including age and baseline hematoma volume. Early intensive blood pressure-lowering treatment did not increase the odds of SNI. CONCLUSIONS: SNI from 24 hours to 7 days is common after intracerebral hemorrhage and predicts a lower likelihood of death or major disability. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT00716079.

BackgroundThe effect of renal impairment in patients who receive intravenous thrombolysis for acute ischemic stroke (AIS) is unclear. We aimed to determine the associations of renal impairment and clinical outcomes and any modification of the effect of intensive versus guideline-recommended blood pressure (BP) control in the BP arm of the International Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED).MethodsWe conducted a post-hoc analysis of the ENCHANTED BP arm, which involved 2,196 thrombolyzed AIS patients. Logistic regression models were used to define the association between eGFR and clinical outcomes of death, death or major disability [modified Rankin scale (mRS) scores 3–6], and major disability (mRS 3–5) at 90 days.ResultsOf the 2,151 patients with available baseline renal function data (mean age 66.9 years; 38% women), 993 (46.2%), 822 (38.2%), and 336 (15.6%) had normal (eGFR ≥ 90 mL/min/1.73 m2), mildly (60–89), and moderate-to-severely impaired (<60) renal function, respectively. Compared with patients with normal eGFR, mortality was higher in those with moderate-to-severe renal impairment (adjusted odds ratio 1.77, 95% confidence interval 1.05–2.99; p = 0.031 for trend). However, the difference in death or major disability (mRS 3–6) was not significant between groups. There was no heterogeneity in the effect of intensive versus guideline-recommended BP-lowering treatment on death by grades of renal function (p for interaction = 0.545).DiscussionThe presence of moderate-to-severe renal impairment is associated with increased mortality in thrombolyzed patients with AIS. Renal function does not modify the effect of early intensive BP-lowering treatment on death in this patient group.

1AbstractThe OPTIMIST trial aims to determine whether low-intensity monitoring is at least as effective (“non-inferior”) to standard monitoring, on the functional recovery of patients who have received recombinant tissue plasminogen activator or equivalent lytic reperfusion treatment for acute ischaemic stroke. It is designed as an international, multicenter, stepped-wedge (4 periods/3 steps) cluster randomized trial. This statistical analysis plan pre-specifies the method of analysis for every outcome and key variable collected in the trial.The primary outcome is an “unfavourable outcome” at Day 90, defined as a score of 2 to 6 on the modified Rankin scale. The primary analysis will consist in a log-binomial regression adjusted for the effect of time and for clustering by site using a random effect. The non-inferiority margin was pre-specified as a relative risk of 1.15 for a bad outcome; thus, non-inferiority will be declared if the upper bound of the 95% confidence interval around the relative risk is lower than 1.15.The primary analysis will adjust for calendar time (6-month intervals) and will be based on imputed data. The analysis plan also includes planned sensitivity analyses including covariate adjustments and subgroup analyses.2Administrative information2.1Study identifiersProtocol Number: GI-AU-NMH-2019-CA Version: 3.0, Date: 3 March 2021ClinicalTrials.gov register Identifier:NCT03734640Australian New Zealand Clinical Trial Registry: ACTRN 126190015561342.2Revision history2.3Contributors to the statistical analysis planLB – Main author; developed the initial draft and prepared subsequent versions. SB - Prepared initial draft and reviewed subsequent versions. MO, CA - Reviewed every draft and approved final version. LX - Prepared economic analysis section and approved final version. SJ - Comments on economic analysis plan; approved final draft. XW, AM, BJ, DS, PK, PM-V, DD, YS, LS, WAWZ, NHT, CD, TR, RIL - Approved final draft.

Introduction: Accurately predicting a patient's prognosis is an important component of decision-making in intracerebral hemorrhage (ICH). We aimed to determine clinicians' ability to predict survival, functional recovery, and return to premorbid activities in patients with ICH. Methods: Pre-specified secondary analysis of the third intensive care bundle with blood pressure reduction in acute cerebral hemorrhage trial (INTERACT3), an international, multicenter, stepped-wedge cluster randomized controlled trial. Clinician perspectives on prognosis were collected at hospital admission and Day 7 (or before discharge). Prognosis questions were the likelihood of (i) survival at 48 h and 6 months, (ii) favorable functional outcome (recovery walking and self-care), and (iii) return to usual activities at 6 months. Clinician predictions were compared with actual outcomes. Results: Most clinician participants were from neurosurgery (75%) with a median of 8 working years (IQR 5-14) of experience. Of the 6,305 randomized patients who survived 48 h, 213 (3.4%) were predicted to die (positive predictive value [PPV] 0.99, 95% confidence interval [CI] 0.99-0.99). Of 5,435 patients who survived 6 months, 209 (3.8%) were predicted to die (PPV 0.93, 95% CI: 0.92-0.93). Predictions on the favorable functional outcome (PPV 0.54, 95% CI: 0.52-0.56) and satisfied ability to return to usual activities (PPV 0.50, 95% CI: 0.49-0.52) were poor. Prediction accuracy varied by working years and region of practice. Conclusions: In patients with ICH, clinician estimates of death are very good but conversely they are poor in predicting higher levels of functional recovery and activities.

Background There are few proven treatments for acute spontaneous intracerebral haemorrhage, and they all target reducing expansion of the haematoma. The traditional Chinese medicine FYTF-919 (Zhongfeng Xingnao) in an oral solution is comprised of several Chinese herbs that are widely used to treat patients with intracerebral haemorrhage in China on the understanding that they enhance resorption of the haematoma and reduce neuroinflammation. We aimed to provide a reliable assessment of the safety and efficacy of FYTF-919 in patients with moderate to severe acute intracerebral haemorrhage. Methods We did a pragmatic, multicentre, randomised, double-blind, placebo-controlled trial at 26 hospitals in China. We enrolled adults (age >= 18 years) with a diagnosis of symptomatic spontaneous intracerebral haemorrhage (confirmed by brain imaging) within 48 h after the onset of symptoms (or last seen well), which resulted in moderate to severe neurological impairment defined by scores of at least 8 on the National Institute of Health Stroke Scale or between 7 and 14 inclusive on the Glasgow Coma Scale. Randomisation (1:1) was via a central internet-based system with a block grouping method stratified by provincial location of the hospital, severity of neurological impairment, and site of the haematoma in the brain. FYTF-919 and the placebo were masked through consistency in appearance, smell, taste, and other aspects. Participants were allocated to receive 33 mL (or 25 mL via a nasogastric tube if a participant's swallowing was impaired) of either oral liquid FYTF-919 or matching placebo administered at least 30 min after a meal every 8 h (or 6 h via nasogastric tube) over 24 h for 28 days. The primary efficacy outcome was the utility weighted modified Rankin Scale (a seven-level ordinal scale that ranges from 0 [no symptoms] to 6 [death], in which the utility weights of 097, 088, 074, 055, 020, -019, and 000 were assigned to the seven levels respectively, with higher scores indicating a better outcome according to the participants' perspective) at 90 days analysed in a general linear model with adjustment for baseline factors. We did several adjusted and sensitivity analyses. Primary analyses were assessed in the intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT05066620 and is complete. Findings Between Nov 24, 2021, and Dec 28, 2023, of 9000 patients screened, 1648 were randomly assigned to treatment, 817 to the FYTF-919 group and 831 to the placebo group. Before receiving any treatment two patients in the FYTF-919 group and five patients in the placebo group immediately withdrew their consent leaving 1641 participants with available primary outcome data in the intention-to-treat population, 815 in the FYTF-919 group and 826 in the placebo group. 1242 (757%) participants consumed 80% or more of the study medication and 994 (606%) consumed all of it within 28 days. Mean utility weighted modified Rankin Scale scores at 90 days were 044 in the FYTF-919 group and 044 in the placebo group (difference 001, 95% CI -002 to 004; p=063). The neutral result was consistent in adjusted and sensitivity analyses. There was no significant difference in serious adverse events. Interpretation This large, randomised, placebo-controlled, double-blind, clinical trial showed no effect of the traditional Chinese medicine herbal compound FYTF-919 on functional recovery, survival, and health-related quality of life in patients with moderate to severe intracerebral haemorrhage. The results reaffirm the need for methodologically rigorous, randomised controlled trials to evaluate the effectiveness of existing therapies, including traditional Chinese medicines that are already in widespread use throughout the world. Copyright (c) 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.

BACKGROUND:Long-term patterns of functional outcome after intracerebral hemorrhage (ICH) have not been well elucidated in population-based studies from low- and middle-income countries. The aim of this study was to define long-term functional outcomes, associated prognostic factors, and recovery patterns for patients with acute ICH.METHODS:We conducted a prospective population-based stroke incidence study in Ulaanbaatar, Mongolia, with prospective follow-up. Multiple overlapping strategies were used to prospectively ascertain all strokes over 2 years. Patients were followed up at 28, 90, and 365 days. Associated factors of unfavorable outcome (defined as modified Rankin Scale scores, 3-6) and death at 365 days were identified using separate binary logistic regressions. Recovery pattern in terms of the proportions of patients with favorable outcomes (defined as modified Rankin Scale scores, 0-2) as the outcome was analyzed over time at 28, 90, and 365 days using generalized estimating equations with baseline covariates.RESULTS:A total of 1172 first-ever ICH cases were registered. Among these patients, 625 (56.4% of available modified Rankin Scale) cases had died and 853 (77.0%) had an unfavorable outcome at 365 days. The proportion of favorable outcomes increased from 12.1% at day 28 to 17.4% at day 90 and then to 23.0% at 1 year. Multivariable analysis revealed that older age, low socioeconomic status, absence of hypertension, hospital admission, neurosurgical intervention, and ICH severity, side, and intraventricular extension were independently associated with death/unfavorable outcome 365 days post-ICH. Most of these factors were also associated with the recovery pattern.CONCLUSIONS:The prognosis from ICH in low- and middle-income countries is dismal, with 56% of patients dead and 77% having an unfavorable functional outcome at 365 days, although there was a pattern of continuous recovery over this time period. These findings stress the importance of developing effective primary prevention and continuous active care for survivors to reduce the burden of ICH in low- and middle-income countries.

Metal phosphide anode materials encounter poor reversibility of the discharge product (metal and Na3P) and large volume variation, resulting in low initial Coulombic efficiency (ICE) and severe capacity degradation. Herein, a bimetallic phosphide (CoMoP) with three-dimensional ordered porous (3DOP) nanoconstruction was fabricated, which presents a reduced Gibbs free energy change (ΔG) of redox reaction between Co-Mo/Na3P and CoMoP and improved conductivity compared to CoP and MoP. Additionally, the 3DOP architecture could disperse stress and reduce strain during cycling, thus improving structural stability of CoMoP. In situ and ex situ characterizations and electrochemical measurements suggest that 3DOP CoMoP exhibits highly reversible sodium storage with an ICE of 58% at 0.1 A g-1, enhanced reaction dynamics, and good cycling stability with around 0.04% capacity decay per cycle at 1 A g-1 after 1000 cycles. Consequently, this work offers a new perspective to solve issues of reversibility of redox chemistry and volume expansion for secondary batteries.

Introduction: The effectiveness of thromboelastography (TEG)-guided antiplatelet therapy in patients with ischemic cerebrocardiovascular diseases is not well-established. This systematic review evaluates the efficacy and safety of TEG-guided antiplatelet therapy compared to standard treatment in patients with ischemic cerebrocardiovascular diseases. Methods: Randomized controlled trials (RCTs) and observational studies comparing TEG-guided antiplatelet therapy with standard therapy in patients suffering from ischemic stroke (IS) or coronary artery disease (CAD) were identified. The primary efficacy measure was a composite of ischemic and hemorrhagic events. Secondary efficacy measures included any ischemic events, while safety was assessed by the occurrence of bleeding events. Results: Ten studies involving 4 RCTs and 6 observational studies with a total of 1,678 patients were included. When considering a composite of ischemic and hemorrhagic events in RCTs, a significant reduction was observed in IS or CAD patients under TEG-guided therapy compared to standard therapy (OR: 0.45, 95% CI: 0.27-0.75, p = 0.002). After pooling RCTs and observational studies together, compared to standard antiplatelet therapy, TEG-guided therapy significantly reduced the risk of a composite of ischemic and hemorrhagic events (OR: 0.26, 95% CI: 0.19-0.37; p < 0.00001), ischemic events (OR: 0.28, 95% CI: 0.19-0.41; p < 0.00001), and bleeding events (OR: 0.31, 95% CI: 0.16-0.62; p = 0.0009) in patients with IS or CAD. Conclusion: TEG-guided antiplatelet therapy appears to be both effective and safe for patients with IS or CAD. These findings support the use of TEG testing to tailor antiplatelet therapy in individuals with ischemic cerebrocardiovascular diseases.

Introduction: The popular traditional Chinese medicine (TCM) compound FYTF-919 (Zhong Feng Xing Nao prescription) may improve outcome from acute intracerebral hemorrhage (ICH) through effects on brain edema, hematoma absorption, and the immune system. This study is to assess whether FYTF-919 is safe and effective as compared to matching placebo treatment in patients with acute ICH. Methods: The ongoing Chinese Herbal medicine in patients with Acute INtracerebral hemorrhage (CHAIN) is a multicenter, prospective, randomized, double-blind placebo-controlled trial of FYTF-919 in patients with acute ICH at 20-30 hospital sites in China. Eligible ICH patients presenting within 48 h after symptom onset are randomly allocated to receive either FYTF-919 (100 mL per day x 28 d, oral) or matching placebo. A sample size of 1504 patients is estimated to provide 90% power (alpha 0.05) to detect a >= 20% improvement in average utility-weight scores on the modified Rankin scale (UW-mRS) assessed at 90 days, with 6% non-adherence, and 10% lost to follow-up. The primary efficacy outcome is UW-mRS at 90 days. Secondary outcomes include binary measures of the mRS, neurological impairment on the National Institute of Health Stroke Scale, and health-related quality of life on the EuroQol EQ-5D-5L scale at different time points over 6 months of follow-up. The key safety measure is serious adverse events. Conclusion: CHAIN is on schedule to provide reliable evidence over the benefits of a popular herbal TCM for the treatment of acute ICH. Trial registration: Clinicaltrial.gov NCT05066620.

ObjectiveOur aim was to elucidate the polycyclic aromatic hydrocarbon (PAH) metabolites exposure levels of pregnant women in the underdeveloped region of Zunyi, southwest China.MethodsSociodemographic information was collected via questionnaires, and urine samples were collected at the same time. A total of 3047 pregnant women participated in the study. Gas chromatography/mass spectrometry was used to detect the urine concentrations of 10 PAH metabolites. A generalised linear model (GLM) was used to identify predictive factors of PAH metabolites.ResultsAll PAH metabolites had a detection rate greater than 60% (67.21%–90.57%) except for 4-OH-PHE at 55.54%. The median concentrations were 0.02–0.11 µg/g Cre except for 1-OH-NAP, 2-OH-NAP, 2-OH-FLU and 9-OH-FLU (0.36–0.50 µg/g Cre). The cluster analysis identified the phenanthrene and fluorene metabolite clusters (containing no other metabolites), while naphthalene metabolites (1-OH-NAP, 2-OH-NAP) could not be clustered without other metabolites. GLM analysis identified that pregnant women with the following characteristics have high urinary concentration of PAH metabolites: overweight, in the last trimester of pregnancy, distance between their house and main traffic lines as <5 m, use fuel for cooking, passive smoking, renovated their residence for less than 3 years, middle family income and office workers.ConclusionThe results clarified pregnant women from the economically underdeveloped area could be the victims of PAHs. In addition, PAHs present a demographic and seasonal differential distribution, which will aid in the development of targeted interventions and reduce exposure to PAHs during pregnancy.

Introduction Careful monitoring of patients who receive intravenous thrombolysis (IVT) for acute ischemic stroke (AIS) is resource-intensive, and potentially less relevant in those with mild degrees of neurological impairment who are at low-risk of symptomatic intracerebral hemorrhage (sICH) and other complications. \ Methods OPTIMISTmain is an international, multicenter, prospective, stepped wedge, cluster randomized, blinded outcome assessed trial aims to determine whether a less-intensity monitoring protocol is at least as effective, safe and efficient as standard post-IVT monitoring in patients with mild deficits post-AIS. Clinically-stable adult patients with mild AIS (defined by a NIHSS <10) who do not require intensive care within 2 hours post-IVT are recruited at hospitals in Australia, Chile, China, Malaysia, Mexico, UK, US and Vietnam. An average of 15 patients recruited per period (overall 60 patient participants) at 120 sites for a total of 7200 IVT-treated AIS patients will provide 90% power (one-sided α 0.025). The initiation of eligible hospitals is based on a rolling process whenever ready, stratified by country. Hospitals are randomly allocated using permuted blocks into 3 sequences of implementation, stratified by country and the projected number of patients to be recruited over 12 months. These sequences have four periods that dictate the order in which they are to switch from control (usual care) to intervention (implementation of low intensity monitoring protocol) to different clusters of patients in a stepped manner. Compared to standard monitoring, the low-intensity monitoring protocol includes assessments of neurological and vital signs every 15 minutes for 2 hours, 2 hourly (versus every 30 minutes) for 8 hours, and 4 hourly (versus every 1 hour) until 24 hours, post-IVT. The primary outcome measure is functional recovery, defined by the modified Rankin scale (mRS) at 90 days, a seven-point ordinal scale (0 [no residual symptom] to 6 [death]). Secondary outcomes include death or dependency, length of hospital stay, and health-related quality of life, sICH and serious adverse events. Conclusion OPTIMISTmain will provide Level I evidence for the safety and effectiveness of a low-intensity post-IVT monitoring protocol in patients with mild severity of AIS.

Background Bone mineral density (BMD) and prevalence of osteoporosis may differ between urban and rural populations. This study aimed to investigate the differences in BMD characteristics between urban and rural populations in Jiangsu, China. Methods A total of 2,711 participants aged 20 years and older were included in the cross-sectional study. Multistage and stratified cluster random sampling was used as the sampling strategy. BMD was measured by the method of dual-energy x-ray absorptiometry (DXA). Data were collected through questionnaires/interview. BMD values at the lumbar spine (L1-L4), femoral neck, total hip, and greater trochanter were collected. Descriptive statistics were used to demonstrate the characteristics of urban and rural participants. Multivariate logistic regression analysis was utilized to analyze the factors that may be associated with osteoporosis in urban and rural populations. Results Of these participants, 1,540 (50.49%) were females and 1,363 (42.14%) were from urban. The prevalence of osteoporosis in urban and rural populations was 5.52% and 10.33%, respectively. In terms of gender, the prevalence of osteoporosis was 2.68% in males and 13.82% in females. For menopausal status, the prevalence of osteoporosis was 30.34% in postmenopausal females and 4.78% in premenopausal females. In urban populations, older age [adjusted odds ratio (AOR) = 2.36, 95%CI, 2.35–2.36), hypertension (AOR = 1.37, 95%CI, 1.36–1.37), unmarried (AOR = 4.04, 95%CI, 3.99–4.09), smoking everyday (AOR = 2.26, 95%CI, 2.23–2.28), family history of osteoporosis (AOR = 1.66, 95%CI, 1.65–1.67), dyslipidemia (AOR = 1.05, 95%CI, 1.04–1.05), and higher β-crosslaps (β-CTX) level (AOR = 1.02, 95%CI, 1.02–1.02) were associated with an increased risk of osteoporosis, while males (AOR = 0.04, 95%CI, 0.04–0.04), higher education level (AOR = 0.95, 95%CI, 0.95–0.95), and aquatic product intake (AOR = 0.99, 95%CI, 0.99–0.99) were related to decreased risk of osteoporosis. Similar results were also observed in rural populations, and (all P < 0.05). Conclusion The prevalence of osteoporosis in rural populations was higher than that in urban populations, and the factors associated with the risk of osteoporosis were similar in urban and rural populations.

Background: Limited data exist on the relationship between blood pressure variability and cognitive decline in low- and middle- income countries. We determined associations of systolic blood pressure change and blood pressure variability on cognition performance in a nationally representative population-based cohort study.Methods: The China Health and Retirement Longitudinal Study included 5,696 participants (age ≥45 years) in four waves during 2011-2018. Blood pressure variability was measured using within-individual standard deviation of systolic blood pressure (in the first three wave visits) and coefficient of variation. Global cognition score was summed from a short screening test supplemented with the addition of word recall and figure copying tests, with higher scores indicating higher cognitive function. Multivariable linear regression models were used to examine associations of systolic blood pressure change and blood pressure variability, and cognition performance as well as decline in cognitive function.Findings: Of 5,696 participants (mean age 57.7 years, 47.4% female), 27.8% showed decline in cognition over 8 years of follow-up. Standard deviation of blood pressure variability significantly reduced the odds of good cognitive function (coefficient -0.140, 95% confidence interval [CI] -0.222 to -0.058]). Similar findings were found for the coefficient of variation. Compared to having good systolic blood pressure control, those with poor control were more likely to show low global cognition scores (coefficient -0.519, 95%CI -0.997 to -0.041). Subgroup analysis showed significant associations in those without history of hypertension at baseline, not on antihypertensive medication, and rural residents, but no significant relations were seen in people with hypertension, antihypertensive medication use, or urban residents.Interpretation: In middle-aged and older Chinese adults, uncontrolled blood pressure and higher blood pressure variability are independent predictors of accelerated decline in cognitive function. Efforts should be made by policy makers and healthcare providers to prioritize achieving stable and well-controlled blood pressure target as a crucial strategy for reducing the growing burden of cognitive impairment and dementia.Funding: Global Brain Health Initiative Seed Grant.Declaration of Interest: We declare no competing interests.Ethical Approval: The Biomedical Ethics Review Committee of Peking University approved the China Health and Retirement Longitudinal study, and all interviewees were required to provide written informed consent. The ethical approval number was IRB00001052–11015.