Clopidogrel Plus Aspirin vs Aspirin Alone in Patients With Acute Mild to Moderate Stroke: The ATAMIS Randomized Clinical Trial.

Importance: Dual antiplatelet therapy has been demonstrated to be superior to single antiplatelet in reducing recurrent stroke among patients with transient ischemic attack or minor stroke, but robust evidence for its effect in patients with mild to moderate ischemic stroke is lacking. Objective: To evaluate whether dual antiplatelet therapy is superior to single antiplatelet among patients with mild to moderate ischemic stroke. Design, Setting, and Participants: This was a multicenter, open-label, blinded end point, randomized clinical trial conducted at 66 hospitals in China from December 20, 2016, through August 9, 2022. The date of final follow-up was October 30, 2022. The analysis was reported on March 12, 2023. Of 3065 patients with ischemic stroke, 3000 patients with acute mild to moderate stroke within 48 hours of symptom onset were enrolled, after excluding 65 patients who did not meet eligibility criteria or had no randomization outcome. Interventions: Within 48 hours after symptom onset, patients were randomly assigned to receive clopidogrel plus aspirin (n = 1541) or aspirin alone (n = 1459) in a 1:1 ratio. Main Outcomes and Measures: The primary end point was early neurologic deterioration at 7 days, defined as an increase of 2 or more points in National Institutes of Health Stroke Scale (NIHSS) score, but not as a result of cerebral hemorrhage, compared with baseline. The superiority of clopidogrel plus aspirin to aspirin alone was assessed based on a modified intention-to-treat population, which included all randomized participants with at least 1 efficacy evaluation regardless of treatment allocation. Bleeding events were safety end points. Results: Of the 3000 randomized patients, 1942 (64.6%) were men, the mean (SD) age was 65.9 (10.6) years, median (IQR) NIHSS score at admission was 5 (4-6), and 1830 (61.0%) had a stroke of undetermined cause. A total of 2915 patients were included in the modified intention-to-treat analysis. Early neurologic deterioration occurred in 72 of 1502 (4.8%) in the dual antiplatelet therapy group vs 95 of 1413 (6.7%) in the aspirin alone group (risk difference -1.9%; 95% CI, -3.6 to -0.2; P = .03). Similar bleeding events were found between 2 groups. Conclusions and Relevance: Among Chinese patients with acute mild to moderate ischemic stroke, clopidogrel plus aspirin was superior to aspirin alone with regard to reducing early neurologic deterioration at 7 days with similar safety profile. These findings indicate that dual antiplatelet therapy may be a superior choice to aspirin alone in treating patients with acute mild to moderate stroke. Trial Registration: ClinicalTrials.gov Identifier: NCT02869009.

Cancer burden and risk in the Chinese population aged 55 years and above: A systematic analysis and comparison with the USA and Western Europe.

Background: We analysed the cancer burden among elderly Chinese people over the age of 55 years and compared them to USA and Western Europe to explore the cancer model in China. Methods: We retrieved data on 29 cancers with 34 risk factors from the 2019 Global Burden of Disease database to evaluate the cancer burden in Chinese elderly individuals aged 55 years and older. We then used the age-standardised incidence rate (ASIR), age-standardised death rate (ASDR), age-standardised disability-adjusted life year (DALY) rate, and average annual percentage change (AAPC) to compare the characteristics and change trend of cancers among China, USA, and Western Europe. Results: In 2019, the number of incident cases of 29 cancers among people aged 55 years and above in China increased more than 3-fold compared to 1990, while the number of deaths and DALYs approximately doubled. We also found that the cancer population in China was ageing; meanwhile, the cancer burden became significantly higher for men than for women, and the gap between men and women had widened. Cancers with the highest cancer DALYs were lung cancer (13 444 500; 95% uncertainty interval (UI) = 11 307 100, 15 853 700), stomach cancer (7 303 900; 95% UI = 6 094 600, 8 586 500), oesophageal cancer (4 633 500; 95% UI = 3 642 500, 5 601 200), colon and rectum cancer (4 386 500; 95% UI = 3 769 500, 5 067 200), liver cancer (2 915 100, 95% UI = 2 456 300, 3 463 900), and pancreatic cancer (2 028 400; 95% UI = 1 725 000, 2 354 900). Compared with 1990, the DALY rate and incidence rate of stomach cancer, oesophageal cancer, and liver cancer had markedly decreased. The DALY rate and incidence rate of lung, colon, rectum, and pancreatic cancer had increased significantly, as did the incidence rate of breast cancer in women. Smoking and diet were the top two cancer risk factors, and the impact of ambient particulate matter pollution on cancer increased each year. The overall 29 cancers age-standardised DALY rate and ASDR in China, USA, and Western Europe were similar, and all showed downward trend in the past 30 years. Compared with the USA and Western Europe, the age-standardised DALY rate of liver, nasopharyngeal, oesophageal, stomach, and cervical cancers in China was more prominent. The age-standardised DALY rate of lung cancer and colon and rectum cancer decreased annually in Western Europe and the USA, but increased in China. Conclusions: Over the past 30 years, China had made progress in controlling stomach, oesophageal, and liver cancer. However, lung, colon, rectum, pancreatic, and breast cancers had become more prevalent, having risen alongside economic development. The risks of smoking and dietary were major issues that need to be addressed urgently. The cancer situation in China remains serious; future cancer prevention efforts need to balance economic development with people's physical health, identify key groups, improve the health environment of residents and guide them to live a healthy life, and expand the scope of cancer screening.

Management of priming fluids in cardiopulmonary bypass for adult cardiac surgery: network meta-analysis.

BACKGROUND: Cardiopulmonary bypass (CPB) is frequently employed for cardiac surgery, and selecting a suitable priming fluid is a prerequisite for CPB. Currently, the commonly used priming fluids in clinics are classified as crystalloids and colloids, including balanced crystalloids, albumin, dextran, gelatin and hydroxyethyl starch (HES). This network meta-analysis compared the effects of eight fluids used during CPB in adults to determine optimal priming fluid during CPB surgery. METHODS: Randomised controlled trials assessing priming fluids for CPB in adult cardiac surgery published before 13 April 2023 were searched across Ovid MEDLINE(R) ALL, OVID EMbase, and Cochrane Central Register of Controlled Trials. Various priming fluids were classified into eight categories, including balanced crystalloids, 0.9% NaCl, iso-oncotic human albumin, hyperoncotic human albumin, HES with molecular weight 130k, HES with molecular weight 200k, gelatin and dextran. RESULTS: The NMA of platelet counts revealed no significant differences in any result. In direct comparison results, only the comparison of HES with molecular weight 130k vs. gelatin (standard mean difference = -0.40, 95% confidence interval [95%CI: -0.63, -0.16) revealed a significant difference. According to the SUCRA, balanced crystalloids had the highest platelet count, followed by gelatin, and HES with a molecular weight of 130k had the lowest platelet, followed by HES with a molecular weight of 200k. CONCLUSION: Patients using dextran have a low mortality rate and a short mean CPB time, the use of balanced crystalloids is beneficial in terms of platelet count, and HES with molecular weight 130k is beneficial for postoperative urine volume at 24h. However, all priming fluids have pros and cons quite, and the optimal choice of priming fluids remains unsupported by current evidences. When performing CPB surgery, the type of priming fluid should be selected according to the actual situation in CPB for adult cardiac surgery.

When dextran was used as the CPB priming fluid, patients had the lowest mortality and shortest mean CPB time.With iso-oncotic HA, patients had the shortest length of ICU stay, the least blood loss 24h after surgery, and the lowest chest tube output 24h after surgery.The use of balanced crystalloids was beneficial for platelet count, the use of L-HES was beneficial for urine output 24h after surgery, and the use of H-HES resulted in the shortest hospital stay.In summary, each of these fluids has pros and cons quite, and an optimal choice of priming fluids during CPB surgery remains unsupported by current evidence.When performing CPB surgery, the type of priming fluids should be selected according to the actual condition of the patient's body.

Intravenous Tenecteplase for Acute Ischemic Stroke Within 4.5-24 Hours of Onset (ROSE-TNK): A Phase 2, Randomized, Multicenter Study.

BACKGROUND AND PURPOSE: Intravenous tenecteplase (TNK) efficacy has not been well demonstrated in acute ischemic stroke (AIS) beyond 4.5 hours after onset. This study aimed to determine the effect of intravenous TNK for AIS within 4.5 to 24 hours of onset. METHODS: In this pilot trial, eligible AIS patients with diffusion-weighted imaging (DWI)-fluid attenuated inversion recovery (FLAIR) mismatch were randomly allocated to intravenous TNK (0.25 mg/kg) or standard care within 4.5-24 hours of onset. The primary endpoint was excellent functional outcome at 90 days (modified Rankin Scale [mRS] score of 0-1). The primary safety endpoint was symptomatic intracranial hemorrhage (sICH). RESULTS: Of the randomly assigned 80 patients, the primary endpoint occurred in 52.5% (21/40) of TNK group and 50.0% (20/40) of control group, with no significant difference (unadjusted odds ratio, 1.11; 95% confidence interval 0.46-2.66; P=0.82). More early neurological improvement occurred in TNK group than in control group (11 vs. 3, P=0.03), but no significant differences were found in other secondary endpoints, such as mRS 0-2 at 90 days, shift analysis of mRS at 90 days, and change in National Institutes of Health Stroke Scale score at 24 hours and 7 days. There were no cases of sICH in this trial; however, asymptomatic intracranial hemorrhage occurred in 3 of the 40 patients (7.5%) in the TNK group. CONCLUSION: This phase 2, randomized, multicenter study suggests that intravenous TNK within 4.5-24 hours of onset may be safe and feasible in AIS patients with a DWI-FLAIR mismatch.

A randomized trial of Trendelenburg position for acute moderate ischemic stroke.

We aim to explore the effect of head-down position (HDP), initiated within 24 hours of onset, in moderate anterior circulation stroke patients with probable large artery atherosclerosis (LAA) etiology. This investigator-initiated, multi-center trial prospective, randomized, open-label, blinded-endpoint, multi-center and phase-2 trial was conducted in China and completed in 2021. Eligible patients were randomly assigned (1:1) into the HDP group receiving -20° Trendelenburg, or control group receiving standard care according to national guideline. The primary endpoint was proportion of modified Rankin Scale (mRS) of 0 to 2 at 90 days, which is a scale for measuring the degree of disability after stroke. 90-day mRS was assessed by a certified staff member who was blinded to group assignment. A total of 96 patients were randomized (47 in HDP group and 49 in control group) and 94 (97.9%) patients were included in the final analysis: 46 in HDP group and 48 in control group. The proportion of favorable outcome was 65.2% (30/46) in the HDP group versus 50.0% (24/48) in the control group (unadjusted: OR 2.05 [95%CI 0.87-4.82], P = 0.099). No severe adverse event was attributed to HDP procedures. This work suggests that the head-down position seems safe and feasible, but does not improve favorable functional outcome in acute moderate stroke patients with LAA. This trial was registered with ClinicalTrials.gov, NCT03744533.

Global, regional, and national trends of syphilis from 1990 to 2019: the 2019 global burden of disease study.

BACKGROUND: Syphilis is a sexually transmitted disease caused by Treponema pallidum, and the infection source is syphilis patients. This study aimed to estimate the incidence, mortality rate, and disability-adjusted life years (DALYs) of syphilis to improve the understanding of the current global situation of syphilis. METHODS: This study collected data on syphilis incidence, mortality, and DALYs from the 2019 Global Burden of Disease database. RESULTS: The global number of incident cases and age-standardized incidence rate (ASIR) increased from 8,845,220 (95% UI: 6,562,510-11,588,860) in 1990 to 14,114,110 (95% UI: 10,648,490-18,415,970) in 2019 and 160.03/100,000 persons (95% UI: 120.66-208.1) to 178.48/100,000 persons (95% UI: 134.94-232.34), respectively. The estimated annual percentage change (EAPC) in the ASIR was 0.16 (95% CI: 0.07-0.26). The EAPC in the ASIR associated with high and high-middle sociodemographic indices increased. The ASIR increased among males but decreased among females, and the incidence peaked among males and females between the ages of 20 and 30 years. The EAPCs in the age-standardized death rate and age-standardized DALY rate decreased. CONCLUSIONS: The incidence and ASIR of syphilis increased worldwide from 1990 to 2019. Only the regions with high and high-middle sociodemographic indices showed an increase in the ASIR. Moreover, the ASIR increased among males but decreased among females. The age-standardized death rate and DALY rate both declined worldwide. The increase in the global ASIR of syphilis is a challenge.

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To investigate the effects of Spartina alterniflora invasion on mangrove wetland ecosystem, the benthic crustacean and fish samples were collected using cage nets in Zhangjiang Estuary Mangrove Wetland, Fujian Pro-vince in August 2020, January and April 2021. The five sampling sites included two mangroves (Avicennia marina and Kandelia obovata) sites, two S. alterniflora sites, and one mudflat site. The abundance, biomass, index of relative importance (IRI), Shannon diversity index (H), Pielou evenness index (J), and Margalef richness index (D) were used to quantify the dominant species and species diversity of benthic crustaceans and fishes. The functional groups and niche of dominant species were also analyzed. A total of 37 species, from 2 phyla, 2 classes, 8 orders, and 17 families, were identified across the three seasons. Most of them were warm-water and euryhaline species, mainly carnivorous and omnivorous functional groups. The results of two-way analysis of variance and NMDS showed that the community diversity index of benthic crustacean and fish did not change significantly after the invasion of S. alterniflora compared with mudflat. Functional groups had changed significantly, with the species number of plankton functional groups, carnivorous and phytophagous functional groups being increased. Compared with mangrove sites, the number of species of benthic crustacean and fish in S. alterniflora sites was significantly increased. The spatio-temporal niche breadth of dominant species ranged from 0 to 1.4186, with Liza carinata (1.4186), Bostrychus sinensis (1.0168), Metapenaeus ensis (0.9469) and Exopalaemon carinicauda (0.8922) as the top four species.

Effect of Remote Ischemic Conditioning vs Usual Care on Neurologic Function in Patients With Acute Moderate Ischemic Stroke: The RICAMIS Randomized Clinical Trial.

Importance: Preclinical and clinical studies have suggested a neuroprotective effect of remote ischemic conditioning (RIC), which involves repeated occlusion/release cycles on bilateral upper limb arteries; however, robust evidence in patients with ischemic stroke is lacking. Objective: To assess the efficacy of RIC for acute moderate ischemic stroke. Design, Setting, and Participants: This multicenter, open-label, blinded-end point, randomized clinical trial including 1893 patients with acute moderate ischemic stroke was conducted at 55 hospitals in China from December 26, 2018, through January 19, 2021, and the date of final follow-up was April 19, 2021. Interventions: Eligible patients were randomly assigned within 48 hours after symptom onset to receive treatment with RIC (using a pneumatic electronic device and consisting of 5 cycles of cuff inflation for 5 minutes and deflation for 5 minutes to the bilateral upper limbs to 200 mm Hg) for 10 to 14 days as an adjunct to guideline-based treatment (n = 922) or guideline-based treatment alone (n = 971). Main Outcomes and Measures: The primary end point was excellent functional outcome at 90 days, defined as a modified Rankin Scale score of 0 to 1. All end points had blinded assessment and were analyzed on a full analysis set. Results: Among 1893 eligible patients with acute moderate ischemic stroke who were randomized (mean [SD] age, 65 [10.3] years; 606 women [34.1%]), 1776 (93.8%) completed the trial. The number with excellent functional outcome at 90 days was 582 (67.4%) in the RIC group and 566 (62.0%) in the control group (risk difference, 5.4% [95% CI, 1.0%-9.9%]; odds ratio, 1.27 [95% CI, 1.05-1.54]; P = .02). The proportion of patients with any adverse events was 6.8% (59/863) in the RIC group and 5.6% (51/913) in the control group. Conclusions and Relevance: Among adults with acute moderate ischemic stroke, treatment with remote ischemic conditioning compared with usual care significantly increased the likelihood of excellent neurologic function at 90 days. However, these findings require replication in another trial before concluding efficacy for this intervention. Trial Registration: ClinicalTrials.gov Identifier: NCT03740971.

Pharmaceutical administration for severe hypertension during pregnancy: Network meta-analysis.

Aims: To evaluate the efficacy of different pharmacologic treatment for severe hypertension during pregnancy. Methods: Two reviewers searched Ovid MEDLINE, Ovid EMbase, and the Cochrane Library for randomized clinical trials from the establishment of the database to 15 July 2021 that were eligible for inclusion and analyzed the pharmaceuticals used for severe hypertension in pregnancy. Results: 29 relevant trials with 2,521 participants were involved. Compared with diazoxide in rate of achieving target blood pressure, other pharmaceuticals, including epoprostenol (RR:1.58, 95%CI:1.01-2.47), hydralazine\dihydralazine (RR:1.57, 95%CI:1.07-2.31), ketanserin (RR:1.67, 95%CI:1.09-2.55), labetalol (RR:1.54, 95%CI:1.04-2.28), nifedipine (RR:1.54, 95%CI:1.04-2.29), and urapidil (RR:1.57, 95%CI:1.00-2.47), were statistically significant in the rate of achieving target blood pressure. According to the SUCRA, diazoxide showed the best therapeutic effect, followed by nicardipine, nifedipine, labetalol, and nitroglycerine. The three pharmaceuticals with the worst therapeutic effect were ketanserin, hydralazine, and urapidil. It is worth noting that the high ranking of the top two pharmaceuticals, including diazoxide and nicardipine, comes from extremely low sample sizes. Other outcomes were reported in the main text. Conclusion: This comprehensive network meta-analysis demonstrated that the nifedipine should be recommended as a strategy for blood pressure management in pregnant women with severe hypertension. Moreover, the conventional pharmaceuticals, including labetalol and hydralazine, showed limited efficacy. However, it was important to note that the instability of hydralazine reducing blood pressure and the high benefit of labetalol with high dosages intakes should also be of concern to clinicians.