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Cerebral Small Vessel Disease and Prognosis in Intracerebral Hemorrhage: A Systematic Review and Meta-analysis of Cohort Studies
Cheng Z, Zhang W, Zhan Z, Xia L, Han Z
European journal of neurology. 2022
Abstract
BACKGROUND To investigate whether cerebral small vessel disease (CSVD) markers and the total CSVD burden are associated with functional outcome, mortality, stroke recurrence, and hematoma expansion in patients with spontaneous intracerebral hemorrhage (ICH). METHODS Following a previously registered protocol (PROSPERO protocol: CRD42021287743), we systematically searched PubMed, Web of Science, and EMBASE to identify relevant literature up to November 2021. Cohort studies that examined the association between CSVD markers (white matter hyperintensity [WMH], lacune, enlarged perivascular space [EPVS], cerebral microbleed [CMB], and brain atrophy) or CSVD burden and prognosis in patients with ICH were included. The pooled estimates were calculated using random effects models. RESULTS Forty-one studies with 19,752 ICH patients were pooled in the meta-analysis. WMH (OR=1.50, 95% CI=1.32 to 1.70), lacune (OR=1.32, 95% CI=1.18 to 1.49), CMB (OR=2.60, 95% CI=1.13 to 5.97) and brain atrophy (OR=2.22, 95% CI=1.48 to 3.31) were associated with worse functional outcome. CSVD markers concerning increased risk of mortality were WMH (OR=1.57, 95% CI=1.38 to 1.79) and brain atrophy (OR=1.84, 95% CI=1.11 to 3.04), while concerning increased risk of stroke recurrence were WMH (OR=1.62, 95% CI=1.28 to 2.04) and lacune (OR=3.00, 95% CI=1.68 to 5.37). EPVS was not related to prognosis. There was a lack of association between CSVD markers and hematoma expansion. CSVD burden increased the risk of worse functional outcome, mortality, and stroke recurrence by 57%, 150%, and 44%, respectively. CONCLUSIONS In patients with spontaneous ICH, WMH, lacune, CMB, brain atrophy, and the total CSVD burden are associated with substantially increased risk of worse functional outcome, mortality, or stroke recurrence.
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The pharmacodynamic effect of terlipressin versus high-dose octreotide in reducing hepatic venous pressure gradient: a randomized controlled trial
Li B, Chen J, Zhang CQ, Wang GC, Hu JH, Luo JJ, Zhang W, Wei YC, Zeng XQ, Chen SY
Annals of translational medicine. 2021;9(9):793
Abstract
BACKGROUND Vasoactive drugs can reduce portal venous pressure and control variceal bleeding. However, few studies have explored the hemodynamic effects of terlipressin and high-dose octreotide in such patients. Our purpose was to evaluate the hemodynamic changes and safety of using terlipressin and high-dose octreotide in patients with decompensated liver cirrhosis. METHODS A multi-center randomized controlled trial was conducted. Cirrhotic patients with a history of variceal bleeding were included. Terlipressin or high-dose octreotide was administered during the procedure of measuring hepatic venous pressure gradient (HVPG). Hemodynamic parameters and symptoms were recorded. RESULTS A total of 88 patients were included. HVPG was significantly reduced at 10, 20, and 30 min after drug administration in the terlipressin group (16.3±6.4 vs. 14.7±5.9, 14.0±6.1, and 13.8±6.1, respectively, P<0.001) and the high-dose octreotide group (17.4±6.6 vs. 15.1±5.8, 15.3±6.2, and 16.1±6.0, respectively P<0.01). Decreased heart rate and increased mean arterial pressure were more often observed in the terlipressin group. The overall response rates were not significantly different between the groups (52.8% vs. 44.8%, P=0.524). The terlipressin group had significantly higher response rates at 30 min compared to the high-dose octreotide group in those with alcoholic liver cirrhosis [6/6 (100%) vs. 0/4 (0%), P=0.005]. The incidence of adverse drug events was rare and similar in the two groups. CONCLUSIONS Both terlipressin and high-dose octreotide were effective and safe for reducing HVPG. The pharmacodynamic effect of terlipressin persisted longer. The terlipressin group had higher response rates in those with alcoholic cirrhosis (trial number: NCT02119884).
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Hypertension management in elderly with severe intracerebral hemorrhage
Zhao J, Yuan F, Fu F, Liu Y, Xue C, Wang K, Yuan X, Li D, Liu Q, Zhang W, et al
Annals of clinical and translational neurology. 2021;8(10):2059–2069
Abstract
OBJECTIVE To explore the effect of individualized blood pressure (BP)-lowering treatment on the outcomes of elderly patients with severe intracerebral hemorrhage (ICH). METHODS We performed an exploratory analysis of Controlling Hypertension After Severe Cerebrovascular Event (CHASE) trial, which was a multicenter, randomized, controlled clinical trial. Patients with severe ischemic or hemorrhagic stroke (defined as GCS ≤ 12 or NIHSS ≥ 11) were randomized into individualized versus standard BP-lowering treatment in CHASE trial. In this exploratory analysis, patients with severe ICH were included. The primary outcome was the percentage of patients with 90-day functional independence defined as modified Rankin Scale (mRS) ≤2. RESULTS We included 242 patients with severe ICH in the present analysis, consisting of 142 patients aged <65 years and 100 patients aged ≥65 years. There were significant differences between patients aged ≥65 years and <65 years in the proportion of functional independence (47.9% vs. 15.0%, P < 0.001) and good outcome (73.9% vs. 50.0%, P < 0.001) at day 90. In patients aged ≥65 years, the adjusted individualized BP-lowering treatment had an unequivocal effect on the functional independence at day 90 (21.6% vs. 8.2%, odds ratio [OR]: 4.309, 95% confidence interval [CI]: 1.040-17.859, P = 0.044) and improved the neurological deficits at discharge (∆ NIHSS ≥ 4: 64.7% vs. 34.7%, OR: 4.300, 95% CI: 1.599-11.563, P = 0.004). INTERPRETATION Compared with the younger counterparts, the elderly patients (≥65 years) with acute severe ICH might benefit more from individualized BP-lowering treatment.
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Effect of Convalescent Plasma Therapy on Time to Clinical Improvement in Patients With Severe and Life-threatening COVID-19: A Randomized Clinical Trial
Li L, Zhang W, Hu Y, Tong X, Zheng S, Yang J, Kong Y, Ren L, Wei Q, Mei H, et al
Jama. 2020
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Abstract
Importance: Convalescent plasma is a potential therapeutic option for patients with coronavirus disease 2019 (COVID-19), but further data from randomized clinical trials are needed. Objective: To evaluate the efficacy and adverse effects of convalescent plasma therapy for patients with COVID-19. Design, Setting, and Participants: Open-label, multicenter, randomized clinical trial performed in 7 medical centers in Wuhan, China, from February 14, 2020, to April 1, 2020, with final follow-up April 28, 2020. The trial included 103 participants with laboratory-confirmed COVID-19 that was severe (respiratory distress and/or hypoxemia) or life-threatening (shock, organ failure, or requiring mechanical ventilation). The trial was terminated early after 103 of a planned 200 patients were enrolled. Intervention: Convalescent plasma in addition to standard treatment (n = 52) vs standard treatment alone (control) (n = 51), stratified by disease severity. Main Outcomes and Measures: Primary outcome was time to clinical improvement within 28 days, defined as patient discharged alive or reduction of 2 points on a 6-point disease severity scale (ranging from 1 [discharge] to 6 [death]). Secondary outcomes included 28-day mortality, time to discharge, and the rate of viral polymerase chain reaction (PCR) results turned from positive at baseline to negative at up to 72 hours. Results: Of 103 patients who were randomized (median age, 70 years; 60 [58.3%] male), 101 (98.1%) completed the trial. Clinical improvement occurred within 28 days in 51.9% (27/52) of the convalescent plasma group vs 43.1% (22/51) in the control group (difference, 8.8% [95% CI, -10.4% to 28.0%]; hazard ratio [HR], 1.40 [95% CI, 0.79-2.49]; P = .26). Among those with severe disease, the primary outcome occurred in 91.3% (21/23) of the convalescent plasma group vs 68.2% (15/22) of the control group (HR, 2.15 [95% CI, 1.07-4.32]; P = .03); among those with life-threatening disease the primary outcome occurred in 20.7% (6/29) of the convalescent plasma group vs 24.1% (7/29) of the control group (HR, 0.88 [95% CI, 0.30-2.63]; P = .83) (P for interaction = .17). There was no significant difference in 28-day mortality (15.7% vs 24.0%; OR, 0.65 [95% CI, 0.29-1.46]; P = .30) or time from randomization to discharge (51.0% vs 36.0% discharged by day 28; HR, 1.61 [95% CI, 0.88-2.93]; P = .12). Convalescent plasma treatment was associated with a negative conversion rate of viral PCR at 72 hours in 87.2% of the convalescent plasma group vs 37.5% of the control group (OR, 11.39 [95% CI, 3.91-33.18]; P < .001). Two patients in the convalescent plasma group experienced adverse events within hours after transfusion that improved with supportive care. Conclusion and Relevance: Among patients with severe or life-threatening COVID-19, convalescent plasma therapy added to standard treatment, compared with standard treatment alone, did not result in a statistically significant improvement in time to clinical improvement within 28 days. Interpretation is limited by early termination of the trial, which may have been underpowered to detect a clinically important difference. Trial Registration: Chinese Clinical Trial Registry: ChiCTR2000029757.
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Effect of Convalescent Plasma Therapy on Time to Clinical Improvement in Patients With Severe and Life-threatening COVID-19
Li L, Zhang W, Hu Y, Tong X, Zheng S, Yang J, Kong Y, Ren L, Wei Q, Mei H, et al
Jama. 2020
Abstract
ImportanceConvalescent plasma is a potential therapeutic option for patients with coronavirus disease 2019 (COVID-19), but further data from randomized clinical trials are needed ObjectiveTo evaluate the efficacy and adverse effects of convalescent plasma therapy for patients with COVID-19 Design, Setting, and ParticipantsOpen-label, multicenter, randomized clinical trial performed in 7 medical centers in Wuhan, China, from February 14, 2020, to April 1, 2020, with final follow-up April 28, 2020 The trial included 103 participants with laboratory-confirmed COVID-19 that was severe (respiratory distress and/or hypoxemia) or life-threatening (shock, organ failure, or requiring mechanical ventilation) The trial was terminated early after 103 of a planned 200 patients were enrolled InterventionConvalescent plasma in addition to standard treatment (n = 52) vs standard treatment alone (control) (n = 51), stratified by disease severity Main Outcomes and MeasuresPrimary outcome was time to clinical improvement within 28 days, defined as patient discharged alive or reduction of 2 points on a 6-point disease severity scale (ranging from 1 [discharge] to 6 [death]) Secondary outcomes included 28-day mortality, time to discharge, and the rate of viral polymerase chain reaction (PCR) results turned from positive at baseline to negative at up to 72 hours ResultsOf 103 patients who were randomized (median age, 70 years;60 [58 3%] male), 101 (98 1%) completed the trial Clinical improvement occurred within 28 days in 51 9% (27/52) of the convalescent plasma group vs 43 1% (22/51) in the control group (difference, 8 8% [95% CI, −10 4% to 28 0%];hazard ratio [HR], 1 40 [95% CI, 0 79-2 49];P = 26) Among those with severe disease, the primary outcome occurred in 91 3% (21/23) of the convalescent plasma group vs 68 2% (15/22) of the control group (HR, 2 15 [95% CI, 1 07-4 32];P = 03);among those with life-threatening disease the primary outcome occurred in 20 7% (6/29) of the convalescent plasma group vs 24 1% (7/29) of the control group (HR, 0 88 [95% CI, 0 30-2 63];P = 83) (Pfor interaction = 17) There was no significant difference in 28-day mortality (15 7% vs 24 0%;OR, 0 65 [95% CI, 0 29-1 46];P = 30) or time from randomization to discharge (51 0% vs 36 0% discharged by day 28;HR, 1 61 [95% CI, 0 88-2 93];P = 12) Convalescent plasma treatment was associated with a negative conversion rate of viral PCR at 72 hours in 87 2% of the convalescent plasma group vs 37 5% of the control group (OR, 11 39 [95% CI, 3 91-33 18];P < 001) Two patients in the convalescent plasma group experienced adverse events within hours after transfusion that improved with supportive care Conclusion and RelevanceAmong patients with severe or life-threatening COVID-19, convalescent plasma therapy added to standard treatment, compared with standard treatment alone, did not result in a statistically significant improvement in time to clinical improvement within 28 days Interpretation is limited by early termination of the trial, which may have been underpowered to detect a clinically important difference Trial RegistrationChinese Clinical Trial Registry:ChiCTR2000029757
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Intra-articular platelet-rich plasma injections for knee osteoarthritis: an overview of systematic reviews and risk of bias considerations
Xing D, Wang B, Zhang W, Yang Z, Hou Y, Chen Y, Lin J
International Journal of Rheumatic Diseases. 2017;20((11):):1612-1630
Abstract
OBJECTIVES Numerous systematic reviews investigating the efficacy of platelet-rich plasma (PRP) in treating knee osteoarthritis (OA) have been recently published. The purpose of the present study was (1) to perform an overview of overlapping systematic reviews investigating PRP for knee OA via evaluating methodological quality and risk of bias of systematic reviews and (2) to provide recommendations through the best evidence. METHODS A systematic search of systematic reviews published through Feb 2017 was conducted using the MEDLINE, EMBASE and Cochrane Library. The methodological quality and risk of bias of included systematic reviews were assessed by AMSTAR instrument and ROBIS tool respectively. Best evidence choice procedure was conducted according to the Jadad decision algorithm. The systematic reviews with high quality of methodology and low risk of bias were selected ultimately. RESULTS Ten systematic reviews were eligible for inclusion. The Jadad decision making tool suggested that the reviews with highest AMSTAR score should be selected. According to the ROBIS tool, there were 4 systematic reviews with low risk of bias and 6 with high risk of bias. As a result, two systematic reviews conducted by Dai et al and Meheux et al with highest AMSTAR score and low risk of bias were selected as the best evidence. CONCLUSIONS The present overview demonstrates that PRP is an effective intervention in treating knee OA without increased risk of adverse events. Therefore, the present conclusions may help decision makers interpret and choose PRP with more confidence.
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The fragility of randomized controlled trials in intracranial hemorrhage
Shen Y, Cheng X, Zhang W
Neurosurgical Review. 2017
Abstract
Fragility of randomized controlled trials (RCTs) has been evaluated using a novel metric called fragility index (FI), which measures how many events the statistical significance of a dichotomous outcome depends on. This study aimed to evaluate the fragility of RCTs in intracranial hemorrhage. Literature search (PubMed/Embase) identified all RCTs of intracranial hemorrhage since 2006. The overall distribution of FI was evaluated. Subgroup and spearman correlation analyses were made to explore potential factors that may affect FI value. All the included RCTs were divided into two groups (positive and negative trials) according to the statistical significance of selected outcomes. Finally, 47 positive and 51 negative trials were included. Both the median FI ([2; IQR, 1-4] vs. [6; IQR, 4-9], p < 0.001) and the proportion of trials with FI ≤1 (2 vs. 18, p < 0.001) in positive trials were smaller than negative trials. In subgroup comparison within positive trials, sample size ([165; IQR, 87-200] vs. [83; IQR, 60-120], p = 0.015) and number of events ([35; IQR, 20-72] vs. [24; IQR, 11-32], p = 0.015) were higher in subgroup with FI >1 than the subgroup with FI ≤1. Weak positive correlations were found between FI and sample size and number of events. In the field of intracranial hemorrhage, trials reporting significant conclusions often depend on a small number of events. Compared to sample size, this phenomenon is more likely to be affected by statistical approach and trial methodology.
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Effect of acetylsalicylic acid usage and platelet transfusion on postoperative hemorrhage and activities of daily living in patients with acute intracerebral hemorrhage
Li X, Sun Z, Zhao W, Zhang J, Chen J, Li Y, Ye Y, Zhao J, Yang X, Xiang Y, et al
Journal of Neurosurgery. 2013;118((1):):94-103.
Abstract
OBJECT The authors evaluated the effects of acetylsalicylic acid (ASA) usage and transfusion of previously frozen apheresis platelets on postoperative hemorrhage, activities of daily living (ADL) score, and mortality rate in patients with acute hypertensive basal ganglia hemorrhage undergoing craniotomy. METHODS This was a prospective, double-blind, parallel, randomized controlled trial in patients with acute hypertensive basal ganglia hemorrhage, who had either not received ASA therapy (control) or received ASA therapy. The patients who received ASA therapy were divided according to the results of a platelet aggregation test into ASA-resistant, ASA-semiresponsive, and ASA-sensitive groups. All patients required an emergency craniotomy for hematoma removal after hospitalization. The patients who were sensitive to ASA were randomized to receive one of the following transfusion regimens of previously frozen apheresis platelets: no transfusion, 1 therapeutic dose before surgery, or 2 therapeutic doses (1 before surgery and 1 after 24 hours of hospitalization). The postoperative hemorrhage rate and the average postoperative hemorrhage volume were recorded and the ADL scores and mortality rate were measured during a 6-month follow-up period. RESULTS The rate of postoperative hemorrhage, average postoperative hemorrhage volume, and mortality rate were significantly higher in the ASA-sensitive patients who received ASA therapy compared with patients who did not receive ASA therapy (all p < 0.005). The ADL scores were grouped into different grades and the number of cases in the lower grades was higher and the overall scores were poorer in patients who received ASA therapy compared with those who did not (all p < 0.005). After transfusion of previously frozen apheresis platelets, the postoperative hemorrhage rate, average postoperative hemorrhage volume, and mortality rate of the ASA-sensitive patients were significantly lowered (all p < 0.005), and the ADL scores and their classification level were better than those of patients who did not undergo transfusion (all p < 0.005). CONCLUSIONS Transfusion of previously frozen apheresis platelets reduces the rate of postoperative hemorrhage, average postoperative hemorrhage volume, disability rate, and mortality rate in ASA-sensitive patients with acute hypertensive basal ganglia hemorrhage undergoing craniotomy.