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JHEP Reports : Innovation in Hepatology Jan 2023The risk of serious clinical outcomes following cessation of nucleos(t)ide analogues (NUCs) in individuals with chronic hepatitis B remains poorly characterized. This...
BACKGROUND & AIMS
The risk of serious clinical outcomes following cessation of nucleos(t)ide analogues (NUCs) in individuals with chronic hepatitis B remains poorly characterized. This systematic review and meta-analysis aimed to evaluate current literature on this issue.
METHODS
We searched PubMed, Embase, and Web of Science for NUC stop studies that noted clinical outcomes published between January 1, 2006 and August 18, 2022. We performed meta-research analyses to examine the relationships of reported outcomes with study designs and characteristics and also pooled studies with non-overlapping populations to provide risk estimates for the proportions of (1) severe hepatitis flares or hepatic decompensation or (2) hepatitis flare-related death or liver transplantation.
RESULTS
The meta-research analysis included 50 studies of highly heterogeneous designs and characteristics. We found that reporting of safety outcomes varied widely according to outcome definition, follow-up duration, and sample size. Only ten studies prespecified safety events as the study outcome, and only four had an outcome definition to include hepatic insufficiency, a follow-up duration >12 months, and a sample size >100 patients. We further pooled 15 studies with 4,525 individuals and estimated that severe hepatitis flares or decompensation would occur in 1.21% (95% CI 0.70-2.08%), with significant heterogeneity ( = 54%, <0.01), while hepatitis flare-related death or liver transplantation would occur in 0.37% (95% CI 0.20-0.67%), without significant heterogeneity ( = 0.00%, = 1.00).
CONCLUSIONS
Current literature on the risk of serious clinical outcomes following NUC cessation is very limited and highly heterogeneous. Pooled analyses of available data found approximately 1% of patients who stopped NUCs developed severe flares or hepatic decompensation.
IMPACT AND IMPLICATIONS
Current literature regarding the safety concerns surrounding NUC cessation for individuals with chronic hepatitis B is limited and heterogeneous in designs and characteristics, and thus should be interpreted with great caution. Based on currently available data, the proportion of patients that develop severe hepatitis flares or hepatic decompensation was estimated at 1.21% and that of flare-related death or liver transplantation at 0.37%. Our findings are important for individuals receiving nucleos(t)ide analogues for hepatitis B virus infection because we not only pooled currently available data to estimate the risk of serious clinical adverse events following treatment cessation but also uncovered critical limitations of existing literature regarding the safety of finite therapy.
PubMed: 36466989
DOI: 10.1016/j.jhepr.2022.100617 -
Frontiers in Pharmacology 2022: Tong-fu therapeutic method (TFTM) is a traditional Chinese medicine treatment method for ulcerative colitis, which is a novel treatment strategies and have purgative...
: Tong-fu therapeutic method (TFTM) is a traditional Chinese medicine treatment method for ulcerative colitis, which is a novel treatment strategies and have purgative effect. As the most representative medicinal of TFTM, Rhubarb has been reported to have a therapeutic impact on ulcerative colitis by regulating intestinal flora, anti-inflammation, and improving intestinal microcirculation. Although rhubarb has been widely used in Chinese medicine for the treatment of ulcerative colitis, the appropriate protocol is still demanded to its rational use in clinic, which promoted to evaluate the efficacy and safety for rhubarb-based therapy on ulcerative colitis. : Clinical trials were searched through PubMed, Cochrane Library, Web of Science, Excerpta Medica Database, Chinese National Knowledge Infrastructure, WAN FANG Database, Chinese Scientific Journal Database, and Chinese Biomedical Literature Database. The subgroup analyses were performed with three groups: medication, course of treatment, and route of administration. The statistical analyses were performed on Review Manager software (version 5.4.1). : A total of 2, 475 patients in 30 original studies were analyzed in this article. It was found that rhubarb-based therapy could increase clinical efficacy and reduce the recurrence rate. Subgroup analyses showed that rhubarb-based therapy was more effective than 5-aminosalicylic acid or sulfasalazine alone. In addition, the hypercoagulable state of ulcerative colitis could be ameliorated by decreasing platelet (PLT) and fibrinogen (FIB), and increasing prothrombin time (PT) significantly. Moreover, C-reaction protein (CRP), tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-8, and IL-1β expression were significantly reduced, while IL-10 production was increased, which mediated the alleviation of intestinal inflammation stress. : Rhubarb-based therapy could effectively improve ulcerative colitis. Of note, the rhubarb-based medicinal formulas combined with 5-ASA or SASP are more effective than the 5-ASA or SASP alone. In addition, although rhubarb has side effect, the results of our analysis showed that rhubarb-based therapy did not exhibit significant side effects. This means it has a high safety profile in clinical use. Moreover, the use of rhubarb-based therapy is recommend to use within 1-13 weeks or 3 months administered orally or by enema, which is contributes to ensure the curative effect and avoid its toxic and side effects. As an important case of TFTM, rhubarb-based therapy provides evidence for the practical application of TFTM.
PubMed: 36339579
DOI: 10.3389/fphar.2022.1036593 -
Journal of Personalized Medicine Sep 2022Vitamin K antagonists (VKAs) are used in the prophylaxis and treatment of thromboembolic disorders. Despite a high efficacy, their narrow therapeutic window and high... (Review)
Review
Vitamin K antagonists (VKAs) are used in the prophylaxis and treatment of thromboembolic disorders. Despite a high efficacy, their narrow therapeutic window and high response variability hamper their management. Several patients experience fluctuations in dose−response and are at increased risk of over- or under-anticoagulation. Therefore, it is essential to monitor the prothrombin time/international normalized ratio to determine the so-called stable dose and to adjust the dosage accordingly. Three polymorphisms, CYP2C9∗2, CYP2C9∗3 and VKORC1-1639G>A, are associated with increased sensitivity to VKAs. Other polymorphisms are associated with a request for a higher dose and VKA resistance. We described the clinical cases of two patients who were referred to the Clinical Pharmacology and Pharmacogenetics Unit of the University Hospital of Salerno for pharmacological counseling. One of them showed hypersensitivity and the other one was resistant to VKAs. A systematic review was performed to identify randomized clinical trials investigating the impact of pharmacogenetic testing on increased sensitivity and resistance to VKAs. Although international guidelines are available and information on the genotype-guided dosing approach has been included in VKA drug labels, VKA pharmacogenetic testing is not commonly required. The clinical cases and the results of the systematically reviewed RCTs demonstrate that the pharmacogenetic-based VKA dosing model represents a valuable resource for reducing VKA-associated adverse events.
PubMed: 36294717
DOI: 10.3390/jpm12101578 -
Research and Practice in Thrombosis and... May 2022The optimal prophylactic preprocedural management of patients with coagulopathy due to liver disease is not known.
BACKGROUND
The optimal prophylactic preprocedural management of patients with coagulopathy due to liver disease is not known.
OBJECTIVES
Our objective was to compare the efficacy and safety of fresh frozen plasma (FFP) with prothrombin complex concentrate (PCC) in the preprocedural management of patients with coagulopathy of liver disease.
METHODS
We conducted a systematic review to examine published evidence regarding treatment with FFP or PCC in adults with coagulopathy of liver disease undergoing an invasive procedure. Direct comparisons and single-arm studies were eligible. Efficacy outcomes included major bleeding, mortality, and correction of prothrombin time (PT) and/or international normalized ratio (INR). Safety outcomes included thrombosis and transfusion-related complications.
RESULTS
A total of 95 articles were identified for full-text review. Nine studies were eligible and included in the review. No randomized trials comparing FFP versus PCC were identified. Only two studies directly compared FFP versus PCC. In these studies, PCC appeared to result in higher rates of correction of PT/INR, but bleeding outcomes were not different. In the single-arm studies, bleeding events appeared low overall. Volume overload was the most common recorded adverse event in patients receiving FFP. Thromboembolic events occurred rarely, but exclusively in the PCC group. Due to heterogeneity in study definitions and bias, meta-analysis was not possible. Our study found no evidence to favor a specific product over another.
CONCLUSIONS
Insufficient data exist on the effects of FFP versus PCC administration before invasive procedures in patients with coagulopathy of liver disease to make conclusions with respect to relative efficacy or safety.
PubMed: 36204546
DOI: 10.1002/rth2.12724 -
Frontiers in Pharmacology 2022To assess the efficacy of LiangXue JieDu (LXJD) therapy in combination with Western medicine (WM) for acute-on-chronic liver failure (ACLF). Articles on randomized...
To assess the efficacy of LiangXue JieDu (LXJD) therapy in combination with Western medicine (WM) for acute-on-chronic liver failure (ACLF). Articles on randomized controlled trials of LXJD therapy for ACLF were obtained from PubMed, Embase, Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure, VIP, Wanfang, and China Biology Medicine databases, with the search range from database inception to March 2022. We evaluated the quality of data from these articles using the Cochrane risk-of-bias tool. Evaluation indicators were total effective rate, mortality rate, complications, liver and coagulation function, and Traditional Chinese medicine (TCM) syndrome score. We then calculated the risk ratio (RR) for dichotomous variables and mean difference (MD) for continuous variables with a 95% confidence interval (CI). The meta-analysis included 18 studies with moderate quality and totaling 1,609 patients. Compared with WM alone, LXJD therapy plus WM improved total effective rate [RR = 1.34, 95% CI: (1.24, 1.45)], while reducing mortality rate [RR = 0.54, 95% CI: (0.42, 0.70)] and complications [RR = 0.43, 95% CI: (0.26, 0.71)]. The combined treatment also improved prothrombin activity [MD = 1.30, 95% CI: (1.02, 1.59)], prothrombin time [MD = -0.90, 95% CI: (-1.40, -0.39)], international normalized ratio [MD = -0.59, 95% CI: (-0.93, -0.25)], alanine aminotransferase [MD = -0.92, 95% CI: (-1.30, -0.55)], aspartate aminotransferase [MD = -0.57, 95% CI: (-0.93, -0.21)], total bilirubin [MD = -1.07, 95% CI: (-1.38, -0.76)], and TCM syndrome score [MD = -1.70; 95% CI: (-2.03, -1.37)]. This study suggests that LXJD therapy plus WM can significantly improves ACLF clinical symptoms and short-term outcomes. However, more high-quality trials are required to confirm the efficacy of LXJD therapy.
PubMed: 35903334
DOI: 10.3389/fphar.2022.905215 -
BMJ Open Jul 2022There are numerous studies reporting a disproportionally high prevalence of thrombophilia in women with a history of recurrent miscarriage (RM), which has led to...
OBJECTIVE
There are numerous studies reporting a disproportionally high prevalence of thrombophilia in women with a history of recurrent miscarriage (RM), which has led to overdiagnosis and treatment without an improvement in clinical outcomes. The objective of our study was to assess the prevalence of inherited and acquired thrombophilia in a large cohort of women with a history of early RM using internationally agreed diagnostic criteria and inclusion parameters and compare it to the meta-analysis results of existing literature.
METHODS
DESIGN: Retrospective cohort study and systematic review of literature.
SETTING
This is a retrospective cohort study set-up in two dedicated tertiary centres for women with RM in Southwest London and Surrey. We reviewed all the available literature related to causes of RMs. We ascertained the prevalence of thrombophilia in the study population and compared it with historical and published prevalence in the general population.
PARTICIPANTS
1155 women between 2012 and 2017. All patients had three or more first trimester miscarriages and a full thrombophilia screen.
RESULTS
The overall prevalence of thrombophilia in our study population is 9.2% (106/1155) with 8.1% (94/1155) of cases positive for inherited thrombophilia, which is similar to the general population; Factor V Leiden (4.9%; 57/1155) and prothrombin gene mutation (2.9%; 34/1155) were the most common inherited thrombophilias, while only 1% (12/1155) tested positive for acquired thrombophilia. Persistent positive lupus anticoagulant (LA) was found in 0.5% (6/1155) and persistent positive anticardiolipin (ACL) antibodies with a value ≥40 U/mL was found in 0.5% (6/1155) of patients. Tests for LA/ACL were performed a minimum of 12 weeks apart thus meeting the revised Sapporo criteria for a diagnosis of antiphospholipid syndrome.
CONCLUSION
The findings of our study demonstrate that the prevalence of inherited thrombophilia is similar in women with RM to that in the general population. Similarly, the prevalence of acquired thrombophilia, using the revised Sapporo criteria, in the cohort of RMs is similar to that in the general population. Therefore, we do not recommend investigation or treatment of inherited or acquired thrombophilia in women with RM.
PROSPERO REGISTRATION NUMBER
CRD42020223554.
Topics: Abortion, Habitual; Antiphospholipid Syndrome; Cohort Studies; Female; Humans; Pregnancy; Pregnancy Complications, Hematologic; Pregnancy Trimester, First; Retrospective Studies; Thrombophilia
PubMed: 35831047
DOI: 10.1136/bmjopen-2021-059519 -
Journal of Clinical Laboratory Analysis Jul 2022Hypercoagulability in lung cancer patients is associated with a high incidence of mortality and morbidity in the world. Therefore, this meta-analysis aimed to explore... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hypercoagulability in lung cancer patients is associated with a high incidence of mortality and morbidity in the world. Therefore, this meta-analysis aimed to explore the correlation of the basic coagulation abnormalities in lung cancer patients compared with the control.
METHOD
PubMed, Scopus, and other sources were employed to identify eligible studies. The outcome variable was expressed using mean ± standard deviation (SD). Heterogeneity among studies and publication bias were evaluated. The quality of included studies was also assessed based on Newcastle-Ottawa Scale checklist.
RESULT
Finally, through a total of eight studies, prolonged prothrombin time (PT; standard mean difference [SMD]: 1.29; 95% CI: 0.47-2.11), plasma D-dimer value (SMD 3.10; 95% CI 2.08-4.12), fibrinogen (SMD 2.18; 95% CI:1.30-3.06), and platelet (PLT) count (SMD 1.00; 95% CI 0.84-1.16) were significantly higher in lung cancer patients when compared with the control group. The single-arm meta-analysis also showed that compared with control, lung cancer patients had high pooled PT 13.7 (95% CI:12.2-15.58) versus 11.79 (95% CI = 10.56-13.02), high D-dimer 275.99 (95% CI:172.9-11735.9) versus 0.2 (95% CI:0.20-0.37), high plasma fibrinogen 5.50 (95% CI:4.21-6.79) versus 2.5 (95% CI:2.04-2.91), and high PLT count 342.3 (95% CI:236.1-448.5) versus 206.6 (95% CI:176.4-236.7).
CONCLUSION
In conclusion, almost all the coagulation abnormalities were closely associated with lung cancer, and hence coagulation indexes provide an urgent clue for early diagnosis and timely management.
Topics: Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Tests; Fibrin Fibrinogen Degradation Products; Fibrinogen; Humans; Lung Neoplasms
PubMed: 35719003
DOI: 10.1002/jcla.24550 -
Journal of Thoracic Disease May 2022This study aimed to summarize the available data on the association between the severity of (COVID-19) and routine blood indicators, inflammatory, biochemical parameters...
BACKGROUND
This study aimed to summarize the available data on the association between the severity of (COVID-19) and routine blood indicators, inflammatory, biochemical parameters and coagulation parameter.
METHODS
A literature search was conducted of PubMed, EMBASE, and Web of Sciences, CNKI, WanFang database providing relevant data. Random-effects meta-analysis was used to pool effect sizes.
RESULTS
In patients with severe symptoms, interleukin-6, [IL-6; standardized mean difference (SMD) =1.15, 95% confidence interval (95% CI): 1.01, 1.29, P<0.001, n=1,121], interleukin-10 (IL-10; SMD =0.92, 95% CI: 0.75, 1.08, P<0.001, n=782), interleukin-4 (IL-4; SMD =0.2, 95% CI: 0.01, 0.39, P=0.04, n=500), procalcitonin (PCT; SMD =1.16, 95% CI: 0.99, 1.33, P<0.001, n=734), C-reactive protein (CRP; SMD =1.42, 95% CI: 1.27, 1.57, P<0.001, n=1,286), serum amyloid A (SAA; SMD =2.82, 95% CI: 2.53, 3.11, P<0.001, n=502) neutrophil count (SMD =0.63, 95% CI: 0.44, 0.82, P<0.001, n=558), alanine aminotransferase (ALT; SMD =2.72, 95% CI: 2.43, 3.02, P<0.001, n=538), aspartate aminotransferase (AST; SMD =2.75, 95% CI: 2.37, 3.12, P<0.001, n=313), lactate dehydrogenase (LDH; SMD =4.01, 95% CI: 3.79, 4.24, P<0.001, n=1,055), creatine kinase (CK; SMD =2.62, 95% CI: 2.2, 3.03, P<0.001, n=230;), CK-MB isoenzyme (CK-MB; SMD =3.07, 95% CI: 2.81, 3.34, P<0.001, n=600, activated partial thromboplastin time (APTT; SMD =0.63, 95% CI: 0.39, 0.87, P<0.001, n=351), and prothrombin time (P-T; SMD =1.83, 95% CI: 1.55, 2.11, P<0.001, n=351) were significantly higher than in patients with mild symptoms. On the contrary, lymphocyte count (SMD =-1.04, 95% CI: -1.21, -0.86, P<0.001, n=805) platelets (SMD =-1.47, 95% CI: -1.7, -1.24, P<0.001, n=653), monocyte count (SMD =-0.56, 95% CI: -0.8, -0.32, P<0.001, n=403), and albumin (SMD =-2.95, 95% CI: -3.21, -2.7, P<0.001, n=637) was significantly lower in patients with severe symptoms than in patients with mild symptoms. IL-6 (SMD =2.62, 95% CI: 2.15, 3.09, P<0.001, n=185), PCT (SMD =0.2, 95% CI: 0.16, 0.23, P<0.001, n=156), creatinine (SMD =2.29, 95% CI: 1.87, 2.7, P<0.001, n=213), and neutrophil counts (SMD =2.77, 95% CI: 2.38, 3.16, P<0.001, n=260) in patients with COVID-19 in the death group were significantly higher than that in patients in the survival group, while the lymphocyte count was significantly lower.
CONCLUSIONS
In summary, current evidence show that those laboratory indicators are associated with the severity of COVID-19 and thus could be used as prognostic risk stratification of patients with COVID-19.
PubMed: 35693606
DOI: 10.21037/jtd-22-345 -
JAMA Network Open May 2022Clinical prediction models, or risk scores, can be used to risk stratify patients with lower gastrointestinal bleeding (LGIB), although the most discriminative score is... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Clinical prediction models, or risk scores, can be used to risk stratify patients with lower gastrointestinal bleeding (LGIB), although the most discriminative score is unknown.
OBJECTIVE
To identify all LGIB risk scores available and compare their prognostic performance.
DATA SOURCES
A systematic search of Ovid MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from January 1, 1990, through August 31, 2021, was conducted. Non-English-language articles were excluded.
STUDY SELECTION
Observational and interventional studies deriving or validating an LGIB risk score for the prediction of a clinical outcome were included. Studies including patients younger than 16 years or limited to a specific patient population or a specific cause of bleeding were excluded. Two investigators independently screened the studies, and disagreements were resolved by consensus.
DATA EXTRACTION AND SYNTHESIS
Data were abstracted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline independently by 2 investigators and pooled using random-effects models.
MAIN OUTCOMES AND MEASURES
Summary diagnostic performance measures (sensitivity, specificity, and area under the receiver operating characteristic curve [AUROC]) determined a priori were calculated for each risk score and outcome combination.
RESULTS
A total of 3268 citations were identified, of which 9 studies encompassing 12 independent cohorts and 4 risk scores (Oakland, Strate, NOBLADS [nonsteroidal anti-inflammatory drug use, no diarrhea, no abdominal tenderness, blood pressure ≤100 mm Hg, antiplatelet drug use (nonaspirin), albumin <3.0 g/dL, disease score ≥2 (according to the Charlson Comorbidity Index), and syncope], and BLEED [ongoing bleeding, low systolic blood pressure, elevated prothrombin time, erratic mental status, and unstable comorbid disease]) were included in the meta-analysis. For the prediction of safe discharge, the AUROC for the Oakland score was 0.86 (95% CI, 0.82-0.88). For major bleeding, the AUROC was 0.93 (95% CI, 0.90-0.95) for the Oakland score, 0.73 (95% CI, 0.69-0.77) for the Strate score, 0.58 (95% CI, 0.53-0.62) for the NOBLADS score, and 0.65 (95% CI, 0.61-0.69) for the BLEED score. For transfusion, the AUROC was 0.99 (95% CI, 0.98-1.00) for the Oakland score and 0.88 (95% CI, 0.85-0.90) for the NOBLADS score. For hemostasis, the AUROC was 0.36 (95% CI, 0.32-0.40) for the Oakland score, 0.82 (95% CI, 0.79-0.85) for the Strate score, and 0.24 (95% CI, 0.20-0.28) for the NOBLADS score.
CONCLUSIONS AND RELEVANCE
The Oakland score was the most discriminative LGIB risk score for predicting safe discharge, major bleeding, and need for transfusion, whereas the Strate score was best for predicting need for hemostasis. This study suggests that these scores can be used to predict outcomes from LGIB and guide clinical care accordingly.
Topics: Area Under Curve; Gastrointestinal Hemorrhage; Humans; ROC Curve; Risk Assessment; Risk Factors
PubMed: 35622365
DOI: 10.1001/jamanetworkopen.2022.14253 -
AIDS Research and Treatment 2022Coagulation abnormalities are common complications of human immunodeficiency virus (HIV) infection. Highly active antiretroviral treatment (HAART) decreased the... (Review)
Review
BACKGROUND
Coagulation abnormalities are common complications of human immunodeficiency virus (HIV) infection. Highly active antiretroviral treatment (HAART) decreased the mortality of HIV but increased coagulopathies. HIV-related thrombocytopenia, prolonged prothrombin time (PT), activated partial thromboplastin time (APTT), and high D-dimer level commonly manifested in patients with HIV. Thus, this study is aimed to compare coagulation parameters of HAART-treated and HAART-naïve HIV-infected patients with HIV-seronegative controls.
METHODS
A systematic literature search was conducted using the databases PubMed/MEDLINE, Embase, Web of Science, and Google Scholar of studies published until July 2021. The primary outcome of interest was determining the pooled mean difference of coagulation parameters between HIV-infected patients and seronegative controls. The Joana Briggs Institute (JBI) critical appraisal tool was used for quality appraisal. Statistical analyses were performed using Stata11.0 software. The statistical results were expressed as the effect measured by standardized mean difference (SMD) with their related 95% confidence interval (CI).
RESULTS
A total of 7,498 participants (1,144 HAART-naïve patients and 2,270 HAART-treated HIV-infected patients and 3,584 HIV-seronegative controls) from 18 studies were included. HIV-infected patients (both on HAART and HAART-naive) exhibited significantly higher levels of PT than HIV-seronegative controls (SMD = 0.66; 95% CI: 0.53-0.80 and SMD = 1.13; 95% CI: 0.60-2.0, respectively). The value of APTT was significantly higher in patients with HIV on HAART than in seronegative controls. However, the values of PLT count, APTT, and fibrinogen level were significantly higher in seronegative controls. Besides, the level of fibrinogen was significantly higher in HAART-treated than treatment-naïve patients (SMD = 0.32; 95%CI: 0.08, 0.57). Moreover, the level of APTT and PT had no statistical difference between HAART and HAART-naïve HIV-infected patients.
CONCLUSIONS
This study identified that HIV-infected patients are more likely to develop coagulation abnormalities than HIV-seronegative controls. Therefore, coagulation parameters should be assessed regularly to prevent and monitor coagulation disorders in HIV-infected patients.
PubMed: 35492260
DOI: 10.1155/2022/6782595