Treatment-Related Adverse Events with PD-1 or PD-L1 Inhibitors: A Systematic Review and Meta-Analysis

Objective: to evaluate the risk of treatment-related adverse events of different severity and different system with PD-1 or PD-L1 inhibitors. Methods: randomized controlled trials (RCTs) that using PD-1/PD-L1 for cancer treatment were searched in the PubMed, Embase, Cochrane Library, and Web of Science from 1 January 2019 to 31 May 2021. Adverse events data were extracted from clinical trials website or original article by two authors separately. Meta-analysis was used to determine risk ratio (RR) and 95% confidence interval (95% CI) of adverse events in PD-1/PD-L1 inhibitors groups compared to that of control groups. Subgroup analyses were also performed. Results: a total of 5,807 studies were initially identified and after exclusion, 41 studies were included in meta-analysis. All the trials were international multicenter, randomized, phase II/III clinical trials, with the median follow-up of 27.5 months on average. Analysis of all grade adverse events showed that PD-1/PD-L1 inhibitors treatment significantly increased the risk of immune-related adverse events, including pruritus (RR: 2.34, 95% CI: 1.85–2.96), rash (RR: 1.53, 95% CI: 1.25–1.87), ALT elevation (RR 1.54, 95% CI 1.23–1.92), AST elevation (AST: RR 1.49, 95% CI 1.20–1.85), hepatitis (RR: 3.54, 95% CI: 1.96–6.38) and hypothyroid (RR: 5.29, 95% CI: 4.00–6.99) compared with that of control group. Besides that, PD-1/PD-L1 inhibitors were associated with higher risk of adverse events related to respiratory system including cough (RR: 1.33, 95% CI: 1.21–1.48), dyspnea (RR:1.23, 95% CI: 1.12–1.35) and chest pain (RR: 1.26, 95% CI: 1.07–1.47) compared with that of control groups in our meta-analysis and the dyspnea was taken high risk both in all grade and grade 3 or higher (RR: 1.55, 95% CI: 1.13–2.12). The risk of arthralgia was increased with PD-1/PD-L1 inhibitors (RR: 1.27, 95% CI: 1.10–1.47). Although the risk of myalgia was similar with PD-1/PD-L1 inhibitors and control groups, under subgroup analysis, PD-1/PD-L1 inhibitors decreased the risk of myalgia (RR: 0.56, 95% CI: 0.45–0.70) compared with that of chemotherapy. Conclusions: our results provide clear evidence that the risk of treatment-related adverse events in PD-1 or PD-L1 varies widely in different system. In particular, when using PD-1/PD-L1 inhibitors for oncology treatment, besides the common immune-related adverse events like pruritus, rash, hepatitis, and hypothyroid, the respiratory disorders and musculoskeletal disorders, such as cough, dyspnea, arthralgia, and myalgia, should also be taken into consideration.

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Nervous and Muscular Adverse Events after COVID-19 Vaccination: A Systematic Review and Meta-Analysis of Clinical Trials

Vaccines ◽

10.3390/vaccines9080939 ◽

2021 ◽

Vol 9 (8) ◽

pp. 939

Author(s):

Jiaxin Chen ◽

Yuangui Cai ◽

Yicong Chen ◽

Anthony P. Williams ◽

Yifang Gao ◽

...

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Adverse Events ◽

Fixed Effects ◽

Meta Analysis ◽

Phase 1 ◽

Cochrane Library ◽

Categorical Variables ◽

Control Group ◽

Open Label

Background: Nervous and muscular adverse events (NMAEs) have garnered considerable attention after the vaccination against coronavirus disease (COVID-19). However, the incidences of NMAEs remain unclear. We aimed to calculate the pooled event rate of NMAEs after COVID-19 vaccination. Methods: A systematic review and meta-analysis of clinical trials on the incidences of NMAEs after COVID-19 vaccination was conducted. The PubMed, Medline, Embase, Cochrane Library, and Chinese National Knowledge Infrastructure databases were searched from inception to 2 June 2021. Two independent reviewers selected the study and extracted the data. Categorical variables were analyzed using Pearson’s chi-square test. The pooled odds ratio (OR) with the corresponding 95% confidence intervals (CIs) were estimated and generated with random or fixed effects models. The protocol of the present study was registered on PROSPERO (CRD42021240450). Results: In 15 phase 1/2 trials, NMAEs occurred in 29.2% vs. 21.6% (p < 0.001) vaccinated participants and controls. Headache and myalgia accounted for 98.2% and 97.7%, and their incidences were 16.4% vs. 13.9% (OR = 1.97, 95% CI = 1.28–3.06, p = 0.002) and 16.0% vs. 7.9% (OR = 3.31, 95% CI = 2.05–5.35, p < 0.001) in the vaccine and control groups, respectively. Headache and myalgia were more frequent in the newly licensed vaccines (OR = 1.97, 95% CI = 1.28–3.06, p = 0.02 and OR = 3.31, 95% CI = 2.05–5.35, p < 0.001) and younger adults (OR = 1.40, 95% CI = 1.12–1.75, p = 0.003 and OR = 1.54, 95% CI = 1.20–1.96, p < 0.001). In four open-label trials, the incidences of headache, myalgia, and unsolicited NMAEs were 38.7%, 27.4%, and 1.5%. Following vaccination in phase 3 trials, headache and myalgia were still common with a rate of 29.5% and 19.2%, although the unsolicited NMAEs with incidence rates of ≤ 0.7% were not different from the control group in each study. Conclusions: Following the vaccination, NMAEs are common of which headache and myalgia comprised a considerable measure, although life-threatening unsolicited events are rare. NMAEs should be continuously monitored during the ongoing global COVID-19 vaccination program.

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Pomalidomide Based Regimens for Treatment of Relapsed Multiple Myeloma: A Systematic Review and Meta-Analysis of Clinical Trials

Blood ◽

10.1182/blood-2018-99-111439 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 2022-2022

Author(s):

Adeela Mushtaq ◽

Ahmad Iftikhar ◽

Midhat Lakhani ◽

Fnu Sagar ◽

Ahmad Kamal ◽

...

Keyword(s):

Multiple Myeloma ◽

Clinical Trials ◽

Adverse Events ◽

Meta Analysis ◽

Random Effect Model ◽

Pooled Analysis ◽

Cochrane Library ◽

Significant Heterogeneity ◽

Grade 3 ◽

Stratified Analysis

Abstract Introduction Bortezomib, a proteasome inhibitor and lenalidomide (Len), an immunomodulatory drug are the backbone of established treatment regimens for newly diagnosed MM. Patients with dual-refractory (refractory to both bortezomib and lenalidomide) disease have a poor prognosis with overall survival estimated to be less than one year. Pomalidomide (Pom) has distinct anticancer, antiangiogenic and immunomodulatory properties and has demonstrated synergistic antiproliferative activity in combination regimens. The aim of our study is to compare different Pom based regimens to identify the most effective regimen for relapsed refractory multiple myeloma (RRMM) patients. Methods A comprehensive literature search was performed on PubMed, Cochrane library, Web of Science, Embase and AdisInsight databases on 03/29/2018 which identified a total of 1374 studies. We included phase II/III clinical trials on pomalidomide based regimens that have clearly documented efficacy outcomes. All statistical analyses were performed using Comprehensive Meta-analysis (CMA) Version 3. We used the Cochrane Q statistics (p<0.05 considered significant) and I2 index to calculate the degree of heterogeneity of the studies. A random effect model was used if there was significant heterogeneity (p>0.05 or I2 >50%). Studies were classified into subgroups according to the therapeutic regimen: dual and triplet combinations. A separate stratified analysis of triplet regimens based on type of regimen was also performed. Results A total of 35 studies (n = 4623 patients) were included. The most commonly studied regimen was Pom + LoDex (Low dose dexamethasone) with a total of 16 studies on this regimen. All patients included in our study had ≥ 2 prior lines of therapy. Mean number of prior lines of therapy was 6. Most patients were lenalidomide refractory, with 10 patient cohorts of 100% refractoriness and 8 cohorts of ≥ 90% refractoriness. Pooled analysis showed an overall response rate (ORR) of 47.1% across all Pom regimens including both doublet and triplet regimens. An I2 value of 87.3 was found, indicating high heterogeneity across all Pom regimens. With Pom-LoDex, pooled ORR was found to be 35.7% and mean OS 14.37 months. With triplet regimens, pooled ORR was found to be 61.9%. In a separate stratified analysis of triplet regimens based on type of regimen, pooled ORRs with few selected regimens were as follows; Bort-Pom-LoDex (pooled ORR 83.5%, mean PFS 15.7 months [mos]), CFZ-Pom-LoDex (pooled ORR 77.1%, mean PFS 15.3 mos), Pom-LoDex-bendamustine (pooled ORR 74.2%), Pom-Dex-daratumumab (pooled ORR 64.5%), Pom-LoDex-cyclophosphamide (pooled ORR 59.4%, mean PFS 9.5 mos), Pom-LoDex-doxorubicin (pooled ORR 32%). Most frequently reported adverse event with Pom based regimens was myelosuppression. Mean incidences of grade ≥3 hematologic adverse events were neutropenia (47.6%), anemia (26.5%), and thrombocytopenia (20.8%). Mean incidences of grade ≥3 non-hematologic adverse events were infections (29.1%), pneumonia (13.8%) and fatigue (10%). Most of the studies used pomalidomide 4mg daily dosing. Lacy et al. suggested no advantage of 4mg pomalidomide over 2 mg daily dosing. Conclusion From results of pooled analysis, we can infer that triplet combinations of Pom yield almost double response rates (pooled ORR 61.9%) when compared to dual combination of Pom-LoDex (pooled ORR 35.7%). Among three drug combinations, Bort-Pom-LoDex (pooled ORR 83.5%) and CFZ-Pom-LoDex (pooled ORR 77.1%) seem to produce better outcomes. Our study provides useful insight into relative efficacy of various Pom regimens for treatment of RRMM patients. Several trials involving various MoAbs like nivolumab, daratumumab, elotuzumab, isatuximab and pembrolizumab in combination with Pom-LoDex are currently ongoing. Pomalidomide has an acceptable safety profile. Most common treatment emergent adverse events were myelotoxicity and infections that can be effectively managed with supportive care and dose modifications. Disclosures No relevant conflicts of interest to declare.

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Repurposing of drugs for Covid-19: a systematic review and meta-analysis

10.1101/2020.06.07.20124677 ◽

2020 ◽

Cited By ~ 1

Author(s):

Pinky Kotecha ◽

Alexander Light ◽

Enrico Checcucci ◽

Daniele Amparore ◽

Cristian Fiori ◽

...

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Adverse Events ◽

Clinical Improvement ◽

Case Reports ◽

Meta Analysis ◽

Case Series ◽

Cochrane Library ◽

Control Group ◽

Significant Difference

AbstractObjectiveThe aim of this systematic review is to evaluate the data currently available regarding the repurposing of different drugs for Covid-19 treatment. Participants with suspected or diagnosed Covid-19 will be included. The interventions being considered are drugs being repurposed, and comparators will include standard of care treatment or placebo.MethodsWe searched Ovid-MEDLINE, EMBASE, Cochrane library, clinical trial registration site in the UK(NIHR), Europe (clinicaltrialsregister.eu), US (ClinicalTrials.gov) and internationally (isrctn.com), and reviewed the reference lists of articles for eligible articles published up to April 22, 2020. All studies in English that evaluated the efficacy of the listed drugs were included. Cochrane RoB 2.0 and ROBINS-I tool were used to assess study quality. This systematic review adheres to the PRISMA guidelines. The protocol is available at PROSPERO (CRD42020180915).ResultsFrom 708 identified studies or clinical trials, 16 studies and 16 case reports met our eligibility criteria. Of these, 6 were randomized controlled trials (763 patients), 7 cohort studies (321 patients) and 3 case series (191 patients). Chloroquine (CQ) had a 100% discharge rate compared to 50% with lopinavir-ritonavir at day 14, however a trial has recommended against a high dosage due to cardiotoxic events. Hydroxychloroquine (HCQ) has shown no significant improvement in negative seroconversion rate which is also seen in our meta-analysis (p=0.68). Adverse events with HCQ have a significant difference compared to the control group (p=0.001). Lopinavir-ritonavir has shown no improvement in time to clinical improvement which is seen in our meta-analyses (p=0.1). Remdesivir has shown no significant improvement in time to clinical improvement but this trial had insufficient power.DiscussionDue to the paucity in evidence, it is difficult to establish the efficacy of these drugs in the treatment of Covid-19 as currently there is no significant clinical effectiveness of the repurposed drugs. Further large clinical trials are required to achieve more reliable findings. A risk-benefit analysis is required on an individual basis to weigh out the potential improvement in clinical outcome and viral load reduction compared to the risks of the adverse events. (1-16)

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Efficacy and Toxicity Profile of Elotuzumab for Multiple Myeloma: A Systematic Review and Meta-Analysis

Blood ◽

10.1182/blood-2018-99-117209 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 5640-5640

Author(s):

Faiza Jamil ◽

Madeeha Shafqat ◽

Sharoon Samuel ◽

Zunairah Shah ◽

Ceren Durer ◽

...

Keyword(s):

Multiple Myeloma ◽

Clinical Trials ◽

Adverse Events ◽

Meta Analysis ◽

Single Agent ◽

Random Effect Model ◽

Drug Regimen ◽

Pooled Analysis ◽

Cochrane Library ◽

Control Group

Abstract Background: Elotuzumab (elo) is a humanized monoclonal antibody, which has been approved by the FDA for use in combination with lenalidomide (lena) and dexamethasone (dexa) in patients (pts) with relapsed and refractory multiple myeloma (RRMM). Elotuzumab is effective as a single agent, as well as in combination for multiple myeloma treatments, supporting the use of elo in pts with RRMM and newly diagnosed multiple myeloma (NDMM) pts. Method: After review of literature using database searches was done on 6/27/18 (Pubmed, Embase, Cochrane Library, Web of Science and Clinical Trials.gov), 9 prospective and 1 retrospective study with 1128 enrolled pts met the inclusion criteria to date in RRMM and 2 clinical trials including 123 pts in NDMM (Table 1). CMA software v.3 was used for meta-analysis. A random-effect model was applied. Result: Regimens used in RRMM: Based on pooled analysis (95% CI), an overall response rate (ORR) of 66% (54-76.2) was calculated in 685 evaluable pts treated with elo based regimens in RRMM (Figure 1). Most common grade (G) ≥ 3 hematological adverse events (HAE) and non-hematological adverse events (NHAE) based on regimen were calculated using pooled analysis in RRMM pts (Table 2). Anemia was noted in 12.1% ( 7.7-18.6) in 559 pts, while neutropenia in 14.5% (7.5-26.4) out of 591 pts and thrombocytopenia (tcp) in 11.9% (7.9-17.4) in 198 evaluable pts. Diarrhea 5.5% (3.6-8.3), pyrexia 2.4% (1.5-4), peripheral neuropathy (PN) 8.4% (3.8-17.8) were measured in 626, 668 and 143 pts respectively. Elotuzumab as monotherapy: 1 study (n=34) evaluated the efficacy of elo as single agent in RRMM. The median age, time from diagnosis and number of prior therapies were 64.5 years (y) (46-87), 4.4 y (0.9-12.8) and 4.5 y (2-10) respectively. It produced an ORR of 1.4% (0.1-19.1 95% CI) in 34 evaluable pts. Adverse events recorded were pyrexia and fatigue in 17.6% and 8.8% pts respectively. Elotuzumab in two drug regimen: In RRMM, 2 clinical trials (n=49) evaluated the efficacy (95% CI) of elo, ORR of 25% (4.1-72.3) was calculated. The best PFS (progression free survival) produced was in combination of elo 20 mg with bortezumib (bort) 1.3mg/m2 of 9.46 months as compared to 1.8 months when elo10mg/kg + dexamethasone (dexa) 28mg was used. In our analysis for safety, common G≥ 3 HAE calculated were, thrombocytopenia 8.7% (3.3-21.1) n=49, neutropenia 10.7 % (3.5-28.4) n=28 pts and anemia 7.1% (1.8-24.5) n=28 pts. NHAE included diarrhea 1.7% (0.1-22.3), PN 10.7% (3.5-28.4), pyrexia 1.7% (0.1-22.3) in 28 evaluable pts each. Elotuzumab in three drug regimen: In RRMM, 10 clinical trials including 602 pts evaluated the efficacy of elo as a part of triple drug regimen, producing an ORR of 72.2% (54-76.2). The best results were produced with the combination of elo 10-20mg/kg + lenalidomide (lena) 25mg + dexa 40mg producing a PFS of 32.2 mo and 28.62 mo in its phase I and II cohorts respectively. Based on pooled analysis (95% CI) common HAE calculated were neutropenia 17.5% (7.6-35.4) in n=563, thrombocytopenia 12.7% (8.2-19.4) in n=149 and anemia 13% (8-20.5) in n=531 pts. Common G ≥ 3 NHAE estimated were diarrhea 5.7% (3.7-8.6), PN 6.6% (2-19.2), pyrexia 2.5% (1.5-4.1) in 598, 115 and 640 pts respectively. Elotuzumab based regimen in NDMM: A currently ongoing clinical trial NCT02272803 has produced promising results in NDMM pts. As a part of three drug regimen with dose of elo 10mg/kg-20mg/kg, lena 25mg, dexa 20mg in 40 pts produced an ORR of 87.5% (73.2-95.8) versus control group of lena 25mg plus dexa 40mg in 42 pts with an ORR of 73.8% (58-86.1). The PFS rate recorded at 1 year was 93% (79-98%) and 91% (73-97%) respectively. The HAE G ≥ 3 included, neutropenia 18% and leukopenia 15%. In another study with 41 pts, elo was used in combination with lena, bort and dexa producing an ORR of 100% and greater than grade 3 adverse events including Tcp 15%, PN 2%. Conclusion: Results produced in our study suggest that elotuzumab is highly effective when used in pts with RRMM and NDMM. Combination regimens for elo produces an ORR ranging from 79-83% with elo + lena+ dexa, proving that the best results were produced by three drug regimens. Large prospective studies are required to evaluate efficacy and safety of elotuzumab in combination therapies. Disclosures No relevant conflicts of interest to declare.

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Efficacy of preoperative testosterone therapy in hypospadias: a systematic review and meta-analysis

Annals of Pediatric Surgery ◽

10.1186/s43159-021-00117-4 ◽

2021 ◽

Vol 17 (1) ◽

Author(s):

Gozali Sembiring ◽

Yacobda Sigumonrong

Keyword(s):

Meta Analysis ◽

Reoperation Rate ◽

Cochrane Library ◽

Control Group ◽

Control Groups ◽

Testosterone Treatment ◽

Meatal Stenosis ◽

Significant Difference ◽

And Control ◽

The Impact

Abstract Background Bleeding, hematoma, edema, wound infection, and scar formation are the common problems linked with hypospadias reconstruction. Hormone treatment is recommended before surgical treatment to improve intraoperative circumstances. However, no meta-analysis has explored the effectiveness and side effects of testosterone treatment before surgery in hypospadias. Main body of the abstract The purpose of this paperwork is to evaluate the impact of preoperative testosterone treatment in hypospadias based on clinical data from published trials. This study searched MEDLINE, Science Direct, and the Cochrane Library without regard to year. However, only English journals were included, with a manual search using the Preferred Reporting Items for Systematic Reviews and Meta-analysis of Observational Studies in Epidemiology Guidelines supplementing the search. In this meta-analysis, five papers were considered. Two of these investigations were multicenter randomized clinical trials. Two of the studies were prospective, with a median follow-up of varying lengths. A retrospective investigation was conducted. There were 585 patients in all that took part in this trial. After surgery, the complication rate was measured in both the intervention and control groups, including meatal stenosis, fistula, glans dehiscence, scarring, reoperation rate, urethral diverticulum, fine pubic hair, and sexual precocity. The only significant difference between the intervention and control groups was that the intervention group had a decreased frequency of glans dehiscence following surgery (OR 0.40 with the 95% CI of 0.17 until 0.97). Conclusions This study discovered that a patient who got testosterone before surgery had a considerably decreased complication risk for glandular dehiscence. Reoperation rate, urethral-cutaneous fistula, meatal stenosis, and penile scarring in children with hypospadias, on the other hand, revealed no significant difference in the testosterone-treated group against the control group.

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The effectiveness of nonsteroidal anti-inflammatory drugs and acetaminophen in reduce the risk of amyotrophic lateral sclerosis? A meta-analysis

Scientific Reports ◽

10.1038/s41598-020-71813-1 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Min Cheol Chang ◽

Sang Gyu Kwak ◽

Jin-Sung Park ◽

Donghwi Park

Keyword(s):

Confidence Interval ◽

Odds Ratio ◽

Meta Analysis ◽

Convincing Evidence ◽

Cochrane Library ◽

Control Group ◽

Inclusion Criteria ◽

Control Groups ◽

Significant Difference ◽

And Control

Abstract To test the hypothesis that aspirin, non-aspirin nonsteroidal anti-infammatory drugs (NA-NSAIDs), or acetaminophen can reduce the risk of ALS, we conducted a systematic review and meta-analysis of related previous studies. A comprehensive search was conducted on the PubMed, Embase, Cochrane Library and SCOPUS databases. It included studies published up to 29 February 2020 that fulfilled our inclusion criteria. Aspirin, acetaminophen and NA-NSAIDs use information, between the ALS and control groups, was collected for the meta-analysis. Rates of aspirin, NA-NSAID, and acetaminophen use in ALS group, compared with control group were investigated. In the results, only three studies that relate the risk of ALS to aspirin, NA-NSAIDs and acetaminophen use satisfied the inclusion criteria for the meta-analysis. Regarding aspirin, the studies did not show any statistically significant difference in aspirin use between the ALS and control groups (Odds ratio, 1.04 [95% confidence interval, 0.90–1.21]). NA-NSAIDs and acetaminophen use, however, did show up statistically significant differences in between the ALS and control groups. (Odds ratio, 0.82 [95% confidence interval, 0.73–0.91]) and (Odds ratio, 0.80 [95% confidence interval, 0.69–0.93]). However, our study has some limitations. Firstly, we only included a small number of studies. Secondly, the included studies did not control for past medical history, which may have confounded their results, and in turn, could have caused bias in our study. Thirdly, in this meta-analysis, the ALS patients were not subdivided into sporadic or familial type. Lastly, the studies also did not consider the types of NSAIDs and dosages used of each drug. For more convincing evidence regarding the effectiveness of aspirin, NA-NSAIDs and acetaminophen to reduce the risk of ALS occurrence, more qualified prospective studies are required. In conclusion, the use of NA-NSAIDs and acetaminophen is associated with a decreased risk for the development of ALS. In contrast, aspirin did not have any effect on the reduction of the risk of ALS occurrence.

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Indicated preventive interventions for anxiety in children and adolescents: a review and meta-analysis of school based programs

10.31234/osf.io/jadxq ◽

2019 ◽

Author(s):

Siobhan Hugh-Jones ◽

Sophie Beckett ◽

Pavan Mallikarjun

Keyword(s):

Meta Analysis ◽

Child And Adolescent ◽

Sensitivity Analyses ◽

Cochrane Library ◽

Control Groups ◽

Adolescent Anxiety ◽

School Based ◽

Intervention Intensity ◽

Randomised Controlled ◽

And Control

Schools are promising sites for the delivery of prevention and early intervention programs to reduce child and adolescent anxiety. It is unclear whether universal or targeted approaches are most effective. This review and meta-analysis examines the effectiveness of school-based indicated interventions and was registered with PROSPERO [CRD42018087628].MEDLINE, EMBASE, PsycINFO and the Cochrane Library were searched for randomised controlled trials comparing indicated school programs for child and adolescent anxiety to active or inactive control groups. Twenty original studies, with 2076 participants, met the inclusion criteria and 18 were suitable for meta-analysis. Sub-group and sensitivity analyses explored intervention intensity, delivery agent and control type. A small beneficial effect was found for indicated programs compared to controls on self-reported anxiety symptoms at post-test (g = -0.28, CI = -0.50, -0.05, k= 18). The small effect was maintained at 6 (g = -0.35, CI= -0.58, -0.13, k = 9) and 12 months (g = -0.24, CI = -0.48, 0.00, k = 4). Based on two studies, >12 month effects were very small (g = -0.01, CI= -0.38, 0.36). No differences were found based on intervention intensity, delivery agent and control type. There was evidence of publication bias and a relatively high risk of contamination in studies. Findings support the value of school based indicated programs for child and adolescent anxiety. Effects at 12 months outperform many universal programs. High quality, randomised controlled and pragmatic trials are needed, with attention control groups and beyond 12 month diagnostic assessments are needed.

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Efficacy and safety of daratumumab in the treatment of multiple myeloma: a systematic review and meta-analysis

Journal of International Medical Research ◽

10.1177/03000605211038135 ◽

2021 ◽

Vol 49 (8) ◽

pp. 030006052110381

Author(s):

Yin Wang ◽

Yanqing Li ◽

Ye Chai

Keyword(s):

Multiple Myeloma ◽

Meta Analysis ◽

Complete Response ◽

Library Science ◽

Cochrane Library ◽

Control Group ◽

Efficacy And Safety ◽

Risk Patients ◽

Grade 3 ◽

Combination Regimens

Objective To systematically evaluate the efficacy and safety of combination regimens containing daratumumab in patients with multiple myeloma (MM). Methods A systematic search of publications listed on electronic databases (PubMed®, The Cochrane Library, Science Direct and Web of Science) between inception and 13 November 2020 was conducted to find randomized controlled trials (RCTs) that included patients with MM that were treated with combination regimens containing daratumumab. Results A total of seven RCTs were included ( n = 4268 patients). Meta-analysis showed that compared with the control group, the group containing daratumumab showed a significantly better overall response rate and a complete response or better. Daratumumab improved efficacy in both standard-risk and cytogenetically high-risk patients with MM. The prevalence of neutropenia (≥grade 3) and pneumonia was significantly higher in the daratumumab group compared with the control group. Conclusion The available evidence demonstrated that the clinical application of combination regimens containing daratumumab improved the efficacy in patients with MM and had acceptable safety.

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Adjuvant therapy efficacy of Chinese drugs pharmaceutics for COPD patients with respiratory failure: a meta-analysis

Bioscience Reports ◽

10.1042/bsr20182279 ◽

2019 ◽

Vol 39 (4) ◽

Cited By ~ 2

Author(s):

Chunqiu Liu ◽

Yin Li ◽

Xinqiu Wang ◽

Tong Lu ◽

Xuejing Wang

Keyword(s):

Respiratory Failure ◽

Western Medicine ◽

Meta Analysis ◽

Test Group ◽

Cochrane Library ◽

Control Group ◽

Chronic Obstructive ◽

Clinical Effects ◽

Control Groups ◽

Chinese Drugs

Abstract We performed a meta-analysis to evaluate the efficacy and safety of Western medicine combined with Tanreqing for patients with chronic obstructive pulmonary disease (COPD) and respiratory failure. We comprehensively searched several online databases from the times of their inception to November 2018. The trial quality was assessed using the bias risk tool recommended by the Cochrane library. Relative risks (RRs) and their 95% confidence intervals (CIs) for binary outcomes and weighted mean differences (MDs) with 95% CIs for continuous data were calculated. A fixed effect model indicated that integrated Tanreqing group experienced higher overall treatment effectiveness (RR = 1.23, 95% CI: 1.17–1.30, P=0.000). Pooled results from random effects models indicated the oxygen partial pressure of the test group was significantly higher than that of the control groups (MD = 9.55, 95% CI: 4.57–14.52, P<0.000). The carbon dioxide pressure of the test group was significantly lower than that of the control groups (MD = –6.06, 95% CI: –8.19 to –3.93, P=0.000). The lung function score of the test group was significantly higher than that of the control group (MD = 7.87, 95% CI: 4.45–11.29). Sensitivity analysis indicated that the data were statistically robust. Clinical effects of Western medicine combined with Tanreqing used to treat combined COPD/respiratory failure were better than those afforded by Western medicine; no serious adverse reactions were noted. However, publication bias was evident, and further trials with larger sample sizes are required.

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Metabolic complications with the use of mTOR inhibitors for cancer therapy: A systematic review and meta-analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.6_suppl.398 ◽

2013 ◽

Vol 31 (6_suppl) ◽

pp. 398-398 ◽

Cited By ~ 1

Author(s):

Shanthi Sivendran ◽

Jian Ying ◽

Benjamin Adam Gartrell ◽

Neeraj Agarwal ◽

Kenneth M. Boucher ◽

...

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Adverse Events ◽

Incidence Rate ◽

Meta Analysis ◽

Mtor Inhibitors ◽

Incidence Rates ◽

Metabolic Complications ◽

Randomized Controlled Clinical Trials ◽

Grade 3

398 Background: mTOR inhibitors are approved in several malignancies including renal cell carcinoma (RCC). The risk of metabolic complications with these agents is not well characterized. Methods: PubMed was searched for articles published from 2001 until 2011. Eligible studies included prospective randomized trials evaluating temsirolimus, everolimus, and ridaforolimus in patients with all solid tumor malignancies. 16 eligible phase II clinical trials and 8 randomized controlled clinical trials were included in a systematic review and meta-analysis and the number of metabolic related AEs including hyperglycemia, hypercholesterolemia, and hypertriglyceridemia were extracted. Incidence rates and incident rate ratios were calculated. Results: In total, 24 trials (including 4,261 patients) were included. The average incidence rate of any grade metabolic adverse events and grade 3-4 metabolic adverse events was 0.70 per patient and 0.11 (95% CI, 0.08, 0.15) per patient respectively. Analysis of the 3,317 patients across 8 RCT’s revealed that the log incidence rate ratio (IRR) of any grade metabolic adverse events with mTOR inhibitor therapy compared with control was 1.08 (95% CI, 0.84, 1.31) using a random-effects model. The risk of grade 3-4 adverse events was also increased with an IRR of 1.52 (95% CI, 1.05, 1.99). The IRR of all grade hyperglycemia was 1.08 (95% CI, 0.76, 1.40) and of grade 3-4 hyperglycemia was 1.66 (95% CI, 1.12, 2.20). The IRR of all grade hypertriglyceridemia was 0.91 (95% CI, 0.56, 1.26) and of grade 3-4 hypertriglyceridemia was 0.70 (95% CI,- 0.43, 1.83). The IRR of all grade hypercholesterolemia was 1.21 (95% CI, 0.77, 1.65) and of grade 3-4 hypercholesterolemia was 1.21 (95% CI, 0.77, 1.65). These findings suggest a statistically significant increase in the risk of hyperglycemia, hypercholesterolemia (all grades and grade 3 and 4), and all grade hypertriglyceridemia associated with mTOR therapy when compared with control. Conclusions: The risk of all grade and grade 3-4 metabolic adverse events are increased in patients treated with mTOR inhibitors compared with control. However, grade 3-4 metabolic adverse events remain relatively uncommon.

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