Clinical Effectiveness and Safety of Chinese Herbal Medicine Compound Kushen Injection as an Add-On Treatment for Breast Cancer: A Systematic Review and Meta-Analysis

Objective. To systematically evaluate the effect and safety of compound Kushen injection (CKI) as an add-on treatment on the treatment for breast cancer. Methods. We searched eight major electronic databases from their inception to November 1, 2021, for randomized clinical trials (RCTs) comparing CKI plus chemotherapy with chemotherapy alone. Primary outcomes included objective response rate (ORR) and disease control rate (DCR), health-related quality of life (HRQoL), progression-free survival (PFS), and overall survival (OS). Secondary outcomes included adverse drug reactions (ADRs) and tumor marker level. We used Cochrane’s RevMan 5.3 for data analysis. The GRADEpro was used to appraise the certainty of evidence. Trial sequential analysis (TSA) was applied to estimate the required sample size in a meta-analysis and test the robustness of the current results. Results. Thirty RCTs with 2556 participants were totally included. CKI plus chemotherapy showed significant effects in increasing ORR (RR 1.30, 95%CI [1.18, 1.43], I2 = 27%, n = 1694), increasing DCR (RR 1.21, 95%CI [1.15, 1.28], I2 = 16%, n = 1627), increasing HRQol as measured by Karnofsky Performance Scale (KPS) score improvement rate (RR 1.42, 95% CI [1.26, 1.61], I2 = 37%, n = 1172), increasing the PFS (MD 2.24 months, 95%CI [1.26, 3.22], n = 94) and the OS (MD 2.24 months, 95%CI [1.45, 3.43], n = 94), compared to chemotherapy alone. The results showed that CKI plus chemotherapy had a lower risk of ADRs than that of chemotherapy alone group. The certainty of evidence of the included trials was generally low to very low. TSA for ORR and KPS score improvement rate demonstrated that the current results reached a sufficient power regarding both numbers of trials and participants. Conclusions. Low certainty of evidence suggested that the combination of CKI and conventional chemotherapy appeared to improve ORR, DCR, and KPS score in breast cancer patients. Conclusions about PFS and OS could not be drawn due to lack of evidence. Additionally, CKI appeared to relieve the risk of ADRs in patients with breast cancer receiving chemotherapies. However, due to weak evidence, the findings should be further confirmed in large and rigorous trials.

Oral Antihypertensives for Nonsevere Pregnancy Hypertension: Systematic Review, Network Meta- and Trial Sequential Analyses

Background: We aimed to address which antihypertensives are superior to placebo/no therapy or another antihypertensive for controlling nonsevere pregnancy hypertension and provide future sample size estimates for definitive evidence. Methods: Randomized trials of antihypertensives for nonsevere pregnancy hypertension were identified from online electronic databases, to February 28, 2021 (registration URL: https://www.crd.york.ac.uk/PROSPERO/ ; unique identifier: CRD42020188725). Our outcomes were severe hypertension, proteinuria/preeclampsia, fetal/newborn death, small-for-gestational age infants, preterm birth, and admission to neonatal care. A Bayesian random-effects model generated estimates of direct and indirect treatment comparisons. Trial sequential analysis informed future trials needed. Results: Of 1246 publications identified, 72 trials were included; 61 (6923 women) were informative. All commonly prescribed antihypertensives (labetalol, other β-blockers, methyldopa, calcium channel blockers, and mixed/multi-drug therapy) versus placebo/no therapy reduced the risk of severe hypertension by 30% to 70%. Labetalol decreased proteinuria/preeclampsia (odds ratio, 0.73 [95% credible interval, 0.54–0.99]) and fetal/newborn death (odds ratio, 0.54 [0.30–0.98]) compared with placebo/no therapy, and proteinuria/preeclampsia compared with methyldopa (odds ratio, 0.66 [0.44–0.99]) and calcium channel blockers (odds ratio, 0.63 [0.41–0.96]). No other differences were identified, but credible intervals were wide. Trial sequential analysis indicated that 2500 to 10 000 women/arm (severe hypertension or safety outcomes) to >15 000/arm (fetal/newborn death) would be required to provide definitive evidence. Conclusions: In summary, all commonly prescribed antihypertensives in pregnancy reduce the risk of severe hypertension, but labetalol may also decrease proteinuria/preeclampsia and fetal/newborn death. Evidence is lacking for many other safety outcomes. Prohibitive sample sizes are required for definitive evidence. Real-world data are needed to individualize care.

Efficacy And Safety of Wound Infiltration Modalities For Postoperative Pain Management After Cesarean Section: A Systematic Review, Meta-Analysis, And Trial Sequential Analysis Protocol

Background: Inadequately managed postoperative pain after cesarean section has a number of consequences to the mother in the postoperative period. Different postoperative pain management modalities have been practiced after cesarean section over the years. The opioid based analgesics and land mark techniques have undesirable consequences, regional analgesia technique with ultrasound requires resource and expertise while different wound infiltration techniques are new techniques with minimal side effect and easy to administer. However, the effectiveness of each technique is uncertain and needs further investigation.Objective: This systematic review will provide the most effective wound infiltration technique to prevent undesirable adverse effects of opioids and untreated painMethod: A comprehensive search will be conducted in PubMed/Medline, Cochrane, Science direct, CINHAL, and LILACS without date and language restriction. All randomized trials comparing the efficacy of wound infiltration for postoperative pain management after cesarean section will be included. The data will be extracted with two independent authors in a customized format. The methodological quality of included studies will be evaluated using the Cochrane risk of bias tool. The overall quality of the evidence will be determined by GRADEpro software. Trial Sequential Analysis will be conducted to investigate the necessity of further trials.Discussion: The incidence of postoperative acute as well as chronic pain is very high which has a tremendous impact on the mother, family, healthcare providers, and healthcare delivery. It is a basic human right to provide postoperative pain management to every patient that is feasible to everyone in terms of resources, technique, cost, and minimal adverse events profileRegistration: This systematic review protocol was registered in Prospero (CRD42021270710) on September 5, 2021

The Effect of Conservative Oxygen Therapy in Reducing Mortality in Critical Care Patients: A Meta-Analysis and Trial Sequential Analysis

Background: Conservative oxygen therapy can prevent both hypoxemia and hyperoxemia, but the effect on the prognosis of patients admitted to the intensive care unit (ICU) remains controversial.Methods: All controlled studies comparing conservative oxygen therapy and conventional oxygen therapy in adult patients admitted to the ICU were searched. The primary outcome was mortality, and the secondary outcomes were length of ICU stay (ICU LOS), length of hospital stay (hospital LOS), length of mechanical ventilation (MV) hours, new organ failure during ICU stay, and new infections during ICU stay.Results: Nine trials with a total of 5,759 patients were pooled in our final studies. Compared with conventional oxygen therapy, conservative oxygen therapy did not reduce overall mortality (Z = 0.31, p = 0.75) or ICU LOS (Z = 0.17, p = 0.86), with firm evidence from trial sequential analysis, or hospital LOS (Z = 1.98, p = 0.05) or new infections during the ICU stay (Z = 1.45, p = 0.15). However, conservative oxygen therapy was associated with a shorter MV time (Z = 5.05, p < 0.00001), reduction of new organ failure during the ICU stay (Z = 2.15, p = 0.03) and lower risk of renal replacement therapy (RRT) (Z = 2.18, p = 0.03).Conclusion: Conservative oxygen therapy did not reduce mortality but did decrease MV time, new organ failure and risk of RRT in critically ill patients.Systematic Review Registration: identifier [CRD42020171055].

Association between Interleukin-1 Polymorphisms and Susceptibility to Dental Peri-Implant Disease: A Meta-Analysis

Background and objective: Interleukins (ILs), as important biochemical mediators, control the host response to inflammation and are associated with bone resorption. In the present meta-analysis, we investigated the association between IL−1 polymorphisms and susceptibility to dental peri-implant disease (PID). Materials and methods: We searched Web of Science, Cochrane Library, Scopus, and PubMed/Medline databases for studies published until 9 September2021, without any restrictions. We calculated the crude OR and 95% confidence intervals (CI) to estimate the associations between IL−1 polymorphisms and PID risk in the five genetic models. We further performed the subgroup analysis, sensitivity analysis, meta-regression, trial sequential analysis, and calculated the publication bias. Results: Out of 212 retrieved records, sixteen articles were used in the meta-analysis. There was no association between IL−1A (–889), IL−1B (−511), IL−1B (+3953), and IL−1RN (VNTR) polymorphisms and the risk of dental PIDs, but there was an increased risk of IL−1B (+3954) in the patients with PIDs. In addition, an association of the composite genotype of IL−1A (−889)/IL−1B (+3953) was observed with the risk of PIDs, but not for the composite genotype of IL−1A (−889)/IL−1B (+3954). The publication year, the ethnicity, sample size, and the outcome were significantly influenced pooled estimates of some genetic models. Trial sequential analysis showed the lack of sufficient sample sizes in the studies. Conclusions: Among IL−1 polymorphisms evaluated in the meta-analysis, the composite genotype of IL−1A (−889)/IL−1B (+3953) and IL−1B (+3954) were the only polymorphisms associated with the risk of PID. The T allele and CT genotype of IL−1B (+3954) polymorphism were also associated with an elevated risk of PID.