Efficacy and immunogenicity of AS04-HPV-16/18 vaccine in females with existing cervical HR-HPV infection at first vaccination: A pooled analysis of four large clinical trials worldwide.

Females with existing high-risk HPV (HR-HPV) infections remain at risk of subsequent multiple or recurrent infections, on which benefit from HPV vaccines was under-reported. We pooled individual-level data from four large-scale, RCTs of AS04-HPV-16/18 vaccine to evaluate efficacy and immunogenicity in females DNA-positive to any HR-HPV types at first vaccination. Females receiving the AS04-HPV-16/18 vaccine in the original RCTs constituted the vaccine group in the present study, while those unvaccinated served as the control group. Vaccine efficacy (VE) against new infections and associated cervical intraepithelial neoplasia (CIN) 2+ in females DNA-negative to the considered HR-HPV type but positive to any other HR-HPV types, VE against reinfections in females DNA-positive to the considered HR-HPV type but cleared naturally during later follow-up, and levels of anti-HPV-16/18 IgG were assessed. Our final analyses included 5137 females (vaccine group = 2532, control group = 2605). The median follow-up time was 47.88 months (IQR: 45.72-50.04). For the prevention of precancerous lesions related to the non-infected HR-HPV types at baseline, VE against HPV-16/18 related CIN 2+ was 82.70% (95% CI: 63.70-93.00%). For the prevention of reinfections related to the infected HR-HPV types following natural clearance, VE against HPV-16/18 12MPI was non-significant (p > .05), albeit robust immunity persisted for at least 48 months. Females with existing HR-HPV infections at first vaccination still benefit from vaccination in preventing precancers related to the non-infected types at baseline. VE against reinfections related to the infected types following natural clearance remains to be further investigated.

An international consensus on the essential and desirable criteria for an 'organized' cancer screening programme.

BACKGROUND: High variability in the definition and interpretation of organized cancer screening needs to be addressed systematically. Moreover, the relevance of the current practice of categorizing screening programmes dichotomously into organized or non-organized needs to be revisited in the context of considerable heterogeneity that exists in the delivery of cancer screening in the real world. We aimed to identify the essential and desirable criteria for organized cancer screening that serve as a charter of best practices in cancer screening. METHODS: We first did a systematic review of literature to arrive at an exhaustive list of criteria used by various publications to describe or define organized cancer screening, based on which, a consolidated list of criteria was generated. Next, we used a Delphi process comprising of two rounds of online surveys to seek agreement of experts to categorize each criterion into essential, desirable, or neither. Consensus was considered to have been achieved based on a predetermined criterion of agreement from at least 80% of the experts. The outcomes were presented before the experts in a virtual meeting for feedbacks and clarifications. RESULTS: A total of 32 consolidated criteria for an organized screening programme were identified and presented to 24 experts from 20 countries to select the essential criteria in the Delphi first round. Total 16 criteria were selected as essential with the topmost criteria (based on the agreement of 96% of experts) being the availability of a protocol/guideline describing at least the target population, screening intervals, screening tests, referral pathway, management of positive cases and a system being in place to identify the eligible populations. In the second round of Delphi, the experts selected eight desirable criteria out of the rest 16. The most agreed upon desirable criterion was existence of a specified organization or a team responsible for programme implementation and/or coordination. CONCLUSIONS: We established an international consensus on essential and desirable criteria, which screening programmes would aspire to fulfil to be better-organized. The harmonized criteria are a ready-to-use guide for programme managers and policymakers to prioritize interventions and resources rather than supporting the dichotomous and simplistic approach of categorizing programmes as organized or non-organized.

Probiotics for the Prevention of Antibiotic-associated Diarrhea in Adults: A Meta-Analysis of Randomized Placebo-Controlled Trials.

OBJECTIVE: This meta-analysis aims to combine the latest research evidence to assess the effect of probiotics on preventing antibiotic-associated diarrhea (AAD) in adults. METHODS: PubMed, Cochrane Library, EMBASE, and Web of Science were searched for randomized placebo-controlled trials on probiotics preventing AAD. A random or fixed effect model was used to combine the incidence of AAD (primary outcome) and the adverse event rates. The authors performed subgroup analyses to explore the effects of different participants population, probiotics species, and dosage. RESULTS: Thirty-six studies were included with 9312 participants. Probiotics reduced the incidence of AAD by 38% (pooled relative risk, 0.62; 95% confidence interval, 0.51-0.74). The protective effect of probiotics was still significant when grouped by reasons for antibiotics treatment, probiotic duration, probiotic dosage, and time from antibiotic to probiotic. However, there were no statistically significant increased adverse events in the probiotics group (relative risk, 1.00; 95% confidence interval, 0.87-1.14). CONCLUSIONS: This updated meta-analysis suggested that using probiotics as early as possible during antibiotic therapy has a positive and safe effect on preventing AAD in adults. Further studies should focus on the optimal dosage and duration of probiotics to develop a specific recommendation.

Prognostic significance of autophagy-related genes within esophageal carcinoma.

BACKGROUND: Several works suggest the importance of autophagy during esophageal carcinoma development. The aim of the study is to construct a scoring system according to the expression profiles of major autophagy-related genes (ARGs) among esophageal carcinoma cases. METHODS: The Cancer Genome Atlas was employed to obtain the esophageal carcinoma data. Thereafter, the online database Oncolnc ( http://www.oncolnc.org/ ) was employed to verify the accuracy of our results. According to our results, the included ARGs were related to overall survival (OS). RESULTS: We detected the expression patterns of ARG within esophageal carcinoma and normal esophageal tissues. In addition, we identified the autophagy related gene set, including 14 genes displaying remarkable significance in predicting the esophageal carcinoma prognosis. The cox regression results showed that, 7 ARGs (including TBK1, ATG5, HSP90AB1, VAMP7, DNAJB1, GABARAPL2, and MAP2K7) were screened to calculate the ARGs scores. Typically, patients with higher ARGs scores were associated with poorer OS. Moreover, the receiver operating characteristic (ROC) curve analysis suggested that, ARGs accurately distinguished the healthy people from esophageal carcinoma patients, with the area under curve (AUC) value of > 0.6. CONCLUSION: A scoring system is constructed in this study based on the main ARGs, which accurately predicts the outcomes for esophageal carcinoma.

Effect of electronic health (eHealth) on quality of life in women with breast cancer: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Women with breast cancer and improved survival face some specific quality of life (QOL) issues. Electronic health (eHealth) is a useful tool aiming to enhance health services. However, evidence remains controversial about the effect of eHealth on QOL in women with breast cancer. Another unstudied factor is the effect on specific QOL functional domains. Therefore, we undertook a meta-analysis about whether eHealth could improve the overall and specific functional domains of QOL in women with breast cancer. METHODS: PubMed, Cochrane Library, EMBASE, and Web of Science were searched to identify appropriate randomized clinical trials from database inception to March 23, 2022. The standard mean difference (SMD) served as the effect size and the DerSimonian-Laird random effects model was constructed for meta-analysis. Subgroup analyses were conducted according to different participant, intervention, and assessment scale characteristics. RESULTS: We initially identified 1954 articles excluding duplicates and ultimately included 13 of them involving 1448 patients. The meta-analysis revealed that the eHealth group had significantly higher QOL (SMD 0.27, 95% confidence interval [95% CI] 0.13-0.40, p < 0.0001) than the usual care group. Additionally, although not statistically significant, eHealth tended to improve the physical (SMD 2.91, 95% CI -1.18 to 6.99, p = 0.16), cognitive (0.20 [-0.04, 0.43], p = 0.10), social (0.24 [-0.00, 0.49], p = 0.05), role (0.11 [0.10, 0.32], p = 0.32), and emotional (0.18 [0.08, 0.44], p = 0.18) domains of QOL. Overall, consistent benefits were observed in both the subgroup and pooled estimates. CONCLUSIONS: eHealth is superior to usual care in women with breast cancer for improved QOL. Implications for clinical practice should be discussed based on subgroup analysis results. Further confirmation is needed for the effect of different eHealth patterns on specific domains of QOL, which would help improve specific health issues of the target population.

Tackling barriers to scale up human papillomavirus vaccination in China: progress and the way forward.

The human papillomavirus (HPV) vaccine is the first vaccine developed specifically targeting the prevention of cervical cancer. For more than 15 years, China has expedited a series of efforts on research and development of the domestically manufactured HPV vaccines, producing local population-based evidence, promoting free HPV vaccination from pilots, and launching action plans to tackle barriers in the scale-up of HPV vaccination. To further roll out the HPV vaccination program in China, several challenges should be addressed to support the steps forward. The availability of more locally manufactured HPV vaccines, pricing negotiation and local evidence supporting the efficacy of one-dose schedule would greatly alleviate the continued supply and financial constraints in China. Meanwhile, more attention should be paid to girls living in low-resource areas and males to ensure equal access to the HPV vaccination. Furthermore, linkage to secondary prevention and further real-world monitoring and evaluation are warranted to inform effective cervical cancer prevention strategies in the post-vaccine era.

Systematic review and meta-analysis of tocilizumab in persons with coronavirus disease-2019 (COVID-19).

We performed a meta-analysis to determine safety and efficacy of tocilizumab in persons with coronavirus disease-2019 (COVID-19). We searched PubMed, Web of Science and Medline using Boolean operators for studies with the terms coronavirus OR COVID-19 OR 2019-nCoV OR SARS-CoV-2 AND tocilizumab. Review Manager 5.4 was used to analyze data and the modified Newcastle-Ottawa and Jadad scales for quality assessment. We identified 32 studies in 11,487 subjects including three randomized trials and 29 cohort studies with a comparator cohort, including historical controls (N = 5), a matched cohort (N = 12), or concurrent controls (N = 12). Overall, tocilizumab decreased risk of death (Relative Risk [RR] = 0.74; 95% confidence interval [CI], 0.59, 0.93; P = 0.008; I2 = 80%) but not of surrogate endpoints including ICU admission (RR = 1.40 [0.64,3.06]; P = 0.4; I2 = 88%), invasive mechanical ventilation (RR = 0.83 [0.57,1.22]; P = 0.34; I2 = 65%) or secondary infections (RR = 1.30 [0.97,1.74]; P = 0.08; I2 = 65%) and increased interval of hospitalization of subjects discharged alive(mean difference [MD] = 2 days [<1, 4 days]; P = 0.006; I2 = 0). RRs of death in studies with historical controls (RR = 0.28 [0.16,0.49; P < 0.001]; I2 = 62%) or a matched cohort (RR = 0.68 [0.53, 0.87]; P = 0.002; I2 = 42%) were decreased. In contrast, RRs of death in studies with a concurrent control (RR = 1.10 [0.77, 1.56]; P = 0.60; I2 = 85%) or randomized (RR = 1.18 [0.57,2.44]; P = 0.66; I2 = 0) were not decreased. A reduced risk of death was not confirmed in our analyses which questions safety and efficacy of tocilizumab in persons with COVID-19.

Habitual consumption of alcohol with meals and lung cancer: a Mendelian randomization study.

BACKGROUND: The objective of this study was to determine the causal relationship between habitual alcohol consumption with meals and lung cancer. METHODS: Public genetic summary data from two large consortia [the Neale Lab and the International Lung Cancer Consortium (ILCCO)] were used for analysis. As the instrumental variables of habitual alcohol consumption with meals, data on genetic variants were retrieved from Neale Lab. Additionally, genetic data from other consortia [Global Lipid Genetics Consortium (GLGC), Tobacco, Alcohol and Genetics (TAG), Genetic Investigation of Anthropocentric Traits (GIANT)] were utilized to determine whether alcohol could causally alter some general risk factors for lung cancer. The primary outcome was the risk of lung cancer (11,348 cases and 15,861 controls in the ILCCO). The R package TwoSampleMR was used for analysis. RESULTS: Based on the inverse variance weighted method, the results of the two-sample Mendelian randomization (MR) analyses indicated that commonly consuming alcohol with meals was a protective factor, reducing lung cancer risk [odds ratio (OR) 0.175, 95% confidence interval (CI): 0.045-0.682, P=0.012]. The heterogeneity analysis revealed that the causal relationship analyses of different types of lung cancer all had low heterogeneity (P>0.05). The horizontal pleiotropic study showed that major bias was unlikely. The MR assumptions did not seem to be violated. The causal relationship analyses between habitual alcohol consumption with meals and some risk factors for cancers showed that this alcohol consumption habit was a beneficial factor for reducing body mass index (BMI) and the number of cigarettes smoked per day. CONCLUSIONS: Habitual appropriate alcohol consumption with meals is a protective factor for the development of lung cancer.

Probiotics Used for Postoperative Infections in Patients Undergoing Colorectal Cancer Surgery.

OBJECTIVE: The objective of this study was to conduct a systematic review and meta-analysis about probiotics to improve postoperative infections in patients undergoing colorectal cancer surgery. METHODS: The PubMed and the Web of Science were used to search for appropriate randomized clinical trials (RCTs) comparing probiotics with placebo for the patients undergoing colorectal cancer surgery. The RevMan 5.3 was performed for meta-analysis to evaluate the postoperative infection, including the total infection, surgical site infection, central line infection, pneumonia, urinary tract infection, septicemia, and postoperative leakage. RESULTS: Our meta-analysis included 6 studies involving a total of 803 patients. For the incidence of total postoperative infection (odd ratios (OR) 0.31, 95% confidence interval (CI) 0.15-0.64, I 2 = 0%), surgical site infection (OR 0.62, 95% CI 0.39-0.99, I 2 = 0%), surgical site infection (OR 0.62, 95% CI 0.39-0.99, I 2 = 0%), surgical site infection (OR 0.62, 95% CI 0.39-0.99, I 2 = 0%), surgical site infection (OR 0.62, 95% CI 0.39-0.99, I 2 = 0%), surgical site infection (OR 0.62, 95% CI 0.39-0.99, I 2 = 0%), surgical site infection (OR 0.62, 95% CI 0.39-0.99, I 2 = 0%), surgical site infection (OR 0.62, 95% CI 0.39-0.99. CONCLUSIONS: Probiotics is beneficial to prevent postoperative infections (including total postoperative infection, surgical site infection, pneumonia, urinary tract infection, and septicemia) in patients with colorectal cancer.

Effects of autophagy-associated genes on the prognosis for lung adenocarcinoma.

BACKGROUND: Several studies show that autophagy plays an important part in the biological processes of lung adenocarcinoma. Therefore, this work aimed to establish one scoring system on the basis of the expression profiles of differentially expressed autophagy-related genes (DEARGs) in patients with lung adenocarcinoma. METHODS: The Cancer Genome Atlas (TCGA) was applied to retrieve lung adenocarcinoma data. The overall survival (OS)-associated DEARGs were selected for the DEARG scoring scale. Moreover, the online database Kaplan-Meier Plotter (www.Kmplot.com) was employed to verify the accuracy of our results. RESULTS: The expression patterns of DEARG were detected in lung adenocarcinoma as well as normal lung tissues. A gene set related to autophagy was identified, along with 9 genes that showed marked significance in predicting the lung adenocarcinoma prognosis. According to the cox regression results, DEARGs (including ITGB4, BIRC5, ERO1A, and NLRC4) were applied to calculate the DEARGs risk score. Patients with lower DEARGs risk scores were associated with better OS. Moreover, based on analysis with the receiver operating characteristic (ROC) curve, DEARGs accurately distinguished the healthy tissues from lung adenocarcinoma tissues [area under the curve (AUC) value of >0.6]. CONCLUSIONS: A scoring system is constructed based on the primary DEARGs, which accurately predicts the outcomes of lung adenocarcinoma.

The Change of Laboratory Tests Could Be Predictive Factors for Infection after McKeown Esophagogastrectomy.

AIM: To analyze whether the change of laboratory tests (postoperative day 1 (POD1) minus pre-operation) could be predictive factors for postoperative infection in patients who have undergone McKeown esophagogastrectomy. METHODS: We retrospectively investigated the clinical data of 358 patients who have undergone McKeown esophagogastrectomy, and divided them into infection and noninfection groups. SPSS 22.0 software was performed for data analysis. RESULTS: In the two groups, smoking status (66.7% vs. 42.3%; P = 0.014), male gender (86.1% vs. 72.0%; P < 0.001), hoarseness (23.6% vs. 8.7%; P < 0.001), poor coughing ability (51.4% vs. 9.1%; P < 0.001), the change of WBC count (5.59 ± 4.75 × 109/L vs. 4.51 ± 4.11 × 109/L; P = 0.05), the change of glucose (6.03 ± 3.97 g/L vs. 3.78 ± 3.18 g/L), the change of ALB (-12.83 ± 3.45 g/L vs. -10.69 ± 3.86 g/L), the change of CRE (0.17 ± 19.94 umol/L vs. -4.02 ± 15.40 umol/L, P = 0.047) were significantly different. These factors were assessed using logistic regression analysis, and factors with P ≤ 0.05 in the univariate analysis were entered into multivariate analysis based on the forward stepwise (conditional) method. Poor coughing ability (odds ratio [OR], 11.034, 95% confidence interval [CI], 5.358-22.724), smoking status (OR, 4.218; 95% CI, 2.110-8.431), the change of WBC count (OR, 1.079; 95% CI, 1.000-1.164), the change of serum ALB level (OR, 0.849; 95% CI, 0.772-0.935), and the change of blood glucose levels (OR, 1.237; 95% CI, 1.117-1.371) were determined as independent risk factors for postoperative infection. We established a scoring system based on these 5 factors, and the area under the curve for this predictive model was 0.843 (range, 0.793-0.894); the sensitivity, specificity, and cut-off score were 70.8%, 85.3%, and 2.500, respectively. CONCLUSION: Poor coughing ability, smoking habit, the high change of WBC and blood glucose levels, and low change of serum ALB levels can be used to predict the occurrence of postoperative infections among patients who have undergone McKeown esophagogastrectomy.

Neurally adjusted ventilatory assist versus pressure support ventilation in patient-ventilator interaction and clinical outcomes: a meta-analysis of clinical trials.

BACKGROUND: The objective of this study was to conduct a meta-analysis comparing neurally adjusted ventilatory assist (NAVA) with pressure support ventilation (PSV) in adult ventilated patients with patient-ventilator interaction and clinical outcomes. METHODS: The PubMed, the Web of Science, Scopus, and Medline were searched for appropriate clinical trials (CTs) comparing NAVA with PSV for the adult ventilated patients. RevMan 5.3 was performed for comparing NAVA with PSV in asynchrony index (AI), ineffective efforts, auto-triggering, double asynchrony, premature asynchrony, breathing pattern (Peak airway pressure (Pawpeek), mean airway pressure (Pawmean), tidal volume (VT, mL/kg), minute volume (MV), respiratory muscle unloading (peak electricity of diaphragm (EAdipeak), P 0.1, VT/EAdi), clinical outcomes (ICU mortality, duration of ventilation days, ICU stay time, hospital stay time). RESULTS: Our meta-analysis included 12 studies involving a total of 331 adult ventilated patients, AI was significantly lower in NAVA group [mean difference (MD) -12.82, 95% confidence interval (CI): -21.20 to -4.44, I2=88%], and using subgroup analysis, grouped by mechanical ventilation, the results showed that NAVA also had lower AI than PSV (Mechanical ventilation, MD -9.52, 95% CI: -17.85 to -1.20, I2=87%), (Non-invasive ventilation (NIV), MD -24.55, 95% CI: -35.40 to -13.70, I2=0%). NAVA was significantly lower than the PSV in auto-triggering (MD -0.28, 95% CI: -0.51 to -0.05, I2=10%), and premature triggering (MD -2.49, 95% CI: -3.77 to -1.21, I2=29%). There were no significant differences in double triggering, ineffective efforts, breathing pattern (Pawmean, Pawpeak, VT, MV), and respiratory muscle unloading (EAdipeak, P 0.1, VT/EAdi). For clinical outcomes, NAVA was significantly lower than the PSV (MD -2.82, 95% CI: -5.55 to -0.08, I2=0%) in the duration of ventilation, but two groups did not show significant differences in ICU mortality, ICU stay time, and hospital stay time. CONCLUSIONS: NAVA is more beneficial in patient-ventilator interaction than PSV, and could decrease the duration of ventilation.

Nocturnal supports for patients with central sleep apnea and heart failure: a systemic review and network meta-analysis of randomized controlled trials.

BACKGROUND: Sleep apnea probably brings poor outcomes of chronic heart failure (CHF), and some methods show benefit to patients with heart failure (HF) and central sleep apnea (CSA). Our study based on the randomized controlled trials (RCTs) to find out the most beneficial therapy of nocturnal support to decrease the apnea hypopnea index (AHI). METHODS: The PubMed, and the Web of Science were used to find out the included studies. RevMan 5.3 and Stata 15.1 were performed to this systemic review and network meta-analysis. RESULTS: After searching and screening the articles, finally we included 14 articles with total 919 patients, and 4 arms [adaptive servo ventilation (ASV), continuous positive airway pressure (CPAP), oxygen treatment, control]. Compared with the control group, the therapeutic regimens did not show significant difference in AHI. Ranking the different nocturnal supports in the order of estimated probabilities of each treatment by using the network meta-analysis, the result showed that ASV was the best one (87.8%), followed by oxygen (12.2%), CPAP (0%), and control (0%). CONCLUSIONS: Based on our study, the adoptive servo ventilation is probably the best choice to down the AHI in patients with HF and CSA.

Combination era, using combined vasopressors showed benefits in treating septic shock patients: a network meta-analysis of randomized controlled trials.

BACKGROUND: Septic shock is one of the major healthcare problems, affecting millions of people around the world every year. The object of this study is to find the best kind of regimen of vasopressors treatment in septic shock. METHODS: The PubMed, and the Web of Science were used to find the included studies. Stata 15.1 was performed to this systemic review and network meta-analysis. RESULTS: After searching and screening the articles, finally we included articles about 31 randomized controlled trials (RCTs), 11 arms (dopamine, dopexamine, epinephrine, norepinephrine, norepinephrine + dobutamine, norepinephrine + dopexamine, norepinephrine + epinephrine, norepinephrine + vasopressin, phenylephrine, terlipressin, vasopressin) and total 5,928 patients with septic shock. Compared with dopamine, the regimens (epinephrine, norepinephrine, norepinephrine + dobutamine, and vasopressin) have significantly lower 28-day mortality. Ranking the regimens in the order of estimated probabilities of each treatment by using the network meta-analysis for 28-day mortality, the result showed that norepinephrine + dopexamine was the best one (57.3%), followed by norepinephrine + epinephrine (14.8%), norepinephrine + dobutamine (10.9%), dopexamine (11.2%), terlipressin (9.8%), norepinephrine + vasopressin (2.4%), phenylephrine (1.2%), epinephrine (1.0%), vasopressin (0.5%), norepinephrine (0.0%), and dopamine (0.0%). In addition, for the results of arrhythmia and increased heart rate, the combination regimens groups did not showed inferiority to other single regimen groups. CONCLUSIONS: Single dopamine had significantly higher 28d mortality. Combination regimens of vasopressors accounted for the best three therapeutic regimens. In treating patients with septic shock, using combining regimens probably gets more benefits.