Gefitinib, erlotinib and afatinib are three widely used epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) for treating advanced non‐small cell lung cancer (NSCLC) with proven efficacy. We undertook a systematic review and meta‐analysis to synthesize existing studies with direct comparisons of EGFR TKIs in NSCLC in terms of both efficacy and safety. Eight randomized trials and 82 cohort studies with a total of 17,621 patients were included for analysis. Gefitinib and erlotinib demonstrated comparable effects on progression‐free survival (hazard ratio [HR], 1.00; 95% confidence interval [CI], 0.95 to 1.04), overall survival (HR, 0.99; 95% CI, 0.93 to 1.06), overall response rate (risk ratio [RR], 1.05; 95% CI, 1.00 to 1.11), and disease control rate (RR, 0.98; 95% CI, 0.96 to 1.01), which did not vary considerably with EGFR mutation status, ethnicity, line of treatment, and baseline brain metastasis status. Gefitinib was associated with more grade 3/4 liver dysfunction, but tended to cause lower rates of dose reduction, treatment discontinuation, total grade 3/4 adverse events (RR, 0.78; 95% CI 0.65 to 0.94), and a number of specific adverse events such as rash and diarrhea. No solid evidence was found that afatinib had greater efficacy than gefitinib or erlotinib in first‐line treatment of EGFR‐mutant NSCLC. However, afatinib was more effective than erlotinib as second‐line treatment of patients with advanced squamous cell carcinoma. The grade 3/4 adverse events rate of afatinib was comparable to that of erlotinib but higher than that of gefitinib.

The efficacy of SARS-CoV-2 vaccines in preventing severe COVID-19 illness and death is uncertain due to the rarity of data in individual trials. How well the antibody concentrations can predict the efficacy is also uncertain. We aimed to assess the efficacy of these vaccines in preventing SARS-CoV-2 infections of different severities and the dose-response relationship between the antibody concentrations and efficacy. We did a systematic review and meta-analysis of randomised controlled trials (RCTs). We searched PubMed, Embase, Scopus, Web of Science, Cochrane Library, WHO, bioRxiv, and medRxiv for papers published between Jan 1, 2020 and Sep 12, 2022. RCTs on the efficacy of SARS-CoV-2 vaccines were eligible. Risk of bias was assessed using the Cochrane tool. A frequentist, random-effects model was used to combine efficacy for common outcomes (ie, symptomatic and asymptomatic infections) and a Bayesian random-effects model was used for rare outcomes (ie, hospital admission, severe infection, and death). Potential sources of heterogeneity were investigated. The dose-response relationships of neutralising, spike-specific IgG and receptor binding domain-specific IgG antibody titres with efficacy in preventing SARS-CoV-2 symptomatic and severe infections were examined by meta-regression. This systematic review is registered with PROSPERO, CRD42021287238. 28 RCTs (n=286 915 in vaccination groups and n=233 236 in placebo groups; median follow-up 1-6 months after last vaccination) across 32 publications were included in this review. The combined efficacy of full vaccination was 44·5% (95% CI 27·8-57·4) for preventing asymptomatic infections, 76·5% (69·8-81·7) for preventing symptomatic infections, 95·4% (95% credible interval 88·0-98·7) for preventing hospitalisation, 90·8% (85·5-95·1) for preventing severe infection, and 85·8% (68·7-94·6) for preventing death. There was heterogeneity in the efficacy of SARS-CoV-2 vaccines against asymptomatic and symptomatic infections but insufficient evidence to suggest whether the efficacy could differ according to the type of vaccine, age of the vaccinated individual, and between-dose interval (p>0·05 for all). Vaccine efficacy against symptomatic infection waned over time after full vaccination, with an average decrease of 13·6% (95% CI 5·5-22·3; p=0·0007) per month but can be enhanced by a booster. We found a significant non-linear relationship between each type of antibody and efficacy against symptomatic and severe infections (p<0·0001 for all), but there remained considerable heterogeneity in the efficacy, which cannot be explained by antibody concentrations. The risk of bias was low in most studies. The efficacy of SARS-CoV-2 vaccines is higher for preventing severe infection and death than for preventing milder infection. Vaccine efficacy wanes over time but can be enhanced by a booster. Higher antibody titres are associated with higher estimates of efficacy but precise predictions are difficult due to large unexplained heterogeneity. These findings provide an important knowledge base for interpretation and application of future studies on these issues. Shenzhen Science and Technology Programs.

Objectives: Previous meta-analyses of a small number of trials showed that acceptance and commitment therapy (ACT) might improve chronic pain. Many new trials have been published afterward, and the factors that may impact the efficacy of ACT are less understood. We, therefore, conducted an updated systematic review with meta-analysis to investigate the efficacy of ACT for people with chronic pain. Methods: Randomized controlled trials that investigated the efficacy of ACT in clinical or community setting for adult populations with chronic pain were included. The methodological quality of trials was assessed with the Cochrane Risk of Bias tool. Standardized mean differences between ACT and comparison groups in their effects on 6 outcomes (ie, pain acceptance, quality of life, pain-related functioning, pain intensity, anxiety, and depression) were pooled across studies. Results: Of the 3171 records identified, 21 trials with 1962 participants were included for analysis. The comparison groups included active treatment and waitlist control/usual care. The standardized mean difference was 0.67 (95% CI: 0.48, 0.87) for pain acceptance, 0.43 (95% CI: 0.29, 0.57) for quality of life, −0.88 (95% CI: −1.14, −0.63) for pain-related functioning, −0.45 (95% CI: −0.62, −0.27) for pain intensity, −0.35 (95% CI: −0.54, −0.15) for anxiety, and −0.74 (95% CI, −0.98, −0.50) for depression, all favoring ACT. Subgroup analyses showed that the effects were statistically significant across almost all subgroups and for some outcomes were greater in the trials conducted in people with a specific diagnosis (as compared with those conducted in people with general chronic pain), the trials with waitlist or usual care control, the trials with a greater number of sessions of ACT, and the trials with a longer ACT intervention. Discussion: ACT is effective and comparable to, if not better than, some other available active treatments for chronic pain.

The coronavirus disease 2019 (COVID-19) emerged by end of 2019, and became a serious public health threat globally in less than half a year. The generation interval and latent period, though both are of importance in understanding the features of COVID-19 transmission, are difficult to observe, and thus they can rarely be learnt from surveillance data empirically. In this study, we develop a likelihood framework to estimate the generation interval and incubation period simultaneously by using the contact tracing data of COVID-19 cases, and infer the pre-symptomatic transmission proportion and latent period thereafter. We estimate the mean of incubation period at 6.8 days (95 %CI: 6.2, 7.5) and SD at 4.1 days (95 %CI: 3.7, 4.8), and the mean of generation interval at 6.7 days (95 %CI: 5.4, 7.6) and SD at 1.8 days (95 %CI: 0.3, 3.8). The basic reproduction number is estimated ranging from 1.9 to 3.6, and there are 49.8 % (95 %CI: 33.3, 71.5) of the secondary COVID-19 infections likely due to pre-symptomatic transmission. Using the best estimates of model parameters, we further infer the mean latent period at 3.3 days (95 %CI: 0.2, 7.9). Our findings highlight the importance of both isolation for symptomatic cases, and for the pre-symptomatic and asymptomatic cases.

Summary: Background: The outbreak of coronavirus disease 2019 (COVID-19) has been declared a pandemic by the World Health Organization, while several key epidemiological parameters of the disease remain to be clarified. This study aimed to obtain robust estimates of the incubation period, upper limit of latent period (interval between infector’s exposure and infectee’s exposure), serial interval, time point of exposure (the day of infectee’s exposure to infector relative to the latter’s symptom onset date) and basic reproduction number (R ₀ ) of COVID-19. Methods: Between late February and early March of 2020, the individual data of laboratory confirmed cases of COVID-19 were retrieved from 10728 publicly available reports released by the health authorities of and outside China and from 1790 publications identified in PubMed and CNKI. To be eligible, a report had to contain the data that allowed for estimation of at least one parameter. As relevant data mainly came from clustering cases, the clusters for which no evidence was available to establish transmission order were all excluded to ensure accuracy of estimates. Additionally, only the cases with an exposure period spanning 3 days or less were included in the estimation of parameters involving exposure date, and a simple method for determining exposure date was adopted to ensure the error of estimates be small (< 0.3 day). Depending on specific parameters, three or four of normal, lognormal, Weibull, and gamma distributions were fitted to the datasets and the results from appropriate models were presented. Findings: In total, 1155 cases from China, Japan, Singapore, South Korea, Vietnam, Germany and Malaysia were included for the final analysis. The mean and standard deviation were 7.44 days and 4.39 days for incubation period, 2.52 days and 3.95 days for the upper limit of latent period, 6.70 days and 5.20 days for serial interval, and −0.19 day (i.e., 0.19 day before infector’s symptom onset) and 3.32 days for time point of exposure. R ₀ was estimated to be 1.70 and 1.78 based on two different formulas. For 39 (6.64%) cases, the incubation periods were longer than 14 days. In 102 (43.78%) infector-infectee pairs, transmission occurred before infectors’ symptom onsets. In 27 (3.92%) infector-infectee pairs, infectees’ symptom onsets occurred before those of infectors. Stratified analysis showed that incubation period and serial interval were consistently longer for those with less severe disease and for those whose primary cases had less severe disease. Asymptomatic transmission was also observed. Interpretation: This study obtained robust estimates of several key epidemiological parameters of COVID-19. The findings support current practice of 14-day quarantine of persons with potential exposure, but also suggest that longer monitoring periods might be needed for selected groups. The estimates of serial interval, time point of exposure and latent period provide consistent evidence on pre-symptomatic transmission. This together with asymptomatic transmission and the generally longer incubation and serial interval of less severe cases suggests a high risk of long-term epidemic in the absence of appropriate control measures. Funding: This work received no funding from any source.

To date, published systematic reviews concerning the effects of Kinesio Taping (KT) on muscle strength have not analysed facilitatory and inhibitory applications separately. As a result, their results could be substantially affected by clinical heterogeneity. This meta-analysis was conducted to determine the effectiveness of using a facilitatory application of KT for lower limb muscle strength and functional performance (distance in a single-leg hop and vertical jump height) in individuals without disabilities and in those with musculoskeletal conditions (muscle fatigue, chronic musculoskeletal diseases, and post-operative orthopaedic conditions). Searches were conducted on six major electronic databases. Randomised controlled trials that used facilitatory KT were included. Standardised mean differences (SMDs) were calculated and random-effects models were used for analysis. Thirty-seven randomised controlled trials were included. KT was superior to controls for improving lower limb muscle strength in individuals with muscle fatigue (short-term effect, pooled SMD = 0.53, 95% CI = 0.09 to 0.96; long-term effect, pooled SMD = 0.61, 95% CI = 0.12 to 1.11) and in individuals with chronic musculoskeletal diseases (pooled SMD = 1.24, 95% CI = 0.33 to 2.16) with large effect sizes. The use of KT in populations without disabilities was not supported. There is insufficient evidence for the effect of KT on functional performance in individuals with musculoskeletal conditions. Contrary to prior research, the existing evidence shows that KT can improve lower limb muscle strength in individuals with muscle fatigue and chronic musculoskeletal diseases. The effect sizes produced in this meta-analysis show that KT may be superior to some existing treatments for these conditions. In addition, this study suggests that practitioners may wish to avoid the use of KT in individuals without disabilities. PROSPERO registration number CRD42017075490 , registered on 21 November 2017.