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Frontiers in Oncology 2024The predictive value of programmed death-ligand 1 (PD-L1) expression in nasopharyngeal cancer (NPC) patients receiving immune checkpoint inhibitors (ICIs) remains...
PD-L1 expression as a potential predictor of immune checkpoint inhibitor efficacy and survival in patients with recurrent or metastatic nasopharyngeal cancer: a systematic review and meta-analysis of prospective trials.
BACKGROUND
The predictive value of programmed death-ligand 1 (PD-L1) expression in nasopharyngeal cancer (NPC) patients receiving immune checkpoint inhibitors (ICIs) remains controversial. This study aimed to evaluate the optimal threshold of PD-L1 expression in predicting the efficacy of ICIs in patients with recurrent or metastatic (R/M) NPC.
METHODS
A meta-analysis was performed by retrieving relevant literature from PubMed, EMBASE, and Cochrane Library databases. Data on the pooled risk ratio (RR), mean overall survival (OS), progression-free survival (PFS), overall response rate (ORR) with 95% confidence interval, and 1%, 10%, and 25% PD-L1 expression cutoff points were obtained to examine the role of PD-L1 as a biomarker in R/M NPC patients receiving immunotherapy.
RESULTS
In total, 1,312 patients from 14 studies were included. An improvement in PFS was observed in both patients with PD-L1 ≥ 1% (RR = 0.76, 95% CI 0.62-0.92, P = 0.005) and those with PD-L1 < 1% (RR = 0.68, 95% CI: 0.35-1.32, P = 0.26) who received first-line treatment with immunotherapy, with no significant difference between these subgroups. The pooled ORR was significantly higher in patients with PD-L1 ≥ 1% (ORR = 0.37) than in those with PD-L1 < 1% (ORR = 0.22) (P < 0.01) undergoing subsequent-line treatment. However, when we used the PD-L1 cutoff values of 10% and 25%, there was no significant difference between the positive (PD-L1 expression ≥ the cutoff value) and negative (PD-L1 expression < the cutoff value) subgroups. PD-L1 ≥ 1% also tended to be associated with better PFS and OS.
CONCLUSIONS
Our meta-analysis suggested that first-line immunotherapy could significantly improve PFS in R/M NPC patients, regardless of the PD-L1 expression levels. Positive PD-L1 expression (≥ 1%) might be a potential predictive biomarker for a better overall response to immunotherapy in R/M NPC patients in subsequent-line setting.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024495841 PROSPERO, identifier CRD42024495841.
PubMed: 38887234
DOI: 10.3389/fonc.2024.1386381 -
BMC Infectious Diseases Jun 2024The SARS-CoV-2 pandemic underscored the need for pandemic preparedness, with respiratory-transmitted viruses considered as a substantial risk. In pandemics, long-term...
How to protect long-term care facilities from pandemic-like events? - A systematic review on the effectiveness of non-pharmacological measures to prevent viral respiratory infections.
BACKGROUND
The SARS-CoV-2 pandemic underscored the need for pandemic preparedness, with respiratory-transmitted viruses considered as a substantial risk. In pandemics, long-term care facilities (LTCFs) are a high-risk setting with severe outbreaks and burden of disease. Non-pharmacological interventions (NPIs) constitute the primary defence mechanism when pharmacological interventions are not available. However, evidence on the effectiveness of NPIs implemented in LTCFs remains unclear.
METHODS
We conducted a systematic review assessing the effectiveness of NPIs implemented in LTCFs to protect residents and staff from viral respiratory pathogens with pandemic potential. We searched Medline, Embase, CINAHL, and two COVID-19 registries in 09/2022. Screening and data extraction was conducted independently by two experienced researchers. We included randomized controlled trials and non-randomized observational studies of intervention effects. Quality appraisal was conducted using ROBINS-I and RoB2. Primary outcomes encompassed number of outbreaks, infections, hospitalizations, and deaths. We synthesized findings narratively, focusing on the direction of effect. Certainty of evidence (CoE) was assessed using GRADE.
RESULTS
We analysed 13 observational studies and three (cluster) randomized controlled trials. All studies were conducted in high-income countries, all but three focused on SARS-CoV-2 with the rest focusing on influenza or upper-respiratory tract infections. The evidence indicates that a combination of different measures and hand hygiene interventions can be effective in protecting residents and staff from infection-related outcomes (moderate CoE). Self-confinement of staff with residents, compartmentalization of staff in the LTCF, and the routine testing of residents and/or staff in LTCFs, among others, may be effective (low CoE). Other measures, such as restricting shared spaces, serving meals in room, cohorting infected and non-infected residents may be effective (very low CoE). An evidence gap map highlights the lack of evidence on important interventions, encompassing visiting restrictions, pre-entry testing, and air filtration systems.
CONCLUSIONS
Although CoE of interventions was low or very low for most outcomes, the implementation of NPIs identified as potentially effective in this review often constitutes the sole viable option, particularly prior to the availability of vaccinations. Our evidence-gap map underscores the imperative for further research on several interventions. These gaps need to be addressed to prepare LTCFs for future pandemics.
TRIAL REGISTRATION
CRD42022344149.
Topics: Humans; COVID-19; Long-Term Care; Respiratory Tract Infections; SARS-CoV-2; Pandemics; Infection Control; Randomized Controlled Trials as Topic
PubMed: 38880893
DOI: 10.1186/s12879-024-09271-7 -
BMC Public Health Jun 2024Cardiovascular disease (CVD) is the leading cause of death worldwide. It has been known for some considerable time that radiation is associated with excess risk of CVD....
BACKGROUND
Cardiovascular disease (CVD) is the leading cause of death worldwide. It has been known for some considerable time that radiation is associated with excess risk of CVD. A recent systematic review of radiation and CVD highlighted substantial inter-study heterogeneity in effect, possibly a result of confounding or modifications of radiation effect by non-radiation factors, in particular by the major lifestyle/environmental/medical risk factors and latent period.
METHODS
We assessed effects of confounding by lifestyle/environmental/medical risk factors on radiation-associated CVD and investigated evidence for modifying effects of these variables on CVD radiation dose-response, using data assembled for a recent systematic review.
RESULTS
There are 43 epidemiologic studies which are informative on effects of adjustment for confounding or risk modifying factors on radiation-associated CVD. Of these 22 were studies of groups exposed to substantial doses of medical radiation for therapy or diagnosis. The remaining 21 studies were of groups exposed at much lower levels of dose and/or dose rate. Only four studies suggest substantial effects of adjustment for lifestyle/environmental/medical risk factors on radiation risk of CVD; however, there were also substantial uncertainties in the estimates in all of these studies. There are fewer suggestions of effects that modify the radiation dose response; only two studies, both at lower levels of dose, report the most serious level of modifying effect.
CONCLUSIONS
There are still large uncertainties about confounding factors or lifestyle/environmental/medical variables that may influence radiation-associated CVD, although indications are that there are not many studies in which there are substantial confounding effects of these risk factors.
Topics: Humans; Cardiovascular Diseases; Confounding Factors, Epidemiologic; Environmental Exposure; Life Style; Risk Factors
PubMed: 38879521
DOI: 10.1186/s12889-024-18701-9 -
Journal of Clinical Epidemiology Jun 2024Observational cohort studies are used to evaluate the effectiveness of screening mammography in women offered screening. Because screening mammography has no effect on...
OBJECTIVE
Observational cohort studies are used to evaluate the effectiveness of screening mammography in women offered screening. Because screening mammography has no effect on causes of death other than breast cancer, cohort studies should show reductions in the risk of breast cancer death substantially greater than possible reductions in the risk of all cause death. We assessed the risk of breast cancer death and of all-cause (or of non-breast cancer) death associated with screening mammography attendance reported in cohort studies.
STUDY DESIGN AND SETTING
Cohort studies published from 2002 to 2022 on women invited to screening mammography were searched in PubMed, Web of Sciences, Scopus and in review articles. Random effect meta-analyses were performed using relative risks of death between women who attended screening compared to women who did not attend screening.
RESULTS
Eighteen cohort studies were identified, nine that reported relative risks of breast cancer death only, five that reported relative risks of all cause death only, and four that reported relative risks for both breast cancer death and all cause death. The latter four cohort studies reported 12 to 76 times more all-cause deaths than breast cancer deaths. The random-effect summary relative risk for breast cancer mortality in screening attenders vs. nonattenders was 0.55 (95% CI: 0.50-0.60) in 13 cohort studies. The summary relative risk for all-cause mortality was 0.54 (0.50-0.58) in 10 cohort studies. In the four cohort studies that evaluated both outcomes, the summary relative risks were 0.63 (0.43-0.83) for breast cancer mortality and of 0.54 (0.44-0.64) for all-cause mortality.
CONCLUSION
The similar relative reductions in breast- and all-cause (or non-breast cancer) mortality indicates that screening mammography attendance is an indicator of characteristics associated with a lower risk of dying from any cause, including from breast cancer, which observational studies have falsely interpreted as a screening effect.
PubMed: 38878837
DOI: 10.1016/j.jclinepi.2024.111426 -
European Journal of Radiology Jun 2024Laryngeal and Hypopharyngeal Carcinomas (LC/HPC) constitute about 24 % of head and neck cancers, causing more than 90,000 annual deaths worldwide. Diffusion-Weighted... (Review)
Review
The clinical utility of diffusion-weighted imaging in diagnosing and predicting treatment response of laryngeal and hypopharyngeal carcinoma: A systematic review and meta-analysis.
PURPOSE
Laryngeal and Hypopharyngeal Carcinomas (LC/HPC) constitute about 24 % of head and neck cancers, causing more than 90,000 annual deaths worldwide. Diffusion-Weighted Imaging (DWI), is currently widely studied in oncologic imaging and can aid in distinguishing cellular tumors from other tissues. Our objective was to review the effectiveness of DWI in three areas: diagnosing, predicting prognosis, and predicting treatment response in patients with LC/HPC.
METHODS
A systematic search was conducted in PubMed, Web of Science, and Embase. A meta-analysis by calculating Standardized Mean Difference (SMD) and 95 % Confidence Interval (CI) was conducted on diagnostic studies.
RESULTS
A total of 16 studies were included. All diagnostic studies (n = 9) were able to differentiate between the LC/HPC and other benign laryngeal/hypopharyngeal lesions. These studies found that LC/HPC had lower Apparent Diffusion Coefficient (ADC) values than non-cancerous lesions. Our meta-analysis of 7 diagnostic studies, that provided ADC values of malignant and non-malignant tissues, demonstrated significantly lower ADC values in LC/HPC compared to non-malignant lesions (SMD = -1.71, 95 %CI: [-2.00, -1.42], ADC cut-off = 1.2 × 10 mm/s). Furthermore, among the studies predicting prognosis, 67 % (4/6) accurately predicted outcomes based on pretreatment ADC values. Similarly, among studies predicting treatment response, 50 % (2/4) successfully predicted outcomes based on pretreatment ADC values. Overall, the studies that looked at prognosis or treatment response in LC/HPC found a positive correlation between pretreatment ADC values in larynx/hypopharynx and favorable outcomes.
CONCLUSION
DWI aids significantly in the LC/HPC diagnosis. However, further research is needed to establish DWI's reliability in predicting prognosis and treatment response in patients with LC/HPC.
PubMed: 38878501
DOI: 10.1016/j.ejrad.2024.111550 -
BMJ Mental Health Jun 2024To describe the pattern of the prevalence of mental health problems during the first year of the COVID-19 pandemic and examine the impact of containment measures on... (Meta-Analysis)
Meta-Analysis
AIM
To describe the pattern of the prevalence of mental health problems during the first year of the COVID-19 pandemic and examine the impact of containment measures on these trends.
METHODS
We identified articles published until 30 August 2021 that reported the prevalence of mental health problems in the general population at two or more time points. A crowd of 114 reviewers extracted data on prevalence, study and participant characteristics. We collected information on the number of days since the first SARS-CoV-2 infection in the study country, the stringency of containment measures and the number of cases and deaths. We synthesised changes in prevalence during the pandemic using a random-effects model. We used dose-response meta-analysis to evaluate the trajectory of the changes in mental health problems.
RESULTS
We included 41 studies for 7 mental health conditions. The average odds of symptoms increased during the pandemic (mean OR ranging from 1.23 to 2.08). Heterogeneity was very large and could not be explained by differences in participants or study characteristics. Average odds of psychological distress, depression and anxiety increased during the first 2 months of the pandemic, with increased stringency of the measures, reported infections and deaths. The confidence in the evidence was low to very low.
CONCLUSIONS
We observed an initial increase in the average risk of psychological distress, depression-related and anxiety-related problems during the first 2 months of the pandemic. However, large heterogeneity suggests that different populations had different responses to the challenges imposed by the pandemic.
Topics: Humans; COVID-19; Prevalence; Mental Disorders; SARS-CoV-2; Pandemics; Anxiety; Mental Health; Depression
PubMed: 38876492
DOI: 10.1136/bmjment-2024-301018 -
Journal of the American Heart... Jun 2024Sinus venosus atrial septal defect (SVASD) is a rare congenital cardiac anomaly comprising 5% to 10% of all atrial septal defects. Although surgical closure is the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Sinus venosus atrial septal defect (SVASD) is a rare congenital cardiac anomaly comprising 5% to 10% of all atrial septal defects. Although surgical closure is the standard treatment for SVASD, data on outcomes have been confined to small cohorts. Thus, we conducted a systematic review of the outcomes of SVASD repair.
METHODS AND RESULTS
The primary outcome was death. Secondary outcomes encompassed atrial fibrillation, sinus node dysfunction, pacemaker insertion, cerebrovascular accident, reoperation, residual septal defect, superior vena cava obstruction, and reimplanted pulmonary vein obstruction. Pooled incidences of outcomes were calculated using a random-effects model. Forty studies involving 1320 patients who underwent SVASD repair were included. The majority were male patients (55.4%), with 88.0% presenting with associated anomalous pulmonary venous connection. The weighted mean age was 18.6±12.5 years, and the overall weighted mean follow-up period was 8.6±10.4 years. The in-hospital mortality rate was 0.24%, with a 30-day mortality rate of 0.5% reported in 780 patients. Incidences of atrial fibrillation, sinus node dysfunction, pacemaker insertion, and cerebrovascular accident over the long-term follow-up were 3.3% (2.18%-4.93%), 6.5% (5.09%-8.2%), 2.23% (1.34%-3.57%), and 2.03% (0.89%-2.46%) respectively. Reoperation occurred in 1.36% (0.68%-2.42%) of surgeries, residual septal defect in 1.34% (0.69%-2.42%), superior vena cava obstruction in 1.76% (1.02%-2.9%), and reimplanted pulmonary vein obstruction in 1.4% (0.7%-2.49%).
CONCLUSIONS
This is the first comprehensive analysis of outcomes following surgical repair of SVASD. The findings affirm the safety and effectiveness of surgery, establishing a reference point for evaluating emerging transcatheter therapies. Safety and efficacy profiles comparable to surgical repair are essential for widespread adoption of transcatheter treatments.
Topics: Humans; Heart Septal Defects, Atrial; Treatment Outcome; Cardiac Surgical Procedures; Postoperative Complications; Male; Adolescent; Young Adult; Female; Child; Hospital Mortality; Adult
PubMed: 38874063
DOI: 10.1161/JAHA.123.033686 -
Renal Failure Dec 2024This study aimed to investigate the efficacy and safety of sacubitril/valsartan in abnormal renal function (eGFR < 60 ml/min/1.73m) patients combined with heart... (Meta-Analysis)
Meta-Analysis Review
AIMS
This study aimed to investigate the efficacy and safety of sacubitril/valsartan in abnormal renal function (eGFR < 60 ml/min/1.73m) patients combined with heart failure based on randomized controlled trials (RCTs) and observational studies.
METHODS
The Embase, PubMed and the Cochrane Library were searched for relevant studies from inception to December 2023. Dichotomous variables were described as event counts with the odds ratio (OR) and 95% confidence interval (CI) values. Continuous variables were expressed as mean standard deviation (SD) with 95% CIs.
RESULTS
A total of 6 RCTs and 8 observational studies were included, involving 17335 eGFR below 60 ml/min/1.73m patients combined with heart failure. In terms of efficacy, we analyzed the incidence of cardiovascular events and found that sacubitril/valsartan significantly reduced the risk of cardiovascular death or heart failure hospitalization in chronic kidney disease (CKD) stages 3-5 patients with heart failure (OR: 0.65, 95%CI: 0.54-0.78). Moreover, sacubitril/valsartan prevented the serum creatinine elevation (OR: 0.81, 95%CI: 0.68-0.95), the eGFR decline (OR: 0.83, 95% CI: 0.73-0.95) and the development of end-stage renal disease in this population (OR:0.73, 95%CI:0.60-0.89). As for safety outcomes, we did not find that the rate of hyperkalemia (OR:1.31, 95%CI:0.79-2.17) and hypotension (OR:1.57, 95%CI:0.94-2.62) were increased in sacubitril/valsartan group among CKD stages 3-5 patients with heart failure.
CONCLUSIONS
Our meta-analysis proves that sacubitril/valsartan has a favorable effect on cardiac function without obvious risk of adverse events in abnormal renal function patients combined with heart failure, indicating that sacubitril/valsartan has the potential to become perspective treatment for these patients.
Topics: Valsartan; Humans; Biphenyl Compounds; Aminobutyrates; Drug Combinations; Heart Failure; Tetrazoles; Angiotensin Receptor Antagonists; Glomerular Filtration Rate; Renal Insufficiency, Chronic; Randomized Controlled Trials as Topic; Creatinine
PubMed: 38869007
DOI: 10.1080/0886022X.2024.2349135 -
Stem Cell Research & Therapy Jun 2024Mesenchymal stem cells (MSCs) have emerged as living biodrugs for myocardial repair and regeneration. Recent randomized controlled trials (RCTs) have reported that... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Mesenchymal stem cells (MSCs) have emerged as living biodrugs for myocardial repair and regeneration. Recent randomized controlled trials (RCTs) have reported that MSC-based therapy is safe and effective in heart failure patients; however, its dose-response relationship has yet to be established. We aimed to determine the optimal MSC dose for treating HF patients with reduced ejection fraction (EF) (HFrEF).
METHODS
The preferred reporting items for systematic reviews and meta-analyses (PRISMA) and Cochrane Handbook guidelines were followed. Four databases and registries, i.e., PubMed, EBSCO, clinicaltrials.gov, ICTRP, and other websites, were searched for RCTs. Eleven RCTs with 1098 participants (treatment group, n = 606; control group, n = 492) were selected based on our inclusion/exclusion criteria. Two independent assessors extracted the data and performed quality assessments. The data from all eligible studies were plotted for death, major adverse cardiac events (MACE), left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), and 6-minute walk distance (6-MWD) as safety, efficacy, and performance parameters. For dose-escalation assessment, studies were categorized as low-dose (< 100 million cells) or high-dose (≥ 100 million cells).
RESULTS
MSC-based treatment is safe across low and high doses, with nonsignificant effects. However, low-dose treatment had a more significant protective effect than high-dose treatment. Subgroup analysis revealed the superiority of low-dose treatment in improving LVEF by 3.01% (95% CI; 0.65-5.38%) compared with high-dose treatment (-0.48%; 95% CI; -2.14-1.18). MSC treatment significantly improved the 6-MWD by 26.74 m (95% CI; 3.74-49.74 m) in the low-dose treatment group and by 36.73 m (95% CI; 6.74-66.72 m) in the high-dose treatment group. The exclusion of studies using ADRCs resulted in better safety and a significant improvement in LVEF from low- and high-dose MSC treatment.
CONCLUSION
Low-dose MSC treatment was safe and superior to high-dose treatment in restoring efficacy and functional outcomes in heart failure patients, and further analysis in a larger patient group is warranted.
Topics: Humans; Heart Failure; Randomized Controlled Trials as Topic; Mesenchymal Stem Cell Transplantation; Stroke Volume; Mesenchymal Stem Cells; Ventricular Function, Left
PubMed: 38867306
DOI: 10.1186/s13287-024-03713-4 -
Frontiers in Pharmacology 2024Sacubitril-valsartan has been widely reported for reducing the risk of cardiovascular death and improving left ventricular remodeling in patients with heart failure...
Effect of sacubitril-valsartan on left ventricular remodeling in patients with acute myocardial infarction after primary percutaneous coronary intervention: a systematic review and meta-analysis.
BACKGROUND
Sacubitril-valsartan has been widely reported for reducing the risk of cardiovascular death and improving left ventricular remodeling in patients with heart failure (HF). However, the effect of sacubitril-valsartan in patients with acute myocardial infarction (AMI) remains controversial. Therefore, we conducted this meta-analysis to investigate whether sacubitril-valsartan could reverse left ventricular remodeling and reduce cardiovascular adverse events in AMI patients after primary percutaneous coronary intervention (PPCI).
MATERIALS AND METHODS
Two researchers independently retrieved the relevant literature from PubMed, Embase, The Cochrane Library, China National Knowledge Infrastructure (CNKI), and the Wanfang database. The retrieval time was limited from inception to 1 June 2023. Randomized controlled trials (RCTs) meeting the inclusion criteria were included and analyzed.
RESULTS
In total, 21 RCTs involving 2442 AMI patients who underwent PPCI for revascularization were included in this meta-analysis. The meta-analysis showed that compared with the angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB), sacubitril-valsartan treatment in AMI patients after PPCI significantly reduced left ventricular end-diastolic dimension (LVEDD) (weighted mean difference (WMD) -3.11, 95%CI: -4.05∼-2.16, < 0.001), left ventricular end-diastolic volume (LVEDV) (WMD -7.76, 95%CI: -12.24∼-3.27, = 0.001), left ventricular end-systolic volume (LVESV) (WMD -6.80, 95%CI: -9.45∼-4.15, < 0.001) and left ventricular end-systolic dimension (LVESD) (WMD -2.53, 95%CI: -5.30-0.24, < 0.001). Subgroup analysis according to the dose of sacubitril-valsartan yielded a similar result. Meanwhile, PPCI patients using sacubitril-valsartan therapy showed lower risk of major adverse cardiac events (MACE) (OR = 0.36, 95%CI: 0.28-0.46, < 0.001), myocardial reinfarction (OR = 0.54, 95%CI: 0.30-0.98, = 0.041) and HF (OR = 0.35, 95%CI: 0.26-0.47, < 0.001) without increasing the risk of renal insufficiency, hyperkalemia, or symptomatic hypotension. At the same time, the change of LV ejection fraction (LVEF) (WMD 3.91, 95%CI: 3.41-4.41, < 0.001), 6 min walk test (6MWT) (WMD 43.56, 95%CI: 29.37-57.76, < 0.001) and NT-proBNP level (WMD -130.27, 95%CI: -159.14∼-101.40, < 0.001) were statistically significant.
CONCLUSION
In conclusion, our meta-analysis indicates that compared with ACEI/ARB, sacubitril-valsartan may be superior to reverse left ventricular remodeling, improve cardiac function, and effectively reduce the risk of MACE, myocardial reinfarction, and HF in AMI patients after PPCI during follow-up without increasing the risk of adverse reactions including renal insufficiency, hyperkalemia, and symptomatic hypotension.
PubMed: 38863978
DOI: 10.3389/fphar.2024.1366035