BACKGROUND: Comparative studies on surgical treatments with time-to-event endpoints have provided substantial evidence for clinical practice, but the accurate use of survival data analysis and the control of confounding bias remain big challenges.
METHODS: This was a survey of surgical studies with survival outcomes published in four general medical journals and five general surgical journals in 2021. The two most concerned statistical issues were evaluated, including confounding control by propensity score analysis (PSA) or multivariable analysis and testing of proportional hazards (PH) assumption in Cox model.
RESULTS: A total of 74 studies were included, comprising 63 observational studies and 11 randomized controlled trials. Among the observational studies, the proportion of studies utilizing PSA in surgical oncology and non-oncology studies was similar (40.9 % versus 36.8 %, P = 0.762). However, the former reported a significantly lower proportion of PH assumption assessments compared to the latter (13.6 % versus 42.1 %, P = 0.020). Twenty-five observational studies (25/63) used PSA methods, but two-thirds of them (17/25) showed unclear balance of baseline data after PSA. And the proportion of PH assumption testing after PSA was slightly lower than that before PSA, but the difference was not statistically significant (24.0 % versus 28.0 %, P = 0.317). Comprehensive suggestions were given on confounding control in survival analysis and alternative resolutions for non-compliance with PH assumption.
CONCLUSIONS: This study highlights suboptimal reporting of PH assumption evaluation in observational surgical studies both before and after PSA. Efforts and consensus are needed with respect to the underlying assumptions of statistical methods.

UNASSIGNED: This study aimed to investigate the efficacy and safety of sacubitril/valsartan in abnormal renal function (eGFR < 60 ml/min/1.73m2) patients combined with heart failure based on randomized controlled trials (RCTs) and observational studies.
UNASSIGNED: 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.
UNASSIGNED: A total of 6 RCTs and 8 observational studies were included, involving 17335 eGFR below 60 ml/min/1.73m2 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.
UNASSIGNED: 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.

BACKGROUND: Hepatocellular carcinoma (HCC) is a disease demonstrating increasing morbidity and mortality, especially in patients with chronic viral hepatitis. Studies have shown that aspirin can reduce the incidence of liver cancer; however, the degree of benefit in patients with viral hepatitis is unclear. This study focused on the association between aspirin use and HCC risk in patients with chronic viral hepatitis.
METHODS: A systematic search of the PubMed, Embase, Web of Science, and Cochrane Library databases was performed from the earliest available date to December 16, 2023. The primary outcome was HCC incidence, and the secondary outcome was gastrointestinal bleeding. The results were expressed as hazard ratios (HRs) and 95% confidence intervals (CIs). Meta-analyses were performed by using random or fixed-effects models based on the heterogeneity assessed via the I2 statistic.
RESULTS: A total of 13 articles (303,414 participants and 14,423 HCC patients) were included in the analysis. The incidence of HCC in aspirin users was lower than that in non-aspirin users (HR 0.75; 95% CI, 0.68-0.83; P < 0.001; I2 = 90.0%). Subgroup analysis further showed that this effect may be more obvious in HCV patients, non-cirrhotic patients, patients with statins, and long-term aspirin users, but it may have the risk of gastrointestinal bleeding (HR 1.13; 95% CI, 1.07-1.20; P = 0.906; I2 = 0.0%).
CONCLUSIONS: Our meta-analysis shows that in patients with chronic viral hepatitis, aspirin use is associated with a significantly reduced risk of liver cancer, but attention should be paid to the possible risk of gastrointestinal bleeding, and this conclusion needs further validation in the future.

Recently, there has been a growing interest in variable selection for causal inference within the context of high-dimensional data. However, when the outcome exhibits a skewed distribution, ensuring the accuracy of variable selection and causal effect estimation might be challenging. Here, we introduce the generalized median adaptive lasso (GMAL) for covariate selection to achieve an accurate estimation of causal effect even when the outcome follows skewed distributions. A distinctive feature of our proposed method is that we utilize a linear median regression model for constructing penalty weights, thereby maintaining the accuracy of variable selection and causal effect estimation even when the outcome presents extremely skewed distributions. Simulation results showed that our proposed method performs comparably to existing methods in variable selection when the outcome follows a symmetric distribution. Besides, the proposed method exhibited obvious superiority over the existing methods when the outcome follows a skewed distribution. Meanwhile, our proposed method consistently outperformed the existing methods in causal estimation, as indicated by smaller root-mean-square error. We also utilized the GMAL method on a deoxyribonucleic acid methylation dataset from the Alzheimer\'s disease (AD) neuroimaging initiative database to investigate the association between cerebrospinal fluid tau protein levels and the severity of AD.

To identify and summarize the presence and characteristics of dental patient-reported outcomes (dPROs) and dental patient-reported outcome measures (dPROMs) within comparative observational studies published in 5 leading orthodontic journals.
Electronic searching was performed to identify intervention (therapeutic or preventive) related comparative observational studies published in selected journals between 2015 and 2021. Two authors extracted the characteristics of each included study independently and in duplicate and summarized the dPROs and dPROMs used in these studies. All dPROs were classified into 2 general types (oral health-related quality of life [OHRQoL] and others), while dPROMs were divided into 3 categories (single-item questionnaires, generic multiple-item questionnaires, and specific multiple-item questionnaires). In addition, dPROMs were examined, if they evaluated the 4 dimensions of OHRQoL (oral function, orofacial pain, orofacial appearance, and psychosocial impact).
A total of 683 observational studies were eligible and included of which 117 (17.1%) used dPROs and dPROMs. Seven different dPROs (OHRQoL, patients\' satisfaction with treatment, preferences, concerns, compliance, duration, and unwanted events) and 33 different dPROMs (including 8 single-item questionnaires, 11 generic multiple-item questionnaires, and 14 specific multiple-item questionnaires) were identified in these studies. OHRQoL was the most commonly used dPRO (92/117, 78.6%), while Oral Health Impact Profile 14 (OHIP-14) was the most frequently used dPROM (20/92, 21.7%). In terms of study design, cross-sectional studies had the highest proportion of dPRO usage (62/148, 41.9%), followed by cohort studies (63/505, 12.5%) and case-control studies (1/30, 3.3%).
Only one-sixth of comparative observational studies published in leading orthodontic journals could reflect patients\' perspectives. Observational studies in orthodontics need to provide more patient-important information through the use of dPROs and dPROMs.

BACKGROUND: The association between antihypertensive medication and schizophrenia has received increasing attention; however, evidence of the impact of antihypertensive medication on subsequent schizophrenia based on large-scale observational studies is limited. We aimed to compare the schizophrenia risk in large claims-based US and Korea cohort of patients with hypertension using angiotensin-converting enzyme (ACE) inhibitors versus those using angiotensin receptor blockers (ARBs) or thiazide diuretics.
METHODS: Adults aged 18 years who were newly diagnosed with hypertension and received ACE inhibitors, ARBs, or thiazide diuretics as first-line antihypertensive medications were included. The study population was sub-grouped based on age (> 45 years). The comparison groups were matched using a large-scale propensity score (PS)-matching algorithm. The primary endpoint was incidence of schizophrenia.
RESULTS: 5,907,522; 2,923,423; and 1,971,549 patients used ACE inhibitors, ARBs, and thiazide diuretics, respectively. After PS matching, the risk of schizophrenia was not significantly different among the groups (ACE inhibitor vs. ARB: summary hazard ratio [HR] 1.15 [95% confidence interval, CI, 0.99-1.33]; ACE inhibitor vs. thiazide diuretics: summary HR 0.91 [95% CI, 0.78-1.07]). In the older subgroup, there was no significant difference between ACE inhibitors and thiazide diuretics (summary HR, 0.91 [95% CI, 0.71-1.16]). The risk for schizophrenia was significantly higher in the ACE inhibitor group than in the ARB group (summary HR, 1.23 [95% CI, 1.05-1.43]).
CONCLUSIONS: The risk of schizophrenia was not significantly different between the ACE inhibitor vs. ARB and ACE inhibitor vs. thiazide diuretic groups. Further investigations are needed to determine the risk of schizophrenia associated with antihypertensive drugs, especially in people aged > 45 years.

Objective: It remains unclear whether sleep apnea (SA) is associated with tinnitus in adults. Based on a systematic review and meta-analysis of observational studies, we investigated the association between SA and tinnitus in adult population. Methods: Observational studies relevant to our research were identified by searching PubMed, Embase, Web of Science, Wanfang, and China National Knowledge Infrastructure databases. Random-effects models were used when significant heterogeneity was observed; otherwise, fixed-effects models were used. Results: Eight case-control or cross-sectional studies, including 132,292 adults were included, and 1556 of them had SA. It was shown that SA was related to a higher prevalence of tinnitus (odds ratio [OR]: 1.65, 95% confidence interval: 1.14-2.39, P < .001) with moderate heterogeneity (P for Cochrane Q test = 0.04, I2 = 53%). Seven studies reported the association between obstructive SA and tinnitus, while the other one study reported the association between overall SA and tinnitus. Subgroup analyses showed that the association was not significant for mild (OR: 1.80, P = .17) or moderate (OR: 1.25, P = .53), but significant for severe SA (OR: 2.25, P = .008). In addition, the association between SA and tinnitus seemed to be stronger in studies from Italy or United States as compared to those from China (OR: 2.91 vs 1.35, P for subgroup difference = .02). The association was not significantly affected by study design, mean age, proportion of men, methods for diagnosis of SA, and controlling of age and sex (P for subgroup difference all > .05). Conclusion: Severe SA may be related to tinnitus in adults.

OBJECTIVE: The relationship between circulating 25-hydroxyvitamin D [25(OH)D] and pancreatic cancer has been well studied but remains unclear. The purpose of this study was to elucidate the association between circulating 25(OH)D and pancreatic cancer by using a meta-analytic approach.
METHODS: PubMed, Embase, and Wed of Science databases were searched through October 15, 2022. A random or fixed-effects model was used to estimate the pooled odds ratio (OR), risk ratio (RR), hazard ratio (HR) and their 95% confidence intervals (CIs).
RESULTS: A total of 16 studies including 529,917 participants met the inclusion criteria, of which 10 reported incidence and 6 reported mortality. For the highest versus lowest categories of circulating 25(OH)D, the pooled OR of pancreatic cancer incidence in case-control studies was 0.98 (95% CI 0.69-1.27), and the pooled HRs of pancreatic cancer mortality in cohort and case-control studies were 0.64 (95% CI 0.45-0.82) and 0.78 (95% CI 0.62-0.95), respectively. The leave-one-out sensitivity analyses found no outliers and Galbraith plots indicated no substantial heterogeneity.
CONCLUSIONS: Evidence from this meta-analysis suggested that high circulating 25(OH)D levels may be associated with decreased mortality but not incidence of pancreatic cancer. Our findings may provide some clues for the treatment of pancreatic cancer and remind us to be cautious about widespread vitamin D supplementation for the prevention of pancreatic cancer.

OBJECTIVE: An overrepresentation of epilepsy has been suggested in patients with type 1 diabetes (T1D). This meta-analysis was conducted to evaluate if type 1 diabetes is associated with a higher incidence of epilepsy.
METHODS: Longitudinal observational studies which are relevant to the purpose of the meta-analysis were screened and obtained by searching PubMed, Embase, and Web of Science databases. Random-effects models were used when significant heterogeneity was observed; otherwise, fixed-effects models were used.
RESULTS: Six observational studies involving 10 datasets of 8,001,899 participants were included, with six datasets including children and only one dataset including older people. Among them, 100,414 (1.25%) had type 1 diabetes. During the follow-up duration of 5.4-15.2 years (mean: 9.5 years), 98,644 cases (1.23%) of epilepsy were observed. Compared with participants with normoglycemia, those with type 1 diabetes were shown to have a higher incidence of epilepsy (risk ratio [RR]: 2.41, 95% confidence interval 1.69-3.44, P < 0.001; I2  = 95%) after adjustment of potential confounding variables including age and sex. Subgroup analysis showed consistent results in nested case-control and retrospective cohort studies, and in studies of children, non-elderly adult, and older participants (P for subgroup difference = 0.42 and 0.07). In addition, a stronger association of type 1 diabetes and epilepsy was suggested in studies with follow-up duration <10 years compared with those ≥10 years (RR: 3.34 vs 1.61, P for subgroup difference < 0.001).
CONCLUSIONS: Patients with type 1 diabetes may have a higher risk of epilepsy, which was mainly driven by datasets including children.

OBJECTIVE: Studies have shown an association between eosinophilia and clinical outcomes in acute exacerbation of chronic obstructive pulmonary disease (AECOPD). However, contradictory findings exist. Our study aims to systematically evaluate the association between elevated peripheral blood eosinophils and clinical outcome of patients with AECOPD.
METHODS: An electronic search was conducted for relevant studies published from database inception to February 28, 2023, on PubMed, EMBASE, Cochrane Library, and Web of Science. The analysis covered studies on the correlation between EOS AECOPD and mortality, hospital stay duration, readmission and hospitalization rates, and invasive mechanical ventilation. Where applicable, relative risk (RR) and weighted mean difference (WMD) were extracted, pooled, and assessed using meta-analysis. Sensitivity analysis was performed to explore the source of heterogeneity.
RESULTS: Fifteen high-quality studies including 14 cohort studies and one case-control study were included in the meta-analysis. Compared with non-eosinophilic AECOPD patients, those with eosinophilic AECOPD had a lower risk of mortality (RR = 0.65, 95 % confidence interval [CI] 0.54, 0.77, P < 0.001), shorter length of hospital stay (WMD = -1.56, 95%CI -2.16, -0.96, P < 0.001), and higher readmission rate (RR = 1.07, 95%CI 1.01,1.13, P = 0.029). No difference was found concerning the rate of hospitalization and invasive mechanical ventilation between the two groups.
CONCLUSIONS: Individuals diagnosed with eosinophilic AECOPD had a reduced mortality rate, a truncated period of hospitalization, and an insubstantial increase in the probability of readmission relative to their non-eosinophilic AECOPD counterparts. The level of eosinophils in blood has been shown to serve as a potential predictive biomarker for AECOPD patients.