UNASSIGNED: Research examining the bidirectional relationship between C-reactive protein (CRP) and depressive symptoms, while accounting for cumulative effect of repeated episodes of CRP or depressive symptoms, is currently deficient in non-Western populations.
UNASSIGNED: A nationally representative population-based cohort data from the Chinese Health and Retirement Longitudinal Study (CHARLS) was utilized. In bi-directional analysis, we considered both single determinations and two successive determinations of CRP or depressive symptoms. Multivariate logistic regression assessed the association between elevated CRP levels at baseline or repeated episodes of CRP elevations over two successive determinations and subsequent elevated depressive symptoms, and vice versa.
UNASSIGNED: Although single determinations of CRP or depressive symptoms yielded non-significant results in both directions, full multivariate models, adjusting for baseline depressive symptoms, socio-demographic characteristics, health-related behaviors, metabolic measures, and health status, revealed a significantly positive association based on two successive determinations of CRP or depressive symptoms. This significant association was observed between cumulative effects of sustained CRP elevations over two successive determinations (2 vs. 0) and subsequent elevated depressive symptoms (OR=1.58; 95% CI: 1.15 to 2.17) and between cumulative effect of repeated episodes of depression (2 vs. 0) and later elevated CRP (OR=1.26; 95% CI: 1.02 to 1.56). Furthermore, sex-stratified analyses confirmed the robustness of these relationships.
UNASSIGNED: There are bidirectional associations between depressive symptoms and CRP, driven by the cumulative effect of repeated episodes of CRP or depressive symptoms among middle-aged and older Chinese adults. These findings hold significant clinical implications, highlighting the potential of both anti-inflammatory and anti-depression approaches.

Emerging preclinical and clinical studies suggest that altered gut microbiome composition and functions are associated with coronavirus 2019 (COVID- 19) severity and its long-term complications. We hypothesize that COVID-19 outcome is associated with gut microbiome status in population-based settings.
Gut metagenomic data of the adult population consisting of 2871 subjects from 16 countries were obtained from ExperimentHub through R, while the dynamic death data of COVID-19 patients between January 22, 2020 and December 8, 2020 in each country was acquired from Johns Hopkins Coronavirus Resource Center. An adjusted stable mortality rate (SMR) was used to represent these countries\' mortality and correlated with the mean relative abundance (mRA) of healthy adult gut microbiome species.
After excluding bacterial species with low prevalence (prevalence <0.2 in the included countries), the β-diversity was significantly higher in the countries with high SMR when compared with those with median or low SMR (p <0.001). We then identified the mRA of two butyrate producers, Eubacterium rectale and Roseburia intestinalis, that were negatively correlated with SMR during the study period. And the reduction of these species was associated with severer COVID-19 manifestation.
Population-based microbiome signatures with the stable mortality rate of COVID-19 in different countries suggest that altered gut microbiome composition and functions are associated with mortality of COVID-19.

Reduced cancer deaths have led to an increase in the number of cancer survivors and the risk of the second primary tumor. This study explored the surgical outcomes of patients with non-small cell lung cancer as the second primary tumor and the impact of previous extra-pulmonary malignancies. Patients\' data were obtained from Surveillance, Epidemiology and End Results database. The patients were divided into lung surgery and non-surgery groups. Propensity-score matching was used to balance potential confounders. Kaplan-Meier curves were generated to test the overall survival and lung-cancer-specific survival. Cox regression analysis was performed to calculate death risk. In total 3054 lung surgery and 1094 non-surgery patients with stage I-II non-small cell lung cancer as the second primary tumor were included. The surgery group showed longer overall survival (68 vs. 22 months) and lung cancer-specific survival (not reached vs. 37 months) than those of non-surgery groups (both P < 0.001). Patients with previous hormone-dependent malignancies had similar survival rates (overall survival: 22 vs. 20 months, P = 0.666; lung cancer-specific survival: 38 vs. 37 months, P = 0.292) as those with non-hormone dependent malignancies in the non-surgery group. Significantly longer overall survival (90 vs. 60 months, P = 0.001) was observed in patients with hormone-dependent malignancies in the surgery group; however, there was no difference in lung cancer-specific survival (P = 0.225). Competing risk analysis showed that for patients undergoing lung surgery, there was higher previous malignancy-induced mortality in patients with non-hormone dependent malignancies than in patients with hormone-dependent malignancies. However, there was no difference in lung cancer-induced mortality between the two groups. Patients who underwent lobectomy showed longer survival than those who underwent pneumonectomy and other resection types (89, 27.5 and 65 months, P < 0.001). In summary, lung surgery is beneficial for patients with stage I-II non-small cell lung cancer as the second primary tumor after hormone-dependent malignancy resection.

The neonatal period is the most vulnerable period during childhood, with the risk of death being the highest even in developed countries/regions. Hong Kong\'s neonatal mortality (1‰) is among the world\'s lowest and has remained similar for 15 years. This study aimed to explore neonatal deaths in Hong Kong in detail and determine whether neonatal mortality is reducible at such a low level.
Live births in public hospitals in Hong Kong during 01 Jan 2006-31 Dec 2017 were included. Relevant data were extracted from the electronic medical records. Gestational age-specific mortality was calculated, and the trends were analyzed using the Cochran-Armitage trend test. Causes of death were summarized, and risk factors were identified in multivariate logistic regression analysis.
In 490,034 live births, 755 cases (1.54‰) died during the neonatal period, and 293 (0.6‰) died during the post-neonatal period. The neonatal mortality remained similar overall (P = 0.17) and among infants born at 24-29 weeks\' gestation (P = 0.4), while it decreased in those born at 23 (P = 0.04), 30-36 (P < 0.001) and ≥ 37 (P < 0.001) weeks\' gestation. Neonates born at < 27 weeks\' gestation accounted for a significantly increased proportion among cases who died (27.6% to 51.9%), with hemorrhagic conditions (24%) being the leading cause of death. Congenital anomalies were the leading cause of death in neonates born ≥ 27 weeks\' gestation (52%), but its cause-specific mortality decreased (P = 0.002, 0.6‰ to 0.41‰), with most of the decrease attributed to trisomy 13/18 and multiple anomalies.
Reduction of neonatal mortality in developed regions may heavily rely on improved quality of perinatal and neonatal care among extremely preterm infants.

Objectives: To investigate whether there is an elevated neoplasm risk in patients with rheumatic diseases treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Methods: A population-based nested case-control study was performed by retrieving all patients newly diagnosed with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and psoriatic arthritis (PsA) or psoriasis vulgaris (PsO) from the 2000 Longitudinal Health Insurance Database (LHID 2000) in Taiwan. Two hundred and sixty-one patients with neoplasm from 1997 to 2013 were enrolled in this study, and controls were matched in a 1:1 ratio with age, sex, and year of enrollment. Composition of demographic indices, comorbidities, medication usage, and differences in days of prescription of different medications between neoplasm and neoplasm-free (control) groups were compared. Results: Between the control and neoplasm groups, no differences in ratio were observed in the usage of hydroxychloroquine (50.96 vs. 49.04%, p = 0.6616), methotrexate (26.82 vs. 27.59%, p = 0.8441), azathioprine (3.45 vs. 3.07%, p = 0.8052), and cyclophosphamide (1.15 vs. 2.30%, p = 0.3131) from enrollment to index date. Medications within 3 years before the index date in patients that had ≥3 months of comparable duration also showed no difference (hydroxychloroquine: 33.06 vs. 30.25%, p = 0.6404; methotrexate: 20.66 vs. 25.21%, p = 0.4018; azathioprine: 2.48 vs. 2.52%, p = 0.9835; cyclophosphamide: 0.83 vs. 0.84%, p = 0.9906). We also made a subgroup analysis focusing on RA and SLE patients; no difference between control and neoplasm group in both the ratio of usage and days of prescription of hydroxychloroquine, methotrexate, azathioprine, and cyclophosphamide was observed. Conclusion: Neoplasm risk in patients with rheumatic diseases has no correlation with csDMARD usage.

Helicobacter pylori (HP) infection is associated with systemic lupus erythematosus (SLE), but the related results have been controversial. Therefore, this study investigated the association between HP infection and SLE by using a nationwide longitudinal population-based cohort. We identified 41,651 patients with HP infection and 83,302 matched controls between 2000 and 2013 from the Longitudinal Health Insurance Research Database of the National Taiwan Insurance Research Database. Age, gender, comorbidities, and medical visits were matched at a 1:2 ratio by using propensity score analysis. The adjusted hazard ratio (aHR) of SLE was calculated by multiple Cox regression. Furthermore, sensitivity test and stratified analysis were performed. The SLE incidence rate was 1.17 [95% confidence interval (CI): 0.89-1.54] per 100,000 person-months in the HP cohort, and the hazard ratio was 1.63 (95% CI: 1.12-2.37) in comparison with the propensity score-matched control cohort. After multivariate adjustment, patients with HP infection had a significantly high overall aHR (1.58; 95% CI: 1.08-2.30) of SLE. Stratified analysis revealed the aHR of 8.23 (95% CI: 1.77-38.32) in patients <30 years old, and the p for interaction between age and HP infection was 0.039. For age-sex subgroup analysis, the highest aHR was 12.74 (95% CI: 1.55-104.59) in young (aged <30 years) female patients with HP infection. HP infection is associated with a 1.63-fold increased SLE risk, particularly with female patients aged <30 years. Future research is required to elucidate the underlying mechanism of this association.

Background: The actual incidence rate of suicide attempt and the suicide-related fatality rate (completed suicide) in patients with chronic pancreatitis (CP) have not been mentioned in the literature. Methods: We conducted a nationwide population-based cohort study by analyzing data from Taiwan\'s National Health Insurance Research Database (NHIRD) to compare the rate of suicide attempt between a CP cohort and a non-CP cohort. For the study cohort, we identified 17,733 patients (age ≥ 20 years) diagnosed as having CP between 2000 and 2010 from the NHIRD in Taiwan. Beneficiaries with no history of CP were matched with the study cohort at a 2:1 ratio according to age, sex, and index date. To determine the incidence of suicide, all patients were followed until the end of 2011 or until their withdrawal from the Taiwan National Health Insurance program. Results: Patients with CP had an increased risk of suicide attempt, compared with those without CP (adjusted hazard ratio [aHR] = 2.72, 95% confidence interval [CI] = 1.69-4.37). The suicide-related fatality in the CP cohort was higher than that in the non-CP cohort, but the difference was not statistically significant (aHR = 1.21, 95% CI = 0.39-3.78). Conclusion: Our population-based cohort study reveals a close association between CP and subsequent suicide attempt. Compared with the non-CP cohort, the suicide-related fatality was higher in the CP cohort, although the result was not statistically significant. These findings necessitate surveying patients with CP and providing psychological support to prevent suicide.

BACKGROUND: Preeclampsia is a possible risk factor for childhood asthma in the offspring. Our aim was to find whether preeclampsia is associated with childhood asthma. We also aimed to study whether a possible association can be explained by factors shared by siblings.
METHODS: All eligible live singletons born in Denmark during 1993-2007 were identified (N = 923,533), and the occurrence of preeclampsia during the index pregnancy was determined. The children were followed from their 3rd birthday to the first hospitalization, outpatient contact or prescription for asthma, emigration, death, their 18th birthday, or the end of 2010, whichever came first. We carried out a nested case-control and a case-sibling study with density sampling to estimate incidence rate ratio (IRR) of asthma as a function of maternal preeclampsia, using conditional logistic regression.
RESULTS: A total of 115,522 asthma cases were identified during 1996-2010. In the case-control analysis, the overall IRR of asthma for those exposed to maternal preeclampsia was 1.19 (95% confidence interval (CI): 1.15, 1.24). The IRRs for asthma according to early and late onset preeclampsia were 1.88 (95% CI: 1.67, 2.11) and 1.14 (95% CI: 1.10, 1.19). In the case-sibling analysis, the corresponding IRRs were 1.06 (95% CI: 0.98, 1.14), 1.15 (95% CI: 1.02, 1.29), and 1.02 (95% CI: 0.93, 1.11), respectively.
CONCLUSIONS: Early onset preeclampsia was associated with an increased risk of asthma in the offspring, but part of this association may be due to confounding by factors shared by siblings.