Association between chronic viral infection-related hospitalization and risk of cardiovascular disease: A population-based cohort study.

Chronic viral infection induces immunosenescence and systemic low-grade inflammation, leading to worsened long-term outcomes. We sought to explore the short- and long-term effects of chronic viral infection on cardiovascular disease (CVD). Based on UK Biobank data, exposed group was identified as individuals who had chronic virus infection-related hospitalization (IRH). Unexposed group was randomly selected, matched by 5-year age interval, sex, and Charlson comorbidity index at a ratio up to 1:10. Restricted cubic splines were used to model time-varying effects of IRH in nonproportional Cox models. A cut-off value of 5 years was recorded and used in piecewise Cox proportional hazards models as we estimated short- and long-term effects of IRH on CVD. A total of 2826 exposed participants and 28 212 matched unexposed participants were included. Chronic viral IRH was associated with increased risk of CVD (0-5 years: hazard ratio, 1.57 [95% confidence interval: 1.32, 1.87] and 5+ years: 1.31 [1.06, 1.61]). Elevated risk of stroke was only observed within the initial 5-year follow-up (0-5 years: 1.91 [1.30, 2.81]). The short- and long-term associations were observed in herpes or hepatitis virus IRH with risk of CVD (all p < 0.05). Subgroup analysis revealed long-term association between chronic viral IRH and CVD among female (5+ years: 1.68 [1.27, 2.22]) but not among male. The association between chronic viral infection and elevated CVD risk appeared to be stronger among individuals who did not take cholesterol-lowering medication, antithrombotic medication, or certain antihypertensive medications (all p for interaction < 0.05). The risk of CVD event remained persistently higher within and over 5 years following chronic viral IRH, especially in individuals infected with herpes and hepatitis virus.

House dust mite SCIT reduces asthma risk and significantly improves long-term rhinitis and asthma control-A RWE study.

BACKGROUND: The German Therapy Allergen Ordinance (TAO) triggered an ongoing upheaval in the market for house dust mite (HDM) allergen immunotherapy (AIT) products. Three HDM subcutaneous AIT (SCIT) products hold approval in Germany and therefore will be available after the scheduled completion of the TAO procedure in 2026. In general, data from clinical trials on the long-term effectiveness of HDM AIT are rare. We evaluated real-world data (RWD) in a retrospective, observational cohort study based on a longitudinal claims database including 60% of all German statutory healthcare prescriptions to show the long-term effectiveness of one of these products in daily life. Aim of this analysis was to provide a per product analysis on effectiveness of mite AIT as it is demanded by international guidelines on AIT. METHODS: Subjects between 5 and 70 years receiving their first (index) prescription of SCIT with a native HDM product (SCIT group) between 2009 and 2013 were included. The exactly 3:1 matched control group received prescriptions for only symptomatic AR medication (non-AIT group); the evaluation period for up to 6 years of follow-up ended in February 2017. Study endpoints were the progression of allergic rhinitis (AR) and asthma, asthma occurrence and time to the onset of asthma after at least 2 treatment years. RESULTS: In total, 892 subjects (608 adults and 284 children/adolescents) were included in the SCIT group and 2676 subjects (1824 adults and 852 children/adolescents) in the non-AIT group. During the follow-up period after at least 2 years of SCIT, the number of prescriptions in the SCIT group was reduced by 62.8% (p < .0001) for AR medication and by 42.4% for asthma medication (p = .0003). New-onset asthma risk was significantly reduced in the SCIT vs non-AIT group by 27.0% (p = .0212). The asthma-preventive effect of SCIT occurred 15 months after start of the treatment. In the SCIT group, the time to onset of asthma was prolonged compared to the non-AIT group (p = .0010). CONCLUSION: In this first product based RWD analysis on SCIT with a native HDM product, patients aged 5 to 70 years benefited from AIT in the long term in terms of reduced progression of AR and asthma after at least 2 years of treatment. The effects seemed to last for up to 6 years after treatment termination. A significantly reduced risk of asthma onset was observed, starting after 15 months of treatment.

Differential decline of SARS-CoV-2-specific antibody levels, innate and adaptive immune cells, and shift of Th1/inflammatory to Th2 serum cytokine levels long after first COVID-19.

BACKGROUND: SARS-CoV-2 has triggered a pandemic and contributes to long-lasting morbidity. Several studies have investigated immediate cellular and humoral immune responses during acute infection. However, little is known about long-term effects of COVID-19 on the immune system. METHODS: We performed a longitudinal investigation of cellular and humoral immune parameters in 106 non-vaccinated subjects ten weeks (10 w) and ten months (10 m) after their first SARS-CoV-2 infection. Peripheral blood immune cells were analyzed by multiparametric flow cytometry, serum cytokines were examined by multiplex technology. Antibodies specific for the Spike protein (S), the receptor-binding domain (RBD) and the nucleocapsid protein (NC) were determined. All parameters measured 10 w and 10 m after infection were compared with those of a matched, noninfected control group (n = 98). RESULTS: Whole blood flow cytometric analyses revealed that 10 m after COVID-19, convalescent patients compared to controls had reduced absolute granulocyte, monocyte, and lymphocyte counts, involving T, B, and NK cells, in particular CD3+CD45RA+CD62L+CD31+ recent thymic emigrant T cells and non-class-switched CD19+IgD+CD27+ memory B cells. Cellular changes were associated with a reversal from Th1- to Th2-dominated serum cytokine patterns. Strong declines of NC- and S-specific antibody levels were associated with younger age (by 10.3 years, p < .01) and fewer CD3-CD56+ NK and CD19+CD27+ B memory cells. Changes of T-cell subsets at 10 m such as normalization of effector and Treg numbers, decline of RTE, and increase of central memory T cell numbers were independent of antibody decline pattern. CONCLUSIONS: COVID-19 causes long-term reduction of innate and adaptive immune cells which is associated with a Th2 serum cytokine profile. This may provide an immunological mechanism for long-term sequelae after COVID-19.

Vitamin D deficiency and effect of treatment on seizure frequency and quality of life parameters in patients with drug-resistant epilepsy: A randomized clinical trial.

OBJECTIVE: This study was undertaken to assess the effect of treatment of vitamin D deficiency in drug-resistant epilepsy. METHODS: We conducted a multicenter, double-blind, placebo-controlled, randomized clinical trial, including patients aged ≥15 years with drug-resistant focal or generalized epilepsy. Patients with 25-hydroxyvitamin D (25[OH]D) < 30 ng/mL were randomized to an experimental group (EG) receiving vitamin D3 (cholecalciferol, 100 000 IU, five doses in 3 months) or a control group (CG) receiving matched placebo. During the open-label study, EG patients received 100 000 IU/month for 6 months, whereas CG patients received five doses in 3 months then 1/month for 3 months. Monitoring included seizure frequency (SF), 25(OH)D, calcium, albumin, creatinine assays, and standardized scales for fatigue, anxiety-depression, and quality of life (Modified Fatigue Impact Scale [M-FIS], Hospital Anxiety and Depression Scale, Quality of Life in Epilepsy [QOLIE-31]) at 3, 6, and 12 months. The primary efficacy outcome was the percentage of SF reduction compared to the reference period and CG at 3 months. Secondary outcomes were SF and bilateral tonic-clonic seizure (BTCS) reduction, scale score changes, and correlations with 25(OH)D during the follow-up. RESULTS: Eighty-eight patients were enrolled in the study (56 females, aged 17-74 years), with median baseline SF per 3 months = 16.5 and ≥2 antiseizure medications in 88.6%. In 75 patients (85%), 25(OH)D was <30 ng/mL; 40 of them were randomly assigned to EG and 34 to CG. After the 3-month blinded period, SF reduction did not significantly differ between groups. However, during the open-label period, SF significantly decreased (30% median SF reduction, 33% responder rate at 12 months). BTCSs were reduced by 52%. M-FIS and QOLIE-31 scores were significantly improved at the whole group level. SF reduction correlated with 25(OH)D > 30 ng/mL for >6 months. SIGNIFICANCE: Despite no proven effect after the 3-month blinded period, the open-label study suggests that long-term vitamin D3 supplementation with optimal 25(OH)D may reduce SF and BTCSs, with a positive effect on fatigue and quality of life. These findings need to be confirmed by further long-term studies. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03475225 (03-22-2018).

Potential impact of blood cholesterol guidelines on statin treatment in the U.S. population using interrupted time series analysis.

BACKGROUND: The 2013 ACC/AHA Guideline was a paradigm shift in lipid management and identified the four statin-benefit groups. Many have studied the guideline's potential impact, but few have investigated its potential long-term impact on MACE. Furthermore, most studies also ignored the confounding effect from the earlier release of generic atorvastatin in Dec 2011. METHODS: To evaluate the potential (long-term) impact of the 2013 ACC/AHA Guideline release in Nov 2013 in the U.S., we investigated the association of the 2013 ACC/AHA Guideline with the trend changes in 5-Year MACE survival and three other statin-related outcomes (statin use, optimal statin use, and statin adherence) while controlling for generic atorvastatin availability using interrupted time series analysis, called the Chow's test. Specifically, we conducted a retrospective study using U.S. nationwide de-identified claims and electronic health records from Optum Labs Database Warehouse (OLDW) to follow the trends of 5-Year MACE survival and statin-related outcomes among four statin-benefit groups that were identified in the 2013 ACC/AHA Guideline. Then, Chow's test was used to discern trend changes between generic atorvastatin availability and guideline potential impact. RESULTS: 197,021 patients were included (ASCVD: 19,060; High-LDL: 33,907; Diabetes: 138,159; High-ASCVD-Risk: 5,895). After the guideline release, the long-term trend (slope) of 5-Year MACE Survival for the Diabetes group improved significantly (P = 0.002). Optimal statin use for the ASCVD group also showed immediate improvement (intercept) and long-term positive changes (slope) after the release (P < 0.001). Statin uses did not have significant trend changes and statin adherence remained unchanged in all statin-benefit groups. Although no other statistically significant trend changes were found, overall positive trend change or no changes were observed after the 2013 ACC/AHA Guideline release. CONCLUSIONS: The 2013 ACA/AHA Guideline release is associated with trend improvements in the long-term MACE Survival for Diabetes group and optimal statin use for ASCVD group. These significant associations might indicate a potential positive long-term impact of the 2013 ACA/AHA Guideline on better health outcomes for primary prevention groups and an immediate potential impact on statin prescribing behaviors in higher-at-risk groups. However, further investigation is required to confirm the causal effect of the 2013 ACA/AHA Guideline.

Obesity as an independent risk factor for poor long-term outcome after mid-urethral sling surgery.

INTRODUCTION: High body mass index (BMI) is a risk-factor for stress urinary incontinence (SUI). Mid-urethral sling (MUS) surgery is an effective treatment of SUI. The aim of this study was to investigate if there is an association between BMI at time of MUS-surgery and the long-term outcome at 10 years. MATERIAL AND METHODS: Women who went through MUS surgery in Sweden between 2006 and 2010 and had been registered in the Swedish National Quality Register of Gynecological Surgery were invited to participate in the 10-year follow-up. A questionnaire was sent out asking if they were currently suffering from SUI or not and their rated satisfaction, as well as current BMI. SUI at 10 years was correlated to BMI at the time of surgery. SUI at 1 year was assessed by the postoperative questionnaire sent out by the registry. The primary aim of the study was to investigate if there is an association between BMI at surgery and the long-term outcome, subjective SUI at 10 years after MUS surgery. Our secondary aims were to assess whether BMI at surgery is associated with subjective SUI at 1-year follow-up and satisfaction at 10-year follow-up. RESULTS: The subjective cure rate after 10 years was reported by 2108 out of 2157 women. Higher BMI at the time of surgery turned out to be a risk factor for SUI at long-term follow-up. Women with BMI <25 reported subjective SUI in 30%, those with BMI 25-<30 in 40%, those with BMI 30-<35 in 47% and those with BMI ≥35 in 59% (p < 0.001). Furthermore, subjective SUI at 1 year was reported higher by women with BMI ≥30, than among women with BMI <30 (33% vs. 20%, p < 0.001). Satisfaction at 10-year follow-up was 82% among women with BMI <30 vs 63% if BMI ≥30 (p < 0.001). CONCLUSIONS: We found that higher BMI at the time of MUS surgery is a risk factor for short- and long-term failure compared to normal BMI.

Post-traumatic growth in later-life cognitive function? Evidence from the 1976 Great Tangshan Earthquake.

OBJECTIVES: This study aimed to explore the long-term impacts of exposure to earthquake in adolescence on later-life cognitive function in China. METHODS: Data were from the 2015 China Health and Retirement Longitudinal Study (CHARLS). Our analytical sample comprised 4394 participants aged 49 to 78 from two birth cohorts born between 1937 and 1966: exposed cohort during adolescence (born between 1952 and 1966), and non-exposed cohort during adolescence (born between 1937 and 1951). We defined earthquake exposure as the exposure severity of the 1976 Great Tangshan Earthquake (GTE). We selected community environmental characteristics as our key moderators. A difference-in-differences (DID) method was employed to estimate the long-term impact of the GTE on later-life cognitive function. RESULTS: We found that exposure to the earthquake during adolescence resulted in higher scores of later-life cognitive function (for males: ß = 2.18; 95% CI: 0.70-3.66; for females: ß = 1.22; 95% CI: 0.11-2.33). For males, this impact was moderated by community environmental characteristics including the old-age allowance program (ß = 3.07; 95% CI: 1.94-4.19) and the condition of basic community infrastructures (ß = 1.52; 95% CI: 0.84-2.19). CONCLUSIONS: Our study supports the post-traumatic growth theory. This finding suggest that individuals with early-life traumatic exposure need to be focused on. Additionally, improving the conditions of community infrastructures and establishing a community environment with comfort and security may be pretty important for promoting cognitive function and post-traumatic growth.

How long-term PM exposure may affect all-site cancer mortality: Evidence from a large cohort in southern China.

BACKGROUND: Evidence of a potential causal link between long-term exposure to particulate matter (PM) and all-site cancer mortality from large population cohorts remained limited and suffered from residual confounding issues with traditional statistical methods. AIMS: We aimed to examine the potential causal relationship between long-term PM exposure and all-site cancer mortality in South China using causal inference methods. METHODS: We used a cohort in southern China that recruited 580,757 participants from 2009 through 2015 and tracked until 2020. Annual averages of PM1, PM2.5, and PM10 concentrations were generated with validated spatiotemporal models. We employed a causal inference approach, the Marginal Structural Cox model, based on observational data to evaluate the association between long-term exposure to PM and all-site cancer mortality. RESULTS: With an increase of 1 µg/m³ in PM1, PM2.5, and PM10, the hazard ratios (HRs) and 95% confidence interval (CI) for all-site cancer were 1.033 (95% CI: 1.025-1.041), 1.032 (95% CI: 1.027-1.038), and 1.020 (95% CI: 1.016-1.025), respectively. The HRs (95% CI) for digestive system and respiratory system cancer mortality associated with each 1 µg/m³ increase in PM1 were 1.022 (1.009-1.035) and 1.053 (1.038-1.068), respectively. In addition, inactive participants, who never smoked, or who lived in areas of low surrounding greenness were more susceptible to the effects of PM exposure, the HRs (95% CI) for all-site cancer mortality were 1.042 (1.031-1.053), 1.041 (1.032-1.050), and 1.0473 (1.025-1.070) for every 1 µg/m³ increase in PM1, respectively. The effect of PM1 tended to be more pronounced in the low-exposure group than in the general population, and multiple sensitivity analyses confirmed the robustness of the results. CONCLUSION: This study provided evidence that long-term exposure to PM may elevate the risk of all-site cancer mortality, emphasizing the potential health benefits of improving air quality for cancer prevention.

Chemical exposure from the Hebei spirit oil spill accident and its long-term effects on mental health.

While evidence indicates that exposure to oil spill incidents can affect mental health, it is unclear whether the mental health effects result from the incident itself or from exposure to associated chemicals. Oil contains chemicals that can impact mental health and these chemicals may have long-term effects due to their persistence in the environment. To address the gap in current knowledge, we conducted cross-sectional and prospective analyses of data from adults who participated in the Health Effects of the Hebei Spirit Oil Spill study. To assess chemical exposure from oil spills, we used indirect exposure indicators such as distance from the contaminated oil band to residences and duration of clean-up work, along with direct exposure indicators such as urine metabolite concentrations of volatile organic compounds and polycyclic aromatic hydrocarbons. Mental health assessments covered posttraumatic stress disorder (PTSD), depression, state anxiety, and trait anxiety. In the cross-sectional analyses, all four mental health issues were found to be associated with proximity to the oil band (p-value<0.05) and showed a positive association with clean-up work duration (p-value<0.05). Cox regression analysis revealed that higher urinary t, t-muconic acid levels were associated with an increased risk of depression (Hazard Ratio [HR] = 1.55, 95 % Confidence Interval [CI] = 1.05-2.28), and elevated 1-hydroxypyrene levels increased the risk of PTSD (HR = 1.60, 95 % CI = 1.03-2.48). Additionally, higher urinary 2-naphthol levels were associated with increased state anxiety (HR = 1.39, 95 % CI = 1.00-1.93) and trait anxiety (HR = 1.64, 95 % CI = 1.15-2.32). These associations persisted even after controlling for distance and duration variables related to psychosocial exposure. Our findings suggest that environmental disaster response plans should prioritize minimizing chemical exposure while also considering the duration and nature of the mental health impacts.

Interprofessional collaboration skills and motivation one year after an interprofessional educational intervention for undergraduate medical and nursing students.

BACKGROUND: The increasingly complex patient care in the twenty-first century is delivered by interprofessional health care teams. Interprofessional collaboration can be taught during interprofessional education. However, whether a long-term change in collaborative competencies can be achieved by interprofessional education has not been studied sufficiently. Our research questions were: How does motivation for interprofessional collaboration and interprofessional collaborative skills change up to one year after an interprofessional educational intervention? How are they related to each other? METHODS: During a one-year period, undergraduate medical and nursing students attended four interprofessional (intervention) or uniprofessional (control group) education sessions. Self-determination Theory was used as the theoretical framework. Autonomous and controlled motivation scores for interprofessional collaboration were calculated using the Academic Self-Regulation Questionnaire, before (T1), directly after (T2) and one year post-intervention (T3). At T3, the students also filled out the Interprofessional Collaborative Competencies Attainment Survey (ICCAS), which measured the perceived attainment of collaborative competencies by a retrospective pre-test/post-test design. We used linear mixed effects models to analyse the motivation scores and linear regression for the relation between motivation and competence. RESULTS: In the interprofessional group, autonomous motivation scores of the participants were significantly lower at T2 vs. T1. Controlled motivation scores were significantly higher at T3 vs. T1. Controlled motivation scores for T2 were significantly higher in the uniprofessional group than in the interprofessional group. Perceived competence was related to higher autonomous motivation scores. At T3 the interprofessional collaborative competencies seemed to have grown more among students in the interprofessional group. CONCLUSIONS: The perceived growth in interprofessional collaboration competence lasted at least up to one year after the intervention, and was measurable with the ICCAS. The growth was significantly more in the IPE students than in the UPE students. The few differences found in motivation scores for interprofessional collaboration were probably caused by an imbalance of nursing versus medical students over the different time points. This finding indicates that classroom based IPE can contribute to interprofessional collaboration skills of nursing and medical students at least up to one year after an intervention.

Examining the long-term effects of COVID-19 in surgical nurses: Case of Aegean Region.

PURPOSE: To examine the long-term effects of COVID-19 on surgical nurses. BACKGROUND: Individuals contaminated with COVID-19 may face several metabolic or psychological issues, primarily in the respiratory, cardiovascular, nervous, musculoskeletal and renal systems during the late period. However, the long-term epidemiology is still not clear. DESIGN: Descriptive cross-sectional study. METHODS: The study included nurses (n = 509) who had been diagnosed with COVID-19 at least 12 weeks before and worked in surgical departments. We collected the study data via an online survey using the snowball sampling method between December 2021 and May 2022. This study followed the Reporting of Observational Studies in Epidemiology Guideline. RESULTS: The mean age of the nurses was 31.66 ± 8.74 years. Nurses stated that they were diagnosed with COVID-19 approximately 36 weeks before participating in this study. We found that the nurses mostly experienced palpitation (83.5%), headache (73.5%), dyspnea (64.1%), anosmia (57.6%), arthralgia (55.7%) and burnout (58.4%) during the late period after COVID-19. CONCLUSION: The long-term effects of COVID-19 were related to multiple organ dysfunctions. NO PATIENT OR PUBLIC CONTRIBUTION: Since the study was conducted with healthy individuals who had previously experienced COVID-19, there is no patient contribution. RELEVANCE TO CLINICAL PRACTICE: This study focuses on the long-term effects of COVID-19 on nurses. The results support the long-term effects of COVID-19 and are thought to contribute to the literature.

Racial differences in long-term social, physical, and psychological health among adolescent and young adult cancer survivors.

BACKGROUND: The current guidelines for survivorship in adolescents and young adults (AYA) cancer are based on studies conducted in the United States and European AYA survivors. However, previous studies have shown that the health-related quality of life in cancer survivors can vary depending on race, yet the long-term health differences among AYA survivors by race/ethnicity have not been fully explored. Therefore, our aim is to compare the psychosocial and physical health of AYA survivors and their matched controls across different racial and ethnic groups. METHODS: We conducted a cross-sectional study using US National Health and Nutrition Examination Survey (NHANES) and the Korea NHANES from 2007 to 2018. We included AYA cancer survivors who were diagnosed with any type of cancer aged between 15 and 39 years, and who were adult with aged over 18 years old at survey year. We then stratified the study population by race/ethnicity with Non-Hispanic White (NHW, n = 310), African American (AA, n = 42), Hispanic (n = 81) from NHANES, and Asian (n = 389) from the Korea NHANES. We also selected 5 times age-, sex-, race-, and survey year-matched general population among participants who had never been diagnosed with cancer (N = 4110). Variables were defined using questionnaire data, physical exams, and laboratory tests. RESULTS: Compared to NHW, Hispanics (aOR 1.15, 95% CI 1.00-1.32) had poor or fair general health, lower education (aOR 1.23, 95% CI 1.07-1.40), and lower household income (aOR 1.16, 95% CI 1.01-1.33). AA survivors were more likely to be non-coupled (aOR 1.35, 95% 1.15-1.60) and have hypertension (aOR 1.18, 95% CI 1.03-1.36). Asians were more former/current drinkers (aOR 1.21, 95% CI 1.05-1.40). NHW are more likely to experience psychological limitation. Compared to matched general, NHW and Asian survivors had poor general health and psychological health. CONCLUSIONS: This study provides evidence for future studies concerning long-term health after AYA cancer survivorship that may vary according to race.

Attenuated cognitive functioning decades after preeclampsia.

BACKGROUND: Preeclampsia, a hypertensive pregnancy disorder, is a leading cause of maternal and fetal morbidity and mortality, with remote cardio- and cerebrovascular implications. After preeclampsia, women may report serious disabling cognitive complaints, especially involving executive function, but the extent and time course of these complaints are unknown. OBJECTIVE: This study aimed to determine the impact of preeclampsia on perceived maternal cognitive functioning decades after pregnancy. STUDY DESIGN: This study is part of a cross-sectional case-control study named Queen of Hearts (ClinicalTrials.gov Identifier: NCT02347540), a collaboration study of 5 tertiary referral centers within the Netherlands investigating long-term effects of preeclampsia. Eligible participants were female patients aged ≥18 years after preeclampsia and after normotensive pregnancy between 6 months and 30 years after their first (complicated) pregnancy. Preeclampsia was defined as new-onset hypertension after 20 weeks of gestation along with proteinuria, fetal growth restriction, or other maternal organ dysfunction. Women with a history of hypertension, autoimmune disease, or kidney disease before their first pregnancy were excluded. Attenuation of higher-order cognitive functions, that is, executive function, was measured with the Behavior Rating Inventory of Executive Function for Adults. Crude and covariate-adjusted absolute and relative risks of clinical attenuation over time after (complicated) pregnancy were determined with moderated logistic and log-binomial regression. RESULTS: This study included 1036 women with a history of preeclampsia and 527 women with normotensive pregnancies. Regarding overall executive function, 23.2% (95% confidence interval, 19.0-28.1) of women experienced clinically relevant attenuation after preeclampsia, as opposed to 2.2% (95% confidence interval, 0.8-6.0) of controls immediately after childbirth (adjusted relative risk, 9.20 [95% confidence interval, 3.33-25.38]). Group differences diminished yet remained statistically significant (P < .05) at least 19 years postpartum. Regardless of history of preeclampsia, women with lower educational attainment, mood or anxiety disorders, or obesity were especially at risk. Neither severity of preeclampsia, multiple gestation, method of delivery, preterm birth, nor perinatal death was related to overall executive function. CONCLUSION: After preeclampsia, women were 9 times more likely to experience clinical attenuation of higher-order cognitive functions as opposed to after normotensive pregnancy. Despite overall steady improvement, elevated risks persisted over decades after childbirth.

Two years after lockdown: Longitudinal trajectories of sleep disturbances and mental health over the COVID-19 pandemic, and the effects of age, gender and chronotype.

Since the first lockdown of Spring 2020, the COVID-19 contagion waves pervasively disrupted the sleep and mental health of the worldwide population. Notwithstanding the largest vaccination campaign in human history, the pandemic has continued to impact the everyday life of the general population for 2 years now. The present study provides the first evidence of the longitudinal trajectories of sleep disturbances and mental health throughout the pandemic in Italy, also describing the differential time course of age groups, genders and chronotypes. A total of 1062 Italians participated in a three-time-point longitudinal study covering two critical stages of the emergency (the first lockdown in April 2020 and the second partial lockdown in December 2020) and providing a long-term overview 2 years after the pandemic outbreak (April 2022). We administered validated questionnaires to evaluate sleep quality/habits, insomnia, depression, stress and anxiety symptoms. Analyses showed a gradual improvement in sleep disturbances, depression and anxiety. Conversely, sleep duration progressively decreased, particularly in evening-type and younger people. Participants reported substantial earlier bedtime and get-up time. Stress levels increased during December 2020 and then stabilised. This effect was stronger in the population groups apparently more resilient during the first lockdown (older people, men and morning-types). Our results describe a promising scenario 2 years after the pandemic onset. However, the improvements were relatively small, the perceived stress increased, and the re-establishment of pre-existing social/working dynamics led to general sleep curtailment. Further long-term monitoring is required to claim the end of the COVID-19 emergency on Italians' sleep and mental health.

The Effects of Online Health Information-Seeking Behavior on Sexually Transmitted Disease in China: Infodemiology Study of the Internet Search Queries.

BACKGROUND: Sexually transmitted diseases (STDs) are a serious issue worldwide. With the popularity of the internet, online health information-seeking behavior (OHISB) has been widely adopted to improve health and prevent disease. OBJECTIVE: This study aimed to investigate the short-term and long-term effects of different types of OHISBs on STDs, including syphilis, gonorrhea, and AIDS due to HIV, based on the Baidu index. METHODS: Multisource big data were collected, including case numbers of STDs, search queries based on the Baidu index, provincial total population, male-female ratio, the proportion of the population older than 65 years, gross regional domestic product (GRDP), and health institution number data in 2011-2018 in mainland China. We categorized OHISBs into 4 types: concept, symptoms, treatment, and prevention. Before and after controlling for socioeconomic and medical conditions, we applied multiple linear regression to analyze associations between the Baidu search index (BSI) and Baidu search rate (BSR) and STD case numbers. In addition, we compared the effects of 4 types of OHISBs and performed time lag cross-correlation analyses to investigate the long-term effect of OHISB. RESULTS: The distributions of both STD case numbers and OHISBs presented variability. For case number, syphilis, and gonorrhea, cases were mainly distributed in southeastern and northwestern areas of China, while HIV/AIDS cases were mostly distributed in southwestern areas. For the search query, the eastern region had the highest BSI and BSR, while the western region had the lowest ones. For 4 types of OHISB for 3 diseases, the BSI was positively related to the case number, while the BSR was significantly negatively related to the case number (P<.05). Different categories of OHISB have different effects on STD case numbers. Searches for prevention tended to have a larger impact, while searches for treatment tended to have a smaller impact. Besides, due to the time lag effect, those impacts would increase over time. CONCLUSIONS: Our study validated the significant associations between 4 types of OHISBs and STD case numbers, and the impact of OHISBs on STDs became stronger over time. It may provide insights into how to use internet big data to better achieve disease surveillance and prevention goals.

Long-term inhibition of chlortetracycline antibiotics on anaerobic digestion of swine manure.

This study aimed to identify whether chronic effects are present in the anaerobic digestion (AD) of swine manure (SM) containing chlortetracycline (CTC), which is one of the major broad-spectrum veterinary antibiotics, and to elucidate the long-term inhibitory effects and recovery from the inhibition based on AD performance and microbial community. Two continuous-stirred tank reactors treating SM with and without CTC spiking (3 mg/L) were operated for 900 days. Due to the degradation and transformation, the total concentration including CTC's epimer and isomer in the test reactor was 1.5 mg/L. The exposure level was determined according to probabilistically estimated concentrations with uncertainties in field conditions. Until the cessation of CTC exposure on day 585, the methane generation of test reactor continuously decreased to 55 ± 17 mL/g-VS/day, 53% that of control. The methane generation and organic removal were not recovered within 300 days after the CTC exposure was stopped. During the experiment, stability parameters such as pH, total ammonium nitrogen, the composition of methane and alkalinity were the same for both reactors. The concentration and composition of VFAs in the test reactor were different with those of control but not in inhibition level. Microbial profiles revealed that reduction in bacterial diversity and changed balance in microbial species resulted in the performance downgrade under the long-term antibiotic pressure. Since it is hard to recover from the inhibition and difficult to predict the inhibition using physicochemical indicators, continuous exposure to CTC needs to be avoided for the sustainable management of AD plants treating SM.

[The efficacy of radiotherapy based combined therapy for unresectable locally invasive bladder cancer and its associated factors analysis].

Objective: Retrospective analysis of the efficacy and influencing factors of bladder preservation integrated therapy for unresectable invasive bladder cancer confined to the pelvis was done, also including the bladder function preservation and adverse effects analysis. Methods: Sixty-nine patients with unresectable locally invasive bladder cancer who received radiotherapy-based combination therapy from March 1999 to December 2021 at our hospital were selected. Among them, 42 patients received concurrent chemoradiotherapy, 32 underwent neoadjuvant chemotherapyand 43 with transurethral resection of bladder tumors (TURBT) prior to radiotherapy. The late adverse effect of radiotherapy, preservation of bladder function, replase and metastasis and survival were followed-up. Cox proportional hazards models were applied for the multifactorial analysis. Results: The median age was 69 years. There were 63 cases (91.3%) of uroepithelial carcinoma, 64 of stage Ⅲ and 4 of stage Ⅳ. The median duration of follow-up was 76 months. There were 7 grade 2 late genito urinary toxicities, 2 grade 2 gastrointestinal toxicities, no grade 3 or higher adverse events occurred. All patients maintained normal bladder function, except for 8 cases who lost bladder function due to uncontrolled tumor in the bladder. Seventeen cases recurred locally. There were 11 cases in the concurrent chemoradiotherapy group with a local recurrence rate of 26.2% (11/42) and 6 cases in the non-concurrent chemoradiotherapy group with a local recurrence rate of 22.2% (6/27), and the difference in local recurrence rate between the two groups was not statistically significant (P=0.709). There were 23 cases of distant metastasis (including 2 cases of local recurrence with distant metastasis), including 10 cases in the concurrent chemoradiotherapy group with a distant metastasis rate of 23.8% (10/42) and 13 cases in the non-concurrent chemoradiotherapy group with a distant metastasis rate of 48.1% (13/27), and the distant metastasis rate in the non-concurrent chemoradiotherapy group was higher than that in the concurrent chemoradiotherapy group (P=0.036). The median 5-year overall survival (OS) time was 59 months and the OS rate was 47.8%. The 5-year progression-free survival (PFS) time was 20 months and the PFS rate was 34.4%. The 5-year OS rates of concurrent and non-concurrent chemoradiotherapy group were 62.9% and 27.6% (P<0.001), and 5-year PFS rates were 45.4% and 20.0%, respectively (P=0.022). The 5-year OS rates of with or without neoadjuvant chemotherapy were 78.4% and 30.1% (P=0.002), and the 5-year PFS rates were 49.1% and 25.1% (P=0.087), respectively. The 5-year OS rates with or without TURBT before radiotherapy were 45.5% and 51.9% (P=0.233) and the 5-year PFS rates were 30.8% and 39.9% (P=0.198), respectively. Multivariate Cox regression analysis results showed that the clinical stage (HR=0.422, 95% CI: 0.205-0.869) was independent prognostic factor for PFS of invasive bladder cancer. The multivariate analysis showed that clinical stages (HR=0.278, 95% CI: 0.114-0.678), concurrent chemoradiotherapy (HR=0.391, 95% CI: 0.165-0.930), neoadjuvant chemotherapy (HR=0.188, 95% CI: 0.058-0.611), and recurrences (HR=10.855, 95% CI: 3.655-32.638) were independent prognostic factors for OS of invasive bladder cancer. Conclusion: Unresectable localized invasive bladder cancer can achieve satisfactory long-term outcomes with bladder-preserving combination therapy based on radiotherapy, most patients can retain normal bladder function with acceptable late adverse effects and improved survival particularly evident in patients with early, concurrent chemoradiotherapy and neoadjuvant chemotherapy.

[Evidence-based inpatient psychotherapy in borderline personality disorder]. / Evidenzbasierte stationäre Psychotherapie der Borderline-Persönlichkeitsstörung.

BACKGROUND: Borderline personality disorder (BPD) is frequent (prevalence in Germany between 0.7% and 4.5%) [11] and is associated with a high level of psychological stress and frequent emergency inpatient admissions. The provision of disorder-specific outpatient psychotherapy is still insufficient also in Germany. OBJECTIVE: This article provides an overview of the available data on the effectiveness of inpatient psychotherapy for BPD. MATERIAL AND METHODS: A qualitative review on the effectiveness and therapy outcome predictors was conducted based on a literature search in PubMed. RESULTS: Overall, very few randomized controlled trials are available; in contrast uncontrolled studies are predominant. Most evidence is available for dialectical behavior therapy (DBT) but other approaches, including psychodynamic procedures, have also been studied. DISCUSSION: The currently available data suggest an efficacy of inpatient psychotherapy for BPD; however, randomized trials with larger samples and sufficient representation including male patients are largely lacking. There is also no substantial direct evidence for the superiority of inpatient compared to outpatient psychotherapy.

Long-term expression changes of immune-related genes in prostate cancer after radiotherapy.

The expression of immune-related genes in cancer cells can alter the anti-tumor immune response and thereby impact patient outcomes. Radiotherapy has been shown to modulate immune-related genes dependent on the fractionation regimen. To identify long-term changes in gene expression after irradiation, PC3 (p53 deleted) and LNCaP (p53 wildtype) prostate cancer cells were irradiated with either a single dose (SD, 10 Gy) or a fractionated regimen (MF) of 10 fractions (1 Gy per fraction). Whole human genome arrays were used to determine gene expression at 24 h and 2 months after irradiation. Immune pathway activation was analyzed with Ingenuity Pathway Analysis software. Additionally, 3D colony formation assays and T-cell cytotoxicity assays were performed. LNCaP had a higher basal expression of immunogenic genes and was more efficiently killed by cytotoxic T-cells compared to PC3. In both cell lines, MF irradiation resulted in an increase in multiple immune-related genes immediately after irradiation, while at 2 months, SD irradiation had a more pronounced effect on radiation-induced gene expression. Both immunogenic and immunosuppressive genes were upregulated in the long term in PC3 cells by a 10 Gy SD irradiation but not in LNCaP. T-cell-mediated cytotoxicity was significantly increased in 10 Gy SD PC3 cells compared to the unirradiated control and could be further enhanced by treatment with immune checkpoint inhibitors. Irradiation impacts the expression of immune-related genes in cancer cells in a fractionation-dependent manner. Understanding and targeting these changes may be a promising strategy for primary prostate cancer and recurrent tumors.

Norwegian population-based study of long-term effects, safety, and predictors of response of vagus nerve stimulation treatment in drug-resistant epilepsy: The NORPulse study.

OBJECTIVE: This study was undertaken to evaluate the efficacy of vagus nerve stimulation (VNS) over time, and to determine which patient groups derive the most benefit. METHODS: Long-term outcomes are reported in 436 epilepsy patients from a VNS quality registry (52.8% adults, 47.2% children), with a median follow-up of 75 months. Patients were stratified according to evolution of response into constant responders, fluctuating responders, and nonresponders. The effect was evaluated at 6, 12, 24, 36, and 60 months. Multivariate regression analysis was used to identify predictors of response. RESULTS: The cumulative probability of ≥50% seizure reduction was 60%; however, 15% of patients showed a fluctuating course. Of those becoming responders, 89.5% (230/257) did so within 2 years. A steady increase in effect was observed among constant responders, with 48.7% (19/39) of those becoming seizure-free and 29.3% (39/133) with ≥75% seizure reduction achieving these effects within 2-5 years. Some effect (25%-<50%) at 6 months was a positive predictor of becoming a responder (odds ratio [OR] = 10.18, p < .0001) and having ≥75% reduction at 2 years (OR = 3.34, p = .03). Patients without intellectual disability had ORs of 3.34 and 3.11 of having ≥75% reduction at 2 and 5 years, respectively, and an OR of 6.22 of being seizure-free at last observation. Patients with unchanged antiseizure medication over the observation period showed better responder rates at 2 (63.0% vs. 43.1%, p = .002) and 5 years (63.4% vs. 46.3%, p = .031) than patients whose antiseizure medication was modified. Responder rates were higher for posttraumatic (70.6%, p = .048) and poststroke epilepsies (75.0%, p = .05) than other etiologies (46.5%). SIGNIFICANCE: Our data indicate that the effect of VNS increases over time and that there are important clinical decision points at 6 and 24 months for evaluating and adjusting the treatment. There should be better selection of candidates, as certain patient groups and epilepsy etiologies respond more favorably.