A case-crossover study on the impact of air pollution on the number of pediatric respiratory outpatient and emergency visits in a hospital in Shanghai / 公共卫生与预防医学

Objective To investigate the correlation between the concentration of air pollutants (PM10, SO2, NO2) and the number of outpatient and emergency visits for pediatric respiratory diseases in a general hospital in Shanghai. Methods Data including pediatric respiratory disease outpatient and emergency visits in a hospital in Pudong New Area of Shanghai from May 1, 2013 to March 20, 2022 were collected. Daily concentration of air pollutants including PM10, SO2 and NO2 and meteorological data in Pudong New Area during the same period were collected. A case-crossover study with distributed lag non-linear model was conducted to explore the correlation between air pollutants (PM10, SO2, NO2) and the number of outpatient and emergency visits for pediatric respiratory diseases. Results The concentrations of PM10, SO2 and NO2 were positively with the number of outpatient and emergency visits for pediatric respiratory diseases. The strongest cumulative effect was observed on six days lag (Lag0-5) for PM10. For a 10 μg/m3 increase of the concentrations of PM10, the corresponding increase of cumulative pediatric respiratory disease outpatients was 1.10% (95%CI:0.97%, 1.23%) in Lag0-5. The strongest cumulative effect was observed on eight days lag (Lag0-7) for SO2 and NO2. For a 10 μg /m3 increase of the concentrations of SO2 and NO2, the corresponding increase of cumulative pediatric respiratory disease outpatients was 5.64% (95%CI:5.16%, 6.13%) and 5.41% (95%CI:5.15%, 5.66%) in Lag 0-7, respectively. The association of PM10 and SO2 with the number of pediatric respiratory disease visits in males was significantly stronger than that in females. The impact of PM10 on the number of pediatric respiratory disease visits in children aged 0-6 was higher than that in children aged 7-14, while the impact of SO2 and NO2 on the number of pediatric respiratory disease visits in children aged 7-14 was higher than that in children aged 0-6. Conclusion The concentration of ambient PM10, SO2, and NO2 is positively correlated with outpatient and emergency visits for pediatric respiratory diseases, with obvious lag and cumulative effect. Boys and children aged 0-6 are more susceptible to the hazard of air pollution.

Epidemiological characteristics of heat stroke and association between heatwave and heat stroke in Jinan City, 2017—2022 / 环境与职业医学

Background In recent years, regional high-temperature weather in summer occurs frequently in China. Heat stroke is the most representative meteorological disease caused by high temperature. In order to improve monitoring, early warning, prevention, and control of heat stroke, it is of great significance to understand the epidemiological characteristics of heat stroke and the associated impact of heatwave. Objective To understand the epidemiological characteristics of heat stroke cases in Jinan City, and to explore the effects of heatwave exposure on heat stroke. Methods Case reports of heat stroke and daily data of meteorological factors in Jinan City from 2017 to 2022 were collected. We described the temporal, population, and regional distribution characteristics of heat stroke cases in Jinan City, and used a time-stratified case-crossover design combined with conditional logistic regression model to explore the effects of heatwave exposure on heat stroke under 12 heatwave definitions (different combinations of intensity and duration). The cut-off percentiles used for heatwave definitions were the 90th (P90), 95th (P95), 97.5th (P97.5), and 99th (P99) percentiles of daily mean temperature; the durations were ≥ 2 d, ≥ 3 d, and ≥ 4 d, respectively. Pi(k), where i is temperature threshold, and k is duration. For example, the definition of a heatwave was notated as P90(2), indicating that the daily mean temperature is ≥ P90 and lasts for ≥ 2 d. Alternatively, lag01 denotes the cumulative lag effect with a 1 d lag, and so on. Results A total of 1394 cases of heat stroke were reported in Jinan City from 2017 to 2022, including 581 mild cases and 813 severe cases, and 85 deaths were reported, with a cumulative fatality rate of 6.10%. The cases of heat stroke reported each year during the study period were concentrated from June to August and peaked in July (665 cases, 47.70%). The sex ratio of males to females in heat stroke cases was 2.02:1. A high incidence of heat stroke was in 50-89 years, with a smaller peak occurring in the age group of 50-59 years and a larger peak in the age group of 70-79 years, respectively. The high-incidence areas of heat stroke were distributed in the western part of Jinan City where city centers situated (Tianqiao District, 274 cases, 19.66%; Huaiyin District, 223 cases, 16.00%) and in the surrounding rural areas (Pingyin County, 254 cases, 18.22%). The effect of heatwave exposure on heat stroke was statistically significant during the study period. The largest effect estimates for the effect on heat stroke occurred under the heatwave definitions of P99(2), P97.5(3), and P97.5(4) at lag04, lag03, and lag04, where corresponding OR (95%CI) values were 9.27 (4.71, 14.24), 8.95 (6.17, 12.98), and 8.22 (4.91, 13.78), respectively. The exposure-response curve showed that the risk of heat stroke tended to increase with the increase of average daily temperature. Conclusion July is the key period for the occurrence of heat stroke among Jinan City residents, while male cases are predominant, more serious cases, age concentration in the 50-89 years. The occurrence of heatwave can further increase the risk of heat stroke with a significant lag effect.

A case-crossover study on association between short-term atmospheric NO2 exposure and outpatient visits due to pediatric neurological system conditions in Shijiazhuang / 环境与职业医学

Background Nitrogen dioxide (NO2), a crucial component of traffic pollutants, has been shown in studies to exert toxic effects on the nervous system. However, there is a limited body of research examining the relationship between NO2 exposure and neurological disorders in children. Objective To explore the impact of short-term NO2 exposure on the outpatient visits due to pediatric neurological diseases in Shijiazhuang. Methods From 2013 to 2021, we collected outpatient data related to neurological diseases at the Children's Hospital in Shijiazhuang, Hebei Province. We also collected air pollution data and meteorological data of the same city. The air pollution data included daily average concentrations of inhalable particles (PM10), fine particulate matter (PM2.5), sulfur dioxide (SO2), NO2, carbon monoxide (CO), and daily maximum 8-hour average concentration of ozone (O3). The meteorological data comprised daily average atmospheric pressure, temperature, relative humidity, wind speed, and sunshine duration. Employing a time-stratified case-crossover design, we used conditional logistic regression models to analyze the association between NO2 and pediatric outpatient visits for neurological diseases. Stratification analyses were conducted based on gender (male, female) and age groups (0-6 years, 7-14 years). Results The study included a total of 154348 valid pediatric outpatient visits for neurological diseases. The daily average concentration of NO2 was 49.3 μg·m−3 for the study period. The results from the single-pollutant model indicated that NO2 increased the risk of pediatric neurological outpatient visits, with the highest association observed at lag0. Specifically, for every 10 μg·m⁻³ increase in atmospheric NO2 exposure, there was a 1.40% increase (95%CI: 1.05%, 1.74%) in pediatric neurological outpatient visits. The stratification analyses revealed that increased atmospheric NO2 exposure was associated with an elevated risk of neurological outpatient visits for girls (ER=1.54, 95%CI: 1.01, 2.08) and children aged 7-14 years (ER=2.35, 95%CI: 1.68, 3.02). Even after introducing PM2.5 (ER=1.96, 95%CI: 1.49, 2.43), SO2 (ER=2.09, 95%CI: 1.62, 2.55), and O3 (ER=1.40, 95%CI: 1.06, 1.74) to the models, the impact of NO2 exposure on pediatric neurological outpatient visits remained statistically significant. The results of the multi-pollutant model also indicated a significant association (ER=2.53, 95%CI: 1.97, 3.08). Conclusion The effect of short-term exposure to atmospheric NO2 on the outpatient visits of children with neurological diseases in Shijiazhuang is acute and independent, especially for children aged 7-14.

The understanding of epidemiology and study designs

The goal of health care systems is to keep patients healthy by monitoring, diagnosing, and treating their illnesses. These complex systems have many objectives, such as improving the quality of health care, making healthcare accessible to all people who are in need, extending people’s life span, preventing illnesses, etc. Promoting healthy lifestyles along with the prevention of illnesses to improve people’s health is also a fundamental principle of public health, and now it also become a fundamental principle of health care and integrating into health and social care strategies across the world. Epidemiology is the system of ultimate reasoning focused on creating and examining theories in systematic fields such as biology, physics, behavioral sciences. Epidemiology rationalize the health-associated states and events and provide the justification for further suitable real-world public health measures. While working in the field, I observed that allied healthcare professionals lacked basic knowledge about epidemiology and related study designs. The input from this healthcare professional not only assists in building meaningful research studies but also demonstrates its powerful impact on patients’ healthcare through preventive measures and study results. The goal of this article is to provide basic knowledge of epidemiology and its various study designs in a simplistic language to allied healthcare professionals working in the field. In this article, I have described a general overview of epidemiology and various study designs, along with examples. I hope this information could be beneficial for a better understanding of epidemiology to healthcare professionals working in the field.

Construction of AQHI based on joint effects of multi-pollutants in 5 provinces of China / 环境与职业医学

Background Air pollution is a major public health concern. Air Quality Health Index (AQHI) is a very important air quality risk communication tool. However, AQHI is usually constructed by single-pollutant model, which has obvious disadvantages. Objective To construct an AQHI based on the joint effects of multiple air pollutants (J-AQHI), and to provide a scientific tool for health risk warning and risk communication of air pollution. Methods Data on non-accidental deaths in Yunnan, Guangdong, Hunan, Zhejiang, and Jilin provinces from January 1, 2013 to December 31, 2018 were obtained from the corresponding provincial disease surveillance points systems (DSPS), including date of death, age, gender, and cause of death. Daily meteorological (temperature and relative humidity) and air pollution data (SO2, NO2, CO, PM2.5, PM10, and maximum 8 h O3 concentrations) at the same period were respectively derived from China Meteorological Data Sharing Service System and National Urban Air Quality Real-time Publishing Platform. Lasso regression was first applied to select air pollutants, then a time-stratified case-crossover design was applied. Each case was matched to 3 or 4 control days which were selected on the same days of the week in the same calendar month. Then a distributed lag nonlinear model (DLNM) was used to estimate the exposure-response relationship between selected air pollutants and mortality, which was used to construct the AQHI. Finally, AQHI was classified into four levels according to the air pollutant guidance limit values from World Health Organization Global Air Quality Guidelines (AQG 2021), and the excess risks (ERs) were calculated to compare the AQHI based on single-pollutant model and the J-AQHI based on multi-pollutant model. Results PM2.5, NO2, SO2, and O3 were selected by Lasso regression to establish DLNM model. The ERs for an interquartile range (IQR) increase and 95% confidence intervals (CI) for PM2.5, NO2, SO2 and O3 were 0.71% (0.34%–1.09%), 2.46% (1.78%–3.15%), 1.25% (0.9%–1.6%), and 0.27% (−0.11%–0.65%) respectively. The distribution of J-AQHI was right-skewed, and it was divided into four levels, with ranges of 0-1 for low risk, 2-3 for moderate risk, 4-5 for high health risk, and ≥6 for severe risk, and the corresponding proportions were 11.25%, 64.61%, 19.33%, and 4.81%, respectively. The ER (95%CI) of mortality risk increased by 3.61% (2.93–4.29) for each IQR increase of the multi-pollutant based J-AQHI , while it was 3.39% (2.68–4.11) for the single-pollutant based AQHI . Conclusion The J-AQHI generated by multi-pollutant model demonstrates the actual exposure health risk of air pollution in the population and provides new ideas for further improvement of AQHI calculation methods.

Development and application of a rapid gene manipulating toolbox for Pseudomonas aeruginosa / 生物工程学报

Manipulation of genes, including knock-out or knock-in, replacement of gene elements (such as promoters), fusion with a fluorescent protein gene, and construction of in situ gene reporter, is required in most of the biotechnological laboratories. The widely used gene manipulating methods based on two-step allelic exchange are cumbersome in terms of constructing plasmids, transforming and screening. In addition, the efficiency of using this method for long fragment knockout is low. To simplify the process of gene manipulation, we constructed a minimized integrative vector pln2. When a gene needs to be inactivated, an internal fragment of the target gene (non-frameshift) is cloned into the pln2 plasmid. Once the single-crossover recombination between genome and the constructed plasmid occurs, the endogenous gene is segmented by the plasmid backbone and thus inactivated. We developed a toolbox based on pln2 that can be used for different genomic operation mentioned above. With the help of this toolbox, we successfully knocked out large fragments of 20-270 kb.

A Case of Prosthesis Penetrating the Bladder by Crossover Bypass in the Pelvic Cavity / 日本心臓血管外科学会雑誌

A 73-year-old man who had undergone right common iliac-right femoral-left femoral artery bypass, and left femoral-popliteal artery bypass at 60, and stent graft for abdominal aortic aneurysm at 69, had a pseudoaneurysm repaired at the left femoral artery anastomosis site at 72. Retention of fluid continued around the prosthesis, so drainage and sartorius muscle flap were carried out at 72. Due to the occlusion of the left popliteal bypass, a cross over bypass was performed from the right iliac artery position to the left above knee popliteal artery through the left obturator foramen route. One month later, CT revealed that the prosthesis had penetrated the bladder. In open surgery, the bladder was incised, and the prosthesis was taken out of it. The postoperative course was uneventful. Oral antibiotics were continued for 3 months. Currently, there are no signs of infection. There are very few opportunities to choose an obturator foramen route. It was necessary to identify the bladder wall under direct vision with great care.

Effectiveness of artificial intelligence-endoscopic ultrasound biliary and pancreatic recognition system: a crossover study / 中华消化内镜杂志

Objective:To explore the effectiveness of the artificial intelligence-endoscopic ultrasound (AI-EUS) biliary and pancreatic recognition system in assisting the recognition of EUS images.Methods:Subjects who received EUS due to suspicious biliary and pancreatic diseases from December 2019 to August 2020 were prospectively collected from the database of Department of Gastroenterology, Renmin Hospital of Wuhan University. Pancreatic EUS images of 28 subjects were included for recognition of pancreas standard station. EUS images of bile duct of 29 subjects were included for recognition of bile duct standard station. Eight new endoscopists from the Gastroenterology Department of Renmin Hospital of Wuhan University read the 57 EUS videos with and without the assistance of AI-EUS biliary and pancreatic recognition system. Accuracy of endoscopists' identification of biliary and pancreatic standard sites with and without the assistance of AI-EUS was compared.Results:The accuracy of pancreas standard station identification of the new endoscopists increased from 67.2% (903/1 344) to 78.4% (1 054/1 344) with the assistance of AI-EUS. The accuracy of bile duct standard station identification increased from 56.4% (523/928) to 73.8% (685/928).Conclusion:AI-EUS biliary and pancreatic recognition system can improve the accuracy of EUS images recognition of biliary and pancreatic system, which can assist diagnosis in clinical work.

Association between vaccination and the risk of immunoglobulin A vasculitis in children / 中国当代儿科杂志

OBJECTIVES@#To study the effect of vaccination on the short-term risk of immunoglobulin A vasculitis (IgAV) in children.@*METHODS@#A retrospective analysis was conducted on the general data and the vaccination history within one year prior to onset in children with IgAV hospitalized in the Children's Hospital Affiliated to Zhengzhou University from November 2021 to January 2023. Vaccine exposure rates in the risk period (3 months prior to IgAV onset) and the control period were compared by autocontrol-case crossover analysis, and the odds ratio and 95% confidence interval (95%CI) were calculated. A sensitivity analysis for the one-month and two-month risk periods was conducted.@*RESULTS@#A total of 193 children with IgAV were included, with a median age of 7.0 years. Among the 193 children, 36 (18.7%) received at least one dose of the vaccine within 1 year prior to IgAV onset, and 14 (7.3%) received at least one dose of the vaccine during the 3-month risk period. Compared to the unvaccinated IgAV group, the vaccinated IgAV group had a significantly younger age of onset (P<0.05). There were no significant differences in the proportions of children with gastrointestinal involvement, renal involvement, and joint involvement between the two groups (P>0.05). The odds ratio for developing IgAV after receiving any type of vaccine within 3 months prior to IgAV onset was 2.08 (95%CI: 0.82-5.27, P>0.05). Further sensitivity analysis for the 1-month and 2-month risk periods demonstrated that the odds ratios for developing IgAV after receiving any type of vaccine were 2.74 (95%CI: 0.72-10.48, P>0.05) and 2.72 (95%CI: 0.95-7.77, P>0.05), respectively.@*CONCLUSIONS@#Vaccination dose not increase the risk of IgAV, nor does it exacerbate clinical symptoms in children with IgAV.

Cross-lagged analysis of upward social comparison and online aggressive behavior among college students / 中国学校卫生

Objective@#To explore the longitudinal relationship between upward social comparison and online aggressive behavior among college students, in order to provide an empirical evidence for educators to carry out mental health promotion for college students.@*Methods@#From December 2021 to March 2022, 539 college students from one university in Inner Mongolia were recruited to complete the Upward Social Comparison Questionnaire (USCQ) and Online Aggressive Behavior Scale (OABS) in a 4 month follow-up study. The structural equation model was used to conduct cross-lagged analysis.@*Results@#The mean scores of upward social comparison for college students tracked at baseline (T1) and 4 months follow-up (T2) were (2.77±0.93, 2.70±1.00) points, and the mean scores of online aggressive behavior were (1.06±0.13, 1.05±0.11) points. There were positive relations between upward social comparison and online aggressive behavior of college students at both cross-sectional levels ( r=0.14-0.19, P <0.05). In the autoregression, T1 upward social comparison could positively predict T2 upward social comparison ( β =0.66), and T1 online aggressive behavior could positively predict T2 online aggressive behavior ( β =0.47)( P <0.01); In the cross-lagged regression, T1 upward social comparison could positively predict T2 online aggressive behavior ( β=0.10, P <0.01), whereas T1 online aggressive behavior could not predict T2 upward social comparison ( β=0.04, P >0.05).@*Conclusion@#Upward social comparison is the cause of online aggressive behavior among college students. The probability of online aggressive behavior among college students should be reduced by guiding students to correctly view the gap between themselves and others.

Association between ambient air pollution and fatal stroke mortality in Songjiang District of Shanghai / 上海预防医学

Objective To investigate the risk of fatal stroke mortality associated with short-term exposure to air pollution， and to determine the susceptible population. Methods In this study， daily stroke mortalities of adults between 2012 and 2014 in Songjiang District， Shanghai were collected. Time-stratified case-crossover approach was used to assess the association between daily concentrations of air pollutants and fatal stroke mortalities. Results This study included 514 patients who died from acute strokes. The average concentrations during the study period were 77.45 μg·m-3 for PM2.5， 21.22 μg·m-3 for SO2， and 57.59 μg·m-3 for NO2. The fatal stroke mortality of adults under the age of 65 was found to be significantly associated with NO2. At the time of a Lag of 2 d and 03 d， a significantly higher risk of fatal stroke mortality in relation to NO2 exposure was observed， and the OR values of ischemic stroke mortality for people were 3.86 （1.53-9.75） and 5.83 （1.40-24.34） respectively. People over the age of 65 were more sensitive to increased PM2.5 concentrations， at the time of a Lag of 03 d， fatal strokes increased by 28% when PM2.5 levels increased. A significantly higher risk of fatal stroke mortality in relation to increase of NO2 concentration was observed among people who were overweight or obese. Conclusion A significantly higher risk of fatal stroke mortality is associated with the increase of PM2.5 and NO2. The results also suggest that the susceptible population should take additional precautions to avoid or reduce the risk of fatal strokes.

Case-crossover study on association between temperature and non-accidental mortality in Tibet Plateau, China / 环境与职业医学

Background Under the background of global climate change, temperature has increased dramatically. Most studies about association between temperature and human health are conducted in low-altitude areas, but rarely focus on plateau areas. Objective To examine the association between temperature and non-accidental mortality risk in Tibet Plateau, China and to identify vulnerable populations for formulating targeted policies of climate change adaptation. Methods The mortality data, meteorological data, and pollutant data of Tibet area between 2013 to 2019 were collected. Based on time-stratified case-crossover design, conditional logistic regression models were used to analyze the exposure-response relationship between temperature and cause-specific mortality, which was linearized to obtain excess risk for 1 ℃ change; attributable fraction was calculated for assessing burden attributable to temperature; and stratified analyses were further conducted by gender, age (＜65 years old, ≥65 years old), and causes of death (cardiovascular diseases, cerebrovascular diseases, and respiratory diseases). Sensitivity analyses were conducted by adjusting model parameters and variables. Results A total of 26 045 non-accidental deaths were collected in Tibet during 2013 and 2019, and the P50 of temperature was 5.0 ℃. The non-accidental mortality risk increased as temperature become colder. A 1 ℃ decrease in temperature was associated with a 2.01% (95%CI: 0.94%-3.07%) increase in total non-accidental mortality, while the association changed to 2.05% (95%CI: 0.62%-3.47%) for male and 1.96% (95%CI: 0.34%-3.56%) for female, both of statistial significance; 1.45% (95%CI: −0.10%-2.98%) for the people <65 years old (not of significance) and 2.52% (95% CI : 1.04%-3.99%) for the people ≥65 years old (of significance); the excess risk for cardiovascular mortality was 2.65% (95%CI: 1.03%-4.24%), for cerebrovascular mortality was 3.70% (95%CI: 0.74%-6.57%), both of statistical significance, and for respiratory mortality was 2.18% (95%CI: −0.14%-4.44%), without significance. The total attribution number of non-accidental mortality was 5340 (95%CI: 2719-7528), and the total attributable fraction was 20.50% (95%CI: 10.44%-28.91%). The attributable fractions were higher in specific subgroups like male (20.72%), people ≥65 years (23.33%), and people with cardiovascular diseases (26.07%). Conclusion The exposure-response relationship between temperature and non-accidental mortality in Tibet showes that the non-accidental mortality risk increase as temperature become colder. The attributable burden of disease is heavy. Residents being male, ≥65 years, with cardiovascular diseases and respiratory diseases may be vulnerable to nonoptimal temperature.

How to use analysis of variance correctly——an analysis of variance for the univariate quantitative data collected from the crossover design / 四川精神卫生

The purpose of the paper was to introduce the calculation formulas and the SAS implementation of the analysis of variance for the quantitative data of the crossover design. In the calculation， three test statistics were involved， namely Ftreatment， Fstage and Findividual. They were three test statistics used to evaluate the statistical significance of the effect of the treatment factor， the stage factor， and the individual factor on the quantitative outcome variable， respectively. In general， it was assumed that there was no or negligible interaction among the three factors in a crossover design， so there was no need to evaluate whether the interaction term was statistically significant. With the help of SAS software， this paper conducted the univariate analysis of variance for the quantitative data of crossover designs for three examples of 2×2 crossover design， 3×3 crossover design and three-stage crossover design， and presented the calculation results and drew the statistical and professional conclusions.

Clinical and imaging analysis of 8 cases with ipsilateral hemiparesis in ischemic stroke / 中风与神经疾病杂志

@#To summarize the clinical and imaging features of ipsilateral limb weakness caused by cerebral infarction，and to explore the possible physiological mechanism of the disease. Methods The clinical data of patients with ipside-limb weakness caused by acute cerebral infarction hospitalized in our department from January 1，2016 to December 30，2016 were collected，and the neurological symptoms and signs，magnetic resonance imaging （MRI） and other examination results of the patients were analyzed descriptively. Results 8 cases of ipsilateral hemiparesis （0.18%） were found in 4495 patients with acute cerebral infarction，all 8 patients were lacunar cerebral infarction，4 cases with previous medical history of cerebral infarction，3 cases have old infarcts in Contralateral cerebral hemisphere，DTI of 1 case showed pyramidal tract was not cross，the lesions of 2 cases were in the brain stem，2 cases in centrum semiovale，3 cases in capsule，One was in the putamen and one in the frontal cortex. Conclusion Most of the patients with ipside hemiparesis caused by cerebral infarction had a history of previous pyramidal tract injury，which was mostly lacunar lesions，mostly located in the configuration area of ipside-pyramidal tract.

O impacto do uso de diários hospitalares na incidência de Transtorno de Estresse Pós-Traumático e de sofrimento psíquico em familiares de crianças gravemente doentes: um estudo de intervenção em Unidades de Terapia Intensiva Pediátricas no Rio de Janeiro / The impact of hospital diaries in Postraumatic Stress Disorder and psychological distress incidence in relatives of critically ill children: an intervention study in Pediatric Intensive Care Units in Rio de Janeiro

Mais de um terço dos familiares de pacientes internados em Unidades de Terapia Intensiva Pediátricas (UTIP) evoluem com ansiedade, depressão e Transtorno de Estresse Pós- Traumático (TEPT), com consequente diminuição da qualidade de vida e grande impacto social. A estas complicações, alcunhou-se o termo Síndrome Pós-Terapia Intensiva Familiar (PICS- F), com o objetivo de aumentar a conscientização sobre o assunto visto que os dados disponíveis na literatura são ainda escassos e de baixa qualidade. Estratégias que minimizem estes desfechos negativos após a alta vêm sendo adotadas em UTIP de diferentes países. O objetivo desta tese foi avaliar o impacto de um programa de diários hospitalares na incidência de TEPT e de sofrimento psíquico em familiares de pacientes pediátricos criticamente doentes. Entre dezembro de 2019 e dezembro de 2021, realizamos um estudo de intervenção randomizado por clusters e alocado em crossover, com dois braços e dois períodos em quatro UTIP do estado do Rio de Janeiro. Foram elegíveis os familiares de crianças de 29 dias a 12 anos que estiveram internadas na UTIP por mais de 36 horas por motivos clínicos ou cirúrgicos. O uso de diários de UTIP foi comparado com a prática padrão. Os diários foram preenchidos pela equipe de saúde e familiares, tiveram fotografias inseridas e foram entregues aos familiares na alta da UTIP. Os desfechos primários foram: (a) a incidência de TEPT aferida com o instrumento PCL- 5 (Posttraumatic Stress Disorder Checklist for DSM-5 - Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition); e (b) a incidência de sofrimento psíquico aferida com o instrumento Hospital Anxiety and Depression Score (HADS). Ambos os desfechos foram aferidos em familiares de crianças graves, 45 a 60 dias após sua alta da UTIP. Também foi realizada uma análise de sensibilidade para avaliar o impacto de níveis diferentes de adesão ao diário nos desfechos. Um total de 339 participantes foi analisado, 170 no grupo que fez uso do diário e 169 no grupo controle. As características dos participantes foram semelhantes nos dois grupos de estudo. O uso de diários diminuiu em média 2,57 pontos no escore total do PCL 5 dos familiares (IC 95% -2,58 a -2,57; p<0,001) e foi encontrada razão de taxa de incidência (IRR) de 0,60 (IC 95% 0,57 a 0,64; p<0,001), significando uma redução de 40% na incidência de TEPT no grupo intervenção quando comparado ao controle. Com relação ao sofrimento psíquico, o uso de diários resultou em um IRR de 0,78 (IC 95% 0,77 a 0,78). A análise de conteúdo dos diários mostrou que a adesão total foi ainda mais impactante do que a adesão parcial aos diários. Os resultados apresentados nesta tese corroboram a hipótese de que diários têm efeito protetor sobre a incidência de TEPT e de sofrimento psíquico em familiares de crianças criticamente doentes, sendo, portanto, benéficos na prevenção de PICS-F.

More than a third of family members of critically ill children in Pediatric Intensive Care Units (PICU) develop anxiety, depression, and Post Traumatic Stress Disorder (PTSD), with a consequent decrease in quality of life and great social impact. Hence, the term Post- Intensive Family Therapy Syndrome (PICS-F) was created to raise awareness of these complications and define a global research agenda. Data on this theme available in the literature are still scarce and of low quality. After discharge, strategies that minimize these negative outcomes have been adopted in PICUs in different countries. This thesis aimed to evaluate the impact of a hospital diary program on PTSD and psychological distress incidence in family members of critically ill pediatric patients. Between December 2019 and December 2021, we conducted a cluster-randomized, crossover, two-arm, two-period intervention study in four PICUs. Relatives of children aged 29 days to 12 years who were hospitalized in the PICU for more than 36 hours for clinical or surgical reasons were eligible. The use of PICU diaries was compared with standard practice. The diaries were filled in by the health professionals and family members, had photographs inserted, and were handed to family members upon PICU discharge. The primary outcomes were: (a) the incidence of PTSD measured with the PCL-5 instrument (Posttraumatic Stress Disorder Checklist for DSM-5 - Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition); and (b) the incidence of psychological distress measured with the Hospital Anxiety and Depression Score (HADS) instrument. Both outcomes were measured in family members of critically ill children 45 to 60 days after discharge from the PICU. A sensitivity analysis was also performed on adherence to the diary by evaluating its content. A total of 339 participants were analyzed, 170 in the diary group and 169 in the control group. Participant characteristics were similar in the two study groups. The use of diaries decreased an average of 2.57 points in the total PCL-5 score of family members (95% CI -2.58 to -2.57; p<0.001) and an incidence rate ratio (IRR) of 0.60 (95% CI 0.57 to 0.64; p< 0.001), resulting in a 40% reduction in PTSD incidence. Regarding psychological distress, the use of diaries resulted in an IRR of 0.78 (95% CI 0.77 to 0.78). The content analysis of the diaries showed that full adherence was even more impactful than partial adherence to the diaries (IRR 0.68 [CI 95% 0.57 to 0.81] and IRR 0.77 [CI 95% 0. 70 to 0.86], respectively). Therefore, the more complete the diaries, the greater their effect on reducing psychological distress incidence. The results presented in this thesis support the hypothesis that diaries have a protective effect on PTSD and psychological distress in family members of critically ill children and are beneficial in preventing PICS-F.

Is the N-of-1 method applicable in bodywork research? Lessons learned using a trial as a methodological pilot / 中西医结合学报

N-of-1 trial designs have rarely been used in bodywork research. Using a recent trial as a methodological pilot, critical issues related to the applicability of N-of-1 trials to bodywork are discussed. These include the issues of carry-over effects, bias-controlling approaches and statistical analysis. The discussion highlights the importance of mixed methods and draws some suggestions for a future research program. N-of-1 trials could be used to provide insights about some essential elements of bodywork modalities and their effectiveness.

Crossover patterns under meiotic chromosome program / 亚洲男科学杂志(英文版)

Repairing DNA double-strand breaks (DSBs) with homologous chromosomes as templates is the hallmark of meiosis. The critical outcome of meiotic homologous recombination is crossovers, which ensure faithful chromosome segregation and promote genetic diversity of progenies. Crossover patterns are tightly controlled and exhibit three characteristics: obligatory crossover, crossover interference, and crossover homeostasis. Aberrant crossover patterns are the leading cause of infertility, miscarriage, and congenital disease. Crossover recombination occurs in the context of meiotic chromosomes, and it is tightly integrated with and regulated by meiotic chromosome structure both locally and globally. Meiotic chromosomes are organized in a loop-axis architecture. Diverse evidence shows that chromosome axis length determines crossover frequency. Interestingly, short chromosomes show different crossover patterns compared to long chromosomes. A high frequency of human embryos are aneuploid, primarily derived from female meiosis errors. Dramatically increased aneuploidy in older women is the well-known "maternal age effect." However, a high frequency of aneuploidy also occurs in young women, derived from crossover maturation inefficiency in human females. In addition, frequency of human aneuploidy also shows other age-dependent alterations. Here, current advances in the understanding of these issues are reviewed, regulation of crossover patterns by meiotic chromosomes are discussed, and issues that remain to be investigated are suggested.

The organization, regulation, and biological functions of the synaptonemal complex / 亚洲男科学杂志(英文版)

The synaptonemal complex (SC) is a meiosis-specific proteinaceous macromolecular structure that assembles between paired homologous chromosomes during meiosis in various eukaryotes. The SC has a highly conserved ultrastructure and plays critical roles in controlling multiple steps in meiotic recombination and crossover formation, ensuring accurate meiotic chromosome segregation. Recent studies in different organisms, facilitated by advances in super-resolution microscopy, have provided insights into the macromolecular structure of the SC, including the internal organization of the meiotic chromosome axis and SC central region, the regulatory pathways that control SC assembly and dynamics, and the biological functions exerted by the SC and its substructures. This review summarizes recent discoveries about how the SC is organized and regulated that help to explain the biological functions associated with this meiosis-specific structure.

The formation and repair of DNA double-strand breaks in mammalian meiosis / 亚洲男科学杂志(英文版)

Programmed DNA double-strand breaks (DSBs) are necessary for meiosis in mammals. A sufficient number of DSBs ensure the normal pairing/synapsis of homologous chromosomes. Abnormal DSB repair undermines meiosis, leading to sterility in mammals. The DSBs that initiate recombination are repaired as crossovers and noncrossovers, and crossovers are required for correct chromosome separation. Thus, the placement, timing, and frequency of crossover formation must be tightly controlled. Importantly, mutations in many genes related to the formation and repair of DSB result in infertility in humans. These mutations cause nonobstructive azoospermia in men, premature ovarian insufficiency and ovarian dysgenesis in women. Here, we have illustrated the formation and repair of DSB in mammals, summarized major factors influencing the formation of DSB and the theories of crossover regulation.

Two-stage estimation on adjustment for cross-over in oncology trials / 中国临床药理学与治疗学

AIM: To investigate the application of two-stage estimation (TSE) on adjustment for treatment switch in oncology trials. METHODS: The theory and implementation of TSE method was described, and was applied to adjust the data from a two-arm randomized controlled trial of anti-tumor drugs. The changes of survival curves and hazard ratio of two groups after adjustment for cross-over were evaluated. In addition, the results of two-stage estimation and rank preserving structural failure time model (RPSFT) were compared. RESULTS: After adjustment for cross-over using TSE methods, the results showed that the median survival time of control group was shorter than the original one, and the hazard ratio was lower than the observed value. Moreover, TSE method showed similar results to rank preserving structural failure time model. CONCLUSION: The TSE method is relatively simple to use, reliable and has a good practice property in cross-over analysis of oncology trials. At the same time, it is necessary to pay attention to its application scopes.