Identifying Safety Subgroups at Risk: Assessing the Agreement Between Statistical Alerting and Patient Subgroup Risk: An International Journal of Medical Toxicology and Drug Experience

Introduction Identifying individual characteristics or underlying conditions linked to adverse drug reactions (ADRs) can help optimise the benefit-risk ratio for individuals. A systematic evaluation of statistical methods to identify subgroups potentially at risk using spontaneous ADR report datasets is lacking. Objectives In this study, we aimed to assess concordance between subgroup disproportionality scores and European Medicines Agency Pharmacovigilance Risk Assessment Committee (PRAC) discussions of potential subgroup risk. Methods The subgroup disproportionality method described by Sandberg et al., and variants, were applied to statistically screen for subgroups at potential increased risk of ADRs, using data from the US FDA Adverse Event Reporting System (FAERS) cumulative from 2004 to quarter 2 2021. The reference set used to assess concordance was manually extracted from PRAC minutes from 2015 to 2019. Mentions of subgroups presenting potential differentiated risk and overlapping with the Sandberg method were included. Results Twenty-seven PRAC subgroup examples representing 1719 subgroup drug-event combinations (DECs) in FAERS were included. Using the Sandberg methodology, 2 of the 27 could be detected (one for age and one for sex). No subgroup examples for pregnancy and underlying condition were detected. With a methodological variant, 14 of 27 examples could be detected. Conclusions We observed low concordance between subgroup disproportionality scores and PRAC discussions of potential subgroup risk. Subgroup analyses performed better for age and sex, while for covariates not well-captured in FAERS, such as underlying condition and pregnancy, additional data sources should be considered.

Newly Characterized Porcine Epidemic Diarrhea Virus GII Subtype Strain

Diarrhea outbreaks in piglets on pig farms are commonly attributed to porcine epidemic diarrhea virus (PEDV) infection. This research analyzed the S gene prevalence variation and recombination patterns in PEDV GII strains. Throughout the previous two years, 172 clinical samples of piglet diarrhea have been collected, from which 24 PEDV isolates have been isolated. Analysis of the evolutionary relationships among all 24 S genes revealed that 21 were most closely related to strains within the GII-a subgroup. The 2 isolates grouped into one clade with the GII-b subgroup. According to the mutation analysis of the amino acids (aa) that encode the S protein, 43 of the common aa in strains of the GII subtype were found to have undergone a change in polarity or charge, and 36 of these aa had a mutation frequency of more than 90%. Three different aa mutation sites were identified as exclusive to GII-a subtype strains. The genomes of three PEDV isolates were sequenced, and the resulting range in genome length was 28,035−28,041 nt. The results of recombination analysis showed that the SD1 isolate is a novel strain recombinant from the foreign S-INDEL strain and a domestic GII subtype strain. Based on the findings, the PEDV GII-a strain has been the most circulating strain in several parts of China during the previous two years. Our study reveals for the first time the unique change of aa mutations in the S protein of the GII-a subtype strain and the new characteristics of the recombination of foreign strains and domestic GII subtype strains, indicating that it is crucial to monitor the epidemic dynamics of PEDV promptly to prevent and control the occurrence of PED effectively.

Self-Reported Changes in Personal Development and Meaning in Life among Older Adults during the COVID-19 Pandemic: Results from the Longitudinal Aging Study Amsterdam

Objectives. The aim of this study was to explore self-reported changes in personal development and meaning in life of older adults in the Netherlands during the COVID-19 pandemic and characteristics of the groups that reported these changes. Methods. Older adults from the Longitudinal Aging Study Amsterdam completed a questionnaire on the impact of the COVID-19 pandemic. Participants were asked to rate changes in personal development and meaning in life. These variables were descriptively analysed and logistic regression analyses were used to explore characteristics of the groups that reported these changes. Results. Of the 1099 older adults (aged 62–102 years), 25.7% paid more attention to things one enjoys doing in spare time, 36.6% reflected more on important things in life, and 16.8% made less future plans during the COVID-19 pandemic. Self-reported changes in meaning in life and personal development differed between specific subgroups of older adults. The largest changes in aspects of personal development and meaning in life were reported by older adults who experienced personal adverse experiences such as death of a loved one (ORs 2.03) and/or health problems such as functional limitations (ORs ranging from 1.59 to 2.84) and depression (ORs ranging from 1.69 to 2.77). Discussion and Implications. A substantial share of the participants reported changes in specific aspects of personal development and meaning in life. This was especially true for certain subgroups of older adults. Relatives and caregivers should be aware of changes in personal development and meaning in life since lower scores are known to be associated with poor physical, psychological, and social well-being outcomes.

The Analytic Solutions of the Fractional-Order Model for the Spatial Epidemiology of the COVID-19 Infection

This paper provides a mathematical fractional-order model that accounts for the mindset of patients in the transmission of COVID-19 disease, the continuous inflow of foreigners into the country, immunization of population subjects, and temporary loss of immunity by recovered individuals. The analytic solutions, which are given as series solutions, are derived using the fractional power series method (FPSM) and the residual power series method (RPSM). In comparison, the series solution for the number of susceptible members, using the FPSM, is proportional to the series solution, using the RPSM for the first two terms, with a proportional constant of ψΓnα+1, where ψ is the natural birth rate of the baby into the susceptible population, Γ is the gamma function, n is the nth term of the series, and α is the fractional order as the initial number of susceptible individuals approaches the population size of Ghana. However, the variation in the two series solutions of the number of members who are susceptible to the COVID-19 disease begins at the third term and continues through the remaining terms. This is brought on by the nonlinear function present in the equation for the susceptible subgroup. The similar finding is made in the series solution of the number of exposed individuals. The series solutions for the number of deviant people, the number of nondeviant people, the number of people quarantined, and the number of people recovered using the FPSM are unquestionably almost identical to the series solutions for same subgroups using the RPSM, with the exception that these series solutions have initial conditions of the subgroup of the population size. It is observed that, in this paper, the series solutions of the nonlinear system of fractional partial differential equations (PDEs) provided by the RPSM are more in line with the field data than the series solutions provided by the FPSM.

Adaptive immune system in severe COVID-19 patients in the first week of illness: A pilot study.

Introduction: The presentation of the course of COVID-19-related T-cell responses in the first week of the disease may be a more specific period for adaptive immune response assessment. This study aimed to clarify the relationship between changes in peripheral blood lymphocyte counts and death in patients with COVID-19 pneumonia. Methods: Thirty-three patients (14 females and 19 males) admitted for severe and desaturated COVID-19 pneumonia confirmed by polymerase chain reaction were included. Lymphocyte subsets and CD4+/CD8+ and CD16+/CD56+ rates were measured using flow cytometry from peripheral blood at admission and on the day of death or hospital discharge. Results: Twenty-eight patients survived and five died. On the day of admission, the CD4+ cell count was significantly higher and the saturation of O2 was significantly lower in the deceased patients compared to the survivors (P < 0.05). The CD16+/CD56+ rate was significantly lower on the day of death in the deceased patients than in discharge day for the survivors (P = 0.013). Conclusion: CD4+ lymphocyte percentages and O2 saturation in samples taken on the day of admission to the hospital and CD16+/CD56+ ratios taken at the time of discharge from the hospital were found to be associated with the mortality in patients with severe COVID-19.

Impacts of the COVID‐19 outbreak on older‐age cohorts in European Labor Markets: A machine learning exploration of vulnerable groups

We identify vulnerable groups through the examination of their employment status in the face of the initial coronavirus disease 2019 (COVID‐19) shock through the application of tree‐based ensemble machine learning algorithms on a sample of individuals over 50 years old. The present study elaborates on the findings through various interpretable machine learning techniques, namely Shapley values, individual conditional expectations, partial dependences, and variable importance scores. The structure of the data obtained from the Survey of Health, Aging and Retirement in Europe (SHARE) dataset enables us to specifically observe the before versus the after effects of the pandemic shock on individual job status in spatial labor markets. We identify small but distinct subgroups that may require particular policy interventions. We find that the persons in these groups are prone to pandemic‐related job loss owing to different sets of individual‐level factors such as employment type and sector, age, education, and prepandemic health status in addition to location‐specific factors such as drops in mobility and stringency policies affecting particular regions or countries.Alternate :Este estudio identificó grupos vulnerables mediante el examen de su situación laboral ante la conmoción inicial de la enfermedad por coronavirus 2019 (COVID‐19) mediante la aplicación de algoritmos de aprendizaje automático por conjuntos basados en árboles de toma de decisiones sobre una muestra de individuos mayores de 50 años. El presente estudio profundiza en los resultados a través de varias técnicas interpretables de aprendizaje automático, como los valores de Shapley, las expectativas condicionales individuales, las dependencias parciales y las puntuaciones de importancia de las variables. La estructura de los datos obtenidos del conjunto de datos de la Encuesta de Salud, Envejecimiento y Jubilación en Europa (SHARE, por sus siglas en inglés) nos permite observar específicamente los efectos del antes y el después de la conmoción de la pandemia en la situación laboral individual en los mercados laborales espaciales. Se identificaron subgrupos pequeños pero distintos que pueden requerir intervenciones políticas específicas. Se encontró que las personas de estos grupos son propensas a la pérdida de empleo relacionada con la pandemia debido a diferentes conjuntos de factores a nivel individual, como el tipo de empleo y el sector, la edad, la educación y el estado de salud previo a la pandemia, además de factores específicos de la ubicación, como las caídas en la movilidad y las políticas de rigor que afectan a determinadas regiones o países.Alternate :抄録我々は、新型コロナウイルス感æŸ"ç—‡ (COVID‐19)の最初のショックに直面した時の雇用状況ã‚'、50歳以上の個人データサンプルã‚'ツリーベースのアンサンブル法による機械学ç¿'アルゴリズムに適用して調査し、脆弱な集団ã‚'ç‰¹å®šã™ã‚‹ã€‚æœ¬ç ”ç©¶ã§ã¯ã€æ§˜ã€…ãªè§£é‡ˆãŒå¯èƒ½ãªæ©Ÿæ¢°å­¦ç¿'技è¡"によって得られた知見、すなわちシャープレイ値、個別条件付き期待値、部分å¾"属、および変数重要度スコアについて詳述する。ヨーロッパの健康と老化に関する調査 (Survey of Health, Aging and Retirement in Europe:SHARE)ã®ãƒ‡ãƒ¼ã‚¿ã‚»ãƒƒãƒˆã‹ã‚‰å¾—ã‚‰ã‚ŒãŸãƒ‡ãƒ¼ã‚¿ã®æ§‹é€ ã‹ã‚‰ã€ç©ºé–"çš„åŠ´åƒå¸‚å ´ã«ãŠã‘ã‚‹å€‹äººã®é›‡ç”¨çŠ¶æ³ã«å¯¾ã™ã‚‹ãƒ‘ãƒ³ãƒ‡ãƒŸãƒƒã‚¯ã‚·ãƒ§ãƒƒã‚¯å½±éŸ¿ã®å‰ã¨å¾Œã‚'明確に観察するã"とができる。我々は、特定の政策介入ã‚'必要とする可能性がある、規模は小さいが歴然たるサブ集団ã‚'特定した。ã"の集団の人々は、特定の地域または国に影響ã‚'åŠã¼ã™ã€ç§»å‹•æ€§ã®æ€¥æ¿€ãªä½Žä¸‹ã‚„åŽ³æ ¼åŒ–æ”¿ç­–ãªã©ã®å ´æ‰€ç‰¹ç•°çš„å› å­ã«åŠ ãˆã¦ã€é›‡ç”¨å½¢æ…‹ã‚„æ¥­ç¨®ã€å¹´é½¢ã€å­¦æ­´ã€ãƒ‘ãƒ³ãƒ‡ãƒŸãƒƒã‚¯å‰ã®å¥åº·çŠ¶æ…‹ãªã©ã®æ§˜ã€…ãªå€‹äººãƒ¬ãƒ™ãƒ«ã®å› å­ã®ãŸã‚ã«ã€ãƒ‘ãƒ³ãƒ‡ãƒŸãƒƒã‚¯ã«ã‚ˆã‚Šå¤±æ¥­ã—ã‚„ã™ã „å‚¾å‘ãŒã‚ã‚‹ã"とが分かった。

A Porcine Epidemic Diarrhea Virus Isolated from a Sow Farm Vaccinated with CV777 Strain in Yinchuan, China: Characterization, Antigenicity, and Pathogenicity

Porcine epidemic diarrhea virus (PEDV) is a porcine enteric coronavirus globally, causing serious economic losses to the global pig industry since 2010. Here, a PEDV CH/Yinchuan/2021 strain was isolated in a CV777-vaccinated sow farm which experienced a large-scale PEDV invasion in Yinchuan, China, in 2021. Our results demonstrated that the CH/Yinchuan/2021 isolate could efficiently propagate in Vero cells, and its proliferation ability was weaker than that of CV777 at 10 passages (P10). Phylogenetic analysis of the S gene revealed that CH/Yinchuan/2021 was clustered into subgroup GIIa, forming an independent branch with 2020-2021 isolates in China. Moreover, GII was obviously allocated into four clades, showing regional and temporal differences in PEDV global isolates. Notably, CH/Yinchuan/2021 was analyzed as a recombinant originated from an American isolate and a Chinese isolate, with a big recombinant region spanning ORF1a and S1. Importantly, we found that CH/Yinchuan/2021 harbored multiple mutations relative to CV777 in neutralizing epitopes (S10, S1A, COE, and SS6). Homology modelling showed that these amino acid differences in S protein occur on the surface of its structure, especially the insertion and deletion of multiple consecutive residues at the S10 epitope. In addition, cross-neutralization analysis confirmed that the differences in the S protein of CH/Yinchuan/2021 changed its antigenicity compared with the CV777 strain, resulting in a different neutralization profile. Animal pathogenicity test showed that CH/Yinchuan/2021 caused PEDV-typified symptoms and 100% mortality in 3-day-old piglets. These data will provide valuable information to understand the epidemiology, molecular characteristics, evolution, and antigenicity of PEDV circulating in China.

Measuring Quality of Life in Residential Aged Care Using the EQ-5D-5L: A Cross-Sectional Study on the Impact of Cognition Level and Proxy Perspective on Interrater Agreement

Quality of life (QoL) is an important outcome in aged care, but self-report is not always possible due to the high prevalence of cognitive impairment in older aged care residents. This study aims to assess the impact of family member proxy perspective (proxy-proxy or proxy-person) on interrater agreement with resident self-report by different cognition levels. The influence of proxy perspective and cognition level is a significant gap in the extant literature which this study seeks to address. A cross-sectional study was undertaken with residents classified into cognition subgroups according to the Mini Mental State Examination. Residents completed the self-report EQ-5D-5L, a well-established generic measure of health-related quality of life (HRQoL). Family member proxies completed EQ-5D-5L proxy version 1 (proxy-proxy perspective, where the proxy responds based on their own opinions) and proxy version 2 (proxy-person perspective, where the proxy responds as they believe the person would). Interrater agreement was assessed using the concordance correlation coefficient (CCC) for utility scores and the weighted kappa for dimension-level responses. Sixty-three residents (n = 22 no cognitive impairment, n = 27 mild impairment, and n = 14 moderate impairment) and proxies participated. EQ-5D-5L utility scores were lower for proxies compared with residents (self-report = 0.522, proxy-proxy = 0.299, and proxy-person = 0.408). Interrater agreement with self-report was higher for proxy-person (CCC = 0.691) than for proxy-proxy (CCC = 0.609). Agreement at the dimension level was higher for more easily observable dimensions, such as mobility, compared to less observable dimensions, such as anxiety/depression. Resident self-reported and proxy family member-reported HRQoL assessments, using the EQ-5D-5L, are different but may be more closely aligned when the proxy is specifically guided to respond from the person's perspective. Further research is needed to address the impact of divergences in self-report and proxy-report ratings of HRQoL for quality assessment and economic evaluation in aged care.

Assessing the poverty impact of the COVID-19-induced tourism crisis in Tanzania: a social accounting matrix microsimulation analysis

The COVID-19 pandemic has caused major disruptions to international tourism and has stimulated research interest. This study examines links between COVID-19-induced tourism disruption and poverty in Tanzania. Unlike previous studies linking COVID-19, tourism and poverty, this paper uses a social accounting matrix (SAM) microsimulation analysis that allows decomposition of poverty indices by population subgroup and assessment of the drivers of aggregate poverty. The results of the SAM multiplier analysis indicate that all households will experience reduced incomes, and that this effect will be more pronounced in urban than rural households. The microsimulation results suggest that the COVID-19-induced tourism crisis will exacerbate the poverty headcount, poverty gap and poverty severity, with urban and rural non-farm households being most affected. The results of the poverty decomposition show that the growth effect has a stronger impact than the inequality effect on increased poverty. Poverty increases and inequality decreases simultaneously. The paper suggests several demand- and supply-side policies that may help to build tourism resilience and recovery and alleviate poverty in Tanzania in the post-COVID world.

Synthesis of evidence from the PROTECT UK national core study: exploring occupational risks of SARS-CoV-2 infection and COVID-19 mortality

IntroductionThe PROTECT National Core Study was funded by the UK Health and Safety Executive (HSE) to investigate how SARS-CoV-2 is transmitted from person to person, and how this varies in different settings.One area of research aimed to compare relative differences between occupational groups and sectors in SARS-CoV-2 infection and COVID-19 mortality over time and explore the likely reasons.MethodsWe brought together evidence from nine published epidemiological studies supported by PROTECT relating to four data sets, plus new analyses relating to the Omicron period. We organised these studies into the following categories: those that specifically compared risks of infection mortality;and those that looked at risk factors for SARS-CoV-2 infection and/or COVID-19 mortality. We extracted descriptive study level data and results. We investigated risk across four pandemic waves using forest plots for key occupational groups by time. A workshop was organised in Oct 2022 with authors from each study to discuss and document key strengths and expected biases.ResultsHealthcare and social care sectors saw elevated risks of SARS-CoV-2 infection and COVID-19 mortality early in the pandemic but thereafter these declined and varied by specific occupational subgroup. The education sector saw sustained elevated risks of infection after the initial lockdown period with little evidence of elevated mortality. Results were largely consistent across different studies with differing expected biases, although unmeasured confounding cannot be ruled out.ConclusionDifferences between occupations and sectors in the UK in terms of COVID-19 risks that were observed in the early stages of the pandemic largely dissipated over time. Studies investigating risk factors suggest that reasons could include vaccination roll out, introduction of risk mitigation within high risk sectors, changes in patterns of home-working and lifting of restriction on social mixing (thereby reducing the relative effect of work).

Understanding the Digital Resilience of Physicians during the COVID-19 Pandemic: An Empirical Study

The COVID-19 pandemic has underscored the urgent need for healthcare entities to develop resilient strategies to cope with disruptions caused by the pandemic. This study focuses on the digital resilience of certified physicians who adopted an online healthcare community (OHC) to acquire patients and conduct telemedicine services during the pandemic. We synthesize the resilience literature and identify two effects of digital resilience-the resistance effect and the recovery effect. We use a proprietary dataset that matches online and offline data sources to study the digital resilience of physicians. A difference-in-differences (DID) analysis shows that physicians who adopted an OHC had strong resistance and recovery effects during the pandemic. Remarkably, after the COVID-19 outbreak, these physicians had 35.0% less reduction in medical consultations in the immediate period and 31.0% more bounce-back in the subsequent period as compared to physicians who did not adopt the OHC. We further analyze the sources of physicians' digital resilience by distinguishing between new and existing patients from both online and offline channels. Our subgroup analysis shows that, in general, digital resilience is more pronounced when physicians have a higher online reputation rating or have more positive interactions with patients on the OHC platform, providing further support for the mechanisms underlying digital resilience. Our research has significant theoretical and managerial implications beyond the context of the pandemic.

Changes in structure and function of social networks of independently living middle-aged and older adults in diverse sociodemographic subgroups during the COVID-19 pandemic: a longitudinal study.

BACKGROUND: Social networks, i.e., all social relationships that people have, contribute to well-being and health. Governmental measures against COVID-19 were explicitly aimed to decrease physical social contact. We evaluated ego-centric social network structure and function, and changes therein, among various sociodemographic subgroups before and during the COVID-19 pandemic. METHODS: Independently living Dutch adults aged 40 years and older participating in the SaNAE longitudinal cohort study filled in online questionnaires in 2019 and 2020. Changes in network size (network structure) and social supporters (network function) were assessed. Associations with risk for changes (versus stable) were assessed for sociodemographic subgroups (sex, age, educational level, and urbanization level) using multivariable regression analyses, adjusted for confounders. RESULTS: Of 3,344 respondents 55% were men with a mean age of 65 years (age range 41-95 in 2020). In all assessed sociodemographic subgroups, decreases were observed in mean network size (total population: 11.4 to 9.8), the number of emotional supporters (7.2 to 6.1), and practical supporters (2.2 to 1.8), and an increase in the number of informational supporters (4.1 to 4.7). In all subgroups, the networks changed to being more family oriented. Some individuals increased their network size or number of supporters; they were more often women, higher-educated, or living in rural areas. CONCLUSION: The COVID-19 pandemic impacted social networks of people aged 40 years and older, as they increased informational support and reduced the number of their social relationships, mainly in terms of emotional and practical supporters. Notably, some individuals did not show such unfavorable trends and managed to reorganize their networks to attribute social support roles more centrally.

Competitive Intelligence in Pharmacovigilance-A Case Study on Two Covid-19 Vaccines: An International Journal of Medical Toxicology and Drug Experience

Introduction: The comparison of safety profiles for products recently on the market is difficult. There is a lack of methodology for quantifying the potential differences between products that have the same indication. Objective: Provide the tools to quantify the differences in spontaneous reporting between two products Methods: Under the null assumption that two products have the same safety profile, the scatterplot of the Empirical Bayes Geometric Mean (EBGM) measured for the different MedDRA Preferred Terms (PTs) post Product A (axis x) and post Product B (axis y) should follow the diagonal line. An Euclidian distance from the EBGM to the diagonal line measures the deviation from what would have been expected under the null assumption of similar safety profiles. As the deviation does not capture the statistical uncertainty around the estimate, we propose as measure of the deviation the minimal distance of the four Euclidian distances calculated from each of the credibility intervals around the EBGM post Product A and Product B. Results: We quantified the most significant differences in reporting between the two vaccines that were approved in the US against covid19 using publicly available data from the Vaccine Adverse Event Reporting System (VAERS). A visualization capturing the global trend of the most substantial differences in reporting was generated. Conclusion: This relatively simple method can provide quantification of the differences in reporting and could help prioritize one product over the other for some population subgroups.

Role of Background Incidence in Signal Detection;Observed/ Expected Analysis of Classical Thromboembolism with COVID 19 Vaccines in The Netherlands: An International Journal of Medical Toxicology and Drug Experience

Introduction: Spontaneous reporting (SR) is a key method for monitoring the safety of COVID-19 vaccines used in the pandemic in 2021. SR led to early warnings of vaccine-induced-thrombosis-withthrombocytopenia (VITT) with the vector vaccines of AstraZeneca and Janssen [1-3]. In addition, an increase of reports of other thromboembolic events with both vector and mRNA vaccines was seen. For now, venous thromboembolism (VTE) is labelled for Janssen and cerebral-venous-thrombosis (CVST) for the AstraZeneca vaccines [4,5]. Because a large population is vaccinated in a short period of time and the fact that venous (VTE) and arterial thrombosis (ATE) are quite common conditions, the number of reports should be compared with background incidence rates as part of signal detection. Objective: We evaluated the use of Standardised Morbidity Rates (SMR) to compare spontaneously reported cases of thromboembolism with COVID-19 vaccines with stratified Dutch background incidence rates from 2019 in the vaccine exposed population. Methods: SMRs are calculated by dividing the reported as observed (O) cases by the expected (E) number within risk windows of 14/28 days following each dose and vaccine. SMR >1 indicates that more cases were reported than expected [6]. Results: Until 9 December 2021, 2080 reports were received concerning at least one thromboembolic event with 24 million administered COVID-19 vaccines. These concerned 1000 of VTE, 956 of ATE, 19 of CVST and 134 reports of miscellaneous forms of thrombosis. Cases of VITT (TTS) were excluded. In the table the main results are summarized and highlighted. For AstraZeneca, SMRs reach or exceed 1 for VTE, ATE and CVST, especially in people aged < 60 years. With the second dose of mRNA vaccines more cases of the rare condition CVST were observed in men, although absolute numbers are low;n = 3 for men with 2nd dose of Pfizer (14 days) and n = 1 for men with 2nd dose of Moderna (28 days). Conclusion: SMRs can be used when the exposed population is defined, stratified background incidence rates are available and the reporting rate is substantial. The rate of underreporting is unknown, differs in population subgroups, and is influenced by media attention. Therefore, SMRs near 1 are also considered to be 'high'. Our data cannot confirm nor exclude a potential signal of other types of thromboembolism with COVID-19 vaccines. But the potential signal initiated further epidemiological research to confirm and quantify a potential increased risk of thromboembolism with COVID-19 vaccines.

Network Structure Features and Influencing Factors of Tourism Flow in Rural Areas: Evidence from China

Exploring the spatial network structure of tourism flow and its influencing factors is of great significance to the transmission of characteristic culture and the sustainable development of tourism in tourist destinations, especially in backward rural areas. Taking Qiandongnan Miao and Dong Autonomous Prefecture (hereinafter referred to as Qiandongnan Prefecture) as an example, this paper adopts social network analysis and Quadratic Assignment Procedure regression analysis to study the network structural characteristics and influencing factors of tourism flow using online travel blog data. The results show that: (1) There are seasonal changes in tourism flow, but the attractions that tourists pay attention to do not change with the seasons. (2) The tightness of the tourism flow network structure is poor. The core nodes are unevenly distributed, and there are obvious structural holes. (3) The density of the tourism flow network is low. There is a clear core–periphery structure in the network, and the core area has a weak driving effect on the periphery area. There are more cohesive subgroups in the network, but the degree of connectedness between the subgroups varies greatly. (4) Geographical adjacency, transportation accessibility, and tourism resource endowment influence tourism flow network structure. The study found that the influencing factors of tourism flow in rural areas are different from those in urban areas. These results provide useful information for the marketing and development of tourism management departments in rural areas.

COVID-19 TANISI ALAN ÇOCUKLARIN B LENFOSÍT HÜCRELERÍNÍN VE ALT GRUPLARININ AKIŞ SÍTOMETRÍK DEĞERLENDÍRÍLMESÍ

Objective: During viral infections, antibody production of B cells are critical for protective immunity. It is known that the COVID-19 disease has a milder course in children. It is crucial to evaluate the causes of this situation from a pediatrician’s perspective to determine the treatment goals of the disease. We aimed to examine the flow cytometric changes in B cells and subtypes observed in children diagnosed with the COVID-19 infection. Materials and Methods: This is a prospective cohort study including 22 children aged 0-18 who had been diagnosed with COVID-19. CD19+B cells, CD27-IgD+ naive B, CD21low immature B, CD21lowCD- 38low active B, CD27-IgD- double-negative B, CD27- non-memory B, CD27+ memory B, CD27+IgD- switched memory B, and CD27+IgD+ non-switched memory B cells were studied using flow cytometry. Results: B cells counts decreased as a percentage in the 2-5 years age group and the 10-16 age group as an absolute number. Naive and non-memory B cell frequencies increased in the 5-10 years old and over 16 years old groups. Double negative B cells were normal in all age groups. Non-memory B cells increased in the 5-10 and over 16 years old groups, whereas memory B cells decreased. In all groups, switched memory B cells decreased. Non-switched memory B cell counts were within reference ranges in all groups except for the over 16 years group. Conclusion: Although the decrease in B cell count is associated with the severity of the disease, naive B cell subgroups did not decrease in the pediatric patients included in the study. All groups showed increased switched memory B cell counts, in accordance with the literature. Unlike adults, naive B cells, non-switched memory B cells, and double-negative B cells were normal in children. (English) [ FROM AUTHOR] Amaç: Viral enfeksiyonlar sırasında B hücrelerinin antikor üretimi, koruyucu bağışıklık için kritiktir. Çocuklarda COVID-19 hastalığının daha hafif seyrettiği bilinmektedir. Bu durumun nedenlerini çocuk doktoru gözüyle değerlendirmek, hastalığın tedavi hedeflerini belirlemek açısından çok önemlidir. COVID-19 enfeksiyonu tanısı alan çocuklarda gözlenen B hücre ve alt tiplerinde akım sitometrik değişiklikleri incelemeyi amaçladık. Gereç ve Yöntem: Çalışmamız 0-18 yaş arası COVID-19 teşhisi konulan 22 çocuğu içeren prospektif kohort bir araştırmadır. CD19+B hücreleri, CD27-IgD+ saf B, CD21düşük olgunlaşmamış B, CD21düşükCD38düşük aktif B, CD27-IgD- çift negatif B, CD27- bellek B, CD27+ bellek B, CD27+IgD- dönüşmüş (switched) bellek B, CD27+IgD+ dönüşmemiş (non-switched) bellek B hücreleri akış sitometrisi ile incelenmiştir. Bulgular: B hücre sayısı 2-5 yaş grubunda yüzde olarak, 10-16 yaş grubunda ise mutlak sayı olarak azaldı. 5-10 yaş ve 16 yaş üstü gruplarda naif ve hafıza dışı B hücrelerinin oranları arttı. Çift negatif B hücreleri tüm yaş gruplarında normaldi. Bellek dışı B hücreleri 5-10 yaş arasında ve 16 yaş üzerinde artarken, aynı gruplarda bellek B hücreleri azaldı. Dönüşmüş bellek B hücreleri tüm yaş gruplarında azaldı. Dönüşmemiş bellek B hücreleri, 16 yaşın üzerinde azaldı ve diğer tüm yaş gruplarında normal görünüyordu. Sonuç: B hücre sayısındaki azalma hastalığın şiddeti ile ilişkili olmasına rağmen, çalışmaya dâhil edilen çocuk hastalarımızda naif B hücre alt gruplarında azalma olmadı. Literatüre uygun olarak tüm gruplarda dönüşmüş bellek B hücreleri arttı. Çocuklarda yetişkinlerden farklı olarak naif B hücreleri, dönüşmemiş bellek B hücreleri ve çift negatif B hücreleri normaldi. (Turkish) [ FROM AUTHOR] Copyright of Istanbul Tip Fakültesi Dergisi is the property of Istanbul Tip Fakultesi Dergisi and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Immunotherapy for people with clinically isolated syndrome or relapsing-remitting multiple sclerosis: treatment response by demographic, clinical, and biomarker subgroups (PROMISE)-a systematic review protocol.

BACKGROUND: Multiple sclerosis (MS) is an inflammatory and degenerative disease of the central nervous system with an increasing worldwide prevalence. Since 1993, more than 15 disease-modifying immunotherapies (DMTs) have been licenced and have shown moderate efficacy in clinical trials. Based on the heterogeneity of the disease and the partial effectiveness of therapies, a personalised medicine approach would be valuable taking individual prognosis and suitability of a chosen therapy into account to gain the best possible treatment effect. The primary objective of this review is to assess the differential treatment effects of all approved DMTs in subgroups of adults with clinically isolated syndrome or relapsing forms of MS. We will analyse possible treatment effect modifiers (TEM) defined by baseline demographic characteristics (gender, age), and diagnostic (i.e. MRI measures) and clinical (i.e. relapses, disability level) measures of MS disease activity. METHODS: We will include all published and accessible unpublished primary and secondary analyses of randomised controlled trials (RCTs) with a follow-up of at least 12 months investigating the efficacy of at least one approved DMT, with placebo or other approved DMTs as control intervention(s) in subgroups of trial participants. As the primary outcome, we will address disability as defined by the Expanded Disability Status Scale or multiple sclerosis functional composite scores followed by relapse frequency, quality of life measures, and side effects. MRI data will be analysed as secondary outcomes. MEDLINE, EMBASE, CINAHL, LILACS, CENTRAL and major trial registers will be searched for suitable studies. Titles and abstracts and full texts will be screened by two persons independently using Covidence. The risk of bias will be analysed based on the Cochrane "Risk of Bias 2" tool, and the certainty of evidence will be assessed using GRADE. Treatment effects will be reported as rate ratio or odds ratio. Primary analyses will follow the intention-to-treat principle. Meta-analyses will be carried out using random-effects models. DISCUSSION: Given that individual patient data from clinical studies are often not available, the review will allow to analyse the evidence on TEM in MS immunotherapy and thus support clinical decision making in individual cases. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021279665 .

A FLOW CYTOMETRIC EVALUATION OF B LYMPHOCYTE CELLS AND SUBGROUPS OF CHILDREN DIAGNOSED WITH COVID-19

Objective: During viral infections, antibody production of B cells are critical for protective immunity. It is known that the COVID-19 disease has a milder course in children. It is crucial to evaluate the causes of this situation from a pediatrician's perspective to determine the treatment goals of the disease. We aimed to examine the flow cytometric changes in B cells and subtypes observed in children diagnosed with the COVID-19 infection. Materials and Methods: This is a prospective cohort study including 22 children aged 0-18 who had been diagnosed with COVID-19. CD19(+)B cells, CD27(-)IgD(+) naive B, CD21(low )immature B, CD21(low)CD38(low) active B, CD27(-)IgD(-) double-negative B, CD27(-) non-memory B, CD27(+) memory B, CD27(+)IgD(-) switched memory B, and CD27(+)IgD(+) non-switched memory B cells were studied using flow cytometry. Results: B cells counts decreased as a percentage in the 2-5 years age group and the 10-16 age group as an absolute number. Naive and non-memory B cell frequencies increased in the 5-10 years old and over 16 years old groups. Double negative B cells were normal in all age groups. Non-memory B cells increased in the 5-10 and over 16 years old groups, whereas memory B cells decreased. In all groups, switched memory B cells decreased. Non-switched memory B cell counts were within reference ranges in all groups except for the over 16 years group. Conclusion: Although the decrease in B cell count is associated with the severity of the disease, naive B cell subgroups did not decrease in the pediatric patients included in the study. All groups showed increased switched memory B cell counts, in accordance with the literature. Unlike adults, naive B cells, non-switched memory B cells, and double-negative B cells were normal in children.

‘Down to the person, the individual patient themselves’: A qualitative study of treatment decision‐making for shoulder pain

IntroductionMany inconsistencies have been identified in the translation of evidence‐based treatment recommendations for musculoskeletal shoulder pain into healthcare services, with little known about factors influencing decision‐making. The objective of this study was to explore the views and experiences of healthcare providers (HCPs) and people living with shoulder pain on treatment decision‐making.MethodsAdopting a qualitative design, purposeful sampling was employed to recruit 13 individuals with nonspecific musculoskeletal shoulder pain and 30 HCPs. Data were collected through 1:1 semi‐structured interviews and analysed using an approach informed by Constructivist Grounded Theory. To facilitate analysis, two patient and public involvement (PPI) meetings were conducted.ResultsMost participants (69%) had shoulder pain of ≥1‐year duration. Biomechanical beliefs about shoulder pain predominated and were heavily influential in decision‐making for both patients and HCPs. Despite a consensus that therapeutic alliance facilitated decision‐making, the extent of collaboration between HCPs and patients in treatment decision‐making was rather limited. In addition to condition‐specific factors, Individual patient characteristics and resources also influenced treatment decisions.ConclusionFindings revealed the complexity of the decision‐making process for both patients and HCPs, exposing substantial gaps between the reported views and experiences of participants and the principles of client‐centred and evidence‐based practice. There is a pressing need to enhance the translation of evidence‐based knowledge into practice in this clinical area.Patient or Public ContributionIn line with a consultative approach to collaborative data analysis, a subgroup of participants attended two PPI meetings to provide commentary and feedback on preliminary findings.

Identifying higher risk subgroups of health care workers for priority vaccination against COVID-19.

Background: Health care workers (HCWs) are exposed to high risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection due to close contact with infected patients in hospital. The objective of this study was to estimate the seroprevalence and to identify the exposure risk of various subgroups among HCWs to prioritize them for early vaccination. Methods: This was a multicentre cross-sectional study conducted between 15 and 29 June 2020. A total of 987 HCWs were recruited randomly from two major tertiary-care hospitals of Peshawar city, Pakistan. The HCWs included doctors, nurses, paramedics and hospital support staff. The US Food and Drug Administration (FDA)-approved kit was used for the detection of SARS-CoV-2 antibodies. Results: Overall, 310 (31.4%) HCWs were seropositive for SARS-CoV-2 antibodies (95% confidence interval, CI: 28.5-34.4). Seroprevalence was higher in males (33.5%) and in age group 51-60 years (40.9%). Seropositivity increased with increasing age from 8.3% in age group ⩽20 to 40.9% in 51-60 years of age group (p < 0.05). The highest seroprevalence was identified in paramedical staff (42·5%, 95% CI: 36.6-48.6) followed by nursing staff (38·8%, 95% CI: 32.1-45.7). In logistic regression, being a male HCW led to higher risk of seropositivity (odds ratio, OR: 1.50, 95% CI: 1·06-2.13. p < 0.05) compared with female staff members. The odds of seropositivity was higher in nurses (OR: 3·47, 95% CI: 1.99-6.05. p < 0.01), paramedical staff (OR: 3·19, 95% CI: 1.93-5.28. p < 0.01) and hospital support staff (OR: 2·47, 95% CI: 1.29-4.7. p < 0.01) compared with consultants. Conclusion: Overall, our results concluded that nursing and paramedical staff are at higher risk and should be vaccinated on priority.