Spanish-speaking Hispanic people (90%) had the highest satisfaction with WIC nutrition education. Preferential differences among participants suggest that providing flexible options may improve program satisfaction and emphasizes the need for future studies to examine WIC services by race and ethnicity.Understanding satisfaction of nutrition education and other services provided in the Special Supplemental Nutrition Program for Women, Infants and Children (WIC) is needed to ensure the program is responsive to the needs of diverse populations. This study examined the variation of WIC participants’ perceptions and satisfaction with WIC nutrition education and services by race, ethnicity, and language preference. Phone surveys were conducted in 2019 with California WIC families with children aged 1–4 years. While most participants (86%) preferred one-on-one nutrition education, online/mobile apps were also favored (69%). The majority (89%) found nutrition education equally important to receiving the WIC food package. Racial/ethnic groups differed in which WIC service they primarily valued as 20% of non-Hispanic White people rated the food package as more important than nutrition education compared to 5% of Spanish- and 6% of English-speaking Hispanic people, respectively. More Spanish (91%) and English-speaking Hispanic people (87%) than non-Hispanic white (79%) or Black people (74%) changed a behavior because of something they learned at WIC ( The Special Supplemental Nutrition Program for Women, Infants and Children (WIC) provides nutrition education and supplemental healthy foods to 6.4 million nutritionally at-risk low-income women, infants, and young children in the United States . AdminisWIC is the only USDA FNS program federally required to provide nutrition education, which is intended to improve nutritional status, prevent nutrition-related problems , and impUnderstanding WIC participant satisfaction with nutrition education ensures its most unique service is accommodating to individual needs and meets current public health challenges, a mission of WIC’s Revitalizing Quality Nutrition Services (RQNS) program . TherefoA multi-disciplinary team from the California WIC program, Public Health Foundation Enterprises (PHFE) WIC Program, and the Nutrition Policy Institute at the University of California Division of Agriculture and Natural Resources conducted the study. The California Health and Human Services Agency’s Committee for the Protection of Human Subjects approved the study.A sample of nearly 10,000 children, ages 1–4 years with an active WIC certification record as of August 2018 was randomly selected from state administrative records to reach a goal of 3000 survey respondents. This goal was selected assuming a 5% type 1 error rate and 90% power to detect a 2–3% difference in the proportion of respondents reporting a behavior before and after the main study’s EBT rollout in California . In OctoSurvey questions were adapted from previous surveys ,20,21, pDemographics and variables of interest were collected from two sources, WIC administrative records and survey data. WIC administrative records were used to determine child sex and the following sociodemographic information was collected from respondents in the survey: race and ethnicity, primary language preference (English or Spanish), highest level of education completed, current employment status, number of young children in the household (<5 years old), current participation in SNAP and Medicaid, total duration and current participation in WIC, and child age. Questions with multiple response options were asked to evaluate respondent satisfaction with WIC nutrition education and reasons for remaining on the program, and household food insecurity was determined using the USDA 2-item validated screener .p < 0.003 (p = 0.05/15). Data are presented for the total sample and stratified by racial–ethnic groups. Data were analyzed using SAS software .The following respondent racial and ethnic and language groups were examined: non-Hispanic White (hereafter referred to as White), English-speaking Hispanic, Spanish-speaking Hispanic, Non-Hispanic Black (hereafter referred to as Black), Asian, and Other . English and Spanish-speaking Hispanic respondents were examined separately based on prior studies showing differences in satisfaction with WIC based on primary language ,22. Racin = 60) or had insufficient data (n = 4) were excluded from analyses, bringing the analytical sample to 2933  for all groups. Compared to other groups, more Spanish-speaking Hispanic respondents attended group sessions (70.7%) and fewer used online education (43.5%). Asian respondents (42.7%) reported the most use of two-way texting compared to White respondents (22.5%) who reported the least. Videos/DVDs were reported most by Spanish-speaking Hispanic respondents (77.5%) and least used by White respondents (67.9%).Most survey respondents reported receiving one-on-one nutrition education from WIC staff (91.3%), followed by watching a video or DVD (74.7%), attending a group session (62.5%), or taking an online class (57.5%) . Two-wayIn terms of the preferred modes of receiving WIC nutrition education in the future, in-person one-on-one mode was selected by 86.4% of survey respondents, followed by video/DVD (75.9%), online (68.9%), group session (62.3%), and two-way texting (55.4%) modes . Over twOverall, most respondents were very satisfied with WIC nutrition education (83.6%) and customer service (87.2%). Levels of satisfaction with nutrition education were highest among Spanish-speaking Hispanic respondents (90.1%) and lowest among respondents in the Other racial–ethnic group (77.8%) . Respondp < 0.001). Spanish-speaking Hispanic respondents selected more reasons for participating in WIC while White, Asian, and Black respondents selected fewer reasons. When asked whether WIC food or education benefits were more important or both were equally important, 89.6% of the overall sample reported that both were equally important. Spanish-speaking Hispanic respondents (93.7%) were more likely than other groups to report that foods and nutrition education were equally important. Compared to the other racial and ethnic groups, more respondents in the White (20.4%) and Other (12.4%) groups rated WIC foods as more important than WIC nutrition education or both.When asked about reasons for continuing to participate in WIC, most survey respondents reported the fruits and vegetables provided in the child WIC food package (92.5%), followed by information from WIC staff (87.0%), support from WIC staff (86.0%), and classes and group sessions (65.7%) . The mosStudy findings in 2019, before the COVID-19 pandemic, suggest that caregivers with young children in WIC were highly satisfied with the nutrition education and customer service provided in California. Overall, Spanish-speaking Hispanic respondents valued WIC nutrition education more than other racial and ethnic groups did. This was also determined in a study focused on WIC food package changes which reported a higher percentage of Spanish-speaking participants being satisfied compared to English speakers . All racIn the current study, Spanish-speaking Hispanic respondents were the only group to choose videos/DVDs as their secondary mode of education delivery, whereas other groups chose either online or mobile app. When comparing online and WIC mobile app education, all groups preferred online education except Spanish-speaking Hispanic and Black respondents. This is supported by previous research that showed low-income Hispanic and Black individuals often underutilize the internet as they are more likely to be mobile-only users; however, differences between English- and Spanish-speaking Hispanic individuals were not reported . It has Pre-pandemic in-person nutrition education, especially one-on-one education, offered the benefit of a personalized experience allowing the participant to establish their own nutrition goals which has been shown to be more effective . HoweverA national study on WIC nutrition education determined that WIC staff reported difficulty in delivering nutrition education to participants that are more interested in solely receiving cash benefits from WIC . HoweverLanguage barriers have been identified in prior studies as one challenge with WIC participation ,30. For A strength of this study is the fact that California serves one in seven of all WIC participants nationally and accommodates some of the most racially and ethnically diverse populations. Therefore, understanding perceptions of California WIC’s nutrition education program is crucial to understanding the program nationally. Few studies exploring the impacts of WIC services have been able to determine a direct benefit of nutrition education on the nutritional behavior of participants. The study also has limitations, as it was conducted pre-pandemic. While participant preferences in modality of education may have changed, this study emphasizes the importance of future studies examining WIC nutrition education by race and ethnicity and language, as differences do exist. Another limitation is that all survey responses were self-reported to an interviewer, which may have biased responses given that respondents were informed that the survey was being conducted by WIC. In addition, results are not representative of California as a whole, as Spanish speakers were overrepresented in the total sample.Overall, WIC services were highly rated by California WIC participants who has children in the program, regardless of race and ethnicity and language spoken. These findings suggest that offering flexible options for nutrition education and more fruits and vegetables in the food package may improve long-term retention of children in WIC. As California WIC’s response to the COVID-19 pandemic has shifted most of WIC operations to remote services, this study highlights participants’ value of in-person interactions supporting a future ‘hybrid’ model. Future studies are warranted to evaluate newly adapted WIC nutrition educational practices on participant satisfaction and future preferences.


Studies in several sub-Saharan geographies conducted early in the COVID-19 pandemic suggested little impact on contraceptive behaviours. Initial results may mask widening disparities with rising poverty, and changes to women’s pregnancy desires and contraceptive use amid prolonged health service disruptions. This study examined trends in contraceptive behaviours in four sub-Saharan African settings 1 year into the pandemic.Nationally and regionally representative longitudinal surveys.Burkina Faso, Kenya, Democratic Republic of Congo (Kinshasa) and Nigeria (Lagos).Women aged 15–49 years with sample size ranging from 1469 in Nigeria to 9477 in Kenya.Fertility preferences, contraceptive use and unintended pregnancies measured before COVID-19 (November 2019 to January 2020) and during COVID-19 (November 2020 to January 2021).We described population-level and individual-level changes by socioeconomic characteristics using generalised equation modelling. We used logistic regression models to identify factors related to contraceptive adoption and discontinuation and to experiencing an unintended pregnancy.At the population level, we found no change in women’s exposure to unintended pregnancy risk, alongside 5–9 percentage point increases in contraceptive prevalence in Burkina Faso, Kenya and Lagos. Reliance on provider-dependent methods dropped by 2 and 4 percentage points in Kenya and Burkina Faso, respectively, although these declines were not statistically significant. Between 1.0% and 2.8% of women across sites experienced an unintended pregnancy during COVID-19, with no significant change over time. Individual-level trajectories showed contraceptive adoption was more common than discontinuation in Burkina Faso, Kenya and Lagos, with little difference by sociodemographic characteristics. Women’s COVID-19-related economic vulnerability was unrelated to unintended pregnancy across sites.This study highlights the resilience of African women across diverse settings in sustaining contraceptive practices amid the COVID-19 pandemic. However, with reports of rising poverty in sub-Saharan Africa, there is continued need to monitor access to essential sexual and reproductive health services. The study uses a longitudinal design to assess individual change in contraceptive behaviours since the onset of the COVID-19 pandemic.Nationally or regionally representative survey data were used to evaluate population-level change in contraceptive behaviours since the onset of the COVID-19 pandemic.This investigation spans four diverse geographies in sub-Saharan Africa, allowing for a comparison of COVID-19 impact by social and pandemic contexts.Rates of loss to follow-up ranged from 21% to 27%, likely affecting study estimates, although the use of poststratification weights reduces attrition biases.Data from two time points prevent the estimation of gaps in contraceptive use over the entire COVID-19 pandemic.The COVID-19 pandemic, which started in late 2019, quickly traversed the globe, creating health and economic crisis. By the end of 2020, the SARS-CoV-2 virus had resulted in nearly 2 million deaths,3Loss of household income,15While these initial studies were pivotal in reporting early pandemic trends, the longer term societal impacts of COVID-19, including rising poverty22Expanding on these results, the present study describes population-level and individual-level changes in women’s fertility preferences, contraceptive behaviours and unintended pregnancy experiences in the first year of the COVID-19 pandemic using cross-sectional representative data and panel data collected in the same sub-Saharan African geographies. Specifically, we examined how these trends differed by sociodemographic characteristics and COVID-19-related economic hardship. Finally, we assessed factors related to individual-level changes in contraceptive behaviours and to experiencing an unintended pregnancy during the pandemic.www.pmadata.org) collected in November 2019 to January 2020 (3–4 months before the pandemic) and 1 year later (November 2020 to January 2021) from nationally or regionally representative, population-based surveys. Surveys were implemented by the PMA project among women aged 15–49 years in four sub-Saharan African geographies. Surveys are nationally representative in Burkina Faso and Kenya, and regionally representative in Kinshasa province in DRC and Lagos state in Nigeria. We did not include data from Kongo Central in the DRC and Kano state in Nigeria, also collected through the PMA platform due to smaller sample size and lack of statistical power to show any reduction in contraceptive use in these two geographies.We used two rounds of publicly available data  after stratifying by rural and urban areas (in Kenya and Burkina Faso), followed by the random selection of 35 households per EA. All women of reproductive age (15–49 years) from the selected households were eligible for inclusion. Sample sizes were determined to produce modern contraceptive prevalence rates with a precision of ±3% at the national or regional level, leading to sample size variation by geography .This study is a population-based study that does not include patients. The public was not involved in this research.www.pmadata.org).Prepandemic data (PMA’s phase 1 surveys) were collected face to face by trained resident interviewers before COVID-19 (November 2019 to January 2020). Women who consented to be followed up as part of PMA’s panel design were reinterviewed in person, 1 year later (PMA’s phase 2 surveys), during the pandemic (November 2020 to January 2021). Replacement households from the EA were also included in phase 2 to account for attrition at the household level (projected at 15%). The survey design allows for longitudinal analysis to examine individual-level changes since the onset of COVID-19 and for annual cross-sectional analysis to track national or regional-level indicators (including household replacements). Follow-up rates between phase 1 and phase 2 surveys ranged from 73% in Kenya to 79% in Burkina Faso . No diffAt each survey, women were asked about their current pregnancy status, whether the pregnancy was wanted or happened at the right time, future fertility intentions and current contraceptive behaviours. This information was operationalised as indicators used for population-level comparisons  and for individual-level trends analysis .Women’s fertility intentions for the next year distinguished women who intended to have a child in the next year from those who wanted no more children or wanted to delay childbearing for more than 1 year. Exposure to the risk of unintended pregnancy (yes/no) classified women who had sexual intercourse in the last 12 months, were fecund and were not pregnant or trying to have a child in the next year as being ‘at risk’. Among women at risk of unintended pregnancy, use of contraception (yes/no) classified women who were using barrier and natural methods, pills, injectables, patches, rings, implants, intrauterine devices (IUDs) and sterilisation as using contraception. Among contraceptive users, use of a provider-dependent method (yes/no) classified women using methods generally requiring interaction with a healthcare provider  as provider-dependent method users. We also considered a three-category measure of contraceptive method type, grouping contraceptive users according to the effectiveness of their contraceptive method—users of less effective methods , users of effective methods  and users of highly effective methods . Pregnancy status identified women who were pregnant at the time of each survey (yes/no), while an indicator of unintended pregnancy (yes/no) identified women who were pregnant and indicated they had not wanted to become pregnant or wanted to become pregnant later.We explored six measures reflecting women’s SRH experiences before and during the pandemic. exposure to the risk of unintended pregnancy, contraceptive use and experience of an unintended pregnancy . Changes in women’s exposure to unintended pregnancy risk across the two surveys were categorised into four categories: (1) no risk—never at risk before or during COVID-19; (2) acquired risk—newly at risk during COVID-19 (no risk before pandemic); (3) ceased risk—no longer at risk during COVID-19 (at risk before pandemic); (4) sustained risk—at risk before and during COVID-19. Likewise, we defined a four-category variable describing trends in any contraceptive use: (1) continued non-use—non-use before or during COVID-19; (2) adoption—during COVID-19 (non-use before pandemic); (3) discontinuation—non-use during COVID-19 following use before pandemic; (4) continued use—use before and during COVID-19. Finally, we considered the three-category indicator of contraceptive effectiveness (less effective/effective/highly effective) and a binary indicator of unintended pregnancy (yes/no) during phase 2 , as previously defined.We also explored individual-level changes in women’s We considered several sociodemographic and COVID-19-related factors that could impact women’s use of contraception. Specifically, we assessed age, parity, marital status (in union/not in union), education, household wealth in tertiles and residence . During COVID-19, we also considered two indicators of household economic vulnerability: loss of income in the last 12 months  and food insecurity .We first examined population-level trends in reproductive health indicators comparing phase 1 and phase 2 cross-sectional samples across our six indicators . We conducted the same analysis stratified by rural and urban residence in Burkina Faso and Kenya to compare trends across urban localities . Statistically significant differences were determined based on non-overlapping CIs between phase 1 and phase 2 estimates.Next, we conducted individual-level analysis, focusing on the sample of women completing both surveys. We evaluated changes in exposure to unintended pregnancy risk and changes in contraceptive behaviours (among women at risk at both time points). We used generalised estimation equation (GEE) models to test for differential trends in the use of any contraception between phase 1 and phase 2 by women’s sociodemographic characteristics (measured at phase 1) and their experience of economic instability (measured at phase 2) . Next, w10.1136/bmjopen-2022-062385.supp1Supplementary dataAll analyses applied survey and poststratification weights to account for the complex survey design, clustering of women within EAs and differential loss to follow-up in the case of the longitudinal sample. All analyses were conducted in Stata V.16.1 with statistical significance set a priori at p<0.05.The characteristics of prepandemic study samples by setting are presented in At the population level, 6.2%–16.8% of women intended a birth in the next 12 months across geographies, with no significant change during the pandemic , includiContraceptive use (any method) varied widely by setting and was lowest in Burkina Faso and highest in Kenya and Kinshasa province in the DRC. During the pandemic, contraceptive use rose significantly by 9 percentage points in Burkina Faso and 5 percentage points in Kenya. The rise in contraceptive use among women in Burkina Faso was twice as elevated in rural settings (10 percentage points) compared with urban settings  while increases were comparable and statistically significant in rural and urban Kenya . ContracBetween 5.1% of women in Kenya and 8.5% of women in Burkina Faso were pregnant at the time of the survey with no change over time. Finally, between 1.0% and 2.8% of women across sites had an unintended pregnancy at the time of the phase 2 survey, this proportion remaining stable over time in all sites . No signAssessment of individual-level trajectories of women who responded to both surveys indicated that changes in exposure to unintended pregnancy risk among all women ranged from 16.9% in Kinshasa-DRC to 31.5% in Burkina Faso . PatternWhile results from GEE models identified few statistically significant interactions between time and women’s characteristics, signalling limited differences in contraceptive trends by sociodemographic characteristics, some patterns emerged . For exaFew factors were related to contraceptive adoption among women who were not using a method before the pandemic and to contraceptive discontinuation among those using contraception before the pandemic . The oddFinally, factors associated with characterising an unintended pregnancy during COVID-19 among women who had sexual intercourse in the last 12 months are reported in This study confirms women’s resiliency in contraceptive use to prevent unintended pregnancies across a diversity of sub-Saharan contexts, despite the profound economic and social disruptions caused by the COVID-19 pandemic.These results challenge the initial forecasts of rising unintended pregnancies due to service disruptions to SRH services in low and middle-income countries.23First, while disruptions to SRH services were reported in the early stage of the pandemic,23 27–29Further, it is possible that the quality of facility-based registers, including clients’ family planning records, was impacted due to understaffing amid COVID-19-related disruptions and, thus, early pandemic provision of care was under-reported.30At the same time, the expansion or continued use of high-impact practices in family planning,25www.pmadata.org). Self-provision of contraceptive pill/oral contraceptives during the COVID-19 is likely to have facilitated women’s access to short-acting contraception,A third explanation lies in the resilience of women in intensifying their efforts or finding alternative solutions to access contraception and self-manage their contraceptive needs.https://fp2030.org/FP2030-commitment-makers), including increased public funding, and expansion of free access to contraception in some countries, such as Burkina Faso in 2019, are likely to have mitigated the economic impact of COVID-19, but the affordability of contraception remains a prominent concern for women experiencing economic hardship.18These overall trends remain encouraging, but a critical concern over widening social disparities in family planning access may still arise in the face of increasing economic hardships.Our results should be considered with several limitations in mind. Specifically, the loss to follow-up rate ranged from 21% to 27% across geographies, which is likely to affect the reported estimates of change. However, the use of replacement households in phase 2 of data collection was designed to minimise impacts to population-level estimates. Further, poststratification weights were used in panel analysis to limit the potential for attrition biases; stable estimates of sociodemographic distributions across samples were observed . A seconOur study also has several strengths. First, our population-based approach provides a complimentary perspective to data collected via Health Management Information Systems, showing little change in behaviours and SRH outcomes, despite facility-based disruptions, suggesting the importance of non-facility-based services and self-care practices in ensuring continuity of family planning care.25 26In conclusion, the current study provides important insights on the resilience of women across geographically and socially diverse contexts in sub-Saharan Africa in sustaining contraceptive practices amid the COVID-19 pandemic. Renewed national and international commitments to family planning made as part of the 2011 Ouagadougou Partnership


Objectives: This study aimed to explore perceptions and willingness to get coronavirus disease 2019 (COVID-19) booster vaccination among pregnant and lactating women in Jordan.Methods: A cross-sectional study using a 29-item web-based questionnaire was conducted. Sociodemographic characteristics, vaccine acceptance, confidence in the booster dose of COVID-19 vaccine, perception of risk for COVID-19, and acceptance to participate in COVID-19 booster vaccine clinical trials were prospectively evaluated. Logistic regression was used to identify factors that might affect the participants’ acceptance of a COVID-19 vaccine and their willingness to enroll in clinical trials of a booster dose of COVID-19 vaccine.Results: Among all participants , 328 (56.2%) intended to receive the booster dose of the COVID-19 vaccine. Predictors of booster dose acceptance were a medical-related degree , income , living residency , knowing pregnant/lactating women previously infected with infectious microbe , commitment to immunization for children , receiving an influenza vaccine , and worried about infectious microbes . Among participants, only 22.9% were willing to participate in clinical trials of the booster dose of COVID-19 vaccine. The biggest motivator for participation was the participants’ desire to help find the best vaccine during pregnancy/lactation (57.5%) while the main barrier towards participation was not wanting to expose themselves and their babies to more side effects (88.0%).Conclusion: This study reported reasonable acceptance of vaccination in a sample of pregnant/lactating women. Vaccination hesitancy for the booster dose was in-line with similar studies on the primary series around the globe, but the willingness to participate in clinical trials was lower than non-pregnant/non-lactating women. Pregnant women with coronavirus disease 2019 (COVID-19) infection are at increased risk for pregnancy complications, such as preterm birth and pregnancy loss, and neonatal intensive care unit admission [Due to limited data concerning maternal-infant transmission of COVID-19 during breastfeeding, literature on breastfeeding management in confirmed COVID-19 mothers did not recommend breastfeeding in suspected and uncured cases and also while taking lopinavir/ritonavir treatment . In addiVaccination during pregnancy and lactation is common to prevent both maternal and infant morbidity caused by other infectious diseases, such as influenza and pertussis. The clinical data on safety and efficacy of such vaccines are abundant ,6. HowevAdditionally, in 2021, the ACOG recommended booster doses (third vaccination dose) for pregnant and post-partum women due to their increased risk of COVID-19-related consequences. Previous trials on pregnant women found that booster dose was associated with higher maternal antibody levels and thus lower risk for severe COVID-19-related outcomes  as well Even though recent guidance indicates that COVID-19 vaccines including booster doses should not be withheld from pregnant and lactating women, there is no consensus regarding vaccination during pregnancy/lactation and vaccine hesitancy among women still existed.In January 2021, Jordan began its vaccination campaign against COVID-19, with healthcare workers and the elderly prioritized for the first shots. Thereafter, in September 2021, the Jordan Ministry of Health authorized the booster shot for people 60 years old and above, the immunocompromised, including those with chronic illnesses, and health workers . The preThis was a cross-sectional study conducted from November 2021 to January 2022 among pregnant and lactating women in Jordan. The sample population was a convenience sample targeted through social media platforms, i.e., Facebook groups. A minimum of 383 patients based on maximum annual deliveries of 80,000, 5% margin of error, 95% confidence level, and 50% response distribution were required. Any pregnant and lactating woman living in Jordan at the time of the study was eligible to participate. A detailed explanation about the study was provided to potential participants and consent about anonymity of the survey and voluntary participation was then obtained for each participant. The used platform allowed participants to move through sections only when their answers were completely obtained. The study was approved by the Ethical Approval Committee of the Institutional Review Board of Yarmouk University .The questionnaire of this study was structured based on a broad literature search using MEDLINE/PubMed and Google Scholar. Most relevant articles have been retrieved and then the questionnaire was designed -18. The The survey consisted of 29 questions. Questions 1-15 captured demographics and current health status. Questions 16-19 were about the acceptance of vaccines in general. Questions 20-22 were about confidence in the COVID-19 booster vaccine. Questions 23-26 queried the perceived risks of the virus. Question 27 queried whether the participant was willing to participate in a COVID-19 vaccine (booster dose) clinical trial during pregnancy/lactation. Questions 28 and 29 were detailed questions that evaluated motivations that may encourage and barriers that may discourage participation in a clinical trial.The survey data was analyzed using social science software, SPSS® version 26 . The mean, standard deviation, frequencies, and percentages were used for continuous and categorical variables as needed. Analytical graphs were used as appropriate. Logistic regression was used to identify factors that might affect the participants’ acceptance of a COVID-19 vaccine and their willingness to enroll in clinical trials of a booster dose of COVID-19 vaccine. Statistical significance was at a p < 0.05.Demographic characteristicsAmong 584 respondents, 37.3% n = 218) and 59.9% (n = 350) were pregnant and lactating, respectively, at the time of taking the survey  stated their likelihood to vaccinate their children with routine national immunization program. In addition, the results showed that 84.1% and 84.6% believed that such vaccines are safe and effective, respectively. On the other hand, only 26.4% (n = 154) of participants received a previous seasonal influenza vaccine.Confidence in COVID-19 vaccine booster doseAmong participants, 56.2% (n = 328) intended to receive the third dose of COVID-19 vaccination during their pregnancy/lactation period if efficacy and safety were achieved. Figure Perceived risk/precautions of the virusWomen’s level of worry about COVID-19 during pregnancy/lactation in the present study was high; 64.0% (n = 374) thought that they perceived a risk to catch COVID-19 during pregnancy/lactation. In regard to commitment to safety measures, 55.0% (n = 321) totally complied with face masks, social distancing guidelines, and other prevention measures. Despite this, only 15.8% seriously followed COVID-19 news .Acceptance to participate in a third dose COVID-19 vaccine clinical trialRegarding participants’ acceptance to enroll in a COVID-19 vaccine clinical trial during pregnancy/lactation, the answers demonstrated that only 22.9% of participants (n = 134) were willing to participate in clinical trials while the remaining 77.1% (n = 450) refused  . HoweverThe strongest predictors of COVID-19 vaccine booster dose acceptance among participants were among women who are having a health-related educational level, higher income, living in Middle or South Jordan, being a lactating rather than pregnant woman, knowing pregnant/lactating women previously infected with COVID-19, committed to routine immunization for children, received seasonal influenza vaccines, and worried about COVID-19.Although evidence confirming elevated risk from COVID-19 infection in pregnancy was reported, pregnant women have been excluded from most studies of COVID-19 treatments as well as from COVID-19 vaccine trials . This exA wide range of vaccine acceptance rate was previously reported in many countries based on income; those who live in low-income countries were found to have lower acceptance rates than those who live in higher-income countries . These rThe present study found that mothers who live in the middle and south regions of Jordan had higher acceptance rates of a booster dose of COVID-19 vaccine. This could be justified by their belief in the importance of vaccines to people living in these tourist sites of the country as tourism destinations were negatively affected by the COVID-19 pandemic, with almost 100 travel agencies, 80% of hotels (three stars and below), and 800 restaurants and local cafes closed. Moreover, around 14,000 employees lost their sources of income, many of them live and work at tourist sites .Our results showed that pregnant respondents were more likely to decline vaccination compared to lactating respondents. This finding is in line with a previously published survey on vaccine acceptance . The latGlobally, routine immunization for children is relatively high and for instance, 83% of the world’s children receive full doses of the diphtheria-tetanus-pertussis vaccine (DTP3) every year . SimilarThe results also showed that the perceived risk of COVID-19 for pregnant/lactating women, as measured by their worries toward COVID-19 was a strong predictor for acceptance of having COVID-19 vaccine booster dose. Even though this factor is being influenced by the current pandemic status, it seems that it has previously affected vaccine hesitancy .The study also showed that a low proportion (23%) of participants had willingness to participate in clinical trials for COVID-19 vaccine; which was lower than the rate reported in France and China ,25. The Apart from the limitations related to online surveys, where only those who had access to the technology, resources, and ability to navigate the internet were approached and enrolled, the study included enrollment of women in any trimester of pregnancy and any time during the lactation period which limits the generalizability to each category. Although the number of respondents was not large, it was very diverse. Furthermore, vaccine acceptance levels among people might change over time as more data will be accrued.This study reported 56.2% acceptance of COVID-19 booster dose vaccination in a sample of pregnant/lactating women. Since booster vaccine against COVID-19 in pregnancy and during lactation can further control the burden of the disease and decrease morbidity and mortality during pregnancy/lactation, strategies to reduce vaccination hesitancy among the unvaccinated pregnant/lactating women as well as offering boosters to all already-vaccinated ones should be implemented to accomplish efficient COVID-19 immunization among this population. Relying on that and furthermore, vaccination trials in Jordan for pregnant/lactating women with a focus on short- and long-term safety and effectiveness data from vaccination during pregnancy and lactation periods are needed.


While the combined approach was associated with a significantly higher DY for lung cancer diagnosis  and sarcoidosis , no significant differences in DY were calculated for subgroups with smaller sample sizes such as lymphoma. No major adverse events were observed. Using a 1.5 mm mini-forceps is a safe and feasible technique for biopsy of mediastinal or hilar LAD or masses with superior overall DY compared to EBUS-TBNA as a standalone technique.When evaluating mediastinal/hilar lymphadenopathy (LAD) or masses, guidelines recommend endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA) as an initial technique for tissue analysis and diagnosis. However, owing to the small sample size obtained by needle aspiration, its diagnostic yield (DY) is limited. EBUS transbronchial forceps biopsy (TBFB) used as a complimentary technique to EBUS-TBNA might allow for better histopathological evaluation, thus improving DY. In this retrospective bicentric study, we assessed the DY and safety of an EBUS-guided 1.5 mm mini-forceps biopsy combined with EBUS-TBNA for the diagnosis of mediastinal/hilar LAD or masses compared to EBUS-TBNA alone. In total, 105 patients were enrolled. The overall DY was 61.9% and 85.7% for TBNA alone and EBUS-TBNA combined with EBUS-TBFB, respectively ( Endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA) is established as a safe and minimally invasive technique for cytological examination of mediastinal and hilar lymphadenopathy (LAD) with a high diagnostic yield (DY) ,2,3. AccTo overcome the abovementioned limitations, the use of an EBUS-guided transbronchial forceps biopsy (TBFB) has been proposed and evaluated in several studies yielding improved diagnostic accuracy ,16,17,18For the present retrospective study, we enrolled all patients with mediastinal/hilar LAD or masses detected by chest computed tomography (CT) who underwent EBUS-TBNA and subsequent EBUS-TBFB performed by three experienced interventional pulmonologists  at the University Hospital Zurich or at the Clinic St. Anna, Lucerne from 1 January 2020 to 31 December 2020 when sarcoidosis, lymphoma, or infection including tuberculosis was suspected, or when sufficient tissue was required for cancer staging or diagnosis. Patients were included if they were 18 years or older and written informed consent was obtained.The primary outcome was the overall DY of EBUS-TBFB in addition to EBUS-TBNA compared to EBUS-TBNA alone. The secondary outcome was safety  and technical feasibility. The study was approved by the Competent Ethics Committee of the Cantons of Zurich (BASEC-ID 2019-02479) and Lucerne (BASEC-ID 2020-00136-L).All bronchoscopies were performed under either moderate sedation or general anesthesia according to the examiner’s decision in in- or outpatient setting. Following airway inspection using a flexible Olympus bronchoscope (190 series), the lymph node stations 2, 4, 7, 10, and 11 from both sides, in addition to a possible mediastinal/hilar mass, were systematically assessed using an Olympus EBUS bronchoscope . Lymph nodes with a diameter equal or greater than 10 mm were sampled with three passes with a minimum of 10 advances per site using a 19-gauge needle  or a 22-gauge needle  according to the discretion of the bronchoscopist.After identification of the target lymph node or mass by EBUS for subsequent TBFB according to size and appearance of malignancy, another pass with the EBUS needle was added. In order to augment the puncture hole, the needle sheath was advanced through the bronchial wall into the lymph node/lesion and moved forward and backward several times. After extraction of the EBUS needle and sheath, respectively, a closed mini-forceps  was advanced through the working channel of the EBUS bronchoscope to re-enter the lymph node or mass through the pre-existing puncture hole while avoiding any movement of the bronchoscope. After penetration of the capsule of the lymph node, the forceps was opened and advanced until reaching the distal end of the lymph node. At the distal end, the forceps was closed and pulled for each specimen. This procedure was repeated four to five times under real-time imaging using EBUS. Finally, the closed mini-forceps was withdrawn through the working channel.Cytological specimens obtained using EBUS-TBNA were processed per institutional protocol and examined on a per node basis. The specimens were preserved in normal saline and immediately transferred to the respective Institutes of Pathology.EBUS-TBFB specimens were processed as histology specimens and placed into formalin solution for permanent fixation. All specimens were analyzed by pathologists at the pathology departments of the University Hospital Zurich and at the Lucerne Cantonal Hospital, respectively.All patients were routinely screened for pneumothorax with immediate lung ultrasound (LUS) and a chest radiograph (CXR) within 2 h post procedure. In addition, patients were asked to measure their body temperature daily during 7 days after the intervention and report temperatures above 38.5 °C lasting for more than 24 h to screen for a possible pneumonia or mediastinitis.The primary endpoint was the DY of EBUS-TBNA and EBUS-TBNA combined with EBUS-TBFB overall and among the subgroups. Secondary endpoints were its technical feasibility and safety. The DY was defined as the percentage of patients for whom at least one of the respective samples  was diagnostic. At least one of the samples of TBNA or TBFB had to be diagnostic to define the procedure as diagnostic. The detection of atypical or highly suspicious cells was not deemed diagnostic and, therefore, considered as negative cases. If EBUS-TBNA or EBUS-TBFB samples correctly excluded an alternative diagnosis, e.g., the exclusion of sarcoidosis, the procedure was also considered diagnostic.If EBUS-TBNA or EBUS-TBFB specimens were not diagnostic or suitable for analysis, the final diagnosis was made either by surgical biopsy (mediastinoscopy or through sampling at another site), by re-bronchoscopy or by follow-up.p-value < 0.05.Descriptive statistics were used to illustrate demographics and patient characteristics. Groups were compared with McNemar’s test using the SPSS version 26.0.0.0. . Statistical significance was defined as a In 1 year, 179 patients were enrolled in the study. A total of 36 patients were excluded because EBUS-TBFB was technically not possible, mostly due to the inability to penetrate the bronchial wall. Among these 36 patients, the 19-gauge needle was used in 28 patients (77.8%). Both TBNA and TBFB were successfully conducted in the remaining 143 patients, of which 105 ) were totally included . Most prn = 2, thymus carcinoma n = 1, melanoma n = 1, breast cancer n = 1, sarcoma n = 1, and ovarian carcinosarcoma n = 1), and other diagnosis in 18 (17.1%) patients. Other diagnoses included infectious diseases, inflammatory diseases, pneumoconiosis, and interstitial lung diseases.Indications for EBUS-TBNA and EBUS-TBFB, separated by the final diagnoses, are presented in p < 0.001). Thus, the combination of EBUS-TBFB and EBUS-TBNA provided additional or superior diagnostic information in 25 patients (23.8%) as compared to EBUS-TBNA alone . Conversely, in 10 patients (9.5%), the diagnosis was exclusively established by TBNA . Overall, no significant difference in DY between 19-gauge TBNA biopsies and 22-gauge TBNA biopsies was calculated .Overall, EBUS-TBNA as a standalone procedure yielded the final diagnosis in 61.9% of the patients compared to 85.7% when combining EBUS-TBNA and EBUS-TBFB, resulting in a significant difference in DY between the two techniques  cases. A total of 15 patients with a nondiagnostic bronchoscopy after TBNA and TBFB sampling underwent further diagnostics or follow-up to provide a classifying diagnosis in all patients .p = 0.016) and sarcoidosis . Among the other subgroups, the DY between the two procedures was similar , of which 18 were treated with topical use of vasoconstrictors. In two patients, there was respiratory failure requiring noninvasive ventilation in one case and hospitalization for observation in the other case.In this retrospective bicentric study, we tested for the DY and safety of EBUS-TBFB in addition to EBUS-TBNA as a complementary sampling technique using a 1.5 mm forceps for diagnostic tissue acquisition from mediastinal/hilar LAD or masses compared to standard EBUS-TBNA alone. We were able to demonstrate a significantly higher overall DY of the combined technique as compared to EBUS-TBNA alone in a large cohort of 105 patients. In the subgroup analysis, we found a significantly superior DY for the diagnosis of lung cancer and sarcoidosis. However, EBUS-TBFB was technically not feasible in a significant number of patients.Basically, it is not surprising that histological specimens yield higher diagnostic accuracy as compared to cytology. For this reason, video-assisted mediastinoscopy (VAM) is recommended according to the guidelines by the European Society of Thoracic Surgery (ESTS) when EBUS/EUS-TBNA remains nondiagnostic . HoweverIn a recent meta-analysis by Agrawal et al., the reported pooled DY of EBUS-TBNA was 67% and 92% when EBUS-TBNA was combined with EBUS-TBFB . CompareRegarding sarcoidosis, both techniques demonstrated a marginally lower DY for the diagnosis than reported in former studies ,17,18. TThe superior value of histological specimens compared to EBUS-TBNA cytology samples for the diagnosis of lymphoma has been reported recently . Yet, thAnother approach to provide tissue samples with greater volume in mediastinal lesions was proposed by Zhang et al. using transbronchial cryobiopsy performed under EBUS guidance . They reRegarding our secondary endpoint, EBUS-guided TBFB permits a safe lymph node or tumor biopsy through the bronchial wall with a favorable complication rate. EBUS-TBFB was generally safe, and no major complications occurred. This finding matches previous reported complication rates . Owing tIn addition to the retrospective study design, there were several limitations that need to be considered. Selection bias introduced by the exclusion of patients in which EBUS-TBFB was technically not possible to perform failed to ensure that our study sample is representative of the wider patient population with unknown hilar LAD or masses. Approximately 20% of the initially enrolled patients were excluded, mostly because of the inability of the forceps to pass the bronchial wall. Given that the 19-gauge needle was used for TBNA in approximately 80% of these cases, the results might imply a correlation between needle size and technical feasibility. However, the outer diameter of both needles is identical, and this supposition will require further study. Mehta et al. used a flexible electrocautery knife to create a tract for the forceps with a successful penetration of the bronchial wall [Compared to needle aspiration with an average sampling of three different lymph nodes per patient, only one was sampled by TBFB. Moreover, the fact that forceps biopsies were always conducted at the same location of the mass or lymph node resulted in the diagnostic accuracy of TBFB only being evaluated within one region of the lesion. Either way, TBFB may have missed diseased tissue, which we assume limits the diagnostic power of forceps biopsy.Although the results are in favor of better quality of EBUS-TBFB specimens compared to EBUS-TBNA specimens, we did not directly assess and compare specimen quality. This study did not clarify whether any advantage of EBUS-TBFB biopsies over EBUS-TBNA specimens exists regarding the amount and quality of tissue.In conclusion, our study demonstrated a safe and feasible technique for biopsy of enlarged mediastinal LAD or masses using a 1.5 mm mini-forceps in a large cohort with superior overall DY compared to EBUS-TBNA as a standalone technique. Among the subgroups, we found a significantly superior DY for the diagnosis of lung cancer and sarcoidosis. However, regarding the lower DY of EBUS-TBNA in lung cancer diagnosis in our own study compared to the current literature, the benefit of EBUS-TBFB might have been overestimated. Using an individualized patient approach based on preprocedural examination and imaging, we recommend the use of complementary EBUS-TBFB in mediastinal/hilar LAD or masses suggestive of sarcoidosis. However, technical issues are a major obstacle. A randomized study would be needed to investigate EBUS-TBFB in comparison to EBUS-TBNA and to upcoming techniques, such as transbronchial cryobiopsy.


Inflammation is thought to be a risk factor for kidney disease. However, whether inflammatory status is either a cause or an outcome of chronic kidney disease remains controversial. We aimed to investigate the causal relationship between high-sensitivity C-reactive protein (hs-CRP) and estimated glomerular filtration rate (eGFR) using Mendelian randomization (MR) approaches.CRP and IVAsian, based on SNPs previously identified in European and Asian populations. IVCRP and IVAsian explained 3.4% and 3.9% of the variation in hs-CRP, respectively.A total of 10,521 participants of the Japan Multi-institutional Collaborative Cohort Study was analyzed in this study. We used two-sample MR approaches (the inverse-variance weighted (IVW), the weighted median (WM), and the MR-Egger method) to estimate the effect of genetically determined hs-CRP on kidney function. We selected four and three hs-CRP associated single nucleotide polymorphisms (SNPs) as two instrumental variables (IV): IVCRP, genetically determined hs-CRP was not significantly associated with eGFR in the IVW and the WM methods (estimate per 1 unit increase in ln(hs-CRP), 0.000; 95% confidence interval [CI], −0.019 to 0.020 and −0.003; 95% CI, −0.019 to 0.014, respectively). For IVAsian, we found similar results using the IVW and the WM methods . The MR-Egger method also showed no causal relationships between hs-CRP and eGFR .Using the IVOur two-sample MR analyses with different IVs did not support a causal effect of hs-CRP on eGFR. Although the previous longitudinal studies have examined the association between CRP levels and CKD in different populations, evidence on the causality of this association remains controversial.5–7 However, some researchers demonstrated the effect of CRP-oriented biological functions on kidney function.8,9 One researcher also has published a meta-analysis suggesting that vitamin D supplementations could lower circulating CRP levels.10 Taken together, these studies suggest that interventions on CRP may help to improve renal function.Systemic inflammation is considered as one of the risk factors for common chronic diseases, including diabetes mellitus,11 The development of MR analysis consecutively occurred after identifying single nucleotide polymorphisms (SNP) in genome wide association studies (GWAS). As with other health outcomes, previous GWAS identified SNPs associated with CRP levels, including the CRP gene in chromosome 1.12,13 Interestingly, it is known that serum CRP levels are affected by genetic polymorphisms,14 which indicates that SNPs associated with CRP levels may reflect the long-time exposure to higher/lower CRP level. Therefore, SNPs which associated with serum CRP levels are suitable for IVs to investigate the causal relationships between CRP and several pathophysiological conditions, and used in previous MR studies among adults in European countries.15–17In the last few years, the Mendelian randomization (MR) approach has attracted much attention in genetic epidemiology. The biggest advantage of this method is to investigate a causal relationship between an exposure (X) and an outcome (Y) from an observational dataset using genetic variants as instrumental variables (G: IV).18–20 These studies enable researchers to conduct MR study using CRP-associated SNPs in Asian populations, which seems to be important in terms of ethnic difference. Therefore, we investigated whether genetically determined hs-CRP levels using two different IVs, based on SNPs identified in European and Asian populations, were causally related to kidney function in a Japanese population using MR approaches.In Asian countries, large-scale cohort studies have collected human genome and performed genotyping in the past several decades. Several researchers conducted GWAS and found novel loci associated with CRP levels in Asian populations.http://www.jmicc.com).21,22 The selection process of participants is shown in https://www.cog-genomics.org/plink2) identified 388 relative pairs (pi-hat >0.1875) and one sample of each pair was excluded. Principal component analysis with a 1,000 Genomes reference panel (phase 3)  detected 34 subjects whose estimated ancestries were outlier from the Japanese population. The 34 samples were excluded. Among all the remaining 14,091 samples, five subjects withdrew their consent to participate, leaving 14,086 subjects for the final analyses. Of which, the values of serum hs-CRP were available only at three study sites. Therefore, we decided to use two-sample MR study design, rather than single sample MR for a smaller dataset. We divided the participants into two groups; 1) 2,503 participants (available for hs-CRP) and 2) 12,501 participants (non-overlapping participants), which are in accordance with a basic principle of two-sample MR .23 After excluding participants who had an extremely high value for hs-CRP  and eGFR , and lower than the limit of quantification for hs-CRP (n = 8), a total of 10,521 Japanese  were analyzed in the two-sample MR of this study. Written informed consent was obtained from all participants of this study. The J-MICC Study was conducted with adherence to the Ethical guidelines for the Human Genome and Genetic Sequencing Research. The procedure of this study was approved by the Ethics Review Committee of the Nagoya University Graduate School of Medicine (939-14), Aichi Cancer Center and all research institutes. We performed analyses using the dataset of version 20190728.The study subjects were participants of the Japan Multi-institutional Collaborative Cohort (J-MICC) Study which was conducted in 14 study areas throughout Japan. The purpose of the J-MICC Study was to find out the risk factor of cancer and other diseases by examining the relationship between genetic variants, lifestyle habits, blood components, and disease. The eligibility for the J-MICC Study was adults aged 35–69 years living in each study area. The details of the J-MICC Study have been described previously elsewhere and the latest information is available on its website (2) = 194 × serum creatinine (mg/dL)−1.094 × age−0.287 (× 0.739 for women).24Serum samples were collected from all participants. We measured hs-CRP using a latex-enhanced nephelometry. Serum creatinine was basically measured using an enzymatic method. Some institutes measured serum creatinine using the Jaffe method, and then transformed to the equivalent value of the enzymatic method. eGFR was calculated using the Japanese equation proposed by the Japanese Society of Nephrology: eGFR , and narrowed down to the studies according to the following criteria: 1) a study conducted in an Asian population, and 2) a study with both of the discovery and the replication phase. After the web-based selection, we finally selected 13 SNPs. For 151233628, due to low imputation quality (MAF <0.05 and r2 < 0.3), this SNP was not included in the original J-MICC dataset. Of remaining 12 SNPs, 6 SNPs  were excluded because these SNPs were not significantly associated with hs-CRP in our dataset (P > 0.0042 = 0.05/12). Next, rs814295 (GCKR) and rs429358 (APOE) were likely to have pleiotropic effects on kidney function. rs3093059 was excluded due to the high linkage disequilibrium (LD) with rs3093068 in CRP dataset (r2 > 0.9). Finally, three SNPs  were included in our analysis, and were called as IVAsian (Table 2).The list of candidate SNPs for IVs is shown in 25–27 The inverse-variance weighted method (IVW) is a conventional approach to estimate a causal effect on a study outcome from different studies in meta-analysis.25 In the setting of MR analysis, the IVW method can provide a combined estimate weighted using the inverse variances of the causal effect of per-allele. However, this method can be biased when a genetic variant violates the assumptions of MR .27 Therefore, we also performed two other methods (the weighted median (WM) and the MR-Egger method) which can provide consistent estimates even under the weaker assumption.25 The MR-Egger analysis is also useful to detect either/both directional pleiotropy or/and violation of the Instrument Strength Independent of Direct Effect (InSIDE) assumption. Additionally, the F-statistic was calculated for each IV from linear regression analyses to test whether IVs are strongly associated with exposure (referred to as relevance assumption).28 We performed linear regression analyses using lm function in R and included all SNPs used in each IV in models. An arbitrary threshold of F-statistic >10 was used to avoid using weak genetic instruments in this study.29 All statistical analyses were performed using the software R version 3.5.0 . In particular, a R package of “MendelianRandomization” was used for two-sample MR analyses.30To confirm the cross-sectional association between hs-CRP and eGFR, multiple linear regression analysis was performed with adjustment for sex, age, and study sites. We performed two-sample MR approaches after dividing the participants into two datasets (CRP and eGFR datasets) as described above. Methods for two-sample MR were different from one-sample MR method, which was described in previous methodological papers.2 .Table CRP were significantly associated with ln(hs-CRP), but not for the other two SNPs (rs1130864 and rs1800947) (Table Asian were associated with ln(hs-CRP). Combining these SNPs, both of IVCRP and IVAsian had a F-statistic >10 , which indicated that two IVs met a criterion for relevance assumption. Four SNPs in IVCRP and three SNPs in IVAsian explained 3.4% and 3.9% of the variation in hs-CRP, respectively.Two SNPs (rs3093077 and rs1205) in IVP = 3.26 × 10−4), after adjustment for sex, age, and study sites. The scatter plot for the association between ln(hs-CRP) and ln(eGFR) is shown in Before the MR analysis, we performed the conventional statistical analysis for the cross-sectional association between hs-CRP and eGFR. Among 1,598 participants who were available on both of hs-CRP and eGFR, ln(hs-CRP) was strongly associated with ln(eGFR)  = 0.000; 95% CI, −0.019 to 0.020; P = 0.97)  and the MR-Egger method (estimate per 1 unit increase in ln(hs-CRP) = −0.008; 95% CI, −0.058 to 0.042; P = 0.75). The intercept estimated in the MR-Egger method was likely to be zero . The scatter plot using IVCRP is provided as Using the IVAsian) was not significant, which was consistent with the result using IVCRP  and −0.004 , respectively. The result in the MR-Egger was directionally inconsistent with two other methods, but still insignificant . The intercept in the MR-Egger method was equal to zero . The scatter plot using IVAsian is provided as The estimated causal relationship using the genetic instruments reported in Asian populations (IVCRP and IVAsian). Neither of the two instrumental variables for hs-CRP was associated with eGFR levels in two-sample MR analysis. These results suggested no significant causal relationship between hsCRP and eGFR in this population.We assessed causality between genetically-determined inflammation and kidney function employing MR approaches in a Japanese population. In this study, we used four and three SNPs as different genetic instruments  within the CRP gene as instrumental variables. A previous study reported that these four SNPs were selected as a set of tagging SNPs in the CRP gene.17 One of the previous MR studies in Caucasian reported that genetically determined CRP was not significantly associated with creatinine-based eGFR . Interestingly, this previous study used the same SNP set (IVCRP) as in this study, and the effect size of IV on eGFR was similar to that observed in the present study. Therefore, this insignificant association between genetically determined CRP level and eGFR is likely to be consistent across different ethnic groups.We found that IVCRP were originally selected among individuals of European descent. Moreover, it is well known that the CRP level in Asian population was lower than that of Caucasians.31 Therefore, we tried to develop the IV specific for Asian people and selected three CRP-associated SNPs  found in previous GWAS in Asian populations.18–20 However, no evidence found that IVAsian was associated with eGFR in the study population.The SNPs in IVAsian was relatively small (F-statistic = 22.5). Although this value barely satisfied the assumption of IV (F-statistic >10), the results were likely to be empirically verifiable for relevance assumption. Considering that we adopted the top significantly associated SNPs as IVs of CRP, which was not associated with renal functions, the contributions of genetically determined CRP on the risk of renal disease may be relatively limited compared to the multiple risk factors of this complex disease.32,33IV requires the following three key assumptions: 1) relevance assumption (IV is associated with exposure), 2) exclusion restriction assumption (IV affects the outcome only through the exposure), and 3) exchangeability assumption (the effect of outcome is not confounded). Regarding relevance assumption, in this study, we restricted to only three SNPs in the robust selection process, thereby F-statistics of IV34 This methodological review provided multiple scenarios violating this assumption . For scenarios of inadequate phenotype definition and measurement error, we used hs-CRP levels as an exposure variable. This is a clear definition of exposure and can lead to less measurement error compared with questionnaire-based phenotyping. For a scenario for the presence of LD, we carefully excluded either one of the SNPs in LD, which seems to have adequately addressed the problem. The scenarios of time-varying exposure and reverse causality are closely related and is usually worrisome for retrospective case-control study, where data on the exposure is collected after diagnosis of the outcomes. As above, we adequately addressed these problems, or our analysis has no substantial possibility to meet these scenarios. In addition to these scenarios, horizontal pleiotropy can violate exclusion restriction assumption. IVAsian consisted of SNPs not only in CRP gene, but in HNF1A. Although previous studies suggested the SNP in HNF1A may have other pleiotropies,35–37 sensitivity analyses (MR-Egger and WM methods) in this study indicate that the IVW estimate was not biased by the average horizontal pleiotropic effect .Another key assumption for MR analysis is exclusion restriction assumption.Asian might provide a meaningful approach of causal inference in Asian population. The present study also has limitations to be discussed. First, we created IVAsian in this study, but investigated the association only in a Japanese population. Therefore, it remains unclear whether this result is consistent across Asian groups. Further studies are needed to examine this association in other Asian populations. Second, the number of SNPs used in IVs was small. Both of the two IVs met relevance assumption of IV in MR but were relatively weak. Given the relatively low variance of blood CRP levels and existence of a number of other determinants of CRP in human environments, such as bacterial infections or other inflammatory diseases not derived from inherited CRP levels, the contribution of genetically determined blood CRP levels may be limited in the development of human renal disease. Potentially, the bigger the number of SNPs in IV, the bigger the explained variance of the exposure. On the contrary, with an increment of SNPs in IV, the pleiotropic effects will also increase. In a recent paper, a researcher suggested that there was no need to exclude SNPs with pleiotropic effects.37,38 In this study, however, we prioritized selecting SNPs within the CRP gene over explanatory rate . In the future study, selection of IV will be more important. Third, the study sample size was relatively large in Asian populations, but this sample size may lead to limited power for two-sample MR (The main strength of this study is that we used the IV specific for Asian populations. Given that CRP level is different in each population, the construction of IVample MR . TherefoIn conclusion, the present MR analyses investigated the causal relationship between hs-CRP and kidney function. Our two-sample MR analyses with two different IVs did not support a causal effect of hs-CRP on eGFR in this population.


Urogenital dysfunction is recognized as a serious complication affecting patient quality of life after rectal cancer surgery to treat rectal cancer; however, the studies focus on the urogenital function after robot-assisted rectal cancer surgery compared to laparoscopic surgery are limited.Male patients undergoing robotic total mesorectal excision (R-TME) or laparoscopic total mesorectal excision (L-TME) were prospectively enrolled. The International Prostate Symptom Score (IPSS) and the five-item version of the International Index of Erectile Function (IIEF-5) scale were used to compare the urogenital function of the two groups preoperatively and 3, 6, and 12 months postoperatively.Eighty-nine patients who planned to undergo R-TME and L-TME were prospectively enrolled; 77 patients of these patients (86.5%) completed all questionnaires at all time points and were thus included in the final analysis. Of the included patients, 38 underwent R-TME and 39 underwent L-TME. There was no significant difference in age, BMI, American Society of Anesthesiologists (ASA) score, tumor location, neoadjuvant therapy, operation method, postoperative pathological results and adjuvant therapy between the two groups. Preoperative urogenital function was similar in both groups; however, the IPSS was significantly lower in R-TME patients than that in T-TME patients at 6 months and 12 months . IIEF-5 scores decreased 3 months after R-TME and L-TME surgery  and then gradually increased; at 12 months, IIEF-5 scores were comparable to those at baseline in both groups. IIEF-5 scores were higher in R-TME patients than those in L-TME patients at 6 months , but there was no significant difference between the two groups at 12 months .The robotic approach for TME was associated with more rapid restoration of male urogenital function than the laparoscopic approach. Rectal cancer is one of the most common malignant cancers worldwide, and its incidence is increasing in young people , 2. SurgAt present, laparoscopy is widely used in the surgical treatment of rectal cancer, and its safety and oncologic outcomes are acknowledged , 9. LapaIn recent years, robotic surgery has gained greater popularity worldwide. This technique has several advantages over laparoscopic surgery, including an immersive three-dimensional view of the surgical field, better surgical dexterity, and a stable camera platform. Such innovative technology can alleviate some of the maneuverability and visibility challenges that surgeons encounter in narrow pelvic cavities . PatientTherefore, in this study, we evaluated urogenital function at several time points in male patients who underwent robotic-assisted or laparoscopic surgery for rectal cancer to determine which surgery had better urogenital function outcomes.This was a single-center, prospective, cohort study from the First Affiliated Hospital of Nanchang University in Jiangxi, China. Male patients with rectal cancer, tumors located within 12 cm of the anal verge, age ≤ 60 years, and normal urogenital function before surgery and who underwent robotic or laparoscopic surgery were included. The exclusion criteria included emergency operations, patients with distant metastases, a history of previous pelvic organ operations, or conversion to laparotomy, and patients that refused to join the study. The choice of surgical approach (robotic or laparoscopic) was determined in accordance with the wishes of the patient. The study received ethical approval from the First Affiliated Hospital of Nanchang University, and all patients provided informed consent for participation in the study.All operations were performed by one surgeon. All patients enrolled in the study underwent TME with PANP utilizing a medial-to-lateral approach. Lymph node dissection was performed to the root of the inferior mesenteric artery (IMA). High or low ligation was performed according to the length of the colon and rectum. All rectal cancer resections adhered to the principles of TME. For PANP, the superior hypogastric plexus (SHP) was preserved at the root of the IMA. The hypogastric plexus (HP) and pelvic splanchnic nerves (PSN) were preserved when dissecting the mesorectum posteriorly, the inferior hypogastric plexus (IHP), PSN and the neurovascular bundle (NVB) of its branches were preserved when dissecting the mesorectum laterally and anteriorly respectively. Linear stapler devices were used to transect the rectum 1–2 cm below the tumor. The specimen was extracted through a 4- to 5-cm mini-laparotomy in the lower abdomen with a wound protector. The bowel was anastomosed using a circular stapler. Ileostomy was conducted according to the risk factors for anastomotic leakage and reversed at 3 months after surgery. Abdominoperineal resection was performed if the distal resection margin of 1–2 cm cannot be confirmed with negative in low anterior resection.The International Prostate Symptom Score (IPSS)  was usedThe five-item version of the International Index of Erectile Function (IIEF-5) scale  was usedBoth questionnaires were administered preoperatively and 3, 6, and 12 months postoperatively.Statistical analyses were performed using SPSS 24.0. Categorical variables were compared with Chi-square tests; continuous variables were compared with Student’s t tests or Mann–Whitney U tests. P values < 0.05 were considered statistically significant.From June 2018 to July 2020, 89 patients who were going to undergo R-TME or L-TME at the First Affiliated Hospital of Nanchang University were prospectively enrolled in this study. Seventy-seven patients (86.5%) who completed all the questionnaires at all time points were included in the final analysis: 38 underwent surgery with a robotic approach and 39 underwent laparoscopy. The two groups did not significantly differ in age, body mass index (BMI), American Society of Anesthesiologists (ASA) score, tumor location, neoadjuvant therapy, operation method, postoperative pathological results and adjuvant therapy ], , but there was no significant difference between the two groups at 12 months , (Table Given the continuous advances in early diagnosis, surgical techniques chemo-radiotherapy, targeted therapy and immunotherapy, the survival of patients with rectal cancer has greatly improved; however, urogenital dysfunction resulting from rectal cancer surgery is a major problem affecting their quality of life . PANP prAge, tumor location, use of preoperative radiotherapy, the operation method and the stoma can affect postoperative urogenital function , 21–23. Our results showed that male urinary function decreased at 3 months in the two groups and then gradually improved. Urinary function recovered to baseline scores after 6 months in the robotic group, while in the laparoscopic group, urinary function still had not recovered after 12 months. This finding was similar to the studies of Kim et al. , 25, robIn this study, IIEF-5 scores decreased 3 months after surgery and then gradually increased; at 12 months, scores were comparable to those at baseline in both groups. However, IIEF-5 scores were higher in the robotic group than in the laparoscopic group at 6 months, which was in line with previous studies , 27, 29.Our study also had some limitations. First, this study was not a randomized controlled trial; thus, the validity of our data may be weaker. Second, the evaluation indices of genitourinary function in this study were subjective and easily affected by psychological factors, making it difficult to distinguish whether symptoms were caused by psychological factors or physiological factors. Third, due to ethical and cultural factors, the sample size of this study was small and did not evaluate female genitourinary function.Our study found that the robotic approach for TME was associated with a more rapid restoration of male urogenital function compared to that of the laparoscopic approach. Multicenter randomized controlled trials are needed to confirm the advantages of robotic surgery for rectal cancer.


This increase was accompanied by increased limb amputations performed during the first lockdown, post-lockdown and the second lockdown in 2020, compared to respective time periods in 2019 . No SARS-CoV-2 infection was observed among patients with PAD during the observation period. Conclusions: Strict lockdown protocols adversely affected the care of PAD patients, with persisting aftereffects, including increased emergency admission with unsuccessful revascularization attempts leading to limb amputation, even after the peak of the pandemic had passed. We believe that providing continuous care to PAD patients, even in times of global pandemics, will prevent the unfavorable outcomes observed during the COVID-19 pandemic in 2020.Background: To optimize our strategic planning, we aimed to investigate the impact of the COVID-19 pandemic on the treatment of patients with peripheral artery disease (PAD) at our tertiary care hospital. Methods: We performed a retrospective single-center cohort study. In total, 1210 patients were included: 611 patients admitted between March and December 2020, compared to retrospective data from 599 patients from the same period in 2019. Results: Emergency admissions involving patients with advanced stage PAD increased significantly during the pandemic period of 2020, compared to the same period in 2019 ( Peripheral artery disease (PAD), one of the most prevalent manifestations of atherosclerotic vascular disorder, affects more than 200 million individuals with a rapid increasing frequency worldwide . It encoHowever, to our knowledge, scarce evidence exists on the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with PAD. Nevertheless, due to the presence of predisposing factors for developing severe SARS-CoV-2 infection, including cardiac disorders, diabetes, and hypertension, the follow-up care for patients with PAD was discontinued during the COVID-19 pandemic in 2020. Instead, all resources were dedicated to protecting patients from the pandemic, and the rising burden of the underlying PAD was neglected. In the first lockdown (LD) period of the COVID-19 pandemic, concerns about the shortage of health care resources necessary to manage the pandemic abounded, which led to consequential changes in daily clinical practice. These included split-team policy, postponement of outpatient appointments, scaling down and rescheduling elective surgeries to after the LD period, and conducting only emergency surgeries. At first glance, these protocols led to a temporary decrease in the daily SARS-CoV-2 infection rate among the general population, but ended up causing harm to patients with advanced PAD, regardless of their SARS-CoV-2 infection status ,6.Despite growing knowledge about the management of cardiac disorders, limited data exist concerning the care of patients with PAD during the COVID-19 pandemic. Therefore, we sought to investigate the impact of the COVID-19 pandemic and strict safety measures on the treatment of patients with PAD at our tertiary care hospital.This study employed a retrospective, single-center, observational cohort design from a prospectively maintained database at a large tertiary care hospital in Austria.Inclusion criteria: we investigated clinical data from all patients older than 18 years admitted to our hospital with vascular disorders between March 16 and 7 December 2020.Exclusion criteria: patients younger than 18 years or admitted to our hospital with a diagnosis other than vascular disorders.The first LD in Austria was implemented from March 16 to 4 May 2020. We defined the time from May 5 to 16 November 2020, as the post-LD period. Then, the second LD in Austria was implemented from November 17 to 7 December 2020. We also compared our findings with retrospectively collected clinical data sourced from VPs between March 16 and 7 December 2019. In addition, we collected data from all VPs admitted to our hospital between March 16 to 7 December 2019 and March 16 to 7 December 2020.All private information of the patients were de-identified. This study was registered with the ClinicalTrials.gov Identifier NCT04838093. Patients’ clinical status was assessed using the functional classification system of Rutherford .The endpoint of the present study was the impact of the COVID-19 pandemic on the treatment of patients with PAD in a tertiary care hospital, which was investigated by determining the number of emergency hospital admissions, acutely performed open surgeries, endovascular interventions and amputations following the implementation of institutional and governmental safety measures.We compiled the following cohorts:PAD patient cohort: patients with PAD consecutively admitted to our hospital from March 16 to 7 December 2020.Control cohort: patients with PAD consecutively admitted to our hospital from March 16 to 7 December 2019.Vascular patient cohort: patients with vascular disorders consecutively admitted to our hospital from March 16 to 7 December 2020 .Beginning in March 2020, nasal or pharyngeal respiratory swabs were routinely collected from each patient admitted to our hospital and repeated regularly at 48-h intervals during the entirety of their inpatient stay. Testing was performed in the Department of Laboratory Medicine, Medical University of Vienna, Austria, using real-time polymerase chain reaction. The comparability of the results of all test methods used was confirmed by participation in international quality control ring trials  were admitted to our hospital departments. Patient characteristics are depicted in p = 0.7301). The number of admissions during the first LD in 2020  was significantly lower than that during the same time period in 2019  (p = 0.0056). The number of admissions during the post-LD in 2020  was somewhat higher than that during the same time period in 2019  (p = 0.0796). This measurement was not significantly different during the second LD 2020 compared to the same time period in 2019 (p = 0.8415). Data are depicted in Overall admission numbers for patients with PAD were higher in 2020  than in 2019  (p = 0.3577).The number of admitted female patients was higher during the entire observation period in 2020  as compared with 2019 , but the difference was not significant (p = 0.0209).According to our findings, patients admitted to our departments in 2020 [median age: 68 (1–99) years] were significantly younger than those admitted in 2019 [median age: 70 (25–91) years] (p < 0.0098). There was also a highly significant trend toward greater emergency admissions during the first LD period  when compared to the same time period in 2019  (p < 0.0001). Even during the second LD, we still observed an increased proportion of emergency admissions  relative to during the same time period in 2019 , though the difference was not significant (p = 0.4285). The first LD also involved higher proportions of emergency admissions  than the post-LD period  and the second LD  (p = 0.0007).We observed a highly significant increase in the absolute number and in the proportion of emergency admissions in 2020  relative to in 2019  (p < 0.0001), which persisted even during the post-LD period  in 2020, compared to  in 2019 (p < 0.0001), albeit appearing somewhat less pronounced during the second LD  in 2020 compared to 2019  (p = 0.3243).The number of patients recorded with advanced stage PAD differed between 2020 and 2019. Specifically, a proportional increase in cases of stage 4–6 PAD, defined by Rutherford classification , was obsIn 2020 (n = 586 in 422 patients), we carried out slightly more operations than we did in 2019 (n = 461 in 368 patients). During the first LD, the absolute number of performed operations (n = 75 in 51 patients) was smaller than that in 2019 (n = 107 in 74 patients). However, absolute number of performed operations increased during post-LD (n = 462 in 347 patients), and second LD (n = 49 in 24 patients) periods in 2020 relative to the respective time periods in 2019 (n = 321 in 264 patients and n = 33 in 30 patients). Treatment data of patients with PAD are depicted in p < 0.0001). This increase was particularly apparent when comparing the first LD period in 2020  and the same period in 2019 , with a greater than fourfold increase in the amputation rate recorded (p = 0.0003). An increased risk for amputation was also observed for the post-LD  and second LD  periods in 2020, relative to the respective time periods in 2019 . Each amputated patient was considered as one case regardless of number of follow-up resections. Data are depicted in During the pandemic period in 2020, the risk for unsuccessful revascularization in PAD patients with critical limb ischemia almost quadrupled  in comparison with that recorded during 2019   in 2020 and 2.3% (95% CI: 1.3–3.8%) in 2019.To determine the frequency of SARS-CoV-2 infection among VPs, we assessed the prevalence of this viral infection in our patient population. Patient characteristics are depicted in During the observation period, a total of five SARS-CoV-2 infections were detected, with infections in three men and two women. In one asymptomatic patient with extracranial artery disorder, SARS-CoV-2 infection was detected one day before elective admission, which was postponed. In two other cases, an asymptomatic infection was detected two days after elective admission, and both patients only noticed a mild fever. Meanwhile, two symptomatic cases were admitted to an acute setting with confirmed SARS-CoV-2 infection. One patient was found to have an acute myocardial infarction, and one patient was in critical condition with respiratory distress in urgent need of extracorporeal membrane oxygenation. These individuals were co-diagnosed with coronary artery disease and pulmonary comorbidities. No SARS-CoV-2-related deaths were observed, and all five patients achieved viral clearance (polymerase chain reaction cycle threshold > 35) at 12 to 27 days after testing positive.The proportion of VPs with positive SARS-CoV-2 test results during the first LD period was 0.34% (95% CI: 0.06–1.9%). Meanwhile, the calculated proportion for the same in the post-LD period was 0.17% (95% CI: 0.06–0.5%), and that for the second LD period was 0.50% (95% CI: 0.09–2.75%). The proportion of patients with positive SARS-CoV-2 test results during the entire observation period was 0.22% (95% CI: 0.10–0.52%), but only three patients  tested positive at admission, for a proportion of 0.13% (95% CI: 0.05–0.39%). No SARS-CoV-2 infection was detected in admitted patients with PAD.p < 0.0001)  .This was in line with Schuivens  and Senap = 0.0056), consequently increased during the post-LD period (p = 0.0796), and then remained consistent during the second LD period. This was in line with data reported by Stabile et al., who recorded a reduced hospitalization rate among patients with chronic limb-threatening ischemia during the first LD period [Our findings indicated an increased number of overall admissions occurred during the COVID-19 pandemic among the PAD patient population. More precisely, the number of admissions decreased significantly during the first LD period . More interestingly, patients admitted post-LD were younger than those admitted during the first LD. This was in line with the data presented by Mesnier et al., in which the proportion of elderly patients decreased in the post-LD period [According to our observations, patients admitted during the COVID-19 pandemic were significantly younger than those admitted in 2019 (D period . We consThere has recently been growing evidence that pre-existing cardiovascular disease is associated with worse clinical outcomes in the case of SARS-CoV-2 infection . FurtherIn addition, there was a significant increase in emergency admissions during the pandemic and an increased proportion of stage 4–6 PAD, according to Rutherford classification , especiaThis raises concerns about the disproportionate prioritization of COVID-19-related conditions leading to insufficient health care services provided to others. We are aware of the necessity of smart safety measures to prevent uncontrolled viral spread, but we also believe that the definition of standards to simplify patient access to health care facilities, even in times of global pandemics, would prevent the unfavorable outcomes observed during and after the first pandemic-related LD in 2020. In addition, as we have demonstrated, during the 16 weeks of the post-LD period, the real impact of extensive LD presented itself in the post-LD period with a backlog of acute-on-chronic conditions requiring treatment. This trend appeared to persist even long after the peak of the pandemic had passed. As reflected by Di Giovanni et al.  and LopeLimitations: One limitation of our study was that we could not specify the cause of every amputation in detail, for example, regarding the course of treatment. Another limitation was that there could be a high number of unrecorded at-home infections with SARS-CoV-2 that we could not include in this study. Further investigations using nationwide registry data would be necessary to address this matter more precisely.Conclusion: This study highlights the fact that the pandemic-related obstacles that must be faced not only include hypercoagulation- and infection-related deaths, but also the neglect of noninfected patients dealing with chronic conditions in need of continuous health care, especially patients with PAD.