The effect of SARS-CoV-2 infection and vaccination on Th17 and regulatory T cells in a pregnancy cohort in NYC.

Disturbances in T-cells, specifically the Th17/Treg balance, have been implicated in adverse pregnancy outcomes. We investigated these two T-cell populations following pre-pregnancy and pregnancy SARS-CoV-2 infection and COVID-19 vaccination in 351 participants from a pregnancy cohort in New York City (Generation C; 2020-2022). SARS-CoV-2 infection status was determined via laboratory or medical diagnosis and COVID-19 vaccination status via survey and electronic medical records data. Peripheral blood mononuclear cells (PBMCs) were collected at routine prenatal visits throughout gestation (median 108 days; IQR 67-191 days) with repeated measures for 104 participants (29.6%). T-cell populations CD4+/CD3+, Th17/CD4+, Treg/CD4+ and the Th17/Treg ratio were quantified using flow cytometry. Results showed that inter-individual differences are a main influencing factor in Th17 and Treg variance, however total variance explained remained small (R2 = 15-39%). Overall, Th17 and Treg populations were not significantly affected by SARS-CoV-2 infection during pregnancy in adjusted linear mixed models (p>0.05), however comparison of repeated measures among SARS-CoV-2 infected participants and non-infected controls suggests a relative increase of the Th17/Treg ratio following infection. In addition, the Th17/Treg ratio was significantly higher after SARS-CoV-2 infection prior to pregnancy (10-138 weeks) compared to controls (ß=0.48, p=0.003). COVID-19 vaccination was not associated with Th17 and Treg cells. Our findings suggest an impact of SARS-CoV-2 infection on the Th17/Treg ratio, likely depending on severity of infection, yet the observed trends and their potential consequences for pregnancy outcomes require further investigation. Our study contributes to growing evidence that COVID-19 vaccination during pregnancy does not lead to an exacerbated immune response.

SARS-CoV-2 infection, inflammation and birth outcomes in a prospective NYC pregnancy cohort.

Associations between antenatal SARS-CoV-2 infection and pregnancy outcomes have been conflicting and the role of the immune system is currently unclear. This prospective cohort study investigated the interaction of antenatal SARS-CoV-2 infection, changes in cytokine and HS-CRP levels, birthweight and gestational age at birth. 2352 pregnant participants from New York City (2020-2022) were included. Plasma levels of interleukin (IL)-1ß, IL-6, IL-17A and high-sensitivity C-reactive protein (HS-CRP) were quantified in blood specimens obtained across pregnancy. Quantile and linear regression models were conducted to 1) assess the impact of antenatal SARS-CoV-2 infection, overall and by timing of detection of SARS-CoV-2 positivity (< 20 weeks versus ≥ 20 weeks), on birthweight and gestational age at delivery; 2) examine the relationship between SARS-CoV-2 infection and maternal immune changes during pregnancy. All models were adjusted for maternal demographic and obstetric factors and pandemic timing. Birthweight models were additionally adjusted for gestational age at delivery and fetal sex. Immune marker models were also adjusted for gestational age at specimen collection and multiplex assay batch. 371 (15.8%) participants were infected with SARS-CoV-2 during pregnancy, of which 98 (26.4%) were infected at < 20 weeks gestation. Neither SARS-CoV-2 infection in general nor in early or late pregnancy was associated with lower birthweight nor earlier gestational age at delivery. Further, we did not observe cytokine or HS-CRP changes in response to SARS-CoV-2 infection and thus found no evidence to support a potential association between immune dysregulation and the diversity in pregnancy outcomes following infection.

Increased postpartum anxiety symptoms after perinatal SARS-CoV-2 infection in a large, prospective pregnancy cohort in New York City.

Numerous studies reported an increase of postpartum mood symptoms during the COVID-19 pandemic. Yet, the link between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and perinatal mental health is less well understood. We investigated the associations between prenatal SARS-CoV-2 infection and postpartum depressive and anxiety symptoms, including examinations of infection timing and pandemic timeline. We included 595 participants from Generation C, a prospective pregnancy cohort in New York City (2020-2022). Prenatal SARS-CoV-2 infection was determined via laboratory or medical diagnosis. Depression and anxiety symptoms were measured 4-12 weeks postpartum using the Edinburgh Postnatal Depression Scale (EPDS) and Generalized Anxiety Disorder questionnaire (GAD), respectively. Quantile regressions were conducted with prenatal SARS-CoV-2 infection as exposure and continuously measured EPDS and GAD scores as outcomes. We reran the analyses in those with COVID-19-like symptoms in the trimester during which infection occurred. 120 (20.1%) participants had prenatal SARS-CoV-2 infection. After adjusting for socio-demographic, obstetric and other maternal health factors, prenatal SARS-CoV-2 infection was associated with higher median postpartum anxiety scores (b = 0.55, 95% CI = 0.15; 0.96). Late gestation infection (b = 1.15, 95% CI = 0.22; 2.09) and symptomatic infection (b = 1.15, 95% CI = 0.12; 2.18) were also associated with higher median postpartum anxiety scores. No associations were found with depressive symptoms. The associations were not moderated by time since the start of the pandemic. This study suggests that prenatal SARS-CoV-2 infection increases the risk of postpartum anxiety symptoms among participants reporting median anxiety symptoms. Given that this association was not affected by pandemic timing and that SARS-CoV-2 transmission continues, individuals infected with SARS-CoV-2 during pregnancy should be monitored for postpartum anxiety symptoms.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Antibody Titer Levels in Pregnant Individuals After Infection, Vaccination, or Both.

We examined differences in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody responses in pregnant individuals with natural, vaccine-induced, or combined immunity. Participants had live or nonlive births between 2020 and 2022, were seropositive (SARS-CoV-2 spike protein, anti-S), and had available mRNA vaccination and infection information (n=260). We compared titer levels among three immunity profiles: 1) natural immunity (n=191), 2) vaccine-induced immunity (n=37), and 3) combined immunity (ie, natural and vaccine-induced immunity; n=32). We applied linear regression to compare anti-S titers between the groups, controlling for age, race and ethnicity, and time between vaccination or infection (whichever came last) and sample collection. Anti-S titers were 57.3% and 94.4% lower among those with vaccine-induced and natural immunity, respectively, compared with those with combined immunity ( P <.001, P =.005).

Impact of prenatal COVID-19 vaccination on delivery and neonatal outcomes: Results from a New York City cohort.

Research suggest prenatal vaccination against coronavirus disease-19 (COVID-19) is safe. However, previous studies utilized retrospectively collected data or examined late pregnancy vaccinations. We investigated the associations of COVID-19 vaccination throughout pregnancy with delivery and neonatal outcomes. We included 1,794 mother-neonate dyads enrolled in the Generation C Study with known prenatal COVID-19 vaccination status and complete covariate and outcome data. We used multivariable quantile regressions to estimate the effect of prenatal COVID-19 vaccination on birthweight, delivery gestational age, and blood loss at delivery; and Poisson generalized linear models for Caesarean delivery (CD) and Neonatal Intensive Care Unit (NICU) admission. Using the above methods, we estimated effects of trimester of vaccine initiation on these outcomes. In our sample, 13.7% (n = 250) received at least one prenatal dose of any COVID-19 vaccine. Vaccination was not associated with birthweight (ß = 12.42 g [-90.5, 114.8]), gestational age (ß = 0.2 days [-1.1, 1.5]), blood loss (ß = -50.6 ml [-107.0, 5.8]), the risks of CD (RR = 0.8; [0.6, 1.1]) or NICU admission (RR = 0.9 [0.5, 1.7]). Trimester of vaccine initiation was also not associated with these outcomes. Our findings suggest that there is no associated risk between prenatal COVID-19 vaccination and adverse delivery and neonatal outcomes in a cohort sample from NYC.

Cross-sectional associations of maternal PFAS exposure on SARS-CoV-2 IgG antibody levels during pregnancy.

BACKGROUND: Perfluoroalkylated substances (PFAS) are man-made, persistent organic compounds with immune-modulating potentials. Given that pregnancy itself represents an altered state of immunity, PFAS exposure-related immunotoxicity is an important environmental factor to consider in SARS-CoV-2 infection during pregnancy as it may further affect humoral immune responses. AIM: To investigate the relationship between maternal plasma PFAS concentrations and SARS-CoV-2 antibody levels in a NYC-based pregnancy cohort. METHODS: Maternal plasma was collected from 72 SARS-CoV-2 IgG + participants of the Generation C Study, a birth cohort established at the beginning of the COVID-19 pandemic in New York City. Maternal SARS-CoV-2 anti-spike IgG antibody levels were measured using ELISA. A panel of 16 PFAS congeners were measured in maternal plasma using a targeted UHPLC-MS/MS-based assay. Spearman correlations and linear regressions were employed to explore associations between maternal IgG antibody levels and plasma PFAS concentrations. Weighted quantile sum (WQS) regression was also used to evaluate mixture effects of PFAS. Models were adjusted for maternal age, gestational age at which SARS-CoV-2 IgG titer was measured, COVID-19 vaccination status prior to IgG titer measurement, maternal race/ethnicity, parity, type of insurance and pre-pregnancy BMI. RESULTS: Our study population is ethnically diverse with an average maternal age of 32 years. Of the 16 PFAS congeners measured, nine were detected in more than 60% samples. Importantly, all nine congeners were negatively correlated with SARS-CoV-2 anti-spike IgG antibody levels; n-PFOA and PFHxS, PFHpS, and PFHxA reached statistical significance (p < 0.05) in multivariable analyses. When we examined the mixture effects using WQS, a quartile increase in the PFAS mixture-index was significantly associated with lower maternal IgG antibody titers (beta [95% CI] = -0.35 [-0.52, -0.17]). PFHxA was the top contributor to the overall mixture effect. CONCLUSIONS: Our study results support the notion that PFAS, including short-chain emerging PFAS, act as immunosuppressants during pregnancy. Whether such compromised immune activity leads to downstream health effects, such as the severity of COVID-19 symptoms, adverse obstetric outcomes or neonatal immune responses remains to be investigated.

Gestational SARS-CoV-2 infection is associated with placental expression of immune and trophoblast genes.

INTRODUCTION: Maternal SARS-CoV-2 infection during pregnancy is associated with adverse pregnancy outcomes and can have effects on the placenta, even in the absence of severe disease or vertical transmission to the fetus. This study aimed to evaluate histopathologic and molecular effects in the placenta after SARS-CoV-2 infection during pregnancy. METHODS: We performed a study of 45 pregnant participants from the Generation C prospective cohort study at the Mount Sinai Health System in New York City. We compared histologic features and the expression of 48 immune and trophoblast genes in placentas delivered from 15 SARS-CoV-2 IgG antibody positive and 30 IgG SARS-CoV-2 antibody negative mothers. Statistical analyses were performed using Fisher's exact tests, Spearman correlations and linear regression models. RESULTS: The median gestational age at the time of SARS-CoV-2 IgG serology test was 35 weeks. Two of the IgG positive participants also had a positive RT-PCR nasal swab at delivery. 82.2% of the infants were delivered at term (≥37 weeks), and gestational age at delivery did not differ between the SARS-CoV-2 antibody positive and negative groups. No significant differences were detected between the groups in placental histopathology features. Differential expression analyses revealed decreased expression of two trophoblast genes (PSG3 and CGB3) and increased expression of three immune genes (CXCL10, TLR3 and DDX58) in placentas delivered from SARS-CoV-2 IgG positive participants. DISCUSSION: SARS-CoV-2 infection during pregnancy is associated with gene expression changes of immune and trophoblast genes in the placenta at birth which could potentially contribute to long-term health effects in the offspring.

Stress and the Psychological Impact of the COVID-19 Pandemic on Frontline Obstetrics and Gynecology Providers.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic rapidly overwhelmed global health care systems in 2020, with New York City (NYC) marking the first epicenter in the United States. High levels of stress amongst health care workers have been reported in pandemics, but less is known about stress amongst Obstetrics and Gynecology (OB/GYN) providers. We sought to describe levels of stress, anxiety, depression, and other aspects of mental health among OB/GYN health care workers during the first wave of the COVID-19 pandemic. STUDY DESIGN: We conducted an anonymous cross-sectional electronic survey of a wide range of OB/GYN clinicians in a large NYC hospital system in the spring of 2020. We used both original survey questions and validated screening tools to assess stress, anxiety, depression, and burnout. We calculated median scores for these tools and compared median score between provider types. We also adapted questions on pandemic-related stressors from the MERS and SARS pandemics to fit the context of the COVID-19 pandemic and OB/GYN providers. RESULTS: A total of 464 providers met study inclusion criteria, and 163 providers completed the survey (response rate = 35.1%). Approximately 35% of providers screened positive for anxiety and 21% for depression. Scores for depression, burnout, and fulfillment varied by provider type, with nurses scoring higher than physicians (p <0.05). The majority of respondents reported stress from pandemic and OB-specific stressors, including the possibility of transmitting COVID-19 to friends and family (83.9%, [95% confidence interval or CI 78.0-89.8%]), uncertainty regarding the pandemic's trajectory (91.3% [86.7-95.8%]), and frequent policy changes on labor and delivery (72.7% [65.1-80.3%]). CONCLUSION: OB/GYN providers reported high levels of stress during the COVID-19 pandemic. The stress of caring for laboring patients during a pandemic may disproportionately affect nurses and trainees and highlights the need to provide interventions to ameliorate the negative impact of a pandemic on the mental health of our OB/GYN health care workers. KEY POINTS: · COVID-19 led to stress amongst OB/GYN providers.. · Some stressors were unique to providing obstetric care.. · Nurses and trainees were more affected by this stress..

The influence of structural racism, pandemic stress, and SARS-CoV-2 infection during pregnancy with adverse birth outcomes.

BACKGROUND: Structural racism and pandemic-related stress from the COVID-19 pandemic may increase the risk of adverse birth outcomes. OBJECTIVE: Our objective was to examine associations between neighborhood measures of structural racism and pandemic stress with 3 outcomes: SARS-CoV-2 infection, preterm birth, and delivering small-for-gestational-age newborns. Our secondary objective was to investigate the joint association of SARS-CoV-2 infection during pregnancy and neighborhood measures with preterm birth and delivering small-for-gestational-age newborns. STUDY DESIGN: We analyzed data of 967 patients from a prospective cohort of pregnant persons in New York City, comprising 367 White (38%), 169 Black (17%), 293 Latina (30%), and 87 Asian persons (9%), 41 persons of other race or ethnicity (4%), and 10 of unknown race or ethnicity (1%). We evaluated structural racism (social/built structural disadvantage, racial-economic segregation) and pandemic-related stress (community COVID-19 mortality, community unemployment rate increase) in quartiles by zone improvement plan code. SARS-CoV-2 serologic enzyme-linked immunosorbent assay was performed on blood samples from pregnant persons. We obtained data on preterm birth and small-for-gestational-age newborns from an electronic medical record database. We used log-binomial regression with robust standard error for clustering by zone improvement plan code to estimate associations of each neighborhood measure separately with 3 outcomes: SARS-CoV-2 infection, preterm birth, and small-for-gestational-age newborns. Covariates included maternal age, parity, insurance status, and body mass index. Models with preterm birth and small-for-gestational-age newborns as the dependent variables additionally adjusted for SARS-CoV-2 infection. RESULTS: A total of 193 (20%) persons were SARS-CoV-2-seropositive, and the overall risks of preterm birth and small-for-gestational-age newborns were 8.4% and 9.8%, respectively. Among birthing persons in neighborhoods in the highest quartile of structural disadvantage (n=190), 94% were non-White, 50% had public insurance, 41% were obese, 32% were seropositive, 11% delivered preterm, and 12% delivered a small-for-gestational-age infant. Among birthing persons in neighborhoods in the lowest quartile of structural disadvantage (n=360), 39% were non-White, 17% had public insurance, 15% were obese, 9% were seropositive, 6% delivered preterm, and 10% delivered a small-for-gestational-age infant. In adjusted analyses, structural racism measures and community unemployment were associated with both SARS-CoV-2 infection and preterm birth, but not small-for-gestational-age infants. High vs low structural disadvantage was associated with an adjusted relative risk of 2.6 for infection (95% confidence interval, 1.7-3.9) and 1.7 for preterm birth (95% confidence interval, 1.0-2.9); high vs low racial-economic segregation was associated with adjusted relative risk of 1.9 (95% confidence interval, 1.3-2.8) for infection and 2.0 (95% confidence interval, 1.3-3.2) for preterm birth; high vs low community unemployment increase was associated with adjusted relative risk of 1.7 (95% confidence interval, 1.2-1.5) for infection and 1.6 (95% confidence interval, 1.0-2.8) for preterm birth. COVID-19 mortality rate was associated with SARS-CoV-2 infection but not preterm birth or small-for-gestational-age infants. SARS-CoV-2 infection was not independently associated with birth outcomes. We found no interaction between SARS-CoV-2 infection and neighborhood measures on preterm birth or small-for-gestational-age infants. CONCLUSION: Neighborhood measures of structural racism were associated with both SARS-CoV-2 infection and preterm birth, but these associations were independent and did not have a synergistic effect. Community unemployment rate increases were also associated with an increased risk of preterm birth independently of SARS-CoV-2 infection. Mitigating these factors might reduce the impact of the pandemic on pregnant people.

SARS-CoV-2 during pregnancy and associated outcomes: Results from an ongoing prospective cohort.

BACKGROUND: The COVID-19 pandemic is an ongoing global health threat, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Questions remain about how SARS-CoV-2 impacts pregnant individuals and their children. OBJECTIVE: To expand our understanding of the effects of SARS-CoV-2 infection during pregnancy on pregnancy outcomes, regardless of symptomatology, by using serological tests to measure IgG antibody levels. METHODS: The Generation C Study is an ongoing prospective cohort study conducted at the Mount Sinai Health System. All pregnant individuals receiving obstetrical care at the Mount Sinai Healthcare System from 20 April 2020 onwards are eligible for participation. For the current analysis, we included participants who had given birth to a liveborn singleton infant on or before 22 September 2020. For each woman, we tested the latest prenatal blood sample available to establish seropositivity using a SARS-CoV-2 serologic enzyme-linked immunosorbent assay. Additionally, RT-PCR testing was performed on a nasopharyngeal swab taken during labour. Pregnancy outcomes of interest (i.e., gestational age at delivery, preterm birth, small for gestational age, Apgar scores, maternal and neonatal intensive care unit admission, and length of neonatal hospital stay) and covariates were extracted from medical records. Excluding individuals who tested RT-PCR positive at delivery, we conducted crude and adjusted regression models to compare antibody positive with antibody negative individuals at delivery. We stratified analyses by race/ethnicity to examine potential effect modification. RESULTS: The SARS-CoV-2 seroprevalence based on IgG measurement was 16.4% (95% confidence interval 13.7, 19.3; n=116). Twelve individuals (1.7%) were SARS-CoV-2 RT-PCR positive at delivery. Seropositive individuals were generally younger, more often Black or Hispanic, and more often had public insurance and higher pre-pregnancy BMI compared with seronegative individuals. None of the examined pregnancy outcomes differed by seropositivity, overall or stratified by race/ethnicity. CONCLUSION: Seropositivity for SARS-CoV-2 without RT-PCR positivity at delivery (suggesting that infection occurred earlier during pregnancy) was not associated with selected adverse maternal or neonatal outcomes among live births in a cohort sample from New York City.

Prevalence of Hepatitis B and C Among Healthcare Workers in a Tertiary Care Center in Monrovia Liberia.

Background: Viral hepatitis is a leading cause of death worldwide, with a higher mortality rate than that from human immunodeficiency virus (HIV), tuberculosis (TB) or malaria. In order to meet the WHO's goal of eliminating hepatitis B and C by 2030, there is a dire need to establish baseline prevalence rates and increase public health awareness of this detrimental disease, especially in low and middle-income countries (LMICs) where establishing prevalence rates of hepatitis B (HBV) and hepatitis (HCV) continues to be a problem. Objective: To establish baseline rates of hepatitis B and C among healthcare workers at the national medical center of Liberia. Methods: Between October 2017 to 2018 we performed a prospective study to determine rates of hepatitis B and hepatitis C among healthcare workers at John F. Kennedy (JFK) Medical Center, the national medical center of Liberia. All healthcare workers were offered one-time point of care hepatitis B antigen (HBsAg) and hepatitis C antibody testing. Findings: Two hundred forty-five participants were tested for hepatitis B and C. 15 participants (6.12%) tested positive for hepatitis B [95% CI, 3.47%, 9.90%]. Eleven of the fifteen (73.3%) participants received confirmatory hepatitis B profile testing, and eight (72%) of those were found to be chronic hepatitis B carriers. No participants tested positive for hepatitis C Ab. Conclusion: Our finding of a greater than 5% prevalence rate, during first line testing, of chronic hepatitis B among health care workers, should help fuel efforts for national testing, vaccination, and treatment efforts in order to align with the WHO goals of elimination of hepatitis B and C by 2030.

Community-Institutional Partnerships to Strengthen Maternal Health Care: Case Study of the First Obstetrics and Gynecology Specialty Training Program in Liberia.

Despite major setbacks to its health infrastructure and health workforce capacity, Liberia began its first post-graduate training program for physicians in 2013. Specialty training in Internal Medicine, Pediatrics, General Surgery and Obstetrics and Gynecology were the four inaugural Residency programs that recruited graduates from the country's only medical school, A.M. Dogliotti College of Medicine. The Obstetrics and Gynecology residency program was designed to combat the rising maternal mortality and strengthen health systems to improve maternal care. The program adapted in the face of challenges posed by limited financial support, lack of specialist-faculty and general physician shortages and the Ebola virus outbreak. The manuscript discusses the challenges and successes of the program and demonstrates how the shortage of teaching faculty was addressed by developing a collaboration between local government and educational communities, a United States (US) academic institution and volunteers from the Global Health Service Partnership.

Cervical cancer risk factors and screening preferences among Muslim women in Monrovia, Liberia.

Cervical cancer is the most common cancer in reproductive aged women in Liberia. Lack of awareness and screening capacity are both major contributors to the prevalence of this disease. The minority Muslim population in this country is largely unscreened. The objective of the study was to assess cervical cancer risk factors and screening preferences among Muslim women living in Monrovia, Liberia and to offer self-screening with HPV testing. A multiple step implementation strategy was devised in order to outreach to the Muslim population with the engagement of community and religious leaders, about an upcoming screening program and informational session at a local clinic. Over 150 Muslim women attended the session, 120 completed the HPV screening, and 55 women completed the questionnaires. Questionnaire data revealed overall low risk factors for cervical cancer, but also low use of family planning as well as low knowledge about cervical cancer and HPV. Participants showed an interest in screening and a majority preferred self-collected tests. These preferences should be incorporated in future programming. To engage minority populations in screening programs, there may be success with targeted messages, involvement of community religious leaders, and eliciting feedback to incorporate preferred strategies and improve participation and programming.

Human Papillomavirus Knowledge, Attitudes, Practices, and Prevalence Among Men Who Have Sex With Men in Monrovia, Liberia.

OBJECTIVE: The aim of this study was to assess human papillomavirus (HPV) prevalence, knowledge, attitudes, and practices, among men who have sex with men (MSM) in Monrovia, Liberia. MATERIALS AND METHOD: This cross-sectional study was conducted with 107 MSM, aged 18 to 58 years, completing questionnaires and anal HPV screenings. Using peer-educators and direct community involvement, demographics, risk factors, and HPV knowledge data were collected. RESULTS: Forty-eight participants (45%) were HPV positive and 21 participants (19.6%) self-identified as HIV positive. When examining HPV risk factors, 22 participants reported first sexual experience before the age of 15 years. Approximately half of participants (n = 58, 54.2%) have receptive anal sex and 40 (37.4%) reported more than 20 lifetime sexual partners. Eight participants (7.5%) had no formal education and 80 (74.8%) were not formally employed. Two-thirds of participants (64%) had never heard of HPV. Education was not significantly correlated with HPV knowledge. χ tests of independence were performed, and the relation between oral and anal sex and HPV knowledge was significant (χ (1) = 5.08, p < .05; χ (1) = 4.18, p < .05), respectively, such that those who engaged in oral and anal sex had lower levels of HPV knowledge. CONCLUSIONS: Among the MSM population, HPV prevalence is high, as are high-risk practices. Participants lack HPV knowledge, independent of educational achievement, and are eager to receive educational information. Future studies should focus on identifying additional risk factors and implementing public health educational interventions.

Recruitment and retention strategies in a clinical trial for children with chronic hepatitis C infection.

Successful strategies for recruitment and retention (R & R) in pediatric trials are needed. The purpose of our study was to analyze the effectiveness of R&R in a trial for children with hepatitis C. Recruitment strategies were (1) Initial (months 0-12) and (2) extra effort (months 13-18). Initial strategies enrolled 70/114 (61%) of patients. Extra effort strategies included: (1) radio broadcasts, (2) contact with adult hepatologists, (3) dissemination of study material and (4) modification of the exclusion criteria. The overall retention rate was 84% at 2 years. Lessons learned will be valuable in designing future pediatric trials.

Astragalus-based Chinese herbs and platinum-based chemotherapy for advanced non-small-cell lung cancer: meta-analysis of randomized trials.

PURPOSE: Systemic treatments for advanced non-small-cell lung cancer have low efficacy and high toxicity. Some Chinese herbal medicines have been reported to increase chemotherapy efficacy and reduce toxicity. In particular, Astragalus has been shown to have immunologic benefits by stimulating macrophage and natural killer cell activity and inhibiting T-helper cell type 2 cytokines. Many published studies have assessed the use of Astragalus and other Chinese herbal medicines in combination with chemotherapy. We sought to evaluate evidence from randomized trials that Astragalus-based Chinese herbal medicine combined with platinum-based chemotherapy (versus platinum-based chemotherapy alone) improves survival, increases tumor response, improves performance status, or reduces chemotherapy toxicity. METHODS: We searched CBM, MEDLINE, TCMLARS, EMBASE, Cochrane Library, and CCRCT databases for studies in any language. We grouped studies using the same herbal combinations for random-effects meta-analysis. RESULTS: Of 1,305 potentially relevant publications, 34 randomized studies representing 2,815 patients met inclusion criteria. Twelve studies (n = 940 patients) reported reduced risk of death at 12 months (risk ratio [RR] = 0.67; 95% CI, 0.52 to 0.87). Thirty studies (n = 2,472) reported improved tumor response data (RR = 1.34; 95% CI, 1.24 to 1.46). In subgroup analyses, Jin Fu Kang in two studies (n = 221 patients) reduced risk of death at 24 months (RR = 0.58; 95% CI, 0.49 to 0.68) and in three studies (n = 411) increased tumor response (RR = 1.76; 95% CI, 1.23 to 2.53). Ai Di injection (four studies; n = 257) stabilized or improved Karnofsky performance status (RR = 1.28; 95% CI, 1.12 to 1.46). CONCLUSION: Astragalus-based Chinese herbal medicine may increase effectiveness of platinum-based chemotherapy when combined with chemotherapy. These results require confirmation with rigorously controlled trials.