Bias analyses to investigate the impact of differential participation: Application to a birth defects case-control study.

BACKGROUND: Certain associations observed in the National Birth Defects Prevention Study (NBDPS) contrasted with other research or were from areas with mixed findings, including no decrease in odds of spina bifida with periconceptional folic acid supplementation, moderately increased cleft palate odds with ondansetron use and reduced hypospadias odds with maternal smoking. OBJECTIVES: To investigate the plausibility and extent of differential participation to produce effect estimates observed in NBDPS. METHODS: We searched the literature for factors related to these exposures and participation and conducted deterministic quantitative bias analyses. We estimated case-control participation and expected exposure prevalence based on internal and external reports, respectively. For the folic acid-spina bifida and ondansetron-cleft palate analyses, we hypothesized the true odds ratio (OR) based on prior studies and quantified the degree of exposure over- (or under-) representation to produce the crude OR (cOR) in NBDPS. For the smoking-hypospadias analysis, we estimated the extent of selection bias needed to nullify the association as well as the maximum potential harmful OR. RESULTS: Under our assumptions (participation, exposure prevalence, true OR), there was overrepresentation of folic acid use and underrepresentation of ondansetron use and smoking among participants. Folic acid-exposed spina bifida cases would need to have been ≥1.2× more likely to participate than exposed controls to yield the observed null cOR. Ondansetron-exposed cleft palate cases would need to have been 1.6× more likely to participate than exposed controls if the true OR is null. Smoking-exposed hypospadias cases would need to have been ≥1.2 times less likely to participate than exposed controls for the association to falsely appear protective (upper bound of selection bias adjusted smoking-hypospadias OR = 2.02). CONCLUSIONS: Differential participation could partly explain certain associations observed in NBDPS, but questions remain about why. Potential impacts of other systematic errors (e.g. exposure misclassification) could be informed by additional research.

Early pregnancy vitamin D status and risk of select congenital anomalies in the National Birth Defects Prevention Study.

INTRODUCTION: Vitamin D deficiency is associated with adverse pregnancy events. However, its role in the etiology of congenital anomalies remains unclear. We examined the association between vitamin D status, measured through prepregnancy diet, UV exposure, season of conception, and congenital anomalies. METHODS: We used data from the National Birth Defects Prevention Study, a U.S. population-based case-control study (1997-2011). Prepregnancy dietary vitamin D was calculated from food frequency questionnaires and evaluated using tertiles, based on the distribution in controls. We used the National Oceanic and Atmospheric Administration Weather Service to assign UV indices based on location and estimated date of conception, then dichotomized UV exposure (low vs. high). Seasons of conception was categorized as fall/winter spring/summer. We used logistic regression to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI). RESULTS: Lower prepregnancy dietary vitamin D intake (<65.21 IU/d vs. >107.55 IU/d) was associated with increased odds of anencephaly (aOR = 1.28, 95% CI 1.01, 1.63), hypospadias (aOR = 1.21, 95% CI 1.04, 1.40), septal defects (aOR = 1.16, 95% CI 1.05, 1.30), diaphragmatic hernia (aOR = 1.42, 95% CI 1.13, 1.79), and gastroschisis (aOR = 1.27, 95% CI 1.07, 1.52). Findings were consistent when we stratified by UV exposure and season of conception. CONCLUSIONS: Our findings suggest lower dietary intake of vitamin D may be associated with increased risk of select congenital anomalies. Further investigations are warranted to evaluate the effects of other nutrients and appropriate thresholds and sources of vitamin D using serum.

Feasibility and acceptability of nationwide HPV vaccine introduction in Senegal: Findings from community-level cross-sectional surveys, 2020.

In Senegal, cervical cancer is the most common cancer among women and the leading cause of morbidity and mortality from all cancers. In 2018, Senegal launched a national human papillomavirus (HPV) vaccination program with Gavi, the Vaccine Alliance (Gavi), support. HPV vaccination was incorporated into the national immunization program as a two-dose schedule, with a 6-12-month interval, to nine-year-old girls via routine immunization (RI) services at health facilities, schools and community outreach services throughout the year. During February to March 2020, we conducted interviews to assess the awareness, feasibility, and acceptability of the HPV vaccination program with a cross-sectional convenience sample of healthcare workers (HCWs), school personnel, community healthcare workers (cHCWs), parents, and community leaders from 77 rural and urban health facility catchment areas. Participants were asked questions on HPV vaccine knowledge, delivery, training, and community acceptability of the program. We conducted a descriptive analysis stratified by respondent type. Data were collected from 465 individuals: 77 HCW, 78 school personnel, 78 cHCWs, 152 parents, and community leaders. The majority of HCWs (83.1%) and cHCWs (74.4%) and school personnel (57.7%) attended a training on HPV vaccine before program launch. Of all respondents, most (52.5-87.2%) were able to correctly identify the target population. The majority of respondents (60.2-77.5%) felt that the vaccine was very accepted or accepted in the community. Senegal's HPV vaccine introduction program, among the first national programs in the African region, was accepted by community stakeholders. Training rates were high, and most respondents identified the target population correctly. However, continued technical support is needed for the integration of HPV vaccination as a RI activity for this non-traditional age group. The Senegal experience can be a useful resource for countries planning to introduce the HPV vaccine.

National introduction of HPV vaccination in Senegal-Successes, challenges, and lessons learned.

Following successful school-based demonstration programs in 2014-2016, the human papillomavirus (HPV) vaccine was introduced nationwide in Senegal for 9-year-old girls in 2018, using a routine service delivery strategy at health facilities, schools, and other outreach sites. We reviewed the HPV vaccine introduction in Senegal to understand the successes, challenges, and lessons learned. Focusing on three key domains (program decision-making, planning, and implementation), we conducted ten semi-structured interviews during 2019-2020 with purposively selected national-level stakeholders (government, expert advisory committee, key technical and implementation partners) and comprehensive desk reviews of country documents on HPV vaccine introduction. Due to the global HPV vaccine shortage, the introduction was limited to a single-age cohort; therefore, 9-year-old girls were chosen. This strategy enabled Senegal to potentially reach more girls in primary education because school enrolment rates decline thereafter. Vaccination through routine delivery platforms (i.e., health facility, school-based, and community outreach) was perceived to be more cost-effective than a campaign approach. High-level political commitment and collaborations between immunization and education partners were frequently cited by key informants as reasons for a successful vaccine introduction. All key informants reported that the health care worker (HCW) strike, rumors, and vaccine hesitancy negatively impacted the introduction. Other challenges noted included insufficient information on attitudes towards HPV vaccination among HCWs, teachers, and community members. Senegal successfully introduced HPV vaccine into the national immunization schedule, using a routine delivery strategy. Strong leadership and a multi-sectoral approach likely contributed to this success. To build sustainability of the HPV vaccination program in the future, it is important to improve the understanding and engagement among all stakeholders, including HCWs and community members, and to strengthen and innovate communication and crisis management strategies. To better understand the efficiency and effectiveness of Senegal's vaccination strategy, additional assessments of the operational costs and coverage achieved are needed.

Mask adherence and rate of COVID-19 across the United States.

Mask wearing has been advocated by public health officials as a way to reduce the spread of COVID-19. In the United States, policies on mask wearing have varied from state to state over the course of the pandemic. Even as more and more states encourage or even mandate mask wearing, many citizens still resist the notion. Our research examines mask wearing policy and adherence in association with COVID-19 case rates. We used state-level data on mask wearing policy for the general public and on proportion of residents who stated they always wear masks in public. For all 50 states and the District of Columbia (DC), these data were abstracted by month for April ─ September 2020 to measure their impact on COVID-19 rates in the subsequent month (May ─ October 2020). Monthly COVID-19 case rates (number of cases per capita over two weeks) >200 per 100,000 residents were considered high. Fourteen of the 15 states with no mask wearing policy for the general public through September reported a high COVID-19 rate. Of the 8 states with at least 75% mask adherence, none reported a high COVID-19 rate. States with the lowest levels of mask adherence were most likely to have high COVID-19 rates in the subsequent month, independent of mask policy or demographic factors. Mean COVID-19 rates for states with at least 75% mask adherence in the preceding month was 109.26 per 100,000 compared to 249.99 per 100,000 for those with less adherence. Our analysis suggests high adherence to mask wearing could be a key factor in reducing the spread of COVID-19. This association between high mask adherence and reduced COVID-19 rates should influence policy makers and public health officials to focus on ways to improve mask adherence across the population in order to mitigate the spread of COVID-19.

Trends in first-trimester nausea and vomiting of pregnancy and use of select treatments: Findings from the National Birth Defects Prevention Study.

BACKGROUND: Although nausea and vomiting of pregnancy (NVP) is common, the secular and demographic trends of NVP and its treatments are not well-studied. OBJECTIVES: To describe the prevalence and patterns of first-trimester NVP and selected treatments among controls in the National Birth Defects Prevention Study (NBDPS). METHODS: National Birth Defects Prevention Study is a population-based case-control study of birth defects in the United States (1997-2011). We collected self-reported data about NVP and use of commonly reported pharmacological and herbal/natural treatments (ondansetron, promethazine, pyridoxine, metoclopramide, doxylamine succinate, ginger, phosphorated carbohydrate solution, and prochlorperazine) from mothers of non-malformed control infants. We estimated the prevalence of NVP and selected treatments and examined secular and demographic trends (education, race/ethnicity, and maternal age) for such use, adjusting for study centre. RESULTS: Among 10 540 mothers of controls, 7393 women (70.1%) reported first-trimester NVP, and 12.2% of those used one or more of the commonly reported treatments. Specific treatment use varied after adjustment for study centre (ondansetron: 3.4%; promethazine: 4.2%; pyridoxine: 3.2%; metoclopramide: 0.7%; doxylamine succinate: 1.7%; ginger: 1.0%; phosphorated carbohydrate solution: 0.4%; and prochlorperazine: 0.3%). Treatment use increased for each agent over the study period. Women with more years of education reported more NVP and treatment use. White (72%), Hispanic (71%), and other race (73%) women reported more NVP than Black women (67%); White women used selected NVP treatments most frequently, and Black women used them more than Hispanic women. Though women aged 25-34 years reported more NVP (72%) than younger (69%) or older (67%) women, the frequency of medication use was similar among women aged 25-34 and ≥35, and lower among women aged <25 years. CONCLUSIONS: National Birth Defects Prevention Study controls reported NVP at frequencies similar to those previously reported. Of note, we observed an increase in use of selected treatments over time, and variations in NVP and treatments by study site and demographic factors.

Vasoactive exposures and risk of amniotic band syndrome and terminal transverse limb deficiencies.

INTRODUCTION: Amniotic band syndrome (ABS) includes limb deficiencies accompanied by fibrous strands originating from the amniotic lining. Terminal transverse limb deficiencies (TTLD) appear to be similar but lack fibrous strands. Both are hypothesized to result from vascular disruption. For ABS, limb deficiencies are considered secondary to amnion rupture. We explored an alternative possibility-that TTLD is the primary defect and ABS is secondary. METHODS: Using data from the National Birth Defects Prevention Study, we expanded on a previous study. We examined smoking, alcohol, and medications categorized by indicated vasoactivity as markers of vascular disruption. Logistic regression models with Firth's penalized likelihood were used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). RESULTS: Use of bronchodilators and aspirin appeared to increase the risk of ABS, while decongestants and nonaspirin NSAIDs increased the risk of TTLD. The risk of ABS was markedly increased in cases reporting combinations of vasoactive exposures, particularly alcohol and aspirin (aOR 3.7, 95% CI 1.6, 7.8), and alcohol and bronchodilators (aOR 3.4, 95% CI 1.4, 7.5). Increased risk of TTLD due to combinations of vasoactive exposures was only observed for smoking and decongestants (aOR 2.3, 95% CI 1.4, 3.6). CONCLUSIONS: Exposures associated with increased risk of ABS had no apparent association with TTLD, supporting previous evidence that these may be distinct phenotypes. ABS appears to be associated with combined exposures with vasodilation properties, such as alcohol and bronchodilators, while increased risk of TTLD may be associated with smoking and decongestants, both vasoconstrictive exposures.

Differences between coverage of yellow fever vaccine and the first dose of measles-containing vaccine: A desk review of global data sources.

INTRODUCTION: The strategy to Eliminate Yellow Fever Epidemics (EYE) is a global initiative that includes all countries with risk of yellow fever (YF) virus transmission. Of these, 40 countries (27 in Africa and 13 in the Americas) are considered high-risk and targeted for interventions to increase coverage of YF vaccine. Even though the World Health Organization (WHO) recommends that YF vaccine be given concurrently with the first dose of measles-containing vaccine (MCV1) in YF-endemic settings, estimated coverage for MCV1 and YF vaccine have varied widely. The objective of this study was to review global data sources to assess discrepancies in YF vaccine and MCV1 coverage and identify plausible reasons for these discrepancies. METHODS: We conducted a desk review of data from 34 countries (22 in Africa, 12 in Latin America), from 2006 to 2016, with national introduction of YF vaccine and listed as high-risk by the EYE strategy. Data reviewed included procured and administered doses, immunization schedules, routine coverage estimates and reported vaccine stock-outs. In the 30 countries included in the comparitive analysis, differences greater than 3 percentage points between YF vaccine and MCV1 coverage were considered meaningful. RESULTS: In America, there were meaningful differences (7-45%) in coverage of the two vaccines in 6 (67%) of the 9 countries. In Africa, there were meaningful differences (4-27%) in coverage of the two vaccines in 9 (43%) of the 21 countries. Nine countries (26%) reported MVC1 stock-outs while sixteen countries (47%) reported YF vaccine stock-outs for three or more years during 2006-2016. CONCLUSION: In countries reporting significant differences in coverage of the two vaccines, differences may be driven by different target populations and vaccine availability. However,these were not sufficient to completely explain observed differences. Further follow-up is needed to identify possible reasons for differences in coverage rates in several countries where these could not fully be explained.

Cholera Epidemic - Lusaka, Zambia, October 2017-May 2018.

On October 6, 2017, an outbreak of cholera was declared in Zambia after laboratory confirmation of Vibrio cholerae O1, biotype El Tor, serotype Ogawa, from stool specimens from two patients with acute watery diarrhea. The two patients had gone to a clinic in Lusaka, the capital city, on October 4. Cholera cases increased rapidly, from several hundred cases in early December 2017 to approximately 2,000 by early January 2018 (Figure). In collaboration with partners, the Zambia Ministry of Health (MoH) launched a multifaceted public health response that included increased chlorination of the Lusaka municipal water supply, provision of emergency water supplies, water quality monitoring and testing, enhanced surveillance, epidemiologic investigations, a cholera vaccination campaign, aggressive case management and health care worker training, and laboratory testing of clinical samples. In late December 2017, a number of water-related preventive actions were initiated, including increasing chlorine levels throughout the city's water distribution system and placing emergency tanks of chlorinated water in the most affected neighborhoods; cholera cases declined sharply in January 2018. During January 10-February 14, 2018, approximately 2 million doses of oral cholera vaccine were administered to Lusaka residents aged ≥1 year. However, in mid-March, heavy flooding and widespread water shortages occurred, leading to a resurgence of cholera. As of May 12, 2018, the outbreak had affected seven of the 10 provinces in Zambia, with 5,905 suspected cases and a case fatality rate (CFR) of 1.9%. Among the suspected cases, 5,414 (91.7%), including 98 deaths (CFR = 1.8%), occurred in Lusaka residents.

Infection Prevention and Control for Ebola in Health Care Settings - West Africa and United States.

The 2014-2016 Ebola virus disease (Ebola) epidemic in West Africa underscores the need for health care infection prevention and control (IPC) practices to be implemented properly and consistently to interrupt transmission of pathogens in health care settings to patients and health care workers. Training and assessing IPC practices in general health care facilities not designated as Ebola treatment units or centers became a priority for CDC as the number of Ebola virus transmissions among health care workers in West Africa began to affect the West African health care system and increasingly more persons became infected. CDC and partners developed policies, procedures, and training materials tailored to the affected countries. Safety training courses were also provided to U.S. health care workers intending to work with Ebola patients in West Africa. As the Ebola epidemic continued in West Africa, the possibility that patients with Ebola could be identified and treated in the United States became more realistic. In response, CDC, other federal components (e.g., Office of the Assistant Secretary for Preparedness and Response) and public health partners focused on health care worker training and preparedness for U.S. health care facilities. CDC used the input from these partners to develop guidelines on IPC for hospitalized patients with known or suspected Ebola, which was updated based on feedback from partners who provided care for Ebola patients in the United States. Strengthening and sustaining IPC helps health care systems be better prepared to prevent and respond to current and future infectious disease threats.The activities summarized in this report would not have been possible without collaboration with many U.S. and international partners (http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/partners.html).