Prevalence and duration of anti-SARS-CoV-2 antibodies in healthcare workers

Introduction. Knowledge of the seroprevalence and duration of antibodies against SARS-CoV-2 was needed in the early phases of the COVID-19 pandemic and is still necessary for policy makers and healthcare professionals. This information allows us to better understand the risk of reinfection in previously infected individuals. Methods. We investigated the prevalence and duration of detectable antibodies against SARS-CoV-2 in sequentially collected samples from 379 healthcare professionals. Results. SARS-CoV-2 seroprevalence at inclusion was 5.3% (95% confidence interval (CI): 3.3-8.0%) and 25% of seropositive participants reverted during follow-up. At the end of follow-up, the calculated probability of having detectable antibodies among former seropositive participants was 72.2% (95% CI: 54.2-96.2%). Conclusion. Antibodies against SARS-CoV-2 were detectable in a subset of infected individuals for a minimum of 39 weeks.

Implementing Substance Use Prevention Programming in Rural Utah During COVID-19

Introduction: Although a relatively healthy state (i.e., low cancer rates, low use of alcohol/tobacco), Utah ranked seventh in the nation from 2013-2015 for drug overdose deaths, the majority being opioid related. From 2000-2015, Utah saw a 400% increase in deaths resulting from the misuse and abuse of prescription drugs. Utah sought to address this issue in three rural counties, including one that in 2014 had more than twice the state average and more than 2.4 times the national rate of opioid deaths per 100,000. The strategy used to address this public health crisis mobilized the Utah State Extension system and communities, to use the PROSPER (S2S) Framework and the 4-H Thriving Model. This approach utilized family- and school-based education programs that promote resiliency and developmental strengths for middle-school aged youth and their families. Method(s): The elements of the PROSPER delivery system include delivering the Botvin LifeSkills Training program to 6th grade students, enrolling the students in 4-H programming, and inviting them to participate with their parents in the Strengthening Families 10-14 program developed by Iowa State University. While the PROSPER system was designed to be implemented in-person, the impacts of the COVID-19 pandemic necessitated several adaptations of the program in order to adhere to public health guidelines during the pandemic. Extension faculty and staff relied heavily on partnerships with local school districts to implement the classroom-based LifeSkills Training program since school district policies prevented volunteers from entering classrooms during the pandemic. The state PROSPER team worked with State University to implement virtual and socially distant in-person Strengthening Families 10-14 sessions. During the pandemic, over 300 youth and 37 families have received prevention programming through these adaptations. The evaluation of the PROSPER LifeSkills Program follows a pre-post and cross-sectional hybrid design to assess short-term outcomes with respect to anti-drug knowledge, life skills, and anti-drug attitudes. Result(s): Preliminary evaluation results indicate that after completing the classroom-based LifeSkills Training program, students demonstrated positive anti-drug (M = 4.80, SD = 0.33), anti-smoking (M = 4.82, SD = 0.32), and anti-drinking (M = 4.78, SD = 0.37) attitudes. Students also expressed strong drug refusal skills (M = 4.00, SD = 1.67). Conclusion(s): Despite the challenges of delivering programs to rural communities during the pandemic, preliminary evaluation of participant surveys shows significant drug refusal skills by program participants. Qualitative data from participants also shows increased relationship skills, which are crucial to healthy youth development. By adapting the PROSPER delivery system to meet the needs of rural communities battling the COVID-19 pandemic, Utah State University Extension has been able to continue serving high-risk communities and impacting the lives of local youth.

Prevalence and duration of anti-SARS-CoV-2 antibodies in healthcare workers

Introduction. Knowledge of the seroprevalence and duration of antibodies against SARS-CoV-2 was needed in the early phases of the COVID-19 pandemic and is still necessary for policy makers and healthcare professionals. This information allows us to better understand the risk of reinfection in previously infected individuals. Methods. We investigated the prevalence and duration of detectable antibodies against SARS-CoV-2 in sequentially collected samples from 379 healthcare professionals. Results. SARS-CoV-2 seroprevalence at inclusion was 5.3% (95% confidence interval (CI): 3.3-8.0%) and 25% of seropositive participants reverted during follow-up. At the end of follow-up, the calculated probability of having detectable antibodies among former seropositive participants was 72.2% (95% CI: 54.2-96.2%). Conclusion. Antibodies against SARS-CoV-2 were detectable in a subset of infected individuals for a minimum of 39 weeks.

IMPACT OF THE COVID-19 PANDEMIC ON FECAL IMMUNOCHEMICAL TESTING, COLONOSCOPY SERVICES, AND COLORECTAL NEOPLASIA DETECTION IN A LARGE UNITED STATES COMMUNITY-BASED POPULATION

Background and Aims: The COVID-19 pandemic profoundly impacted clinical services globally, including colorectal cancer (CRC) testing such as fecal immunochemical test (FIT) screening and colonoscopy. We investigated the impact of the pandemic on FIT and colonoscopy utilization, and colorectal neoplasia detection in a large community-based population in the United States. Methods: We performed a retrospective cohort study of patients ages 18-89 years undergoing FIT screening or colonoscopy in 2019 and 2020 within Kaiser Permanente Northern California (KPNC), a large integrated healthcare organization. We calculated percentage changes in FIT kits mailed, FITs completed, positive FITs, colonoscopies performed overall and by indication, and colorectal neoplasia detection (advanced adenoma and CRC) in 2020 compared to 2019. Results: FIT kit mailings ceased in mid- March through April 2020 but rebounded thereafter leading to an 8.7% increase in total FIT kits mailed in 2020 compared to 2019. However, with the later mailing of FIT kits, there were 9.0% fewer FITs completed and 10.1% fewer positive tests in 2020 compared to 2019. Colonoscopy volumes nadired in April 2020, with a 79.4% reduction compared with April 2019, but recovered to near pre-pandemic monthly volumes in September through December 2020. However, overall, there was a 26.9% decline in colonoscopies performed in 2020 compared to 2019. Declines of 41.5%, 38,3%, 19.9%, and 20.0% were seen for screening, surveillance, diagnostic, and FIT positive colonoscopies, respectively, in 2020 compared to 2019. With the gradual recovery of colonoscopy volumes after the initial pandemic lockdown, by November and December 2020 the numbers of patients with advanced adenomas or CRC detected by colonoscopy were comparable to those same months in 2019. However, the total number of patients with advanced adenomas or CRC detected by colonoscopy declined by 26.9% and 8.7%, respectively, in 2020 compared to 2019. Conclusions: The COVID-19 pandemic led to fewer FIT screenings and colonoscopies performed in 2020 compared with 2019. However, after the lifting of regional lockdowns, FIT screenings exceeded, and colonoscopy volumes nearly reached numbers from those same months in 2019. Overall, the pandemic led to 27% and 9% reductions in advanced adenoma and CRC detection, respectively, in 2020 compared to 2019, validating concerns about the potential for stage progression for cancers that went undetected due to the pandemic. Strategies to identify high-risk patients for expedited colonoscopy procedure scheduling and resolve remaining colonoscopy procedure backlogs are needed to mitigate this risk.(Figure Presented)Figure 1. Number of FIT kits mailed, completed, and positive in 2019 and 2020(Figure Presented)Figure 2. Number of colonoscopies and advanced adenomas and colorectal cancers detected by colonoscopy in 2019 and 2020

Patterns of disease on admission to children's wards and changes during a COVID-19 outbreak in KwaZulu-Natal Province, South Africa.

BACKGROUND: Major causes of under-5 child deaths in South Africa (SA) are well recognised, and child mortality rates are falling. The focus of child health is therefore shifting from survival to disease prevention and thriving, but local data on the non-fatal disease burden are limited. Furthermore, COVID-19 has affected children's health and wellbeing, both directly and indirectly. OBJECTIVES: To describe the pattern of disease on admission of children at different levels of care, and assess whether this has been affected by COVID-19. METHODS: Retrospective reviews of children's admission and discharge registers were conducted for all general hospitals in iLembe and uMgungundlovu districts in KwaZulu-Natal Province, SA, from January 2018 to September 2020. The Global Burden of Disease framework was adapted to create a data capture sheet with four broad diagnostic categories and 37 specific cause categories. Monthly admission numbers were recorded per cause category, and basic descriptive analysis was completed in Microsoft Excel. RESULTS: Overall, 36 288 admissions were recorded across 18 hospital wards, 32.0% at district, 49.8% at regional and 18.2% at tertiary level. Communicable diseases, perinatal conditions and nutritional deficiencies (CPNs) accounted for 37.4% of admissions, non-communicable diseases (NCDs) for 43.5% and injuries for 17.1%. The distribution of broad diagnostic categories varied across levels of care, with CPNs being more common at district level and NCDs more common at regional and tertiary levels. Unintentional injuries represented the most common cause category (16.6%), ahead of lower respiratory tract infections (16.1%), neurological conditions (13.6%) and diarrhoeal disease (8.4%). The start of the local COVID-19 outbreak coincided with a 43.1% decline in the mean number of monthly admissions. Admissions due to neonatal conditions and intentional injuries remained constant during the COVID-19 outbreak, while those due to other disease groups (particularly respiratory infections) declined. CONCLUSIONS: Our study confirms previous concerns around a high burden of childhood injuries in our context. Continued efforts are needed to prevent and treat traditional neonatal and childhood illnesses. Concurrently, the management of NCDs should be prioritised, and evidence-based strategies are sorely needed to address the high injury burden in SA.

Event innovation in times of uncertainty

Purpose This study highlights areas of key importance for building event resilience and provides best-practice industry examples that foster innovative, adaptable and transformative event environments, which are areas of high academic and managerial relevance in times of uncertainty. Design/methodology/approach The study employs a multicase study research design that draws on interviews with the leaders of four event organizations in Denmark and Norway: (1) the Steinkjer Festival, (2) Run Alone Denmark, (3) FC Midtjylland and (4) the Bergen International Festival. Findings The events demonstrated the critical necessity of understanding innovation and its contribution to resilience in the event sector, particularly in times of uncertainty, such as the COVID-19 pandemic. These organizations achieved success by continuously fostering innovative environments before COVID-19 by being value-driven and customer-centric organizations. Digital technologies were not used as makeshift solutions but rather to enhance event attendees' experiential platforms and expand each event's business potential. Practical implications The paper answers the call for event and festival research during the COVID-19 pandemic to explore the importance of understanding failure, crisis, innovation and recovery. Originality/value The paper's contributions to event management research are (1) adding to the ongoing discussion about building a resilient event sector in times of uncertainty, (2) screening how event organizers achieve innovation in their organizations and (3) providing insights on future requirements for events in a post-COVID world.

IMPACT OF THE COVID-19 PANDEMIC ON A LARGE ORGANIZED COLORECTAL CANCER SCREENING PROGRAM BASED ON FECAL IMMUNOCHEMICAL TESTING AND OPPORTUNISTIC COLONOSCOPY

BACKGROUND AND AIM: Colorectal cancer (CRC) screening reduces CRC mortality by early detection and CRC incidence by polypectomy. Kaiser Permanente Northern California (KPNC) initiated organized CRC screening in 2006 using annual mailed fecal immunochemi-cal test (FIT) screening and opportunistic colonoscopy, with high screening rates. Public health guidance related to the COVID-19 pandemic led to elective colonoscopies and mailed FIT outreach being paused in March 2020. This study evaluated the impact of the pandemic on CRC screening at KPNC. METHODS: For January-December 2019 and January-October 2020, we evaluated: the KPNC screening-eligible population aged 50-75;those up to date with screening due to colonoscopy;eligible for a FIT;mailed a FIT kit;completed a FIT;completed a follow-up colonoscopy after a positive FIT;completed a colonoscopy unrelated to a positive FIT;and up to date with screening by end of follow-up (i.e., 2019 and end of October 2020, respectively). RESULTS: There were 913,873 and 941,763 eligible members in 2019 and 2020;151,252 (16.6%) and 150,407 (16.0%) were up to date with screening due to prior colonoscopy, leaving 762,621 and 791,356 eligible for FIT, respectively. Compared to 2019, when FIT kits were mailed to 627,260 of 762,621 (82.3%) FIT-eligible members, FIT kits were mailed to 521,239 of 791,356 (65.9%) eligible members by the end of October 2020, with mailings ongoing. Declines in FIT mailings occurred in March-May 2020 but rebounded quickly thereafter (Fig 1a). FIT kits were returned by 504,152 of 762,621 (66.1%) members in 2019, and 365,972 of 791,356 (46.2%) members through October 2020, with lower returns in March-June 2020 (Fig 1b). In 2019, 11,119 of 15,402 (72.2%) FIT-positive patients received a follow-up colonoscopy by year end, and through October 2020, 6,856 of 10,922 (62.8%) received a follow-up colonoscopy after a positive FIT (Fig 1c). Another 14,420 of 762,621 (1.9%) and 9,902 of 791,356 (1.3%) members completed a colonoscopy during 2019 and 2020, respectively (Fig 2). By the end of 2019, 665,541 of 913,873 (72.8%) were up to date with screening, and through October 2020, 522,215 of 941,763 (55.5%) were up to date with screening (Fig 2). CONCLUSION: The COVID-19 pandemic resulted in temporary delays in the mailing and return of FITs;and a reduction in colonoscopies performed, due, in part, to patient reluctance to respond to FIT outreach or complete follow-up colonoscopy during the pandemic. Also, fewer individuals were up to date with screening, although outreach continues through December 2020. The organized mailed FIT program allowed for the rapid resumption of outreach;however, follow-up is needed to assess the impact of screening delays on CRC outcomes and to identify ways to improve adherence with FIT screening, including colonoscopy follow-up after a positive FIT.(Figure presented) (Figure presented) (Figure presented) (Figure presented)

A major outbreak of covid-19 at a residential care home

INTRODUCTION SARS-CoV-2 outbreaks at care homes are associated with a high morbidity and mortality. We aimed to study the molecular epidemiology of a major care home outbreak in Denmark. METHODS After a staff member had been tested positive on 16 November 2020, a bundle approach programme was initiated including frequent surveillance screenings of residents and staff, isolation and cohorting procedures. This approach also involved limiting the number of visitors and enhancing the use of personal protective equipment, hand hygiene, and environmental cleaning. Naso/oropharyngeal swabs were tested for SARS-CoV-2 by polymerase chain reaction. Available positive samples were sequenced and phylogenetic relationships between the outbreak and local circulating strains were reconstructed. RESULTS In all, 50% (56/114) of residents and 26% (49/190) of staff members became infected during the 46-day outbreak period. Altogether 16% of the infected residents died within 30 days after becoming infected. A total of 44% (46/105) of the samples with SARS-CoV-2 were sequenced. and phylogenetic analysis demonstrated a dominant outbreak lineage belonging to Global Lineage B.1.1.29 containing the mutation I233V in the S gene. The outbreak lineage was detected in the community 28 days before its introduction into the care home. CONCLUSIONS Introduction of SARS-CoV-2 to care homes is associated with severe outbreaks. Initiation of a bundle approach infection control programme in addition to measures ensuring enhanced herd immunity were successful in controlling the outbreak. Genome sequencing proved to be a powerful tool to describe the relatedness of the various clones and may help focusing outbreak interventions. © 2021, Almindelige Danske Laegeforening. All rights reserved.

Implementing virtual mind-body programming to support cancer patients during COVID-19

Background: Despite growing evidence of mindbody therapies for physical and psychological health among patients with cancer, their access remains limited. The COVID-19 pandemic has further disrupted the delivery of necessary cancer and supportive care;thus, the need to support patients with cancer is unprecedented. To expand the reach and access of mind-body therapies, we developed, implemented, and evaluated a novel virtual mind-body program for patients with cancer. Methods: We rapidly developed a 7-day a week virtual mind-body program, Integrative Medicine at Home (IM@Home), for patients with cancer (ages ≥18 years) and deployed it on April 1 , 2020. IM@Home included mind-body group therapy classes in fitness, meditation, yoga, dance, tai chi, and music delivered using Zoom video conferencing. Classes ranged from 30-45 minutes and were led by an integrative medicine clinician. Patients had the option to register for a 1-month, 3-month, or 6-month membership to gain unlimited access to all virtual mind-body classes. Multi-method evaluation was conducted using the RE-AIM conceptual framework to guide surveys and qualitative interviews. Surveys were analyzed using descriptive statistics and interviews were analyzed using grounded theory. Results: Between April 2020 and January 2021, IM@Home registered over 32,000 class participants, with a weekly average attendance of 700-800 participants. In a 4-month postdeployment survey (n = 131), nearly all participants were satisfied with IM@Home (93.9%) and would recommend the program to friends and family (95.4%). A majority of participants also found IM@Home to be simple to use (87.0%) and said the program had a variety of classes that interested them (93.1%). Three-quarters of participants (74.8%) were taking 3 to 7 classes a week (range: 1 to 15 classes), among which the most popular classes were fitness (88.7%), chair yoga (37.1%), and tai chi (33.1%). Most participants preferred a 3- month membership (51.6%), followed by a 6- month membership (19.5%). In qualitative interviews (n = 30), participants reported IM@Home helped them to: 1) maintain structured routines and stay motivated to exercise;2) cope with COVID-19-related and cancer-related stressors;and 3) connect with their fellow cancer patient community and foster social relationships during a time of isolation. Conclusions: Virtual mind-body programming, through IM@Home, reached many patients with cancer to address their physical and psychological challenges during COVID-19. As patients with cancer experience high physical and psychological symptom burden following diagnosis, future clinical trials are needed to evaluate the specific effects of IM@Home when integrated into active treatment and survivorship care.

Child health services during a COVID-19 outbreak in KwaZulu-Natal Province, South Africa.

BACKGROUND: Current evidence indicates that children are relatively spared from direct COVID-19-related morbidity and mortality, but that the indirect effects of the pandemic pose significant risks to their health and wellbeing. OBJECTIVES: To assess the impact of the local COVID-19 outbreak on routine child health services. METHODS: The District Health Information System data set for KwaZulu-Natal (KZN) provincial health services was accessed, and monthly child health-related data were extracted for the period January 2018 - June 2020. Chronological and geographical variations in sentinel indicators for service access, service delivery and the wellbeing of children were assessed. RESULTS: During April - June 2020, following the start of the COVID-19 outbreak in KZN, significant declines were seen for clinic attendance (36%; p=0.001) and hospital admissions (50%; p=0.005) of children aged <5 years, with a modest recovery in clinic attendance only. Among service delivery indicators, immunisation coverage recovered most rapidly, with vitamin A supplementation, deworming and food supplementation remaining low. Changes were less pronounced for in- and out-of-hospital births and uptake rates of infant polymerase chain reaction testing for HIV at birth, albeit with wide interdistrict variations, indicating inequalities in access to and provision of maternal and neonatal care. A temporary 47% increase in neonatal facility deaths was reported in May 2020 that could potentially be attributed to COVID-19-related disruption and diversion of health resources. CONCLUSIONS: Multiple indicators demonstrated disruption in service access, service delivery and child wellbeing. Further studies are needed to establish the intermediate- and long-term impacts of the COVID-19 outbreak on child health, as well as strategies to mitigate these.

Child health services during a COVID-19 outbreak in KwaZulu-Natal Province, South Africa.

BACKGROUND: Current evidence indicates that children are relatively spared from direct COVID-19-related morbidity and mortality, but that the indirect effects of the pandemic pose significant risks to their health and wellbeing. OBJECTIVES: To assess the impact of the local COVID-19 outbreak on routine child health services. METHODS: The District Health Information System data set for KwaZulu-Natal (KZN) provincial health services was accessed, and monthly child health-related data were extracted for the period January 2018 - June 2020. Chronological and geographical variations in sentinel indicators for service access, service delivery and the wellbeing of children were assessed. RESULTS: During April - June 2020, following the start of the COVID-19 outbreak in KZN, significant declines were seen for clinic attendance (36%; p=0.001) and hospital admissions (50%; p=0.005) of children aged <5 years, with a modest recovery in clinic attendance only. Among service delivery indicators, immunisation coverage recovered most rapidly, with vitamin A supplementation, deworming and food supplementation remaining low. Changes were less pronounced for in- and out-of-hospital births and uptake rates of infant polymerase chain reaction testing for HIV at birth, albeit with wide interdistrict variations, indicating inequalities in access to and provision of maternal and neonatal care. A temporary 47% increase in neonatal facility deaths was reported in May 2020 that could potentially be attributed to COVID-19-related disruption and diversion of health resources. CONCLUSIONS: Multiple indicators demonstrated disruption in service access, service delivery and child wellbeing. Further studies are needed to establish the intermediate- and long-term impact of the COVID-19 outbreak on child health, as well as strategies to mitigate these.

SARS-CoV-2 in first trimester pregnancy: a cohort study.

STUDY QUESTION: Does maternal infection with severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) in first trimester pregnancy have an impact on the fetal development as measured by nuchal translucency thickness and pregnancy loss? SUMMARY ANSWER: Nuchal translucency thickness at the first trimester scan was not significantly different in pregnant women with versus without SARS-CoV-2 infection in early pregnancy and there was no significantly increased risk of pregnancy loss in women with SARS-CoV-2 infection in the first trimester. WHAT IS KNOWN ALREADY: Pregnant women are more vulnerable to viral infections. Previous coronavirus epidemics have been associated with increased maternal morbidity, mortality and adverse obstetric outcomes. Currently, no evidence exists regarding possible effects of SARS-CoV-2 in first trimester pregnancies. STUDY DESIGN, SIZE, DURATION: Cohort study of 1019 women with a double test taken between 17 February and 23 April 2020, as a part of the combined first trimester risk assessment, and 36 women with a first trimester pregnancy loss between 14 April and 21 May 2020, prior to the double test. The study period was during the first SARS-CoV-2 epidemic wave in Denmark. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cohort 1 included pregnant women with a double test taken within the study period. The excess serum from each double test was analyzed for SARS-CoV-2 antibodies. Results were correlated to the nuchal translucency thickness and the number of pregnancy losses before or at the time of the first trimester scan. Cohort 2 included women with a pregnancy loss before the gestational age for double test sample. Serum from a blood test taken the day the pregnancy loss was identified was analyzed for SARS-CoV-2 antibodies. The study was conducted at a public university hospital serving ∼12% of pregnant women and births in Denmark. All participants in the study provided written informed consent. MAIN RESULTS AND THE ROLE OF CHANCE: Eighteen (1.8%) women had SARS-CoV-2 antibodies in the serum from the double test suggestive of SARS-CoV-2 infection in early pregnancy. There was no significant difference in nuchal translucency thickness for women testing positive for previous SARS-CoV-2 infection (n = 16) versus negative (n = 966) (P = 0.62). There was no significantly increased risk of pregnancy loss for women with antibodies (n = 1) (OR 3.4, 0.08-24.3 95% CI, P = 0.27). None of the women had been hospitalized due to SARS-CoV-2 infection. None of the women with pregnancy loss prior to the double test (Cohort 2) had SARS-CoV-2 antibodies. LIMITATIONS, REASONS FOR CAUTION: These results may only apply to similar populations and to patients who do not require hospitalization due to SARS-CoV-2 infection. A limitation of the study is that only 1.8% of the study population had SARS-CoV-2 antibodies suggestive of previous infection. WIDER IMPLICATION OF THE FINDINGS: Maternal SARS-CoV-2 infection had no effect on the nuchal translucency thickness and there was no significantly increased risk of pregnancy loss for women with SARS-CoV-2 infection in first trimester pregnancy. Evidence concerning COVID-19 in pregnancy is still limited. These data indicate that infection with SARS-CoV-2 in not hospitalized women does not pose a significant threat in first trimester pregnancies. Follow-up studies are needed to establish any risk to a fetus exposed to maternal SARS-CoV-2 infection. STUDY FUNDING/COMPETING INTEREST(S): Prof. H.S.N. and colleagues received a grant from the Danish Ministry of Research and Education for research of COVID-19 among pregnant women. The Danish government was not involved in the study design, data collection, analysis, interpretation of data, writing of the report or decision to submit the paper for publication. A.I., J.O.-L., J.B.-R., D.M.S., J.E.-F. and E.R.H. received funding from a Novo Nordisk Foundation (NNF) Young Investigator Grant (NNF15OC0016662) and a Danish National Science Foundation Center Grant (6110-00344B). A.I. received a Novo Scholarship. J.O.-L. is funded by an NNF Pregraduate Fellowship (NNF19OC0058982). D.W. is funded by the NNF (NNF18SA0034956, NNF14CC0001, NNF17OC0027594). A.M.K. is funded by a grant from the Rigshospitalet's research fund. H.S.N. has received speaker's fees from Ferring Pharmaceuticals, Merck Denmark A/S and Ibsa Nordic (outside the submitted work). N.l.C.F. has received a grant from Gedeon Richter (outside the submitted work). A.M.K. has received speaker's fee from Merck (outside the submitted work). The other authors did not report any potential conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.