National Collaborative Study Research Articles

From Lab to Nursery: Novel Approaches of Seed Disinfection for Managing Pine Pitch Canker Propagation

Fusarium circinatum, the causative agent of pine pitch canker disease, is a pathogenic fungus that poses a significant threat to pine forests globally. It infects various Pinus species, causing resinous cankers, needle discoloration, and tree death. The disease severely impacts forest ecosystems, necessitating cost-effective and environmentally friendly management strategies. Contaminated pine seeds and seedlings are the main pathways for introducing this fungus to disease-free areas. To mitigate this disease and prevent its spread, it is crucial to implement new processes in forest plant production systems that align with the existing conditions of forest nurseries, ensuring effective and sustainable management. With this in mind, a national collaborative study involving 14 Portuguese partners was initiated to develop new prevention and mitigation strategies. In this work, four different treatments—MennoFlorades, Captan, ethanol, and hot water—were tested for their ability to eliminate F. circinatum from contaminated Pinus seeds in vitro. The most effective treatments were selected for further in vitro assays and real-context nursery germination trials to assess their impacts on seed germination, plant production, and certification. MennoFlorades, Captan, and hot water were tested in the nursery, with hot water showing the most promising results due to its negligible impact on seedlings, eco-friendly nature, ease of implementation, and cost-effectiveness. These findings offer promising prospects for preventing pine pitch canker outbreaks in nurseries and, consequently, in forests.

Using Data to Improve Healthcare: A Case Study of Pancreatic Enzyme Replacement in Pancreatic Cancer

ObjectivesIn the UK, guidelines recommend pancreatic enzyme replacement therapy (PERT) to all people with unresectable pancreatic cancer. In 2023, we published a national audit of PERT which showed suboptimal prescribing and wide regional variation in England. The aim of this manuscript was to describe how we used the PERT audit to drive improvements in healthcare. MethodsBuilding on the PERT audit, we deployed an online dashboard which will deliver ongoing updates of the PERT audit. We developed a collaborative intervention with cancer nurse specialists (CNS) to improve care delivered to people with pancreatic cancer. The intervention called Creating a natiOnAL CNS pancrEatic cancer network to Standardise and improve CarE (COALESCE) will use the dashboard to evaluate improvements in prescribing of PERT. ResultsWe demonstrated how large databases of electronic healthcare records (EHRs) can be used to improve cancer care. The PERT audit was implemented into a dashboard for tracking the progress of COALESCE. We will measure improvements in PERT prescribing as the intervention with CNS progresses. ConclusionsImproving healthcare is an ongoing and iterative process. By implementing the PERT dashboard, we created a resource-efficient, automated evaluation method enabling COALESCE to deliver a sustainable change. National-scale databases of EHRs enable rapid cycles of audits, providing regular feedback to interventions, working systematically to deliver change. Here, the focus is on pancreatic cancer. However, this methodology is transferable to other areas of healthcare. Implications for Nursing PracticeNurses play a key role in collecting good quality data which are needed in clinical audits to identify shortcomings in healthcare. Nurse-driven interventions can be designed to improve healthcare. In this study, we capitalize on the unique role of CNS coordinating care for every patient with cancer. COALESCE is the first national collaborative study which uses CNS as researchers and change agents.

HINDFOOT ANKLE RECONSTRUCTION NAIL TRIAL (HARNT): POPULATION ANALYSIS OF SURGICAL TREATMENT OF COMPLEX ANKLE FRACTURES IN THE UNITED KINGDOM

IntroductionThe management of open or unstable ankle and distal tibial fractures pose many challenges. In certain situations, hindfoot nailing (HFN) is indicated, however this depends on surgeon preference and regional variations exist. This study sought to establish the current management and outcomes of complex ankle fractures in the UK.MethodsA National collaborative study in affiliation with BOTA was conducted and data retrospectively collected between January 1st – June 30th 2019. Adult patients with open and closed complex ankle fractures (AO43/44) were included. Complex fractures included the following patient characteristics: diabetes ± neuropathy, rheumatoid arthritis, alcoholism, polytrauma and cognitive impairment. We obtained data on fixation choice and patient outcomes. Institutional approval was obtained by all centres, and statistical analysis was performed including propensity matching.ResultsFifty-six centres provided data for 1360 patients. The average age of the cohort was 53.9 years ±19 (SD) with a male/female ratio of 1:1.3. 920 patients were ASA 1/2, 440 were ASA 3/4; 316 had diabetes, and 275 were open fractures. Most fractures were AO44 (71.2%) and more commonly associated with diabetes (P<0.001), alcoholism (P<0.007), open (P<0.013), and advanced age (55.7 vs. 46.3). 1227 patients underwent primary-fixation (111 HFN), with the remainder treated with external-fixation (84 definitive). Of the 111 HFN, 35% underwent primary fusion. Wound complication and thromboembolic rates were greater in the HFN group compared to ORIF groups (P<0.003), being more evident in the HFN group with primary fusion even after propensity matching. However, 1081 patients were non-weightbearing post-op contrary to the BOAST guidance.ConclusionThis is the first National collaborative audit of complex ankle fractures. Hindfoot nails were used in 9% of patients and we observed more complications in this group when compared to other cohorts. Despite BOAST guidance, only 21% of patients undergoing operative management were instructed to fully weightbear post-operatively.

CleftED: A National Collaborative Study of Undergraduate Education and Exposure to Cleft lip and Palate Within the United Kingdom

Introduction Cleft Lip and/or Palate (CLP) are the most common congenital orofacial anomalies. Those involved in CLP care may extend beyond the core members of the Cleft multidisciplinary team (MDT) with a variety of medical healthcare professionals destined to contribute to the management of CLP patients at some point during their respective careers. Therefore, it seems essential that a basic understanding of CLP, CLP-associated problems, and potential avenues for direct or indirect involvement in CLP care be introduced at undergraduate level. Aims To investigate penultimate and final year undergraduate medical student CLP knowledge and exposure obtained whilst at medical school. Methodology An online questionnaire was distributed to penultimate and final year medical students throughout the UK. Results A total of 3102 responses were received from 35 medical schools. 44.3% (n = 1374) of respondents had no exposure to CLP teaching up until their current year of education. 61.3% (n = 1903) of respondents had never been involved in the care of a CLP patient. 53.6% (n = 1662) of respondents were not confident in their current knowledge of CLP. 78.5% (n = 2257) of respondents indicated a desire to be involved in the care of CLP patients in their future career. Conclusion More than half of the medical student survey respondents were not confident in their current knowledge of CLP and had limited involvement in CLP care. This may translate to a delay in diagnosis when students qualify. Improving CLP education and exposure during undergraduate training can help achieve national CLP standards for early diagnosis.

Lymphoma in Patients with Inflammatory Bowel Disease: A Multicentre Collaborative Study Between GETAID and LYSA.

Inflammatory bowel disease [IBD] is associated with an increased risk of developing lymphoma. Although recent data have clarified the epidemiology of lymphoma in IBD patients, the clinical and pathological characteristics of lymphoma in IBD remain poorly known. Patients with IBD and lymphoma were retrospectively identified in the framework of a national collaborative study including the Groupe d'Étude Thérapeutique des Affections Inflammatoires du Tube Digestif [GETAID] and the Lymphoma Study Association [LYSA]. We characterized clinical and prognostic features for the three most frequent lymphoma subtypes occurring in IBD. We performed a multicentre case-control study. Controls [lymphoma de novo] were matched [5:1] to cases on gender, age at diagnosis, lymphoma subtype, year of diagnosis, and IPI/FLIPI indexes. Overall survival and progression-free survival were compared between cases and controls. In total, 133 IBD patients with lymphoma were included [males = 62.4%, median age at lymphoma diagnosis = 49 years in males; 42 years in females]. Most had Crohn's disease [73.7%] and were exposed to thiopurines [59.4%]. The most frequent lymphoma subtypes were diffuse large B cell lymphoma [DLBCL, 45.1%], Hodgkin lymphoma [HL, 18.8%], and follicular lymphoma [FL, 10.5%]. When matched with 365 controls, prognosis was improved in IBD patients with DLBCL compared to controls [p = 0.0064, hazard ratio = 0.36] or similar [HL and FL]. Lymphomas occurring in IBD patients do not seem to have a worse outcome than in patients without IBD. Due to the rarity of this situation, such patients should be managed in expert centres.

State-Level Support for Recovery Housing: Results from a National Collaborative Study of U.S. Single State Agencies

ABSTRACT Single State Agencies (SSAs) are responsible for managing the publicly funded alcohol and other drug prevention, treatment, and recovery service system. Recovery housing (RH) is an important recovery support service (RSS) for individuals experiencing substance use disorder (SUD). Despite its effectiveness, information on state utilization and support is limited. To assess state-level support for RH and its incorporation within the SSA-managed SUD service systems, we administered a survey with SSAs in the 50 United States and the District of Columbia. In total, 48 out of the 51 SSAs responded, yielding a 94% response rate. Findings indicate strong state-level support for RH in terms of it being an integral RSS (98%), part of state-level strategic plans (73%) and prioritized for funding (87.5%). States are making progress to formalize RH with 68% reporting RH had been defined formally or within their agency. However, activities around understanding the capacity and need for RH are limited, with 44% indicating a needs assessment had not been conducted. At the same time, states perceive RH as a priority RSS, with growing recognition of its positive impact on long-term SUD recovery. This research identifies the opportunities for stakeholders to further evolve and expand RH at the federal, state, and local levels.

Streptococcus pneumoniae serotyping and antimicrobial susceptibility: assessment for vaccine efficacy in Canada after the introduction of PCV13.

Streptococcus pneumoniae continues to be an important bacterial pathogen associated with invasive (e.g. bacteraemia, meningitis) and non-invasive (e.g. community-acquired respiratory tract) infections worldwide. Surveillance studies conducted nationally and globally assist in determining trends over geographical areas and allow comparisons between countries. To characterize invasive isolates of S. pneumoniae in terms of their serotype, antimicrobial resistance, genotype and virulence and to use the serotype data to determine the level of coverage by different generations of pneumococcal vaccines. SAVE (Streptococcus pneumoniae Serotyping and Antimicrobial Susceptibility: Assessment for Vaccine Efficacy in Canada) is an ongoing, annual, national collaborative study between the Canadian Antimicrobial Resistance Alliance (CARE) and the National Microbiology Laboratory, focused on characterizing invasive isolates of S. pneumoniae obtained across Canada. Clinical isolates from normally sterile sites were forwarded by participating hospital public health laboratories to the Public Health Agency of Canada-National Microbiology Laboratory and CARE for centralized phenotypic and genotypic investigation. The four articles in this Supplement provide a comprehensive examination of the changing patterns of antimicrobial resistance and MDR, serotype distribution, genotypic relatedness and virulence of invasive S. pneumoniae obtained across Canada over a 10 year period (2011-2020). The data highlight the evolution of S. pneumoniae under pressure by vaccination and antimicrobial usage, as well as vaccine coverage, allowing both clinicians and researchers nationally and globally to view the current status of invasive pneumococcal infections in Canada.

Elbow conditions: research priorities setting in partnership with the James Lind Alliance

ObjectiveTo undertake a UK-based James Lind Alliance (JLA) Priority Setting Partnership for elbow conditions and be representative of the views of patients, carers and healthcare professionals (HCPs).SettingThis was a national...

Incidence of type 1 diabetes in children in Dominican Republic, 2010-2019: A national collaborative study.

The Dominican Republic has no recent data on type 1 diabetes (T1D) incidence in children. Therefore, a study was undertaken to determine this in persons aged <15 years (y). Data were collected on all new T1D diagnoses between 2010-2019 from the four institutions caring for children with T1D. Diagnosis was made according to standard criteria. No secondary ascertainment source was available. The trend and the effect of age and sex of T1D incidence was analyzed using Poisson regression. A total of 1224 new cases of T1D were diagnosed <15 y; mean ±standard deviation (range) 122 ± 12 (96-135) cases per year. Age at T1D diagnosis was 8.8± 3.7 y, with a significant female preponderance (n= 708, 57.8%, p< 0.001). When examined per 5-y age group, cases were consistently highest in 10-14 y, and lowest in 0-4 y in all study years. Mean crude T1D annual incidence was 4.3 (95% CI 3.5-5.1) per 100,000 population. There was no significant difference between incidence across the country's three departments (regions): Southeast (4.4 [3.4-5.7]/100,000 population), North (4.1 [2.9-5.6]), and Southwest (3.9 [2.4-5.9]). Mean standardized annual incidence was 4.1 (4.1-4.2) per 100,000 population, with no significant trend of increase over the study period. The incidence of T1D in children aged <15 y is relatively low in Dominican Republic, but consistent with the limited data from other countries in the region. However, the incidence is eight times higher than the previous estimate during 1995-1999. Ongoing surveillance is warranted.

Outcomes of COVID-19 in children with cancer – Report from the Indian Pediatric Oncology Group (InPOG) COVID-19 registry in India

IntroductionThe clinical outcomes of COVID-19 infection in children with cancer have been variable worldwide. Therefore, we aimed to collect data from all regions in India through a national collaborative study and identify factors that cause mortality directly related to COVID-19 infection. MethodsData was collected prospectively on children across India on cancer therapy and diagnosed with COVID-19 infections from 47 centers from April 2020 to October 2021. Information was recorded on the demographics, the number of children that required intervention, and the outcome of the infection. In addition, we analyzed the impact of the delta variant in 2021. ResultsA total of 659 children were studied, of whom 64% were male and 36% were female. The data from the eastern region was sparse, and this was a collection bias. COVID-19 infection was predominantly seen in children less than five years. The delta variant had a higher impact in the southern region, and this was statistically significant. Of the 659 children, 30 children died (4.5%), however only 7 of the deaths were directly attributed to COVID-19 infection (1%). ConclusionThe study reports the largest nationally representative cohort of children with cancer and COVID-19 to date in India. We identified demographic and clinical factors associated with increased all-cause mortality in patients with cancer. Complete characterization of the cohort has provided further insights into the effects of COVID-19 on cancer outcomes. The low mortality allows us to recommend that specific cancer treatments be continued without delays in therapy.

Study protocol for a national retrospective review of femoral periprosthetic fracture management. Is there variation in practice?

Abstract Introduction The incidence of femoral periprosthetic fractures (PPFs) in the UK is on the rise. This rising incidence presents a clinical and an economic burden on the national health care services. There is also uncertainty about the most effective treatment modality for femoral PPFs, as well as a lack of evidence for a standardized management approach. We aimed to identify the true incidence and any variation in the management of femoral PPFs nationally. Methods and analysis This multicentre national collaborative study has been designed by a trainee led research network in collaboration with a well-established university research organization. Data will be collected from participating centres over a period of 10 years (2010–2019). All adults presenting with a femoral PPF will be identified, and the mode of treatment for each fracture subtype will be recorded. Other measures will evaluate patient and treatment variables, objective and subjective outcome measures. Univariate and multivariate regression analyses will be used, as well as the coefficient of determination (R) in an attempt to measure the degree to which the models could explain the variation in management. Ethics and dissemination This multicentre national project was approved by the local clinical governance department at each participating hospital site. The results of this study will be submitted to international peer reviewed journals and appropriate national and international conferences.

Safety and Efficacy of Convalescent Plasma to Treat Severe COVID-19: Protocol for the Saudi Collaborative Multicenter Phase II Study.

BackgroundThe COVID-19 pandemic is expected to cause significant morbidity and mortality. The development of an effective vaccine will take several months to become available, and its affordability is unpredictable. Transfusion of convalescent plasma (CP) may provide passive immunity. Based on initial data from China, a group of hematologists, infectious disease specialists, and intensivists drafted this protocol in March 2020.ObjectiveThe aim of this study is to test the feasibility, safety, and efficacy of CP in treating patients with COVID-19 across Saudi Arabia.MethodsEligible patients with COVID-19 will be recruited for CP infusion according to the inclusion criteria. As COVID-19 has proven to be a moving target as far as its management is concerned, we will use current definitions according to the Ministry of Health (MOH) guidelines for diagnosis, treatment, and recovery. All CP recipients will receive supportive management including all available recommended therapies according to the available MOH guidelines. Eligible CP donors will be patients with COVID-19 who have fully recovered from their disease according to MOH recovery criteria as detailed in the inclusion criteria. CP donors have to qualify as blood donors according to MOH regulations except for the history of COVID-19 in the recent past. We will also test the CP donors for the presence of SARS-CoV-2 antibodies by a rapid test, and aliquots will be archived for future antibody titration. Due to the perceived benefit of CP, randomization was not considered. However, we will compare the outcome of the cohort treated with CP with those who did not receive CP due to a lack of consent or lack of availability. In this national collaborative study, there is a likelihood of not finding exactly matched control group patients. Hence, we plan to perform a propensity score matching of the CP recipients with the comparator group patients for the major characteristics. We plan to collect demographic, clinical, and laboratory characteristics of both groups and compare the outcomes. A total sample size of 575 patients, 115 CP recipients and 460 matched controls (1:4 ratio), will be sufficient to detect a clinically important hospital stay and 30-day mortality difference between the two groups with 80% power and a 5% level of significance.ResultsAt present, patient recruitment is still ongoing, and the interim analysis of the first 40 patients will be shared soon.ConclusionsIn this paper, we present a protocol for a national collaborative multicenter phase II study in Saudi Arabia for assessing the feasibility, safety, and potential efficacy of CP in treating patients with severe COVID-19. We plan to publish an interim report of the first 40 CP recipients and their matched comparators soon.Trial RegistrationClinicalTrials.gov NCT04347681; https://clinicaltrials.gov/ct2/show/NCT04347681International Registered Report Identifier (IRRID)PRR1-10.2196/23543

Outcomes of hydrocephalus secondary to congenital toxoplasmosis.

Hydrocephalus occurs in children with congenital toxoplasmosis and can lead to severe disability. In these cases, the decision to intervene is often influenced by the expectation of neurological recovery. In this study, clinical responses to neurosurgical intervention in children with hydrocephalus secondary to congenital toxoplasmosis are characterized. Sixty-five participants with hydrocephalus due to congenital Toxoplasma gondii infection were evaluated as part of the National Collaborative Chicago-based Congenital Toxoplasmosis Study, and their neuroradiographic findings were reviewed. Clinical outcomes were scored on the basis of cognition and motor skills through the use of IQ scores and Gross Motor Function Classification System (GMFCS) level. Outcomes were then analyzed in relation to approach to management, anatomy of hydrocephalus, and time from diagnosis of hydrocephalus to surgical intervention. There was considerable variation in the outcomes of patients whose hydrocephalus was treated in early life, ranging from normal cognitive and motor function to profound developmental delay and functional limitation. Of the 65 participants included in the study, IQ and GMFCS level were available for 46 (70.8%). IQ and motor score were highly correlated (r = -0.82, p < 0.001). There were people with differing patterns of hydrocephalus or thickness of cortical mantle on initial presentation who had favorable outcomes. Time to neurosurgical intervention data were available for 31 patients who underwent ventriculoperitoneal (VP) shunt placement. Delayed shunt placement beyond 25 days after diagnosis of hydrocephalus was associated with greater cognitive impairment (p = 0.02). Motor impairment also appeared to be associated with shunt placement beyond 25 days but the difference did not achieve statistical significance (p = 0.13). Among those with shunt placement within 25 days after diagnosis (n = 19), the mean GMFCS level was 1.9 ± 1.6 (range 1-5). Five (29.4%) of 17 of these patients were too disabled to participate in formal cognitive testing, after excluding 2 patients with visual difficulties or language barriers that precluded IQ testing. Of the patients who had VP shunt placement 25 or more days after diagnosis (n = 12), the mean GMFCS level was 2.7 ± 1.4 (range 1-4). Of these, 1 could not participate in IQ testing due to severe visual difficulties and 8 (72.7%) of the remaining 11 due to cognitive disability. VP shunt placement in patients with hydrocephalus caused by congenital toxoplasmosis can contribute to favorable clinical outcomes, even in cases with severe hydrocephalus on neuroimaging. Shunt placement within 25 days of diagnosis was statistically associated with more favorable cognitive outcomes. Motor function appeared to follow the same pattern although it did not achieve statistical significance.

The cascade of care for children and adolescents with HIV in the UK and Ireland, 2010 to 2016.

IntroductionThe UNAIDS 90‐90‐90 targets for the cascade of care are widely used to monitor the success of HIV care programmes but there are few studies in children. We assessed the cascade for children and adolescents living with HIV in the national Collaborative HIV Paediatric Study (CHIPS) in the UK and Ireland.MethodsUtilizing longitudinal data from CHIPS we compared the cascade of care for 2010, 2013 and 2016. Among children diagnosed with HIV and not known to be lost to follow‐up at the start of each calendar year, we summarized the proportion in active paediatric care during that year (defined as having ≥1 clinic visit, CD4 or viral load measurement, or change to antiretroviral therapy (ART) regimen), and of these, the proportion on ART at last visit in that year. Among those on ART, the proportion with viral suppression (<200 copies/mL) and good immune status (WHO immunological stage none‐/mild‐for‐age) at last visit in the year were summarized. Among those in care in 2016, outcomes were compared by current age, place of birth (born abroad vs. UK/Ireland) and sex.ResultsOf children in paediatric HIV care at the start of 2010, 2013 and 2016 (n = 1249, 1157, 905 respectively), the proportion in active care during that calendar year was high throughout at 97 to 99%. Of those in active care, the proportion on ART increased from 79% to 85% and 92% respectively (p < 0.001). Among those on ART, the proportion with viral suppression and good immune status was stable at 83% to 86% and 85% to 88%, respectively, across the years. Among children in care in 2016, those aged ≥15 years were less likely to be virally suppressed (79% vs. 91%, p < 0.001) or to have good immune status (78% vs. 94%, p < 0.001) compared to younger children; there were no differences by place of birth or sex.ConclusionsChildren and adolescents in the UK and Ireland national cohort had high retention in care. The proportion on ART increased significantly over time although there was no change in viral suppression or good immune status. Poorer outcomes among adolescents highlight the need for targeted support for this population.

Policies for reirradiation of recurrent high-grade gliomas: a survey among Italian radiation oncologists.

To assess the contribution of Italian radiation oncologists in the current management of recurrent high-grade gliomas (HGG), focusing on a reirradiation (reRT) approach. In 2015, the Reirradiation and the Central Nervous System Study Groups on behalf of the Italian Association of Radiation Oncology (AIRO) proposed a survey. All Italian radiation oncologists were individually invited to complete an online questionnaire regarding their clinical management of recurrent HGG, focusing on a reRT approach. A total of 37 of 210 questionnaires were returned (18% of all centers): 16 (43%) from nonacademic hospitals, 14 (38%) from academic hospitals, 5 (13%) from private institutions, and 2 (6%) from hadron therapy centers. The majority of responding centers (59%) treated ≤5 cases per year. Performance status at the time of recurrence, along with a target diameter <5 cm and an interval from primary radiation ≥6 months, were the prevalent predictive factors considered for reRT. Sixty percent of reirradiated patients had already received a salvage therapy, either chemotherapy (40%) or reoperation (20%). The most common approach for reRT was fractionated stereotactic radiotherapy to a mean (photon) dose of 41.6 Gy. Although there were wide variations in the clinical practice of reRT across the 37 centers, the core activities were reasonably consistent. These findings provide a basis for encouraging a national collaborative study to develop, implement, and monitor the use of reRT in this challenging clinical setting.

Clinical Status of Adolescents with Perinatal HIV at Transfer to Adult Care in the UK/Ireland.

Increasing numbers of children infected perinatally with human immunodeficiency virus (HIV) are surviving to adolescence and transitioning to adult care, yet there are scarce data on their clinical status at transfer. We analyzed prospective cohort data from the UK/Ireland national Collaborative HIV Pediatric Study (CHIPS). Clinical status at last pediatric clinic visit prior to transfer was described. Factors associated with higher CD4 cell count and viral load (VL) suppression<400 c/mL among patients on antiretroviral therapy (ART) at transfer were assessed using linear and logistic regression, respectively. Data were matched with the UK HIV Drug Resistance Database (UKHIVDRB) to assess cumulative resistance profiles at transfer. Of 1,907 children followed in CHIPS from 1996 to November 2014, 644 (34%) transferred to adult care: 53% were female, 62% born outside the UK/Ireland, 75% black African. At last pediatric follow-up, median age was 17.4 years [interquartile range 16.5,18.1], 27% had previous AIDS diagnosis, CD4 was 444 cells/mm3 [280, 643], 76% were on ART, 13% off-ART, and 11% ART-naive. Among patients on ART, 74% had VL<400 c/mL. In multivariable analysis, higher CD4 at transfer was associated with younger age, higher CD4 at ART initiation and lower VL at transfer (P ≤ .001). Predictors of viral suppression include no AIDS diagnosis and later year of transfer (P ≤ .05). Of 291 patients with resistance data, 82% had resistance to ≥1 drug class, 56% to ≥2 classes and 12% had triple-class resistance. Three-quarters of adolescents were on stable ART at transfer, of whom 74% were virologically suppressed. The prevalence of triple-class resistance was relatively low at 12%.

Clustering ofToxoplasma gondiiInfections Within Families of Congenitally Infected Infants

Family clusters and epidemics of toxoplasmosis in North, Central, and South America led us to determine whether fathers of congenitally infected infants in the National Collaborative Chicago-Based Congenital Toxoplasmosis Study (NCCCTS) have a high incidence of Toxoplasma gondii infection. We analyzed serum samples collected from NCCCTS families between 1981 and 2013. Paternal serum samples were tested for T. gondii antibodies with immunoglobulin (Ig) G dye test and IgM enzyme-linked immunosorbent assay. Additional testing of paternal serum samples was performed with differential-agglutination and IgG avidity tests when T. gondii IgG and IgM results were positive and serum samples were collected by the 1-year visit of the congenitally infected child. Prevalence of paternal seropositivity and incidence of recent infection were calculated. We analyzed whether certain demographics, maternal parasite serotype, risk factors, or maternal/infant clinical manifestations were associated with paternal T. gondii infection status. Serologic testing revealed a high prevalence (29 of 81; 36%) of T. gondii infection in fathers, relative to the average seropositivity rate of 9.8% for boys and men aged 12-49 years in the United States between 1994 and 2004 (P < .001). Moreover, there was a higher-than-expected incidence of recent infections among fathers with serum samples collected by the 1-year visit of their child (6 of 45; 13%; P < .001). No demographic patterns or clinical manifestations in mothers or infants were associated with paternal infections, except for sandbox exposure. The high prevalence of chronic and incidence of recent T. gondii infections in fathers of congenitally infected children indicates that T. gondii infections cluster within families in North America. When a recently infected person is identified, family clustering and community risk factors should be investigated for appropriate clinical management.

Patterns of Hydrocephalus Caused by Congenital Toxoplasma gondii Infection Associate With Parasite Genetics.

Four anatomical patterns of hydrocephalus secondary to congenital Toxoplasma gondii infection were identified and characterized for infants enrolled in the National Collaborative Chicago-based Congenital Toxoplasmosis Study. Analysis of parasite serotype revealed that different anatomical patterns associate with Type-II vs Not-Exclusively Type-II strains (NE-II) (P = .035).

WS17.2 Identification of CF mutations in deep intronic regions: Design of antisense oligonucleotides for a targeted therapeutic approach

Considering that the extensive study of the CFTR gene classically performed in molecular diagnosis does not detect all disease-causing mutations, we previously developed an approach for a complete resequencing of the CFTR locus to search for mutations deeply located in introns (Bonini et al. Genet Med, 2015). After identifying candidate intronic mutations, we now aim to restore full-length CFTR transcripts by using antisense oligonucleotides also named Target Site Blockers (TSB). DNA from 15 patients with only one CF mutation were collected through a national collaborative study. Enrichments of the CFTR locus (250 kb) by long-range PCR or targeted capture were sequenced using 454 GS Junior and MiSeq Illumina platforms. TSB (Exiqon) were specifically designed for the deleterious variants. Out of 200 variations detected, our in-house pipeline pointed out 10 intronic variations, per DNA in average. In silico analysis tools predicted that 13 variants (for the 15 patients) had a deleterious effect on CFTR splicing by promoting inclusion of pseudoexons. TSB were tested whether the splicing defect was confirmed. For instance, TSB used on bronchial and primary nasal cells transfected with minigene constructs, significantly restored the full-length CFTR transcript for the well-known mutation c.1680–886A>G and a new identified c.1680–883A>G. Two new mutations in introns 18 and 23 are being tested. Finally, our massively parallel sequencing strategy lead to the identification of new CF-causing mutations in introns. Our findings also demonstrate the efficiency of antisense oligonucleotides for a targeted therapeutic for cystic fibrosis. Work supported by Vaincre La Mucoviscidose.

Promoting research and audit at medical school: evaluating the educational impact of participation in a student-led national collaborative study.

BackgroundMedical students often struggle to engage in extra-curricular research and audit. The Student Audit and Research in Surgery (STARSurg) network is a novel student-led, national research collaborative. Student collaborators contribute data to national, clinical studies while gaining an understanding of audit and research methodology and ethical principles. This study aimed to evaluate the educational impact of participation.MethodsParticipation in the national, clinical project was supported with training interventions, including an academic training day, an online e-learning module, weekly discussion forums and YouTube® educational videos. A non-mandatory, online questionnaire assessed collaborators’ self-reported confidence in performing key academic skills and their perceptions of audit and research prior to and following participation.ResultsThe group completed its first national clinical study (“STARSurgUK”) with 273 student collaborators across 109 hospital centres. Ninety-seven paired pre- and post-study participation responses (35.5%) were received (male = 51.5%; median age = 23). Participation led to increased confidence in key academic domains including: communication with local research governance bodies (p < 0.001), approaching clinical staff to initiate local collaboration (p < 0.001), data collection in a clinical setting (p < 0.001) and presentation of scientific results (p < 0.013). Collaborators also reported an increased appreciation of research, audit and study design (p < 0.001).ConclusionsEngagement with the STARSurg network empowered students to participate in a national clinical study, which increased their confidence and appreciation of academic principles and skills. Encouraging active participation in collaborative, student-led, national studies offers a novel approach for delivering essential academic training.Electronic supplementary materialThe online version of this article (doi:10.1186/s12909-015-0326-1) contains supplementary material, which is available to authorized users.