Postnatal Myelomeningocele Repair in the United States: Rates and Disparities Before and After the Management of Myelomeningocele Study Trial.

BACKGROUND AND OBJECTIVES: Evolving technologies have influenced the practice of myelomeningocele repair (MMCr), including mandatory folic acid fortification, advances in prenatal diagnosis, and the 2011 Management of Myelomeningocele Study (MOMS) trial demonstrating benefits of fetal over postnatal MMCr in select individuals. Postnatal MMCr continues to be performed, especially for those with limitations in prenatal diagnosis, health care access, anatomy, or personal preference. A comprehensive, updated national perspective on the trajectory of postnatal MMCr volumes and patient disparities is absent. We characterize national trends in postnatal MMCr rates before and after the MOMS trial publication (2000-2010 vs 2011-2019) and examine whether historical disparities persist. METHODS: This retrospective, cross-sectional analysis queried Nationwide Inpatient Sample data for postnatal MMCr admissions. Annual and race/ethnicity-specific rates were calculated using national birth registry data. Time series analysis assessed for trends relative to the year 2011. Patient, admission, and outcome characteristics were compared between pre-MOMS and post-MOMS cohorts. RESULTS: Between 2000 and 2019, 12 426 postnatal MMCr operations were estimated nationwide. After 2011, there was a gradual, incremental decline in the annual rate of postnatal MMCr. Post-MOMS admissions were increasingly associated with Medicaid insurance and the lowest income quartiles, as well as increased risk indices, length of stay, and hospital charges. By 2019, race/ethnicity-adjusted rates seemed to converge. The mortality rate remained low in both eras, and there was a lower rate of same-admission shunting post-MOMS. CONCLUSION: National rates of postnatal MMCr gradually declined in the post-MOMS era. Medicaid and low-income patients comprise an increasing majority of MMCr patients post-MOMS, whereas historical race/ethnicity-specific disparities are improving. Now more than ever, we must address disparities in the care of MMC patients before and after birth.

Primary care experiences in the 'Let's test for HPV' study: a qualitative analysis.

Introduction The National Cervical Screening Programme (NCSP) will switch from cervical cytology to Human Papillomavirus (HPV) testing as the primary cervical screening modality in 2023. To prepare for rollout an implementation study of HPV testing in primary care commenced in August 2022 in three different geographic regions in NZ. Aims This study explores Primary Care Staff's experience of using the HPV testing pathway in the 'Let's test for HPV' study so that recommendations can be made to improve the testing process before nationwide roll-out. Method Thirty-nine primary care staff were interviewed across all 17 practices in the Capital and Coast, Canterbury and Whanganui region participating in the 'Let's Test For HPV' study. In total 19 interviews took place which followed a semi-structured approach. These interviews were recorded and transcribed. Template analysis was carried out on transcripts to aid in identifying themes. Results Three key themes, with additional subthemes, were identified. Staff were strongly supportive of the new testing regime. Interviewees identified some issues with the new pathway. Educational needs for both patients and clinicians were identified. Conclusion Primary care staff described the experience of using the HPV testing pathway positively; however, there were requests for ongoing additional support and nationwide rollout to be supported by practitioner and patient education programmes. With the right support this new pathway for cervical cancer screening has the potential to improve access for previously underserved and unserved groups.

Demographics of first-time donors returning for donation during the pandemic: COVID-19 convalescent plasma versus standard blood product donors.

BACKGROUND: Previous studies have demonstrated low first-time donor return rates (DRR) following catastrophic events. Little is known, however, about the influence of demographic factors on the DRR of first-time donors during the COVID-19 pandemic, including the unique motivation of COVID-19 convalescent plasma (CCP) donors as compared to non-CCP donors. STUDY DESIGN AND METHODS: Thirteen blood collection organizations submitted deidentified data from first-time CCP and non-CCP donors returning for regular (non-CCP) donations during the pandemic. DRR was calculated as frequencies. Demographic factors associated with returning donors: race/ethnicity, gender, and generation (Gen Z: 19-24, Millennial: 25-40, Gen X: 41-56, and Boomer: ≥57 years old), within the CCP and non-CCP first-time cohorts were compared using chi-square test at p < .05 statistical significance. RESULTS: From March 2020 through December 2021, there were a total of 44,274 first-time CCP and 980,201 first-time non-CCP donors. DRR were 14.6% (range 11.9%-43.3%) and 46.6% (range 10.0%-76.9%) for CCP and non-CCP cohorts, respectively. Age over 40 years (Gen X and Boomers), female gender, and White race were each associated with higher return in both donor cohorts (p < .001). For the non-CCP return donor cohort, the Millennial and Boomers were comparable. CONCLUSION: The findings demonstrate differences in returning donor trends between the two donor cohorts. The motivation of a first-time CCP donor may be different than that of a non-CCP donor. Further study to improve first-time donor engagement would be worthwhile to expand the donor base with a focus on blood donor diversity emphasizing engagement of underrepresented minorities and younger donors.

Protocol for a cluster randomised controlled feasibility study of Prehospital Optimal Shock Energy for Defibrillation (POSED).

Aims: The Prehospital Optimal Shock Energy for Defibrillation (POSED) study will assess the feasibility of conducting a cluster randomised controlled study of clinical effectiveness in UK ambulance services to identify the optimal shock energy for defibrillation. Methods: POSED is a pragmatic, allocation concealed, open label, cluster randomised, controlled feasibility study. Defibrillators within a single UK ambulance service will be randomised in an equal ratio to deliver one of three shock strategies 120-150-200 J, 150-200-200 J, 200-200-200 J. Consecutive adults (≥18 years) presenting with out of hospital cardiac arrest requiring defibrillation will be eligible. The study plans to enrol 90 patients (30 in each group). Patients (or their relatives for non-survivors) will be informed about trial participation after the initial emergency has resolved. Survivors will be invited to consent to participate in follow-up (i.e., at 30 days or discharge).The primary feasibility outcome is the proportion of eligible patients who receive the randomised study intervention. Secondary feasibility outcomes will include recruitment rate, adherence to allocated treatment and data completeness. Clinical outcomes will include Return of an Organised Rhythm (ROOR) at 2 minutes post-shock, refibrillation rate, Return of Spontaneous Circulation (ROSC) at hospital handover, survival and neurological outcome at 30 days. Conclusion: The POSED study will assess the feasibility of a large-scale trial and explore opportunities to optimise the trial protocol.Trial registration: ISRCTN16327029.

Paediatric Outpatient Parenteral Antimicrobial Therapy (OPAT): An e-survey of the experiences of parents and clinicians.

BACKGROUND: Little evidence exists about parental satisfaction and their influence on referral to paediatric Outpatient Parenteral Antimicrobial Therapy (OPAT). AIM: This study aimed to examine the experiences of parents, children and clinicians of OPAT at a large tertiary children's hospital. METHOD: A prospective e-survey, using closed and open questions, of parents (n = 33) of 33 children who had received OPAT (3 children completed a survey), and clinicians (n = 31) involved in OPAT at a tertiary hospital. Data were collected September 2016 to July 2018. RESULTS: Data were analysed using simple descriptive statistics. The results show that OPAT offered benefits (less stress, re-establishment of family life) compared to hospital-based treatment for parents and children, although some were anxious. Clinicians' referral judgements were based on child, home, and clinical factors. Some clinicians found the process of referral complex. CONCLUSION: Most parents and children were satisfied with the OPAT service and preferred the option of home-based treatment as it promoted the child's comfort and recovery and supported family routines.

Unintentional Window Falls in Children and Adolescents.

OBJECTIVE: Unintentional window falls represent a preventable source of injury and death in children. Despite major campaigns in some larger cities, there continue to be unintentional falls from windows throughout the United States. We aimed to identify risk factors and trends in unintentional window falls in the pediatric population in a national and regional sample. METHODS: A retrospective analysis of annual emergency department (ED) visits from the National Electronic Injury Surveillance System using product codes specific to windows, as well as patient encounters for unintentional window falls from January 2007 to August 2017 using site-specific trauma registries from 10 tertiary care children's hospitals in New England. National and state-specific census population estimates were used to compute rates per 100,000 population. RESULTS: There were 38,840 ED visits and 496 regional patients who unintentionally fell from a window across the study period between 0 and 17 years old. The majority of falls occurred in children under the age of 6 and were related to falls from a second story or below. A decreased trend in national ED visits was seen, but no change in rates over time for regional trauma center encounters. A high number of falls was found to occur in smaller cities surrounding metropolitan areas and from single family residences. CONCLUSIONS: Falls from windows represent a low proportion of overall types of unintentional sources of injury in children but are a high risk for severe disability. These results provide updated epidemiologic data for targeted intervention programs, as well as raise awareness for continued education and advocacy.

Factors affecting opioid management for injured children after hospital discharge.

INTRODUCTION: Prescription opioid misuse is a national crisis. Injured children often receive opioid medication at hospital discharge, but the role these prescriptions play in the opioid crisis has not been fully elucidated. Whether these opioids are administered, the duration of severe pain requiring opioids, and what the final disposition of unused opioids is in this population remain unknown. METHODS: A survey of parent/guardian perceptions of their child's pain after injury, duration of opioid administration, opioid storage and disposal, and perceptions of opioid education was designed. During a 12-month period, parents of injured children admitted to an ACS Level 1 Pediatric Trauma Center were prospectively enrolled by convenience sample. Surveys were in two steps with an enrollment survey prior to discharge and a follow-up survey 7-10 days after discharge. RESULTS: Seventy of 114 (61.4%) enrolled parents/guardians completed follow-up survey. Of the 79.1% that reported an opioid prescription for their child, 92.5% filled it. Of those reporting on opioid usage, 10.4% never used the opioid, 75% used opioids <3 days, 12.5% 4-7 days, 2% >7 days. Of those who filled the opioid prescription, 83.7% reported having leftover doses. Reasons for discontinuing opioids included the child no longer had pain (87.2%), the child ran out of medication (5.1%), other (7.7%). Regarding storage, 53.3% reported utilizing an unlocked bathroom cabinet, and 81.3% unlocked kitchen space. Of those reporting unused opioids, 83.3% reported not disposing them, and 38.2% reported no plan for disposal. CONCLUSION: The majority of parents/guardians of injured children report resolution of severe pain requiring opioids within 72 h of hospital discharge, and virtually all by 7 days. The majority of injured children were prescribed a greater number of doses than they needed to treat their pain. Many parents/guardians store opioids in unsecure locations and a significant proportion report no plan to dispose of unused opioid doses. Further investigation is warranted to quantify and address the gap between pain control needs and opioid prescribing practices. The rate of unsecure storage and plan to retain unused opioids are potential targets for discharge opioid education. TYPE OF STUDY: Cross-sectional survey. LEVEL OF EVIDENCE: Level IV.

Minimizing Individual Learning Curves in a Mature Endoscopic Fetal Surgery Program.

INTRODUCTION: Twin-to-twin transfusion syndrome affects monochorionic twin pregnancies and can result in fetal death. Endoscopic laser treatment remains a relatively infrequent procedure for this condition. This presents difficulties for maintaining proficiency and for training new personnel. OBJECTIVE: The dual mentoring program at our institution allows for continuous mentoring of new providers. We hypothesize that this approach stabilizes program proficiency despite the addition of new practitioners. METHODS: Query of the fetal treatment program database returned 146 cases of laser ablation between 2000 and 2019. Patient and pregnancy characteristics as well as operative time and outcomes were recorded. The learning curve-cumulative summation method and rolling averages were used to analyze outcomes. RESULTS: Overall survival was 69%, and survival of at least 1 twin was 89%. Mean operative time was 53.6 ± 20.9 min. Overall twin survival stabilized after the first 40 cases. Rolling averages for operative time decreased from 71 to 49 min for the most recent cases. These results were not affected by the introduction of new surgeons. CONCLUSIONS: Creative mentoring can maintain stable overall program outcomes despite changes in team composition. This training approach may be applicable to other rare procedures in fetal surgery.

Being 'at-home' on outpatient parenteral antimicrobial therapy (OPAT): a qualitative study of parents' experiences of paediatric OPAT.

OBJECTIVE: To better understand the factors that facilitate and hinder a positive experience of paediatric outpatient parenteral antimicrobial therapy (OPAT). DESIGN: Qualitative study using semistructured interviews. SETTING: A dedicated paediatric consultant-led hospital-based, outreach OPAT service in England. PARTICIPANTS: Participants were primarily parents of children who had received OPAT; one child participated. METHODS: Children and parents of children who received OPAT and who had participated in the survey phase of the larger study were invited to be interviewed. RESULTS: 12 parents (10 mothers and 2 fathers) of 10 children participated; one child (aged 15 years). Data analysis resulted in one meta-theme, 'At-homeness' with OPAT, this reflected the overall sense of home being a place in which the children and their parents could be where they wanted to be. Four key themes were identified that reflect the ways in which parents and children experienced being at-home on OPAT: 'Comfort, security, freedom, and control'; 'Faith, trust and confidence'; 'Explanations and communication' and 'Concerns, restrictions and inconveniences'. CONCLUSIONS: Despite feeling anxious at times, parents reported that they and their children generally had a positive experience of OPAT; being at-home brought many benefits compared with in-patient care. Recommendations arising from the study include a 'whole-system' approach to discharge home that includes support related to return to school/nursery, reduction in disruptions to home-based routines, more clarity on choice and preparation for managing potential anxiety, better consideration of dose timing and enhanced preparation and information.

Acute Hemolytic Transfusion Reaction due to Anti-P1: A Case Report and Review of Institutional Experience.

BACKGROUND: Here we report a case of acute hemolytic transfusion reaction (HTR) due to anti-P1 and review our institutional database for prevalence of anti-P1 antibodies and frequency of anti-P1-mediated HTR. Anti-P1 antibodies, reported to be present in up to two-thirds of P2 individuals, are usually clinically insignificant. However, rare cases of acute HTR due to anti-P1 are reported. Case Report: We report the clinical and laboratory features of a mild acute HTR due to an IgM anti-P1 not detected by a routinely used antibody screening method. We reviewed our institutional database to investigate prevalence of anti-P1 antibodies identified in our patient population and frequency of HTR in patients with anti-P1. RESULTS: Analysis of RBC transfusion recipient data over the 10-year period from 2006 to 2015 showed prevalence of anti-P1 identified in our laboratory of 174 per 100,000 individuals. Frequency of HTR in patients with anti-P1 identified in our laboratory over a 10-year period was 1 in 1,429 RBC transfusions (0.07%). Conclusion: Our reported case of HTR mediated by IgM anti-P1 reactive at 37 °C confirms the potential of antibody screening methods designed to detect IgG antibodies to miss rare clinically significant IgM antibodies.

Strategic Talent Management: Implementation and Impact of a Leadership Development Program in Radiology.

The rapidity of change and increasing complexity of the academic medical center environment require a talented and engaged workforce with competencies in adaptability, capacity for working in empowered and diverse interprofessional teams, and self-efficacy. Radiology-a crosscutting field that interfaces with most other biomedical disciplines and that is often at the forefront of technological disruption-is a potentially ideal venue to focus professional and leadership development to create positive organizational value. In this report, we detail the design of and 9-year experience with a departmental leadership academy at a large academic center intended to foster team-based skills in early to midcareer faculty and staff. Over the past decade, 100 participants have completed the program with 80% retention, substantial professional growth, and increased capacity for mentoring others. This in-house, customized leadership development program is aligned with our strategic and cultural imperative to promote nimble, engaged, and empowered teams in a diverse and inclusive setting.

Delivery, setting and outcomes of paediatric Outpatient Parenteral Antimicrobial Therapy (OPAT): a scoping review.

BACKGROUND: There has been little detailed systematic consideration of the delivery, setting and outcomes of paediatric Outpatient Parenteral Antimicrobial Therapy (OPAT), although individual studies report that it is a safe and effective treatment. OBJECTIVE: This scoping review aimed to examine what is known about the delivery, settings and outcomes of paediatric OPAT and to identify key knowledge deficits. DESIGN: A scoping review using Arksey and O'Malley's framework was undertaken. DATA SOURCES: Keywords were identified and used to search MEDLINE and CINAHL. STUDY APPRAISAL METHODS: Primary research studies were included if samples comprised children and young people 21 or under, who had received OPAT at home or in a day treatment centre. The Mixed Methods Appraisal Tool was used to review the methodological quality of the studies MAIN FINDINGS: From a preliminary pool of 157 articles, 51 papers were selected for full review. 19 studies fitted the inclusion criteria. Factors influencing delivery of OPAT were diverse and included child's condition, home environment, child-related factors, parental compliance, training and monitoring. There is little consensus as to what constitutes success of and adverse events in OPAT. CONCLUSIONS: Future studies need to clearly define and use success indicators and adverse events in order to provide evidence that paediatric OPAT is safe and effective. IMPLICATIONS: Consensus outcomes that include child and parent perspectives need to be developed to allow a clearer appreciation of a successful paediatric OPAT service.

Clinical and Molecular Epidemiology of Staphylococcal Toxic Shock Syndrome in the United Kingdom.

Staphylococcal toxic shock syndrome (TSS) was originally described in menstruating women and linked to TSS toxin 1 (TSST-1)-producing Staphylococcus aureus. Using UK national surveillance data, we ascertained clinical, molecular and superantigenic characteristics of TSS cases. Average annual TSS incidence was 0.07/100,000 population. Patients with nonmenstrual TSS were younger than those with menstrual TSS but had the same mortality rate. Children <16 years of age accounted for 39% of TSS cases, most caused by burns and skin and soft tissue infections. Nonmenstrual TSS is now more common than menstrual TSS in the UK, although both types are strongly associated with the tst+ clonal complex (CC) 30 methicillin-sensitive S. aureus lineage, which accounted for 49.4% of all TSS and produced more TSST-1 and superantigen bioactivity than did tst+ CC30 methicillin-resistant S. aureus strains. Better understanding of this MSSA lineage and infections in children could focus interventions to prevent TSS in the future.

Correlation of Checkerboard Synergy Testing with Time-Kill Analysis and Clinical Outcomes of Extensively Drug-Resistant Acinetobacter baumannii Respiratory Infections.

We tested 76 extensively drug-resistant (XDR) Acinetobacter baumannii isolates by the checkerboard method using only wells containing serum-achievable concentrations (SACs) of drugs. Checkerboard results were correlated by time-kill assay and clinical outcomes. Minocycline-colistin was the best combination in vitro, as it inhibited growth in one or more SAC wells in all isolates. Patients who received a combination that inhibited growth in one or more SAC wells demonstrated better microbiological clearance than those who did not (88% versus 30%; P = 0.025). The checkerboard platform may have clinical utility for XDR A. baumannii infections.

Identification of commonly expressed exoproteins and proteolytic cleavage events by proteomic mining of clinically relevant UK isolates of Staphylococcus aureus.

The range of exoproteins and core exoproteome of 14 Staphylococcus aureus isolates representing major lineages associated with asymptomatic carriage and clinical disease in the UK was identified by MS proteomics using a combined database incorporating sequences derived from 39 S. aureus genomes. In all, 632 different proteins were identified and, of these, only 52 (8 %) were found in all 14 isolates whereas 144 (23 %) were found in just a single isolate. Comparison of the observed mass of each protein (based on migration by SDS-PAGE) with its predicted mass (based on amino acid sequence) suggested that 95 % of the proteins identified were not subject to any major post-translational modification. Migration of 5 % of the proteins was not as expected: 1 % of the proteins migrated at a mass greater than predicted, while 4 % appeared to have undergone proteolytic cleavage; these included SsaA2, Aur, SspP, Ebh as well as BlaR1, MecR1, FsH, OatA and LtaS. Intriguingly, a truncated SasG was produced by a single CC8 USA300-like strain. The analysis provided evidence of the marked heterogeneity in protein expression by S. aureus in broth, while yielding a core but narrow common exoproteome.

Nonoperative treatment of acute appendicitis in children: A feasibility study.

PURPOSE: Nonoperative treatment of acute appendicitis appears to be feasible in adults. It is unclear whether the same is true for children. METHODS: Children 5-18 years with <48 h symptoms of acute appendicitis were offered nonoperative treatment: 2 doses of piperacillin IV, then ampicillin/clavulanate ×1 week. Treatment failure (worsening on therapy) and recurrence (after completion of therapy) were noted. Patients who declined enrollment were asked to participate as controls. Cost-utility analysis was performed using Pediatric Quality of Life Scale (PedsQL®) to calculate quality-adjusted life month (QALM) for study and control patients. RESULTS: Twenty-four patients agreed to undergo nonoperative management, and 50 acted as controls. At a mean follow-up of 14 months, three of the 24 failed on therapy, and 2/21 returned with recurrent appendicitis at 43 and 52 days, respectively. Two patients elected to undergo an interval appendectomy despite absence of symptoms. Appendectomy-free rate at one year was therefore 71% (C.I. 50-87%). No patient developed perforation or other complications. Cost-utility analysis shows a 0.007-0.03 QALM increase and a $1359 savings from $4130 to $2771 per nonoperatively treated patient. CONCLUSION: Despite occasional late recurrences, antibiotic-only treatment of early appendicitis in children is feasible, safe, cost-effective and is experienced more favorably by patients and parents.

Patient-centered outcomes research in appendicitis in children: Bridging the knowledge gap.

PURPOSE: Patient-centered outcomes research (PCOR) aims to give patients a better understanding of the treatment options to enable optimal decision-making. As nonoperative alternatives are now being evaluated in children for acute appendicitis, we surveyed patients and their families regarding their knowledge of appendicitis and evaluated whether providing basic medical information would affect their perception of the disease and allow them to more rationally consider the treatment alternatives. METHODS: Families of children aged 5-18 presenting to the Emergency Department with suspected appendicitis were recruited for a tablet-based interactive educational survey. One hundred subjects (caregivers and patients ≥ 15 years) were questioned before and after an education session about their understanding of appendicitis, including questions on three hypothetical treatment options: urgent appendectomy, antibiotics alone, or initial antibiotics followed by elective appendectomy. Subjects were clearly informed that urgent appendectomy is currently the standard of care. RESULTS: Only 14% of respondents correctly identified the mortality rate of appendicitis (17 deaths/year according to the 2010 US census) when compared with other extremely rare causes of death. Fifty-four and 31% thought it was more common than death from lightning (40/year) and hunting-associated deaths (44/year), respectively. Eighty-two percent of respondents believed it "likely" or "very likely" that the appendix would rupture if operation was at all delayed, and 81% believed that rupture of the appendix would rapidly lead to severe complications and death. In univariate analysis, this perception was significantly more prevalent for mothers (odds ratio, (OR) 5.19, confidence interval (CI) 1.33-21.15), and subjects who knew at least one friend or relative who had a negative experience with appendicitis (OR 5.53, CI 1.40-25.47). Following education, these perceptions changed significantly (53% still believed that immediate operation was necessary, and 47% believed perforation led to great morbidity and potential mortality, P<0.001). In a survey of potential appendicitis treatment options, urgent appendectomy was considered a "good" or "very good" option by 74% of subjects, compared with 68% for antibiotics only without appendectomy and 49% for initial antibiotic therapy followed by elective outpatient appendectomy. CONCLUSION: There was a striking knowledge gap in the participant perception of appendicitis. Appropriate education can correct anecdotally supported misconceptions. Adequate education may empower patients to make better-informed decisions about their medical care and may be important for future studies in alternative treatments for appendicitis in children.

Characterization of the HBB: c.*233G > C Variant: No Evidence of a ß-Thalassemic Phenotype.

ß-Thalassemia (ß-thal) results from homozygous or compound heterozygous inheritance of ß-globin alleles that yield decreased or absent synthesis of the ß chain. Disease is frequently severe, requiring lifelong transfusion therapy. Heterozygosity for a ß-thal allele results in an asymptomatic carrier state with mild but characteristic hematological findings. More than 200 ß-globin alleles have been demonstrated to produce ß-thal. For populations with a high prevalence of ß-thal, screening for carrier status, genetic counseling and prenatal diagnosis are important components of efforts to both reduce disease incidence and provide early diagnosis and treatment. It is therefore important to define and characterize potential ß-thal alleles. We sought to further characterize the previously reported ß-thal allele, HBB: c.*233G > C. This variant is provisionally included in the HbVar database based on a study of Palestinians in the Gaza Strip with ß-thal disease or carrier status (known or suspected) where 4.2% of subjects were found to have HBB: c.*233G > C. In our patient population, we detected the HBB: c.*233G > C variant in 17.3% of individuals (17 heterozygotes, one homozygote) undergoing ß hemoglobin (Hb) gene sequencing at our laboratory over a 25-month period. Hematological parameters were analyzed to determine if these individuals demonstrated findings consistent with inheritance of a ß-thal allele. Individuals with the HBB: c.*233G > C variant did not demonstrate any abnormalities in hematological parameters characteristic of ß-thal carrier state (17 heterozygotes) or clinical evidence of disease (homozygote). Our data demonstrate no evidence for pathogenicity of the HBB: c.*233G > C variant but rather demonstrate that this variant is a common benign polymorphism.

Acute and subchronic toxicity of inhaled toluene in male Long-Evans rats: Oxidative stress markers in brain.

The effects of exposure to volatile organic compounds (VOCs), which are of concern to the EPA, are poorly understood, in part because of insufficient characterization of how human exposure duration impacts VOC effects. Two inhalation studies with multiple endpoints, one acute and one subchronic, were conducted to seek effects of the VOC, toluene, in rats and to compare the effects between acute and subchronic exposures. Adult male Long-Evans rats were exposed to toluene vapor (n=6 per group) at a concentration of 0 or 1019 ± 14 ppm for 6h in the acute study and at 0 ± 0, 10 ± 1.4, 97 ± 7, or 995 ± 43 ppm for 6h/d, 5d/week for 13 weeks in the subchronic study. For the acute study, brains were dissected on ice within 30 min of the end of exposure, while for the subchronic study, brains were dissected 18 h after the last exposure. Frontal cortex, hippocampus, cerebellum, and striatum were assayed for a variety of oxidative stress (OS) parameters including total aconitase (TA), protein carbonyls, glutathione peroxidase (GPX), glutathione reductase (GRD), glutathione transferase (GST), γ-glutamylcysteine synthetase (GCS), superoxide dismutase (SOD), total antioxidants (TAS), NADPH quinone oxidoreductase-1 (NQO1), and NADH ubiquinone reductase (UBIQ-RD) activities using commercially available kits. Following acute exposure, UBIQ-RD, GCS and GRD were increased significantly only in the cerebellum, while TAS was increased in frontal cortex. On the other hand, subchronic exposure affected several OS markers including increases in NQO1 and UBIQ-RD. The effect of subchronic toluene exposure on SOD and TAS was greater in the striatum than in the other brain regions. TA activity (involved in maintaining iron homeostasis and an indicator of DNA damage) was inhibited in striatum and cerebellum, increased in hippocampus, and unchanged in frontal cortex. Protein carbonyls increased significantly in both the frontal cortex and cerebellum. In general, the results showed that acute exposure to toluene affected OS parameters to a lesser extent than did subchronic exposure. These results suggest that toluene exposure induces OS in the brain and this may be a component of an adverse outcome pathway for some of the neurotoxic effects reported following toluene exposure.

A qualitative investigation into nurses' perceptions of factors influencing staff injuries sustained during physical interventions employed in response to service user violence within one secure learning disability service.

AIMS AND OBJECTIVES: The aim of the study was to examine learning disability nurses' perceptions of incidents involving physical intervention, particularly factors contributing to injuries sustained by this group. BACKGROUND: This article reports on a qualitative study undertaken within one secure NHS Trust to respond to concerns about staff injuries sustained during physical interventions to prevent incidents of service user violence from escalating out of control. The context of the study relates to increasing debate about the most effective approaches to incidents of violence and agression. DESIGN: A qualitative research design was utilized for the study. METHODS: Semi-structured interviews were undertaken with 20 participants, two from each of the 10 incidents involving staff injury sustained during physical intervention. RESULTS: Four themes were produced by the analysis, the first, knowledge and understanding, contextualized the other three, which related to the physical intervention techniques employed, the interpretation of the incident and the impact on staff. CONCLUSION: Service user violence consistently poses nurses with the challenge of balancing the need to respond in order to maintain the safety of everyone whilst simultaneous supporting and caring for people with complex needs. This study highlights the need for further exploration of the contributory factors to the escalation of potentially violent situations. RELEVANCE TO CLINICAL PRACTICE: Services may have good systems in place for responding to and managing service user violence but appear less effective in understanding the reasons for and developing strategies to prevent violence occurring.