Search

Background: Procalcitonin (PCT) is a blood marker used to help diagnose bacterial infections and guide antibiotic treatment. PCT testing was widely used/adopted during the COVID-19 pandemic in the UK., Objectives: Primary: to measure the difference in length of early (during first 7 days) antibiotic prescribing between patients with COVID-19 who did/did not have baseline PCT testing during the first wave of the pandemic. Secondary: to measure differences in length of hospital/ICU stay, mortality, total days of antibiotic prescribing and resistant bacterial infections between these groups., Methods: Multi-centre, retrospective, observational, cohort study using patient-level clinical data from acute hospital Trusts/Health Boards in England/Wales. Inclusion: patients ≥16 years, admitted to participating Trusts/Health Boards and with a confirmed positive COVID-19 test between 1 February 2020 and 30 June 2020., Results: Data from 5960 patients were analysed: 1548 (26.0%) had a baseline PCT test and 4412 (74.0%) did not. Using propensity-score matching, baseline PCT testing was associated with an average reduction in early antibiotic prescribing of 0.43 days [95% confidence interval (CI): 0.22-0.64 days, P < 0.001) and of 0.72 days (95% CI: 0.06-1.38 days, P = 0.03] in total antibiotic prescribing. Baseline PCT testing was not associated with increased mortality or hospital/ICU length of stay or with the rate of antimicrobial-resistant secondary bacterial infections., Conclusions: Baseline PCT testing appears to have been an effective antimicrobial stewardship tool early in the pandemic: it reduced antibiotic prescribing without evidence of harm. Our study highlights the need for embedded, rapid evaluations of infection diagnostics in the National Health Service so that even in challenging circumstances, introduction into clinical practice is supported by evidence for clinical utility., Study Registration Number: ISRCTN66682918., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Background: Abnormal gait kinematics are common in youth with cerebral palsy (CP), but prior studies have not analyzed their longitudinal change throughout childhood. This study examines how age and orthopaedic surgery influence gait kinematics throughout childhood in those with ambulatory CP., Methods: In this institutional review board-approved prospective cohort study, children with spastic CP (GMFCS I-III) were recruited at age 17-40 months. Instrumented gait analysis was performed at 3-year intervals from age 4 to 21 years, collecting longitudinal kinematic data in bare feet at a self-selected speed. The change in Gait Profile Score (ΔGPS) between each pair of gait analyses (intervals) was analyzed by age distribution (<10, 10-15, ≥15 years) and by presence/absence of orthopaedic surgery., Results: The study included 31 children (GMFCS: I [13], II [14], III [4]). A baseline instrumented gait analysis was performed at age 5.8 ± 1.6 years with subsequent analysis at 2.5 ± 1.3-year intervals. Examining ΔGPS from baseline to final outcome, 87% of limbs were improved/unchanged; 298 intervals of ΔGPS were analyzed and classified as nonsurgical or surgical. Analysis revealed greater GPS improvement in intervals with surgery versus intervals without ( p = 0.0004). Surgical intervals had significantly greater GPS improvement in the <10- vs. >15-year-old groups, p = 0.0063., Conclusions: Improvement in gait kinematics in children with CP is significantly influenced by age and timing of orthopaedic surgical intervention for gait correction, and was most pronounced for children <10 years old. Although surgery was associated with improved outcomes in all age groups, these improvements were significantly less for children >10 years old. These results reinforce the importance of considering the timing of orthopaedic surgery.

Background/aims: The value of using qualitative methods within clinical trials is widely recognised. How qualitative research is integrated within trials units to achieve this is less clear. This paper describes the process through which qualitative research has been integrated within Cardiff University's Centre for Trials Research (CTR) in Wales, UK. We highlight facilitators of, and challenges to, integration., Methods: We held group discussions on the work of the Qualitative Research Group (QRG) within CTR. The content of these discussions, materials for a presentation in CTR, and documents relating to the development of the QRG were interpreted at a workshop attended by group members. Normalisation Process Theory (NPT) was used to structure analysis. A writing group prepared a document for input from members of CTR, forming the basis of this paper., Results: Actions to integrate qualitative research comprised: its inclusion in Centre strategies; formation of a QRG with dedicated funding/roles; embedding of qualitative research within operating systems; capacity building/training; monitoring opportunities to include qualitative methods in studies; maximising the quality of qualitative research and developing methodological innovation. Facilitators of these actions included: the influence of the broader methodological landscape within trial/study design and its promotion of the value of qualitative research; and close physical proximity of CTR qualitative staff/students allowing sharing of methodological approaches. Introduction of innovative qualitative methods generated interest among other staff groups. Challenges included: pressure to under-resource qualitative components of research, preference for a statistical stance historically in some research areas and funding structures, and difficulties faced by qualitative researchers carving out individual academic profiles when working across trials/studies., Conclusions: Given that CTUs are pivotal to the design and conduct of RCTs and related study types across multiple disciplines, integrating qualitative research into trials units is crucial if its contribution is to be fully realised. We have made explicit one trials unit's experience of embedding qualitative research and present this to open dialogue on ways to operationalise and optimise qualitative research in trials. NPT provides a valuable framework with which to theorise these processes, including the importance of sense-making and legitimisation when introducing new practices within organisations., (© 2024. The Author(s).)

Background: Half of mental health problems are established by the age of 14 years and 75% by 24 years. Early intervention and prevention of mental ill health are therefore vitally important. However, increased demand over recent years has meant that access to child mental health services is often restricted to those in severest need. Watch Me Play! (WMP) is an early intervention designed to support caregiver attunement and attention to the child to promote social-emotional well-being and thereby mental health resilience. Originally developed in the context of a local authority mental health service for children in care, it is now also delivered online as a low intensity, scalable, preventative intervention. Although WMP shows promise and is already used in some services, we do not yet know whether it is effective., Methods: A non-randomised single group feasibility study with embedded process evaluation. We propose to recruit up to 40 parents/carers of children aged 0-8 years who have been referred to early years and children's services in the UK. WMP involves a parent watching the child play and talking to their child about their play (or for babies, observing and following signals) for up to 20 min per session. Some sessions are facilitated by a trained practitioner who provides prompts where necessary, gives feedback, and discusses the child's play with the caregiver. Services will offer five facilitated sessions, and parents will be asked to do at least 10 additional sessions on their own with their child in a 5-week period. Feasibility outcomes examined are as follows: (i) recruitment, (ii) retention, (iii) adherence, (iv) fidelity of delivery, (v) barriers and facilitators of participation, (vi) intervention acceptability, (vii) description of usual care, and (viii) data collection procedures. Intervention mechanisms will be examined through qualitative interview data. Economic evaluation will be conducted estimating cost of the intervention and cost of service use for child and parents/carers quality-adjusted life years., Discussion: This study will address feasibility questions associated with progression to a future randomised trial of WMP., Trial Registration: ISRCTN13644899 . Registered on 14th April 2023., (© 2024. The Author(s).)

Introduction: Maximizing patient satisfaction is now a significant focus in many outpatient orthopedic clinics as it has been shown to affect many facets of healthcare. With this quality improvement study, we sought to determine the areas of the longest patient wait time during their clinical encounter and evaluate the effect of an identification card system on those times. We hypothesized that utilizing an identification card system would expedite the time patients spend in the clinic and decrease wait times., Methods: This quality improvement study was conducted in an orthopedic hand surgery clinic within a military treatment facility. Pre-intervention and intervention data collection consisted of a time sheet that was filled out by surgeons and clinic staff as the patient progressed through their appointment. The intervention consisted of a card system to track the patient throughout their encounter and mark their order in the queue., Results: There were a total of 130 patients in the pre-intervention group and 113 in the intervention group. Compared with the pre-intervention group, the intervention group patients had significantly less time from check-in to being roomed by the clinic staff with a mean of 13 ± 13  vs. 21 ± 19 minutes in the pre-intervention group (P < .001). In the pre-intervention cohort, the average clinic encounter was 66 ± 38 minutes compared to 57 ± 35 minutes in the intervention cohort, which was not statistically significant (P = .112). The time spent with the orthopedic surgeon and occupational therapists increased in the intervention group., Conclusion: We provided a simple way to decrease patient wait times and increase time with the healthcare team, utilizing our existing clinic space. Time with the orthopedic surgeon significantly increased because of our intervention, while the overall clinic time trended down., (© The Association of Military Surgeons of the United States 2022. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: SARS-CoV-2 is a respiratory virus with neurological complications including the loss of smell and taste, headache, and confusion that can persist for months or longer. Severe neuronal cell damage has also been reported in some cases. The objective of this study was to compare the infectivity of the wild-type virus, Delta (B.1.617.2) and Omicron (B.1.1.529) variants in transgenic mice that express the human angiotensin-converting enzyme 2 (hACE2) receptor under the control of the keratin 18 promoter (K18) and characterize the progression of infection and inflammatory response in the lungs, brain, medulla oblongata, and olfactory bulbs of these animals. We hypothesized that wild type, Delta and Omicron differentially infect K18-hACE2 mice, thereby inducing distinct cellular responses., Methods: K18-hACE2 female mice were intranasally infected with wild-type, Delta, or Omicron variants and euthanized either at 3 days post-infection (dpi) or at the humane endpoint. None of the animals infected with the Omicron variant reached the humane endpoint and were euthanized at day 8 dpi. Virological and immunological analyses were performed in the lungs, brains, medulla oblongata and olfactory bulbs isolated from infected mice., Results: At 3 dpi, mice infected with wild type and Delta displayed significantly higher levels of viral RNA in the lungs than mice infected with Omicron, while in the brain, Delta and Omicron resulted in higher levels of viral RNA than with the wild type. Viral RNA was also detected in the medulla oblongata of mice infected by all these virus strains. At this time point, the mice infected with wild type and Delta displayed a marked upregulation of many inflammatory markers in the lungs. On the other hand, the upregulation of inflammatory markers was observed only in the brains of mice infected with Delta and Omicron. At the humane endpoint, we observed a significant increase in the levels of viral RNA in the lungs and brains of mice infected with wild type and Delta, which was accompanied by the elevated expression of many inflammatory markers. In contrast, mice which survived infection with the Omicron variant showed high levels of viral RNA and the upregulation of cytokine and chemokine expression only in the lungs at 8 dpi, suggesting that infection and inflammatory response by this variant is attenuated in the brain. Reduced RNA levels and the downregulation of inflammatory markers was also observed in the medulla oblongata and olfactory bulbs of mice infected with Omicron at 8 dpi as compared with mice infected with wild-type and Delta at the humane end point. Collectively, these data demonstrate that wild-type, Delta, and Omicron SARS-CoV-2 induce distinct levels of infection and inflammatory responses in K18-hACE2 mice. Notably, sustained brain infection accompanied by the upregulation of inflammatory markers is a critical outcome in mice infected with wild type and Delta but not Omicron.

Objective: To explore and model factors affecting antibiotic prescribing decision-making early in the pandemic., Design: Semistructured qualitative interview study., Setting: National Health Service (NHS) trusts/health boards in England and Wales., Participants: Clinicians from NHS trusts/health boards in England and Wales., Method: Individual semistructured interviews were conducted with clinicians in six NHS trusts/health boards in England and Wales as part of the Procalcitonin Evaluation of Antibiotic use in COVID-19 Hospitalised patients study, a wider study that included statistical analysis of procalcitonin (PCT) use in hospitals during the first wave of the pandemic. Thematic analysis was used to identify key factors influencing antibiotic prescribing decisions for patients with COVID-19 pneumonia during the first wave of the pandemic (March to May 2020), including how much influence PCT test results had on these decisions., Results: During the first wave of the pandemic, recommendations to prescribe antibiotics for patients with COVID-19 pneumonia were based on concerns about secondary bacterial infections. However, as clinicians gained more experience with COVID-19, they reported increasing confidence in their ability to distinguish between symptoms and signs caused by SARS-CoV-2 viral infection alone, and secondary bacterial infections. Antibiotic prescribing decisions were influenced by factors such as clinician experience, confidence, senior support, situational factors and organisational influences. A decision-making model was developed., Conclusion: This study provides insight into the decision-making process around antibiotic prescribing for patients with COVID-19 pneumonia during the first wave of the pandemic. The importance of clinician experience and of senior review of decisions as factors in optimising antibiotic stewardship is highlighted. In addition, situational and organisational factors were identified that could be optimised. The model presented in the study can be used as a tool to aid understanding of the complexity of the decision-making process around antibiotic prescribing and planning antimicrobial stewardship support in the context of a pandemic., Trial Registration Number: ISRCTN66682918., Competing Interests: Competing interests: All authors (with the exception of RH) and members of the PEACH consortium received funding from NIHR COVID Learning and Recovery Call programme (NIHR132254) for the PEACH Study and for the delivery of this manuscript. ET-J, JE, LB-H, PP and WM (main authors) and ST (consortium) all received funding from NIHR-HTA programme for delivery of the PRONTO trial (NIHR17/136/13). EC, ET-J, PP and LB-H received funding from NIHR for the BATCH trial (15/188/42). EC, ET-J and PP received funding from MRC-NIHR EME for contribution to the PRECISE study (NIHR129960). PH received funding from Abbot Laboratories for attending the European Network for Antimicrobial Stewardship in Point of Care. PH has also previously held post as Vice Chancellor for British Society for Antimicrobial Chemotherapy (BSAC) and is currently a committee member., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Penile carcinomas represent a rare malignancy associated with significant psychosocial impacts that deter afflicted individuals from seeking medical attention, thus, worsening prognosis. Following the dramatic shift in healthcare delivery to virtual platforms, it is suspected that prevalent psychosocial impacts have been further compounded by the COVID-19 pandemic, resulting in several late-stage presentations and engendering poorer outcomes., Methods: A retrospective chart review of surgically managed cases of penile cancer was conducted from January 2020 to June 2022 to identify patients that may have been unduly impacted by the COVID-19 pandemic. Included cases were analyzed in quantifying diagnostic and treatment delays, along with patient outcomes. Relevant epidemiological and pathological markers were also examined., Results: Ten patients met the inclusion criteria. Average time delay from first complaint of a penile lesion to surgical management was 75 days, with 60% of patients experiencing a time delay of two months or more. The average delay from first complaint to diagnosis was 62 days in 2020 and 18 days in 2021. Advanced-stage disease was present in six (60%) individuals at presentation, while four (40%) patients perished during the study period., Conclusions: In cases of concern for penile malignancy, virtual care cannot replace the necessity of physical exams in preventing diagnostic and treatment delays. The present study further highlights the necessity of initial physical examination of penile abnormalities in preventing fatal outcomes for those afflicted. Such consideration warrants urgent examination of referred males with genital abnormalities to prevent further exacerbation of delays.

One of the major pathogenesis mechanisms of SARS-CoV-2 is its potent suppression of innate immunity, including blocking the production of type I interferons. However, it is unknown whether and how the virus interacts with different innate-like T cells, including NKT, MAIT and γδ T cells. Here we reported that upon SARS-CoV-2 infection, invariant NKT (iNKT) cells rapidly trafficked to infected lung tissues from the periphery. We discovered that the envelope (E) protein of SARS-CoV-2 efficiently down-regulated the cell surface expression of the antigen-presenting molecule, CD1d, to suppress the function of iNKT cells. E protein is a small membrane protein and a viroporin that plays important roles in virion packaging and envelopment during viral morphogenesis. We showed that the transmembrane domain of E protein was responsible for suppressing CD1d expression by specifically reducing the level of mature, post-ER forms of CD1d, suggesting that it suppressed the trafficking of CD1d proteins and led to their degradation. Point mutations demonstrated that the putative ion channel function was required for suppression of CD1d expression and inhibition of the ion channel function using small chemicals rescued the CD1d expression. Importantly, we discovered that among seven human coronaviruses, only E proteins from highly pathogenic coronaviruses including SARS-CoV-2, SARS-CoV and MERS suppressed CD1d expression, whereas the E proteins of human common cold coronaviruses, HCoV-OC43, HCoV-229E, HCoV-NL63 and HCoV-HKU1, did not. These results suggested that E protein-mediated evasion of NKT cell function was likely an important pathogenesis factor, enhancing the virulence of these highly pathogenic coronaviruses. Remarkably, activation of iNKT cells with their glycolipid ligands, both prophylactically and therapeutically, overcame the putative viral immune evasion, significantly mitigated viral pathogenesis and improved host survival in mice. Our results suggested a novel NKT cell-based anti-SARS-CoV-2 therapeutic approach., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Lu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: In response to viral infection, neutrophils release inflammatory mediators as part of the innate immune response, contributing to pathogen clearance through virus internalization and killing. Pre- existing co-morbidities correlating to incidence to severe COVID-19 are associated with chronic airway neutrophilia. Furthermore, examination of COVID-19 explanted lung tissue revealed a series of epithelial pathologies associated with the infiltration and activation of neutrophils, indicating neutrophil activity in response to SARS-CoV-2 infection., Methods: To determine the impact of neutrophil-epithelial interactions on the infectivity and inflammatory responses to SARS-CoV-2 infection, we developed a co-culture model of airway neutrophilia. This model was infected with live SARS-CoV-2 virus the epithelial response to infection was evaluated., Results: SARS-CoV-2 infection of airway epithelium alone does not result in a notable pro-inflammatory response from the epithelium. The addition of neutrophils induces the release of proinflammatory cytokines and stimulates a significantly augmented proinflammatory response subsequent SARS-CoV-2 infection. The resulting inflammatory responses are polarized with differential release from the apical and basolateral side of the epithelium. Additionally, the integrity of the \epithelial barrier is impaired with notable epithelial damage and infection of basal stem cells., Conclusions: This study reveals a key role for neutrophil-epithelial interactions in determining inflammation and infectivity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Calvert, Quiroz, Lorenzana, Doan, Kim, Senger, Anders, Wallace, Salomon, Henley and Ryan.)

Background: Based on the principles of Narrative Medicine, this study explored a narrative-based workshop for multi-level interdisciplinary clinicians who have EOL conversations., Methods: Fifty-two clinicians participated in narrative-based interactive workshops. Participants engaged narrative in three forms: viewing narratives, writing/sharing narratives, and co-constructing narratives. Post workshop interviews were conducted and thematically analyzed., Results: Five themes characterized how the workshop shaped learning and subsequent care experiences: (1) learning to enter/respond to the patient stories, (2) communicating across professions and disciplines, (3) practicing self-care. Additional themes emphasized (4) barriers to narrative learning and (5) obstacles to applying narrative to practice., Discussion: Results highlight the function/utility of narrative forms such as the value of processing emotions via reflective writing, feeling vulnerable while sharing narratives, and appreciating colleagues' obstacles while observing patient-clinician simulations. Challenges associated with narrative such as writing anxiety and barriers to implementation such as time constraints are detailed to inform future initiatives.

Background: Arthrogryposis multiplex congenita (AMC) is characterized by joint contractures in 2 or more body areas, often resulting in clubfoot deformities that are typically stiffer than those seen in idiopathic clubfoot deformities. While surgery is routinely used to treat clubfoot in AMC, it has a high rate of recurrence and complications. Current literature suggests serial casting (SC) could be useful in treating clubfoot in AMC, though evidence of its effectiveness is limited., Methods: Passive range of motion (PROM), dynamic foot pressure, parent-reported Pediatric Outcomes Data Collection Instrument, brace tolerance, and the need for post-casting surgery were evaluated retrospectively in children with AMC treated with SC to address clubfoot deformities. Analysis of variance or paired t tests were used as appropriate on pre-casting, short-term (within 6 mo after SC) and/or longer-term (6 to 18 mo after SC) parameters to determine the effectiveness of SC. Brace tolerance before and after SC was analyzed using the Global Test for Symmetry, and medical records were reviewed to determine the need for surgery post-SC., Results: Forty-six children (6.1±3.1 y old) were cast an average of 2.5±1.9 times, resulting in 206 SC episodes. PROM showed improvement in ankle dorsiflexion and forefoot abduction in the short term (P<0.05), returning to baseline measurements in the long term (P=0.09). Brace tolerance improved after casting (P<0.05). Only 15% of feet required surgery at follow-up at 10.3±5.5 years. There were no significant changes in dynamic foot pressure or Pediatric Outcomes Data Collection Instrument results after SC, except for an increase in the pain subtest (P<0.05)., Conclusions: Serial casting in children with AMC can be effective in temporarily improving PROM and improving brace tolerance, but it does not impact dynamic barefoot position. Positive impact of conservative management in children with AMC can potentially delay or reduce the need for invasive surgical intervention by improving PROM and brace tolerance., Level of Evidence: Level III, Retrospective Comparative Study., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Children with cerebral palsy (CP) at Gross Motor Function Classification System (GMFCS) levels III/IV are at risk for losses in standing function during adolescence and transition to adulthood. Multilevel surgery (MLS) is an effective treatment to improve gait, but its effects on standing function are not well documented. The objectives of our study were to describe standing function in children with CP classified as GMFCS levels III/IV and evaluate change after MLS., Methods: This retrospective study included children with CP (GMFCS III/IV) ages 6 to 20 years who underwent instrumented gait analysis. A subset who underwent MLS were evaluated for change. Primary outcome measures were Gross Motor Function Measure dimension D, gait velocity, functional mobility scale, and the Pediatric Outcomes Data Collection Instrument (PODCI). Additional impairment level measures included foot pressure, knee extension during stance phase of gait, and knee extension passive range of motion., Results: Four hundred thirty-seven instrumented gait analysis sessions from 321 children with CP (ages 13.7±4.8 y; GMFCS III-81%/IV-19%) were included. The GMFCS III group had higher Gross Motor Function Measure dimension D, gait velocity, PODCI scores, and better knee extension compared with the GMFCS IV group ( P <0.05); 94 MLS were evaluated for postoperative change 15.3±4.2 months after MLS. Children at GMFCS level III had improved PODCI scores ( P <0.05), better knee extension passive range of motion ( P <0.01), and improved coronal plane foot pressure ( P <0.05) post MLS. Maximum knee extension during stance and heel impulse improved significantly in both groups ( P <0.01)., Conclusions: Standing function of children with CP at GMFCS IV was significantly more limited than at GMFCS III. After MLS, both groups (III/IV) showed improvement in impairment level outcomes (knee extension and foot position), whereas only those functioning at GMFCS III had improvement in activity/participation outcomes according to the PODCI. For children with CP at GMFCS levels IV, MLS may improve standing function, but appropriate goals related to assisted standing and measurement protocols sensitive to limited functional mobility should be adopted., Level of Evidence: Level III-retrospective comparative study., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Benefits of hamstring lengthening surgery on the sagittal plane in children with cerebral palsy have been previously demonstrated, but there is limited information on its effects on the transverse plane. This study compared the effects of medial hamstring lengthening (MHL) with those of medial and lateral hamstring lengthening (MLHL) procedures in the transverse plane. Children with gross motor function classification system (GMFCS) levels I-III who had MHL or MLHL were included. Baseline, short- (1-2 years), and long-term (3+ years) postoperative three-dimensional gait analysis outcomes were compared using analysis of variance. Children were excluded if they had concurrent osteotomies or tendon transfers. One hundred fifty children (235 limbs) were included, with 110 limbs in the MHL group (age 8.5 ± 4.1 years, GMFCS I-27%, II-52%, and III-21%) and 125 limbs in the MLHL group (age 10.0 ± 4.0 years, GMFCS I-23%, II-41%, and III-37%). Time between surgery and short- and long-term follow-up gait analysis was 1.5 ± 0.6 years and 6.6 ± 2.9 years, respectively. Transmalleolar axis became more external after MHL at both short and long terms ( P < 0.05), whereas there were only significant differences at long term in MLHL ( P < 0.05). Although hamstring lengthening has a positive impact on stance phase knee extension in children with cerebral palsy, intact lateral hamstrings after MHL likely contribute to increased tibial external rotation after surgery. Significant increases in external rotation at the knee in the long term are likely related to a trend present with growth in children with cerebral palsy rather than a direct result of surgical intervention., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Women with overweight (a body mass index of ≥ 25 kg/m 2 ) or obesity (a body mass index of ≥ 30 kg/m 2 ) are at greater risk of experiencing complications during pregnancy and labour than women with a healthy weight. Women who remove their long-acting reversible contraception (i.e. coils or implants) are one of the few groups of people who contact services as part of their preparation for conception, creating an opportunity to offer a weight loss intervention., Objectives: The objectives were to understand if routine NHS data captured the pathway from long-acting reversible contraception removal to pregnancy and included body mass index; to identify the suitable components of a preconception weight loss intervention; and to engage with key stakeholders to determine the acceptability and feasibility of asking women with overweight/obesity to delay the removal of their long-acting reversible contraception in order to take part in a preconception weight loss intervention., Design: This was a preparatory mixed-methods study, assessing the acceptability and feasibility of a potential intervention, using routine NHS data and purposefully collected qualitative data., Participants: The NHS routine data included all women with a long-acting reversible contraception code. There were three groups of participants in the surveys and interviews: health-care practitioners who remove long-acting reversible contraception; weight management consultants; and women of reproductive age with experience of overweight/obesity and of using long-acting reversible contraception., Setting: UK-based health-care practitioners recruited at professional meetings; and weight management consultants and contraceptive users recruited via social media., Data Sources: Anonymised routine data from UK sexual health clinics and the Clinical Practice Research Datalink, including the Pregnancy Register; and online surveys and qualitative interviews with stakeholders., Results: The records of 2,632,871 women aged 16-48 years showed that 318,040 had at least one long-acting reversible contraception event, with 62% of records including a body mass index. Given the identified limitations of the routine NHS data sets, it would not be feasible to reliably identify women with overweight/obesity who request a long-acting reversible contraception removal with an intention to become pregnant. Online surveys were completed by 100 health-care practitioners, four weight management consultants and 243 contraceptive users. Ten health-care practitioners and 20 long-acting reversible contraception users completed qualitative interviews. A realist-informed approach generated a hypothesised programme theory. The combination of weight discussions and the delay of long-acting reversible contraception removal was unacceptable as an intervention to contraceptive users for ethical and practical reasons. However, a preconception health intervention incorporating weight loss could be acceptable, and one potential programme is outlined., Limitations: There was very limited engagement with weight management consultants, and the sample of participating stakeholders may not be representative., Conclusions: An intervention that asks women to delay long-acting reversible contraception removal to participate in a preconception weight loss intervention would be neither feasible nor acceptable. A preconception health programme, including weight management, would be welcomed but requires risk communication training of health-care practitioners., Future Work: Work to improve routine data sets, increase awareness of the importance of preconception health and overcome health-care practitioner barriers to discussing weight as part of preconception care is a priority., Trial Registration: This trial is registered as ISRCTN14733020., Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 27, No. 1.

Gamma-aminobutyric acid (GABA) and GABA-receptors (GABA-Rs) form a major neurotransmitter system in the brain. GABA-Rs are also expressed by 1) cells of the innate and adaptive immune system and act to inhibit their inflammatory activities, and 2) lung epithelial cells and GABA-R agonists/potentiators have been observed to limit acute lung injuries. These biological properties suggest that GABA-R agonists may have potential for treating COVID-19. We previously reported that GABA-R agonist treatments protected mice from severe disease induced by infection with a lethal mouse coronavirus (MHV-1). Because MHV-1 targets different cellular receptors and is biologically distinct from SARS-CoV-2, we sought to test GABA therapy in K18-hACE2 mice which develop severe pneumonitis with high lethality following SARS-CoV-2 infection. We observed that GABA treatment initiated immediately after SARS-CoV-2 infection, or 2 days later near the peak of lung viral load, reduced pneumonitis severity and death rates in K18-hACE2 mice. GABA-treated mice had reduced lung viral loads and displayed shifts in their serum cytokine/chemokine levels that are associated with better outcomes in COVID-19 patients. Thus, GABA-R activation had multiple effects that are also desirable for the treatment of COVID-19. The protective effects of GABA against two very different beta coronaviruses (SARS-CoV-2 and MHV-1) suggest that it may provide a generalizable off-the-shelf therapy to help treat diseases induced by new SARS-CoV-2 variants and novel coronaviruses that evade immune responses and antiviral medications. GABA is inexpensive, safe for human use, and stable at room temperature, making it an attractive candidate for testing in clinical trials. We also discuss the potential of GABA-R agonists for limiting COVID-19-associated neuroinflammation., Competing Interests: DLK and JT are inventors of GABA-related patents. DLK serves on the Scientific Advisory Board of Diamyd Medical. DLK gifted the Immunotherapeutics Research Fund. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tian, Dillion, Henley, Comai and Kaufman.)

Background: Having a body mass index (BMI) which is classified as overweight (BMI ≥ 25) or obese (BMI ≥ 30) increases the risk of complications during pregnancy and labour. Weight-management interventions which target excess gestational weight gain during pregnancy have had limited success. Women who use long-acting reversible contraception (LARC) are in contact with services as part of their preparation for conception, creating a potential opportunity to offer a preconception weight-loss intervention. The aims of this mixed methods study were to assess the acceptability and practicability of a weight-loss intervention which asked people to delay LARC removal in order to lose weight before conceiving., Methods: Routine UK NHS data were analysed to identify pathways from LARC removal to pregnancy. Qualitative surveys and advisory group discussions with service providers and LARC users with experience of being overweight were conducted and analysed thematically., Results: Three hundred fifteen thousand seven hundred fifty-five UK women aged 16-48 years between 2009-2018 had at least one LARC-related event (e.g. insertion, removal) and 1.7% of those events were recorded as related to planning a pregnancy. BMI was included in 62% of women's records, with 54% of those BMI being classified as overweight or obese. Online surveys were completed by 100 healthcare practitioners and 243 LARC users. Stakeholders identified facilitators and barriers associated with the proposed intervention including sensitivities of discussing weight, service-user past experiences, practitioner skills, the setting and ethical implications of the proposed intervention., Conclusions: Although women and service providers recognised potential benefits, a preconception weight-loss intervention asking people to delay LARC removal posed many barriers, due mainly to the acceptability of such an intervention to women and healthcare practitioners. Weight-loss interventions that target the general population, together with a focus on improving public knowledge of preconception health, may be more acceptable than interventions which solely focus on LARC users. Many of the barriers identified, including communication, understanding and beliefs about weight and risk, appointment systems and the limitations of routine datasets also have relevance for any preconception weight-loss intervention. Work to improve routine datasets and reducing communication barriers to discussing weight are priorities., Trial Registration: ISRCTN14733020 registered 10.05.2019., (© 2022. The Author(s).)

The COVID-19 pandemic profoundly affected American families and children, including through the closure or change in the nature of their care and school settings. As the pandemic has persisted, many children remain in remote schooling and those attending in-person childcare or school have contended with unpredictable closures. This study investigated the frequency and consequences of disruptions to children's childcare and school arrangements during Fall 2020. The sample is parents who were hourly service-sector workers prior to the pandemic, had a young child between the ages of 3 and 8, and were at least partially responsible for their children's school and/or care in Fall 2020 ( N = 676); half of the sample were non-Hispanic Black, 22% were Hispanic, and 18% are non-Hispanic White. Parents were asked to complete 30 days of daily surveys about whether their care and school arrangements went smoothly and as predicted that day, about their mood, parenting behaviors, and children's behavior. Results showed that daily disruptions to care and school were common, with families reporting a disruption on 24% of days. Families with children in exclusively remote schooling experienced more frequent disruption than families with children in in-person care or school. For all families, care or school disruptions were related to worse child behavior, more negative parental mood, and increased likelihood of losing temper and punishment. Within-family mediation suggests that parents' difficulties supporting children's learning, and to a lesser degree their mood and parenting behaviors, partially mediate effects of disruptions on child behavior. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolves rapidly under the pressure of host immunity, as evidenced by waves of emerging variants despite effective vaccinations, highlighting the need for complementing antivirals. We report that targeting a pyrimidine synthesis enzyme restores inflammatory response and depletes the nucleotide pool to impede SARS-CoV-2 infection. SARS-CoV-2 deploys Nsp9 to activate carbamoyl-phosphate synthetase, aspartate transcarbamoylase, and dihydroorotase (CAD) that catalyzes the rate-limiting steps of the de novo pyrimidine synthesis. Activated CAD not only fuels de novo nucleotide synthesis but also deamidates RelA. While RelA deamidation shuts down NF-κB activation and subsequent inflammatory response, it up-regulates key glycolytic enzymes to promote aerobic glycolysis that provides metabolites for de novo nucleotide synthesis. A newly synthesized small-molecule inhibitor of CAD restores antiviral inflammatory response and depletes the pyrimidine pool, thus effectively impeding SARS-CoV-2 replication. Targeting an essential cellular metabolic enzyme thus offers an antiviral strategy that would be more refractory to SARS-CoV-2 genetic changes.

Microbial drug discovery programs rely heavily on accessing bacterial diversity from the environment to acquire new specialized metabolite (SM) lead compounds for the therapeutic pipeline. Therefore, knowledge of how commonly culturable bacterial taxa are distributed in nature, in addition to the degree of variation of SM production within those taxa, is critical to informing these front-end discovery efforts and making the overall sample collection and bacterial library creation process more efficient. In the current study, we employed MALDI-TOF mass spectrometry and the bioinformatics pipeline IDBac to analyze diversity within phylotype groupings and SM profiles of hundreds of bacterial isolates from two Eunapius fragilis freshwater sponges, collected 1.5 km apart. We demonstrated that within two sponge samples of the same species, the culturable bacterial populations contained significant overlap in approximate genus-level phylotypes but mostly nonoverlapping populations of isolates when grouped lower than the level of genus. Further, correlations between bacterial phylotype and SM production varied at the species level and below, suggesting SM distribution within bacterial taxa must be analyzed on a case-by-case basis. Our results suggest that two E. fragilis freshwater sponges collected in similar environments can exhibit large culturable diversity on a species-level scale, thus researchers should scrutinize the isolates with analyses that take both phylogeny and SM production into account to optimize the chemical space entering into a downstream bacterial library., (© 2022. The Author(s).)

Caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), COVID-19 is a virus-induced inflammatory disease of the airways and lungs that leads to severe multi-organ damage and death. Here we show that cellular lipid synthesis is required for SARS-CoV-2 replication and offers an opportunity for pharmacological intervention. Screening a short-hairpin RNA sublibrary that targets metabolic genes, we identified genes that either inhibit or promote SARS-CoV-2 viral infection, including two key candidate genes, ACACA and FASN, which operate in the same lipid synthesis pathway. We further screened and identified several potent inhibitors of fatty acid synthase (encoded by FASN), including the US Food and Drug Administration-approved anti-obesity drug orlistat, and found that it inhibits in vitro replication of SARS-CoV-2 variants, including more contagious new variants, such as Delta. In a mouse model of SARS-CoV-2 infection (K18-hACE2 transgenic mice), injections of orlistat resulted in lower SARS-CoV-2 viral levels in the lung, reduced lung pathology and increased mouse survival. Our findings identify fatty acid synthase inhibitors as drug candidates for the prevention and treatment of COVID-19 by inhibiting SARS-CoV-2 replication. Clinical trials are needed to evaluate the efficacy of repurposing fatty acid synthase inhibitors for severe COVID-19 in humans., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: This prospective study used instrumented gait analysis, patient-reported outcomes, and portable accelerometers to examine walking activity in adults with cerebral palsy (CP)., Research Question: This study aimed to provide objective data and evaluate factors associated with walking activity in adults with CP., Methods: Participants with CP (ages 25-45 years) completed instrumented gait analysis and patient-reported outcomes, including the Patient Reported Outcome Measurement Information System (PROMIS) and Satisfaction with Life Score (SWLS), and wore a StepWatch for 8 days. Average strides per day, stratified by Gross Motor Function Classification System (GMFCS), were compared with nondisabled adults ages 30-39 years utilizing Welch's t-tests with Bonferroni corrections. Correlation coefficients and stepwise multiple linear regression analyses examined relationships between walking activity and GMFCS, gait deviation index (GDI), gait velocity, PROMIS physical function, SWLS, body mass index (BMI), and employment., Results: Participants included 109 adults with CP, ages 29 ± 4 years, classified at GMFCS levels I/II (73 %) and III/IV (27 %). Compared with nondisabled adults, daily stride count was significantly lower in both groups of adults with CP (p < 0.00025), with a progressive decline according to GMFCS level. Walking activity correlated with PROMIS physical function (r = .42), GDI (r = .48), and gait velocity (r = .58). Association for employment was lower (r = 0.27) but significant, while age, SWLS, and BMI were not individually correlated with walking activity. Stepwise, multiple linear regression modeled with Akaike information criterion explained 40.9 % of the observed variability in walking activity in this cohort of adults with CP., Significance: Physical function, as classified by GMFCS or measured by PROMIS and self-selected walking velocity, has the strongest association with and is the most significant predictor of walking activity in adults with CP. After accounting for physical function, a small amount of the variation in walking activity can be explained by GDI, employment, and age., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Previous studies have looked at the short-term effectiveness of conservative and surgical treatment of children with cerebral palsy (CP), but few have explored the long-term outcomes into adulthood using gait analysis and patient-reported outcome measures., Research Question: How do gait, mobility, and patient-reported outcomes in adults with CP who received specialized pediatric orthopedic care change from adolescence?, Methods: We identified 645 adults with 1) CP, 2) age 25-45 years, and 3) an adolescent instrumented gait analysis (IGA) at our center. Measurement outcomes included physical examination, IGA, and select domains of the Patient-Reported Outcomes Measurement Information System (PROMIS)., Results: Participants included 136 adults with CP; Gross Motor Function Classification System levels I (21 %), II (51 %), III (22 %), and IV (7%); 57 % males; and average age 16 ± 3/29 ± 3 years (adolescent/adult visits). There was no significant difference in gait deviation index, stride length, or gross motor function between adolescent and adult visits. There were statistically significant but not clinically meaningful declines in gait velocity. At adulthood, PROMIS results revealed limitations in physical function compared with a normative sample but no differences in depression, participation, or pain interference., Significance: In this relatively homogeneous group of adults with CP who received orthopedic care from one center, gait and gross motor function showed no clinically meaningful change from adolescence, which differs from recent reports of declining mobility in adulthood. Expert orthopedic care, guided by IGA, may prevent losses in functional mobility for adults with CP., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Population-based analyses of COVID-19 data, by race and ethnicity can identify and monitor disparities in COVID-19 outcomes and vaccination coverage. CDC recommends that information about race and ethnicity be collected to identify disparities and ensure equitable access to protective measures such as vaccines; however, this information is often missing in COVID-19 data reported to CDC. Baseline data collection requirements of the Office of Management and Budget's Standards for the Classification of Federal Data on Race and Ethnicity (Statistical Policy Directive No. 15) include two ethnicity categories and a minimum of five race categories (1). Using available COVID-19 case and vaccination data, CDC compared the current method for grouping persons by race and ethnicity, which prioritizes ethnicity (in alignment with the policy directive), with two alternative methods (methods A and B) that used race information when ethnicity information was missing. Method A assumed non-Hispanic ethnicity when ethnicity data were unknown or missing and used the same population groupings (denominators) for rate calculations as the current method (Hispanic persons for the Hispanic group and race category and non-Hispanic persons for the different racial groups). Method B grouped persons into ethnicity and race categories that are not mutually exclusive, unlike the current method and method A. Denominators for rate calculations using method B were Hispanic persons for the Hispanic group and persons of Hispanic or non-Hispanic ethnicity for the different racial groups. Compared with the current method, the alternative methods resulted in higher counts of COVID-19 cases and fully vaccinated persons across race categories (American Indian or Alaska Native [AI/AN], Asian, Black or African American [Black], Native Hawaiian or Other Pacific Islander [NH/PI], and White persons). When method B was used, the largest relative increase in cases (58.5%) was among AI/AN persons and the largest relative increase in the number of those fully vaccinated persons was among NH/PI persons (51.6%). Compared with the current method, method A resulted in higher cumulative incidence and vaccination coverage rates for the five racial groups. Method B resulted in decreasing cumulative incidence rates for two groups (AI/AN and NH/PI persons) and decreasing cumulative vaccination coverage rates for AI/AN persons. The rate ratio for having a case of COVID-19 by racial and ethnic group compared with that for White persons varied by method but was <1 for Asian persons and >1 for other groups across all three methods. The likelihood of being fully vaccinated was highest among NH/PI persons across all three methods. This analysis demonstrates that alternative methods for analyzing race and ethnicity data when data are incomplete can lead to different conclusions about disparities. These methods have limitations, however, and warrant further examination of potential bias and consultation with experts to identify additional methods for analyzing and tracking disparities when race and ethnicity data are incomplete., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

The hostile environment that older lesbian, gay, bisexual and transgender (LGBT) people faced at younger ages in the United Kingdom (UK) may have a lasting negative impact on their health. This systematic scoping review adds to the current knowledge base through comprehensively synthesising evidence on what is known about the extent and nature of health and care inequalities, as well as highlighting gaps in the evidence which point the way towards future research priorities. We searched four databases, undertook manual searching, and included studies which presented empirical findings on LGBT people aged 50+ in the UK and their physical and mental health or social care status. From a total of 5,738 records, 48 papers from 42 studies were eligible and included for data extraction. The synthesis finds that inequities exist across physical and mental health, as well as in social care, exposure to violence and loneliness. Social care environments appeared as a focal point for inequities and formal care environments severely compromised the identity and relationships that older LGBT people developed over their lifecourse. Conversely, the literature demonstrated how some older LGBT people successfully negotiated age-related transitions, e.g. emphasising the important role of LGBT-focused social groups in offsetting social isolation and loneliness. While there exist clear policy implications around the requirement for formal care environments to change to accommodate an increasingly diverse older population, there is also a need to explore how to support older LGBT people to maintain their independence for longer, reducing the need for formal care., (© Cambridge University Press 2019.)

Background: Efforts to resolve the longstanding and growing staffing crisis in midwifery in the United Kingdom have been hampered by very poor retention rates, with early career midwives the most likely to report burnout and intention to leave the profession., Aims: To establish the key, self-described factors of satisfaction and dissatisfaction at work for early career midwives in the United Kingdom, and suggest appropriate and effective retention strategies., Methods: Thematic analysis was undertaken on a subset of free text responses from midwives who had been qualified for five years or less, collected as part of the United Kingdom arm of the Work, Health and Emotional Lives of Midwives project., Findings: Midwives described feeling immense pressure caused by an unremittingly heavy workload and poor staffing. Where relationships with colleagues were strong, they were described as a protective factor against stress; conversely, negative working relationships compounded pressures. Despite the challenges, many of the midwives reported taking great pleasure in their work, describing it as a source of pride and self-esteem. Midwives valued being treated as individuals and having some control over their shift pattern and area of work., Discussion: These results, which reveal the strain on early career midwives, are consistent with the findings of other large studies on midwives' wellbeing. All available levers should be used to retain and motivate existing staff, and recruit new staff; in the meantime, considerable creativity and effort should be exercised to improve working conditions., Conclusion: This analysis provides a 'roadmap' for improving staff wellbeing and potentially retention., (Copyright © 2020 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.)

Background and Objectives: The outbreak of coronavirus disease 2019 has changed American society in ways that are difficult to capture in a timely manner. With this study, we take advantage of daily survey data collected before and after the crisis started to investigate the hypothesis that the crisis has worsened parents' and children's psychological well-being. We also examine the extent of crisis-related hardships and evaluate the hypothesis that the accumulation of hardships will be associated with parent and child psychological well-being., Methods: Daily survey data were collected between February 20 and April 27, 2020, from hourly service workers with a young child (aged 2-7) in a large US city ( N = 8222 person-days from 645 individuals). A subsample completed a one-time survey about the effects of the crisis fielded between March 23 and April 26 (subsample n = 561)., Results: Ordered probit models revealed that the frequency of parent-reported daily negative mood increased significantly since the start of the crisis. Many families have experienced hardships during the crisis, including job loss, income loss, caregiving burden, and illness. Both parents' and children's well-being in the postcrisis period was strongly associated with the number of crisis-related hardships that the family experienced., Conclusions: Consistent with our hypotheses, in families that have experienced multiple hardships related to the coronavirus disease 2019 crisis, both parents' and children's mental health is worse. As the crisis continues to unfold, pediatricians should screen for mental health, with particular attention to children whose families are especially vulnerable to economic and disease aspects of the crisis., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2020 by the American Academy of Pediatrics.)

Background: The Ponseti method effectively treats idiopathic clubfoot, but its effectiveness in treating the stiffer clubfoot associated with arthrogryposis is less clear. The purpose of this study was to assess the comparative effectiveness of the Ponseti method in 5-year-old children with either idiopathic clubfoot or clubfoot due to arthrogryposis., Methods: The outcomes of the Ponseti method were retrospectively evaluated in children with idiopathic clubfoot and clubfoot associated with arthrogryposis. The children with clubfoot were seen at our hospital between 2012 and 2019 and were 4.0 to 6.9 years old at the time of their evaluation. Outcomes of the 2 groups of children with clubfoot were assessed using passive range of motion, foot pressure analysis, the Gross Motor Function Measure Dimension-D, and parent report using the Pediatric Outcomes Data Collection Instrument. These results were also compared with the same measures from a group of typically developing children. Surgical and bracing history was also recorded., Results: A total of 117 children were included (89 idiopathic clubfoot and 28 associated with arthrogryposis) with an average age of 4.8±0.8 years. The historical gait analyses of 72 typically developing children were used as a control, with an average age of 5.2±0.8 years. Significant residual equinovarus was seen in both children with idiopathic clubfoot and associated with arthrogryposis according to passive range of motion and foot pressure analysis when compared with normative data. Children with arthrogryposis demonstrated limited transfer and basic mobility, sports functioning, and global functioning while children with idiopathic clubfoot were significantly different from their typically developing peers in only transfer and basic mobility., Conclusions: Although children with idiopathic clubfoot continue with some level of residual deformity, the Ponseti method is effective in creating a pain-free, highly functional foot. In children with clubfoot associated with arthrogryposis, the Ponseti method is successful in creating a braceable foot that can delay the need for invasive surgical intervention., Level of Evidence: Level III, Therapeutic Studies-Investigating the Results of Treatment.

Objective: To establish the prevalence and determinants of loneliness among people living with dementia., Methods: Using data from the baseline wave of the Improving the experience of Dementia and Enhancing Active Life (IDEAL) cohort study, we examined the prevalence and predictors of loneliness in 1547 people with mild-to-moderate dementia. Loneliness was assessed using the six-item De Jong Gierveld loneliness scale., Results: About 30.1% of people with dementia reported feeling moderately lonely and 5.2% severely lonely. Depressive symptoms and increased risk of social isolation were associated with both moderate and severe loneliness. Those living alone were more likely to experience severe loneliness as were those reporting poorer quality of life. Marital status was not associated with loneliness nor were dementia diagnosis or cognitive function., Conclusions: This is one of the few large-scale studies to explore the prevalence of and determinants of loneliness among people living with dementia. Social isolation, depression and living alone were associated with experiencing loneliness. Longitudinal studies are needed to determine the directionality of these associations., (© 2020 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd.)

Objective: The overall study aim was to explore the relationship between the emotional wellbeing of UK midwives and their work environment. Specific research questions were to: assess levels of burnout, depression, anxiety and stress experienced by UK midwives; compare levels of burnout, depression, anxiety and stress identified in this sample of UK midwives, with levels reported in Australia, New Zealand and Sweden; identify demographic and work-related factors associated with elevated levels of burnout, depression, anxiety and stress., Design: Cross sectional research design using an online survey. The WHELM survey tool was developed within the Australian maternity context and includes a number of validated measures: The Copenhagen Burnout Inventory (CBI), Depression, Anxiety and Stress Scale (DASS-21), as well as items from the Royal College of Midwives (RCM) 'Why Midwives Leave' study (Ball et al., 2002)., Setting: United Kingdom., Participants: An on-line survey was distributed via the RCM to all full midwife members in 2017 (n = 31,898)., Data Analysis: The demographic and work-related characteristics of the sample were analysed using descriptive analyses. Levels of depression, anxiety, stress and burnout, measured by the CBI and DASS scores, were analysed using non-parametric statistical tests. Comparisons were made between groups based on demographic and work characteristics. Mann-Whitney U tests were used for two group comparisons, and Kruskal Wallis tests were used for groups with 2+ groups. Given the large number of analyses undertaken, statistically significant comparisons were identified with a conservative alpha level (p < .01)., Findings: A total of 1997 midwives responded to the survey, representing 16% of the RCM membership. The key results indicate that the UK's midwifery workforce is experiencing significant levels of emotional distress. 83% (n = 1464) of participants scored moderate and above for personal burnout and 67% (n = 1167) recorded moderate and above for work-related burnout. Client-related burnout was low at 15.5% (n = 268). Over one third of participants scored in the moderate/severe/extreme range for stress (36.7%), anxiety (38%) and depression (33%). Personal and work-related burnout scores, and stress, anxiety and depression scores were well above results from other countries in which the WHELM study has been conducted to date. Midwives were more likely to record high levels of burnout, depression, anxiety and stress if they were aged 40 and below; reported having a disability; had less than 10 years' experience; worked in a clinical midwifery setting, particularly if they worked in rotation in hospital and in integrated hospital/community settings., Key Conclusions and Implications for Practice: Many UK midwives are experiencing high levels of stress, burnout, anxiety and depression, which should be of serious concern to the profession and its leaders. NHS employed clinical midwives are at much greater risk of emotional distress than others surveyed, which has serious implications for the delivery of high quality, safe maternity care. It is also of serious concern that younger, more recently qualified midwives recorded some of the highest burnout, stress, anxiety and depression scores, as did midwives who self-reported a disability. There is considerable scope for change across the service. Proactive support needs to be offered to younger, recently qualified midwives and midwives with a disability to help sustain their emotional wellbeing. The profession needs to lobby for systems level changes in how UK maternity care is resourced and provided. Making this happen will require support and commitment from a range of relevant stakeholders, at regional and national levels., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

This letter seeks to synthesise methodological challenges encountered in a cohort of Wellcome Trust-funded research projects focusing on sexualities and health. The ten Wellcome Trust projects span a diversity of gender and sexual orientations and identities, settings; institutional and non-institutional contexts, lifecourse stages, and explore a range of health-related interventions.  As researchers, we originate from a breadth of disciplinary traditions, use a variety of research methods and data sources. Despite this breadth, four common themes are found across the projects: (i) inclusivity, representations and representativeness, (ii) lumping together of diverse groups, (iii) institutions and closed settings (iv) ethical and governance barriers., Competing Interests: No competing interests were disclosed., (Copyright: © 2019 Kneale D et al.)

In this retrospective study, children with cerebral palsy underwent a unilateral femoral derotation osteotomy and had a preoperative (PO), short-term postoperative (1-3 years), and a long-term postoperative (≥5 years) gait analysis. Patients were subdivided into groups by the PO pelvic presentation and Gross Motor Function Classification System level. In children with PO pelvic external rotation, femoral derotation osteotomy decreased the hip internal rotation and decreased the pelvic external rotation. These results could influence surgical planning to achieve long-term pelvic asymmetry.

This study evaluated knee hyperextension course in children with cerebral palsy over a 5-year follow-up. Knee hyperextension was identified in 308 knees, of which 97 had follow-up greater than 5 years. Between the tests, 40% of limbs had plantar flexor lengthening (PFL). Overall, knee flexion and ankle dorsiflexion in stance increased (P<0.0001). Similar changes were noted between limbs that had PFL and those that did not. PFL is indicated in cases associated with equinus. However, the role of multilevel surgery in the treatment of knee hyperextension needs to be further determined.

Background : The Convergence Insufficiency Symptom Survey (CISS) is being utilized as an assessment measure following concussion despite minimal research. This study explored the sensitivity and specificity of the CISS in identifying receded near point of convergence (NPC) post-concussion. Methods : Prospective study of 130 patients post-concussion aged 11-25, classified into normal NPC (n = 94) and CI (n = 36) groups (i.e., NPC >5 cm), completed the CISS, VOMS, and PCSS. Sensitivity and specificity identifying receded NPC were explored with published CISS cutoff score (>16). ROC with AUC analysis was conducted to determine an alternate CISS cutoff score to yield optimal sensitivity and specificity in patients with concussion. Results : Utilizing the published cutoff score, the CISS demonstrated adequate sensitivity (.78 [95% CI = .60-.89]) but poor specificity (.35 [95%CI = .26-.46]). ROC curve demonstrated that CISS score was significant ( P = .01) in predicting a positive test result (i.e., NPC >5) with AUC of .65 (95%CI .54-.76). An alternative cutoff score (CISS>23) maximized sensitivity (.70) and specificity (.53) for identifying receded NPC. Conclusions : Both the previously published CISS cutoff and our sample-based cutoff score yielded a high rate of false positives for receded NPC. CISS scores post-concussion may help the clinician understand difficulties with visual tasks but is not a suitable diagnostic tool in this patient population.

Aims and Objectives: To investigate challenges nurses face when providing care for oncology patients transitioning from curative to palliative care and to identify educational and support opportunities for nurses., Background: Communicating with oncology patients/families transitioning from curative treatments to care focused on comfort can be problematic for a variety of reasons. Research suggests discrepancies exist between physicians' and patients' perceptions of probable length of life. These disconnects can deepen suffering. Oncology and palliative care nurses are well positioned to facilitate this transition. However, they receive little formal instruction regarding these complex scenarios beyond what occurs through on-the-job training., Methods: Twenty-eight nurses working in oncology (n = 14) and palliative care (n = 14) settings participated. The constant comparative method was used to analyse the data., Results: Four themes emerged that characterise oncology and palliative care nurses' experiences: (a) coping with interprofessional communication errors during the transition, (b) responding to patient/family reactions to miscommunication about the goals of care, (c) navigating emotional connection to patients, and (d) adapting to sociocultural factors that influence information exchange., Conclusions: This study supports previous research regarding challenges related to patient reactions, family relationships and emotional burden during end-of-life care. However, it adds to the literature by a providing a more in-depth explication of interprofessional and patient-physician communication barriers that negatively impact care., Relevance to Clinical Practice: Misunderstandings between patients, physicians and nurses have the potential to distress complicate nurses' efforts to support patients and families. Nurses reported a problematic power dynamic that impedes their ability to facilitate communication between patient and physician or to offer insights that could enhance patient care. Medical education and continuing education initiatives are needed to build understanding across professional roles and specialties and to improve comfort discussing worsening prognosis and end-of-life issues., (© 2018 John Wiley & Sons Ltd.)

Background: Many skin-mounted three-dimensional multi-segmented foot models are currently in use for gait analysis. Evidence regarding the repeatability of models, including between trial and between assessors, is mixed, and there are no between model comparisons of kinematic results., Research Question: This study explores differences in kinematics and repeatability between five three-dimensional multi-segmented foot models. The five models include duPont, Heidelberg, Oxford Child, Leardini, and Utah., Methods: Hind foot, forefoot, and hallux angles were calculated with each model for ten individuals. Two physical therapists applied markers three times to each individual to assess within and between therapist variability. Standard deviations were used to evaluate marker placement variability. Locally weighted regression smoothing with alpha-adjusted serial T tests analysis was used to assess kinematic similarities., Results: All five models had similar variability, however, the Leardini model showed high standard deviations in plantarflexion/dorsiflexion angles. P-value curves for the gait cycle were used to assess kinematic similarities. The duPont and Oxford models had the most similar kinematics., Conclusions: All models demonstrated similar marker placement variability. Lower variability was noted in the sagittal and coronal planes compared to rotation in the transverse plane, suggesting a higher minimal detectable change when clinically considering rotation and a need for additional research. Between the five models, the duPont and Oxford shared the most kinematic similarities. While patterns of movement were very similar between all models, offsets were often present and need to be considered when evaluating published data., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The effect of a continuous intrathecal infusion of baclofen (CITB) was retrospectively studied in 19 ambulatory children with cerebral palsy (aged 12.4±4.9 years at CITB initiation). The mean clinical follow-up was 5.1±2.4 years and the mean follow-up gait analysis was 2.8±1.9 years. Spastic cerebral palsy diagnosis [14 (74%)] was most frequent. Most patients [11 (58%)] were Gross Motor Function Classification System level III. CITB significantly improved muscle tone and knee flexion at initial contact (P<0.05), but it did not lead to improved gait speed or gross motor function.

This study aimed to assess the effects of plantar flexor lengthening (PFL) on dynamic foot pressures of children with cerebral palsy using pedobarographs. Of 97 enrolled, 13 children with 18 legs had PFL. Age at surgery was 4.7 (2.8-8.8) years. A significant increase in ankle dorsiflexion and heel impulse was achieved postoperatively and was maintained at 5 years. The coronal plane pressure index increased postoperatively, but reverted to preoperative levels at the 5-year follow-up. Children tend to have more valgus after PFL. In young children, there caution should be exercised to avoid over treating varus at the time of equinus correction to avoid overcorrection.

Background: Internal tibial torsion (ITT) is a common boney deformity in children with cerebral palsy (CP). The current recommended treatment is tibial derotation osteotomy (TDO) to improve gait biomechanics. Satisfactory short-term results after TDO have been reported but long-term results have not been studied. The purpose of this study was to evaluate the long-term outcome after external TDO performed to correct ITT in ambulatory children with CP., Methods: Following IRB approval, gait kinematics and passive range of motion measurements were retrospectively evaluated in children with spastic CP who underwent TDO due to ITT comparing preoperative (E0), short-term postoperative (E1; 1 to 3 y post), and long-term postoperative (E2; >5 y post) results. Limbs were categorized as corrected, undercorrected, or overcorrected at both E1 and E2, by comparing the subjects mean tibial rotation (MTR) in gait to a group of typically developing children. Age at surgery, preop MTR (at E0), preop gait velocity (at E0), gross motor function classification system score, and foot deformity were evaluated to determine their influence on long-term results., Results: The study sample consisted of 36 legs (with E0 and E2) and 17 legs (with E0, E1, and E2). The mean age at surgery was 7.4±2.8 (range, 4 to 16.6) years. Comparing the changes over time, kinematic MTR improved from 17±11 degrees initially (E0) to -10±14 degrees short term (E1) and progressed to -23±13 degrees long term (E2) (P<0.05 E0/E1/E2; internal rotation is positive). At E2, 16 legs (44%) were found to be in the kinematic corrected group and 20 legs (56%) in the kinematic overcorrected group. There were no significant differences between the corrected and overcorrected groups of children in respect to age of surgery, gross motor function classification system, E0 MTR, gait velocity, or foot deformity., Conclusions: Although external TDO is an accepted form of treatment in children with CP, in the long term a tendency to move into external tibial torsion is common. Therefore, caution is warranted with children who initially present with ITT to avoid overcorrection., Level of Evidence: Level IV-therapeutic study.

Background: Excessive hip internal rotation is frequently seen in children with cerebral palsy (CP). Femoral derotational osteotomy (FDO) is effective in the short term, but factors associated with long-term correction remain unclear. The purposes of this study were to define the incidence of persistence and recurrence of hip internal rotation following FDO in ambulatory children with CP and to evaluate factors that influence outcome., Methods: Following IRB approval, kinematic and passive range of motion (PROM) variables were retrospectively evaluated in children with spastic CP who had FDO to correct hip internal rotation as part of clinical care at a children's specialty hospital. Children included had a preoperative evaluation (Vpre), a short-term postoperative evaluation (Vshort, 1 to 3 y post), and, in some cases, a long-term postoperative evaluation (Vlong, ≥5 y post). Age at surgery, physical exam measures, and kinematics variables were evaluated as predictors for dynamic and static recurrence., Results: Kinematic hip rotation improved from 14±12 degrees (Vpre; internal positive) to 4±13 degrees (Vshort) and relapsed to 9±15 degrees long term (P<0.05 Vpre/Vshort/Vlong; 99 limbs). Hip PROM midpoint improved from 23±9 degrees (Vpre) to 8±11 degrees (Vshort) and relapsed to 14±13 degrees (P<0.01 Vpre/Vshort/Vlong). Persistent hip internal rotation was noted in 41% (kinematics) and 18% (PROM) of limbs at Vshort (105 children, 178 limbs). Of limbs that showed initial improvement at Vshort (62 children, 95 limbs), recurrence was seen in 40% (kinematic hip rotation) and 39% (hip midpoint) at Vlong. Comparing children who had recurrent hip internal rotation and those who maintained long-term correction, we saw higher levels of spasticity and lower gait velocity in the recurrent group (P<0.05)., Conclusions: Although FDO is an accepted treatment in children with CP, persistence and recurrence of hip internal rotation can occur. Recurrence is associated with spasticity and slower gait velocity. Predictor variables may be useful for surgeons during preoperative discussions of expected outcome with families of FDO candidates., Level of Evidence: Level III.

Background: External tibial torsion (ETT) is a common bony deformity in children with cerebral palsy (CP). The current recommended treatment is tibial derotation osteotomy (TDO) to improve gait biomechanics. Satisfactory short-term results after TDO have been reported but long-term results have not been studied. The purpose of this study was to evaluate the long-term outcome following TDO to correct ETT in ambulatory children with CP., Methods: Following IRB approval, gait kinematics and passive range of motion measurements were retrospectively evaluated in children with spastic CP who underwent TDO due to ETT comparing preoperative (E0), short-term postoperative (E1; 1 to 3 y post), and long-term postoperative (E2; >5 y post) results. Limbs were categorized as corrected, undercorrected, or overcorrected at both E1 and E2, by comparing mean tibial rotation (MTR) in gait to a group of typically developing children. Age at surgery, E0 MTR, E0 gait velocity, gross motor function classification system (GMFCS) score, and foot deformity were evaluated to determine their influence on long-term results., Results: The study sample consisted of 43 legs (with E0 and E2) and 22 legs (with E0, E1, and E2). The mean age at surgery was 10.3±3.4 years (range, 6 to 19.2 y). In the group MTR trended toward improvement moving from -26±17 degrees (E0, external negative) to -16±16 degrees (E1) and relapsed to -23±17 degrees at the long term (P=0.071, E0/E1; P=0.589, E0/E2). Improvement was also seen in the transmalleolar axis (P=0.074), mean ankle rotation, and mean foot orientation (P<0.05, E0/E2). At the long-term evaluation, 16 legs (37%) were found to be in the kinematic corrected group, 25 legs (58%) in the kinematic undercorrected group, and 2 legs (5%) in the kinematic overcorrected group. There were no significant differences between the corrected and undercorrected groups of children with respect to age at surgery, GMFCS, E0 MTR, gait velocity, or foot deformity., Conclusions: Although internal TDO improves ETT in the short term, recurrence is frequent with an apparent developmental trend toward external rotation of the tibia., Levels of Evidence: Level IV-therapeutic study.

Purpose: Foot deformities are common in children with cerebral palsy (CP), yet the evolution of such deformities is not well documented. We aimed to observe and analyse changes in foot posture during growth in children with CP. Methods We followed 51 children (16 unilateral, 35 bilateral; 37 Gross Motor Function Classification Scale (GMFCS) I/II, 14 III/IV) aged two to 12 years in this level II, IRB-approved prospective longitudinal study. Data after bony foot corrections were excluded. Outcome measures included coronal plane pressure index (CPPI) and pressure impulses from the heel, medial midfoot and medial forefoot. Data were LOESS smoothed and resulting models were compared for significant differences across time using a derived FANOVA method., Results: The GMFCS I/II group had more foot valgus than typically developing (TD) children until seven years which normalised thereafter. From two to 12 years, GMFCS III/IV children had more foot valgus than TD children. Heel impulse was significantly reduced in both GMFCS groups compared with TD children, and the III/IV group had less heel contact than the I/II group., Conclusions: Due to early variability and the tendency for resolving valgus foot posture in children with CP, conservative management of coronal plane foot deformity is suggested in early childhood, especially for children classified as GMFCS I and II.

Agresta, CE, Church, C, Henley, J, Duer, T, and O'Brien, K. Single-leg squat performance in active adolescents aged 8-17 years. J Strength Cond Res 31(5): 1187-1191, 2017-More than 30 million U.S. adolescents participate in sport and exercise. Lower extremity injury from sport participation accounts for up to 89% of injuries each year. The single-leg squat (SLS) is a simple clinical tool that assesses lower extremity mechanics often associated with injury risk. To date, there is limited information regarding SLS performance in healthy children. Such information could be useful when assessing youth athletes to determine if mechanics demonstrated are different than is to be expected and puts them at the risk for injury. Furthermore, maturity status is thought to influence motor performance. Currently, there is no information regarding the influence of maturity status on SLS performance in adolescents. The purpose of our study was to determine SLS performance in relation to age and maturity level in adolescents. Forty-five children aged 8-17 years were videotaped performing a series of 10 squats using a standardized protocol. Standing height, seated height, and leg length measures were collected. Investigators scored the SLS test using specific scoring criteria. Adolescents were categorized into 3 maturity levels using a peak height velocity calculation. Multiple linear regression analyses and analysis of variance were used to analyze the data. Chronological age was a significant predictor of SLS performance with younger children having poorer SLS scores. Coaches and trainers should consider the chronological age of the youth athlete when assessing SLS performance. Furthermore, tailored training programs by age may help to address faulty areas, like single-leg stability, and improve overall functional performance.

Objective  The objective of this study was to determine the time to hematologic recovery and the incidence of secondary sepsis and mortality among neutropenic infants treated or not treated with granulocyte colony-stimulating factor (G-CSF). Study Design  We identified all neutropenic infants discharged from 348 neonatal intensive care units from 1997 to 2012. Neutropenia was defined as an absolute neutrophil count ≤ 1,500/µL for ≥ 1 day during the first 120 days of life. Incidence of secondary sepsis and mortality and number of days required to reach an absolute neutrophil count > 1,500/µL for infants exposed to G-CSF were compared with those of unexposed infants. Results  We identified 30,705 neutropenic infants, including 2,142 infants (7%) treated with G-CSF. Treated infants had a shorter adjusted time to hematologic recovery (hazard ratio: 1.36, 95% confidence interval [CI]: 1.30-1.44) and higher adjusted odds of secondary sepsis (odds ratio [OR]: 1.50, 95% CI: 1.20-1.87), death (OR: 1.33, 95% CI: 1.05-1.68), and the combined outcome of sepsis or death (OR: 1.41, 95% CI: 1.19-1.67) at day 14 compared with untreated infants. These differences persisted at day 28. Conclusion  G-CSF treatment decreased the time to hematologic recovery but was associated with increased odds of secondary sepsis and mortality in neutropenic infants. G-CSF should not routinely be used for infants with neutropenia., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Hands play a critical role in the transmission of microbiota on one's own body, between individuals, and on environmental surfaces. Effectively measuring the composition of the hand microbiome is important to hand hygiene science, which has implications for human health. Hand hygiene products are evaluated using standard culture-based methods, but standard test methods for culture-independent microbiome characterization are lacking. We sampled the hands of 50 participants using swab-based and glove-based methods prior to and following four hand hygiene treatments (using a nonantimicrobial hand wash, alcohol-based hand sanitizer [ABHS], a 70% ethanol solution, or tap water). We compared results among culture plate counts, 16S rRNA gene sequencing of DNA extracted directly from hands, and sequencing of DNA extracted from culture plates. Glove-based sampling yielded higher numbers of unique operational taxonomic units (OTUs) but had less diversity in bacterial community composition than swab-based sampling. We detected treatment-induced changes in diversity only by using swab-based samples ( P < 0.001); we were unable to detect changes with glove-based samples. Bacterial cell counts significantly decreased with use of the ABHS ( P < 0.05) and ethanol control ( P < 0.05). Skin hydration at baseline correlated with bacterial abundances, bacterial community composition, pH, and redness across subjects. The importance of the method choice was substantial. These findings are important to ensure improvement of hand hygiene industry methods and for future hand microbiome studies. On the basis of our results and previously published studies, we propose recommendations for best practices in hand microbiome research. IMPORTANCE The hand microbiome is a critical area of research for diverse fields, such as public health and forensics. The suitability of culture-independent methods for assessing effects of hygiene products on microbiota has not been demonstrated. This is the first controlled laboratory clinical hand study to have compared traditional hand hygiene test methods with newer culture-independent characterization methods typically used by skin microbiologists. This study resulted in recommendations for hand hygiene product testing, development of methods, and future hand skin microbiome research. It also demonstrated the importance of inclusion of skin physiological metadata in skin microbiome research, which is atypical for skin microbiome studies., (Copyright © 2017 Zapka et al.)

Previous studies have indicated that presynaptic α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors (AMPARs) contribute to the regulation of neurotransmitter release. In hippocampal synapses, the presynaptic surface expression of several AMPAR subunits, including GluA2, is regulated in a ligand-dependent manner. However, the molecular mechanisms underlying the presynaptic trafficking of AMPARs are still unknown. Here, using bright-field immunocytochemistry, western blots, and quantitative immunogold electron microscopy of the hippocampal CA1 area from intact adult rat brain, we demonstrate the association of AMPA receptors with the presynaptic active zone and with small presynaptic vesicles, in Schaffer collateral synapses in CA1 of the hippocampus. Furthermore, we show that GluA2 and protein interacting with C kinase 1 (PICK1) are colocalized at presynaptic vesicles. Similar to postsynaptic mechanisms, overexpression of either PICK1 or pep2m, which inhibit the N-ethylmaleimide sensitive fusion protein (NSF)-GluA2 interaction, decreases the concentration of GluA2 in the presynaptic active zone membrane. These data suggest that the interacting proteins PICK1 and NSF act as regulators of presynaptic GluA2-containing AMPAR trafficking between the active zone and a vesicle pool that may provide the basis of presynaptic components of synaptic plasticity., (Copyright © 2017 IBRO. All rights reserved.)

Aims: The goal of this study was to explore various models for describing viral persistence (infectivity) on fomites and identify the best fit models., Methods and Results: The persistence of poliovirus over time was studied on three different fomite materials: steel, cotton and plastic. Known concentrations of poliovirus type 1 were applied to the surface coupons in an indoor environment for various lengths of time. Viruses were recovered from the surfaces by vortexing in phosphate buffer. Seven different mathematical models of relative persistence over time were fit to the data, and the preferred model for each surface was selected based on the Bayesian information criterion., Conclusions: While the preferred model varied by fomite type, the virus showed a rapid initial decay on all of the fomite types, followed by a transition to a more gradual decay after about 4-8 days. Estimates of the time for 99% reduction ranged from 81 h for plastic to 143 h for cotton. A 6 log reduction of recoverable infectivity of poliovirus did not occur during the 3-week duration of the experiment for any of the fomites., Significance and Impact of the Study: In protected indoor environments poliovirus can remain infective for weeks. The models identified by this study can be used in risk assessments to identify appropriate strategies for managing this risk., (© 2016 The Society for Applied Microbiology.)