Changes in the number of new takeaway food outlets associated with adoption of management zones around schools: A natural experimental evaluation in England

© 2024 The Author(s). Published by Elsevier Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/By the end of 2017, 35 local authorities (LAs) across England had adopted takeaway management zones (or “exclusion zones”) around schools as a means to curb proliferation of new takeaways. In this nationwide, natural experimental study, we evaluated the impact of management zones on takeaway retail, including unintended displacement of takeaways to areas immediately beyond management zones, and impacts on chain fast-food outlets. We used uncontrolled interrupted time series analyses to estimate changes from up to six years pre- and post-adoption of takeaway management zones around schools. We evaluated three outcomes: mean number of new takeaways within management zones (and by three identified sub-types: full management, town centre exempt and time management zones); mean number on the periphery of management zones (i.e. within an additional 100 m of the edge of zones); and presence of new chain fast-food outlets within management zones. For 26 LAs, we observed an overall decrease in the number of new takeaways opening within management zones. Six years post-intervention, we observed 0.83 (95% CI -0.30, −1.03) fewer new outlets opening per LA than would have been expected in absence of the intervention, equivalent to an 81.0% (95% CI -29.1, −100) reduction in the number of new outlets. Cumulatively, 12 (54%) fewer new takeaways opened than would have been expected over the six-year post-intervention period. When stratified by policy type, effects were most prominent for full management zones and town centre exempt zones. Estimates of intervention effects on numbers of new takeaways on the periphery of management zones, and on the presence of new chain fast-food outlets within management zones, did not meet statistical significance. Our findings suggest that management zone policies were able to demonstrably curb the proliferation of new takeaways. Modelling studies are required to measure the possible population health impacts associated with this change.Peer reviewe

JAK inhibition in Aicardi-Goutières syndrome: a monocentric multidisciplinary real-world approach study

International audienceThe paradigm type I interferonopathy Aicardi-Goutières syndrome (AGS) is most typically characterized by severe neurological involvement. AGS is considered an immune-mediated disease, poorly responsive to conventional immunosuppression. Premised on a chronic enhancement of type I interferon signaling, JAK1/2 inhibition has been trialed in AGS, with clear improvements in cutaneous and systemic disease manifestations. Contrastingly, treatment efficacy at the level of the neurological system has been less conclusive. Here, we report our real-word approach study of JAK1/2 inhibition in 11 patients with AGS, providing extensive assessments of clinical and radiological status; interferon signaling, including in cerebrospinal fluid (CSF); and drug concentrations in blood and CSF. Over a median follow-up of 17 months, we observed a clear benefit of JAK1/2 inhibition on certain systemic features of AGS, and reproduced results reported using the AGS neurologic severity scale. In contrast, there was no change in other scales assessing neurological status; using the caregiver scale, only patient comfort, but no other domain of everyday-life care, was improved. Serious bacterial infections occurred in 4 out of the 11 patients. Overall, our data lead us to conclude that other approaches to treatment are urgently required for the neurologic features of AGS. We suggest that earlier diagnosis and adequate central nervous system penetration likely remain the major factors determining the efficacy of therapy in preventing irreversible brain damage, implying the importance of early and rapid genetic testing and the consideration of intrathecal drug delivery

Overcoming the barriers of teaching physical examination at the bedside: More than just curriculum design

Background: Physicians in training must achieve a high degree of proficiency in performing physical examinations and must strive to become experts in the field. Concerns are emerging about physicians' abilities to perform these basic skills, essential for clinical decision making. Learning at the bedside has the potential to support skill acquisition through deliberate practice. Previous skills improvement programs, targeted at teaching physical examinations, have been successful at increasing the frequency of performing and teaching physical examinations. It remains unclear what barriers might persist after such program implementation. This study explores residents' and physicians' perceptions of physical examinations teaching at the bedside following the implementation of a new structured bedside curriculum: What are the potentially persisting barriers and proposed solutions for improvement? Methods: The study used a constructivist approach using a qualitative inductive thematic analysis that was oriented to construct an understanding of the barriers and facilitators of physical examination teaching in the context of a new bedside curriculum. Participants took part in individual interviews and subsequently focus groups. Transcripts were coded and themes were identified. Results: Data analyses yielded three main themes: (1) the culture of teaching physical examination at the bedside is shaped and threatened by the lack of hospital support, physicians' motivation and expertise, residents' attitudes and dependence on technology, (2) the hospital environment makes bedside teaching difficult because of its chaotic nature, time constraints and conflicting responsibilities, and finally (3) structured physical examination curricula create missed opportunities in being restrictive and pose difficulties in identifying patients with findings. Conclusions: Despite the implementation of a structured bedside curriculum for physical examination teaching, our study suggests that cultural, environmental and curriculum-related barriers remain important issues to be addressed. Institutions wishing to develop and implement similar bedside curricula should prioritize recruitment of expert clinical teachers, recognizing their time and efforts. Teaching should be delivered in a protected environment, away from clinical duties, and with patients with real findings. Physicians must value teaching and learning of physical examination skills, with multiple hands-on opportunities for direct role modeling, coaching, observation and deliberate practice. Ideally, clinical teachers should master the art of combining both patient care and educational activities

Rheumatoid arthritis - treatment: 180. Utility of Body Weight Classified Low-Dose Leflunomide in Japanese Rheumatoid Arthritis

Background: In Japan, more than 20 rheumatoid arthritis (RA) patients died of interstitial pneumonia (IP) caused by leflunomide (LEF) were reported, but many of them were considered as the victims of opportunistic infection currently. In this paper, efficacy and safety of low-dose LEF classified by body weight (BW) were studied. Methods: Fifty-nine RA patients were started to administrate LEF from July 2007 to July 2009. Among them, 25 patients were excluded because of the combination with tacrolimus, and medication modification within 3 months before LEF. Remaining 34 RA patients administered 20 to 50 mg/week of LEF were followed up for 1 year and enrolled in this study. Dose of LEF was classified by BW (50 mg/week for over 50 kg, 40 mg/week for 40 to 50 kg and 20 to 30 mg/week for under 40 kg). The average age and RA duration of enrolled patients were 55.5 years old and 10.2 years. Prednisolone (PSL), methotrexate (MTX) and etanercept were used in 23, 28 and 2 patients, respectively. In case of insufficient response or adverse effect, dosage change or discontinuance of LEF were considered. Failure was defined as dosages up of PSL and MTX, or dosages down or discontinuance of LEF. Last observation carried forward method was used for the evaluation of failed patients at 1 year. Results: At 1 year after LEF start, good/ moderate/ no response assessed by the European League Against Rheumatism (EULAR) response criteria using Disease Activity Score, including a 28-joint count (DAS28)-C reactive protein (CRP) were showed in 14/ 10/ 10 patients, respectively. The dosage changes of LEF at 1 year were dosage up: 10, same dosage: 5, dosage down: 8 and discontinuance: 11 patients. The survival rate of patients in this study was 23.5% (24 patients failed) but actual LEF continuous rate was 67.6% (11 patients discontinued) at 1 year. The major reason of failure was liver dysfunction, and pneumocystis pneumonia was occurred in 1 patient resulted in full recovery. One patient died of sepsis caused by decubitus ulcer infection. DAS28-CRP score was decreased from 3.9 to 2.7 significantly. Although CRP was decreased from 1.50 to 0.93 mg/dl, it wasn't significant. Matrix metalloproteinase (MMP)-3 was decreased from 220.0 to 174.2 ng/ml significantly. Glutamate pyruvate transaminase (GPT) was increased from 19 to 35 U/l and number of leukocyte was decreased from 7832 to 6271 significantly. DAS28-CRP, CRP, and MMP-3 were improved significantly with MTX, although they weren't without MTX. Increase of GPT and leukopenia were seen significantly with MTX, although they weren't without MTX. Conclusions: It was reported that the risks of IP caused by LEF in Japanese RA patients were past IP history, loading dose administration and low BW. Addition of low-dose LEF is a potent safe alternative for the patients showing unsatisfactory response to current medicines, but need to pay attention for liver function and infection caused by leukopenia, especially with MTX. Disclosure statement: The authors have declared no conflicts of interes

Bone Marrow Transplant

Mucopolysaccharidosis type I-H (MPS I-H) is a rare lysosomal storage disorder caused by α-L-Iduronidase deficiency. Early haematopoietic stem cell transplantation (HSCT) is the sole available therapeutic option to preserve neurocognitive functions. We report long-term follow-up (median 9 years, interquartile range 8-16.5) for 51 MPS I-H patients who underwent HSCT between 1986 and 2018 in France. 4 patients died from complications of HSCT and one from disease progression. Complete chimerism and normal α-L-Iduronidase activity were obtained in 84% and 71% of patients respectively. No difference of outcomes was observed between bone marrow and cord blood stem cell sources. All patients acquired independent walking and 91% and 78% acquired intelligible language or reading and writing. Intelligence Quotient evaluation (n = 23) showed that 69% had IQ ≥ 70 at last follow-up. 58% of patients had normal or remedial schooling and 62% of the 13 adults had good socio-professional insertion. Skeletal dysplasia as well as vision and hearing impairments progressed despite HSCT, with significant disability. These results provide a long-term assessment of HSCT efficacy in MPS I-H and could be useful in the evaluation of novel promising treatments such as gene therapy

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes

Tephrochronology and its application: A review

Tephrochronology (from tephra, Gk ‘ashes’) is a unique stratigraphic method for linking, dating, and synchronizing geological, palaeoenvironmental, or archaeological sequences or events. As well as utilising the Law of Superposition, tephrochronology in practise requires tephra deposits to be characterized (or ‘fingerprinted’) using physical properties evident in the field together with those obtained from laboratory analyses. Such analyses include mineralogical examination (petrography) or geochemical analysis of glass shards or crystals using an electron microprobe or other analytical tools including laser-ablation-based mass spectrometry or the ion microprobe. The palaeoenvironmental or archaeological context in which a tephra occurs may also be useful for correlational purposes. Tephrochronology provides greatest utility when a numerical age obtained for a tephra or cryptotephra is transferrable from one site to another using stratigraphy and by comparing and matching inherent compositional features of the deposits with a high degree of likelihood. Used this way, tephrochronology is an age-equivalent dating method that provides an exceptionally precise volcanic-event stratigraphy. Such age transfers are valid because the primary tephra deposits from an eruption essentially have the same short-lived age everywhere they occur, forming isochrons very soon after the eruption (normally within a year). As well as providing isochrons for palaeoenvironmental and archaeological reconstructions, tephras through their geochemical analysis allow insight into volcanic and magmatic processes, and provide a comprehensive record of explosive volcanism and recurrence rates in the Quaternary (or earlier) that can be used to establish time-space relationships of relevance to volcanic hazard analysis. The basis and application of tephrochronology as a central stratigraphic and geochronological tool for Quaternary studies are presented and discussed in this review. Topics covered include principles of tephrochronology, defining isochrons, tephra nomenclature, mapping and correlating tephras from proximal to distal locations at metre- through to sub-millimetre-scale, cryptotephras, mineralogical and geochemical fingerprinting methods, numerical and statistical correlation techniques, and developments and applications in dating including the use of flexible depositional age-modelling techniques based on Bayesian statistics. Along with reference to wide-ranging examples and the identification of important recent advances in tephrochronology, such as the development of new geoanalytical approaches that enable individual small glass shards to be analysed near-routinely for major, trace, and rare-earth elements, potential problems such as miscorrelation, erroneous-age transfer, and tephra reworking and taphonomy (especially relating to cryptotephras) are also examined. Some of the challenges for future tephrochronological studies include refining geochemical analytical methods further, improving understanding of cryptotephra distribution and preservation patterns, improving age modelling including via new or enhanced radiometric or incremental techniques and Bayesian-derived models, evaluating and quantifying uncertainty in tephrochronology to a greater degree than at present, constructing comprehensive regional databases, and integrating tephrochronology with spatially referenced environmental and archaeometric data into 3-D reconstructions using GIS and geostatistics

Large-scale sequencing identifies multiple genes and rare variants associated with Crohn’s disease susceptibility

peer reviewe