Successful stopping of biologic therapy for remission in children and young people with juvenile idiopathic arthritis.

OBJECTIVES: Clinicians concerned about long-term safety of biologics in JIA may consider tapering or stopping treatment once remission is achieved despite uncertainty in maintaining drug-free remission. This analysis aims to (i) calculate how many patients with JIA stop biologics for remission, (ii) calculate how many later re-start therapy and after how long, and (iii) identify factors associated with re-starting biologics. METHODS: Patients starting biologics between 1 January 2010 and 7 September 2021 in the UK JIA Biologics Register were included. Patients stopping biologics for physician-reported remission, those re-starting biologics and factors associated with re-starting, were identified. Multiple imputation accounted for missing data. RESULTS: Of 1451 patients with median follow-up of 2.7 years (IQR 1.4, 4.0), 269 (19%) stopped biologics for remission after a median of 2.2 years (IQR 1.7, 3.0). Of those with follow-up data (N = 220), 118 (54%) later re-started therapy after a median of 4.7 months, with 84% re-starting the same biologic. Patients on any-line tocilizumab (prior to stopping) were less likely to re-start biologics (vs etanercept; odds ratio [OR] 0.3; 95% CI: 0.2, 0.7), while those with a longer disease duration prior to biologics (OR 1.1 per year increase; 95% CI: 1.0, 1.2) or prior uveitis were more likely to re-start biologics (OR 2.5; 95% CI: 1.3, 4.9). CONCLUSIONS: This analysis identified factors associated with successful cessation of biologics for remission in JIA as absence of uveitis, prior treatment with tocilizumab and starting biologics earlier in the disease course. Further research is needed to guide clinical recommendations.

CAPTURE-JIA: a consensus-derived core dataset to improve clinical care for children and young people with juvenile idiopathic arthritis.

OBJECTIVES: Data collected during routine clinic visits are key to driving successful quality improvement in clinical services and enabling integration of research into routine care. The purpose of this study was to develop a standardized core dataset for juvenile idiopathic arthritis (JIA) (termed CAPTURE-JIA), enabling routine clinical collection of research-quality patient data useful to all relevant stakeholder groups (clinicians, service-providers, researchers, health service planners and patients/families) and including outcomes of relevance to patients/families. METHODS: Collaborative consensus-based approaches (including Delphi and World Café methodologies) were employed. The study was divided into discrete phases, including collaborative working with other groups developing relevant core datasets and a two-stage Delphi process, with the aim of rationalizing the initially long data item list to a clinically feasible size. RESULTS: The initial stage of the process identified collection of 297 discrete data items by one or more of fifteen NHS paediatric rheumatology centres. Following the two-stage Delphi process, culminating in a consensus workshop (May 2015), the final approved CAPTURE-JIA dataset consists of 62 discrete and defined clinical data items including novel JIA-specific patient-reported outcome and experience measures. CONCLUSIONS: CAPTURE-JIA is the first 'JIA core dataset' to include data items considered essential by key stakeholder groups engaged with leading and improving the clinical care of children and young people with JIA. Collecting essential patient information in a standard way is a major step towards improving the quality and consistency of clinical services, facilitating collaborative and effective working, benchmarking clinical services against quality indicators and aligning treatment strategies and clinical research opportunities.

Development of a national audit tool for juvenile idiopathic arthritis: a BSPAR project funded by the Health Care Quality Improvement Partnership.

Objective: Timely access to holistic multidisciplinary care is the core principle underpinning management of juvenile idiopathic arthritis (JIA). Data collected in national clinical audit programmes fundamentally aim to improve health outcomes of disease, ensuring clinical care is equitable, safe and patient-centred. The aim of this study was to develop a tool for national audit of JIA in the UK. Methods: A staged and consultative methodology was used across a broad group of relevant stakeholders to develop a national audit tool, with reference to pre-existing standards of care for JIA. The tool comprises key service delivery quality measures assessed against two aspects of impact, namely disease-related outcome measures and patient/carer reported outcome and experience measures. Results: Eleven service-related quality measures were identified, including those that map to current standards for commissioning of JIA clinical services in the UK. The three-variable Juvenile Arthritis Disease Activity Score and presence/absence of sacro-iliitis in patients with enthesitis-related arthritis were identified as the primary disease-related outcome measures, with presence/absence of uveitis a secondary outcome. Novel patient/carer reported outcomes and patient/carer reported experience measures were developed and face validity confirmed by relevant patient/carer groups. Conclusion: A tool for national audit of JIA has been developed with the aim of benchmarking current clinical practice and setting future standards and targets for improvement. Staged implementation of this national audit tool should facilitate investigation of variability in levels of care and drive quality improvement. This will require engagement from patients and carers, clinical teams and commissioners of JIA services.

The contribution of motor vehicle emissions to ambient fine particulate matter public health impacts in New York City: a health burden assessment.

BACKGROUND: On-road vehicles are an important source of fine particulate matter (PM2.5) in cities, but spatially varying traffic emissions and vulnerable populations make it difficult to assess impacts to inform policy and the public. METHODS: We estimated PM2.5-attributable mortality and morbidity from on-road vehicle generated air pollution in the New York City (NYC) region using high-spatial-resolution emissions estimates, air quality modeling, and local health incidence data to evaluate variations in impacts by vehicle class, neighborhood, and area socioeconomic status. We developed multiple 'zero-out' emission scenarios focused on regional and local cars, trucks, and buses in the NYC region. We simulated PM2.5 concentrations using the Community Multi-scale Air Quality Model at a 1-km spatial resolution over NYC and combined modeled estimates with monitored data from 2010 to 2012. We applied health impact functions and local health data to quantify the PM2.5-attributable health burden on NYC residents within 42 city neighborhoods. RESULTS: We estimate that all on-road mobile sources in the NYC region contribute to 320 (95 % Confidence Interval (CI): 220-420) deaths and 870 (95 % CI: 440-1280) hospitalizations and emergency department visits annually within NYC due to PM2.5 exposures, accounting for 5850 (95 % CI: 4020-7620) years of life lost. Trucks and buses within NYC accounted for the largest share of on-road mobile-attributable ambient PM2.5, contributing up to 14.9 % of annual average levels across 1-km grid cells, and were associated with 170 (95 % CI: 110-220) PM2.5-attributable deaths each year. These contributions were not evenly distributed, with high poverty neighborhoods experiencing a larger share of the exposure and health burden than low poverty neighborhoods. CONCLUSION: Reducing motor vehicle emissions, especially from trucks and buses, could produce significant health benefits and reduce disparities in impacts. Our high-spatial-resolution modeling approach could improve assessment of on-road vehicle health impacts in other cities.

The public health benefits of reducing fine particulate matter through conversion to cleaner heating fuels in New York City.

In recent years, both New York State and City issued regulations to reduce emissions from burning heating oil. To assess the benefits of these programs in New York City, where the density of emissions and vulnerable populations vary greatly, we simulated the air quality benefits of scenarios reflecting no action, partial, and complete phase-out of high-sulfur heating fuels using the Community MultiScale Air Quality (CMAQ) model conducted at a high spatial resolution (1 km). We evaluated the premature mortality and morbidity benefits of the scenarios within 42 city neighborhoods and computed benefits by neighborhood poverty status. The complete phase-out scenario reduces annual average fine particulate matter (PM2.5) by an estimated 0.71 µg/m(3) city-wide (average of 1 km estimates, 10-90th percentile: 0.1-1.6 µg/m(3)), avoiding an estimated 290 premature deaths, 180 hospital admissions for respiratory and cardiovascular disease, and 550 emergency department visits for asthma each year. The largest improvements were seen in areas of highest building and population density and the majority of benefits have occurred through the partial phase out of high-sulfur heating fuel already achieved. While emissions reductions were greatest in low-poverty neighborhoods, health benefits are estimated to be greatest in high-poverty neighborhoods due to higher baseline morbidity and mortality rates.

Outcomes after anti-tumour necrosis factor originator to biosimilar switching in children and young people with juvenile idiopathic arthritis in the UK: a national cohort study.

BACKGROUND: For cost-saving purposes, children and young people with juvenile idiopathic arthritis (JIA) are being switched (for non-medical reasons) from biological originators to biosimilars. Here, we aimed to investigate those who switched from an anti-tumour necrosis factor (TNF) originator to a biosimilar, regarding drug survival and disease activity, compared with a matched cohort who continued the originator. METHODS: This analysis included all patients in the UK JIA Biologics Register switching directly from an anti-TNF originator to a biosimilar of the same product. All patients were matched (age, sex, disease duration, calendar year of when patients started originator therapy, line of therapy, and International League of Associations for Rheumatology [ILAR] category) to patients continuing the originator. For those matched successfully, a Cox proportional hazard model assessed whether drug persistence differed between those who switched compared with those who continued the originator. Overall change in the 71-joint juvenile arthritis disease activity score and the proportion of patients with a clinically important worsening score (by ≥1·7 units) after 6 months was compared between cohorts. This analysis was designed to address a priority research area set by our patient partners. FINDINGS: There were 224 children and young people with non-systemic JIA (139 [62%] were female, and 85 [38%] were male) identified as switching from a biological originator to a biosimilar of the same product from Jan 1, 2017, to July 7, 2023. 143 (64%) patients were originally on adalimumab, 56 (25%) on etanercept, and 25 (11%) on infliximab. Of these, 164 patients were matched successfully to those continuing the originator. There was no evidence that patients switching were more likely to stop treatment compared with those continuing the originator, with a hazard ratio of 1·46 (95% CI 0·93-2·30). Of the 51 patients in the biosimilar group who stopped treatment, 18 (35%) switched back to the originator (14 in the first year), 28 (55%) started a different biological drug, and five (10%) discontinued all treatment by the last follow-up. Of the 87 matched patients with available disease activity, there was no evidence that JADAS-71 worsened more after 6 months, with an odds ratio of 0·71 (95% CI 0·34-1·51; p=0·38). INTERPRETATION: In this matched comparative effectiveness analysis, children and young people with JIA switched from originators to biosimilars. Disease activity was similar between patients switching compared with those continuing the originator. Three quarters of patients were still receiving their biosimilar after 1 year, with switching back to originator uncommon, at only 9% after 1 year, suggesting good tolerability of non-medical switching in this patient population. This information is reassuring to clinicians and patients regarding the effect of non-medical biological switching. FUNDING: British Society for Rheumatology, Versus Arthritis, and National Institutes for Health Research Manchester Biomedical Research Centre.

'Candidatus Phytoplasma pruni', a novel taxon associated with X-disease of stone fruits, Prunus spp.: multilocus characterization based on 16S rRNA, secY, and ribosomal protein genes.

X-disease is one of the most serious diseases known in peach (Prunus persica). Based on RFLP analysis of 16S rRNA gene sequences, peach X-disease phytoplasma strains from eastern and western United States and eastern Canada were classified in 16S rRNA gene RFLP group 16SrIII, subgroup A. Phylogenetic analyses of 16S rRNA gene sequences revealed that the X-disease phytoplasma strains formed a distinct subclade within the phytoplasma clade, supporting the hypothesis that they represented a lineage distinct from those of previously described 'Candidatus Phytoplasma' species. Nucleotide sequence alignments revealed that all studied X-disease phytoplasma strains shared less than 97.5 % 16S rRNA gene sequence similarity with previously described 'Candidatus Phytoplasma' species. Based on unique properties of the DNA, we propose recognition of X-disease phytoplasma strain PX11CT1(R) as representative of a novel taxon, 'Candidatus Phytoplasma pruni'. Results from nucleotide and phylogenetic analyses of secY and ribosomal protein (rp) gene sequences provided additional molecular markers of the 'Ca. Phytoplasma pruni' lineage. We propose that the term 'Ca. Phytoplasma pruni' be applied to phytoplasma strains whose 16S rRNA gene sequences contain the oligonucleotide sequences of unique regions that are designated in the formally published description of the taxon. Such strains include X-disease phytoplasma and--within the tolerance of a single base difference in one unique sequence--peach rosette, peach red suture, and little peach phytoplasmas. Although not employed for taxon delineation in this work, we further propose that secY, rp, and other genetic loci from the reference strain of a taxon, and where possible oligonucleotide sequences of unique regions of those genes that distinguish taxa within a given 16Sr group, be incorporated in emended descriptions and as part of future descriptions of 'Candidatus Phytoplasma' taxa.

Series: Concepts in end-of-life care: palliative care medicine.

The goals of palliative care are to provide the best quality of life for the patient and family at a critical time in the patient's life. Ethical principles of patient autonomy, beneficence, and justice are very important at this time. Good communication is paramount in respecting patients' values and preferences. Appropriate surrogates, as directed by the patient, should be included in discussions and decisions. Physical, social, emotional, and spiritual suffering must be addressed.

Report of the AMA Council on Ethical and Judicial Affairs: professionalism in the use of social media.

Although many physicians have been using the internet for both clinical and social purposes for years, recently concerns have been raised regarding blurred boundaries of the profession as a whole. In both the news media and medical literature, physicians have noted there are unanswered questions in these areas, and that professional self-regulation is needed. This report discusses the ethical implications of physicians' nonclinical use of the internet, including the use of social networking sites, blogs, and other means to post content online. It does not address the clinical use of the internet, such as telemedicine, e-prescribing, online clinical consultations, health-related websites, use of electronic media for clinical collaboration, and e-mailing patients (some of which are already covered in the AMA's Code of Medical Ethics).

Bone mineral density loss during adjuvant chemotherapy in pre-menopausal women with early breast cancer: is it dependent on oestrogen deficiency?

Pre-menopausal women given adjuvant chemotherapy for breast cancer experience both premature ovarian failure and loss of bone mineral density (BMD), and this study was designed to see if these observations are causally linked. Chemotherapy was administered to 41 pre-menopausal women with early breast cancer enrolled prospectively in a study of ovarian function and BMD in such women given systemic therapy. After giving written informed consent, all patients underwent baseline and regular on-treatment measurements of BMD by dual-energy X-ray absorptiometry (DXA) scan, bone turnover and ovarian function by analysis of serum hormone levels and self-reported menstrual diaries. Baseline lumbar spine BMD in the 41 women given chemotherapy was higher than the normal population (Z score 0.28 ± 0.14 (mean ± SEM), P = 0.047), and fell significantly over the first 6 months from a mean of 1.05-1.01 g/m(2), P < 0.0001, and similar but smaller changes were demonstrated in hip BMD. This fall was independent of age at diagnosis, type of chemotherapy, development of amenorrhoea or either baseline or on-treatment estradiol concentration. During the 6 months after completion of adjuvant chemotherapy, BMD fell further only in those women with low estradiol or experiencing amenorrhoea during the first 6 months, although all groups showed evidence of increased bone turnover. This study demonstrates loss of both spine and hip BMD in pre-menopausal women during 6 months' adjuvant systemic chemotherapy to be independent of changes in ovarian function. Ovarian function was, however, related to BMD changes after chemotherapy ceased.

A physician's role following a breach of electronic health information.

The Council on Ethical and Judicial Affairs of the American Medical Association examines physicians' professional ethical responsibility in the event that the security of patients' electronic records is breached.

Medical errors and the trainee: ethical concerns.

How medical errors are handled by individual physicians and hospital systems is a topic of considerable interest. In teaching hospitals, medical students and house officers often observe and commit mistakes. Commission of a mistake is associated with serious emotional turmoil and uncertainty among trainees as well as experienced physicians. Although disclosure is the ethical standard, the consequences of disclosure are feared by many. This article focuses on the issues that surround medical errors as they pertain to medical students and residents. It is important that this group of future physicians has appropriate training, mentoring, and support when dealing with errors.

Caring for adolescent family members of physician colleagues.

It is recommended that physicians do not care for their family members. However, there are also many concerning issues when physicians care for the family members of their colleagues. This can be particularly challenging when the patient is an adolescent. We present the case of Dr. B who is asked to see the teenage daughter of her colleague Dr. A, and discuss the issues of caring for an adolescent family member of a physician colleague. Patient confidentiality, autonomy, and maintenance of the patient-physician relationship are core principles that must be adhered to in this situation. The roles of the treating physician and the parental physician are discussed.