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Un homme de 22 ans a consulte son medecin de famille pour une douleur intense au pied droit, accompagnee d'une coloration sombre et d'une hypoesthesie. Il avait des antecedents de [...]

A 22-year-old man presented to his family physician with intense pain in, dusky discolouration of and reduced sensation to his right foot. He had a history of migraines and 2 [...]

AbstractExcavations at Hellaby, near Rotherham, on a site immediately to the west of Cumwell Lane, investigated part of a co-axial field system which spanned the late pre-Roman Iron Age through to at least the mid-fourth century AD. Over this period, the focus of associated activity shifted from the north end of the site southwards: to a small corner enclosure in the centre of the site in the early Roman period, and then to a larger corner enclosure further south, in use from the late second century and associated with the processing and storage of cereal crops. The site contributes to the growing corpus of evidence towards the understanding of South Yorkshires so-called ‘brickwork’ fields demonstrating a succession of enclosures migrating across the fields over time.

BACKGROUND: It is not established whether the risk of anaphylaxis induced by peanuts or tree nuts in children increases at specific times of the year. We aimed to evaluate the risk of peanut- and tree-nut-induced anaphylaxis during certain cultural holidays in Canadian children. METHODS: We collected data on confirmed pediatric cases of anaphylaxis presenting to emergency departments in 4 Canadian provinces as part of the Cross-Canada Anaphylaxis Registry. We assessed the mean number of cases per day and incidence rate ratio (IRR) of anaphylaxis induced by unknown nuts, peanuts and tree nuts presenting during each of 6 holidays (Halloween, Christmas, Easter, Diwali, Chinese New Year and Eid al-Adha) versus the rest of the year. We estimated IRRs and 95% confidence intervals (CIs) using Poisson regression. RESULTS: Data were collected for 1390 pediatric cases of anaphylaxis between 2011 and 2020. Their median age was 5.4 years, and 864 (62.2%) of the children were boys. During Halloween and Easter, there were higher rates of anaphylaxis to unknown nuts (IRR 1.66, 95% CI 1.13-2.43 and IRR 1.71, 95% CI 1.21-2.42, respectively) and peanuts (IRR 1.86, 95% CI 1.12-3.11 and IRR 1.57, 95% CI 0.94-2.63, respectively) compared to the rest of the year. No increased risk of peanut- or tree-nut-induced anaphylaxis was observed during Christmas, Diwali, Chinese New Year or Eid al-Adha. Anaphylaxis induced by unknown nuts, peanuts and tree nuts was more likely in children aged 6 years or older than in younger children. INTERPRETATION: We found an increased risk of anaphylaxis induced by unknown nuts and peanuts during Halloween and Easter among Canadian children. Educational tools are needed to increase awareness and vigilance in order to decrease the risk of anaphylaxis induced by peanuts and tree nuts in children during these holidays., In Canada, up to 9% of children have at least 1 food allergy. (1-4) Anaphylaxis--an allergic reaction involving at least 2 organ systems or resulting in hypotension (5)--is the most [...]

AbstractExcavations to the southwest of Methley on a site to the north of the River Calder recorded an Iron Age settlement with possible Bronze Age origins, where a small community inhabited at least three phases of roundhouse within a large polygonal enclosure on the top of a hill overlooking the surrounding landscape. This was followed by Romano-British occupation during the mid to late second century AD and the mid third to early fifth century AD further to the south on the hill slope.

To estimate direct and indirect costs associated with neuropsychiatric (NP) events in the Systemic Lupus International Collaborating Clinics inception cohort. NP events were documented annually using American College of Rheumatology definitions for NP events and attributed to systemic lupus erythematosus (SLE) or non‐SLE causes. Patients were stratified into 1 of 3 NP states (no, resolved, or new/ongoing NP event). Change in NP status was characterized by interstate transition rates using multistate modeling. Annual direct costs and indirect costs were based on health care use and impaired productivity over the preceding year. Annual costs associated with NP states and NP events were calculated by averaging all observations in each state and adjusted through random‐effects regressions. Five‐ and 10‐year costs for NP states were predicted by multiplying adjusted annual costs per state by expected state duration, forecasted using multistate modeling. A total of 1,697 patients (49% White race/ethnicity) were followed for a mean of 9.6 years. NP events (n = 1,971) occurred in 956 patients, 32% attributed to SLE. For SLE and non‐SLE NP events, predicted annual, 5‐, and 10‐year direct costs and indirect costs were higher in new/ongoing versus no events. Direct costs were 1.5‐fold higher and indirect costs 1.3‐fold higher in new/ongoing versus no events. Indirect costs exceeded direct costs 3.0 to 5.2 fold. Among frequent SLE NP events, new/ongoing seizure disorder and cerebrovascular disease accounted for the largest increases in annual direct costs. For non‐SLE NP events, new/ongoing polyneuropathy accounted for the largest increase in annual direct costs, and new/ongoing headache and mood disorder for the largest increases in indirect costs. Patients with new/ongoing SLE or non‐SLE NP events incurred higher direct and indirect costs.

The Systemic Lupus International Collaborating Clinics (SLICC), American College of Rheumatology (ACR), and the Lupus Foundation of America are developing a revised systemic lupus erythematosus (SLE) damage index (the SLICC/ACR Damage Index [SDI]). Shifts in the concept of damage in SLE have occurred with new insights into disease manifestations, diagnostics, and therapy. We evaluated contemporary constructs in SLE damage to inform development of the revised SDI. We conducted a 3‐part qualitative study of international SLE experts. Facilitated small groups evaluated the construct underlying the concept of damage in SLE. A consensus meeting using nominal group technique was conducted to achieve agreement on aspects of the conceptual framework and scope of the revised damage index. The framework was finally reviewed and agreed upon by the entire group. Fifty participants from 13 countries were included. The 8 thematic clusters underlying the construct of SLE damage were purpose, items, weighting, reversibility, impact, time frame, attribution, and perspective. The revised SDI will be a discriminative index to measure morbidity in SLE, independent of activity or impact on the patient, and should be related to mortality. The SDI is primarily intended for research purposes and should take a life‐course approach. Damage can occur before a diagnosis of SLE but should be attributable to SLE. Damage to an organ is irreversible, but the functional consequences on that organ may improve over time through physiological adaptation or treatment. We identified shifts in the paradigm of SLE damage and developed a unifying conceptual framework. These data form the groundwork for the next phases of SDI development.

Anne McLaren DBE was born into a privileged family, which affected her future in two distinct ways. Her cut-glass accent and social confidence were advantageous reminders of this early privilege, but her unrelenting rejection of it was evident in her left-wing egalitarian political and social views and actions. Anne was among the pioneers of research into mammalian development—her experiments on embryonic and fetal development in mice led indirectly to ‘test tube’ babies and contributed to our understanding of the relative roles of soma and germ cells in generating the two sexes. However, it is not only her science for which she will be remembered; her social, educational, ethical and political activities in the cause of science were paramount. She was an articulate, logical and extraordinarily confident speaker, always unrelentingly focused and thoroughly prepared. These qualities made her a formidable member of the Warnock Committee of enquiry, which generated the internationally influential guidelines on how human-assisted reproduction should be regulated. She served for 10 years with distinction on the Human Fertilisation and Embryology Authority, the UK regulatory body that resulted from the Warnock enquiry. She was a founder member, and president, of the Association of Women in Science and Engineering. Her interests extended beyond human welfare to that of animals, and she became involved with conservation and biodiversity preservation programmes internationally. She was elected Foreign Secretary of the Royal Society, the first woman to hold this office in its 332 years.

This study was undertaken to assess the effects of a web‐based program, MyLupusGuide,developed to facilitate self‐management in systemic lupus erythematosus (SLE). In this randomized controlled online study, participants received either immediate access to the MyLupusGuide site or delayed access starting on month 3. The primary outcome was the patient activation measure (PAM) score. Secondary outcomes included measurements of health status, self‐efficacy, coping, perceived patient–physician relationship, and medication adherence. Outcomes were measured at the baseline visit and at the 3‐month and 6‐month follow‐up visits. We used linear mixed modeling to compare PAM scores between the 2 groups at months 3 and 6. There were 541 participants included in this study. The mean ± SE age was 50 ± 14 years; 93% were female and 74% were White. The mean ± SE disease duration was 17 ± 12 years, and 56% visited MyLupusGuide at least once. The baseline mean ± SE PAM score was 61.2 ± 13, with 36% scoring low for perceived self‐management skills. After 3 months of exposure to MyLupusGuide, there were no differences in terms of PAM scores between groups. In exploratory analyses, we found significant improvement in PAM scores in those who had low PAM scores at baseline and in male individuals. We observed significant improvements in self‐efficacy before and after access to MyLupusGuide and delayed improvements at month 6 compared to month 3 in terms of mental health and emotional coping. MyLupusGuide increases self‐efficacy but not patient activation. A total of 56% of participants visited the MyLupusGuide site during the study period. Individuals with lupus need support to become activated toward self‐management behaviors.

ObjectiveTo understand how people with chronic immune-mediated inflammatory diseases (IMIDs) trade off the benefits and risks of coronavirus disease 2019 (COVID-19) vaccine options.MethodsWe conducted an online discrete-choice experiment in people with IMIDs to quantify the relative importance (RI) of attributes relevant to COVID-19 vaccination. Participants were recruited between May and August 2021 through patient groups and clinics in Canada, and completed 10 choices where they selected 1 of 2 hypothetical vaccine options or no vaccine. The RI of each attribute was estimated and heterogeneity was explored through latent class analysis.ResultsThe survey was completed by 551 people (89% female, mean age 46 yrs) with a range of IMIDs (inflammatory bowel disease [48%], rheumatoid arthritis [38%], systemic lupus erythematosus [16%]). Most had received 1 (94%) or 2 (64%) COVID-19 vaccinations. Across the ranges of levels considered, vaccine effectiveness was most important (RI = 66%), followed by disease flare (21%), rare but serious risks (9%), and number/timing of injections (4%). Patients would accept a risk of disease flare requiring a treatment change of ≤ 8.8% for a vaccine with a small absolute increase in effectiveness (10%). Of the 3 latent classes, the group with the greatest aversion to disease flare were more likely to be male and have lower incomes, but this group still valued effectiveness higher than other attributes.ConclusionPatients perceived the benefits of COVID-19 vaccination to outweigh rare serious risks and disease flare. This supports COVID-19 vaccine strategies that maximize effectiveness, while recognizing the heterogeneity in preferences that exists.

Prompt epinephrine autoinjector (EAI) use is the primary treatment for anaphylaxis. However, limited Canadian data exist on the impact of reaction location on EAI use for food-induced anaphylaxis (FIA).

Food allergies, particularly peanut, represent the predominant cause of anaphylaxis. Whereas early allergen introduction has emerged as a potential preventive strategy, the precise impact of recent guidelines on peanut-induced anaphylaxis rates in Canada remains unclear.

Data are sparse regarding tree nut-induced anaphylaxis (TNA).

Rhode Island is leading the way in intermodal transportation. Aided by a number of strong partnerships, the Rhode Island Department of Transportation (RIDOT) and the Rhode Island Airport Corporation (RIAC) [...]

Hydroxychloroquine (HCQ) is a key systemic lupus erythematosus (SLE) drug, making concerns of drug shortages grave. Our objective was to evaluate factors associated with poor outcomes after HCQ taper or discontinuation in SLE. We studied 5 Canadian SLE cohorts between 1999 and 2019, following patients from the date of HCQ tapering (cohort 1) or discontinuation (cohort 2). A composite outcome was defined as any of the following: a need for therapy augmentation, an increase (of at least 4 points) in the Systemic Lupus Erythematosus Disease Activity Index 2000 score, or hospitalization for SLE. In each cohort, multivariable Cox regression was used to identify demographic and clinical factors associated with time to the earliest of these events. A third cohort continuing to receive HCQ was also studied, to assess whether the same factors influenced the outcome even when the HCQ dose was unchanged. The poor outcome rate, per 100 person‐years, was 35.7 (95% confidence interval [95% CI] 31.6–40.3) in the HCQ taper cohort (n = 398), 29.0 (95% CI 25.5–33.0) in the discontinuation cohort (n = 395), and 16.1 (95% CI 13.2–19.6) in the maintenance cohort (n = 395). In patients tapering HCQ, baseline prednisone use was independently associated with greater risk of poor outcomes. In the discontinuation cohort, the risk of poor outcomes was greater for Black patients and those diagnosed with SLE at age ≤25 years. Among those maintaining HCQ, baseline immunosuppressive use and First Nations ethnicity were associated with poor outcomes. We identified demographic and clinical factors associated with poor outcomes after HCQ taper/discontinuation. This information is critical in the current setting of potential shortages, but over the long term, such information could inform personalized therapies.

Systemic lupus erythematosus is a chronic autoimmune disease with varied and unpredictable levels of disease activity. The ability to self‐manage lupus is important in controlling disease activity. Our objective was to determine levels of patient activation toward self‐management in lupus. We used baseline results from the MyLupusGuide study, which had recruited 541 lupus patients from 10 lupus centers. We used the Patient Activation Measure (PAM), a validated self‐reported tool designed to measure activation toward self‐management ability, as our primary variable and examined its association with demographic, disease‐related, patient–provider communication and psychosocial variables captured in our study protocol. Univariable and multivariable linear regressions were performed using linear mixed models, with a random effect for centers. The mean ± SD age of participants was 50 ± 14 years, 93% were female, 74% were White, and the mean ± SD disease duration was 17 ± 12 years. The mean ± SD PAM score was 61.2 ± 13.5, with 36% of participants scoring in the 2 lower levels, indicating low activation. Variables associated with low activation included being single, having lower physical health status, lower self‐reported disease activity, lower self‐efficacy, use of more emotional coping and fewer distraction and instrumental coping strategies, and a perceived lack of clarity in patient–doctor communication. Low patient activation was observed in more than one‐third of lupus patients, indicating that a large proportion of patients perceived that they are lacking in lupus self‐management skills. These results highlight a modifiable gap in perceived self‐management ability among patients with lupus.

The Systemic Lupus International Collaborating Clinics (SLICC) frailty index (FI) predicts mortality and damage accrual in systemic lupus erythematosus (SLE), but its association with hospitalizations has not been described. Our objective was to estimate the association of baseline SLICC‐FI values with future hospitalizations in the SLICC inception cohort. Baseline SLICC‐FI scores were calculated. The number and duration of inpatient hospitalizations during follow‐up were recorded. Negative binomial regression was used to estimate the association between baseline SLICC‐FI values and the rate of hospitalizations per patient‐year of follow‐up. Linear regression was used to estimate the association of baseline SLICC‐FI scores with the proportion of follow‐up time spent in the hospital. Multivariable models were adjusted for relevant baseline characteristics. The 1,549 patients with SLE eligible for this analysis were mostly female (88.7%), with a mean ± SD age of 35.7 ± 13.3 years and a median disease duration of 1.2 years (interquartile range 0.9–1.5) at baseline. Mean ± SD baseline SLICC‐FI was 0.17 ± 0.08. During mean ± SD follow‐up of 7.2 ± 3.7 years, 614 patients (39.6%) experienced 1,570 hospitalizations. Higher baseline SLICC‐FI values (per 0.05 increment) were associated with more frequent hospitalizations during follow‐up, with an incidence rate ratio of 1.21 (95% confidence interval [95% CI] 1.13–1.30) after adjustment for baseline age, sex, glucocorticoid use, immunosuppressive use, ethnicity/location, SLE Disease Activity Index 2000 score, SLICC/American College of Rheumatology Damage Index score, and disease duration. Among patients with ≥1 hospitalization, higher baseline SLICC‐FI values predicted a greater proportion of follow‐up time spent hospitalized (relative rate 1.09 [95% CI 1.02–1.16]). The SLICC‐FI predicts future hospitalizations among incident SLE patients, further supporting the SLICC‐FI as a valid health measure in SLE.

To assess cancer risk factors in incident systemic lupus erythematosus (SLE). Clinical variables and cancer outcomes were assessed annually among incident SLE patients. Multivariate hazard regression models (overall risk and most common cancers) included demographic characteristics and time‐dependent medications (corticosteroids, antimalarial drugs, immunosuppressants), smoking, and the adjusted mean Systemic Lupus Erythematosus Disease Activity Index 2000 score. Among 1,668 patients (average 9 years follow‐up), 65 cancers occurred: 15 breast, 10 nonmelanoma skin, 7 lung, 6 hematologic, 6 prostate, 5 melanoma, 3 cervical, 3 renal, 2 each gastric, head and neck, and thyroid, and 1 each rectal, sarcoma, thymoma, and uterine cancers. Half of the cancers (including all lung cancers) occurred in past/current smokers, versus one‐third of patients without cancer. Multivariate analyses indicated that overall cancer risk was related primarily to male sex and older age at SLE diagnosis. In addition, smoking was associated with lung cancer. For breast cancer risk, age was positively associated and antimalarial drugs were negatively associated. Antimalarial drugs and higher disease activity were also negatively associated with nonmelanoma skin cancer risk, whereas age and cyclophosphamide were positively associated. Disease activity was associated positively with hematologic and negatively with nonmelanoma skin cancer risk. Smoking is a key modifiable risk factor, especially for lung cancer, in SLE. Immunosuppressive medications were not clearly associated with higher risk except for cyclophosphamide and nonmelanoma skin cancer. Antimalarials were negatively associated with breast cancer and nonmelanoma skin cancer risk. SLE activity was associated positively with hematologic cancer and negatively with nonmelanoma skin cancer. Since the absolute number of cancers was small, additional follow‐up will help consolidate these findings.

The Systemic Lupus International Collaborating Clinics (SLICC) 2012 systemic lupus erythematosus (SLE) classification criteria and the revised American College of Rheumatology (ACR) 1997 criteria are list based, counting each SLE manifestation equally. We derived a classification rule based on giving variable weights to the SLICC criteria and compared its performance to the revised ACR 1997, the unweighted SLICC 2012, and the newly reported European Alliance of Associations for Rheumatology (EULAR)/ACR 2019 criteria sets. The physician‐rated patient scenarios used to develop the SLICC 2012 classification criteria were reemployed to devise a new weighted classification rule using multiple linear regression. The performance of the rule was evaluated on an independent set of expert‐diagnosed patient scenarios and compared to the performance of the previously reported classification rules. The weighted SLICC criteria and the EULAR/ACR 2019 criteria had less sensitivity but better specificity compared to the list‐based revised ACR 1997 and SLICC 2012 classification criteria. There were no statistically significant differences between any pair of rules with respect to overall agreement with the physician diagnosis. The 2 new weighted classification rules did not perform better than the existing list‐based rules in terms of overall agreement on a data set originally generated to assess the SLICC criteria. Given the added complexity of summing weights, researchers may prefer the unweighted SLICC criteria. However, the performance of a classification rule will always depend on the populations from which the cases and non‐cases are derived and whether the goal is to prioritize sensitivity or specificity.

Objective.Specific risk alleles for childhood-onset systemic lupus erythematosus SLE (cSLE) vs adult-onset SLE (aSLE) patients have not been identified. The aims of this study were to determine if there is an association (1) between non-HLA–related genetic risk score (GRS) and age of SLE diagnosis, and (2) between HLA-related GRS and age of SLE diagnosis.Methods.Genomic DNA was obtained from 2001 multiethnic patients and genotyped using the Immunochip. Following quality control, genetic risk counting (GRCS), weighted (GRWS), standardized counting (GRSCS), and standardized weighted (GRSWS) scores were calculated based on independent single-nucleotide polymorphisms from validated SLE loci. Scores were analyzed in a regression model and adjusted by sex and ancestral population.Results.The analyzed cohort consisted of 1540 patients: 1351 females and 189 males (675 cSLE and 865 aSLE). There were significant negative associations between all non-HLA GRS and age of SLE diagnosis: P= 0.011 and r2= 0.175 for GRWS; P= 0.008 and r2= 0.178 for GRSCS; P= 0.002 and r2= 0.176 for GRSWS (higher GRS correlated with lower age of diagnosis.) All HLA GRS showed significant positive associations with age of diagnosis: P= 0.049 and r2= 0.176 for GRCS; P= 0.022 and r2= 0.176 for GRWS; P= 0.022 and r2= 0.176 for GRSCS; P= 0.011 and r2= 0.177 for GRSWS (higher GRS correlated with higher age of diagnosis).Conclusion.Our data suggest that there is a linear relationship between genetic risk and age of SLE diagnosis and that HLA and non-HLA GRS are associated with age of diagnosis in opposite directions.

In 2015, excavations at Stainton Quarry, Furness, Cumbria, recovered remains that provide a unique insight into Early Neolithic farming in the vicinity. Five pits, a post-hole, and deposits within a tree-throw and three crevices in a limestone outcrop were investigated. The latter deposits yielded potentially the largest assemblage of Carinated Bowl fragments yet recovered in Cumbria. Lipid analysis identified dairy fats within nine of these sherds. This was consistent with previous larger studies but represents the first evidence that dairying was an important component of Early Neolithic subsistence strategies in Cumbria. In addition, two deliberately broken polished stone axes, an Arran pitchstone core, a small number of flint tools and debitage, and a tuff flake were retrieved. The site also produced moderate amounts of charred grain, hazelnut shell, charcoal, and burnt bone. Most of the charred grain came from an Early Neolithic pit and potentially comprises the largest assemblage of such material recovered from Cumbria to date. Radiocarbon dating indicated activity sometime during the 40th–35th centuries cal bcas well as an earlier presence during the 46th–45th centuries. Later activity during the Chalcolithic and the Early Bronze Age was also demonstrated. The dense concentration of material and the fragmentary and abraded nature of the pottery suggested redeposition from an above-ground midden. Furthermore, the data recovered during the investigation has wider implications regarding the nature and use of the surrounding landscape during the Early Neolithic and suggests higher levels of settlement permanence, greater reliance on domesticated resources, and a possible different topographical focus for settlement than currently proposed.

There is a paucity of data regarding health care costs associated with damage accrual in systemic lupus erythematosus. The present study was undertaken to describe costs associated with damage states across the disease course using multistate modeling. Patients from 33 centers in 11 countries were enrolled in the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort within 15 months of diagnosis. Annual data on demographics, disease activity, damage (SLICC/American College of Rheumatology Damage Index [SDI]), hospitalizations, medications, dialysis, and selected procedures were collected. Ten‐year cumulative costs (Canadian dollars) were estimated by multiplying annual costs associated with each SDI state by the expected state duration using a multistate model. A total of 1,687 patients participated; 88.7% were female, 49.0% were white, mean ± SD age at diagnosis was 34.6 ± 13.3 years, and mean time to follow‐up was 8.9 years (range 0.6–18.5 years). Mean annual costs were higher for those with higher SDI scores as follows: $22,006 (Canadian) (95% confidence interval [95% CI] $16,662, $27,350) for SDI scores ≥5 versus $1,833 (95% CI $1,134, $2,532) for SDI scores of 0. Similarly, 10‐year cumulative costs were higher for those with higher SDI scores at the beginning of the 10‐year interval as follows: $189,073 (Canadian) (95% CI $142,318, $235,827) for SDI scores ≥5 versus $21,713 (95% CI $13,639, $29,788) for SDI scores of 0. Patients with the highest SDI scores incur 10‐year cumulative costs that are ~9‐fold higher than those with the lowest SDI scores. By estimating the damage trajectory and incorporating annual costs, data on damage can be used to estimate future costs, which is critical knowledge for evaluating the cost‐effectiveness of novel therapies.

Systemic lupus erythematosus is associated with a small overall increased cancer risk compared with the general population. This risk includes a 4-fold increased risk of non-Hodgkin lymphoma, but a decreased risk of other cancers (such as breast cancer). The pathophysiology underlying the increased risk of hematologic cancer is not fully understood, but many potential mechanisms have been proposed, including dysfunction of the tumor necrosis factor and other pathways. A decreased risk of breast, ovarian, and endometrial cancer might be driven by hormonal factors or lupus-related antibodies, but these links have not been proved.

Objective.Hydroxychloroquine (HCQ) and chloroquine (CQ) are key drugs in systemic lupus (SLE) and related diseases. Retinal toxicity remains the most worrisome complication. We studied factors potentially associated with retinal toxicity, using case-control analyses.Methods.Within our SLE clinic cohort, we identified patients with retinal changes using the Systemic Lupus International Collaborating Clinics Damage Index. We confirmed HCQ/CQ retinopathy with chart review, and selected up to 3 SLE controls for each case, matched by age at SLE diagnosis and SLE duration.Results.Over an average 12.8 years of followup, within 326 patients exposed to antimalarial drugs, 18 (5.5%) developed retinal toxicity. The minimum number of years of HCQ/CQ exposure before retinopathy developed was 8 years (maximum 33 yrs). Median HCQ/CQ duration was statistically similar in cases [19 yrs, interquartile range (IQR) 14–20] and controls (16 yrs, IQR 11–22), likely due to our matching on SLE duration. Versus controls, cases tended to have more renal disease (cases 22.2%, controls 14.8%) and were slightly less likely to be white (cases 61.1%, controls 74.1%), but neither variable reached statistical significance. Among patients with retinal toxicity, the number previously exposed to CQ was more than 3 times that in controls.Conclusion.Just over 5% of patients developed antimalarial retinal complications, over an average of 12.8 years. No cases were detected in the first 5 years of therapy. Past CQ use was more common in cases versus controls. Future studies using larger cohorts are under way to better define the roles of therapy duration, race/ethnicity, and other factors.

Systemic lupus erythematosus (SLE) predominantly affects women. Clinical phenotype and outcomes in SLE may vary by sex and are further complicated by unique concerns that are dependent upon sex‐defined roles. We aimed to describe sex differences in disease‐specific quality of life (QoL) assessment scores using the Lupus Patient‐Reported Outcome (LupusPRO) tool in a large international study. Cross‐sectional data from 1,803 patients with SLE on demographics, self‐identified sex status, LupusPRO, and disease activity were analyzed. The LupusPRO tool has 2 constructs: health‐related QoL (HRQoL) and non‐HRQoL. Disease activity and damage were evaluated using the Safety of Estrogens in Lupus Erythematosus National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index, respectively. Nonparametric tests were used to compare QoL and disease activity by sex. A total of 122 men and 1,681 women with SLE participated. The mean age was similar by sex, but the damage scores were greater among men. Men fared worse on the non‐HRQoL social support domain than women (P= 0.02). When comparing disease and QoL among men and women ages ≤45 years, men were found to have greater damage and worse social support than women. However, women fared significantly worse on lupus symptoms, cognition, and procreation domains with trends for worse functioning on physical health and pain‐vitality domains. In the largest study of a diverse group of SLE patients, utilizing a disease‐specific QoL tool, sex differences in QoL were observed on both HRQoL and non‐HRQoL constructs. Although men performed worse in the social support domain, women (especially those in the reproductive age group) fared worse in other domains. These observations may assist physicians in appropriately addressing QoL issues in a sex‐focused manner.

Previous guidelines recommend prompt epinephrine administration, followed by observation in the emergency department (ED). The need for transfer in all cases of anaphylaxis has recently been challenged.

Egg is the third most common food allergy in children; however, data on pediatric egg-induced anaphylaxis are sparse.

Oral immunotherapy (OIT) has emerged as the most popular therapy for food allergy. However, data on the long-term adherence and efficacy of this approach are sparse.

Cow's milk is one of the most common and burdensome allergens in pediatrics, and it can induce severe anaphylactic reactions in children. However, data on cow's milk-induced anaphylaxis are sparse.

This study focuses on the side effects of cow's milk oral immunotherapy (CM-OIT) using consensus definitions of food-induced anaphylaxis.

The spectrum of antinuclear antibodies (ANAs) is changing to include both nuclear staining as well as cytoplasmic and mitotic cell patterns (CMPs) and accordingly a change is occurring in terminology to anticellular antibodies. This study examined the prevalence of indirect immunofluorescence (IIF) anticellular antibody staining using the Systemic Lupus International Collaborating Clinics inception cohort. Anticellular antibodies were detected by IIFon HEp‐2000 substrate using the baseline serum. Three serologic subsets were examined: ANApositive (presence of either nuclear or mixed nuclear/CMPstaining), anticellular antibody negative (absence of any intracellular staining), and isolated CMPstaining. The odds of being anticellular antibody negative versus ANAor isolated CMPpositive was assessed by multivariable analysis. A total of 1,137 patients were included; 1,049 (92.3%) were ANApositive, 71 (6.2%) were anticellular antibody negative, and 17 (1.5%) had an isolated CMP. The isolated CMP–positive group did not differ from the ANA‐positive or anticellular antibody–negative groups in clinical, demographic, or serologic features. Patients who were older (odds ratio [OR] 1.02 [95% confidence interval (95% CI) 1.00, 1.04]), of white race/ethnicity (OR3.53 [95% CI1.77, 7.03]), or receiving high‐dose glucocorticoids at or prior to enrollment (OR2.39 [95% CI1.39, 4.12]) were more likely to be anticellular antibody negative. Patients on immunosuppressants (OR0.35 [95% CI0.19, 0.64]) or with anti‐SSA/Ro 60 (OR0.41 [95% CI0.23, 0.74]) or anti–U1 RNP(OR0.43 [95% CI0.20, 0.93]) were less likely to be anticellular antibody negative. In newly diagnosed systemic lupus erythematosus, 6.2% of patients were anticellular antibody negative, and 1.5% had an isolated CMP. The prevalence of anticellular antibody–negative systemic lupus erythematosus will likely decrease as emerging nomenclature guidelines recommend that non‐nuclear patterns should also be reported as a positive ANA.

Objective.In cross-sectional studies, elevated osteopontin (OPN) levels have been proposed to reflect, and/or precede, progressive organ damage and disease severity in systemic lupus erythematosus (SLE). We aimed, in a cohort of patients with recent-onset SLE, to determine whether raised serum OPN levels precede damage and/or are associated with disease activity or certain disease phenotypes.Methods.We included 344 patients from the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort who had 5 years of followup data available. All patients fulfilled the 1997 American College of Rheumatology (ACR) criteria. Baseline sera from patients and from age- and sex-matched population-based controls were analyzed for OPN using ELISA. Disease activity and damage were assessed at each annual followup visit using the SLE Disease Activity Index 2000 (SLEDAI-2K) and the SLICC/ACR damage index (SDI), respectively.Results.Compared to controls, baseline OPN was raised 4-fold in SLE cases (p < 0.0001). After relevant adjustments in a binary logistic regression model, OPN levels failed to significantly predict global damage accrual defined as SDI ≥ 1 at 5 years. However, baseline OPN correlated with SLEDAI-2K at enrollment into the cohort (r = 0.27, p < 0.0001), and patients with high disease activity (SLEDAI-2K ≥ 5) had raised serum OPN (p < 0.0001). In addition, higher OPN levels were found in patients with persistent disease activity (p = 0.0006), in cases with renal involvement (p < 0.0001) and impaired estimated glomerular filtration rate (p = 0.01).Conclusion.The performance of OPN to predict development of organ damage was not impressive. However, OPN associated significantly with lupus nephritis and with raised disease activity at enrollment, as well as over time.

Hydroxychloroquine (HCQ) retinopathy may be more common than previously recognized; recent ophthalmology guidelines have revised recommendations from ideal body weight (IBW)-based dosing to actual body weight (ABW)-based dosing. However, contemporary HCQ prescribing trends in the UK remain unknown. We examined a UK general population database to investigate HCQ dosing between 2007 and 2016. We studied trends of excess HCQ dosing per ophthalmology guidelines (defined by exceeding 6.5 mg/kg of IBW and 5.0 mg/kg of ABW) and determined their independent predictors using multivariable logistic regression analyses. Among 20,933 new HCQ users (78% female), the proportions of initial HCQ excess dosing declined from 40% to 36% using IBW and 38% to 30% using ABW, between 2007 and 2016. Among these, 47% of women were excess-dosed (multivariable OR 12.52; 95% CI 10.99–14.26) using IBW and 38% (multivariable OR 1.98; 95% CI,1.81–2.15) using ABW. Applying IBW, 37% of normal and 44% of obese patients were excess-dosed; however, applying ABW, 53% of normal and 10% of obese patients were excess-dosed (multivariable ORs = 1.61 and 0.1 (reference = normal); both p< 0.01). Long-term HCQ users showed similar excess dosing. A substantial proportion of HCQ users in the UK, particularly women, may have excess HCQ dosing per the previous or recent weight-based guidelines despite a modest decline in recent years. Over half of normal-BMI individuals were excess-dosed per the latest guidelines. This implies the potential need to reduce dosing for many patients but also calls for further research to establish unifying evidence-based safe and effective dosing strategies.

To determine the frequency, characteristics, and outcomes of cerebrovascular events (CerVEs), as well as clinical and autoantibody associations in a multiethnic/racial inception cohort of patients with systemic lupus erythematosus (SLE). A total of 1,826 patients were assessed annually for 19 neuropsychiatric (NP) events, including 5 types of CerVEs: 1) stroke, 2) transient ischemia, 3) chronic multifocal ischemia, 4) subarachnoid/intracranial hemorrhage, and 5) sinus thrombosis. Global disease activity (Systemic Lupus Erythematosus Disease [SLE] Activity Index 2000), damage scores (SLEInternational Collaborating Clinics/American College of Rheumatology Damage Index), and Short Form 36 (SF‐36) scores were collected. Time to event, linear and logistic regressions, and multistate models were used as appropriate. CerVEs were the fourth most frequent NPevent: 82 of 1,826 patients had 109 events; of these events, 103 were attributed to SLE, and 44 were identified at the time of enrollment. The predominant events were stroke (60 of 109 patients) and transient ischemia (28 of 109 patients). CerVEs were associated with other NPevents attributed to SLE, non–SLE‐attributed NPevents, African ancestry (at US SLICCsites), and increased organ damage scores. Lupus anticoagulant increased the risk of first stroke and sinus thrombosis and transient ischemic attack. Physician assessment indicated resolution or improvement in the majority of patients, but patients reported sustained reduction in SF‐36 summary and subscale scores following a CerVE. CerVEs, the fourth most frequent NPevent in SLE, are usually attributable to lupus. In contrast to good physician‐reported outcomes, patients reported a sustained reduction in health‐related quality of life following a CerVE.

Little is known about the long‐term costs of lupus nephritis (LN). The costs were compared between patients with and without LN using multistate modeling. Patients from 32 centers in 11 countries were enrolled in the Systemic Lupus International Collaborating Clinics inception cohort within 15 months of diagnosis and provided annual data on renal function, hospitalizations, medications, dialysis, and selected procedures. LN was diagnosed by renal biopsy or the American College of Rheumatology classification criteria. Renal function was assessed annually using the estimated glomerular filtration rate (GFR) or estimated proteinuria. A multistate model was used to predict 10‐year cumulative costs by multiplying annual costs associated with each renal state by the expected state duration. A total of 1,545 patients participated; 89.3% were women, the mean ± age at diagnosis was 35.2 ± 13.4 years, 49% were white, and the mean followup duration was 6.3 ± 3.3 years. LN developed in 39.4% of these patients by the end of followup. Ten‐year cumulative costs were greater in those with LN and an estimated glomerular filtration rate (GFR) <30 ml/minute ($310,579 2015 Canadian dollars versus $19,987 if no LN and estimated GFR >60 ml/minute) or with LN and estimated proteinuria >3 gm/day ($84,040 versus $20,499 if no LN and estimated proteinuria <0.25 gm/day). Patients with estimated GFR <30 ml/minute incurred 10‐year costs 15‐fold higher than those with normal estimated GFR. By estimating the expected duration in each renal state and incorporating associated annual costs, disease severity at presentation can be used to anticipate future health care costs. This is critical knowledge for cost‐effectiveness evaluations of novel therapies.

This paper describes a small Mesolithic structure from the Cairngorm Mountains, Scotland. Excavations at Caochanan Ruadha identified a small oval structure (c. 3m×2.2m) with a central fire setting, in an upland valley (c.540masl). The site was occupied at c. 8200calBP and demonstrates hunter-gatherer use of the uplands during a period of significant climatic deterioration. The interpretation of the structure is primarily based on the distribution of the lithic assemblage, as the heavily podsolised soils have left no trace of light structural features. The lithic assemblage is specialised, dominated by microlith fragments, and functional analysis has identified different uses of different areas inside the structure. The identification of small, specialised Mesolithic sites is unusual and this paper will discuss the evidence for the presence of the structure and its use, compare it to other Mesolithic structures in Britain and highlight some methodological implications.

Limited evidence suggests a potentially increased risk of allergic conditions in offspring born to women with systemic lupus erythematosus (SLE). In a large population‐based study, we aimed to determine if children born to mothers with SLEhave an increased risk of allergic conditions compared to children born to mothers without SLE. Using the Offspring of SLEMothers Registry, we identified children born live to mothers with SLEand their matched controls, and ascertained the number of allergic conditions (asthma, allergic rhinitis, eczema, urticaria, angioedema, and anaphylaxis) based on ≥1 hospitalization or ≥1 or 2 physician(s) visit(s) with a relevant diagnostic code. We adjusted for maternal age, education, race/ethnicity, obstetrics complications, calendar year of birth, sex of the child, and maternal medication. There were 509 women with SLEwho had 719 children, while 5,824 matched controls had 8,493 children. The mean ± SDfollowup period was 9.1 ± 5.8 years. Compared to controls, more children born to mothers with SLEhad evidence of allergic conditions (43.9% [95% confidence interval (95% CI) 40.4–47.6] versus 38.1% [95% CI37.0–39.1]). In multivariate analysis (n = 9,212), children born to mothers with SLEhad an increased risk of allergic conditions versus control children (odds ratio 1.35 [95% CI1.13–1.61]). Compared to children from the general population, children born to women with SLEmay have an increased risk of allergic conditions. Genetics, shared environmental exposures, as well as in utero exposure to maternal autoantibodies and cytokines may mediate this increased risk.

Objective.To assess lung cancer risk in systemic lupus erythematosus (SLE), relative to demographics, drug exposures, smoking, and disease activity.Methods.We analyzed data from 14 SLE cohorts. We calculated adjusted HR estimates for lung cancer in SLE, relative to demographics, smoking, time-dependent medication exposures, and cumulative disease activity [mean adjusted SLE Disease Activity Index (SLEDAI) scores]. This project was approved by the ethics boards of all participating institutions, including the Institutional Review Board of the McGill University Health Centre. The ethics approval number for the Cancer Risk study is GEN-06-031.Results.Within these 14 SLE cohorts, 49 incident lung cancers occurred. Among lung cancer cases, 59.0% were in the highest SLEDAI quartile at baseline versus 40.8% of lung cancer–free SLE controls. The vast majority (84.2%) of SLE lung cancer cases were ever-smokers at baseline, versus 40.1% of those without lung cancer. In adjusted models, the principal factors associated with lung cancer were ever smoking (at cohort entry) and current age. Estimated adjusted effects of all drugs were relatively imprecise, but did not point toward any drug exposures as strong lung cancer risk factors.Conclusion.We saw no clear evidence for drugs as a trigger for lung cancer risk in SLE, although drug risk estimates were relatively imprecise. Smoking may be the most significant modifiable lung cancer risk factor in SLE.

Objective.Few data exist to guide the frequency and type of monitoring in systemic lupus erythematosus (SLE) pregnancies. A systematic literature review was performed to address this gap in the literature.Methods.A systematic review of original articles (1975–2015) was performed using Medline, Embase, and Cochrane Library. We included search terms for SLE, pregnancy, and monitoring. We also hand-searched reference lists, review articles, and grey literature for additional relevant articles.Results.The search yielded a total of 1106 articles. After removing 117 duplicates, 929 articles that were evidently unrelated to our topic based on title and/or abstract, and 7 that were in a language other than English or French, 53 articles were included for full-text review. Following a more in-depth review, 15 were excluded: 6 did not use any measure of SLE activity and 6 did not specifically address SLE monitoring in pregnancy; 1 case series, 1 review, and 1 metaanalysis were removed. Among the 38 included studies, presence of active disease, antiphospholipid (aPL) antibodies positivity, and abnormal uterine and umbilical artery Doppler studies predicted poor pregnancy outcomes. No studies evaluated an evidence-based approach to the frequency of monitoring.Conclusion.Few existing studies address monitoring for optimal care during SLE pregnancies. The available data imply roles for aPL antibodies measurement (prior to pregnancy and/or during the first trimester), uterine and umbilical artery Doppler studies in the second trimester, and following disease activity. Optimal frequency of monitoring is not addressed in the existing literature.

Objective.To develop recommendations for the assessment of people with systemic lupus erythematosus (SLE) in Canada.Methods.Recommendations were developed using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. The Canadian SLE Working Group (panel of Canadian rheumatologists and a patient representative from Canadian Arthritis Patient Alliance) was created. Questions for recommendation development were identified based on the results of a previous survey of SLE practice patterns of members of the Canadian Rheumatology Association. Systematic literature reviews of randomized trials and observational studies were conducted. Evidence to Decision tables were prepared and presented to the panel at 2 face-to-face meetings and online.Results.There are 15 recommendations for assessing and monitoring SLE, with varying applicability to adult and pediatric patients. Three recommendations focus on diagnosis, disease activity, and damage assessment, suggesting the use of a validated disease activity score per visit and annual damage score. Strong recommendations were made for cardiovascular risk assessment and measuring anti-Ro and anti-La antibodies in the peripartum period and conditional recommendations for osteoporosis and osteonecrosis. Two conditional recommendations were made for peripartum assessments, 1 for cervical cancer screening and 2 for hepatitis B and C screening. A strong recommendation was made for annual influenza vaccination.Conclusion.These are considered the first guidelines using the GRADE method for the monitoring of SLE. Existing evidence is largely of low to moderate quality, resulting in more conditional than strong recommendations. Additional rigorous studies and special attention to pediatric SLE populations and patient preferences are needed.

In patients with systemic lupus erythematosus (SLE) there is no serological test that will reliably distinguish neuropsychiatric (NP) events due to active SLE from those due to other causes. Previously we showed that serum levels of nitrated nucleosomes (NN) were elevated in a small number of patients with NPSLE. Here we measured serum NN in samples from a larger population of patients with SLE and NP events to see whether elevated serum NN could be a marker for NPSLE. We obtained serum samples from patients in the Systemic Lupus International Collaborative Clinics (SLICC) inception cohort. This included 216 patients with NP events and two matched controls with SLE but no NP events for each of these patients. For the NP patients we tested samples taken before, during and after the NP event. Twenty-six patients had events attributed to SLE according to the most stringent SLICC attribution rule. In these patients there was no association between onset of event and elevated serum NN. In 190 patients in whom events were not attributed to SLE by the SLICC rules, median serum NN was elevated at the onset of event (P= 0.006). The predominant clinical features in this group of 190 patients were headache, mood disorders and anxiety. Serum NN levels rise at the time of an NP event in a proportion of patients with SLE. Further studies are needed to determine the value of serum NN as a biomarker for NPSLE.

There is recent evidence to suggest that in utero exposure to maternal antibodies and cytokines is an important risk factor for autism spectrum disorders (ASDs). We aimed to systematically review the risk of ASDs in children born to mothers with rheumatoid arthritis (RA) compared to children born to mothers without RA. We conducted a systematic review of original articles using the electronic databases PubMed, Embase, and Web of Science. Our literature search yielded a total of 70 articles. Of the potentially relevant studies retrieved, 67 were excluded for lack of relevance and/or because they did not report original data. Three studies were included in the final analysis. A case–control study found no difference in the prevalence of RAin mothers of children with ASDs versus control mothers. Another case–control study showed a statistically significant 8‐fold increase in autoimmune disorders, including RA, in mothers of offspring with ASDs compared to controls. Forty‐six percent of offspring with ASDs had a first‐degree relative with RA, compared to 26% of controls. And in a population‐based cohort study, investigators observed an increased risk of ASDs in children with a maternal history of RAcompared to children born to unaffected mothers. These studies had methodologic limitations: none controlled for medication exposures, only 1 controlled for obstetric complications and considered the timing of RAdiagnosis in relation to pregnancy, and all but 1 used a case–control study design. Observational studies suggest a potentially increased risk of ASDs in children born to mothers with RAcompared to children born to mothers without RA, although data are limited.