Background The McMaster RARE-Bestpractices project group selected the catastrophic antiphospholipid syndrome (CAPS) for a pilot exercise in guideline development for a rare disease. Objectives The objectives of this exercise were to provide a proof of principle that guidelines can be developed for rare diseases and assist in clinical decision making for CAPS. Patients/Methods The GIN-McMaster Guideline Development checklist and GRADE methodology were followed throughout the guideline process. The CAPS guideline was coordinated by a steering committee, and the guideline panel was formed with representation from all relevant stakeholder groups. Systematic reviews were performed for the key questions. To supplement the published evidence, we piloted novel methods, including use of an expert-based evidence elicitation process and ad hoc analysis of registry data. Results This paper describes the CAPS guideline recommendations, including evidence appraisal and discussion of special circumstances and implementation barriers identified by the panel. Many of these recommendations are conditional, because of subgroup considerations in this heterogeneous disease, as well as variability in patient values and preferences. Conclusions The CAPS clinical practice guideline initiative met the objective of the successful development of a clinical practice guideline in a rare disease using GRADE methodology. We expect that clinicians caring for patients with suspected CAPS will find the guideline useful in assisting with diagnosis and management of this rare disease.

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.

BackgroundPatients are particularly susceptible to medical error during transitions from inpatient to outpatient care. We evaluated discharge summaries produced by incoming postgraduate year 1 (PGY-1) internal medicine residents for their completeness, accuracy, and relevance to family physicians.MethodsConsecutive discharge summaries prepared by PGY-1 residents for patients discharged from internal medicine wards were retrospectively evaluated by two independent reviewers for presence and accuracy of essential domains described by the Joint Commission for Hospital Accreditation. Family physicians rated the relevance of a separate sample of discharge summaries on domains that family physicians deemed important in previous studies.ResultsNinety discharge summaries were assessed for completeness and accuracy. Most items were completely reported with a given item missing in 5% of summaries or fewer, with the exception of the reason for medication changes, which was missing in 15.9% of summaries. Discharge medication lists, medication changes, and the reason for medication changes—when present—were inaccurate in 35.7%, 29.5%, and 37.7% of summaries, respectively. Twenty-one family physicians reviewed 68 discharge summaries. Communication of follow-up plans for further investigations was the most frequently identified area for improvement with 27.7% of summaries rated as insufficient.ConclusionsThis study found that medication details were frequently omitted or inaccurate, and that family physicians identified lack of clarity about follow-up plans regarding further investigations and visits to other consultants as the areas requiring the most improvement. Our findings will aid in the development of educational interventions for residents.

Background Rare diseases are a global public health priority. Though each disease is rare, when taken together the thousands of known rare diseases cause significant morbidity and mortality, impact quality of life, and confer a social and economic burden on families and communities. These conditions are, by their nature, encountered very infrequently by individual clinicians, who may feel unprepared to address their diagnosis and treatment. Clinical practice guidelines are necessary to support clinical and policy decisions. However, creating guidelines for rare diseases presents specific challenges, including a paucity of high certainty evidence to inform panel recommendations. Methods This paper draws from the authors’ experience in the development of clinical practice guidelines for three rare diseases: hemophilia, sickle cell disease, and catastrophic antiphospholipid syndrome. Results We have summarized a number of strategies for eliciting and synthesizing evidence that are compatible with the rigorous, internationally accepted standards for guideline development set out by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. These strategies include: use of pre-existing and ad hoc qualitative research, use of systematic observation forms, use of registry data, and thoughtful use of indirect evidence. Their use in three real guideline development efforts, as well as their theoretical underpinnings, are discussed. Avenues for future research to improve clinical practice guideline creation for rare diseases – and any disease affected by a relative lack of evidence - are also identified. Conclusions Rigorous clinical practice guidelines are needed to improve the care of the millions of people worldwide who suffer from rare diseases. Innovative evidence elicitation and synthesis methods will benefit not only the rare disease community, but also individuals with common diseases who have rare presentations, suffer rare complications, or require nascent therapies. Further refinement and improved uptake of these innovative methods should lead to higher quality clinical practice guidelines in rare diseases.

A 22-year-old Caucasian man presented to hospital with pleuritic chest pain. He had had a history of a sun-sensitive rash a year prior. Workup revealed normal cardiac enzymes and chest X-ray. However, electrocardiogram revealed ST elevation and PR depression, and echocardiogram revealed a slight pericardial effusion without other findings. A diagnosis of pericarditis was made. Subsequently, he was found to be positive for antinuclear antibodies (ANAs), as well as antibodies to SSA, SSB and double-stranded DNA; C3 was low, and C4 was undetectable. A diagnosis of systemic lupus erythematosus was made. The patient initially responded to high-dose ibuprofen. One month later, he developed a new pericardial effusion, this time with concomitant massive left-sided pleural effusion, requiring three separate thoracenteses draining a total of 6 L of pleural fluid. The recurrent effusion failed to respond to high-dose corticosteroid treatment. Owing to the severity and rapidity of the recurrence of pleural and pericardial effusion, intravenous tocilizumab was administered. The patient had excellent clinical and radiographic improvement. This case shows that tocilizumab may have a role in the treatment of intractable pleuropericardial effusion and other forms of lupus-associated serositis.

Background: There is uncertainty regarding the safety and effectiveness of direct oral anticoagulant agents in patients with antiphospholipid syndrome (APS). We performed a multicenter feasibility study to examine our ability to identify and obtain consent from eligible APS patients and to obtain 95% adherence with daily rivaroxaban administration, in order to inform and power a larger study. Clinical outcomes of bleeding and thrombosis were also collected. Methods: APS patients with prior venous thromboembolism (VTE) were recruited over 2 years (Oct 2014-Sept 2016) and followed for ≥ 1 year. Patients were assessed clinically every 3 months and had pill counts performed every 6 months. Numbers of patients fulfilling study criteria, as well as those consenting to participate, were tracked, and percentage adherence based on pill counts was recorded. These data were compared against the feasibility endpoints. Rates of thrombosis and bleeding were calculated. Criterion for feasibility was obtaining consent from 135 of 150 identified APS patients over 2 years. Results: Ninety-six eligible patients were identified, and 14 declined participation. Eighty-two patients were followed for a mean of 19 months, representing 129.8 patient-years. Average rivaroxaban adherence was 95.0%. During follow-up, there were 4 thromboembolic events (2 cerebrovascular and 2 VTE). There were no episodes of major bleeding. Conclusions: Adequately powered comparative trials using patient-important outcomes in APS are unlikely to be successful due to inability to recruit sufficient numbers of study subjects. This study does not reveal a higher than expected risk of recurrent thromboembolic disease compared to historical cohorts; however, this is an uncontrolled study in relatively low-risk APS patients. Trial registration: The study was registered with clinicaltrials.gov, identifier NCT02116036, April 16, 2014.

Objective The purpose of this study was to characterize the role of eculizumab, a monoclonal antibody against the terminal complement component C5, in patients with catastrophic antiphospholipid syndrome (CAPS). Methods We present a case report of a patient with systemic lupus erythematosus (SLE) and CAPS treated with eculizumab, as well as results of a systematic review of the literature. Results Including our patient, we identified 11 case reports of patients with CAPS treated with eculizumab. All of them had partial or total remission of symptoms. Conclusion Data on eculizumab efficacy in CAPS are promising but are limited to single case reports. More studies are needed to develop evidence-based recommendations for eculizumab use in CAPS.

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