Effectiveness and Safety of Endoanchors in Abdominal and Thoracic Endovascular Aneurysm Repair: A Systematic Review and Meta-analysis.

PURPOSE: This systematic review aimed to summarize the effectiveness and safety of endoanchor, a stabilizing device for the proximal endograft designed to prevent endoleak and stent migration in endovascular aneurysm repair (EVAR) and thoracic endovascular aneurysm repair (TEVAR). MATERIALS AND METHODS: A systematic review and meta-analysis was conducted per the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guideline. Literature up to May 31, 2023 was searched and independently screened from 4 databases. Data were pooled for meta-analysis. Primary outcomes included intraoperative and follow-up endoleak, stent migration, and reintervention rates; sac regression; and 30-day all-cause mortality. RESULTS: Sixteen EVAR (n=1145) and 6 TEVAR studies (n=163) using the Heli-Fx EndoAnchor system were included from 2225 retrieved records. For EVAR patients (mean follow-up=11.9 months), the endoleak, graft migration, and reintervention rates were 3.97% (95% confidence interval [CI]=0.36%-1.99%), 0.004% (95% CI=0.00%-0.76%), and 5.43% (95% CI=0.86%-12.54%), respectively. The endoleak rates for primary and revision EVAR were 0.16% (95% CI=0.00%-1.65%) and 3.60% (95% CI=0.14%-9.72%), respectively. Only 4 cases of 30-day mortality (n=4) were reported in the literature. For TEVAR patients, the endoleak, stent migration, and reintervention rates were 7.4% (95% CI=0.03%-0.13%), 0.2% (95% CI=0.00%-0.06%), and 17.1% (95% CI=0.01%-0.45%), respectively. The 30-day mortality was 0.9% (95% CI=0%-0.12%). CONCLUSIONS: Endoanchor fixation in EVAR and TEVAR is effective and safe in preventing and treating endoleak and stent migration. The mortality is minimal in EVAR but higher in TEVAR. CLINICAL IMPACT: Endoleak, graft migration, and reintervention in EVAR and TEVAR with endoanchor use were rare. Mortality in EVAR was low. The adjunctive deployment of endoanchors is an effective and safe means to prevent and treat endoleak and stent migration in EVAR and TEVAR. Yet, long-term efficacy and safety data and randomized controlled trials would be required to definitively recommend endoanchor use in routine clinical practice.

Multicentre, randomised, double-blind, placebo-controlled, proof of concept study of LSALT peptide as prevention of acute respiratory distress syndrome and acute kidney injury in patients infected with SARS-CoV-2 (COVID-19).

OBJECTIVE: Dipeptidase-1 (DPEP-1) is a recently discovered leucocyte adhesion receptor for neutrophils and monocytes in the lungs and kidneys and serves as a potential therapeutic target to attenuate inflammation in moderate-to-severe COVID-19. We aimed to evaluate the safety and efficacy of the DPEP-1 inhibitor, LSALT peptide, to prevent specific organ dysfunction in patients hospitalised with COVID-19. DESIGN: Phase 2a randomised, placebo-controlled, double-blinded, trial. SETTING: Hospitals in Canada, Turkey and the USA. PARTICIPANTS: A total of 61 subjects with moderate-to-severe COVID-19. INTERVENTIONS: Randomisation to LSALT peptide 5 mg intravenously daily or placebo for up to 14 days. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary endpoint was the proportion of subjects alive and free of respiratory failure and/or the need for renal replacement therapy (RRT). Numerous secondary and exploratory endpoints were assessed including ventilation-free days, and changes in kidney function or serum biomarkers. RESULTS: At 28 days, 27 (90.3%) and 28 (93.3%) of subjects in the placebo and LSALT groups were free of respiratory failure and the need for RRT (p=0.86). On days 14 and 28, the number of patients still requiring more intensive respiratory support (O2 ≥6 L/minute, non-invasive or invasive mechanical ventilation or extracorporeal membrane oxygenation) was 6 (19.4%) and 3 (9.7%) in the placebo group versus 2 (6.7%) and 2 (6.7%) in the LSALT group, respectively (p=0.14; p=0.67). Unadjusted analysis of ventilation-free days demonstrated 22.8 days for the LSALT group compared with 20.9 in the placebo group (p=0.4). LSALT-treated subjects had a significant reduction in the fold expression from baseline to end of treatment of serum CXCL10 compared with placebo (p=0.02). Treatment-emergent adverse events were similar between groups. CONCLUSION: In a Phase 2 study, LSALT peptide was demonstrated to be safe and tolerated in patients hospitalised with moderate-to-severe COVID-19. TRIAL REGISTRATION NUMBER: NCT04402957.

Risk Factors and Clinical Outcomes Associated With Sarcopenia in Rheumatoid Arthritis: A Systematic Review and Meta-analysis.

ABSTRACT: Sarcopenia is underrecognized in patients with rheumatoid arthritis (RA). Risk factors of sarcopenia and its impact on outcomes in RA patients are relatively unknown. We conducted a systematic review to identify factors and outcomes associated with sarcopenia in RA. We conducted this review according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 guidelines. We searched PubMed, Embase, CINAHL, and Web of Science databases by combining the following search concepts: (1) RA and (2) sarcopenia. Articles were included if they included RA patients, assessed for sarcopenia using a consensus working group definition, and assessed for clinical outcomes. Meta-analysis was performed using studies that shared the same sarcopenia definition and consistency in reporting patient or disease variables. Our search identified 3602 articles. After removal of duplicates, title and abstract screen, and full-text review, 16 articles were included for final analysis. All studies had observational study designs. The pooled prevalence of sarcopenia ranged from 24% to 30%, depending on the criteria for sarcopenia used. Factors associated with sarcopenia included higher 28-joint Disease Activity Scale scores (+0.39; 95% confidence interval, +0.02 to +0.77) and baseline methotrexate use (odds ratio, 0.70; 95% confidence interval, 0.51-0.97). Baseline glucocorticoid use had a positive correlation with sarcopenia in multiple studies. Several studies found lower bone mineral density and higher incidence of falls and fractures in patients with sarcopenia. Sarcopenia is prevalent in RA, and it may be associated with higher RA disease activity, lower bone mineral density, and increased falls and fractures. Therefore, early screening of sarcopenia in RA patients is important to incorporate into clinical rheumatology practice.

Simulation of vertical dispersion and pollution impact of artificial light at night in urban environment.

The use of artificial light at night (ALAN) enables social and commercial activities for urban living. However, the excessive usage of lighting causes nuisance and waste of energy. Light is provided to illuminate target areas on the street level where activities take place, yet light can also cause trespass to residents at the floors above. While regulations are beginning to cover light design, simulation tools for the outdoor environment have also become more popular for assessing the design condition. Simulation tools allow visualisation of the impact of the selected light sources on those who are affected. However, this cause-and-effect relationship is not easy to determine in the complex urban environment. The current work offers a simple methodology that takes site survey results and correlates them with the simulation model to determine lighting impact on the investigated area in 3D. Four buildings in two mixed commercial and residential streets in Hong Kong were studied. Data collection from each residential building requires lengthy work and permission from each household. Therefore, a valid lighting simulation model could help determine the light pollution impact in the area. A light model using DIALux is developed and calibrated by correlating the simulated data with the actual measured data. The correlation value R2 achieved ranged from 0.95 to 0.99, verifying the accuracy of this model and matched from 340 lx to 46 lx for the lower to higher floors of one building and 10 lx to 4 lx for floors of another building. This model can also be applied to human health research, by providing light-level data on residential windows in an area or determining the environmental impact of a development project.

Impact of the COVID-19 pandemic on patients with rheumatoid arthritis: data from the Ontario Best Practices Research Initiative (OBRI).

Objective: The coronavirus disease 2019 (COVID-19) pandemic created challenges for patients with RA. We examined the potential impact of the pandemic on patient-reported outcomes (PROs), disease activity and medication profiles, comparing the periods pre-pandemic and during the pandemic. Methods: Patients enrolled in the Ontario Best Practices Research Initiative were included if they had at least one visit to a physician or study interviewer within 12 months before and after the start of pandemic-related closures in Ontario (15 March 2020). Baseline characteristics, disease activity, PROs [i.e. health assessment questionnaire disability index, RA disease activity index (RADAI), European quality of life five-dimension questionnaire], medication use and changes were included. Student's paired two-sample t-tests and McNamar's tests were performed for continuous and categorical variables between time periods. Results: The sample for analysis consisted of 1508 patients, with a mean (s.d.) age of 62.7 (12.5) years, and 79% were female. Despite decreases in the number of in-person visits during the pandemic, there was no significant negative impact on disease activity or PRO scores. The DASs in both periods remained low, with either no clinically significant differences or slight improvement. Scores for mental, social and physical health were either stable or improved. There were statistically significant decreases in conventional synthetic DMARD use (P < 0.0001) and increased Janus kinase inhibitor usage (P = 0.0002). Biologic DMARD use remained stable throughout the pandemic. Conclusion: In this cohort, disease activity and PROs of RA patients remained stable during the COVID-19 pandemic. The longer-term outcomes of the pandemic warrant investigation.

Medical cannabis use by rheumatology patients in routine clinical care: results from The Ontario Best Practices Research Initiative.

OBJECTIVES: Medical cannabis is often used to alleviate common symptoms in patients with chronic conditions. With cannabis legalisation in Canada and easier access, it is important that rheumatologists understand its potential impact on their practice. Among patients attending rheumatology clinics in Ontario we assessed: the prevalence of medical cannabis use; symptoms treated; rheumatologists' perceptions. METHODS: Eight rheumatology clinics recruited consecutive adult patients in a 3-part medical cannabis survey: the first completed by rheumatologists; the second by all patients; the third by medical cannabis users. Student's t-test and Chi-square test were used to compare medical cannabis users to never users. RESULTS: 799 patients participated, 163 (20.4%) currently using medical cannabis or within <2 years and 636 never users; most had rheumatoid arthritis (37.8%) or osteoarthritis (34.0%). Compared to never users, current/past-users were younger; more likely to be taking opioids/anti-depressants, have psychiatric/gastrointestinal disorders, and have used recreational cannabis (p<0.05); had higher physician (2.9 vs. 2.1) and patient (6.0 vs. 4.2) global scores, and pain (6.2 vs. 4.7) (p<0.0001). Pain (95.5%), sleeping (82.3%) and anxiety (58.9%) were the most commonly treated symptoms; 78.2% of current/past-users reported medical cannabis was at least somewhat effective. Most rheumatologists reported being uncomfortable to authorise medical cannabis, primarily due to lack of evidence, knowledge, and product standardisation. CONCLUSIONS: Medical cannabis use among rheumatology patients in Ontario was two-fold higher than that reported for the general population of similar age. Use was associated with more severe disease, pain, and prior recreational use. Reported lack of research, knowledge, and product standardisation were barriers for rheumatologist use authorisation.

Light pollution spatial impact assessment in Hong Kong: Measurement and numerical modelling on commercial lights at street level.

With rapid urbanization, the use of external lighting to illuminate cities for night-time activity is on the rise worldwide. Many studies have suggested the excessive use of external lighting causes light pollution, which harms human health and leads to energy wastage. Although more awareness has been raised, there are not many regulations and guidelines available. As one of the cities most affected by light pollution in the world, Hong Kong has started exploring this issue within the general and business communities. However, studies that quantitatively evaluate the problem of light pollution in this city are lacking. This study aimed to assess light pollution quantitatively through measurement and numerical modelling. To achieve this, measurement protocols were developed, and site measurements were carried out in one of the known problem areas, Sai Yeung Choi Street in Mong Kok district. Through this exercise, both vertical and horizontal illuminances on the street level and the light distribution along the street were determined. An average level of 250 lx for the vertical illuminance was found, which was 3-4 times higher than the recommended brightness for normal activity. The light environment of the measured area was also modelled with the simulation program DIALux. This effort complemented the measurements by providing a means to increase the resolution on the light variation and to visualize light pollution in a 3D environment. The simulation results were verified by correlating the numerical model with measurements. The correlated model was exercised in a subsequent sensitivity study to predict possible outcomes with changing lighting pattern and lighting lumen level. This study serves to quantify this issue, which helps with the further development of effective solutions.

Dexamethasone sensitizes to ferroptosis by glucocorticoid receptor-induced dipeptidase-1 expression and glutathione depletion.

Dexamethasone is widely used as an immunosuppressive therapy and recently as COVID-19 treatment. Here, we demonstrate that dexamethasone sensitizes to ferroptosis, a form of iron-catalyzed necrosis, previously suggested to contribute to diseases such as acute kidney injury, myocardial infarction, and stroke, all of which are triggered by glutathione (GSH) depletion. GSH levels were significantly decreased by dexamethasone. Mechanistically, we identified that dexamethasone up-regulated the GSH metabolism regulating protein dipeptidase-1 (DPEP1) in a glucocorticoid receptor (GR)-dependent manner. DPEP1 knockdown reversed the phenotype of dexamethasone-induced ferroptosis sensitization. Ferroptosis inhibitors, the DPEP1 inhibitor cilastatin, or genetic DPEP1 inactivation reversed the dexamethasone-induced increase in tubular necrosis in freshly isolated renal tubules. Our data indicate that dexamethasone sensitizes to ferroptosis by a GR-mediated increase in DPEP1 expression and GSH depletion. Together, we identified a previously unknown mechanism of glucocorticoid-mediated sensitization to ferroptosis bearing clinical and therapeutic implications.

Dipeptidase-1 governs renal inflammation during ischemia reperfusion injury.

The mechanisms that drive leukocyte recruitment to the kidney are incompletely understood. Dipeptidase-1 (DPEP1) is a major neutrophil adhesion receptor highly expressed on proximal tubular cells and peritubular capillaries of the kidney. Renal ischemia reperfusion injury (IRI) induces robust neutrophil and monocyte recruitment and causes acute kidney injury (AKI). Renal inflammation and the AKI phenotype were attenuated in Dpep1-/- mice or mice pretreated with DPEP1 antagonists, including the LSALT peptide, a nonenzymatic DPEP1 inhibitor. DPEP1 deficiency or inhibition primarily blocked neutrophil adhesion to peritubular capillaries and reduced inflammatory monocyte recruitment to the kidney after IRI. CD44 but not ICAM-1 blockade also decreased neutrophil recruitment to the kidney during IRI and was additive to DPEP1 effects. DPEP1, CD44, and ICAM-1 all contributed to the recruitment of monocyte/macrophages to the kidney following IRI. These results identify DPEP1 as a major leukocyte adhesion receptor in the kidney and potential therapeutic target for AKI.

AIM2 Suppresses Inflammation and Epithelial Cell Proliferation during Glomerulonephritis.

Absent in melanoma-2 (AIM2) is an inflammasome-forming innate immune sensor for dsDNA but also exhibits inflammasome-independent functions such as restricting cellular proliferation. AIM2 is expressed in the kidney, but its localization and function are not fully characterized. In normal human glomeruli, AIM2 localized to podocytes. In patients with glomerulonephritis, AIM2 expression increased in CD44+-activated parietal epithelial cells within glomerular crescents. To explore AIM2 effects in glomerular disease, studies in Aim2 -/- mice were performed. Aim2-/- glomeruli showed reduced expression of Wilm tumor gene-1 (WT1), WT1-driven podocyte genes, and increased proliferation in outgrowth assays. In a nephrotoxic serum (NTS)-induced glomerulonephritis model, Aim2-/- (B6) mice exhibited more severe glomerular crescent formation, tubular injury, inflammation, and proteinuria compared with wild-type controls. Inflammasome activation markers were absent in both Aim2 -/- and wild-type kidneys, despite an increased inflammatory transcriptomic signature in Aim2 -/- mice. Aim2 -/- mice also demonstrated dysregulated cellular proliferation and an increase in CD44+ parietal epithelial cells during glomerulonephritis. The augmented inflammation and epithelial cell proliferation in Aim2 -/- (B6) mice was not due to genetic background, as Aim2 -/- (B6.129) mice demonstrated a similar phenotype during NTS glomerulonephritis. The AIM2-like receptor (ALR) locus was necessary for the inflammatory glomerulonephritis phenotype observed in Aim2 -/- mice, as NTS-treated ALR -/- mice displayed equal levels of injury as wild-type controls. Podocyte outgrowth from ALR -/- glomeruli was still increased, however, confirming that the ALR locus is dispensable for AIM2 effects on epithelial cell proliferation. These results identify a noncanonical role for AIM2 in suppressing inflammation and epithelial cell proliferation during glomerulonephritis.

Understanding and Managing Corticosteroid-Induced Osteoporosis.

Glucocorticoids are effective immunosuppressants used in a wide variety of diseases. Their use results in secondary osteoporosis in about 30-50% of chronic glucocorticoid users. Glucocorticoids cause a rapid decline in bone strength within the first 3-6 months mostly due to increased bone resorption by osteoclasts. This is followed by a more gradual loss of bone partly due to decreased osteoblastogenesis and osteoblast and osteocyte apoptosis. The loss of bone strength induced by glucocorticoids is not fully captured by bone mineral density measurements. Other tools such as the trabecular bone score and advanced imaging techniques give insight into bone quality; however, these are not used widely in clinical practice. Glucocorticoid-induced osteoporosis should be seen as a widely preventable disease. Currently, only about 15% of chronic glucocorticoid users are receiving optimal care. Glucocorticoids should be prescribed at the lowest dose and shortest duration. All patients should be counselled on lifestyle measures to maintain bone strength including nutrition and weight-bearing exercise. Pharmacological therapy should be considered for all patients at moderate to high risk of fracture as there is evidence for the prevention of bone loss and fractures with a favourable safety profile. Oral bisphosphonates are the current mainstay of therapy, whereas osteoanabolic agents may be considered for those at highest risk of fracture.

Tissue-selective alternate promoters guide NLRP6 expression.

The pryin domain (PYD) domain is involved in protein interactions that lead to assembly of immune-sensing complexes such as inflammasomes. The repertoire of PYD-containing genes expressed by a cell type arms tissues with responses against a range of stimuli. The transcriptional regulation of the PYD gene family however is incompletely understood. Alternative promoter utilization was identified as a mechanism regulating the tissue distribution of human PYD gene family members, including NLRP6 that is translationally silenced outside of intestinal tissue. Results show that alternative transcriptional promoters mediate NLRP6 silencing in mice and humans, despite no upstream genomic synteny. Human NLRP6 contains an internal alternative promoter within exon 2 of the PYD, resulting in a truncated mRNA in nonintestinal tissue. In mice, a proximal promoter was used that expanded the 5' leader sequence restricting nuclear export and abolishing translational efficiency. Nlrp6 was dispensable in disease models targeting the kidney, which expresses noncanonical isoforms. Thus, alternative promoter use is a critical mechanism not just for isoform modulation but for determining expression profile and function of PYD family members.

Changes in Market Share of Biologic and Targeted Synthetic Disease-Modifying Anti-Rheumatic Drugs for Treatment of Rheumatoid Arthritis: Results from the Ontario Best-Practice Research Initiative Database.

OBJECTIVE: For patients with Rheumatoid Arthritis (RA) who do not achieve adequate clinical response with combined conventional synthetic disease-modifying anti-rheumatic drugs (cs- DMARDs), initiation of advanced therapies such as biologic DMARDs (bDMARDs) or targeted synthetic DMARDs (tsDMARDs) is recommended. Tumour necrosis factor inhibitors (TNFi) are the oldest and most commonly used subgroup of advanced therapies. In the last decade, new non-TNFi advanced therapy options have become available. We described the relative use of TNFi vs. non-TNFi in Ontario-based practices from 2008-2017. METHODS: Adult patients with RA enrolled in the Ontario Best Practices Research Initiative (OBRI) database who started bDMARDs or tsDMARDs anytime during or within 30 days prior to enrollment were included. The proportion of patients treated with TNFi vs. non-TNFi agents between 2008 and 2017 was described for all patients and those initiating their first bDMARD/tsDMARD. All TNFi therapies were included. Non-TNFi included Abatacept, Rituximab, Tocilizumab, and Tofacitinib. RESULTS: A total of 1,057 patients were included, of whom 72.0% were bDMARD/tsDMARD naïve. In 2008, the relative non-TNFi use was 5.4% in all patients while it was 0% in bDMARD/ts- DMARD-naïve patients. In 2017, the proportion of patients using non-TNFi increased to 33.8% among all patients and 33.3% in bDMARD/tsDMARD-naïve patients. CONCLUSION: This descriptive analysis of data from the OBRI cohort reveals that TNFi are still used in the majority of cases; however, there has been an increase in the use of non-TNFi therapies both overall and as first-line advanced therapy. This trend towards non-TNFi therapies as first-line advanced therapy may be partially explained by the shift in guideline recommendations from TNFi as first-line to any of the advanced therapeutics.

Romosozumab in the treatment of osteoporosis.

Osteoporosis is a disease characterized by weakening of the bone architecture, which leads to an increased risk of fracture. There has been interest in the development of osteoanabolic agents that can increase bone mass and reverse the deteriorating architecture of osteoporotic bone. Romosozumab is a new agent for osteoporosis that both promotes bone formation and inhibits bone resorption. It is a monoclonal antibody that inhibits the activity of sclerostin, which allows the Wnt pathway to promote osteoblastogenesis and inhibit the activity of bone-resorbing osteoclasts. In clinical trials, it has proven to be superior to other agents in terms of increasing bone mineral density and reducing the incidence of fractures. This review will highlight the pharmacology, clinical efficacy and safety profile of romosozumab and suggest where this medication may fit within our current management of osteoporosis.

Relationship Between Obesity and Risk of Major Osteoporotic Fracture in Postmenopausal Women: Taking Frailty Into Consideration.

The role of obesity in fracture risk remains uncertain and inconclusive in postmenopausal women. Our study aimed to assess the relationship between obesity and risk of major osteoporotic fracture (MOF; ie, a clinical fracture of upper arm or shoulder, hip, spine, or wrist) in postmenopausal women, after taking frailty into consideration. We used the data from the Global Longitudinal Study of Osteoporosis in Women (GLOW) 5-year Hamilton cohort for this study. Frailty was measured by a frailty index (FI) of deficit accumulation at baseline. We incorporated an interaction term (obesity × FI) in the Cox proportional hazards regression model. We included 3985 women (mean age 69.4 years) for analyses, among which 29% were obese (n = 1118). There were 200 (5.02%) MOF events documented during follow-up: 48 (4.29%) in obese women and 152 (5.65%) in the nonobese group. Significant relationships between obesity, frailty, and MOF risk were found: hazard ratio (HR) = 0.72 (95% confidence interval [CI] 0.67-0.78) for those with an FI of zero regarding MOF risk among obese women, and HR = 1.34 (95% CI 1.11-1.62) per SD increase in the FI among nonobese women. The interaction term was also significant: HR = 1.16 (95% CI 1.02-1.34) per SD increase in the FI among obese women. Increased HRs were found with higher FIs regarding the relationship between obesity and MOF risk, indicating increasing frailty attenuated the protective effect of obesity. For example, although the HR for obesity and MOF risk among those who were not frail (FI = 0) was 0.72 (95% CI 0.67-0.78), among those who were very frail (FI = 0.70), the HR was 0.91 (95% CI 0.85-0.98). To conclude, after taking frailty into consideration, obesity was significantly associated with decreased risk of MOF in postmenopausal women among those who were not frail; however, increasing frailty attenuated this protective effect of obesity. Evaluating frailty status may aid in understanding of the complex relationship between obesity and fracture risk. © 2020 American Society for Bone and Mineral Research (ASBMR).

A Case of Cytomegalovirus-Induced Hemophagocytic Lymphohistiocytosis in a Patient with an Underlying Rheumatic Disease.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition caused by overproduction of inflammatory cytokines and overactivation of macrophages that can progress to multiorgan dysfunction and failure. Although there are guidelines that attempt to recognize the condition in its early stage, diagnosis can be very challenging due to heterogeneous presentations of HLH. Symptoms and clinical findings include fever, neurologic complaints, respiratory issues, liver dysfunction, cytopenias, amongst others most of which are not specific to HLH. In addition, response to treatment can be highly variable, necessitating an individualized treatment plan based on the presentation. We present a case of a 21-year-old female with a history of biopsy-proven inflammatory myositis on azathioprine and prednisone who presented with fever, hypotension, and pancytopenia. Additional imaging studies showed multiorgan involvement, including pneumonia, pyelonephritis, and splenomegaly. A bone marrow biopsy of her iliac crest showed hemophagocytosis and the infectious workup confirmed cytomegalovirus (CMV) infection, which led to the diagnosis of CMV-induced HLH. She was treated initially with anakinra for macrophage activation syndrome (MAS) in addition to dexamethasone and ganciclovir. Unfortunately, she did not respond to anakinra and was subsequently switched to etoposide with dexamethasone and valganciclovir, which subsequently helped our patient to recover clinically. Our case highlights the challenging nature of HLH and the importance of early detection and a personalized treatment plan in achieving optimal outcomes in patients with HLH.

Zoster Sine Herpete Masquerading as Central Nervous System Vasculitis.

Central nervous system (CNS) vasculopathy caused by varicella zoster virus (VZV) is a rare condition. Rarer still is the development of CNS vasculopathy in the absence of a typical zoster rash, a phenomenon known as zoster sine herpete. We report a case of a 34-year-old male with HIV, non-compliant with highly active antiretroviral therapy (HAART), who presented with left-sided temporal headaches and numbness without rash. The patient had a complicated one-month hospital stay when he was initially diagnosed with mycobacterium avium complex (MAC) tuberculosis infection and treated with isoniazid, rifabutin, ethambutol, and azithromycin. Additionally, he was thought to have immune reconstitution inflammatory syndrome (IRIS) and was given steroids. Unfortunately, he presented one day post-discharge with lethargy, aphasia, and dysphagia and was found to have acute/subacute infarcts affecting multiple areas of the brain. CT angiogram (CTA) of the brain showed evidence of multifocal areas of mild to moderate stenosis throughout the intracranial arterial circulation. The patient underwent conventional angiography, which showed segmental arterial constrictions with post-stenotic dilatation consistent with vasculitis. Cerebrospinal fluid (CSF) studies eventually returned positive for VZV by polymerase chain reaction (PCR), confirming a diagnosis of VZV-induced CNS vasculopathy, or more specifically, CNS vasculopathy due to zoster sine herpete. The patient was treated with high-dose steroids as well as IV acyclovir with improvement in his symptoms. He was discharged with advice for a close follow-up with the infectious disease (ID) department. Our case highlights the importance of maintaining a high index of suspicion for varicella infection masquerading as CNS vasculitis, particularly in the absence of classic blistering shingles rash. Early detection may prevent neurological sequelae of the infection, including stroke, dissection, or neuropathy.

Evaluation of the Fracture Liaison Service within the Canadian Healthcare Setting.

Previous studies evaluating fracture liaison service (FLS) programs have found them to be cost-effective, efficient, and reduce the risk of fracture. However, few studies have evaluated the clinical effectiveness of these programs. We compared the patient populations of those referred for osteoporosis management by FLS to those referred by primary care physicians (PCP), within the Canadian healthcare system in the province of Ontario. Specifically, we investigated if a referral from FLS is similarly effective as PCP at identifying patients at risk for future osteoporotic fractures and if osteoporosis therapies have been previously initiated. A retrospective chart review of patients assessed by a single Ontario rheumatology practice affiliated with FLS between January 1, 2014, and December 31, 2017, was performed identifying two groups: those referred by FLS within Hamilton and those referred by their PCP for osteoporosis management. Fracture risk of each patient was determined using FRAX. A total of 573 patients (n = 225 (FLS group) and n = 227 (PCP group)) were evaluated. Between the FLS and PCP groups, there were no significant differences in the absolute 10-year risk of a major osteoporotic fracture (15.6% (SD = 10.2) vs 15.3% (SD = 10.3)) and 10-year risk of hip fracture (4.7% (SD = 8.3) vs 4.7% (SD = 6.8)), respectively. 10.7% of patients referred by FLS and 40.5% of patients referred by their PCP were on osteoporosis medication prior to fracture. Our study suggests that referral from FLS is similarly effective as PCP at identifying patients at risk for future osteoporotic fractures, and clinically effective at identifying the care gap with the previous use of targeted osteoporosis therapies from referral from PCP being low and much lower in those referred by FLS. Interventional programs such as FLS can help close the treatment gap by providing appropriate care to patients that were not previously identified to be at risk for fracture by their primary care physician and initiate proper medical management.

Incorporating adjustments for variability in control group response rates in network meta-analysis: a case study of biologics for rheumatoid arthritis.

BACKGROUND: The importance of adjusting for cross-study heterogeneity in control group response rates when conducting network meta-analyses (NMA) was demonstrated using a case study involving a comparison of biologics for the treatment of moderate-to-severe rheumatoid arthritis. METHODS: Bayesian NMAs were conducted for American College of Rheumatology (ACR) 50 treatment response based upon a set of randomized controlled trials (RCTs) identified by a recently completed systematic review of the literature. In addition to the performance of an unadjusted NMA, a model adjusting for cross-study heterogeneity of control group response rates using meta-regression was fit to the data. Model fit was evaluated, and findings from both analyses were compared with regard to clinical interpretations. RESULTS: ACR 50 response data from a total of 51 RCTs and 16,223 patients were analyzed. Inspection of cross-study variability in control group response rates identified considerable differences between studies. NMA incorporating adjustment for this variability was associated with an average change of 38.1% in the magnitude of the ORs between treatment comparisons, and over 64% of the odds ratio changed by 15% or more. Important changes in the clinical interpretations drawn from treatment comparisons were identified with this improved modeling approach. CONCLUSIONS: In comparing biologics for moderate to severe rheumatoid arthritis, failure to adjust for cross-trial differences in the control arm response rates in NMA can lead to biased estimates of comparative efficacy between treatments.

Determining known-group validity and test-retest reliability in the PEQ (personalized exercise questionnaire).

BACKGROUND: To determine the known-group validity, a type of construct validity, and the test-retest reliability of a newly developed tool, the Personalized Exercise Questionnaire (PEQ), that assesses the barriers, facilitators, and preferences to exercise in individuals with low bone mass and osteoporosis. METHODS: A comparative design was used to assess known-group validity and a test-retest design to examine the reproducibility. Ninety-five participants with low bone mass and osteoporosis were recruited from an outpatient clinic in Hamilton, Ontario. The questionnaire was administered to 95 participants at baseline and a subset of 42 participants completed the survey again one week later. The known-group validity of the PEQ was determined using four hypotheses that compared two known groups based on employment level, age, socioeconomic status, and physical activity level. The reproducibility of individual responses was analyzed using the Kappa Coefficient (κ). RESULTS: There was known-group validity for three of the four hypotheses. Test-retest reliability scores ranged from no agreement to almost perfect agreement; seven items had almost perfect agreement (κ: 0.81-1.00), 12 substantial agreement (κ: 0.68-0.74), six moderate agreement (κ: 0.56-0.60), two fair agreement (κ: 0.36-0.40), one slight agreement (κ = 0.23) and one no agreement (κ = - 0.03). CONCLUSION: Preliminary support for the usefulness of the PEQ is indicated since the majority of the items had at least substantial agreement and known-group validity was moderately supported for some items. TRIAL REGISTRATION: This study was retrospectively registered with ClinicalTrials.gov , NCT03125590, on April 24, 2017.