Managing invasive aspergillosis in haematological patients in the era of resistance polymerase chain reaction and increasing triazole resistance: A modelling study of different strategies

Objectives

Triazole resistance in Aspergillus spp. is emerging and complicates prophylaxis and treatment of invasive aspergillosis (IA) worldwide. New polymerase chain reaction (PCR) tests on broncho-alveolar lavage (BAL) fluid allow for detection of triazole resistance at a genetic level, which has opened up new possibilities for targeted therapy. In the absence of clinical trials, a modelling study delivers estimates of the added value of resistance detection with PCR, and which empiric therapy would be optimal when local resistance rates are known.

Risk of fracture in patients with Guillain-Barré syndrome

Summary

The aim of this study was to evaluate fracture risk in patients with Guillain-Barré syndrome (GBS). No association with risk of fracture was observed for GBS patients compared with controls. Only GBS patients using pain treatment had a doubled risk of fracture.

Introduction

Symptoms of Guillain-Barré syndrome (GBS) may vary from mild difficulty in walking to complete paralysis, which may increase the risk of fractures. Therefore, the aim of this study was to evaluate fracture risk in patients with GBS.

Methods

We conducted a retrospective cohort study using the UK Clinical Practice Research Datalink (1987–2012). Each patient with GBS was matched by year of birth, sex, and practice, up to six patients without a history of GBS. Outcome measure was any fracture.

Results

There were no associations between GBS and any fracture, adjusted hazard ratio (AHR) 1.01 (95 % confidence interval [CI] 0.77–1.33), or osteoporotic fracture, AHR 0.76 (95 % CI 0.50–1.17), compared with controls. Stratification to gender, age, and duration since diagnosis did not show an association either. Only for GBS patients using pain treatment, risk of fracture was doubled AHR 1.97 (95 % confidence CI 1.21–3.21) compared with controls. The risk of fracture in GBS patients exposed to pain treatment was equivalent to risk of fracture among controls exposed to pain treatment.

Conclusions

No association with risk of fracture was observed for GBS patients compared with controls. Only GBS patients using pain treatment had a doubled risk of fracture, but their risk was equivalent to fracture risk among controls exposed to pain treatment.     

Renal Outcomes in Patients with Type 1 Diabetes and Macroalbuminuria

Macroalbuminuria, defined as urine albumin excretion rate (AER)≥300 mg/d, has long been considered a stage of irreversible kidney damage that leads reliably to GFR loss. We examined the long-term renal outcomes of persons with type 1 diabetes who developed incident macroalbuminuria during the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study. One hundred fifty-nine participants developed incident macroalbuminuria and were subsequently followed for a median duration of 9 years (maximum of 25 years). At the time of macroalbuminuria diagnosis, mean (SD) age was 37 (9) years, mean (SD) duration of diabetes was 17 (5) years, median AER was 524 mg/d, and mean (SD) eGFR was 108 (20) ml/min per 1.73 m². Ten years after macroalbuminuria diagnosis, the cumulative incidence of a sustained reduction in AER to <300 mg/d was 52%, mostly but not entirely under treatment with renin-angiotensin system inhibitors. The cumulative incidence of impaired GFR (sustained eGFR<60 ml/min per 1.73 m²) 10 years after macroalbuminuria diagnosis was 32%, including 16% who developed ESRD. Lower hemoglobin A1c and BP and regression to AER<300 mg/d were associated with reduced risk of developing impaired GFR. In conclusion, people with type 1 diabetes who develop macroalbuminuria are at high risk of progressive kidney disease. However, through at least 10 years of follow-up, AER could often be controlled, and GFR frequently remained in the normal range.Macroalbuminuria, defined as urine albumin excretion rate (AER)≥300 mg/d, has long been considered a stage of irreversible kidney damage that leads reliably to GFR loss.¹ In early published type 1 diabetes cohorts, macroalbuminuria was associated with a 15-year cumulative incidence of ESRD as high as 75%.^2,3 However, contemporary long-term renal outcomes of macroalbuminuria have not been fully characterized.The Diabetes Control and Complications Trial (DCCT) and its observational follow-up, the Epidemiology of Diabetes Interventions and Complications (EDIC) study, present a valuable opportunity to examine macroalbuminuria and its long-term clinical outcomes. In DCCT/EDIC, the onset of macroalbuminuria can be defined with confidence using frequent longitudinal measurements of AER, participants have been followed for up to 25 years after the diagnosis of macroalbuminuria, and outcomes were meticulously recorded using standardized methods. Previous work in this cohort has shown that most cases of impaired GFR are preceded by macroalbuminuria,⁴ which is associated with a 50-fold higher risk of developing impaired GFR (eGFR<60 ml/min per 1.73 m²).⁵ Here, we extend these studies by comprehensively evaluating the long-term renal outcomes of incident macroalbuminuria in the DCCT/EDIC cohort and examining the risk factors for its progression to impaired GFR.