High incidence of proliferative and membranous nephritis in SLE patients with low proteinuria in the Accelerating Medicines Partnership.

OBJECTIVE: Delayed detection of LN associates with worse outcomes. There are conflicting recommendations regarding a threshold level of proteinuria at which biopsy will likely yield actionable management. This study addressed the association of urine protein:creatinine ratios (UPCR) with clinical characteristics and investigated the incidence of proliferative and membranous histology in patients with a UPCR between 0.5 and 1. METHODS: A total of 275 SLE patients (113 first biopsy, 162 repeat) were enrolled in the multicentre multi-ethnic/racial Accelerating Medicines Partnership across 15 US sites at the time of a clinically indicated renal biopsy. Patients were followed for 1 year. RESULTS: At biopsy, 54 patients had UPCR <1 and 221 had UPCR ≥1. Independent of UPCR or biopsy number, a majority (92%) of patients had class III, IV, V or mixed histology. Moreover, patients with UPCR <1 and class III, IV, V, or mixed had a median activity index of 4.5 and chronicity index of 3, yet 39% of these patients had an inactive sediment. Neither anti-dsDNA nor low complement distinguished class I or II from III, IV, V or mixed in patients with UPCR <1. Of 29 patients with baseline UPCR <1 and class III, IV, V or mixed, 23 (79%) had a UPCR <0.5 at 1 year. CONCLUSION: In this prospective study, three-quarters of patients with UPCR <1 had histology showing class III, IV, V or mixed with accompanying activity and chronicity despite an inactive sediment or normal serologies. These data support renal biopsy at thresholds lower than a UPCR of 1.

Using a filtration technique to isolate platelet free plasma for assaying pyrophosphate.

BACKGROUND: Vascular calcification (VC) is a strong prognostic marker of mortality from cardiovascular disease. Extracellular inorganic pyrophosphate (PPi) is a critical inhibitor of vascular calcification and it has been reported that hemodialysis patients have reduced plasma PPi levels, suggesting that altered PPi metabolism could contribute to VC in hemodialysis patients. Platelets are rich in PPi and release of PPi from platelets during storage or processing of plasma can lead to falsely elevated plasma PPi levels. To prepare plasma samples that are suitable for measuring PPi levels, ultracentrifugation has been used to remove platelets. Consequently, plasma PPi measurements have been limited to research laboratories since the majority of clinical laboratories do not have access to an ultracentrifuge. The purpose of the present study was to test the validity of an improved method of preparing platelet free plasma that uses filtration with a 300,000 Dalton molecular weight cut-off filter to exclude platelets, while minimizing their release of PPi. METHODS: In 20 maintenance hemodialysis patients, PPi levels were measured in plasma samples prepared by the conventional technique of low-speed centrifugation to remove red and white blood cells versus a novel filtration technique. RESULTS: Plasma prepared by filtration had significantly lower platelet counts (0 vs. 3 - 7 10(3)/microL) and PPi levels (1.39 +/- 0.30 microM vs. 2.74 +/- 1.19 microM; mean +/- SD, p < 0.01). CONCLUSIONS: The filtration method appears effective in excluding platelets without causing trauma to platelets and can be used by clinical laboratories to prepare platelet-depleted plasma for PPi measurement.

Safety of procuring research tissue during a clinically indicated kidney biopsy from patients with lupus: data from the Accelerating Medicines Partnership RA/SLE Network.

OBJECTIVES: In lupus nephritis the pathological diagnosis from tissue retrieved during kidney biopsy drives treatment and management. Despite recent approval of new drugs, complete remission rates remain well under aspirational levels, necessitating identification of new therapeutic targets by greater dissection of the pathways to tissue inflammation and injury. This study assessed the safety of kidney biopsies in patients with SLE enrolled in the Accelerating Medicines Partnership, a consortium formed to molecularly deconstruct nephritis. METHODS: 475 patients with SLE across 15 clinical sites in the USA consented to obtain tissue for research purposes during a clinically indicated kidney biopsy. Adverse events (AEs) were documented for 30 days following the procedure and were determined to be related or unrelated by all site investigators. Serious AEs were defined according to the National Institutes of Health reporting guidelines. RESULTS: 34 patients (7.2%) experienced a procedure-related AE: 30 with haematoma, 2 with jets, 1 with pain and 1 with an arteriovenous fistula. Eighteen (3.8%) experienced a serious AE requiring hospitalisation; four patients (0.8%) required a blood transfusion related to the kidney biopsy. At one site where the number of cores retrieved during the biopsy was recorded, the mean was 3.4 for those who experienced a related AE (n=9) and 3.07 for those who did not experience any AE (n=140). All related AEs resolved. CONCLUSIONS: Procurement of research tissue should be considered feasible, accompanied by a complication risk likely no greater than that incurred for standard clinical purposes. In the quest for targeted treatments personalised based on molecular findings, enhanced diagnostics beyond histology will likely be required.

Comparison between automatic tube compensation and continuous positive airway pressure during spontaneous breathing trials.

BACKGROUND: Various methods to perform spontaneous breathing trials (SBTs) exist, but no one method has been shown to be superior. Automatic tube compensation (ATC) is a new and potentially advantageous ventilation mode to use during SBT. We compared ATC to continuous positive airway pressure (CPAP) during SBTs, to determine their efficacy in identifying patients ready to be liberated from mechanical ventilation. METHODS: We randomized 118 adults in a general intensive care unit on mechanical ventilation for > or = 24 h who were about to undergo an SBT as part of an established respiratory-therapist-driven weaning protocol to undergo 30 min SBT with ATC or CPAP with no pressure support. We predefined the SBT-failure criteria. The primary outcome was duration of weaning (days from first SBT to extubation). Other outcomes included unsuccessful extubation within 48 h, first-SBT-pass rate, and total duration of mechanical ventilation. RESULTS: We found a trend toward less failure of first SBT with ATC, compared to CPAP (3% vs 13% respectively, P = .09), but no difference in duration of weaning, rate of unsuccessful extubation, or duration of mechanical ventilation. CONCLUSIONS: When applied as part of a respiratory-therapist-driven weaning protocol in a general intensive-care population, SBTs with ATC were safe but did not hasten liberation from mechanical ventilation, when compared to CPAP.

Adequacy of outpatient care among hospitalized adult asthmatics in a southwest US border city.

Over 3 years we studied the baseline degree of asthma severity and the adequacy of the usual medical management among asthmatics admitted to a large US-Mexican border county hospital. The study design consisted of 2 years of retrospective chart review and 1 year of prospective semistructured interview collection. Patients were at least 18 years of age and required acute care and hospital admission for asthma exacerbations. The 127 patients studied accounted for 166 hospital admissions for asthma related primary diagnoses. Most were Hispanic and medically indigent, and only 39% of patients whose asthma severity indicated the use of inhaled corticosteroid medications reported taking them. Most of the hospitalized asthmatic patients studied were on inadequate outpatient medical regimens for the baseline severity of their asthma. Underuse of inhaled corticosteroids was the predominant medication deficiency. Other shortcomings identified in their routine management included a lack of pulmonary function testing, basic asthma education, and treatment by a practitioner qualified in the care of chronic asthma.

Changes in breathing variables during a 30-minute spontaneous breathing trial.

BACKGROUND: Spontaneous breathing trials (SBTs) are increasingly performed. Significant changes in monitored breathing variables and the timing of those changes during the trial have important implications for its outcome determination and supervision. We aimed to study the magnitude and timing of change in breathing variables during the course of a 30-min SBT. METHODS: Breathing variables were continuously measured and averaged by minute during the SBT in 32 subjects with trial success and 8 subjects with trial failure from a general ICU population. Percentage changes in breathing variables during the trial and proportions of subjects showing a ≥20% change at different time points relative to the second minute of the trial were calculated. RESULTS: The commonly monitored breathing variables (frequency, tidal volume, their ratio, and minute ventilation) showed median coefficients of variation of <15% throughout the trial and a median change of less than ±20% by the end of the trial. Changes in a detrimental direction of ≥20% at the end of the trial but not already present at 10 min were noted in ≤5% of all subjects. CONCLUSIONS: During the course of a 30-min SBT, breathing variables remain relatively constant, and potentially significant changes in these variables after 10 min into the trial are uncommon. These findings should be considered when addressing aspects of duration and supervision of SBTs in weaning protocols.

Predictive models of prolonged mechanical ventilation yield moderate accuracy.

PURPOSE: To develop a model to predict prolonged mechanical ventilation within 48 hours of its initiation. MATERIALS AND METHODS: In 282 general intensive care unit patients, multiple variables from the first 2 days on mechanical ventilation and their total ventilation duration were prospectively collected. Three models accounting for early deaths were developed using different analyses: (a) multinomial logistic regression to predict duration > 7 days vs duration ≤ 7 days alive vs duration ≤ 7 days death; (b) binary logistic regression to predict duration > 7 days for the entire cohort and for survivors only, separately; and (c) Cox regression to predict time to being free of mechanical ventilation alive. RESULTS: Positive end-expiratory pressure, postoperative state (negatively), and Sequential Organ Failure Assessment score were independently associated with prolonged mechanical ventilation. The multinomial regression model yielded an accuracy (95% confidence interval) of 60% (53%-64%). The binary regression models yielded accuracies of 67% (61%-72%) and 69% (63%-75%) for the entire cohort and for survivors, respectively. The Cox regression model showed an equivalent to area under the curve of 0.67 (0.62-0.71). CONCLUSIONS: Different predictive models of prolonged mechanical ventilation in general intensive care unit patients achieve a moderate level of overall accuracy, likely insufficient to assist in clinical decisions.

Accuracy of early prediction of duration of mechanical ventilation by intensivists.

RATIONALE: Predictions of duration of mechanical ventilation are frequently made by intensivists and influence clinical decisions. OBJECTIVES: We aimed to measure the accuracy of these clinical early predictions. METHODS: One hundred fifty-five patients within 48 hours of initiation of mechanical ventilation on a general intensive care unit had clinical data prospectively collected and were followed to determine actual duration of mechanical ventilation. Intensivists, after evaluating patients in the first 2 consecutive days, predicted each duration of mechanical ventilation by selecting between less than 3, 4 to 7, 8 to 14, or more than 14 days. Accuracy of predictions was evaluated by comparisons between predicted and actual durations. MEASUREMENTS AND MAIN RESULTS: Raw agreement (95% confidence interval) between predicted and actual durations, classified into the four categories, was 37% (29-45%). Predictions of duration of more than 7 and more than 14 days showed raw agreements of 59% (51-66%) and 83% (76-88%); sensitivities of 40% (28-54%) and 29% (13-51%); specificities of 71% (61-80%) and 93% (87-97%); positive predictive values of 48% (34-63%) and 44% (20-70%); and negative predictive values of 64% (54-73%) and 87% (81-92%), respectively. CONCLUSIONS: The accuracy of intensivists' early clinical predictions of duration of mechanical ventilation is limited, particularly for identifying patients who will require prolonged mechanical ventilation.