Diffuse alveolar haemorrhage associated with subsequent development of ANCA positivity and emphysema in three young adults.

BACKGROUND: Diffuse alveolar haemorrhage (DAH) is characterized by the diffuse accumulation of red blood cells within the alveoli, presence of ground glass opacities and/or consolidation on computed tomography (CT). Aside from identifiable non-immune causes, DAH is classically subdivided into idiopathic (idiopathic pulmonary haemosiderosis, IPH) and autoimmune DAH. Here we describe three cases presenting with recurrent pulmonary haemorrhage, initially classified as IPH, who, several years after first presentation, develop anti myeloperoxidase antibodies (MPO) positivity, emphysema on CT and, in one case, renal involvement. CASE PRESENTATION: Patient 1 was diagnosed with IPH aged 14. Her disease remained poorly controlled despite immunosuppression, although ANCA remained negative over the years. Nineteen years from initial presentation, she developed MPO-ANCA positive antibodies and mild renal impairment. She was treated with Rituximab with good response. From first presentation, the chest CT was consistently characterized by diffuse ground-glass opacities and interlobular septal thickening. Ten years later, cystic opacities consistent with emphysema, with a striking peribronchovascular distribution, developed. Patient 2 was diagnosed with IPH aged 32. He was treated with corticosteroids and methotrexate, with fluctuating response. At 11 years from initial presentation, MPO-ANCA positivity was identified, and emphysema with a peribronchovascular distribution was observed on CT, with subsequent significant increase in extent. Patient 3 was diagnosed with IPH at the age of seven, and had recurrent episodes of haemoptysis of varying degree of severity, treated with intermittent courses of corticosteroids until age 11, when he was intubated due to severe DAH. Eight years after the diagnosis emphysematous changes were noted on CT and MPO-ANCA positivity developed for the first time 11 years after initial diagnosis. CONCLUSIONS: We believe these three cases highlight: 1) the possibility of development of ANCA positivity several years down the line from first DAH presentation 2) the possibility that DAH may lead to cystic/emphysematous changes with peribronchovascular distribution on CT. Moreover, the need for ongoing immunosuppressive treatment and the development of emphysema, emphasize a possible role played by autoimmune phenomena, even when DAH is initially diagnosed as "idiopathic". Further studies are required to better understand the relationship between DAH, ANCA positivity and development of emphysema.

Barriers to a full scope of pharmacy practice in primary care: A systematic review of pharmacists' access to laboratory testing.

OBJECTIVES: To describe primary care pharmacists' current scope of practice in relation to laboratory testing. METHOD: A 2-tiered search of key databases (PubMed, EMBASE, MEDLINE) and grey literature with the following MeSH headings: prescribing, pharmacist/pharmacy, laboratory test, collaborative practice, protocols/guidelines. We focused on Canada, the United States, the United Kingdom, New Zealand and Australia for this review. RESULTS: There is limited literature exploring primary care pharmacists' scope of practice in relation to laboratory testing. The majority of literature is from the United States and Canada, with some from the United Kingdom and New Zealand and none from Australia. Overall, there is a difference in regulations between and within these countries, with the key difference being whether pharmacists access and/or order laboratory testing dependently or independently. Canadian pharmacists can access and/or order laboratory tests independently or dependently, depending on the province they practise in. US pharmacists can access and/or order laboratory tests dependently within collaborative practice agreements. In the United Kingdom, laboratory testing can be performed by independent prescribing pharmacists or dependently by supplementary prescribing pharmacists. New Zealand prescribing pharmacists can order laboratory testing independently. Most publications do not report on the types of laboratory tests used by pharmacists, but those that do predominantly resulted in positive patient outcomes. DISCUSSION/CONCLUSION: Primary care pharmacists' scope of practice in laboratory testing is presently limited to certain jurisdictions and is often performed in a dependent fashion. As such, a full scope of pharmacy services is almost entirely unavailable to patients in the United States, the United Kingdom, New Zealand and Australia. Just as in the case for pharmacists prescribing, evidence indicates better patient outcomes when pharmacists can access/order laboratory tests, but more research needs to be done alongside the implementation of local guidelines and practice standards for pharmacists who practise in that realm. Patients around the world deserve to receive a full scope of pharmacists' practice, and lack of access to laboratory testing is one of the major obstacles to this. Can Pharm J (Ott) 2019;152:xx-xx.

Impact of lipoprotein apheresis on thrombotic parameters in patients with refractory angina and raised lipoprotein(a): Findings from a randomized controlled cross-over trial.

BACKGROUND: Raised lipoprotein(a) [Lp(a)] is a cardiovascular risk factor common in patients with refractory angina. The apolipoprotein(a) component of Lp(a) exhibits structural homology with plasminogen and can enhance thrombosis and impair fibrinolysis. OBJECTIVES: The objective of the study was to assess the effect of lipoprotein apheresis on markers of thrombosis and fibrinolysis in patients with high Lp(a). METHODS: In a prospective, single-blind, crossover trial, 20 patients with refractory angina and raised Lp(a) > 50 mg/dL were randomized to three months of weekly lipoprotein apheresis or sham. Blood taken before and after apheresis/sham was assessed using the Global Thrombosis Test, to assess time taken for in vitro thrombus formation (occlusion time) and endogenous fibrinolysis (lysis time), as well as von Willebrand Factor, fibrinogen, D-dimer, thrombin/anti-thrombin III complex, prothrombin fragments 1 + 2, and thrombin generation assays. RESULTS: Lp(a) was significantly reduced by apheresis (100.2 [interquartile range {IQR}, 69.6143.0] vs 24.8 [17.2,34.0] mg/dL, P = .0001) but not by sham (P = .0001 between treatment arms). Apheresis prolonged occlusion time (576 ± 116 s vs 723 ± 142 s, P < .0001) reflecting reduced platelet reactivity and reduced lysis time (1340 [1128, 1682] s vs 847 [685,1302] s, P = .0006) reflecting enhanced fibrinolysis, without corresponding changes with sham. Apheresis, but not sham, reduced von Willebrand Factor (149 [89.0, 164] vs 64.2 [48.5, 89.8] IU/dL, P = .0001), and fibrinogen (3.12 ± 0.68 vs 2.20 ± 0.53 g/L, P < .0001), and increased prothrombin fragments 1 + 2 (158.16 [128.77, 232.09] vs 795.12 [272.55, 1201.00] pmol/L, P = .0006). There was no change in D-dimer, thrombin/anti-thrombin III complex, or thrombin generation assay with apheresis or sham. CONCLUSION: Lipoprotein apheresis reduces Lp(a) and improves some thrombotic and fibrinolytic parameters in patients with refractory angina.

Plantar Plate Repair Using a Direct Plantar Approach: An Outcomes Analysis.

Direct plantar plate repair using a plantar approach has been described previously, but with few reports of the outcomes or clinical results. The purpose of the present study was to determine the outcomes of this technique. We performed a retrospective analysis of patients who had undergone direct plantar plate repair with or without concomitant Weil osteotomy and a prospective patient-reported subjective outcomes analysis. Ultimately, 131 patients (144 toes) were included, and the response rate for the mailed surveys was 53.5% (77 of 144 toes). The clinical outcomes reported a well-aligned toe in 87.1% of cases, with a recurrence rate of 7.6% (11 of 144) and a revision rate of 2.8% (4 of 144). Statistically significant improvement in the overall modified Foot Function Index (p < .001) and subscale scores for pain (p < .001), disability (p < .001), and activity limitation (p = .001) were noted postoperatively compared with the preoperative data. The median postoperative visual analog pain scale level reported at survey completion was 2.0 (range 0.0 to 10.0; mean ± standard deviation 2.3 ± 2.6). Despite the modified Foot Function Index scores, the patient satisfaction questionnaire data reported mixed results. Our modified Foot Function Index results demonstrated that this approach provides excellent postoperative pain relief, improvement of associated disability, and improvement in activity limitations. The importance of managing patient expectations is acknowledged secondary to the discrepancy with the patient satisfaction data and the modified Foot Function Index results. Further prospective study is warranted to compare this technique with alternate dorsal approaches for plantar plate repair with and without associated commercially available suture passing systems.

A medical device-grade T1 and ECV phantom for global T1 mapping quality assurance-the T1 Mapping and ECV Standardization in cardiovascular magnetic resonance (T1MES) program.

BACKGROUND: T1 mapping and extracellular volume (ECV) have the potential to guide patient care and serve as surrogate end-points in clinical trials, but measurements differ between cardiovascular magnetic resonance (CMR) scanners and pulse sequences. To help deliver T1 mapping to global clinical care, we developed a phantom-based quality assurance (QA) system for verification of measurement stability over time at individual sites, with further aims of generalization of results across sites, vendor systems, software versions and imaging sequences. We thus created T1MES: The T1 Mapping and ECV Standardization Program. METHODS: A design collaboration consisting of a specialist MRI small-medium enterprise, clinicians, physicists and national metrology institutes was formed. A phantom was designed covering clinically relevant ranges of T1 and T2 in blood and myocardium, pre and post-contrast, for 1.5 T and 3 T. Reproducible mass manufacture was established. The device received regulatory clearance by the Food and Drug Administration (FDA) and Conformité Européene (CE) marking. RESULTS: The T1MES phantom is an agarose gel-based phantom using nickel chloride as the paramagnetic relaxation modifier. It was reproducibly specified and mass-produced with a rigorously repeatable process. Each phantom contains nine differently-doped agarose gel tubes embedded in a gel/beads matrix. Phantoms were free of air bubbles and susceptibility artifacts at both field strengths and T1 maps were free from off-resonance artifacts. The incorporation of high-density polyethylene beads in the main gel fill was effective at flattening the B 1 field. T1 and T2 values measured in T1MES showed coefficients of variation of 1 % or less between repeat scans indicating good short-term reproducibility. Temperature dependency experiments confirmed that over the range 15-30 °C the short-T1 tubes were more stable with temperature than the long-T1 tubes. A batch of 69 phantoms was mass-produced with random sampling of ten of these showing coefficients of variations for T1 of 0.64 ± 0.45 % and 0.49 ± 0.34 % at 1.5 T and 3 T respectively. CONCLUSION: The T1MES program has developed a T1 mapping phantom to CE/FDA manufacturing standards. An initial 69 phantoms with a multi-vendor user manual are now being scanned fortnightly in centers worldwide. Future results will explore T1 mapping sequences, platform performance, stability and the potential for standardization.

Magnetic resonance imaging phantoms for quality-control of myocardial T1 and ECV mapping: specific formulation, long-term stability and variation with heart rate and temperature.

BACKGROUND: Magnetic resonance imaging (MRI) phantoms are routinely used for quality assurance in MRI centres; however their long term stability for verification of myocardial T1/ extracellular volume fraction (ECV) mapping has never been investigated. METHODS: Nickel-chloride agarose gel phantoms were formulated in a reproducible laboratory procedure to mimic blood and myocardial T1 and T2 values, native and late after Gadolinium administration as used in T1/ECV mapping. The phantoms were imaged weekly with an 11 heart beat MOLLI sequence for T1 and long TR spin-echo sequences for T2, in a carefully controlled reproducible manner for 12 months. RESULTS: There were only small relative changes seen in all the native and post gadolinium T1 values (up to 9.0 % maximal relative change in T1 values) or phantom ECV (up to 8.3 % maximal relative change of ECV, up to 2.2 % maximal absolute change in ECV) during this period. All native and post gadolinium T2 values remained stable over time with <2 % change. Temperature sensitivity testing showed MOLLI T1 values in the long T1 phantoms increasing by 23.9 ms per degree increase and short T1 phantoms increasing by 0.3 ms per degree increase. There was a small absolute increase in ECV of 0.069 % (~0.22 % relative increase in ECV) per degree increase. Variation in heart rate testing showed a 0.13 % absolute increase in ECV (~0.45 % relative increase in ECV) per 10 heart rate increase. CONCLUSIONS: These are the first phantoms reported in the literature modeling T1 and T2 values for blood and myocardium specifically for the T1mapping/ECV mapping application, with stability tested rigorously over a 12 month period. This work has significant implications for the utility of such phantoms in improving the accuracy of serial scans for myocardial tissue characterisation by T1 mapping methods and in multicentre work.

Biomarkers in Persistent AF and Heart Failure: Impact of Catheter Ablation Compared with Rate Control.

BACKGROUND: To investigate the effects of catheter ablation and rate control strategies on cardiac and inflammatory biomarkers in patients with heart failure and persistent atrial fibrillation (AF). METHODS: Patients were recruited from the ARC-HF trial (catheter Ablation vs Rate Control for management of persistent AF in Heart Failure, NCT00878384), which compared ablation with rate control for persistent AF in heart failure. B-type natriuretic peptide (BNP), midregional proatrial natriuretic peptide (MR-proANP), apelin, and interleukin-6 (IL-6) were assayed at baseline, 3 months, 6 months, and 12 months. The primary end point, analyzed per-protocol, was changed from baseline at 12 months. RESULTS: Of 52 recruited patients, 24 ablation and 25 rate control subjects were followed to 12 months. After 1.2 ± 0.5 procedures, sinus rhythm was present in 22 (92%) ablation patients; under rate control, rate criteria were achieved in 23 (96%) of 24 patients remaining in AF. At 12 months, MR-proANP fell significantly in the ablation arm (-106.0 pmol/L, interquartile range [IQR] -228.2 to -60.6) compared with rate control (-28.7 pmol/L, IQR -69 to +9.5, P = 0.028). BNP showed a similar trend toward reduction (P = 0.051), with no significant difference in apelin (P = 0.13) or IL-6 (P = 0.68). Changes in MR-proANP and BNP correlated with peak VO2 and ejection fraction, and MR-proANP additionally with quality-of-life score. CONCLUSIONS: Catheter ablation, compared with rate control, in patients with heart failure and persistent AF was associated with significant reduction in MR-proANP, which correlated with physiological and symptomatic improvement. Ablation-based rhythm control may induce beneficial cardiac remodeling, unrelated to changes in inflammatory state. This may have prognostic implications, which require confirmation by event end point studies.

Six-month follow-up of a brief intervention on self-reported safety belt use among emergency department patients.

OBJECTIVES: Safety belt use (SBU) reduces motor vehicle deaths by 45%. We previously reported that a brief intervention improved self-reported SBU among emergency department (ED) patients at 3 months. We sought to determine if these effects were sustained at 6 months postenrollment. METHODS: This was a prospective, randomized controlled trial of adult patients (age > or = 21 years) at an academic medical center ED from February 2006 to May 2006. Patients were systematically sampled for self-reported SBU. Those with self-reported SBU less than "always" were asked to participate. Subjects were surveyed at baseline with a nine-item series of situational SBU questions scored on a five-point Likert scale (e.g., 5 = always, 1 = never). This nine-item average comprised the mean SBU score. Subjects were randomized to a control group (CG) and an intervention group (IG). The CG received an injury prevention brochure; the IG received a brief motivation interview by a trained interventionist and the brochure. Subjects were phoned at 3 and 6 months to determine interval change in SBU scores via a standard script. Repeated-measures analysis of covariance and t-tests were used to analyze trends in mean SBU scores between groups, as well as to test mean changes in SBU scores from the 3- to 6-month intervals. RESULTS: Of 432 eligible patients, 292 enrolled (mean age = 35 years, SD +/- 11.2 years; 61% male). At baseline, there were no significant demographic differences; the IG (n = 147) and CG (n = 145) had similar mean SBU scores (2.8 vs. 2.6, p = 0.31), and 66% (n = 96 in each) completed both 3- and 6-month follow-up. The mean SBU score at 6 months in the IG was greater than in the CG group (3.6 vs. 2.9, p < 0.001), as were the mean SBU score differences from baseline (IG = 0.84 vs. CG = 0.29, p < 0.001). These differences were sustained from the 3-month interval (IG = -0.02 vs. CG = -0.06, p > 0.05). CONCLUSIONS: The previously reported finding that ED patients who received a brief motivation interview reported higher SBU scores at 3 months compared to a CG was sustained at 6-month follow-up. Although limited by self-report, a brief intervention may enhance lasting SBU behavior among high-risk ED patients.

Attitudes and practices regarding influenza vaccination among emergency department personnel.

In the United States, infections related to influenza result in a huge burden to the health care system and emergency departments (EDs). Influenza vaccinations are a safe, cost-effective means to prevent morbidity and mortality. We sought to understand the factors that contribute to the professional and personal influenza vaccination practices of health care workers in the ED setting by assessing their knowledge, attitudes, and practices with regards to the influenza vaccine. A cross-sectional study of all full-time ED staff (nurses, emergency medicine residents, and emergency medicine faculty) at an urban academic medical center in Boston treating > 90,000 ED patients annually, was performed. We examined knowledge, attitudes, and practices regarding personal influenza vaccination and support of an ED-based influenza vaccination program using an anonymous, self-administered questionnaire. Of 130 ED staff, 126 individuals completed the survey (97% response rate). Overall, 69% of respondents reported that they were very or extremely likely to be vaccinated before the coming influenza season. Residents (94%) and attending physicians (82%) were significantly more likely than nurses (42%) to be vaccinated (p < 0.001). Respondents likely to be vaccinated this year were more likely to support a vaccination program for ED patients (80% vs. 55% of those not vaccinated,p < 0.001). Providing regular education on the efficacy of preventive vaccination therapy and dispelling misconceptions regarding adverse effects may reduce barriers to vaccination programs. An educational initiative may result in acceptance of influenza vaccination by ED providers themselves, which could result in increased support for an influenza vaccination program for ED patients.

Brief motivational intervention to increase self-reported safety belt use among emergency department patients.

OBJECTIVES: Brief motivational interventions have shown promise in reducing harmful behaviors. The authors tested an intervention to increase safety belt use (SBU) among emergency department (ED) patients. METHODS: From February 2006 to May 2006, the authors conducted a randomized trial of adult ED patients at a teaching hospital in Boston. ED patients were systematically sampled for self-reported SBU. Those with SBU other than "always" were asked to participate. At baseline, participants answered a 9-item series of situational SBU questions, each scored on a 5-point Likert scale. SBU was defined as a continuous variable (9-item average) and as a dichotomous variable (response of "always" across all items). Participants were randomized to an intervention or a control group. The intervention group received a 5- to 7-minute intervention, adapted from classic motivational interviewing techniques, by a trained interventionist. Participants completed a 3-month follow-up phone survey to determine changes from baseline SBU. Continuous and dichotomous SBU were analyzed via analysis of covariance and chi-square testing. RESULTS: Of 432 eligible patients, 292 enrolled (mean age 35 years, standard deviation [SD] +/-11 years; 61% male). At baseline, the intervention and control groups had similar mean (+/-SD) SBU scores (2.8 [+/-1.1] vs. 2.6 [+/-1.1], p = 0.31) and SBU prevalence (each 0%). At 3 months, 81% completed follow-up. The intervention group had significantly greater improvement in mean (+/-SD) SBU scores than controls (0.76 [+/-0.91] vs. 0.34 [+/-0.88], p < 0.001). Also, SBU prevalence of "always" was higher for the intervention group than controls (14.4% vs. 5.9%, p = 0.03). CONCLUSIONS: Participants receiving a brief motivational intervention reported higher SBU at follow-up compared to controls. An ED-based intervention may be useful to increase SBU.

Effects of presentation and electrocardiogram on time to treatment of hyperkalemia.

OBJECTIVES: To assess the time to treatment for emergency department (ED) patients with critical hyperkalemia and to determine whether the timing of treatment was associated with clinical characteristics or electrocardiographic abnormalities. METHODS: The authors performed a retrospective chart review of ED patients with the laboratory diagnosis of hyperkalemia (potassium level > 6.0 mmol/L). Patients presenting in cardiac arrest or who were referred for hyperkalemia or dialysis were excluded. Patient charts were reviewed to find whether patients received specific treatment for hyperkalemia and, if so, what clinical attributes were associated with the time to initiation of treatment. RESULTS: Of 175 ED visits that occurred over a 1-year time period, 168 (96%) received specific treatment for hyperkalemia. The median time from triage to initiation of treatment was 117 minutes (interquartile range [IQR] = 59 to 196 minutes). The 7 cases in which hyperkalemia was not treated include 4 cases in which the patient was discharged home, with a missed diagnosis of hyperkalemia. Despite initiation of specific therapy for hyperkalemia in 168 cases, 2 patients died of cardiac arrhythmias. Among the patients who received treatment, 15% had a documented systolic blood pressure (sBP) < 90 mmHg, and 30% of treated patients were admitted to intensive care units. The median potassium value was 6.5 mmol/L (IQR = 6.3 to 7.1 mmol/L). The predominant complaints were dyspnea (20%) and weakness (19%). Thirty-six percent of patients were taking angiotensin-converting enzyme (ACE) inhibitors. Initial electrocardiograms (ECGs) were abnormal in 83% of patient visits, including 24% of ECGs with nonspecific ST abnormalities. Findings of peaked T-wave morphology (34%), first-degree atrioventricular block (17%), and interventricular conduction delay (12%) did not lead to early treatment. Vital sign abnormalities, including hypotension (sBP < 90 mmHg), were not associated with early treatment. The chief complaint of "unresponsive" was most likely to lead to early treatment; treatment delays occurred in patients not transported by ambulance, those with a chief complaint of syncope and those with a history of hypertension. CONCLUSIONS: Recognition of patients with severe hyperkalemia is challenging, and the initiation of appropriate therapy for this disorder is frequently delayed.

Repeatability of sodium and chloride in exhaled breath condensates.

Exhaled breath condensate (EBC) has been proposed as a noninvasive tool to study airway inflammation. The reproducibility of breath condensates was recently questioned. We therefore measured sodium and chloride concentrations in EBC and assessed the repeatability of these measurements in healthy adults and children with airway disease. We investigated technical repeatability and within-day repeatability in five healthy adults, and compared these results with those of 10 asthmatic children and 9 children with cystic fibrosis (CF). We also assessed within-period repeatability in the healthy controls. We report that the variability of measurements was similar for within sample, within day, and between visits, for both normals and children with asthma and CF, and that the major source of variability of sodium and chloride measurements is restricted by the reproducibility of the measurement assay method used. The wide use of EBC is more likely to depend on the development of highly sensitive and reproducible assays, rather than further refinements of the collection technique.