Rivaroxaban in Patients with Atrial Fibrillation and a Bioprosthetic Mitral Valve.

BACKGROUND: The effects of rivaroxaban in patients with atrial fibrillation and a bioprosthetic mitral valve remain uncertain. METHODS: In this randomized trial, we compared rivaroxaban (20 mg once daily) with dose-adjusted warfarin (target international normalized ratio, 2.0 to 3.0) in patients with atrial fibrillation and a bioprosthetic mitral valve. The primary outcome was a composite of death, major cardiovascular events (stroke, transient ischemic attack, systemic embolism, valve thrombosis, or hospitalization for heart failure), or major bleeding at 12 months. RESULTS: A total of 1005 patients were enrolled at 49 sites in Brazil. A primary-outcome event occurred at a mean of 347.5 days in the rivaroxaban group and 340.1 days in the warfarin group (difference calculated as restricted mean survival time, 7.4 days; 95% confidence interval [CI], -1.4 to 16.3; P<0.001 for noninferiority). Death from cardiovascular causes or thromboembolic events occurred in 17 patients (3.4%) in the rivaroxaban group and in 26 (5.1%) in the warfarin group (hazard ratio, 0.65; 95% CI, 0.35 to 1.20). The incidence of stroke was 0.6% in the rivaroxaban group and 2.4% in the warfarin group (hazard ratio, 0.25; 95% CI, 0.07 to 0.88). Major bleeding occurred in 7 patients (1.4%) in the rivaroxaban group and in 13 (2.6%) in the warfarin group (hazard ratio, 0.54; 95% CI, 0.21 to 1.35). The frequency of other serious adverse events was similar in the two groups. CONCLUSIONS: In patients with atrial fibrillation and a bioprosthetic mitral valve, rivaroxaban was noninferior to warfarin with respect to the mean time until the primary outcome of death, major cardiovascular events, or major bleeding at 12 months. (Funded by PROADI-SUS and Bayer; RIVER ClinicalTrials.gov number, NCT02303795.).

Acupuncture-D" - Bilateral Pneumothoraces Following Dry Needling.

Presentation A 24-year-old newly graduated junior doctor presented to the emergency department with acute onset chest pain, haemoptysis and exertional dyspnoea following a dry needling session. Diagnosis Chest x-ray showed bilateral pneumothoraces, worse on the right side. Treatment The bilateral pneumothoraces were treated conservatively with supplemental oxygen initially. On the second day of admission, repeat chest x-ray demonstrated a worsening right sided pneumothorax. While vitally stable, the patient however had become increasingly dyspnoeic, and a needle aspiration was performed on the right side with good effect. Conclusion The anatomical location targeted along with the patients low-normal BMI makes her high-risk when considering the skin-to-pleura distance. Although the incidence of pneumothorax is low, it is imperative that we improve awareness both for the treating physician and the diagnosing clinician. We must begin to fill the distinct lack in available literature surrounding the potential adverse effects of dry needling.

A randomized clinical trial to evaluate the efficacy and safety of rivaroxaban in patients with bioprosthetic mitral valve and atrial fibrillation or flutter: Rationale and design of the RIVER trial.

The efficacy and safety of rivaroxaban in patients with bioprosthetic mitral valves and atrial fibrillation or flutter remain uncertain. DESIGN: RIVER was an academic-led, multicenter, open-label, randomized, non-inferiority trial with blinded outcome adjudication that enrolled 1005 patients from 49 sites in Brazil. Patients with a bioprosthetic mitral valve and atrial fibrillation or flutter were randomly assigned (1:1) to rivaroxaban 20 mg once daily (15 mg in those with creatinine clearance <50 mL/min) or dose-adjusted warfarin (target international normalized ratio 2.0-30.); the follow-up period was 12 months. The primary outcome was a composite of all-cause mortality, stroke, transient ischemic attack, major bleeding, valve thrombosis, systemic embolism, or hospitalization for heart failure. Secondary outcomes included individual components of the primary composite outcome, bleeding events, and venous thromboembolism. SUMMARY: RIVER represents the largest trial specifically designed to assess the efficacy and safety of a direct oral anticoagulant in patients with bioprosthetic mitral valves and atrial fibrillation or flutter. The results of this trial can inform clinical practice and international guidelines.

Thermodynamic Acidity Studies of 6,6'-Dihydroxy-2,2'-bipyridine: A Combined Experimental and Computational Approach.

The organic ligand 6,6'-dihydroxy-2,2'-bipyridine (6,6'-dhbp) is frequently used to bind transition metals in order to form catalysts for many organic and inorganic transformations. 6,6'-dhbp exists in two tautomeric forms, the pyridinol tautomer and the amide (lactam) tautomer with each tautomer having two rotational conformers: cis or trans. Only the cis-pyridinol tautomer has the proper configuration to bind transition metals. The pendant OH (or O- groups when deprotonated) in 6,6'-dhbp typically do not bind the metal when forming the metal catalyst but can facilitate the proton transfer steps in the catalysis process. Electronic structure calculations were used to predict the stability of all possible isomers (including conformers and protonation states) in the gas phase and aqueous solution. These results have been compared to experimental data including UV-vis and NMR spectra as a function of pH. The pKa values for the 6,6'-dhbp ligand in the -2 to +2 structures were predicted, and these ligands show different behavior in the gas phase versus in aqueous solution.

What side effects are problematic for patients prescribed antipsychotic medication? The Maudsley Side Effects (MSE) measure for antipsychotic medication.

BACKGROUND: Capturing service users' perspectives can highlight additional and different concerns to those of clinicians, but there are no up to date, self-report psychometrically sound measures of side effects of antipsychotic medications. Aim To develop a psychometrically sound measure to identify antipsychotic side effects important to service users, the Maudsley Side Effects (MSE) measure. METHOD: An initial item bank was subjected to a Delphi exercise (n = 9) with psychiatrists and pharmacists, followed by service user focus groups and expert panels (n = 15) to determine item relevance and language. Feasibility and comprehensive psychometric properties were established in two samples (N43 and N50). We investigated whether we could predict the three most important side effects for individuals from their frequency, severity and life impact. RESULTS: MSE is a 53-item measure with good reliability and validity. Poorer mental and physical health, but not psychotic symptoms, was related to side-effect burden. Seventy-nine percent of items were chosen as one of the three most important effects. Severity, impact and distress only predicted 'putting on weight' which was more distressing, more severe and had more life impact in those for whom it was most important. CONCLUSIONS: MSE is a self-report questionnaire that identifies reliably the side-effect burden as experienced by patients. Identifying key side effects important to patients can act as a starting point for joint decision making on the type and the dose of medication.

Ruthenium (II) and Iridium (III) Complexes of N-Heterocyclic Carbene and Pyridinol Derived Bidentate Chelates: Synthesis, Characterization, and Reactivity.

We report the synthesis and characterization of new ruthenium(II) and iridium(III) complexes of a new bidentate chelate, NHCR'-pyOR (OR = OMe, OtBu, OH and R' = Me, Et). Synthesis and characterization studies were done on the following compounds: four ligand precursors (1-4); two silver complexes of these NHCR'-pyOR ligands (5-7); six ruthenium complexes of the type [η6-(p-cymene)Ru(NHCR'-pyOR)Cl]X with R' = Me, Et and R = Me, tBu, H and X = OTf-, PF6- and PO2F2- (8-13); and two iridium complexes, [Cp*Ir(NHCMe-pyOtBu)Cl]PF6 (14) and [Cp*Ir(NHCMe-pyOH)Cl]PO2F2 (15). The complexes are air stable and were isolated in moderate yield. However, for the PF6- salts, hydrolysis of the PF6- counter anion to PO2F2- during t-butyl ether deprotection was observed. Most of the complexes were characterized by 1H and 13C-NMR, MS, IR, and X-ray diffraction. The ruthenium complexes [η6-(p-cymene)Ru(NHCMe-pyOR)Cl]OTf (R = Me (8) and tBu (9)) were tested for their ability to accelerate CO2 hydrogenation and formic acid dehydrogenation. However, our studies show that the complexes transform during the reaction and these complexes are best thought of as pre-catalysts.

Studies of the pathways open to copper water oxidation catalysts containing proximal hydroxy groups during basic electrocatalysis.

Water oxidation can lead to a sustainable source of energy, but for water oxidation catalysts to be economical they must use earth abundant metals. We report here 2:1 6,6'-dihydroxybipyridine (6,6'-dhbp)/copper complexes that are capable of electrocatalytic water oxidation in aqueous base (pH = 10-14). Two crystal structures of the complex that contains 6,6'-dhbp and copper(II) in a ratio of 2:1 (complex 1) are presented at different protonation states. The thermodynamic acid dissociation constants were measured for complex 1, and these show that the complex is fully deprotonated above pH = 8.3 (i.e., under water oxidation conditions). CW-EPR, ENDOR, and HYSCORE spectroscopy confirmed that the 6,6'-dhbp ligand is bound to the copper ion over a wide pH range which shows how pH influences precatalyst structure. Additional copper(II) complexes were synthesized from the ligands 4,4'-dhbp (complex 2) and 6,6'-dimethoxybipyridine (complexes 3 and 4). A zinc complex of 6,6'-dhbp was also synthesized (complex 5). Crystal structures are reported for 1 (in two protonation states), 3, 4, and 5. Water oxidation studies using several of the above compounds (1, 2, 4, and 5) at pH = 12.6 have illustrated that both copper and proximal OH groups are necessary for water oxidation at a low overpotential. Our most active catalyst 1 was found to have an overpotential of 477 mV for water oxidation at a moderate rate of kcat = 0.356 s(-1) with a competing irreversible oxidation event at a rate of 1.082 s(-1). Furthermore, our combined work supports previous observations in which OH/O(-) groups on the bipyridine rings can hydrogen bond with metal bound substrate, support unusual binding modes, and potentially facilitate proton coupled electron transfer.

Motor unit properties from three synergistic muscles during ramp isometric elbow extensions.

Many tasks require synergistic activation of muscles that possess different architectural, mechanical, and neural control properties. However, investigations of the motor unit (MU) mechanisms which modulate force are mostly restricted to individual muscles and low forces. To explore the pattern of MU recruitment and discharge behavior among three elbow extensors (lateral and long heads of the triceps brachii, and anconeus) during ramp isometric contractions, recruitment thresholds of 77 MUs in five young men were determined and corresponding MU discharge rates were tracked in 1-s epochs over forces ranging from 0 to 75 % of maximal voluntary isometric force (MVC). Across all forces, MUs in the lateral head discharged at higher rates than those in the anconeus (p < 0.001, Δ = 0.23). When all MUs were considered, recruitment thresholds in the long head of the triceps brachii were higher than the lateral head (p < 0.05, Δ = 0.70) with a trend (p = 0.08, Δ = 0.48) for higher recruitment thresholds in the long head compared with the anconeus. Together, these data indicate a potential mechanical disadvantage of the long head of the triceps brachii at 0° shoulder flexion. However, among low-threshold MUs (<10 % MVC), recruitment thresholds were lower in the anconeus than in both heads of the triceps brachii consistent with the expected twitch contractile and fiber type differences among these muscles. These findings illustrate the importance of considering synergistic relations among muscles used for a coordinated task, and the sensitivity of synergies to muscle architectural, mechanical, and possibly specific synaptic input factors.

Screening and management of renal disease in human immunodeficiency virus-infected patients in Australia.

BACKGROUND: Renal disease has become one of the most important comorbidities observed in the human immunodeficiency virus (HIV)-infected patient cohort. Data are lacking on the current screening and management of renal disease in patients with HIV. We evaluated HIV-infected Australian adults in primary care to determine current practices. METHODS: This prospective, multicentre observational study included two rounds of data collection; the first was followed by an educational programme. Outcomes included screening for renal disease; management of risk factors for kidney disease and other comorbidities associated with renal disease. RESULTS: Fifty-three general practitioners participated with 733 patients enrolled. Most were male (94%); almost 40% were 41-50 years of age, and 6% and 84% were receiving antiretroviral therapy. Comorbidities were common; 19% had hypertension, 5% were diabetic, 32% were dyslipidaemic, and 40% were smokers. Estimated glomerular filtration rate was commonly measured in both rounds of data collection (96% vs 95%). Proteinuria was assessed less frequently; this improved after education (48% vs 71%). Almost 10% of patients tested had proteinuria on urinalysis. Of the 45 patients (6%) with renal impairment (estimated glomerular filtration rate <60 mL/min), none was referred for assessment by a renal specialist. CONCLUSIONS: This large observational study provides important information on renal disease in HIV-infected patients, an area with a paucity of clinical data. Current screening and management practices fall short of suggested guidelines. Failure to refer patients to specialists is a major deficiency. Improvements with education suggest the need to promote awareness of guidelines in primary care doctors.

The effects of acute normobaric hypoxia on vestibular-evoked balance responses in humans.

BACKGROUND: Hypoxia influences standing balance and vestibular function. OBJECTIVE: The purpose here was to investigate the effect of hypoxia on the vestibular control of balance. METHODS: Twenty participants (10 males; 10 females) were tested over two days (normobaric hypoxia and normoxia). Participants stood on a force plate (head rotated leftward) and experienced random, continuous electrical vestibular stimulation (EVS) during trials of eyes open (EO) and closed (EC) at baseline (BL), after 5 (H1), 30 (H2) and 55-min (H3) of hypoxia, and 10-min into normoxic recovery (NR). Vestibular-evoked balance responses were quantified using cumulant density, coherence, and gain functions between EVS and anteroposterior forces. RESULTS: Oxyhemoglobin saturation, end-tidal oxygen and carbon dioxide decreased for H1-3 compared to BL; however, end-tidal carbon dioxide remained reduced at NR with EC (p≤0.003). EVS-AP force peak-to-peak amplitude was lower at H3 and NR than at BL (p≤0.01). At multiple frequencies, EVS-AP force coherence and gain estimates were lower at H3 and NR than BL for females; however, this was only observed for coherence for males. CONCLUSIONS: Overall, vestibular-evoked balance responses are blunted following normobaric hypoxia >30 min, which persists into NR and may contribute to the reported increases in postural sway.

Design and delivery of an e-learning curriculum for physicians involved in the management of pulmonary hypertension.

BACKGROUND: Pulmonary hypertension (PH) is a condition that affects more than 25 million individuals worldwide and causes premature disability and death. Despite advances in our understanding of this condition, education and training of health professionals has not kept pace with the rapid changes in diagnosis and treatment. The net effects of this gap between advancing knowledge and limited educational opportunity likely include clinically significant delays in both the diagnosis and commencement of effective evidence-based treatment - an unacceptable outcome for patients with a lethal condition. AIM: The Actelion Clinical Excellence Programme (ACEP) is an e-learning postgraduate curriculum, the purpose of which is to educate and mentor healthcare professionals, both theoretically and practically, in the diagnosis and treatment of patients with all forms of PH. This article reports on the development and delivery of the programme and outcomes from its first year of operation. RESULTS: Forty-three healthcare professionals from 22 institutions were enroled in the first iteration of the programme. In the 6 months from May to October 2011, participants successfully completed 285 lectures and/or activities. Overall, the programme was considered easily accessible, comprehensive in terms of both quality and quantity, provided an efficient means of self-paced learning, and was a highly regarded as reference source. Ninety-five per cent of participants said that they intended to change their clinical practice as a result of the information presented in the programme. CONCLUSION: ACEP represents a successful physician-industry partnership, which has resulted in a significant impact on clinical teaching and awareness of PH.

Assessment of MMP-9, TIMP-1, and COX-2 in normal tissue and in advanced symptomatic and asymptomatic carotid plaques.

BACKGROUND: Mature carotid plaques are complex structures, and their histological classification is challenging. The carotid plaques of asymptomatic and symptomatic patients could exhibit identical histological components. OBJECTIVES: To investigate whether matrix metalloproteinase 9 (MMP-9), tissue inhibitor of MMP (TIMP), and cyclooxygenase-2 (COX-2) have different expression levels in advanced symptomatic carotid plaques, asymptomatic carotid plaques, and normal tissue. METHODS: Thirty patients admitted for carotid endarterectomy were selected. Each patient was assigned preoperatively to one of two groups: group I consisted of symptomatic patients (n = 16, 12 males, mean age 66.7 ± 6.8 years), and group II consisted of asymptomatic patients (n = 14, 8 males, mean age 67.6 ± 6.81 years). Nine normal carotid arteries were used as control. Tissue specimens were analyzed for fibromuscular, lipid and calcium contents. The expressions of MMP-9, TIMP-1 and COX-2 in each plaque were quantified. RESULTS: Fifty-eight percent of all carotid plaques were classified as Type VI according to the American Heart Association Committee on Vascular Lesions. The control carotid arteries all were classified as Type III. The median percentage of fibromuscular tissue was significantly greater in group II compared to group I (p < 0.05). The median percentage of lipid tissue had a tendency to be greater in group I than in group II (p = 0.057). The percentages of calcification were similar among the two groups. MMP-9 protein expression levels were significantly higher in group II and in the control group when compared with group I (p < 0.001). TIMP-1 expression levels were significantly higher in the control group and in group II when compared to group I, with statistical difference between control group and group I (p = 0.010). COX-2 expression levels did not differ among groups. There was no statistical correlation between MMP-9, COX-2, and TIMP-1 levels and fibrous tissue. CONCLUSIONS: MMP-9 and TIMP-1 are present in all stages of atherosclerotic plaque progression, from normal tissue to advanced lesions. When sections of a plaque are analyzed without preselection, MMP-9 concentration is higher in normal tissues and asymptomatic surgical specimens than in symptomatic specimens, and TIMP-1 concentration is higher in normal tissue than in symptomatic specimens.

Videodensitometric analysis of advanced carotid plaque: correlation with MMP-9 and TIMP-1 expression.

BACKGROUND: Matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of MMP (TIMP) promote derangement of the extracellular matrix, which is ultimately reflected in plaque images seen on ultrasound. Videodensitometry can identify structural disturbances in plaques. OBJECTIVES: To establish the correlations between values determined using videodensitometry in B-mode ultrasound images of advanced carotid plaques and the total expression of MMP-9 and TIMP-1 in these removed plaques. METHODS: Thirty patients underwent ultrasonic tissue characterization of carotid plaques before surgery, using mean gray level (MGL), energy, entropy and homogeneity. Each patient was assigned preoperatively to one of 2 groups: group I, symptomatic patients (n = 16; 12 males; mean age 66.7 ± 6.8 years), and group II, asymptomatic patients (n = 14; 8 males; mean age 67.6 ± 6.81 years). Tissue specimens were analyzed for MMP-9 and TIMP-1 expression. Nine carotid arteries were used as normal tissue controls. RESULTS: MMP-9 expression levels were elevated in group II and in normal tissues compared to group I (p < 0.001). TIMP-1 levels were higher in group II than in group I, and significantly higher in normal tissues than in group I (p = 0.039). The MGL was higher in group II compared to group I (p = 0.038). Energy had greater values in group II compared to group I (p = 0.02). There were no differences between patient groups in homogeneity and entropy. Energy positively correlated with MMP-9 and TIMP-1 expression (p = 0.012 and p = 0.031 respectively). Homogeneity positively correlated with MMP-9 and TIMP-1 expression (p = 0.034 and p = 0.047 respectively). There were no correlations between protein expression and MGL or entropy. CONCLUSIONS: Videodensitometric computer analysis of ultrasound scanning images can be used to identify stable carotid plaques, which have higher total expression levels of MMP-9 and TIMP-1 than unstable plaques.

The Bosentan Patient Registry: long-term survival in pulmonary arterial hypertension.

BACKGROUND/AIMS: The Bosentan Patient Registry (BPR) was a prospective, multicentre, Australian registry funded by Actelion Pharmaceuticals. The primary aim of the registry was to collect survival data in patients with pulmonary arterial hypertension (PAH) treated with bosentan. METHODS: The BPR was initiated in 15 specialized PAH centres. All patients on or starting bosentan were invited to enrol. Treating physicians notified the registry if patients discontinued bosentan, because of either a change in therapy, transplantation, intervention or death. Survival data were validated against the Australian Institute of Health and Welfare National Death Index. RESULTS: Between 2004 and 2007, a total of 528 patients (mean age 59 ± 17 years) were enrolled representing 69% of patients either previously taking or initiated on bosentan during that time. The BPR population was generally older with more advanced functional deficit than patients enrolled in randomized, placebo-controlled trials. Aetiology was idiopathic (iPAH) in 58% and connective tissue disease related (scleroderma (SSc)-PAH) in 42%. For iPAH patients, World Health Organisation functional classes II, III and IV at enrolment was 8.2%, 66.4% and 20.5%, and for the SSc-PAH cohort, 3.2%, 75.8% and 17.9% respectively. The observed annual mortality was 11.8% in patients with iPAH and 16.6% in patients SSc-PAH. CONCLUSION: This large Australian registry provides 'real life' information on the characteristics and management of PAH in clinical practice. Treatment with bosentan improved survival outcomes in both iPAH and SSc-PAH compared with historical controls. Age, disease severity and aetiology were critical factors in determining clinical outcomes.

Survival after the initiation of combination therapy in patients with pulmonary arterial hypertension: an Australian collaborative report.

BACKGROUND: Several cellular pathways are implicated in the pathogenesis of pulmonary arterial hypertension (PAH) and attempts to arrest disease progression with a single drug would not be expected to succeed in the medium term. In clinical practice, combination therapy is often used in patients deteriorating on monotherapy, despite the absence of firm evidence from randomized controlled controls. METHODS: From January 2005 to August 2009, 112 patients with World Health Organisation Functional Class (FC) II-IV PAH deteriorating on monotherapy received non-parenteral combination therapy at six Australian PAH expert hospitals. Combination therapy included bosentan, sitaxentan, ambrisentan, iloprost and sildenafil. Data were prospectively collected for survival status, 6-min walk distance, FC and echocardiographic parameters at the start of monotherapy through to commencement of combination therapy and at 6-monthly intervals thereafter. RESULTS: After varying periods of monotherapy (18.7±13.4onths), survival estimates on combination therapy were 88%, 71% and 61% for the additional 1, 2 and 3years respectively. Survival on dual therapy in patients with idiopathic PAH/familial PAH was 93% at 1year and 79% at 2years, and for scleroderma-related PAH, 72% at 1 year and 48% at year 2 after initiation of combination therapy. In survivors, dual therapy reversed the deterioration in FC, from 3.1±0.6 on monotherapy to 2.2±0.6 at 12months. Similarly, dual therapy improved 6-min walk distance from 316±119m to 406±129m at 12months, and sequential echocardiography demonstrated a fall in pulmonary artery systolic pressure and improved right ventricular function. CONCLUSIONS: Dual non-parenteral therapy appears safe and effective and should be considered for PAH patients who are deteriorating on monotherapy to improve long-term outcomes.

Vancomycin area under the curve to minimum inhibitory concentration ratio predicting clinical outcome: a systematic review and meta-analysis with pooled sensitivity and specificity.

BACKGROUND: Vancomycin is a first-line antibiotic for methicillin-resistant Staphylococcus aureus infections or other Gram-positive infections. The area under the curve (AUC) to minimum inhibitory concentration (MIC) ratio is proposed as a therapeutic drug-monitoring parameter. How well clinical efficacy is predicted by this measure has not been established. OBJECTIVE: Determine the test performance characteristics (TPC) of AUC:MIC of vancomycin for prediction of positive outcome. DATA SOURCES: PubMed and Ovid Medline (1946 to 2018) and EMBASE (1974 to 2018). Study Eligibility Criteria and Participants: Studies of patients treated with vancomycin for any type of infection in peer reviewed publications. All patient populations were included. INTERVENTIONS: Vancomycin AUC:MIC or AUC was related to patient clinical outcome. METHODS: Searches of medical databases using relevant terms were performed. Screening, study reviewing, data extracting and assessing data quality was performed independently by two reviewers. Studies were stratified by type of primary outcome for calculation of pooled sensitivity, specificity and construction of hierarchical summary receiver operating characteristic (HSROC) curves. RESULTS: Nineteen studies including 1699 patients were meta-analysed. Pooled sensitivity and specificity were 0.77 (95% CI 0.67-0.84) and 0.62 (95% CI 0.53-0.71) respectively for the seven studies with primary outcome of mortality and 0.65 (95% CI 0.53-0.75), 0.58 (95% CI 0.48-0.67) for studies with composite or clinical cure outcome (n = 12). HSROC curves suggested considerable heterogeneity. An additional 11 studies were described but could not be included for meta-analysis because data were not available. The majority of these studies (9/11) failed to demonstrate a relationship between AUC:MIC and positive clinical outcome. CONCLUSIONS: Vancomycin AUC:MIC performance was modest and inconsistent. Analysis was limited by studies without sufficient data; therefore, meta-analytic results may overestimate TPC values. Given this, as well as the lack of standardization of methods, widespread adoption of AUC:MIC as the preferred vancomycin monitoring parameter may be premature.

Prevalence of pulmonary arterial hypertension in an Australian scleroderma population: screening allows for earlier diagnosis.

BACKGROUND: We sought to determine the prevalence of pulmonary complications and especially pulmonary arterial hypertension (PAH) in an Australian scleroderma population. METHODS: Between July 2005 and June 2007, physicians in Western Australia were asked to refer patients with scleroderma specifically for pulmonary hypertension screening. All patients were assessed for PAH and other respiratory conditions using echocardiography, lung function testing and clinical assessments. Right heart catheterization was carried out in patients with evidence of increased right ventricular systolic pressure. RESULTS: Of the 184 patients analysed, 44 had possible PAH on echocardiography. Right heart catheterization confirmed the diagnosis in 24 (13%). Diffuse interstitial lung disease was found in 32 patients representing a point prevalence of 17.4%. The severity of PAH at diagnosis varied according to whether the patients were referred for screening (group A) or for diagnostic (group B) purposes. The 6-min-walk test distance and median pulmonary vascular resistance were significantly worse in group B versus group A (324 vs 402 m; P= 0.02 and 884 dynes/s per cm(-5) vs 486 dynes/s per cm(-5); P < 0.01, respectively). CONCLUSION: Screening may result in earlier diagnosis of PAH with, in general more mild disease. This is important, given that early treatment for PAH while patients are less symptomatic is associated with improved exercise tolerance and pulmonary haemodynamics: indices indicative of disease progression and clinical worsening.

Clinical outcomes in patients admitted to a hospitalist service exposed to an antimicrobial stewardship program - a retrospective matched cohort study.

Background: Given global issues with antimicrobial resistance and a need to optimize antimicrobial usage, antimicrobial stewardship (AS) programs are becoming a necessary component of hospitals and are increasingly mandated worldwide. It is important to evaluate these programs with respect to relevant clinical outcomes. Methods: An AS program with a prospective audit and feedback service (PAF) of antimicrobial usage was initiated May 11, 2015 at our tertiary care center, for patients admitted under the hospitalist service. We conducted a retrospective matched cohort study. Patients assessed during the first year of this PAF were considered to be the exposed cohort and were compared to unexposed controls matched on gender, age and infectious diagnosis selected from patients who had been admitted under the hospitalist service prior to initiation of the PAF. Descriptive analysis was completed and a multivariate conditional logistic regression was performed to analyze differences between the exposed and control groups in terms of a composite endpoint of 30 day mortality, 30 day post hospital discharge mortality and hospital re-admission. Results: A total of 348 patients were assessed and received PAF suggestions during the first year were compared to 827 matched control patients who did not receive PAF suggestions. Of 707 PAF suggestions made, the most common was to stop an antimicrobial (23%). A significantly lower (20.7% vs 28.8%, p = 0.008) composite endpoint was found in the group exposed to the PAF (OR 0.71 95%CI 0.52-0.97). This difference persisted when only patients with PAF suggestions that were completely or partially accepted were considered (18.6% vs 28.5%, p = 0.001) but was no longer significant when patients who had their ASP suggestions declined were analyzed (30.2% vs 26.7%, p = 0.610). Conclusions: In this retrospective cohort study, patient admissions in which PAF recommendations were accepted had better clinical outcomes than matched historical controls managed in the absence of this AS service.

Phylogenetic structure of Holbrookia lacerata (Cope 1880) (Squamata: Phrynosomatidae): one species or two?

Species delimitation attempts to match species-level taxonomy with actual evolutionary lineages. Such taxonomic conclusions are typically, but not always, based on patterns of congruence across multiple data sources and methods of analyses. Here, we use this pluralistic approach to species delimitation to help resolve uncertainty in species boundaries of phrynosomatid sand lizards of the genus Holbrookia. Specifically, the Spot-tailed Earless Lizard (H. lacerata) was historically divided into a northern (H. l. lacerata) and southern (H. l. subcaudalis) subspecies based on differences in morphology and allopatry, but no research has been conducted evaluating genetic differences between these taxa. In this study, patterns in sequence data derived from two genes, one nuclear and one mitochondrial, for 66 individuals sampled across 18 counties in Texas revealed three strongly supported, reciprocally monophyletic lineages, each comprised of individuals from a single geographic region. Distinct genetic variation evident across two of these regions corresponds with differences in morphology, differences in environmental niche, and lines up with the presumed geographic barrier, the Balcones Escarpment, which is the historical subspecies boundary. The combined evidence from genetics, morphology and environmental niche is sufficient to consider these subspecies as distinct species with the lizards north of the Balcones Escarpment retaining the name Holbrookia lacerata, and those south of the Balcones Escarpment being designated as Holbrookia subcaudalis.