Improved responsiveness to change in joint space width over 24-month follow-up: comparison of 3D JSW on weight-bearing CT vs 2D JSW on radiographs in the MOST study.

OBJECTIVE: Radiographic joint space width (JSW) has been a standard for measuring knee osteoarthritis (OA) structural change. Limitations in the responsiveness of this approach might be overcome by instead measuring 3D JSW on weight-bearing CT (WBCT). This study compared the responsiveness of 3D JSW measurements using WBCT with the responsiveness of radiographic 2D JSW. DESIGN: Standing, fixed-flexion knee radiographs (XR) and WBCT were acquired ancillary to the 144- and 168-month Multicenter Osteoarthritis Study visits. Tibiofemoral JSW was measured on both XR and WBCT. Responsiveness to change was defined by the standardized response mean (SRM) for change in JSW (1) at predetermined mediolateral locations (JSWx) on both modalities and (2) in the following subregions measured on WBCT images: central medial and lateral femur (CMF/CLF) and tibia (CMT/CLT), and anterior and posterior tibia (AMT/ALT, PMT/MLT). RESULTS: Baseline and 24-month follow-up JSWx measurements were completed for 265 participants (58.1% women). Responsiveness of 3D JSWx for medial tibiofemoral compartment on coronal WBCT (SRM range: -0.18, -0.24) exceeded that for 2D JSWx (-0.10, -0.16). Responsiveness of 3D JSW subregional mean (-0.06, -0.36) and maximal (-1.14, -1.75) CMF and CMT and maximal CLF/CLT 3D JSW changes were statistically significantly greater in comparison with respective medial and lateral 2D JSWx (P ≤ 0.002). CONCLUSIONS: Subregional 3D JSW on WBCT is substantially more responsive to 24-month changes in tibiofemoral joint structure compared to radiographic measurements. Use of subregional 3D JSW on WBCT could enable improved detection of OA structural progression over a 24-month duration in comparison with measurements made on XR.

Randomized controlled trial of honey versus mupirocin to decolonize patients with nasal colonization of meticillin-resistant Staphylococcus aureus.

BACKGROUND: Mupirocin is used specifically for the eradication of nasal meticillin-resistant Staphylococcus aureus (MRSA), but increasing mupirocin resistance restricts its repeated use. The antibacterial effects of manuka honey have been established in vitro; antibacterial activity of other honeys has also been reported. AIM: To describe the learning experience from a randomized controlled trial (RCT) comparing the efficacy of medical-grade honey (MGH) with mupirocin 2% for the eradication of nasal MRSA. METHODS: Patients colonized in the nose with MRSA and age ≥18 years were recruited. Participants received either one or two courses of MGH or mupirocin 2%, three times per day for five consecutive days. FINDINGS: The proportion of patients who were decolonized after one or two courses of treatment was not significantly different between MGH [18/42; 42.8%; 95% confidence interval (CI): 27.7-59.0] and mupirocin 2% (25/44; 56.8%; 95% CI: 41.0-71.7). Non-nasal MRSA colonization was significantly associated with persistent nasal colonization (odds ratio: 5.186; 95% CI: 1.736-5.489; P = 0.003). The rate of new acquisition of mupirocin resistance was 9.75%. CONCLUSION: Although not significant, a decolonization rate of 42.8% for MGH was impressive. Our findings suggest that this strategy, which has the potential to combat antimicrobial resistance, should be assessed in similar but larger studies.

Evaluation of fixed and variable hospital costs due to Clostridium difficile infection: institutional incentives and directions for future research.

BACKGROUND: Economic analysis of Clostridium difficile infection (CDI) should consider the incentives facing institutional decision-makers. To avoid overstating the financial benefits of infection prevention, fixed and variable costs should be distinguished. AIM: To quantify CDI fixed and variable costs in a tertiary referral hospital during August 2015. METHODS: A micro-costing analysis estimated CDI costs per patient, including the additional costs of a CDI outbreak. Resource use was quantified after review of patient charts, pharmacy data, administrative resource input, and records of salary and cleaning/decontamination expenditure. FINDINGS: The incremental cost of CDI was €75,680 (mean: €5,820 per patient) with key cost drivers being cleaning, pharmaceuticals, and length of stay (LOS). Additional LOS ranged from 1.75 to 22.55 days. For seven patients involved in a CDI outbreak, excluding the value of the 58 lost bed-days (€34,585); costs were 30% higher (€7,589 per patient). Therefore, total spending on CDI was €88,062 (mean: €6,773 across all patients). Potential savings from variable costs were €1,026 (17%) or €1,768 (26%) if outbreak costs were included. Investment in an antimicrobial pharmacist would require 47 CDI cases to be prevented annually. Prevention of 5%, 10% and 20% CDI would reduce attributable costs by €4,403, €8,806 and €17,612. Increasing the incremental LOS attributable to CDI to seven days per patient would have increased costs to €7,478 or €8,431 (if outbreak costs were included). CONCLUSION: As much CDI costs are fixed, potential savings from infection prevention are limited. Future analysis must consider more effectively this distinction and its impact on institutional decision-making.

Differential executive functioning performance by phase of bipolar disorder.

OBJECTIVE: This study examined the influence of illness phase on executive functioning performance using factor-derived cognitive scores in a cross-sectional design. METHODS: Healthy control (HC) subjects (n = 57), and euthymic (E-BD) (n = 117), depressed (D-BD) (n = 73), and hypomanic/mixed (HM/M-BD) (n = 26) patients with bipolar disorder (BD) were evaluated using executive functioning measures (Wisconsin Card Sorting Test, Trail Making Test-Parts A and B, Verbal Fluency, Parametric Go/No-Go, Stroop, and Digit Symbol) comprising Conceptual Reasoning and Set-Shifting (CRSS), Processing Speed with Interference Resolution (PSIR), Verbal Fluency and Processing Speed (VFPS), and Inhibitory Control (IC) factor scores. RESULTS: Two of the four executive functioning factors were significantly different between groups based upon phase of illness. The HM/M group was significantly worse than both of the other BD groups and the HC group in IC. The VFPS factor was sensitive to the active phase of BD, with the HM/M-BD and D-BD groups worse than HC. Extending our prior work, the PSIR factor, and now the CRSS factor were significantly worse in BD relative to HC, irrespective of phase of illness. CONCLUSIONS: Phase of illness had differential cognitive profiles in executive functioning factors, even after considering and excluding the impact of clinical features, illness characteristics, medications, and demographics. Consolidating executive functioning tasks into reliable factor scores provides unique information to measure and define cognitive deficiencies throughout phases of BD, and to measure intermediate phenotypes in BD, and may aid in tracking and clarifying treatment focus.

Treatment of pacemaker-induced superior vena cava syndrome by balloon angioplasty and stenting.

Superior vena cava (SVC) syndrome is a rare but serious complication after pacemaker implantation. This report describes three cases of SVC syndrome treated with venoplasty and venous stenting, with an average follow-up of 30.7 (±3.1) months. These cases illustrate that the definitive diagnosis, and the extent and location of venous obstruction, can only be determined by venography.

Coronary plaque burden in patients with stable and unstable coronary artery disease using multislice CT coronary angiography.

PURPOSE: We evaluated the multislice computed tomography (MSCT) coronary plaque burden in patients with stable and unstable angina pectoris. MATERIALS AND METHODS: Twenty-one patients with stable and 20 with unstable angina pectoris scheduled for conventional coronary angiography (CCA) underwent MSCT-CA using a 64-slice scanner offering a fast rotation time (330 ms) and higher X-ray tube output (900 mAs). To determine the MSCT coronary plaque burden, we assessed the extent (number of diseased segments), size (small or large), type (calcific, noncalcific, mixed) of plaque, its anatomic distribution and angiographic appearance in all available ≥2-mm segments. In a subset of 15 (seven stable, eight unstable) patients, the detection and classification of coronary plaques by MSCT was verified by intracoronary ultrasound (ICUS). RESULTS: Sensitivity and specificity of MSCT compared with ICUS to detect significant plaques (defined as ≥1-mm plaque thickness on ICUS) was 83% and 87%. Overall, 473 segments were examined, resulting in 11.6±1.5 segments per patient. Plaques were present in 62% of segments and classified as large in 47% of diseased segments. Thirty-two percent were noncalcific, 25% calcific and 43% mixed. Plaques were most frequently located in the proximal and mid segments. Plaque was found in 33% of segments classified as normal on CCA. Unstable patients had significantly more noncalcific plaques when compared with stable patients (45% vs. 21%, p<0.05). CONCLUSIONS: MSCT-CA provides important information regarding the coronary plaque burden in patients with stable and unstable angina.

Impact of obesity on the severity and therapeutic responsiveness of acute episodes of asthma.

BACKGROUND: It has been suggested that obesity adversely influences both the severity and the therapeutic responsiveness of chronic asthma. However, it is unclear if it also impacts acute situations. METHODS: To determine whether adiposity worsens the clinical and physiological manifestations of acute asthma and limits therapeutic effectiveness of standard treatment, we contrasted signs, symptoms, medication use, arterial oxygen saturation, peak expiratory flow rate, and the bronchodilator response to standard doses of albuterol in 90 non-obese and 90 obese asthmatics as they presented for urgent care. Treatment and clinical decisions were systematized using published care paths and the peak flow was measured with standard techniques. Body mass index (BMI) was calculated according to consensus criteria. RESULTS: Other than BMI (p < .001), there were no between-group differences in age, gender, race, signs, symptoms, pulse oximetry, or pre-presentation medication use. The pretreatment peak flow in the obese population was 22.4% higher on average (p = .007), but there were no differences in the distribution of severity (p = .38), the response to albuterol (p = .61), or admission-discharge ratios (p = .62). CONCLUSIONS: Obesity does not adversely influence the severity or the resolution of acute episodes of asthma.

Auditory memory decrements, without dissimulation, among patients with major depressive disorder.

Questions have been raised about whether poor performance on memory tasks by individuals with major depressive disorder (MDD) might be the result of poor or variable effort or disease-related disruption of neural circuits supporting memory functions. The present study examined performance on a measure of task engagement and on an auditory memory task among 45 patients with MDD (M age = 47.82, SD = 19.55) relative to 32 healthy controls (HC; M age = 51.03, SD = 22.09). One-hundred percent of HC and MDD volunteers performed above the threshold for adequate effort on a formal measure of task engagement. The MDD subjects performed significantly more poorly than the HC subjects on an auditory learning and memory test. The present results suggest that auditory memory difficulties do occur among those with MDD and that decrements in performance in this group may be related to factors other than lack of effort.

Critical comparisons of the clinical performance of oxygen-conserving devices.

RATIONALE: Clinical testing of oxygen-conserving devices is not mandated before marketing. Consequently, little is known about individual or comparative therapeutic effectiveness. OBJECTIVES: To relate oxygen delivery from prototypical instruments to physiological performance. METHODS: Thirteen subjects with obstructive lung disease performed progressive treadmill exercise while inhaling either room air, 2 L O(2)/min, or bolus oxygen from four commercially available conserving devices at regulator settings of 2, 5, and continuous. The devices were studied blindly in random order after first being tested to determine performance characteristics. Pulse oximetry, oxygen delivery, and nasal and oral ventilations were monitored at rest and with exertion. MEASUREMENTS AND MAIN RESULTS: At a setting of 2 at rest, all conservers maintained saturation greater than 90%, but there were significant differences in oxygenation between systems. Only one equaled 2 L O(2)/min. With exertion, saturation decreased with all conservers but not with 2 L O(2)/min. One device did not perform any better than room air. Two systems provided less oxygen than predicted, one more, and in one the expected and actual amounts were equal only at rest. Breath-by-breath performance was highly variable, with irregular activation and inconsistent oxygen bolus size delivery. Increasing oxygen pulse volume to the point of eradicating conservation with the continuous setting did not eliminate all disparities. CONCLUSIONS: The mechanical and clinical performances of current oxygen conservers are highly variable and in some instances actually contribute to limitations in exercise ability. Seemingly equivalent technical features do not guarantee equivalent therapeutic functionality.

Safety of binodenoson, a selective adenosine A2A receptor agonist vasodilator pharmacological stress agent, in healthy subjects with mild intermittent asthma.

BACKGROUND: The pharmacological stress agents adenosine and dipyridamole are contraindicated in asthma patients because of the risk of adenosine receptor-mediated bronchospasm. Binodenoson, a selective adenosine A(2A) receptor agonist, produces maximal coronary hyperemia during pharmacological stress testing yet has a low affinity for the adenosine A(1), A(2B), and A(3) receptors that are probably responsible for bronchospasm. This study was conducted to assess the safety of binodenoson in 87 healthy young adult volunteers with documented mild, intermittent asthma. METHODS AND RESULTS: This study consisted of a dose-escalating, single-blinded phase and a placebo-controlled, double-blinded phase conducted in healthy, young adults with documented mild, intermittent, asthma. In the single-blinded phase, 3 sequential cohorts of 8 subjects received intravenous binodenoson (0.5, 1.0, and 1.5 microg/kg). In the double-blinded phase, commenced after medical review of results from the single-blinded phase, subjects were randomly assigned 2:1 to either binodenoson 1.5 microg/kg (n=41) or placebo (n=22). The primary end point was clinically significant bronchoconstriction, defined as a decrease in forced expiratory volume in 1 second of >/=20% from the preinjection measure. Secondary safety end points were changes from preinjection measure in forced expiratory volume in 1 second, forced vital capacity, and forced expiratory flow during the middle 50% of the forced vital capacity; vital signs; pulse oximetry; and adverse events. Binodenoson caused no clinically significant bronchoconstriction or alterations in pulmonary function parameters and transiently increased heart rate and systolic blood pressure. The most common treatment-emergent adverse events were tachycardia, dizziness, and flushing. CONCLUSIONS: Binodenoson was safe, well tolerated, and caused no clinically significant bronchoconstriction or pulmonary responses in a small population of healthy subjects with mild, intermittent asthma.

Comparison of primary angioplasty and pre-hospital fibrinolysis in acute myocardial infarction (CAPTIM) trial: a 5-year follow-up.

AIMS: The CAPTIM (Comparison of primary Angioplasty and Pre-hospital fibrinolysis In acute Myocardial infarction) study found no evidence that a strategy of primary angioplasty was superior in terms of 30-day outcomes to a strategy of pre-hospital fibrinolysis with transfer to an interventional facility in patients managed early at the acute phase of an acute myocardial infarction. The present analysis was designed to compare both strategies at 5 years. METHODS AND RESULTS: The CAPTIM study included 840 patients managed in a pre-hospital setting within 6 h of an acute ST-segment elevation myocardial infarction. Patients were randomized to either a primary angioplasty (n = 421) or a pre-hospital fibrinolysis (rt-PA) with immediate transfer to a centre with interventional facilities (n = 419). Long-term follow-up was obtained in blinded fashion from 795 patients (94.6%). Using an intent-to-treat analysis, all-cause mortality at 5 years was 9.7% in the pre-hospital fibrinolysis group when compared with 12.6% in the primary angioplasty group [HR 0.75 (95% CI, 0.50-1.14); P = 0.18]. For patients included within 2 h, 5 year mortality was 5.8% in the pre-hospital fibrinolysis group when compared with 11.1% in the primary angioplasty group [HR 0.50 (95% CI, 0.25-0.97); P = 0.04], whereas it was, respectively, 14.5 and 14.4% in patients included after 2 h [HR 1.02, (95% CI 0.59-1.75), P = 0.92]. CONCLUSION: The 5-year follow-up is consistent with the 30-day outcomes of the trial, showing similar mortality for primary percutaneous coronary intervention and a policy of pre-hospital lysis followed by transfer to an interventional center. In addition, for patients treated within 2 h of symptom onset, 5-year mortality was lower with pre-hospital lysis.

Self-rated health does not explain the socioeconomic differential in mortality: a prospective study in the EPIC-Norfolk cohort.

BACKGROUND: Self-rated health (SRH), a subjective measure of health, is strongly predictive of mortality, independently of objective measures of health status and existing known disease. There is a strong social gradient in SRH. An investigation was carried to determine whether SRH can explain the well-known socioeconomic gradient in mortality. METHODS: The effect of adjusting for SRH on the socioeconomic differential in mortality was examined in a prospective study of 20 754 men and women aged 39-79 years, without prevalent disease, living in the general community in Norfolk, UK, recruited using general practice age-sex registers for 1993-1997 and followed up for an average of 10 years. RESULTS: Mortality risk increased with decreasing social class in men and women. There was some attenuation after adjustment for covariates age, body mass index, smoking, history of diabetes, systolic blood pressure, cholesterol level, alcohol consumption, physical activity and educational level, but a gradient remained. Further adjustment for SRH attenuated the association slightly more, but there was still some evidence of a socioeconomic differential in mortality, particularly in class V compared with class I (age- and sex-adjusted hazard ratio 1.57; 95% CI 1.19 to 2.06). CONCLUSIONS: SRH does not substantially explain the socioeconomic differential in mortality beyond that explained by health-related covariates.

Does the association between self-rated health and mortality vary by social class?

Self-rated health (SRH) predicts future mortality. Individuals in different social classes with similar physical health status may have different reference levels and criteria against which they judge their health, therefore the SRH-mortality relationship may vary according to social class. We examine the relationship between SRH and mortality by occupational social class in a prospective study of 22,457 men and women aged 39-79 years, without prevalent disease, living in the general community in Norfolk, United Kingdom, recruited using general practice age-sex registers in 1993-1997 and followed up for an average of 10 years. As expected, SRH was related to subsequent mortality. The age and sex adjusted hazard ratio for mortality for those with poor compared to those with excellent SRH was 4.35 (95% confidence interval 3.38-5.59, P<0.001). The prevalence of poor or moderate SRH was higher in manual than in non-manual classes. However, SRH was similarly related to mortality in manual and non-manual classes: when non-manual classes are compared with manual classes for each category of SRH, the 95% confidence intervals for the mortality hazard ratios overlap. There was no evidence of an interaction between social class and SRH in either men or women. Thus in this population, SRH appears to predict mortality in a similar manner in non-manual and manual classes.

Observations on the physiological interactions between obesity and asthma.

To explore whether asthma and obesity share overlapping pathogenic features, we examined the impact of each alone, and in combination, on multiple aspects of lung function. We reasoned that if they influenced the lungs through similar mechanisms, the individual physiological manifestations in the comorbid state should interact in a complex fashion. If not, then the abnormalities should simply add. We measured specific conductance, spirometry, lung volumes, and airway responsiveness to adrenergic and cholinergic agonists in 52 normal, 53 asthmatic, 52 obese, and 53 asthmatic and obese patients using standard techniques. Six-minute walks were performed in subsets from each group. Asthma significantly lowered specific conductance and the spirometric variables while increasing airway reactivity and residual volume. Obesity also reduced the spirometric variables as well as total lung capacity and functional residual capacity. Residual volume, specific conductance, and airway responsivity were unaltered. With comorbidity, the disease-specific derangements added algebraically. Features that existed in isolation appeared unchanged in the combination, whereas shared ones either added or subtracted depending on the individual directional changes. Synergistic interactions were not observed. Body mass index weakly correlated with spirometry and lung volumes in asthma, but not with specific conductance or bronchial reactivity. Exercise performance did not aid in differentiation. Our findings indicate asthma and obesity appear to influence the respiratory system through different processes.

Validating a guidelines based asthma decision support system: step one.

Purpose. To quantify the accuracy of a computerized decision support system in discerning severe asthma in a clinical setting. Design. A total of 69 consecutive asthmatics examined in an asthma clinic were classified as "severe" or "mild" by the computerized decision support system and expert asthma clinicians. The expert asthma clinicians were the reference standard. Results. The accuracy was 91%, the sensitivity 96%, the specificity 73%, the positive predictive value 93%, and the negative predictive value 85%. Conclusions. The asthma decision support system was able to discern "mild" from "severe" asthma in a similar fashion to expert asthma clinicians.

Clonidine in horses: identification, detection, and clinical pharmacology.

Clonidine is classified as a class 3 performance-enhancing agent by the Association of Racing Commissioners International and thus has the potential to influence the outcome of a race. In this study, the authors developed and validated a sensitive gas chromatograph and mass spectrometer method to determine the pharmacokinetic parameters of clonidine in equine plasma samples after IV administration of a single dose (0.025 mg/kg) of clonidine in horses. At this dose, clonidine produced rapid and profound sedation, which cold be quickly reversed with yohimbine. Clonidine was able to produce an analgesic effect but failed to provide maximal analgesia in all horses; the limited analgesic effect persisted for about 60 minutes.

Impact of race on the severity of acute episodes of asthma and adrenergic responsiveness.

RATIONALE: African Americans acutely ill with asthma come to emergency departments more frequently and are admitted to hospital more often than whites but the reasons are unclear. OBJECTIVES: To determine whether such phenomena represent racial differences in attack severity or limited effectiveness of beta(2)-agonist therapy. METHODS AND MAIN RESULTS: We contrasted clinical features, airflow limitation, and albuterol responsiveness in adults acutely ill with asthma, 155 of whom where African American and 140 white, as they presented to eight emergency departments. Assessments were standardized across institutions using a care path, and admission and discharge decisions were made according to predetermined criteria. The degree of obstruction was measured by peak expiratory flow rates. The clinical features of both groups were similar. The African Americans, however, had lower flow rates (p = 0.002), and more of them experienced severe or potentially life threatening episodes (p < 0.001). Albuterol was equally efficacious in both populations and there were no differences in the post-treatment flow rates achieved irrespective of the initial attack intensity. There were no racial differences in admission/discharge ratios. CONCLUSIONS: Our data indicate that African Americans with asthma tend to present with somewhat more intense attacks than whites, but they respond equally well to routine treatment. Similarly, there were no racial disparities in hospitalizations when standard criteria are employed.