Asthma-chronic obstructive pulmonary disease overlap and cost-related medication non-adherence among older adults in the United States.

BACKGROUND: Cost-related medication non-adherence (CRN) can negatively impact health outcomes in older adults with asthma and chronic obstructive pulmonary disease (COPD) overlap (ACO) by reducing access and adherence to essential medications. The objective of this study is to examine the association of ACO to any CRN and specific forms of CRN among a nationally representative sample of older (age ≥ 65 years) adults. METHODS: We adopted a cross-sectional study design using data from pooled cross-sectional Medicare Current Beneficiary Surveys (MCBS) (2006-2013) and linked fee-for-service Medicare claims. Unadjusted and adjusted logistic regressions that accounted for the complex survey design examined the association of ACO to any CRN and specific forms of CRN. RESULTS: Among older adults with ACO, 16% reported any CRN. The most common form of CRN was "failing to get prescription". As compared to older adults with no asthma and no COPD, those with ACO were more likely to report any CRN (adjusted odds ratios [AOR] = 1.50, 95%CI = [1.14, 1.96]) and all forms of CRN. However, when the number of unique medications was added to the model, there were no statistically significant differences in CRN between the two groups. CONCLUSIONS: Older adults with ACO represent a vulnerable population with increased risk for CRN. Multiple factors can contribute to CRN including: a higher number of prescribed medications, multiple co-morbidities, and cost of therapies. Medication comprehensive review interventions have the potential of reducing the risk of CRN among the older Medicare beneficiaries with ACO.

Occupational musculoskeletal disorders management using Fuzzy TOPSIS Assessment of Repetitive Tasks (ART).

BACKGROUND: In order to evaluate occupational disorders and ergonomic problems in a workplace, Multiple Criteria Decision Making (MCDM) problem solving methods such as Fuzzy Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) can be utilized. OBJECTIVE: In this paper, Musculoskeletal Disorder (MSD) risk factors were evaluated in a manufacturing company in Iran by a method called Assessment of Repetitive Tasks (ART) of the upper limbs integrated with Fuzzy TOPSIS in order to prioritize the corrective actions. METHODS: This study was done with a descriptive-analytical approach. The company under study had 240 employees who were working in seven different shops. Out of all tasks, 13 tasks were included in the study. Required information was gathered by a demographic questionnaire and ART method. Also, Fuzzy TOPSIS was utilized for the prioritization of the company shops based on the ergonomic control needs. RESULTS: Data analysis from ART indicated that 74.6% of the reviewed tasks were high risk. Based on the F- TOPSIS-ART results, Production shop prioritized as the highest need for MSD control. CONCLUSIONS: Because there is time and financial resources limit in ergonomic control activities, a fuzzy prioritization approach such as Fuzzy TOPSIS ART can be used to take advantage of the available resources and control risks to as low as reasonably practicable (ALARP) level.

Molecular mechanism of peroxisome proliferator-activated receptor α activation by WY14643: a new mode of ligand recognition and receptor stabilization.

Peroxisome proliferator-activated receptors (PPARs) are members of a superfamily of nuclear transcription factors. They are involved in mediating numerous physiological effects in humans, including glucose and lipid metabolism. PPARα ligands effectively treat dyslipidemia and have significant antiinflammatory and anti-atherosclerotic activities. These effects and their ligand-dependent activity make nuclear receptors obvious targets for drug design. Here, we present the structure of the human PPARα in complex with WY14643, a member of fibrate class of drug, and a widely used PPAR activator. The crystal structure of this complex suggests that WY14643 induces activation of PPARα in an unusual bipartite mechanism involving conventional direct helix 12 stabilization and an alternative mode that involves a second ligand in the pocket. We present structural observations, molecular dynamics and activity assays that support the importance of the second site in WY14643 action. The unique binding mode of WY14643 reveals a new pattern of nuclear receptor ligand recognition and suggests a novel basis for ligand design, offering clues for improving the binding affinity and selectivity of ligand. We show that binding of WY14643 to PPARα was associated with antiinflammatory disease in a human corneal cell model, suggesting possible applications for PPARα ligands.

Mixed infection with intestinal tape worms in sheep.

In a survey carried out during the period April 2001 to November 2002, the intestines of 3165 slaughtered sheep in the Fars province of Iran were examined for mixed infection with intestinal tape worms. Four point sixty eight percent of animals were found to be infected with one or more than one species of tape worms. The identified species included: Moniezia expansa, Moniezia benedeni, Thysaniezia giardi, Avitellina centripunctata and Stilesia globipunctata. Of all 148 infected sheep, 104 animals (70.3%) were infected with one species, 38 animals (25.7%) were infected with two species and 5 animals (3.4%) were infected with three species of tape worms. No animal was found to be infected with four species but one sheep (0.7%) was found to be infected with all five species of tape worms.

Regulatory proteins alter nucleotide binding to acto-myosin of sliding filaments in motility assays.

The sliding speed of unregulated thin filaments in motility assays is only about half that of the unloaded shortening velocity of muscle fibers. The addition of regulatory proteins, troponin and tropomyosin, is known to increase the sliding speed of thin filaments in the in vitro motility assay. To learn if this effect is related to the rate of MgADP dissociation from the acto-S1 cross-bridge head, the effects of regulatory proteins on nucleotide binding and release in motility assays were measured in the presence and absence of regulatory proteins. The apparent affinity of acto-heavy meromyosin (acto-HMM) for MgATP was reduced by the presence of regulatory proteins. Similarly, the regulatory proteins increase the concentration of MgADP required to inhibit sliding. These results suggest that regulatory proteins either accelerate the rate of MgADP release from acto-HMM-MgADP or slow its binding to acto-HMM. The reduction of temperature also altered the relationship between thin filament sliding speed and the regulatory proteins. At lower temperatures, the regulatory proteins lost their ability to increase thin filament sliding speed above that of unregulated thin filaments. It is hypothesized that structural changes in the actin portion of the acto-myosin interface are induced by regulatory protein binding to actin.

Modulation of myosin function by isoform-specific properties of Saccharomyces cerevisiae and muscle tropomyosins.

Tropomyosin is an extended coiled-coil protein that influences actin function by binding longitudinally along thin filaments. The present work compares cardiac tropomyosin and the two tropomyosins from Saccharomyces cerevisiae, TPM1 and TPM2, that are much shorter than vertebrate tropomyosins. Unlike cardiac tropomyosin, the phase of the coiled-coil-forming heptad repeat of TPM2 is discontinuous; it is interrupted by a 4-residue deletion. TPM1 has two such deletions, which flank the 38-residue partial gene duplication that causes TPM1 to span five actins instead of the four of TPM2. Each of the three tropomyosin isoforms modulates actin-myosin interactions, with isoform-specific effects on cooperativity and strength of myosin binding. These different properties can be explained by a model that combines opposite effects, steric hindrance between myosin and tropomyosin when the latter is bound to a subset of its sites on actin, and also indirect, favorable interactions between tropomyosin and myosin, mediated by mutually promoted changes in actin. Both of these effects are influenced by which tropomyosin isoform is present. Finally, the tropomyosins have isoform-specific effects on in vitro sliding speed and on the myosin concentration dependence of this movement, suggesting that non-muscle tropomyosin isoforms exist, at least in part, to modulate myosin function.

Kinetic differences in cardiac myosins with identical loop 1 sequences.

The kinetics of nucleotide turnover vary considerably among isoforms of vertebrate type II myosin, possibly due to differences in the rate of ADP release from the nucleotide binding pocket. Current ideas about likely mechanisms by which ADP release is regulated have focused on the hyperflexible surface loops of myosin, i.e. loop 1 (ATPase loop) and loop 2 (actin binding loop). In the present study, we investigated the kinetic properties of rat and pig beta-myosin heavy chains (beta-MHC) in which we have found the sequences of loop 1 (residues 204-216) to be virtually identical, i.e. DQSKKDSQTPKG, with a single conservative substitution (rat E210D pig). Pig myocardium normally expresses 100% beta-MHC, whereas rat myocardium was induced to express 100% beta-MHC by surgical thyroidectomy and subsequent treatment with propylthiouracil. Slack test measurements at 15 degrees C yielded unloaded shortening velocities of 1.1 +/- 0.8 muscle lengths/s in rat skinned ventricular myocytes and 0.35 +/- 0.05 muscle lengths/s in pig skinned myocytes. Similarly, solution measurements at the same temperature showed that actin-activated ATPase activity was 2.9-fold greater for rat beta-myosin than for pig beta-myosin. Stopped-flow methods were then used to assess the rates of acto-myosin dissociation by MgATP both in the presence and absence of MgADP. Although the rates of MgATP-induced dissociation of acto-heavy meromyosin (acto-HMM) were virtually identical for the two myosins, the rate of ADP dissociation was approximately 3.8-fold faster for rat beta-myosin (135 s(-)(1)) than for pig beta-myosin (35 s(-)(1)). ATP cleavage rates were nearly 30% faster for rat beta-myosin. Thus, whereas loop 1 appears from other studies to be involved in nucleotide turnover in the pocket, our results show that loop 1 does not account for large differences in turnover kinetics in these two myosin isoforms. Instead, the differences appear to be due to sequence differences in other parts of the MHC backbone.

Mid-term clinical and echocardiographic follow up of patients with CarboMedics valves in the tricuspid position.

BACKGROUND AND AIM OF THE STUDY: Debate continues regarding tricuspid valve replacement (TVR) with a mechanical prosthesis. Experience with bileaflet prostheses is limited; hence the study aim was to explore early and mid-term outcome and hemodynamic data in patients with bileaflet CarboMedics prosthetic valves in the tricuspid position. METHODS: The study population included 25 patients (21 females, four males; mean age 50.5 +/- 13.4 years) who underwent TVR with a CarboMedics valve over a six-year period. Routine clinical examinations and details of transthoracic echocardiography (TTE) were reviewed. Additional TTE, transesophageal echocardiography (TEE) and fluoroscopy were performed as indicated. The number of previous cardiac operations was zero, one and two in 36%, 32% and 32% of patients, respectively. Previous tricuspid surgery was performed in eight cases (32%); concurrent mitral valve replacement was performed in 17 (68%). The hospital mortality rate was 24% and late mortality rate 12%. Seventeen early survivors (13 females, four males) were followed up for 46 +/- 28 months (range: 4-96 months). RESULTS: Among early survivors, the mean and peak transvalvular gradients were 4.0 +/- 1.7 and 7.9 +/- 3.3 mmHg, respectively. Commonly observed INR levels were >2.5 in seven patients (41%), and >3.0 in only three (18%). Five patients (29% of mid-term survivors) experienced a total of 13 episodes of obstructive valve thrombosis, mostly with inappropriate anticoagulation. One patient required emergency re-do surgery; the others responded initially to thrombolysis or intensified antithrombotic treatment, but experienced at least two additional relapses. Aside from thrombotic episodes, all patients but two were in NYHA functional class II-III, and all but four required diuretics. CONCLUSION: TVR with bileaflet mechanical valves carries a high perioperative mortality and mid-term morbidity. Among patients with poor or fair anticoagulation, these valves were associated with a high incidence of obstructive valve thrombosis. If poor patient compliance is anticipated, insertion of a bioprosthesis should be encouraged.

Preparation of the internal thoracic artery by vasodilator drugs: is it really necessary? A randomized double-blind placebo-controlled clinical study.

OBJECTIVE: The internal thoracic artery has become the conduit of choice for coronary artery bypass grafting. To avoid spasm of the artery, and increases in its diameter and flow, various vasodilators have been used either intraluminally or by topical application by different surgeons. In order to define the best vasodilating agent for preparation of the internal thoracic artery, a randomized double-blind placebo-controlled clinical study was performed in a group of patients submitted for elective coronary artery bypass grafting. METHODS AND RESULTS: Eighty (80) consecutive patients submitted for elective first time coronary artery bypass grafting were randomly subdivided into five treatment groups. Free flow of the left internal thoracic artery was measured using an electromagnetic flow meter. The first measurement was performed shortly after the internal thoracic artery was dissected from the chest wall and the second just prior to performing distal anastomosis to the left anterior descending coronary artery. During the time interval between the two measurements the internal thoracic artery was immersed in a special applicator tube containing 20 ml solution of one of the following drugs: papaverin 2 mg/ml, nitroglycerin 1 mg/ml, verapamil 0.5 mg/ml, nitroprusside 0.5 mg/ml, normal saline 0.9%. RESULTS: No statistically significant differences were found between the groups in respect to age, body surface area, bypass time, cross clamping time, and time interval between the two flow measurements. Mean arterial pressure at the time of the first and second internal thoracic artery flow measurements did not show statistically significant differences either within or between the groups. In all five groups, the free flow of the internal thoracic artery increased significantly with time. However, no statistically significant differences were shown between the five groups with respect to second flow (P = 0.2). CONCLUSIONS: Within the limits of our study design, we suggest that preparation of the LITA by topical vasodilator drugs using a special applicator tube does not result in a significantly superior free flow than placebo.

Analyses of coronary graft patency after aprotinin use: results from the International Multicenter Aprotinin Graft Patency Experience (IMAGE) trial.

OBJECTIVE: We examined the effects of aprotinin on graft patency, prevalence of myocardial infarction, and blood loss in patients undergoing primary coronary surgery with cardiopulmonary bypass. METHODS: Patients from 13 international sites were randomized to receive intraoperative aprotinin (n = 436) or placebo (n = 434). Graft angiography was obtained a mean of 10.8 days after the operation. Electrocardiograms, cardiac enzymes, and blood loss and replacement were evaluated. RESULTS: In 796 assessable patients, aprotinin reduced thoracic drainage volume by 43% (P < .0001) and requirement for red blood cell administration by 49% (P < .0001). Among 703 patients with assessable saphenous vein grafts, occlusions occurred in 15.4% of aprotinin-treated patients and 10.9% of patients receiving placebo (P = .03). After we had adjusted for risk factors associated with vein graft occlusion, the aprotinin versus placebo risk ratio decreased from 1.7 to 1.05 (90% confidence interval, 0.6 to 1.8). These factors included female gender, lack of prior aspirin therapy, small and poor distal vessel quality, and possibly use of aprotinin-treated blood as excised vein perfusate. At United States sites, patients had characteristics more favorable for graft patency, and occlusions occurred in 9.4% of the aprotinin group and 9.5% of the placebo group (P = .72). At Danish and Israeli sites, where patients had more adverse characteristics, occlusions occurred in 23.0% of aprotinin- and 12.4% of placebo-treated patients (P = .01). Aprotinin did not affect the occurrence of myocardial infarction (aprotinin: 2.9%; placebo: 3.8%) or mortality (aprotinin: 1.4%; placebo: 1.6%). CONCLUSIONS: In this study, the probability of early vein graft occlusion was increased by aprotinin, but this outcome was promoted by multiple risk factors for graft occlusion.

Massive spontaneous hemothorax as a presenting sign of aneurysmal rupture of the internal thoracic artery. A case report.

Massive spontaneous hemothorax is a very uncommon, life-threatening situation. Acute dissection and ruptured aorta can be one of the differential diagnoses, but usually the clinical feature is completely different, and very few patients have survived this event and received medical attention. Among other causes of spontaneous bleeding, some are extremely rare, demanding precise diagnosis and judicial and immediate intervention. We describe a patient who presented with a massive hemothorax. There was no immediately apparent cause. Emergent angiography revealed active bleeding from an extremely unusual source: aneurysmal dilatation of the internal thoracic artery.

Echocardiography can detect cloth cover tears in fully covered Starr-Edwards valves: a long-term clinical and echocardiographic study.

The incidence of cloth cover tears in fully covered Starr-Edwards valves, as assessed by autopsy or repeat surgery, is approximately 1% per patient-year. However, no echocardiographic study has explored this phenomenon. This study was designed as a one-time observational study and aimed to explore the ability of two-dimensional transthoracic echocardiography to identify cloth cover tears in 35 late survivors with 38 fully covered Starr-Edwards valves who had been operated on 20 to 24 years earlier. The hemodynamic profile, clinical status, and valve-related complications in this highly selected group of late survivors were also studied. Five patients also underwent transesophageal echocardiography. An elongated echogenic mass attached to the prosthetic valve cage and floating downstream was considered indicative of cloth tear. There were 16 patients with aortic valve prostheses, 16 with mitral valve prostheses, and three with double prosthetic valves. In six (17.1%) patients (four with aortic valve prostheses, two with mitral valve prostheses), an echogenic mass suggestive of cloth cover tear was detected, which was confirmed by transesophageal echocardiography in three patients. In two patients the echocardiographic finding was confirmed at surgery. The initial presentation of these six patients was endocarditis, possible embolism, unexplained dyspnea, and weakness in one patient each. Two patients were asymptomatic. There was no evidence of significant prosthetic valve malfunction in any patient. The transvalvular gradients were similar in patients with and without cloth cover tears. Echocardiographic findings highly suggestive of cloth cover tears are not uncommon and can be detected in the third postoperative decade in patients with fully covered Starr-Edwards valves. A prospective study to evaluate the clinical significance of an incidental echocardiographic finding suggestive of cloth cover tears in asymptomatic patients with these valve models is warranted.

[Prosthetic heart valve thrombosis: a 3-year experience].

A series of 12 patients with 16 episodes of prosthetic heart-valve thrombosis over 3 years is presented. Most episodes affected mitral or tricuspid bileaflet prostheses. All patients were inadequately anticoagulated at the time of thrombosis. The clinical presentation was acute and severe in 6 patients, and subacute or chronic in the rest. Physical examination was suggestive of stuck valves in most cases. Transthoracic echocardiography revealed increased transvalvular gradients in most. However, clearer evidence of valve thrombosis was obtained from transesophageal echocardiography or fluoroscopy. 9 patients eventually had their valves re-replaced successfully, and the preoperative diagnosis was confirmed in all. 5 patients were operated as soon as the diagnosis was established. and an additional 4 were operated after failure of anticoagulation. In 4 patients the valve leaflets became completely mobile after a course of thrombolysis. Prosthetic valve thrombosis is a severe and potentially fatal complication in patients with mechanical heart valves. Alertness of physicians at all levels- the general practitioner, the internist and the cardiologist- to the possibility of valve thrombosis and to its clinical presentation may lead to prompt and earlier diagnosis and to comprehensive therapy.

Suture granuloma simulating lung neoplasm occurring after segmentectomy.

A suture granuloma was resected which developed after segmentectomy of a squamous cell carcinoma of the lung and radiologically mimicked a neoplasm. This report emphasises that although the appearance of the lesion may be typical for malignancy, the possibility of a benign suture granuloma should be considered, especially if the lesion appears shortly after surgery.

An unusual cause of recurrent angina two years after coronary artery bypass grafting: fistula between internal mammary artery graft to pulmonary vasculature.

A 55-year-old man developed recurrent angina pectoris 2 years after coronary artery bypass grafting. Cardiac catheterization demonstrated that the venous grafts were patent, but selective left internal mammary angiogram showed multiple fistulous connections between the internal mammary artery and the pulmonary vasculature of the left upper lobe. After surgical correction of the fistula, the angina resolved. Only three previous cases of acquired internal mammary artery graft fistulas draining to the pulmonary vasculature have been described. The etiology, clinical presentation, and management of an internal mammary artery fistula to the pulmonary vasculature are discussed.

Recombinant alpha-interferon may be efficacious in acute hepatitis B.

Whereas, in chronic type B hepatitis, the therapeutic effect of alpha-interferon has been studied extensively, data on the effect of interferon on the course and prognosis of acute hepatitis B are scarce in the literature. We report a case of acute type B hepatitis complicated by life-threatening extrahepatic manifestations where recombinant alpha-interferon facilitated clinical, biochemical, and serological recovery.