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.

Laser technology and applications in gynaecology.

The term 'laser' is an acronym for Light Amplification by Stimulated Emission of Radiation. Lasers are commonly described by the emitted wavelength, which determines the colour of the light, as well as the active lasing medium. Currently, over 40 types of lasers have been developed with a wide range of both industrial and medical uses. Gas and solid-state lasers are frequently used in surgical applications, with CO2 and Ar being the most common examples of gas lasers, and the Nd:YAG and KTP:YAG being the most common examples of solid-state lasers. At present, it appears that the CO2, Nd:YAG, and KTP lasers provide alternative methods for achieving similar results, as opposed to superior results, when compared with traditional endoscopic techniques, such as cold-cutting monopolar and bipolar energy. This review focuses on the physics, tissue interaction, safety and applications of commonly used lasers in gynaecological surgery.

Experience and technique for the endovascular management of iatrogenic subclavian artery injury.

BACKGROUND: Inadvertent subclavian artery catheterization during attempted central venous access is a well-known complication. Historically, these patients are managed with an open operative approach and repair under direct vision via an infraclavicular and/or supraclavicular incision. We describe our experience and technique for endovascular management of these injuries. METHODS: Twenty patients were identified with inadvertent iatrogenic subclavian artery cannulation. All cases were managed via an endovascular technique under local anesthesia. After correcting any coagulopathy, a 4-French glide catheter was percutaneously inserted into the ipsilateral brachial artery and placed in the proximal subclavian artery. Following an arteriogram and localization of the subclavian arterial insertion site, the subclavian catheter was removed and bimanual compression was performed on both sides of the clavicle around the puncture site for 20 min. A second angiogram was performed, and if there was any extravasation, pressure was held for an additional 20 min. If hemostasis was still not obtained, a stent graft was placed via the brachial access site to repair the arterial defect and control the bleeding. RESULTS: Two of the 20 patients required a stent graft for continued bleeding after compression. Both patients were well excluded after endovascular graft placement. Hemostasis was successfully obtained with bimanual compression over the puncture site in the remaining 18 patients. There were no resultant complications at either the subclavian or the brachial puncture site. CONCLUSION: This minimally invasive endovascular approach to iatrogenic subclavian artery injury is a safe alternative to blind removal with manual compression or direct open repair.

Ribosome-membrane interaction. Nondestructive disassembly of rat liver rough microsomes into ribosomal and membranous components.

In a medium of high ionic strength, rat liver rough microsomes can be nondestructively disassembled into ribosomes and stripped membranes if nascent polypeptides are discharged from the bound ribosomes by reaction with puromycin. At 750 mM KCl, 5 mM MgCl(2), 50 mM Tris.HCl, pH 7 5, up to 85% of all bound ribosomes are released from the membranes after incubation at room temperature with 1 mM puromycin. The ribosomes are released as subunits which are active in peptide synthesis if programmed with polyuridylic acid. The ribosome-denuded, or stripped, rough microsomes (RM) can be recovered as intact, essentially unaltered membranous vesicles Judging from the incorporation of [(3)H]puromycin into hot acid-insoluble material and from the release of [(3)H]leucine-labeled nascent polypeptide chains from bound ribosomes, puromycin coupling occurs almost as well at low (25-100 mM) as at high (500-1000 mM) KCl concentrations. Since puromycin-dependent ribosome release only occurs at high ionic strength, it appears that ribosomes are bound to membranes via two types of interactions: a direct one between the membrane and the large ribosomal subunit (labile at high KCl concentration) and an indirect one in which the nascent chain anchors the ribosome to the membrane (puromycin labile). The nascent chains of ribosomes specifically released by puromycin remain tightly associated with the stripped membranes. Some membrane-bound ribosomes (up to 40%) can be nondestructively released in high ionic strength media without puromycin; these appear to consist of a mixture of inactive ribosomes and ribosomes containing relatively short nascent chains. A fraction ( approximately 15%) of the bound ribosomes can only be released from membranes by exposure of RM to ionic conditions which cause extensive unfolding of ribosomal subunits, the nature and significance of these ribosomes is not clear.

An improved cell fractionation procedure for the preparation of rat liver membrane-bound ribosomes.

A cell fractionation procedure is described which allows the preparation from rat liver of a rough microsome population containing almost 50% of the membrane-bound ribosomes of the tissue. The fraction is not contaminated with free ribosomes or smooth microsomes, and, by various other criteria, is suitable for studies of ribosome-membrane interaction.

Multidimensional characterization of carotid artery stenosis using CT imaging: a comparison with ultrasound grading and peak flow measurement.

PURPOSE: Clinical decision making for carotid surgery depends largely upon stenosis grade. While digital subtraction angiography remains the gold standard for stenosis grading, many physicians use less invasive modalities. The purpose of this study was to compare the results of multidimensional Computed tomography (CTA) with ultrasound (US) grading and peak flow velocity (PSV). METHODS: 37 stenosed carotid arteries were studied retrospectively in 36 consecutive patients. US grading and PSV were compared to multidimensional CTA analysis (diameter, area and volumetric measurements), performed by a medical software company. Calculations of stenosis percentage on CTA were made using the NASCET and ECST methodology. Diameter measurements were also performed by a neuroradiologist. RESULTS: All CTA diameter, area and volume measurements had only modest correlation with PSV (r<0.5) and ultrasound grading (p<0.5). There was concordant classification of stenosis grades in only 40-60% of cases. CTA diameter, area and volume measurements had good correlation (0.69

Antibody facilitation of multiple sclerosis-like lesions in a nonhuman primate.

In the human disease multiple sclerosis (MS), the immune mechanisms responsible for selective destruction of central nervous system myelin are unknown. In the common marmoset Callithrix jacchus, a unique demyelinating form of experimental allergic encephalomyelitis resembling MS can be induced by immunization with whole myelin. Here we show that the MS-like lesion can be reproduced by immunization against the extracellular domain of a single myelin protein, myelin/oligodendrocyte glycoprotein (MOG). By contrast, immunization against the quantitatively major myelin proteins myelin basic protein or proteolipid protein results in inflammation but little or no demyelination. Furthermore, in the presence of encephalitogenic (e.g., disease-inducing) T cells, the fully demyelinated lesion is reconstructed by systemic administration of IgG purified from whole myelin-, or MOG-immunized animals, and equally by a monoclonal antibody against MOG, but not by control IgG. Encephalitogenic T cells may contribute to the MS-like lesion through disruption of the blood-brain barrier that permits access of demyelinating antibody into the nervous system. The identification of MOG as a major target antigen for autoimmune demyelination in a nonhuman primate should facilitate development of specific immunotherapies for human MS.

Idiopathic bilateral diaphragmatic dysfunction as a cause of dyspnea.

Diaphragmatic paralysis is an unusual and often underrecognized cause of dyspnea. We present a case of bilateral diaphragmatic paralysis with no identifiable etiology. Our patient is a 73-year-old female with a history of smoking who presented with dyspnea and orthopnea. She was treated for obstructive lung disease with no improvement in dyspnea despite adequate therapy. She had pulmonary function tests (PFTs) that revealed marked decrease in vital capacity and was unable to perform lung volume maneuvers supine due to marked dyspnea. The maximal inspiratory pressure was 37 in the upright position and decreased to 27 in the supine position. She was given a presumptive diagnosis of idiopathic bilateral diaphragmatic dysfunction. Given the history, physical exam, and PFT findings, we felt that the patient did not need further invasive testing. The patient was treated with noninvasive mechanical ventilation due to hypercapnia and her symptoms improved.

Inability of the activated partial thromboplastin time to predict heparin levels. Time to reassess guidelines for heparin assays.

BACKGROUND: In treating venous thromboembolic disorders, patient outcomes appear to correlate with heparin levels. Due to pharmacokinetic and pharmacodynamic variations, a relationship between heparin dose and level cannot be reliably predicted in individual patients. Some patients have low heparin levels despite therapeutic activated partial thromboplastin times (aPTTs), which may increase their risk for recurrent thromboembolism. Patients with high heparin requirements appear to have fewer bleeding episodes with heparin level-guided therapy. The aPTT does not reliably correlate with heparin blood concentrations or antithrombotic effects. Consequently, heparin therapy monitored with heparin levels may be more effective and safer. OBJECTIVES: To prospectively determine whether (1) the aPTT therapeutic range adequately predicts heparin levels in 38 patients used to establish the therapeutic aPTT range as is currently recommended and (2) whether 3 paired sets of aPTT-antifactor Xa levels provide the basis for using aPTTs to predict subsequent heparin levels in individual patients (n = 27) receiving intravenous heparin for coronary artery disease or venous thromboembolic disease. RESULTS: In the therapeutic aPTT range established, the R2 value for the relationship was 0.4. Prediction intervals were wide. For an aPTT of 60 seconds, the 95% prediction interval estimates were heparin levels of 0.05 to 1.0 U/mL. In individual patients, the aPTT-antifactor Xa relationship had an average R2 value of 0.75. There was no consistent relationship between the aPTT and anti-factor Xa level in a significant number of patients. CONCLUSIONS: The aPTT does not appear to be a useful surrogate for heparin levels. These findings suggest that the current recommendations on the use of heparin levels should be expanded.

Intensified tuberculosis case finding among HIV-infected persons using a WHO symptom screen and Xpert(®) MTB/RIF.

SETTING: Human immunodeficiency virus (HIV) clinic in Addis Ababa, Ethiopia. The World Health Organization (WHO) recommends active tuberculosis (TB) case-finding among people living with HIV (PLHIV) in high-burden settings. OBJECTIVE: To evaluate the effectiveness of combining a WHO-recommended symptom screen and the Xpert(®) MTB/RIF test to enhance TB case finding. DESIGN: In this cross-sectional study, PLHIV were screened for TB using a WHO-recommended symptom-based algorithm (cough, fever, night sweats, weight loss). Those with a positive symptom screen (⩾1 symptom) underwent diagnostic testing with smear microscopy, culture, and Xpert. RESULTS: Of 828 PLHIV (89% on antiretroviral therapy), 321 (39%) had a positive symptom screen. In multivariate analysis, an unscheduled clinic visit (aOR 3.78, 95%CI 2.69-5.32), CD4 count <100 cells/µl (aOR 2.62, 95%CI 1.23-5.59) and previous history of TB (aOR 1.62, 95%CI 1.12-2.31) were predictors of a positive symptom screen. Among those with a positive symptom screen, 6% had active pulmonary TB. Smear microscopy sensitivity for TB was poor (30%) compared to culture and Xpert. CONCLUSIONS: A positive symptom screen was common among PLHIV, creating a substantial laboratory burden. Smear microscopy had poor sensitivity for active TB disease. Given the high rate of positive symptom screen, substantial additional resources are needed to implement intensified TB case finding among PLHIV in high-burden areas.

Diagnostic utility of pleural fluid eosinophilia.

It has been stated that pleural fluid eosinophilia (defined as greater than 10 percent eosinophils in the pleural white cell differential count) is not helpful in the diagnosis of exudative effusions. By review of the recent literature, it was found that pleural fluid eosinophilia was associated most often with idiopathic effusions or with air previously introduced into the pleural space. Also, a high proportion of "idiopathic" and benign asbestos effusions were characterized by pleural fluid eosinophilia, a previously unrecognized phenomenon. The diagnostic utility of finding eosinophils in the pleural space was assessed from its impact on prior probabilities of disease. Estimates of pretest likelihoods of malignant versus nonmalignant pleural effusions and the prevalence of eosinophilia in effusions of known cause were obtained from extensive literature review. These were modified by using Bayes' rule to estimate the revised probability of disease in the presence of an eosinophilic effusion. The presence of pleural fluid eosinophilia considerably reduced the probability of malignancy or tuberculosis and increased the likelihood of an underlying benign disorder. Pleural fluid eosinophilia is a useful finding that can aid in the diagnosis of an exudative pleural effusion.

Impact of angiotensin-converting enzyme inhibitor underdosing on rehospitalization rates in congestive heart failure.

In a retrospective, cohort design, clinical usage of digoxin, diuretic, and angiotensin-converting enzyme (ACE) inhibitor was assessed in all patients readmitted over a 36-month period for congestive heart failure (CHF) diagnostic-related group (DRG) 127. ACE inhibitor dose-response analysis used the discharge dose of ACE inhibitor, converted to enalapril-equivalent doses and adjusted for renal function. Principal end points were time-to-readmission and 90-day readmission rate. Of 314 total patients, digoxin was used in 72%, diuretic in 86%, and 67% received an ACE inhibitor. Only 22% of those on an ACE inhibitor received currently recommended doses of enalapril > or = 20 mg/day or equivalent, whereas 41% received enalapril < or = 5 mg/day. Time-to-readmission was increased by an ACE inhibitor (p = 0.002) but not digoxin or diuretic. An ACE inhibitor was the principal covariate of 90-day readmission rate (p <0.05). The readmission rate was not reduced with daily ACE inhibitor doses of < or = 5 mg enalapril, whereas daily doses of > or = 10 mg enalapril reduced 90-day readmission rates by 28% compared to those receiving diuretic or digoxin therapy (p <0.05). Using a dynamic model, the dose required to achieve 90% to 95% of the theoretical maximum ACE inhibitor effect exceeded 100 mg enalapril daily. Thus, CHF readmission rates are lower when daily ACE inhibitor doses exceed 5 mg enalapril or the equivalent daily, but are unaffected by digoxin or diuretic. Modeled maximum ACE inhibitor benefits require doses 8- to 10-fold higher than current usage patterns.

Increased vascular pedicle width preceding burn-related pulmonary edema.

Widening of the vascular pedicle on the chest roentgenogram is a recently identified sign of increased circulating blood volume. To determine whether vascular pedicle enlargement can be detected during the initial day of burn resuscitation and whether this change correlates with the early development of pulmonary edema, we reviewed the serial chest roentgenograms of 42 patients with cutaneous burns and risk factors for inhalation injury. Although no patient had pulmonary edema at the time of vascular pedicle measurements, 18 (42.9 percent) developed this complication during the 3.3 +/- 1.5 days after injury. These patients were significantly older (p less than 0.025) and had received more resuscitative fluid (P less than 0.005) than those without pulmonary edema. Initial vascular pedicle width was similar in both groups (5.9 +/- 0.9 vs 6.0 +/- 1.0 cm) and did not change in patients without pulmonary edema (5.8 +/- 0.7 cm). Vascular pedicle width increased (6.9 +/- 1.2 cm, p less than 0.01) in patients who subsequently developed pulmonary edema, and 12 of the 13 patients who had changes exceeding +1.0 cm had this problem. Enlargement of the vascular pedicle is associated with early burn-related pulmonary edema and might provide a clinically useful predictor of this cardiopulmonary complication.

Changing the infection control paradigm from off-line to real time: the experience at Millard Fillmore Health System.

In 1993, several departments at Millard Fillmore Health System joined efforts to initiate a new approach to infection control. The main emphasis of this program is to move infection control to a real-time mode to manage patient outcomes daily. The principal objective was to decrease the number of nosocomial infections by 10%, with a particular emphasis on surgical-site infections. Besides real-time surveillance, we are critically evaluating several aspects of the management of nosocomial infections. High-level computer support has been the frame-work upon which this program was built. We have microcomputers that are linked directly to microbiology, pharmacy, billing, and admissions, downloading data several times daily. An expert software system merges all of the data, and from this we can target patients for real-time interventions. The computer system allows all inpatients to be screened for either infection control or antibiotic management interventions on a daily basis, with minimal time being spent on data collection and maximal efforts devoted to interventions at the bedside. Additionally, the infection management program will assist in maintaining the extraordinarily low expenditures on antimicrobial agents. During 1993, the Millard Fillmore Health System spent $924,884 on antibiotics, an amount approximately 50% that of comparably sized hospitals.

Changes in antimicrobial agent usage resulting from interactions among clinical pharmacy, the infectious disease division, and the microbiology laboratory.

Rapid reporting of culture and susceptibility data is the first of several important steps in the successful management of infected patients. As has been said many times, rapidly reported data are of little value unless the patient directly benefits. Benefit requires better overall communication and an action plan linked to timely use of these results. In 1989 the Millard Fillmore Hospital Antibiotic Review Committee developed and implemented a prototype approach to hospital wide antimicrobial management. The formulary was revised and the drug use evaluation process modified to enhance effectiveness and to lower the cost of therapy and inventory. Clinical pharmacy antimicrobial agent management specialists were then recruited to individualize patient treatments to the isolated pathogens in conjunction with the Division of Infectious Diseases. To provide the clinical pharmacy specialists with rapid and clinically useful information, a real-time computer link was created between the pharmacy (antibiotic orders) and the microbiology laboratory (culture results). Customized software was implemented to screen all patients automatically for mismatches between pathogens and drugs, or to screen for doses inappropriate to minimum inhibitory concentration or renal function. Special attention was paid to identification of opportunities to target a more appropriate narrow-spectrum regimen after culture results became available. Changes in antimicrobial regimen or dosage were made by contacting the prescribing physician. Over 90% of the recommended changes were made, and virtually all changed regimens had satisfactory clinical outcome. Real dollar expenditures for antimicrobial agents declined by > $200,000 per year. Prior to the institution of this computerized clinical management strategy, antimicrobial purchases were rising yearly at the rate of 12%-15%. The combined efforts of clinical pharmacy, microbiology, and infectious disease personnel successfully optimized antimicrobial therapy on a hospital wide basis. Antimicrobial agent optimization improved patient outcome, and the cost savings more than covered the costs of the program personnel and software.

Transesophageal echocardiographic identification of a retrograde dissection of the ascending aorta caused by inadvertent cannulation of the common carotid artery.

Retrograde aortic dissections can be a complication of vascular procedures. We describe a case of an inadvertent cannulation of the right common carotid artery during an attempt at inserting a pulmonary artery catheter. This resulted in dissection of the right common carotid, subclavian, and innominate arteries. Transesophageal echocardiography was able to visualize a retrograde dissection extending back into the ascending aorta.

Abdominal aortic aneurysms and thoracic aortic atheromas.

BACKGROUND: Abdominal aortic aneurysm (AAA) is associated with atherosclerosis elsewhere. Thoracic aortic atheromas (ATHs) seen on transesophageal echocardiography (TEE) are an important cause of stroke and peripheral embolization. The purposes of this study were to determine whether an association exists between AAA and ATHs and to assess the importance of screening patients with ATHs for AAA. METHODS: For the retrospective analysis, 109 patients with AAA and 109 matched controls were compared for the prevalence of ATHs on TEE and for historical variables. For the prospective analysis, screening for AAA on ultrasonography was performed in 364 patients at the time of TEE. RESULTS: Results of the retrospective analysis showed that ATHs were present in 52% of patients with AAA and in 25% of controls (odds ratio [OR] = 3.3; P =.00003). There was a significantly higher prevalence of hypertension, myocardial infarction, heart failure, smoking, and carotid or peripheral arterial disease in patients with AAA. However, only ATHs were independently associated with AAA on multivariate analysis (P =.001). Results of the prospective analysis showed that screening at the time of TEE in 364 patients revealed AAA in 13.9% of those with ATHs and in 1.4% of those without ATHs (P <.0001; OR = 11.4). CONCLUSIONS: (1) There is a strong, highly significant association between abdominal aneurysm and thoracic atheromas. (2) Patients with AAA may be at high risk for stroke because of the concomitance of thoracic aortic atheromas. (3) The high prevalence of abdominal aneurysm in patients with thoracic atheromas suggests that screening for abdominal aneurysm should be carried out in all patients with thoracic atheromas identified by TEE.

Determinants of antibiotic-associated hypoprothrombinemia.

Hypoprothrombinemia is a relatively uncommon event in the hospitalized patient. When it does occur, it often is associated with surgery, dietary vitamin K deficiency, renal dysfunction, malignancy, and broad-spectrum antibiotic therapy. Several mechanisms have been proposed to account for antibiotic-associated hypoprothrombinemia, including eradication of gastrointestinal bacteria, direct inhibition of vitamin K-dependent coagulation, and indirect inhibition of coagulation. The anecdotal reports and comparative studies of antibiotic-associated hypoprothrombinemia were reviewed; these usually implicated broad-spectrum or the use of several antibiotics. The increased frequency of hypoprothrombinemia associated with moxalactam and cefoperazone also raises questions about the role of their N-methylthiotetrazole (NMTT) side chains. The hypoprothrombinemia associated with NMTT antibiotics does not occur in healthy volunteers and is rare in patients without complicating conditions. Although NMTT inhibits vitamin K-dependent carboxylation in vitro, the parent cephalosporins do not. It is not clear whether NMTT-containing antibiotics liberate sufficient amounts of NMTT in vivo to antagonize clotting in patients. Thus, although moxalactam, and possibly cefoperazone, may in some cases be responsible for increases in prothrombin time, most important question for further study is whether the newer NMTT-containing antibiotics pose a risk of hypoprothrombinemia that is greater than that of antibiotics lacking this side chain.