Adaptive Petal Reflector: In-Lab Software Configurable Optical Testing System Metrology and Modal Wavefront Reconstruction.

This paper addresses two aspects of the metrology of spherical, petal polymer reflectors which are part of an effort by the European Space Agency (ESA) to develop actively controlled foldable reflectors, enabling larger apertures on CubeSats and small satellites. The first problem is that of measuring the surface figure error of the spherical reflector alone during the development phase, and to assess the quality before assembling the telescope (large stroke, low accuracy). The SCOTS (Software Configurable Optical Testing System) appears to provide a fast and satisfactory solution to this problem. The second problem is the wavefront error reconstruction when the petal reflector is mounted on the telescope, because parts of the petals are obscured by the secondary mirror, in such a way that the petals appear completely disconnected, making the gradient-based metrology impossible. Using the fact that the petals have common mechanical boundary conditions at the central support ring, the problem is solved by using a set of orthogonal modes satisfying the same boundary conditions. The vibration modes are used for this purpose; the modal amplitudes are reconstructed from slope data outside the obstruction, allowing for wavefront error reconstruction over the entire surface.

Causes of misdiagnosis of chronic obstructive pulmonary disease: A systematic scoping review.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) has serious implications at both the individual and the societal level. It is crucial that COPD is diagnosed correctly to ensure provision of the right treatment. However, the current diagnostic procedures may lead to misdiagnosis. AIM: The aim of this scoping review was to disseminate knowledge about potential causes of misdiagnosis of COPD. METHODS: A systematic, comprehensive search was performed in PubMed, Embase and Cinahl. RESULTS: A thorough review produced a sample of 73 articles. The synthesis revealed five potential causes of misdiagnosis of COPD, including: the threshold for defining COPD (n = 36), errors made in primary care (n = 15), errors linked to the spirometry test (n = 13), differential diagnoses (n = 10), and patient-related factors (n = 8). CONCLUSIONS: The causes of misdiagnosis of COPD are attributable mainly to spirometry and to the healthcare professional performing the diagnostic assessment. With a view to limiting misdiagnosis of COPD, future research should help clarify strategies for alternative objective tests for determining if a patient has COPD and explore how to better support primary care in the diagnosing of COPD.

Undiagnosed chronic obstructive pulmonary disease in patients admitted to an acute assessment unit.

Introduction: Chronic obstructive pulmonary disease (COPD) is very prevalent worldwide, yet underdiagnosed. Aim: This study investigates feasibility of performing spirometry in patients in need of acute hospital admission as well as the prevalence of undiagnosed COPD in the same cohort. Methods: During a two-week period, all patients admitted to three large acute assessment units were evaluated. Patients ≥ 18 years, able to perform spirometry, with no surgery to the thorax or abdomen within the last weeks and no known COPD was included. Patients with FEV1/FEV6 ≤ 0.7 or FEV1 < 80% or FEV6 < 80% were offered follow-up visit after 6 weeks. Results: Of the 1145 admitted patients, 46% were eligible: 28% of those had an abnormal spirometry. The offered follow-up visit was attended by 51% and in this group 17% were diagnosed with lung disease. COPD was the most prevalent diagnosis (73%), and 2/3 was in GOLD group A. In total, 75% of the patients with airflow obstruction at the initial examination remained obstructive. Conclusion: Performing spirometry in patients in need of acute hospital admission is feasible, abnormal findings are common, and COPD is the most prevalent diagnosis.

Pharmacokinetics and absorption of paromomycin and gentamicin from topical creams used to treat cutaneous leishmaniasis.

This study evaluated the pharmacokinetics of topical creams containing 15% paromomycin ("paromomycin alone") and 15% paromomycin plus 0.5% gentamicin (WR 279,396) in patients with cutaneous leishmaniasis. The investigational creams were applied topically to all lesions once daily for 20 days. Plasma samples were analyzed for simultaneous quantitation of paromomycin and gentamicin isomers and total gentamicin. Pharmacokinetic parameters for gentamicin could not be calculated because detectable levels were rarely evident. After one application, the paromomycin area under the concentration-time curve from 0 to 24 h (AUC0-24) was 2,180 ± 2,621 ng · h/ml (mean ± standard deviation [SD]) for the paromomycin-alone group and 975.6 ± 1,078 ng · h/ml for the WR 279,396 group. After 20 days of application, the paromomycin AUC0-24 and maximum concentration of drug (Cmax) were 5 to 6 times greater than those on day 1 for both treatment groups. For the paromomycin-alone group, the AUC0-24 was 8,575 ± 7,268 ng · h/ml and the Cmax was 1,000 ± 750 ng/ml, compared with 6,037 ± 3,956 ng · h/ml and 660 ± 486 ng/ml for the WR 279,396 group, respectively. Possibly due to large intersubject variability, no differences (P ≥ 0.05) in the AUC0-24 or Cmax were noted between treatment or between sites on day 1 or 20. The percentage of dose absorbed on day 20 was 12.0% ± 6.26% and 9.68% ± 6.05% for paromomycin alone and WR 279,396, respectively. Paromomycin concentrations in plasma after 20 days of application were 5 to 9% of those after intramuscular administration of 15 mg/kg of body weight/day to adults for the systemic treatment of visceral leishmaniasis. Effective topical treatment of cutaneous leishmaniasis appears to be possible with limited paromomycin and gentamicin systemic absorption, thus avoiding drug accumulation and toxicity. (The work described here has been registered at ClinicalTrials.gov under registration no. NCT01032382 and NCT01083576.).

Patients' use of self-monitored readings for managing everyday life with COPD: a qualitative study.

OBJECTIVE: Effects of self-monitoring depend on how patients engage with readings and how this engagement is used for managing chronic disease. This article reports on a study of how chronic obstructive pulmonary disease (COPD) patients made use of readings during 16 weeks of self-monitoring. PATIENTS AND METHODS: Semistructured interviews were conducted with 22 COPD patients three times each: at the beginning, halfway through, and after the monitoring device was collected. Spouses of nine interviewees were present during one or more interviews. The analysis of how patients used self-monitored readings was based on critical psychology. RESULTS: Patients used readings to monitor bodily condition, to judge whether and when to contact health professionals, to communicate with health professionals about health management, to revise planned activities, to engage close relatives, and to motivate exercise and other health behavior. Self-monitoring can produce a sense of security as readings provide grounds for explaining symptoms and widen the scope of possibilities for taking action. Patients experienced readings as encouraging, reassuring, depressing, worrisome, and at times disturbing. A few patients involved themselves with readings in ways that are emotionally challenging and contrary to medical advice. Reasons for not making use of self-monitoring include good health or not regarding monitoring as relevant at the time. CONCLUSIONS: Results can qualify the support health professionals offer in relation to patients' self-monitoring and self-management.

Topical paromomycin with or without gentamicin for cutaneous leishmaniasis.

BACKGROUND: There is a need for a simple and efficacious treatment for cutaneous leishmaniasis with an acceptable side-effect profile. METHODS: We conducted a randomized, vehicle-controlled phase 3 trial of topical treatments containing 15% paromomycin, with and without 0.5% gentamicin, for cutaneous leishmaniasis caused by Leishmania major in Tunisia. We randomly assigned 375 patients with one to five ulcerative lesions from cutaneous leishmaniasis to receive a cream containing 15% paromomycin-0.5% gentamicin (called WR 279,396), 15% paromomycin alone, or vehicle control (with the same base as the other two creams but containing neither paromomycin nor gentamicin). Each lesion was treated once daily for 20 days. The primary end point was the cure of the index lesion. Cure was defined as at least 50% reduction in the size of the index lesion by 42 days, complete reepithelialization by 98 days, and absence of relapse by the end of the trial (168 days). Any withdrawal from the trial was considered a treatment failure. RESULTS: The rate of cure of the index lesion was 81% (95% confidence interval [CI], 73 to 87) for paromomycin-gentamicin, 82% (95% CI, 74 to 87) for paromomycin alone, and 58% (95% CI, 50 to 67) for vehicle control (P<0.001 for each treatment group vs. the vehicle-control group). Cure of the index lesion was accompanied by cure of all other lesions except in five patients, one in each of the paromomycin groups and three in the vehicle-control group. Mild-to-moderate application-site reactions were more frequent in the paromomycin groups than in the vehicle-control group. CONCLUSIONS: This trial provides evidence of the efficacy of paromomycin-gentamicin and paromomycin alone for ulcerative L. major disease. (Funded by the Department of the Army; ClinicalTrials.gov number, NCT00606580.).

Clinical impact of home telemonitoring on patients with chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) affects millions of people worldwide. A complication of COPD is exacerbations that result in increased utilization of healthcare services, readmissions to the hospital, and a decline in health-related quality of life. Home telehealth has been shown both to improve health-related quality of life and to reduce admission rates. Using clinical data from a home telemonitoring group, this study sought to investigate the clinical impact of telemonitoring. SUBJECTS AND METHODS: Fifty-seven subjects with COPD were included in a 4-month telemonitoring project. Differences between the clinical parameters during the first and last months of participation in the project were tested for significance, and the levels for the first month versus the difference were tested for correlation. RESULTS: Significant declines were observed in prescriptions for antibiotics and steroids (p=0.03), clinical consultations (p=0.05), mean systolic blood pressure (p<0.001), standard deviation of systolic blood pressure (p=0.03), and mean diastolic blood pressure (p=0.02). No significant differences were observed for mean of oxygen saturation (p=0.77), standard deviation of oxygen saturation (p=0.36), mean of forced expiratory volume in 1 s (p=0.17), mean of forced vital capacity (p=0.29), mean of pulse rate (p=0.78), standard deviation of pulse rate (p=0.57), and standard deviation of diastolic blood pressure (p=0.27). CONCLUSIONS: The results suggest that telemonitoring improves the condition of the patient by lowering the blood pressure, the number of prescribed antibiotics and steroids, and the number of clinical consultations.

Cost-utility analysis of a telerehabilitation program: a case study of COPD patients.

OBJECTIVE: The present study seeks to conduct cost-utility analysis (CUA) of the Danish TELEKAT (Telehomecare, Chronic Patients and the Integrated Healthcare System) project. The TELEKAT project seeks to test and develop a preventive home monitoring concept across sectors for chronic obstructive pulmonary disease (COPD) patients. The concept of the TELEKAT project is to reduce admissions by enabling the COPD patients to conduct self-monitoring and maintain rehabilitation activities in their own home. COPD patients with severe and very severe COPD were included in the study. SUBJECTS AND METHODS: This economic evaluation follows international guidelines for the conduction of a CUA alongside a clinical randomized controlled trial. The analysis is based on a health sector perspective. RESULTS: The mean incremental cost efficiency ratio, located in the southeast quadrant, shows that telerehabilitation is less costly and more effective than the rehabilitation given to the control group. The telerehabilitation program produces more value for money and generates savings on healthcare budgets. CONCLUSIONS: The telerehabilitation program appears to be more cost-effective than the conventional rehabilitation program for COPD patients. Further studies of cost-effectiveness with a focus on large-scale studies are needed.

Using preventive home monitoring to reduce hospital admission rates and reduce costs: a case study of telehealth among chronic obstructive pulmonary disease patients.

We studied whether preventive home monitoring of patients with chronic obstructive pulmonary disease (COPD) could reduce the frequency of hospital admissions and lower the cost of hospitalization. Patients were recruited from a health centre, general practitioner (GP) or the pulmonary hospital ward. They were randomized to usual care or tele-rehabilitation with a telehealth monitoring device installed in their home for four months. A total of 111 patients were suitable for inclusion and consented to be randomized: 60 patients were allocated to intervention and three were lost to follow-up. In the control group 51 patients were allocated to usual care and three patients were lost to follow-up. In the tele-rehabilitation group, the mean hospital admission rate was 0.49 per patient per 10 months compared to the control group rate of 1.17; this difference was significant (P = 0.041). The mean cost of admissions was €3461 per patient in the intervention group and €4576 in the control group; this difference was not significant. The Kaplan-Meier estimates for time to hospital admission were longer for the intervention group than the controls, but the difference was not significant. Future work requires large-scale studies of prolonged home monitoring with more extended follow-up.

Marked enhancement of the immune response to BioThrax® (Anthrax Vaccine Adsorbed) by the TLR9 agonist CPG 7909 in healthy volunteers.

Immunization with BioThrax(®) (Anthrax Vaccine Adsorbed) is a safe and effective means of preventing anthrax. Animal studies have demonstrated that the addition of CpG DNA adjuvants to BioThrax can markedly increase the immunogenicity of the vaccine, increasing both serum anti-protective antigen (PA) antibody and anthrax toxin-neutralizing antibody (TNA) concentrations. The immune response to CpG-adjuvanted BioThrax in animals was not only stronger, but was also more rapid and led to higher levels of protection in spore challenge models. The B-class CpG DNA adjuvant CPG 7909, a 24-base synthetic, single-strand oligodeoxynucleotide, was evaluated for its safety profile and adjuvant properties in a Phase 1 clinical trial. A double-blind study was performed in which 69 healthy subjects, age 18-45 years, were randomized to receive three doses of either: (1) BioThrax alone, (2) 1 mg of CPG 7909 alone or (3) BioThrax plus 1 mg of CPG 7909, all given intramuscularly on study days 0, 14 and 28. Subjects were monitored for IgG to PA by ELISA and for TNA titers through study day 56 and for safety through month 6. CPG 7909 increased the antibody response by 6-8-fold at peak, and accelerated the response by 3 weeks compared to the response seen in subjects vaccinated with BioThrax alone. No serious adverse events related to study agents were reported, and the combination was considered to be reasonably well tolerated. The marked acceleration and enhancement of the immune response seen by combining BioThrax and CPG 7909 offers the potential to shorten the course of immunization and reduce the time to protection, and may be particularly useful in the setting of post-exposure prophylaxis.

Epidemiology, diagnostic delay and outcome of tuberculosis in North Jutland, Denmark.

INTRODUCTION: The objective of this study was to evaluate the clinical outcome of tuberculosis (TB) with regards to epidemiology, symptoms, delay, diagnostics, use of HIV-test, treatment, treatment outcome and mortality in the North Jutland Region from 2000 through 2008. MATERIAL AND METHODS: The present study is a retrospective study of all new TB cases in the 2000-2008 period. RESULTS: The period saw a total of 251 TB patients (an average of 28 per year). Almost 60% of the patients were not Danish-born, being mostly from Somalia and Greenland. The mean age was 43 years. 31% were alcohol abusers. 2% had AIDS. Cough was the most frequent symptom followed by weight loss, fever and fatigue. In 78.5% of the cases, it was possible to retrieve a positive culture, 53% had a positive sputum smear. However, in 8% of all patients, it was not possible to isolate Mycobacterium tuberculosis and these cases were diagnosed in accordance with the clinical signs. Almost all patients received the standard treatment comprising four antibiotics. 83% were treated successfully, while 5% ended their treatment prematurely. At the end of the study, 14% were dead. In all, 55% of all patients were HIV-tested. Two tested positive before their TB diagnosis and three after. CONCLUSION: The incidence of TB did not seem to decrease over the course of the study period as seen in the rest of Europe. The relatively high rate of alcohol abusers as compared with earlier Danish literature seems to be due to previous underreporting. A treatment success of 83% is high. This first study of HIV testing in Danish TB patients revealed that it was an acceptable result compared with other studies in this field, but the result was not satisfactory because we may miss patients with HIV/TB co-infection when only half of the patients are tested.

Empowering patients with COPD using Tele-homecare technology.

This paper discusses how a tele-rehabilitation program using home tele-monitoring may empower patients with chronic obstructive pulmonary disease (COPD). The paper is based on preliminary findings from an ongoing research and innovation project, called "Tele-homecare, chronic patients and the integrated healthcare system" (the TELEKAT project) that employs triple interventions related to patients, professionals, and the organization of care. The ways COPD patients make use of home tele-monitoring in the TELEKAT project points to the relevance of a concept of empowerment rooted in ideologies of social action, and focusing on the improvement of both personal and social conditions at the intersection of individual, organizational and community development.

An in vivo passive protection assay for the evaluation of immunity in AVA-vaccinated individuals.

Samples of human plasma from anthrax vaccine adsorbed (AVA, BioThrax)-vaccinated individuals were used to demonstrate passive protection of A/J mice from a lethal challenge with the Sterne strain of anthrax bacteria. The maximum concentration of human anti-protective antigen IgG in mouse sera 24 h after injection of 260 microg of anti-PA IgG was 134 microg/ml, declining to 91 microg/ml at 72 h (half-life=101.7 h). Mice showed significant survival (p

Aprotinin may decrease blood loss in complex adult spinal deformity surgery, but it may also increase the risk of acute renal failure.

STUDY DESIGN: Matched cohort comparison. OBJECTIVE: This study examines the potential for aprotinin to conserve blood in adults undergoing long thoracolumbar deformity procedures and characterizes patients at risk for acute renal failure. SUMMARY OF BACKGROUND DATA: Aprotinin has been shown to reduce intraoperative blood loss and reduce transfusion requirement in pediatric spine and cardiac surgery populations. Previous literature (before 2006) has not reported acute renal failure as a potential complication. This study was designed to examine the efficacy of aprotinin in reducing operative blood loss following long spinal arthrodesis in adult spinal deformity patients and to analyze complications. METHODS: Adult spinal deformity patients undergoing long spinal arthrodesis at 1 institution between 2001 and 2005 were analyzed. Patients were matched according to age and type of procedure performed. Forty patients received high-dose aprotinin (Group A) intraoperatively, and 41 patients matched as controls (Group NA) received no aprotinin. Outcome variables included intraoperative blood loss, intraoperative transfusion requirement, early postoperative blood loss and transfusion requirement, and postoperative complications. RESULTS: Average blood loss for Group A was 906 mL and 1.3 L for Group NA. The difference was statistically significant with a P < 0.05. Complications seen in Group A included 4 cases of acute renal failure requiring dialysis and 1 deep venous thrombosis. In Group NA, there was only 1 case of acute renal failure (presumed to be secondary to inadvertent gentamycin overdose) and 1 case of pulmonary embolus. The 4 Group A patients with acute renal failure were female, 61 to 73 years of age, with various comorbidities. All required inpatient hemodialysis. Three averaged 2 months of continued outpatient dialysis before resolution of renal compromise while 1 patient is on chronic dialysis. CONCLUSION: In long spinal arthrodesis for complex adult spinal deformity surgery, aprotinin does reduce intraoperative blood loss, but may increase the risk of acute renal failure, especially in women over the age of 60.

Pathology of inhalation anthrax in cynomolgus monkeys (Macaca fascicularis).

Anthrax is considered a serious biowarfare and bioterrorism threat because of its high lethality, especially by the inhalation route. Rhesus macaques (Macaca mulatta) are the most commonly used nonhuman primate model of human inhalation anthrax exposure. The nonavailability of rhesus macaques necessitated development of an alternate model for vaccine testing and immunologic studies. This report describes the median lethal dose (LD(50)) and pathology of inhalation anthrax in cynomolgus macaques (Macaca fascicularis). Gross and microscopic tissue changes were reviewed in 14 cynomolgus monkeys that died or were killed after aerosol exposure of spores of Bacillus anthracis (Ames strain). The LD(50) and 95% confidence intervals were 61800 (34000 to 110000) colony-forming units. The most common gross lesions were mild splenomegaly, lymph node enlargement, and hemorrhages in various organs, particularly involving the meninges and the lungs. Mediastinitis, manifested as hemorrhage or edema, affected 29% of the monkeys. Microscopically, lymphocytolysis occurred in the intrathoracic lymph nodes and spleens of all animals, and was particularly severe in the spleen and in germinal centers of lymph nodes. Hemorrhages were common in lungs, bronchial lymph nodes, meninges, gastrointestinal tract, and mediastinum. These results demonstrate that the Ames strain of B. anthracis is lethal by the inhalation route in the cynomolgus macaque. The LD(50) of the Ames strain of B. anthracis was within the expected experimental range of previously reported values in the rhesus monkey in an aerosol challenge. The gross and microscopic pathology of inhalation anthrax in the cynomolgus monkey is remarkably similar to that reported in rhesus monkeys and humans. The results of this study are important for the establishment of an alternative nonhuman primate model for evaluation of medical countermeasures against inhalational anthrax.