Does measuring BHR add to guideline derived clinical measures in determining treatment for patients with persistent asthma?

SummaryRationaleLittle is known about the use of biomarkers in guiding treatment decisions in routine asthma management. The objective of this study was to determine whether adding a LABA to an ICS would control bronchial hyperresponsiveness (BHR) at an overall lower dose of ICS when titration of medication was based upon the assessment of routine clinical measures with or without the measurement of BHR.MethodsAfter a 2-week run-in period, subjects (⩾12 years) were randomized to one of three treatment groups. Two groups followed a BHR treatment strategy (based on clinical parameters [lung function, asthma symptoms, and bronchodilator use] and BHR) and were treated with either fluticasone propionate/salmeterol (FSCBHR group) or fluticasone propionate (FPBHR group) (n=156 each). The third group followed a clinical treatment algorithm (based on clinical parameters alone) and were treated with fluticasone propionate (FPREF group; n=154). All treatments were administered via Diskus®. Treatment doses were adjusted as needed every 8 weeks for 40 weeks according to the subject's derived severity class, which was based on clinical measures of asthma control with or without BHR.ResultsThe mean total daily inhaled corticosteroids (ICS) dose during the double-blind treatment period was lower, although not statistically significant, in the FSCBHR group compared with the FPBHR group (a difference of −42.9mcg; p=0.07). Compared with the FPREF group, the mean total daily ICS dose was higher in the FSCBHR group (a difference of 85.2mcg) and was significantly higher in the FPBHR group (a difference of 131.2mcg, p=0.037).ConclusionThis study demonstrated that for most subjects, control of BHR was maintained when treatment was directed toward control of clinical parameters. In addition, there was a trend towards control of BHR and clinical measures at a lower dose of ICS when used concurrently with salmeterol

Određivanje dužine korijenskog kanala: procjena CDR® intraoralnog radiografskog sustava in vivo

The Computed Dental Radiolography System® (CDR: Schick Technologies, Long Island City, NY) is a CCD-based digital intraoral radiographic device which possesses a measurement software algorithm that can be adjusted with respect to an object of known dimension. This “calibration ” algorithm was compared to the CDR® preset mode and analog film using 30 root canals in vivo. The three measurement methods differed significantly from each other for 40% o f the canals sampled. Two o f the three differed significantly for 50% o f canals. No difference existed between the methods for 10% o f the canals. Estimates of tooth length using the calibrated mode differed from those obtained using a conventional radiographic technique by an average o f 1.2 mm, while those using the calibrated mode differed by 1.9 mm. The 1.2 mm average for the calibrated CDR® was judged to be an acceptable degree o f clinical error for most root canal procedures and indicates that the calibration function of the CDR® system should be used when measuring endodontic working lengths. The results demonstrated that calibration to a 15 mm probe when using the Schick CDR® system is more consistent with a comparable measurement, if film is used as the “gold standard”, than are measurements of the tooth length using the CDR® without calibration.Sustav "Kompjuterizirane dentalne radiografije" (CDR: Schick Technologies. Long Island City. NY) je na CDD-u zasnovan uređaj za digitalnu intraoralnu radio grafiju koji posjeduje "Software-ski algoritam" za mjerenja koji se može prilagoditi prema objektu poznate veličine. Ovaj "kalibracijski" algoritam uspoređen je sa sustavom CDR (kompjutorizirane dentalne radiografije) bez mjernog algoritma i analognim filmom rabeći 30 korijenskih kanala in vivo. Tri postupka mjerenja značajno su se razlikovali u 40% mjerenih korijenskih kanala. Dva od tri postupka razlikovala su se u 50% mjerenih kanala. Nikakve razlike između postupaka nije bilo u 10% mjerenih korijenskih kanala. Procjena duljine zuba korištenjem kalibriranog načina razlikovala se od procjene dobivene konvencionalnom (analognom) radio grafskom tehnikom za otprilike 1,2 mm, dok se od digitalnog sustava bez mjernog algoritma razlikovala za prosječno 1,9 mm. Razlika od 1,2 mm za "kalibrirani CDR" se procjenjuje kao prihvatljiva klinička greška za većinu endodontskih postupaka i ukazuje da bi se "kalibracijski sustav CDRa" trebao rabiti pri mjerenju radne duljine korijenskog kanala. Rezultati ukazuju da je kalibracija sonde do 15 mm kad se rabi Schch-ov CDR sustav postojanija s usporednim mjerenjem ako se film koji se mjeri uzme kao "zlatni standard", nego je mjerenje duljine CDR sustavom bez kalibracije

Natural History Of Implantable Cardioverter-Defibrillator Implanted At Or After The Age Of 70 Years In A Veteran Population A Single Center Study

Background: The median age of patients in major Implantable Cardioverter-defibrillator (ICD)trials (MUSTT, MADIT-I, MADIT-II, and SCD-HeFT) was 63-67 years; with only 11% ≥70 years. There is little follow-up data on patients over 70 years of age who received an ICD for primary/secondary prevention of sudden cardiac death, particularly for veterans. Objective: The aim of this study was to study the natural history of ICD implantation for veterans over 70 years of age. Methods: We retrospectively reviewed single center ICD data in 216 patients with a mean age at implantation 76 ± 4 years. The ICD indication was primary prevention in 161 patients and secondary prevention in 55 patients. The ICD indication was unavailable in 4 patients. Results: Mean duration of follow up was 1686 ± 1244 days during which 114 (52%) patients died. Of these, 31% died without receiving any appropriate ICD therapy. Overall, 60/216 (28%) received appropriate therapy and 28/216 (13%) received inappropriate therapy. Patients who had ICD implantation for secondary prophylaxis had statistically more (p= 0.02) appropriate therapies compared to patients who had ICD implantation for primary prevention. Indication for implantation and hypertension predicted appropriate therapy, while age at the time of implantation and presence of atrial fibrillation predicted inappropriate therapies. Overall, 7.7% had device related complications. Conclusions: Although 28% septuagenarians in this study received appropriate ICD therapy, they had high rates of mortality, inappropriate therapy, and device complications. ICD implantation in the elderly merits individualized consideration, with higher benefit for secondary prevention

Određivanje dužine korijenskog kanala: procjena CDR® intraoralnog radiografskog sustava in vivo

The Computed Dental Radiolography System® (CDR: Schick Technologies, Long Island City, NY) is a CCD-based digital intraoral radiographic device which possesses a measurement software algorithm that can be adjusted with respect to an object of known dimension. This “calibration ” algorithm was compared to the CDR® preset mode and analog film using 30 root canals in vivo. The three measurement methods differed significantly from each other for 40% o f the canals sampled. Two o f the three differed significantly for 50% o f canals. No difference existed between the methods for 10% o f the canals. Estimates of tooth length using the calibrated mode differed from those obtained using a conventional radiographic technique by an average o f 1.2 mm, while those using the calibrated mode differed by 1.9 mm. The 1.2 mm average for the calibrated CDR® was judged to be an acceptable degree o f clinical error for most root canal procedures and indicates that the calibration function of the CDR® system should be used when measuring endodontic working lengths. The results demonstrated that calibration to a 15 mm probe when using the Schick CDR® system is more consistent with a comparable measurement, if film is used as the “gold standard”, than are measurements of the tooth length using the CDR® without calibration.Sustav "Kompjuterizirane dentalne radiografije" (CDR: Schick Technologies. Long Island City. NY) je na CDD-u zasnovan uređaj za digitalnu intraoralnu radio grafiju koji posjeduje "Software-ski algoritam" za mjerenja koji se može prilagoditi prema objektu poznate veličine. Ovaj "kalibracijski" algoritam uspoređen je sa sustavom CDR (kompjutorizirane dentalne radiografije) bez mjernog algoritma i analognim filmom rabeći 30 korijenskih kanala in vivo. Tri postupka mjerenja značajno su se razlikovali u 40% mjerenih korijenskih kanala. Dva od tri postupka razlikovala su se u 50% mjerenih kanala. Nikakve razlike između postupaka nije bilo u 10% mjerenih korijenskih kanala. Procjena duljine zuba korištenjem kalibriranog načina razlikovala se od procjene dobivene konvencionalnom (analognom) radio grafskom tehnikom za otprilike 1,2 mm, dok se od digitalnog sustava bez mjernog algoritma razlikovala za prosječno 1,9 mm. Razlika od 1,2 mm za "kalibrirani CDR" se procjenjuje kao prihvatljiva klinička greška za većinu endodontskih postupaka i ukazuje da bi se "kalibracijski sustav CDRa" trebao rabiti pri mjerenju radne duljine korijenskog kanala. Rezultati ukazuju da je kalibracija sonde do 15 mm kad se rabi Schch-ov CDR sustav postojanija s usporednim mjerenjem ako se film koji se mjeri uzme kao "zlatni standard", nego je mjerenje duljine CDR sustavom bez kalibracije

Recruitment and Retention Strategies for Minority or Poor Clinical Research Participants: Lessons From the Healthy Aging in Neighborhoods of Diversity Across the Life Span Study

Purpose of the study: Investigating health disparities requires studies designed to recruit and retain racially and socioeconomically diverse cohorts. It is critical to address the barriers that disproportionately affect participation in clinical research by minorities and the socioeconomically disadvantaged. This study sought to identify and rectify these barriers to recruit and retain a biracial (African American and non-Hispanic White) and socioeconomically diverse cohort for a longitudinal study. Design and Method: The Healthy Aging in Neighborhoods of Diversity across the Life Span study is a 20-year longitudinal examination of how race and socioeconomic status influence the development of age-related health disparities. One goal was to create a multifactorial recruitment and retention strategy. The recruitment paradigm targeted known barriers and identified those unique to the study's urban environment. The retention paradigm mirrored the recruitment plan but was based on specifically developed approaches. Results: This cohort recruitment required attention to developing community partnerships, designing the research study to meet the study hypotheses and to provide benefit to participants, providing a safe community-based site for the research and creating didactics to develop staff cultural proficiency. These efforts facilitated study implementation and enhanced recruitment resulting in accrual of a biracial and socioeconomically diverse cohort of 3,722 participants. Implications: Recruiting and retaining minority or poor research participants is challenging but possible. The essential facets include clear communication of the research hypothesis, focus on providing a direct benefit for participants, and selection of a hypothesis that is directly relevant to the community studie

Naturally Occurring Osmolyte, Trehalose Induces Functional Conformation in an Intrinsically Disordered Activation Domain of Glucocorticoid Receptor

Intrinsically disordered (ID) regions are frequently found in the activation domains of many transcription factors including nuclear hormone receptors. It is believed that these ID regions promote molecular recognition by creating large surfaces suitable for interactions with their specific protein binding partners, which is a critical component of gene regulation by transcription factors. It has been hypothesized that conditional folding of these activation domains may be a prerequisite for their efficient interaction with specific coregulatory proteins, and subsequent transcriptional activity leading to the regulation of target gene(s). In this study, we tested whether a naturally occurring osmolyte, trehalose can promote functionally ordered conformation in glucocorticoid receptor's major activation function domain, AF1, which is found to exist as an ID protein, and requires an efficient interaction with coregulatory proteins for optimal activity. Our data show that trehalose induces an ordered conformation in AF1 such that its interaction with steroid receptor coactivator-1 (SRC-1), a critical coregulator of glucocorticoid receptor's activity, is greatly enhanced

Evaluation of a novel real-time PCR test based on the ssrA gene for the identification of group B streptococci in vaginal swabs

<p>Abstract</p> <p>Background</p> <p>Despite the implementation of prevention guidelines, early-onset group B streptococci (GBS) disease remains a cause of neonatal morbidity and mortality worldwide. Strategies to identify women who are at risk of transmitting GBS to their infant and the administration of intrapartum antibiotics have greatly reduced the incidence of neonatal GBS disease. However, there is a requirement for a rapid diagnostic test for GBS that can be carried out in a labour ward setting especially for women whose GBS colonisation status is unknown at the time of delivery. We report the design and evaluation of a real-time PCR test (<it>RiboSEQ </it>GBS test) for the identification of GBS in vaginal swabs from pregnant women.</p> <p>Methods</p> <p>The qualitative real-time PCR <it>RiboSEQ </it>GBS test was designed based on the bacterial <it>ssrA </it>gene and incorporates a competitive internal standard control. The analytical sensitivity of the test was established using crude lysate extracted from serial dilutions of overnight GBS culture using the IDI Lysis kit. Specificity studies were performed using DNA prepared from a panel of GBS strains, related streptococci and other species found in the genital tract environment. The <it>RiboSEQ </it>GBS test was evaluated on 159 vaginal swabs from pregnant women and compared with the GeneOhm™ StrepB Assay and culture for the identification of GBS.</p> <p>Results</p> <p>The <it>RiboSEQ </it>GBS test is specific and has an analytical sensitivity of 1-10 cell equivalents. The <it>RiboSEQ </it>GBS test was 96.4% sensitive and 95.8% specific compared to "gold standard" culture for the identification of GBS in vaginal swabs from pregnant women. In this study, the <it>RiboSEQ </it>GBS test performed slightly better than the commercial BD GeneOhm™ StrepB Assay which gave a sensitivity of 94.6% and a specificity of 89.6% compared to culture.</p> <p>Conclusion</p> <p>The <it>RiboSEQ </it>GBS test is a valuable method for the rapid, sensitive and specific detection of GBS in pregnant women. This study also validates the <it>ssrA </it>gene as a suitable and versatile target for nucleic acid-based diagnostic tests for bacterial pathogens.</p

The Boston Puerto Rican Health Study, a longitudinal cohort study on health disparities in Puerto Rican adults: challenges and opportunities

BACKGROUND: The Boston Puerto Rican Health Study is an ongoing longitudinal cohort study designed to examine the role of psychosocial stress on presence and development of allostatic load and health outcomes in Puerto Ricans, and potential modification by nutritional status, genetic variation, and social support. METHODS: Self-identified Puerto Ricans, aged 45-75 years and residing in the Boston, MA metro area, were recruited through door-to-door enumeration and community approaches. Participants completed a comprehensive set of questionnaires and tests. Blood, urine and salivary samples were extracted for biomarker and genetic analysis. Measurements are repeated at a two-year follow-up. RESULTS: A total of 1500 eligible participants completed baseline measurements, with nearly 80% two-year follow-up retention. The majority of the cohort is female (70%), and many have less than 8th grade education (48%), and fall below the poverty level (59%). Baseline prevalence of health conditions is high for this age range: considerable physical (26%) and cognitive (7%) impairment, obesity (57%), type 2 diabetes (40%), hypertension (69%), arthritis (50%) and depressive symptomatology (60%). CONCLUSIONS: The enrollment of minority groups presents unique challenges. This report highlights approaches to working with difficult to reach populations, and describes some of the health issues and needs of Puerto Rican older adults. These results may inform future studies and interventions aiming to improve the health of this and similar communities

Reliability of the modified child and adolescent physical activity and nutrition survey, physical activity (CAPANS-PA) questionnaire among chinese-australian youth

Background : Evidence suggests that differences exist in physical activity (PA) participation among Culturally and Linguistically Diverse (CALD) children and adolescents. It is possible that these differences could be influenced by variations in measurement technique and instrument reliability. However, culturally sensitive instruments for examining PA behaviour among CALD populations are lacking. This study tested the reliability of the Child and Adolescent Physical Activity and Nutrition Survey (CAPANS-PA) recall questionnaire among a sample of Chinese-Australian youth.Methods : The psychometric property of the CAPANS-PA questionnaire was examined among a sample of 77 Chinese-Australian youth (aged 11 - 14 y) who completed the questionnaire twice within 7 days. Test-retest reliability of individual items and scales within the CAPANS-PA questionnaire was determined using Kappa statistics for categorical variables and intraclass correlation coefficients (ICC) for continuous variables.Results : The CAPANS-PA questionnaire demonstrated acceptable test-retest reliability for frequency and duration of time spent in weekly Moderate to Vigorous Physical Activity (MVPA) (ICC &ge; 0.70) for all participants. Test-retest reliability for time spent in weekly sedentary activities was acceptable for females (ICC = 0.82) and males (ICC = 0.72).Conclusions : The results suggest the CAPANS-PA questionnaire provides reliable estimates for type, frequency and duration of MVPA participation among Chinese-Australian youth. Further investigation into the reliability of the sedentary items within the CAPANS-PA is required before these items can be used with confidence. This study is novel in that the reliability of instruments among CALD groups nationally and internationally remains sparse and this study contributes to the wider body of available psychometrically tested instruments. In addition, this study is the first to our knowledge to successfully engage and investigate the basic health enhancing behaviours of Chinese-Australian adolescents.<br /

'You give us rangoli, we give you talk': using an art-based activity to elicit data from a seldom heard group

<p>Abstract</p> <p>Background</p> <p>The exclusion from health research of groups most affected by poor health is an issue not only of poor science, but also of ethics and social justice. Even if exclusion is inadvertent and unplanned, policy makers will be uninformed by the data and experiences of these groups. The effect on the allocation of resources is likely to be an exacerbation of health inequalities.</p> <p>Discussion</p> <p>We subject to critical analysis the notion that certain groups, by virtue of sharing a particular identity, are inaccessible to researchers - a phenomenon often problematically referred to as 'hard to reach'. We use the term 'seldom heard' to move the emphasis from a perceived innate characteristic of these groups to a consideration of the methods we choose as researchers. Drawing on a study exploring the intersections of faith, culture, health and food, we describe a process of recruitment, data collection and analysis in which we sought to overcome barriers to participation. As we were interested in the voices of South Asian women, many of whom are largely invisible in public life, we adopted an approach to data collection which was culturally in tune with the women's lives and values. A collaborative activity mirroring food preparation provided a focus for talk and created an environment conducive to data collection. We discuss the importance of what we term 'shoe leather research' which involves visiting the local area, meeting potential gatekeepers, and attending public events in order to develop our profile as researchers in the community. We examine issues of ethics, data quality, management and analysis which were raised by our choice of method.</p> <p>Summary</p> <p>In order to work towards a more theoretical understanding of how material, social and cultural factors are connected and influence each other in ways that have effects on health, researchers must attend to the quality of the data they collect to generate finely grained and contextually relevant findings. This in turn will inform the design of culturally sensitive health care services. To achieve this, researchers need to consider methods of recruitment; the makeup of the research team; issues of gender, faith and culture; and data quality, management and analysis.</p