Viruses are frequently present as the infecting agent in acute exacerbations of chronic obstructive pulmonary disease in patients presenting to hospital.

BACKGROUND: Viral causes of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are well recognised but only recently have rapid tests become available. AIMS: To identify respiratory viruses in the general population and those associated with hospitalisation in AECOPD using polymerase chain reaction (PCR) on nasopharyngeal aspirate (NPA), and the relationship between symptoms, viral detection and inflammatory markers. METHODS: A review of viruses detected in the general population in a health district between August 2014 and July 2015, using multiplex PCR for viruses from NPA samples. In addition, a single hospital, retrospective audit of patients admitted with suspected AECOPD was conducted. RESULTS: Of the 8811 NPA tested, 5599 (64%) were positive for at least one virus and 2069 of these were obtained from adults. In adults, the most common viruses identified were Influenza A (31%), Rhinovirus (27%) and respiratory syncytial virus A/B (10%). Most patients with AECOPD (102 of 153) had NPA sent for viral PCR testing and 59 (58%) were positive. The most common viruses identified were Influenza A (31%), Rhinovirus (24%) and respiratory syncytial virus A/B (17%) with co-infecting bacteria cultured in 22 sputum samples. Patients with influenza-like symptoms were more likely to have a positive viral PCR than those without symptoms (P < 0.004). The median C-reactive protein on admission was lower in the virus-infected than uninfected AECOPD (28 vs 60 mg/L, P < 0.026). CONCLUSION: The spectrum of viruses detected in patients with AECOPD is similar to that of the general population. Viruses are more likely to be identified in patients with AECOPD who present with influenza-like symptoms and a low C-reactive protein.

Laboratory test performance in young adults during influenza outbreaks at World Youth Day 2008.

BACKGROUND: The performance of influenza laboratory diagnostics in young adults and in the setting of outbreaks during mass gatherings has not been well studied. OBJECTIVES: We compare the performance of point-of-care tests (POCTs) and immunofluorescence assays (IFAs) with nucleic acid tests (NATs) and viral culture in pilgrims attending influenza clinics established during a large influenza outbreak (World Youth Day, Sydney, Australia, 2008) to assess their performance under the real-life pressures of a mass influenza outbreak. STUDY DESIGN: Patients with an influenza-like illness (ILI) underwent respiratory specimen sampling. Combined deep nares and throat swabs were collected for POCT by trained or untrained clinic staff; type-specific IFA; NAT and viral culture. Laboratory-confirmed influenza occurred if viral culture and/or NAT were positive; the performance of laboratory tests was calculated against this 'gold standard'. RESULTS: A total of 230 samples were collected from 227 patients (median age, 20 years; interquartile range, 18-28 years), with 95 samples (41.3%) having laboratory-confirmed influenza infection (influenza A, 57; influenza B, 38). IFA and POCT sensitivities were 74.5% and 55%, respectively. Four of 51 (8%) culture-positive specimens were negative by NAT, and several errors in influenza virus typing occurred with IFA, POCT and NAT. A non-significant trend towards better POCT performance with increased operator training was demonstrated. CONCLUSION: Different environments, patient populations, operator experience, laboratory access and practicalities associated with performing tests during mass influenza outbreaks may affect performance of influenza-specific laboratory tests.

Src inhibitors in early breast cancer: a methodology, feasibility and variability study.

Early clinical trials of anticancer agents may be enriched by robust biomarkers of activity. Surrogate measures used in trials of cytotoxic agents, such as tumor size regression, may not be informative when investigating targeted agents that act principally to inhibit invasion or proliferation. This study aimed to determine the validity of invasion-related biomarkers of activity for AZD0530, a potent Src inhibitor currently in clinical development. Focal adhesion kinase (FAK) and paxillin are downstream phosphorylation substrates of Src and mediate tumor cell adhesion and invasiveness. These were therefore selected as biologically relevant markers of Src inhibition. Early breast cancer was chosen as a model as multiple samples can be collected during standard treatment and there is an intervening period in which experimental intervention can be applied. Tumor tissue was collected from diagnostic core biopsies and subsequent surgical tumor excision samples in 29 women with early breast cancer attending a single center. Protein levels were assessed quantitatively by Luminex and qualitatively by immunohistochemistry. AZD0530 inhibited tumor growth in a manner independent of dose and inhibited phosphorylation of FAK and paxillin in a dose-dependent manner in a Calu-6 xenograft model. In the clinical study, agreement of within-visit and also of between-visit measurements was high and the estimated number of patients required to detect a drug effect would be low enough to allow use of these markers as endpoints in future dose selection studies.

Mindfulness-based Cognitive Therapy (MBCT) in bipolar disorder: preliminary evaluation of immediate effects on between-episode functioning.

BACKGROUND: Bipolar disorder is highly recurrent and rates of comorbidity are high. Studies have pointed to anxiety comorbidity as one factor associated with risk of suicide attempts and poor overall outcome. This study aimed to explore the feasibility and potential benefits of a new psychological treatment (Mindfulness-based Cognitive Therapy: MBCT) for people with bipolar disorder focusing on between-episode anxiety and depressive symptoms. METHODS: The study used data from a pilot randomized trial of MBCT for people with bipolar disorder in remission, focusing on between-episode anxiety and depressive symptoms. Immediate effects of MBCT versus waitlist on levels of anxiety and depression were compared between unipolar and bipolar participants. RESULTS: The results suggest that MBCT led to improved immediate outcomes in terms of anxiety which were specific to the bipolar group. Both bipolar and unipolar participants allocated to MBCT showed reductions in residual depressive symptoms relative to those allocated to the waitlist condition. LIMITATIONS: Analyses were based on a small sample, limiting power. Additionally the study recruited participants with suicidal ideation or behaviour so the findings cannot immediately be generalized to individuals without these symptoms. CONCLUSIONS: The study, although preliminary, suggests an immediate effect of MBCT on anxiety and depressive symptoms among bipolar participants with suicidal ideation or behaviour, and indicates that further research into the use of MBCT with bipolar patients may be warranted.

Influenza outbreak in a correctional facility.

The outbreak of influenza in a corrections facility occurred during August 2000. The outbreak progressed following introduction of the disease by a member of the public to the facility. Rapid diagnosis and typing of the influenza isolates was available, although two prisoners required hospital admission due to the severity of complications at the time of diagnosis. The group demonstrated rapid transmission of the virus by the respiratory route and probably by fomites. The identified infecting virus was A/Moscow-like, an H3N2 subtype typically associated with large outbreaks. Prevention of such outbreaks will involve either achieving high rates of vaccination within the risk groups, or rapid (possibly point of care) diagnosis with the institution of antiviral therapy within 48 hours of symptoms. Influenza control within institutions is feasible using such strategies, although it requires considerable planning to have such approaches in place during winter--a time when institutional staff absenteeism is typically high.

Hospital diversification into long-term care.

In the 1990s, acute care hospitals in the United States encountered an unstable operating environment created by a series of transformations in the health care delivery system and long-term-care market. Confronted with an array of economic pressures and demographic changes, hospitals were motivated to engage in long-term-care diversification, such as establishing a long-term-care unit or providing home health services, as a means of entering new markets and ensuring financial stability. This article examines the organizational, market, and community factors associated with this strategic activity among a national sample of urban and rural hospitals.

Dying trajectory in the last year of life: does cancer trajectory fit other diseases?

PURPOSE: To examine differences in the pattern of functional decline among persons dying of cancer and other leading noncancer causes of death. DESIGN: Mortality followback survey of next of kin listed on death certificate. SETTING: Probability sample of all deaths in the United States. PARTICIPANTS: Next of kin for 3,614 decedents that represented 914,335 deaths. MEASUREMENTS: Days of difficulty with activities of daily living and mobility in the last year of life. RESULTS: Relative to other decedents, patients with cancer experienced an increased rate of functional impairment beginning as late as 5 months prior to death. For example, only 13.9% of patients with cancer had difficulty getting out of bed or a chair 1-year prior to death. This increased from 22.2% to 63.0% in the last five months of life. In contrast, decedents from other diseases had higher rates of functional impairment 1 year prior to death (approximately 35% had difficulty getting out of bed or chair) and they manifested a more gradual increase in the level of functional decline (approximately 50% had difficulty getting out of bed). Precipitous functional decline was associated with hospice involvement and dying at home. CONCLUSION: Persons dying of cancer experienced sharp functional decline in the last months of life whereas other decedents' have a more gradual decline. The more precipitous functional decline was associated with hospice involvement and dying at home.

Facility effects on racial differences in nursing home quality of care.

This paper reviews the literature on racial/ethnic differences in nursing home quality, segregated access to nursing home care, and organizational and community factors that may influence access and quality of care. We present illustrative data on county demographics and the racial mix of African American residents in nursing homes in these counties for a sample of four states. We also briefly describe plans for multilevel modeling to test variation in racial/ethnic disparities in care as a function of nursing home structures and processes and community context.

Pharmacokinetics of penicillin G procaine versus penicillin G potassium and procaine hydrochloride in horses.

OBJECTIVE: To compare the pharmacokinetics of penicillin G and procaine in racehorses following i.m. administration of penicillin G procaine (PGP) with pharmacokinetics following i.m. administration of penicillin G potassium and procaine hydrochloride (PH). ANIMALS: 6 healthy adult mares. PROCEDURE: Horses were treated with PGP (22,000 units of penicillin G/kg of body weight, i.m.) and with penicillin G potassium (22,000 U/kg, i.m.) and PH (1.55 mg/kg, i.m.). A minimum of 3 weeks was allowed to elapse between drug treatments. Plasma and urine penicillin G and procaine concentrations were measured by use of high-pressure liquid chromatography. RESULTS: Median elimination phase half-lives of penicillin G were 24.7 and 12.9 hours, respectively, after administration of PGP and penicillin G potassium. Plasma penicillin G concentration 24 hours after administration of penicillin G potassium and PH was not significantly different from concentration 24 hours after administration of PGP. Median elimination phase half-life of procaine following administration of PGP (15.6 hours) was significantly longer than value obtained after administration of penicillin G potassium and PH (1 hour). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that i.m. administration of penicillin G potassium will result in plasma penicillin G concentrations for 24 hours after drug administration comparable to those obtained with administration of PGP Clearance of procaine from plasma following administration of penicillin G potassium and PH was rapid, compared with clearance following administration of PGP.

Presumptive summer influenza A: an outbreak on a trans-Tasman cruise.

A number of recent reports from the Northern Hemisphere have drawn attention to the occurrence of summer outbreaks (May to August) of influenza A among cruise ship passengers and their contacts. In cases amongst passengers returning to Canada from Alaska, exposure appears to have occurred during the land-based Alaskan tour with illness developing during the subsequent cruise. A late summer outbreak of influenza A among passengers and crew on the return leg of a 14-day Sydney-New Zealand-Sydney cruise is reported in this article.

Quantification of penicillin-G and procaine in equine urine and plasma using high-performance liquid chromatography.

A rapid and sensitive method for the extraction and quantification of penicillin-G and procaine in horse urine and plasma samples has been successfully developed. The method involves the use of solid-phase extraction (SPE) for penicillin-G, liquid-liquid extraction (LLE) for procaine, and high-performance liquid chromatography (HPLC) for the quantification of penicillin-G and procaine. The new method described here has been successfully applied in the pharmacokinetic studies of procaine, penicillin-G and procaine-penicillin-G administrations in the horse.

Enhanced neuronal differentiation of NTera-2 cells expressing neuronally restricted beta2 adrenergic receptor.

NTera-2/D1 (NT2) is a human teratocarcinoma cell line which can be cultured as a dividing population of precursor cells that can be manipulated with retinoic acid (RA) to yield post-mitotic neurons. Precursor cells were transfected with the human beta2 adrenergic receptor, controlled by the neuronal cell specific rat synapsin-1 promoter. Transfected precursor cells did not display elevated expression of the beta2 adrenergic receptor. Upon differentiation to a neuronal phenotype with RA, betaSyn2 and betaSyn4 (beta2Syn-NT2; ATCC CRL-12356) displayed elevated beta2 adrenergic receptor levels, and an elevated coupling to cAMP production. It was also observed that the elevated expression of the beta2 adrenergic receptor in the neuronal NT2 cells resulted in an enhanced level of neuronal differentiation compared to the wild type cells. These results demonstrate that the neuronally restricted expression of the human beta2 adrenergic receptor in NT2 neurons results in increased receptor levels and receptor stimulated generation of cAMP, this may result in the observed improvement in neuronal differentiation.

Key challenges in studying organizational issues in the delivery of healthcare to older Americans.

OBJECTIVE: Drawing from the articles presented in this special issue, to provide an overview of three key challenges facing researchers in the area of organizational issues in primary care delivery to older adults. CONCLUSIONS: To improve the quality of research done in this area we would recommend that researchers attend to the complexity of (1) defining an appropriate unit of analysis; (2) reframing our traditional models of service delivery to reflect ongoing changes in healthcare system actors and boundaries; and (3) reconceptualizing the outcomes of care to reflect adequately the reality of care for the aging patient.

Rhodopsin-family receptors associate with small G proteins to activate phospholipase D.

G-protein-coupled receptors of the rhodopsin family transduce many important neural and endocrine signals. These receptors activate heterotrimeric G proteins and in many cases also cause activation of phospholipase D, an enzyme that can be controlled by the small G proteins ARF and RhoA. Here we show that the activation of phospholipase D that is induced by many, but not all, Ca2+-mobilizing G-protein-coupled receptors is sensitive to inhibitors of ARF and of RhoA. Receptors of this type were co-immunoprecipitated with ARF or RhoA on exposure to agonists, and the effects of GTP analogues on ligand binding to the receptor changed to a profile that is characteristic of small G proteins. These receptors contain the amino-acid sequence AsnProXXTyr in their seventh transmembrane domain, whereas receptors capable of activating phospholipase D without involving ARF contain the sequence AspProXXTyr. Mutation of this latter sequence to AsnProXXTyr in the gonadotropin-releasing hormone receptor conferred sensitivity to an inhibitor of ARF, and the reciprocal mutation in the 5-HT2A receptor for 5-hydroxy-tryptamine reduced its sensitivity to the inhibitor. Receptors carrying the AsnProXXTyr motif thus seem to form functional complexes with ARF and RhoA.

Two psychological treatments for hypochondriasis. A randomised controlled trial.

BACKGROUND: Hypochondriasis is generally considered difficult to manage. This study aimed to assess the effectiveness of cognitive therapy and to compare it with an equally credible, alternative treatment. METHOD: Forty-eight patients with hypochondriasis were initially randomly assigned to either cognitive therapy, behavioural stress management or a no treatment waiting list control group. At the end of the waiting period, patients in the control group were randomly assigned to one of the two treatments. Assessments were at pre-, mid- and post-treatment or waiting list and at three-, six- and 12-month post-treatment follow-up. RESULTS: Comparisons with the waiting list group showed both treatments were effective. Comparisons between the treatments showed that cognitive therapy was more effective than behavioural stress management on measures of hypochondriasis, but not general mood disturbance at mid-treatment and at post-treatment. One year after treatment patients who had received either treatment remained significantly better than before treatment, and on almost all measures the two therapies did not differ from each other. CONCLUSIONS: Cognitive therapy is a specific treatment for hypochondriasis. Behavioural stress management is also effective but its specificity remains to be demonstrated.

Linkage strategies of rural hospitals--independent hospital, local health system, and/or externally linked facility.

Strategies associated with ownership or management of a range of health service facilities, service sharing, and other coordination activities are important to the viability of many rural hospitals. This article articulates a set of linkage strategies employed by rural hospitals. Such strategies and their environmental and organizational correlates are assessed in a sample of 46 rural Pennsylvania hospitals.

The suppressive effects of testosterone on growth in young chickens appears to be mediated via a peripheral androgen receptor; studies of the anti-androgen ICI 176,334.

ICI 176,334 is a nonsteroidal anti-androgen that has been shown to selectively block peripheral androgen receptors in rats and is presumed to do so in chickens. In chickens, androgens stimulate secondary sexual characteristics (e.g., comb), but inhibit growth and the immune tissues. The present study examined the effect of dietary ICI 176,334 (5 or 25 mg/kg body weight) on growth in chickens in the presence or absence of testosterone treatment (as 1-cm long silastic implants). Treatments began at 2 wk of age and continued through 6 wk of age. Testosterone alone reduced body growth (average daily gain and shank-toe length, together with weights of the body, skeletal muscle, and the bursa of Fabricius, an immune tissue), and stimulated comb development. At the low dose (5 mg/kg), ICI 176,334 alone had no effect on body growth or organ weight with the exception that comb weight was reduced. At the high dose (25 mg/kg), ICI 176,334 decreased growth (body weight, average daily gain, and shank-toe length) and organ weights (breast muscle, bursa of Fabricius, testis, and comb weights). This effect may represent a toxicity. As might be expected with an anti-androgen, ICI 176,334 (at either 5 or 25 mg/kg) completely suppressed the stimulation of comb growth evoked by testosterone. Similarly, ICI 176,334 (5 mg/kg) overcame, albeit partially, the growth-suppressive effects of testosterone (on body weight, average daily gain, shank-toe length, and breast muscle weight) and also had inhibitory effects on the weights of the testis and bursa of Fabricius. The anti-androgen, ICI 176,334, did not influence the reduction in circulating concentrations of luteinizing hormone occurring after testosterone treatment. The present data are consistent with the growth-suppressive effects of testosterone in chickens being mediated via a peripheral androgen receptor. No effects of either testosterone or ICI 176,334 were observed on circulating concentrations of insulin-like growth factor-I despite the marked changes in growth rate.