Pegylated interferon pharmacokinetics and self-reported depressive symptoms during antiviral treatment for chronic hepatitis C.

BACKGROUND: Pegylated interferon-2a (PegIFN-2a)+ribavirin treatment for chronic hepatitis C is often associated with depressive symptoms. Previous studies have failed to explore whether PegIFN-2a pharmacokinetic variability plays an etiologic role in PegIFN-2a-induced mood disorders. The objective of this investigation was to evaluate the association between trough PegIFN-2a concentration at treatment week 4 ("PegIFN-2a Cmin4") and an increase in depressive symptoms. METHODS: Using data from Virahep-C, the association between PegIFN-2a Cmin4 and the following depression outcomes were evaluated using the Center for Epidemiological Studies-Depression scale (CES-D): (1) change in CES-D score from baseline to week 12; (2) greatest difference in CES-D score between baseline and weeks 4, 12, or 24; and (3) occurrence of severe depressive symptoms (CES-D greater than 23) at weeks 4, 12, or 24. One post-hoc analysis examined whether PegIFN-2a exposure during the first week of treatment was associated with change in CES-D score from baseline to week 4. RESULTS: No significant associations between PegIFN-2a Cmin4 and the depression outcomes were observed (p>0.05). Exploratory analyses suggest a possible relationship between PegIFN-2a exposure during the first week of therapy and CES-D score change from baseline to week 4 (p=0.03). CONCLUSIONS: PegIFN-2a concentration levels from baseline to week 4 do not predict the onset and severity of depressive symptoms during 24 weeks of antiviral therapy; however PegIFN-2a levels during the first week of treatment may predict depressive symptoms in the first 4 weeks, earlier than anticipated and warrants further exploration.

Cardiologists are more willing to prescribe ß-blockers than respiratory physicians: an Australasian clinical scenario survey.

BACKGROUND/AIMS: Recent data show great benefit from beta adrenergic blocking drug (ß-blocker) use in heart failure and has resulted in increased use of these established agents. Older data caution against their use in patients with reversible airways disease because of risks of bronchoconstriction. Anecdotally, we noted a difference in willingness to prescribe ß-blockers by cardiologists and respiratory physicians, especially for patients with coexisting airways disease. We sought to test this difference. METHODS: Nine clinical scenarios were created, tested and emailed to all members of the Cardiac and Thoracic societies of Australasia. Scenarios combined varying degrees of benefit and risk (bronchoconstriction). An inducement to return questionnaires was applied. RESULTS: Cardiologists and respiratory physicians were similarly willing to prescribe ß-blockers for patients at little risk of bronchoconstriction, irrespective of potential benefit. Cardiologists were more willing to prescribe ß-blockers than respiratory physicians for patients at greater risk of bronchoconstriction, particularly when the potential therapeutic benefit was greater. CONCLUSIONS: Our perception that cardiologists were more willing to prescribe ß-blockers than respiratory physicians was confirmed. This probably results from a difference in focus (namely focus on benefit by cardiologists vs focus on risk by respiratory physicians), although other factors including awareness of limitations of pulmonary function testing by respiratory physicians may have been involved. Until better tests are available (that discriminate between patients who are likely to suffer bronchoconstriction from those who are not), it is likely that this difference between the specialties will remain.

Apoptosis-regulatory factors as potential drug targets in the epithelium of normal and inflamed airways.

Airway epithelium (AE) lines the conducting airways of the respiratory system and functions to maintain airway integrity by providing both a physical barrier to inhaled noxious agents and a mechanism for their clearance via the mucociliary escalator. Normal AE cells are relatively refractory to a number of apoptotic stimuli and survival mechanisms are in place to maintain the integrity of the epithelial barrier that is exposed to agents such as reactive oxygen species (ROS) and death receptor ligands secreted by immune cells during inflammation. When damage to AE does occur, there is increased AE apoptosis, such as in the airway damage that occurs in the chronically inflamed airways in diseases like asthma where rates of AE apoptosis can be increased many-fold. The usual treatment for persistent asthma in humans involves a combination of bronchodilator and inhaled corticosteroid; there is however a need to develop strategies to better control other aspects of the disease, including minimizing the ongoing damage to AE and consequent airway remodeling. Targeting of the major apoptosis-regulatory factors in AE may be one such strategy. Here we review what is known about apoptosis and its regulatory factors in normal AE and abnormalities in these factors in the inflamed airways of mice and humans.

Zinc and its specific transporters as potential targets in airway disease.

The dietary group IIb metal zinc (Zn) plays essential housekeeping roles in cellular metabolism and gene expression. It regulates a number of cellular processes including mitosis, apoptosis, secretion and signal transduction as well as critical events in physiological processes as diverse as insulin release, T cell cytokine production, wound healing, vision and neurotransmission. Critical to these processes are the mechanisms that regulate Zn homeostasis in cells and tissues. The proteins that control Zn uptake and compartmentalization are rapidly being identified and characterized. Recently, the first images of sub-cellular pools of Zn in airway epithelium have been obtained. This review discusses what we currently know about Zn in the airways, both in the normal and inflamed states, and then considers how we might target Zn metabolism by developing strategies to monitor and manipulate airway Zn levels in airway disease.

Barriers to success for an evidence-based guideline for chronic obstructive pulmonary disease.

OBJECTIVES: To evaluate 1) barriers to clinical guideline use and 2) the relationship between guideline use and inpatient outcomes in chronic obstructive pulmonary disease (COPD). METHODS: 1) Four focus groups of specific health professions (n = 30), from three metropolitan hospitals, and interview of 99 medical officers (MOs), linked to 349 admissions, both guided by behavioural modelling theory; 2) association between guideline use and patient outcomes (length of hospital stay > or = 14 days, and readmission within 28 or 90 days) was evaluated in a cohort of 405 COPD patients. RESULTS: 1) In focus groups, nurses and allied health professionals emphasized facilitation issues including paperwork duplication and time limitations as barriers, but considered improved patient care outcomes as the major guideline use determinant. There were similar findings in junior MOs (nonconsultants) by both focus group and interview, with the addition of a need for a sense of ownership. Senior MOs (consultants) greatly emphasized sense of ownership. Barriers to guideline use varied between types of units. Behavioural modelling explained 49% of the variation in intention to use the guideline for MOs. For nonconsultants, habit and intention were significantly associated with extent of guideline use. 2) Patient outcomes: guideline use was not associated with length of stay or readmission. CONCLUSIONS: 1) Guideline implementation should address issues relevant to different health professions, units and seniority of profession. 2) Guideline use was not associated with reductions in readmission or length of stay.

Psychological factors and asthma quality of life: a population based study.

BACKGROUND: Reports of psychological conditions in asthmatic subjects have been limited to certain population groups or convenience samples. A study was undertaken of the prevalence of psychological distress in asthma in the general population and its associations with quality of life. METHODS: The WANTS Health and Well-being Survey is a population household interview survey of adults (age > or =18) in Western Australia, the Northern Territory, and South Australia. Data obtained were weighted to the closest census data to provide population representative estimates. Positive answers to two questions: "Have you ever been told by a doctor that you have asthma?" and "Do you still have asthma?" determined current doctor-diagnosed asthma. Other items included the SF-12, the Kessler-10 index of psychological distress, questions on feelings of lack of control in different areas of life, and on mental health conditions. RESULTS: From the available sample of 10 080, 7619 interviews were completed (participation rate 74.8%), with 834 people reporting current doctor-diagnosed asthma (11.2%). Psychological distress was more frequent in those with asthma (17.9% v 12.2%, p<0.01) and a higher proportion with asthma were at higher risk for anxiety or depression (40.5% v 31.2%, p<0.01). Mental health conditions were also more common (16.2% v 10.8%, p<0.01), as was the frequency of those who sometimes or always felt a lack of control over their health (33.5% v 24.3%, p<0.01). People with both asthma and psychological distress had significantly lower scores on the SF-12 physical component summary (PCS) than those with either asthma or distress alone. Among those with psychological distress, mental component summary (MCS) scores did not differ between asthmatic and non-asthmatic respondents. In a multiple regression model the frequency of a feeling of lack of control over health-together with age, family's financial situation, education level, and number of days partially unable to work or perform usual duties-was significantly associated with scores on the PCS (r = 0.73, adjusted r2 = 0.54). CONCLUSION: These results, from a representative population sample, show that psychological distress and decreased feelings of control are common in asthma and are significantly associated with physical health status.

Impact on readmission rates and mortality of a chronic obstructive pulmonary disease inpatient management guideline.

AIMS: Chronic obstructive pulmonary disease (COPD) is a common condition associated with considerable morbidity, mortality and hospital admissions. However, published COPD management guidelines have major limitations and lack practical summaries. We aimed to optimally develop, implement, and evaluate a multidisciplinary COPD inpatient management 'ACCORD' guideline, including prompts for comprehensive day one assessments through to a discharge criteria checklist. METHOD: Two intervention and two control public teaching hospitals in Adelaide, South Australia, took part, with pre-intervention (721 COPD admissions over 7 months) and intervention phases (509 COPD admissions over 7 months). During the intervention stage the ACCORD guideline was placed in the case notes on the day of admission or soon after. Readmissions were categorized as either emergency or elective and compared between the study arms, as were mortality and potential confounders (age, gender, number of comorbidities), with Poisson regression analysis. RESULTS: Of case notes of eligible COPD patients, 60% had the ACCORD guideline placed, of which 76% had evidence of use as judged by completion of guideline entry and tick boxes. The ACCORD guideline was associated with an increase in elective admissions and a reduction in emergency admissions in the intervention group in relation to the control group (P < 0.01), with no difference in overall admissions or death rates. CONCLUSIONS: The ACCORD guideline was associated with a shift from emergency admissions to more planned elective care, suggesting more proactive care of health problems, but without overall reduction in admissions.

Underdiagnosed asthma in South Australia.

BACKGROUND: The prevalence of undiagnosed asthma in the general population and the clinical and demographic characteristics of these patients compared with those with diagnosed asthma are unclear. METHODS: The North West Adelaide Health Survey (NWAHS) is a population household interview survey of adults (age>18 years) in the north western suburbs of Adelaide, South Australia (regional population 0.6 million). Data obtained were weighted to the closest census data to provide population representative estimates. Positive answers to: "Have you ever had asthma?"; "Has it been confirmed by a doctor?"; "Do you still have asthma?" determined current physician diagnosed asthma. A positive bronchodilator response on spirometric testing according to ATS criteria without a physician's diagnosis determined undiagnosed asthma. Other measures included the SF-12 health survey questionnaire, the Selim index of severity of chronic lung disease, skin allergy tests, and demographic data. RESULTS: Of the 3422 individuals interviewed, 2523 (74%) agreed to participate in the clinical assessment. Of these, 292 (11.6%) had asthma, 236 (9.3%) with a doctor's diagnosis of asthma and 56 (2.3%) with undiagnosed asthma defined on spirometric criteria; thus, 19.2% of the total asthma group were undiagnosed. Those undiagnosed were more likely (p<0.05) to be >40 years old, on government benefits, with an income 65 years. Health service use over the previous year was similar for both asthma groups. CONCLUSION: Undiagnosed asthma is common among the Australian population, with a similar clinical spectrum to those with diagnosed asthma.

Health-service use by children with asthma over a 6-month period.

OBJECTIVES: The present study aims to describe the use of health services by children with asthma, and examine disease-specific, parental and sociodemographic variables associated with different levels of health-service utilization. METHODS: Parents of 135 children attending an emergency room (ER) completed questionnaires measuring the children's asthma symptoms, and sociodemographic and psychological variables. Parents were contacted monthly for 6 months to document the number of planned and unplanned visits to hospital and community health-care services for asthma. RESULTS: At least one further unplanned visit to the ER was made by 37% of children, while 62% made at least one unplanned visit to a general practitioner (GP). Fifty-five per cent made planned review visits to a GP, 30% to paediatricians and 5% to hospital clinics. After controlling for the level of asthma symptoms, parental anxiety and parental perceptions of children's vulnerability were associated with unplanned GP visits (P = 0.05 and P = 0.01, respectively); a planned review visit and the child being admitted to hospital for the index attack were associated with unplanned ER visits (P = 0.05 and P = 0.004, respectively). CONCLUSIONS: Children with asthma more frequently attend GP services than hospital services for both planned and unplanned asthma management. Different variables predict the unplanned use of GP and ER services. Understanding these differences is imperative if children and families are to make the most effective use of health services.

Formoterol in patients with chronic obstructive pulmonary disease: a randomized, controlled, 3-month trial.

The aim of this study was to investigate formoterol, an inhaled long-acting beta2-agonist, in patients with chronic obstructive pulmonary disease (COPD). Six-hundred and ninety-two COPD patients, mean baseline forced expiratory volume in one second (FEV1) 54%, FEV1/forced vital capacity 75% of predicted, reversibility 6.4% pred, were treated with formoterol (4.5, 9 or 18 microg b.i.d.) or placebo via Turbuhaler for 12 weeks. Symptoms were recorded daily. Spirometry and the incremental shuttle walking test (SWT) were performed at clinic visits. Compared with placebo, 18 microg b.i.d. formoterol reduced the mean total symptom score by 13% and increased the percentage of nights without awakenings by 15%. Formoterol (9 and 18 microg b.i.d.) significantly reduced symptom scores for breathlessness (-7% and -9%, respectively) and chest tightness (-11% and -8%, respectively), reduced the need for rescue medication (-25% and -18%, respectively), and increased symptom-free days (71% and 86%, respectively). FEV1 improved significantly after all three doses of formoterol (versus placebo). No differences were found between groups in SWT walking distance. No unexpected adverse events were seen. In conclusion, 9 and 18 microg b.i.d. formoterol reduced symptoms and increased the number of symptom-free days in a dose-dependent manner in chronic obstructive pulmonary disease patients. Formoterol improved lung function at a dose of 4.5 microg b.i.d. and higher.

Home care by outreach nursing for chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterised by progressive airflow obstruction, worsening exercise performance and deterioration in health. It is associated with significant morbidity, mortality and costs to health care systems. Care strategies, such as outreach nursing in the community, may reduce this burden. OBJECTIVES: To evaluate the effectiveness of outreach respiratory health care worker programmes for patients with COPD in terms of improving lung function, exercise tolerance and health related quality of life (HRQL) of patient and carer, and reducing mortality and hospital service utilisation. SEARCH STRATEGY: A search was carried out using the Cochrane Airways Group database. Bibliographies of identified RCTs were searched for additional relevant RCTs. Authors of identified RCTS were contacted for other published and unpublished studies. SELECTION CRITERIA: Only randomised control trials of patients with COPD were included. The intervention was an outreach nurse visiting patients in their homes, providing support, education, monitoring patient status and providing liaison with physicians. Interventions that used nurse practitioners who provided therapeutic intervention were also included. Studies in which the therapeutic intervention under test was physical training were not included. DATA COLLECTION AND ANALYSIS: Data extraction and study quality assessment were performed independently by two reviewers. Where further or missing data was required, authors of studies were contacted. MAIN RESULTS: Four studies were found. Three assessed mortality following twelve months of care (n=96, 152 and 301), and one after seven months(n=75). Meta-analysis demonstrated that mortality was not significantly reduced by the intervention, Peto Odds Ratio 0.72; 95 % confidence interval 0.43, 1.21. Post hoc subgroup analysis suggested that mortality was reduced by the outreach nursing programme in patients with less severe disease. Significant improvements in health related quality of life were reported in one study in moderate COPD, but not in a study in patients with severe disease. No changes in lung function or exercise performance were found in the studies where data were available. Hospital admissions were reported in only one study in patients with severe disease and no benefit was observed. A further search was conducted in July 2000 did not yield any more studies for inclusion. REVIEWER'S CONCLUSIONS: Patients with moderate COPD may have mortality and health related quality of life gains from a nursing outreach programme, but there are no data about reductions in hospital utilisation. Patients with severe COPD do not appear to have benefit from such programmes and one large study found no reduction in hospital admissions in such patients.

Increased effective lung volume following lung volume reduction surgery in emphysema.

STUDY OBJECTIVES: Lung volume reduction surgery (LVRS) for emphysema has a variable effect on spirometry with improvement linked to increases in lung elastic recoil. The mechanism by which recoil increases following LVRS has not been described completely. This study examines preoperative and postoperative pulmonary function to describe a mechanism for changes in airflow obstruction. DESIGN: Change in pulmonary function following LVRS. Setting : Public teaching hospital in Australia. PATIENTS: Patients with severe emphysema and pulmonary function measurements made before and after LVRS. MEASUREMENTS: Routine pulmonary function testing performed with ventilated lung alveolar volume (VA) derived from the gas transfer measurement used as a proxy for the effective lung volume. RESULTS: Pulmonary function tests from 36 consecutive patients with measurements made at the same laboratory were analyzed. The mean FEV(1) was 29.1% predicted presurgery and increased following LVRS from 0.900 L (SD, 0.427 L) to 1.283 L (SD, 0.511 L; p < 0.0001) and TLC (143% predicted) decreased from 8.19 L (SD, 1.492 L) to 7.07 L (SD, 1.52 L; p < 0.0001; n = 35). The mean VA increased by 0.674 L (SD, 0.733 L) from 4.04 to 4.72 L (p < 0.0001; n = 34). The change in FEV(1) correlated well with the change in VA (r = 0.63). The change in FEV(1) in those patients whose VAs did not increase (n = 7) was not significant. CONCLUSIONS: The increase in VA reflects an increase of functional or ventilating lung volume and is associated with an improvement in spirometry following LVRS.

Automated attention flags in chronic disease care planning.

OBJECTIVES: To assess the value of computerised decision support in the management of chronic respiratory disease by comparing agreement between three respiratory specialists, general practitioners (care coordinators), and decision support software. METHODS: Care guidelines for two chronic obstructive pulmonary disease projects of the SA HealthPlus Coordinated Care Trial were formulated. Decision support software, Care Plan On-Line (CPOL), was created to represent the intent of these guidelines via automated attention flags to appear in patients' electronic medical records. For a random sample of 20 patients with care plans, decisions about the use of nine additional services (eg, smoking cessation, pneumococcal vaccination) were compared between the respiratory specialists, the patients' GPs and the CPOL attention flags. RESULTS: Agreement among the specialists was at the lower end of moderate (intraclass correlation coefficient [ICC], 0.48; 95% CI, 0.39-0.56), with a 20% rate of contradictory decisions. Agreement with recommendations of specialists was moderate to poor for GPs (kappa, 0.49; 95% CI, 0.33-0.66) and moderate to good for CPOL (kappa, 0.72; 95% CI, 0.55-0.90). CPOL agreement with GPs was moderate to poor (kappa, 0.41; 95% CI, 0.24-0.58). GPs were less likely than specialists or CPOL to decide in favour of an additional service (P<0.001). CPOL was 87% accurate as an indicator of specialist decisions. It gave a 16% false-positive rate according to specialist decisions, and flagged 61% of decisions where GPs said No and specialists said Yes. CONCLUSIONS: Automated decision support may provide GPs with improved access to the intent of guidelines; however, further investigation is required.

Trial of roxithromycin in subjects with asthma and serological evidence of infection with Chlamydia pneumoniae.

An association has been reported between chronic infection with Chlamydia pneumoniae and the severity of asthma, and uncontrolled observations have suggested that treatment with antibiotics active against C. pneumoniae leads to an improvement in asthma control. We studied the effect of roxithromycin in subjects with asthma and immunoglobulin G (IgG) antibodies to C. pneumoniae > or = 1:64 and/or IgA antibodies > or = 1:16. A total of 232 subjects, from Australia, New Zealand, Italy, or Argentina, were randomized to 6 wk of treatment with roxithromycin 150 mg twice a day or placebo. At the end of 6 wk, the increase from baseline in evening peak expiratory flow (PEF) was 15 L/min with roxithromycin and 3 L/min with placebo (p = 0.02). With morning PEF, the increase was 14 L/min with roxithromycin and 8 L/min with placebo (NS). In the Australasian population, the increase in morning PEF was 18 L/min and 4 L/min, respectively (p = 0.04). At 3 mo and 6 mo after the end of treatment, differences between the two groups were smaller and not significant. Six weeks of treatment with roxithromycin led to improvements in asthma control but the benefit was not sustained. Further studies are necessary to determine whether the lack of sustained benefit is due to failure to eradicate C. pneumoniae.

Treatment of trapeziometacarpal arthritis with silastic and metallic implant arthroplasty.

Implant arthroplasty was once viewed as a feasible and effective trapeziometacarpal joint disease. Silastic implants are now used rarely because of concerns of implant failure and particulate synovitis. Metallic implants, including total joint prostheses and those utilizing a spacer concept, have been used with some success. Indications, technical consideration, and potential complications of these implants are discussed.

Quality of life in asthma: a comparison of community and hospital asthma patients.

This study compares the quality of life of a community sample of people with asthma in South Australia, using population norms, people suffering from other chronic diseases, and a sample of asthma patients from two hospital clinics. A representative population survey was performed by trained interviewers in spring 1995 of 3001 respondents aged > or = 15 years. A physician's diagnosis of current asthma was reported by 299 (9.9%). The hospital clinic sample had a physician's diagnosis and lung function evidence of asthma (n = 293). All completed the SF-36 health survey. Standardized SF-36 scores, adjusted for age, sex, and social class, were significantly lower for respondents with asthma, compared with population norms, across all subscales of the SF-36 (p < 0.05). Physical component summary (PCS) and mental component summary (MCS) scores were not significantly different in people in the community sample with asthma from scores in people with diabetes and arthritis. PCS and MCS scores did not differ for those with similar symptom frequency in the community and hospital asthma samples, except that hospital patients with frequent symptoms had significantly lower MCS scores (p < 0.01). Asthma has a major impact on the health-related quality of life in the community, comparable to other chronic diseases. The SF-36 performs uniformly in asthma in different situations.

Impact of the physician's participatory style in asthma outcomes and patient satisfaction.

OBJECTIVES: To identify factors associated with asthma patients' perceptions of the propensity of pulmonologists to involve them in treatment decision-making, and its association with asthma outcomes. DESIGN: Cross-sectional observational study performed from June 1995 to December 1997. SETTING: Pulmonary unit of a university teaching hospital. PATIENTS: Adult patients with asthma (n = 128). MEASUREMENTS AND RESULTS: By patient self-report, mean physician's participatory decision-making (PDM) style score was 72 (maximum 100, 95% CI 65, 79). PDM scores were significantly correlated (P < .0001) with the duration of clinic visits (r = .63), patient satisfaction (r = .53), duration of tenure of doctor-patient relationship (r = .37), and formal education (r = .22, P = .023). Significantly higher PDM style scores were reported when visits lasted longer than 20 minutes and when a patient had a >6-month relationship with a particular doctor. PDM scores were also significantly correlated with possession of a written asthma action plan (r = .54, P < .0001), days affected by asthma (r = .36, P = .0001), asthma symptoms (r = .23, P = .017), and preferences for autonomy in asthma management decisions (r = .28, P = .0035). Those with PDM scores <50 reported significantly lower quality of life for all domains of a disease-specific instrument and the Short-Form 36 health survey version 1.0. In multiple regression analysis, PDM style was associated with the length of the office visit and the duration of tenure of the physician-patient relationship (R2 = 0.47, P = .0009). The adjusted odds ratio, per standard deviation decrease in PDM scores, for an asthma hospitalization was 2.0 (95% CI 1.2, 3.2) and for rehospitalization was 2.5 (95% CI 1.2, 4.2). CONCLUSIONS: Patients' report of their physician's PDM style is significantly associated with health-related quality of life, work disability, and recent need for acute health services. Organizational factors, specifically longer visits and more time seeing a particular physician, are independently associated with more participatory visits. This has significant policy implications for asthma management.