An Organocatalytic Oxy-Cope/Michael Cascade Reaction.

Ethyl diazepane carboxylate catalyzes the oxy-Cope rearrangement of 4-hydroxy- and 4-alkoxy-1,5-hexadiene-2-carboxaldehydes via iminium ion activation. The resulting intermediate undergoes an intramolecular Michael reaction to furnish cyclopentane-containing products. The reaction proceeds with a range of substrates, including both cyclic and acyclic substrates, and tolerates substitution on the vinyl substituent. Substrates fused on a cycloalkane framework undergo net ring expansion/cyclopentannulation with a high degree of stereocontrol via chairlike transition states. The reaction extends iminium organocatalysis to the oxy-Cope rearrangement, embedded within a complexity-generating cascade transformation.

Haematuria and acute kidney injury in elderly patients admitted to hospital with supratherapeutic warfarin anticoagulation.

BACKGROUND AND OBJECTIVES: Warfarin-related nephropathy is reported to occur with an INR >3.0 as a result of glomerular bleeding. There is a lack of prospective studies examining the effect of supratherapeutic warfarin anticoagulation on haematuria and acute kidney injury (AKI). Older patients may be susceptible due to greater warfarin use, prevalence of kidney disease and comorbidities. The objective of this study was to determine the incidence and nature of haematuria and AKI in older patients on warfarin and to determine any association with high INR levels. DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: This was a prospective, observational study of 150 elderly patients receiving warfarin anticoagulation who were acutely hospitalised in a tertiary hospital. AKI was assessed using RIFLE criteria. Urinalysis was performed to quantify haematuria, characterise erythrocyte morphology and measure the albumin-creatinine ratio. Positive cases received follow-up at 4-6 weeks to determine resolution. RESULTS: An INR >3.0 was found in 54 % of patients. Pre-admission antibiotic use increased the risk of excessive anticoagulation. The incidence of isolated AKI, isolated haematuria and both was 18.7, 13.3 and 12 %, respectively. Factors associated with a higher risk of haematuria were an INR >4.0, non-urinary infection, catheterisation and albuminuria. Most cases of AKI were mild, and there was no demonstrable correlation between the admission INR and AKI. Admission with heart failure was significantly associated with an increased risk of persistent kidney impairment at follow-up. CONCLUSIONS: Supratherapeutic warfarin anticoagulation was associated with an increased risk of haematuria, but not with AKI. The majority of cases of haematuria were transient.

From theory to practice of electronic handover.

Clinical handover is an essential process occurring at many levels of inpatient care. Multiple studies within a hospital setting have identified that a breakdown in the handover process can lead to poor patient outcomes and serious adverse events. The use of electronic handover tools is an intervention identified to decrease errors in clinical care arising from poor handover practice. An electronic handover tool was implemented in a general medical unit in a metropolitan tertiary hospital setting. The program was written by a Medical Professional who also used the tool. The program was evaluated with a pre- and post-intervention survey within the medical, allied health and nursing staff members of the multidisciplinary teams. The use of the Electronic Handover program resulted in improved satisfaction of the handover process within the medical, nursing and allied health professions. This trial demonstrates that an electronic handover program can be successfully integrated into normal medical work practice, resulting in positive outcomes for a multidisciplinary staff team. Further work is required to determine whether patient outcomes are improved as a result.

Transcutaneous measurement of carbon dioxide tension during extended monitoring: evaluation of accuracy and stability, and an algorithm for correcting calibration drift.

BACKGROUND: When polysomnography is indicated in a patient with a presumed sleep disorder, continuous monitoring of arterial carbon dioxide tension (P(aCO(2))) is desirable, especially if nocturnal hypoventilation is suspected. Transcutaneous CO(2) monitors (P(tcCO(2))) provide a noninvasive correlate of P(aCO(2)), but their accuracy and stability over extended monitoring have been considered inadequate for the diagnosis of hypoventilation. We examined the stability and accuracy of P(tcCO(2)) measurements and the performance of a previously described linear interpolation technique designed to correct for calibration drift. METHODS: We compared the P(tcCO(2)) values from 2 TINA TCM-3 monitors to P(aCO(2)) values from arterial blood samples obtained at the beginning, every 15 min of the first hour, and then hourly over 8 hours of monitoring in 6 hemodynamically stable, male, intensive care patients (mean age 46 ± 17 y). RESULTS: Time had a significant (P = .002) linear effect on the P(tcCO(2))-P(aCO(2)) difference, suggesting calibration drift over the monitoring period. We found no differences between monitor type or interaction between time and monitor type. For the 2 monitors the uncorrected bias was 3.6 mm Hg and the limits of agreement were -5.1 to 12.3 mm Hg. Our linear interpolation algorithm improved the bias and limits of agreement to 0.4 and -5.5 to 6.4 mm Hg, respectively. CONCLUSIONS: Following stabilization and correction for both offset and drift, P(tcCO(2)) tracks P(aCO(2)) with minimal residual bias over 8 hours of monitoring. Should future research confirm these findings, then interpolated P(tcCO(2)) may have an increased role in detecting sleep hypoventilation and assessing the efficacy of treatment.

A questionnaire for determining prevalence of diabetes related foot disease (Q-DFD): construction and validation.

BACKGROUND: Community based prevalence for diabetes related foot disease (DRFD) has been poorly quantified in Australian populations. The aim of this study was to develop and validate a survey tool to facilitate collection of community based prevalence data for individuals with DRFD via telephone interview. METHODS: Agreed components of DRFD were identified through an electronic literature search. Expert feedback and feedback from a population based construction sample were sought on the initial draft. Survey reliability was tested using a cohort recruited through a general practice, a hospital outpatient clinic and an outpatient podiatry clinic. Level of agreement between survey findings and either medical record or clinical assessment was evaluated. RESULTS: The Questionnaire for Diabetes Related Foot Disease (Q-DFD) comprised 12 questions aimed at determining presence of peripheral sensory neuropathy (PN) and peripheral vascular disease (PVD), based on self report of symptoms and/or clinical history, and self report of foot ulceration, amputation and foot deformity. Survey results for 38 from 46 participants demonstrated agreement with either clinical assessment or medical record (kappa 0.65, sensitivity 89.0%, and specificity 77.8%). Correlation for individual survey components was moderate to excellent. Inter and intrarater reliability and test re-test reliability was moderate to high for all survey domains. CONCLUSION: The development of the Q-DFD provides an opportunity for ongoing collection of prevalence estimates for DRFD across Australia.

Missed opportunities to vaccinate a cohort of hospitalised elderly with pneumococcal and influenza vaccines.

This study examines missed opportunities for recommended influenza vaccine and 23-valent pneumococcal vaccine (23vPPV) among hospitalised elderly persons. 4772 inpatients aged > or = 65 years (cases of pneumonia and frequency-matched randomly selected cohort subjects) participated from two large tertiary Australian hospitals. For subjects unvaccinated with influenza vaccine (past year), 1110/1115 (99.6%) had visited either a doctor (99.4%, mean 11.2 visits) or the same hospital (52.0%, mean 1.5 visits). For those unvaccinated with 23vPPV (past 5 years), 1809/1813 (99.8%) had visited either a doctor (99.7%, mean 11.2 visits) or the same hospital (51.5%, mean 1.5 times) in the past year; 71% had been admitted to the same hospital in the past 5 years (mean 3.4 times). 2.3% of all subjects had vaccination status recorded. No unvaccinated subject was vaccinated during admission, despite approximately 40% reporting acceptability of vaccination if offered. Previous hospitalisation was a risk factor for being unvaccinated. Barriers to implementation of current vaccination policy in the hospital setting require formal evaluation in Australia.

Validity of self-reported influenza and pneumococcal vaccination status among a cohort of hospitalized elderly inpatients.

Use of self-reported vaccination status is commonplace in assessing vaccination coverage for public health programs and individuals, yet limited validity data exist. We compared self-report with provider records for pneumococcal (23vPPV) and influenza vaccine for 4887 subjects aged>or=65 years from two Australian hospitals. Self-reported influenza vaccination status had high sensitivity (98%), positive predictive value (PPV) (88%) and negative predictive value (NPV) (91%), but low specificity (56%). Self-reported 23vPPV (previous 5 years) had a sensitivity of 84%, specificity 77%, PPV 85% and NPV 76%. Clinicians can be reasonably confident of self-reported influenza vaccine status, and for positive self-report for 23vPPV in this setting. For program evaluation, self-reported influenza vaccination coverage among inpatients overestimates true coverage by about 10% versus 1% for 23vPPV. Self-report remains imperfect and whole-of-life immunisation registers a preferable goal.

Prevention of community-acquired pneumonia among a cohort of hospitalized elderly: benefit due to influenza and pneumococcal vaccination not demonstrated.

Benefits from influenza and 23-valent pneumococcal polysaccharide (23vPPV) vaccines against invasive pneumococcal disease and laboratory confirmed influenza have been well documented. However, their effectiveness against pneumonia remains controversial for community-based elderly > or = 65 years. Using a case-cohort design we examined incremental VE of 23vPPV over and above influenza vaccine against hospitalization with community-acquired pneumonia (HCAP) in two large Australian hospitals. 1952 cases (ICD-10-AM codes for pneumonia: J10-J18) and 2927 randomly selected cohort subjects were studied. Vaccination status was confirmed by providers. Benefit against HCAP was not demonstrated in multivariate analysis for influenza vaccine compared with neither vaccine (RR 1.02, 95%CI 0.84-1.20) or for both vaccines compared with influenza vaccine (RR 0.98, 95%CI 0.81-1.18). The current program of funding these vaccines for the elderly is not having a discernable impact on HCAP in this setting.

Validity of the Assessment of Quality of Life (AQoL) utility instrument in patients with operable and inoperable lung cancer.

There have been few longitudinal studies of quality of life in patients with all stages of lung cancer, particularly those that have included measures of utility. The purpose of this study was to examine the psychometric properties of the Assessment of Quality of Life instrument (AQoL) in patients with lung cancer. The AQoL is a health-related quality of life questionnaire and provides a descriptive system for a multi-attribute utility instrument (MAU), so that scores can be used in cost-utility evaluations. In the present study the reliability (internal consistency) of the AQoL was examined and the concurrent validity was assessed using the Medical Outcomes 36-item Short Form Health Survey (SF-36) as the comparator instrument. The sensitivity to different health states of the AQoL and the responsiveness to change over time was also examined. A prospective, non-experimental cohort study was undertaken. Ninety-two participants with all stages of lung cancer were recruited from a tertiary multi-disciplinary lung cancer clinic. Ninety participants had non-small cell lung cancer (NSCLC) and two had limited stage small cell lung cancer. The AQOL and SF-36 surveys were administered concurrently at baseline. In patients with NSCLC the surveys were then repeated 3 and 6 months later. Correlations between the baseline AQoL summary scales and SF-36 summary scales support the divergent and convergent validity of the AQoL. Reliability was also found to be sufficient (Cronbach's Alpha=0.76). In addition, in patients with inoperable NSCLC, baseline AQoL scores were found to be predictive of survival at 6 months in Cox proportional hazards multivariate analysis. However, the physical components summary score of the SF-36 was more sensitive to differences in health states between patients with different stages of NSCLC at 6 months of follow-up and more responsive to change over time in both operable and inoperable patients with NSCLC than the AQoL. The findings support the construct validity and reliability of the AQoL in this population. However, there remains some uncertainty about whether the AQoL has sufficient sensitivity to different health states in this population. Further studies using other MAU instruments may determine whether alternative instruments are more sensitive to different health states in individuals with lung cancer.

Influenza and pneumococcal vaccine coverage among a random sample of hospitalised persons aged 65 years or more, Victoria.

This study was undertaken to assess the uptake of influenza and pneumococcal vaccination based on provider records of the hospitalised elderly, a group at high risk of influenza and pneumococcal disease. The study used a random sample of 3,204 admissions at two Victorian teaching hospitals for patients, aged 65 years or more who were discharged between 1 April 2000 and 31 March 2002. Information on whether the patient had received an influenza vaccination within the year prior to admission or pneumococcal vaccination within the previous five years was ascertained from the patient's nominated medical practitioner/vaccine provider. Vaccination records were obtained from providers for 82 per cent (2,804/2,934) of eligible subjects. Influenza vaccine coverage was 70.9 per cent (95% CI 68.9-72.9), pneumococcal coverage was 52.6 per cent (95% CI 50.4-54.8) and 46.6 per cent (95% CI 44.4-48.8) had received both vaccines. Coverage for each vaccine increased seven per cent over the two study years. For pneumococcal vaccination, there was a marked increase in 1998 coinciding with the introduction of Victoria's publicly funded program. Influenza and pneumococcal vaccine coverage in eligible hospitalised adults was similar to, but did not exceed, estimates in the general elderly population. Pneumococcal vaccination coverage reflected the availability of vaccine through Victoria's publicly funded program. A nationally funded pneumococcal vaccination program for the elderly, as announced recently, should improve coverage. However, these data highlight the need for greater awareness of pneumococcal vaccine among practitioners and for systematic recording of vaccination status, as many of these subjects will soon become eligible for revaccination.

A longitudinal evaluation of sleep and breathing in the first year after cervical spinal cord injury.

OBJECTIVES: To establish the incidence of sleep disordered breathing (SDB) after acute tetraplegia and to determine the relation between the Apnea-Hypopnea Index (AHI) score and the previously postulated predictors of SDB in tetraplegia. DESIGN: Inception cohort. We performed full polysomnography immediately after acute tetraplegia and at 2, 4, 13, 26, and 52 weeks postinjury. Spirometry, maximum inspiratory and expiratory pressures, medication usage, and neck and abdominal girth were also assessed. Preinjury SDB was estimated using the multivariate apnea prediction equation. SETTING: Acute care, subacute care, and community. PARTICIPANTS: Consecutive sample with acute tetraplegia. Thirty subjects (25 men) were initially included. Thirteen completed 12 months of follow-up. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: SDB (AHI score >10 events/h) and respiratory function. RESULTS: Three subjects (10%; 95% confidence interval [CI], 2%-28%) had probable SDB before injury. In the first 48 hours after injury, no subject had SDB. At 2 weeks, 60% (95% CI, 26%-88%) had SDB; at 4 weeks, 62% (95% CI, 38%-82%); at 13 weeks, 83% (95% CI, 61%-95%); at 26 weeks, 68% (95% CI, 44%-88%); and at 52 weeks, 62% (95% CI, 32%-86%). No consistent relation was found between the previously postulated predictors and SDB. CONCLUSIONS: SDB is highly prevalent within 4 weeks of acute tetraplegia.

Cost-effectiveness analysis of screening for lung cancer with low dose spiral CT (computed tomography) in the Australian setting.

INTRODUCTION: Low dose spiral computed tomography (CT) is a sensitive screening tool for lung cancer that is currently being evaluated in both non-randomised studies and randomised controlled trials. METHODS: We conducted a quantitative decision analysis using a Markov model to determine whether, in the Australian setting, offering spiral CT screening for lung cancer to high risk individuals would be cost-effective compared with current practice. This exploratory analysis was undertaken predominantly from the perspective of the government as third-party funder. In the base-case analysis, the costs and health outcomes (life-years saved and quality-adjusted life years) were calculated in a hypothetical cohort of 10,000 male current smokers for two alternatives: (1) screen for lung cancer with annual CT for 5 years starting at age 60 year and treat those diagnosed with cancer or (2) no screening and treat only those who present with symptomatic cancer. RESULTS: For male smokers aged 60-64 years, with an annual incidence of lung cancer of 552 per 100,000, the incremental cost-effectiveness ratio was 57,325 dollars per life-year saved and 105,090 dollars per QALY saved. For females aged 60-64 years with the same annual incidence of lung cancer, the cost-effectiveness ratio was 51,001 dollars per life-year saved and 88,583 dollars per QALY saved. The model was used to examine the relationship between efficacy in terms of the expected reduction in lung cancer mortality at 7 years and cost-effectiveness. In the base-case analysis lung cancer mortality was reduced by 27% and all cause mortality by 2.1%. Changes in the estimated proportion of stage I cancers detected by screening had the greatest impact on the efficacy of the intervention and the cost-effectiveness. The results were also sensitive to assumptions about the test performance characteristics of CT scanning, the proportion of lung cancer cases overdiagnosed by screening, intervention rates for benign disease, the discount rate, the cost of CT, the quality of life in individuals with early stage screen-detected cancer and disutility associated with false positive diagnoses. Given current knowledge and practice, even under favourable assumptions, reductions in lung cancer mortality of less than 20% are unlikely to be cost-effective, using a value of 50,000 dollars per life-year saved as the threshold to define a "cost-effective" intervention. CONCLUSION: The most feasible scenario under which CT screening for lung cancer could be cost-effective would be if very high-risk individuals are targeted and screening is either highly effective or CT screening costs fall substantially.

Incidental lung cancers identified at coronial autopsy: implications for overdiagnosis of lung cancer by screening.

BACKGROUND: The extent to which overdiagnosis occurs in lung cancer screening programmes has been debated. Overdiagnosis refers to the detection by screening of cancers that would not have become clinically apparent or symptomatic before that individual died of other causes. METHODS: A retrospective review of coronial autopsies performed in Victoria between April 1991 and February 2002 was conducted to determine the rate of incidental lung cancer in individuals who died of natural causes. RESULTS: A total of 24,708 autopsy reports were searched electronically. We estimated that in 56% of these death was from natural causes. Amongst individuals who died naturally there were 167 cases of lung cancer, 47 of these were incidental including five carcinoid tumours, three small cell tumours, 11 cases of carcinoma in situ and 28 invasive nonsmall cell lung cancers. Of the incidental invasive nonsmall cell lung cancers, 86% were stage I. CONCLUSIONS: Although incidental lung cancer is uncommon, there are some lung cancers that remain undetected during life and do not contribute to death. These findings support the hypothesis that some lung cancers detected by screening may never progress to cause symptoms or death in that individual's lifetime and therefore may be overdiagnosed by screening.

Overview of observational studies of low-dose helical computed tomography screening for lung cancer.

OBJECTIVE: Lung cancer is a substantial public health problem in Western countries. Evidence from previous controlled trials of chest radiography and sputum cytology does not support lung cancer screening, but computed tomography (CT) screening has recently emerged as a more sensitive screening tool. For the present article, the available observational studies of low-dose helical CT screening for lung cancer were reviewed. METHODOLOGY: An evidence-based review of all published observational studies of low-dose helical CT screening for lung cancer, identified by an extensive search of Medline, was conducted. RESULTS: Eight observational studies of CT screening for lung cancer were identified. Relative to chest radiography, low-dose helical CT is a sensitive screening tool and can detect a high proportion of small lung cancers at an early and resectable stage. The yield of sputum cytology in addition to CT screening appears to be relatively low. To date, 5-year lung cancer survival of all individuals participating in baseline screening has not been reported for any of the studies. CONCLUSIONS: Although these preliminary studies are very promising, it remains to be proven that the early detection and treatment of lung cancer will lead to a reduction in mortality. This issue will be addressed by randomized controlled trials. In the interim, the long-term follow up of these observational studies could provide further insights.

A transitional care service for elderly chronic disease patients at risk of readmission.

BACKGROUND: Multiple hospital admissions, especially those related to chronic disease, represent a particular challenge to the acute health care sector in Australia. OBJECTIVE: To determine whether a nurse-led chronic disease management model of transitional care reduced readmissions to acute care. DESIGN: A quasi-experimental controlled trial. SETTING: A large tertiary metropolitan teaching hospital. PARTICIPANTS: 166 general medical patients aged > or = 65 years with either a history of readmissions to acute care or multiple medical comorbidities. INTERVENTION: Implementation of a chronic disease management model of transitional care aimed at improving patient management and reducing readmissions to acute care. MAIN OUTCOME MEASURES: Readmission rates and emergency department presentation rates at 3-and 6-month follow up. Secondary outcome measures include quality of life, discharge destination, and primary health care service utilisation. RESULTS: There was no difference in readmission rates, emergency department presentation rates, quality of life, discharge destination or primary health care service utilisation. The difficulties inherent in evaluating this type of multifactorial intervention are discussed and consideration is given to patient factors, the difficulty of influencing readmission rates, and local system issues. CONCLUSION: The outcomes of this study reflect the tension that exists between implementing multifaceted integrated health service programs and attempting to evaluate them within complex and changing environments using robust research methodologies.

Sleepiness, sleep-disordered breathing, and accident risk factors in commercial vehicle drivers.

Sleep-disordered breathing and excessive sleepiness may be more common in commercial vehicle drivers than in the general population. The relative importance of factors causing excessive sleepiness and accidents in this population remains unclear. We measured the prevalence of excessive sleepiness and sleep-disordered breathing and assessed accident risk factors in 2,342 respondents to a questionnaire distributed to a random sample of 3,268 Australian commercial vehicle drivers and another 161 drivers among 244 invited to undergo polysomnography. More than half (59.6%) of drivers had sleep-disordered breathing and 15.8% had obstructive sleep apnea syndrome. Twenty-four percent of drivers had excessive sleepiness. Increasing sleepiness was related to an increased accident risk. The sleepiest 5% of drivers on the Epworth Sleepiness Scale and Functional Outcomes of Sleep Questionnaire had an increased risk of an accident (odds ratio [OR] 1.91, p = 0.02 and OR 2.23, p < 0.01, respectively) and multiple accidents (OR 2.67, p < 0.01 and OR 2.39, p = 0.01), adjusted for established risk factors. There was an increased accident risk with narcotic analgesic use (OR 2.40, p < 0.01) and antihistamine use (OR 3.44, p = 0.04). Chronic excessive sleepiness and sleep-disordered breathing are common in Australian commercial vehicle drivers. Accident risk was related to increasing chronic sleepiness and antihistamine and narcotic analgesic use.

Short-stay units and observation medicine: a systematic review.

OBJECTIVES: To conduct a systematic review of how short-stay observation units (SOUs) affect the efficiency of healthcare delivery and the quality of services provided. DATA SOURCES: MEDLINE, CINAHL, Best Evidence and The Cochrane Library were searched for the period 1 January 1960 to 31 July 2000. STUDY SELECTION: Studies were eligible if published in English and rated at National Health and Medical Research Council evidence levels I, II-1, II-2, or II-3; 12 comparative studies published between 1985 and 1998 met these criteria. DATA EXTRACTION: Data pertaining to clinical outcomes, length of stay, re-presentation rates, emergency department efficiency and costs of care were extracted and evaluated independently. DATA SYNTHESIS: As there was considerable heterogeneity in the patient populations and outcomes, results were summarised rather than subjected to meta-analysis. CONCLUSION: SOUs have the potential to increase patient satisfaction, reduce length of stay, improve the efficiency of emergency departments and improve cost effectiveness. However, SOUs have commonly been implemented alongside new clinical protocols, and it is not possible to distinguish the relative benefits of each. As demand increases, providing effective and cost-efficient care will become increasingly important. SOUs may help organisations that are attempting to streamline patient care while maintaining their quality of service delivery.