Validation of a risk stratification tool for a Hospital Outreach Medication Review (HOMR) program.

BACKGROUND: Early hospital readmissions are a challenging and costly experience for both patients and the healthcare service. Reducing hospital readmission rates is a priority for health services globally and this is evident with the establishment of multiple outpatient services to promote early follow-up and to initiate secondary preventative care measures. One such intervention has been the introduction of a pharmacist-led, Hospital Outreach Medication Review (HOMR) service. However, the demand for the service has meant reaching this target has become an increasingly ambitious goal within allocated resources. OBJECTIVE: To validate a risk-stratification tool to identify low-risk patients in whom a telephone medication review would be a safe and effective alternative to a home-based review. METHOD: A risk tool was derived and applied to a retrospective sample to act as the parent cohort. A prospective cohort was stratified into low and high-risk based on this tool, and received either a telephone or a traditional home medication review respectively. RESULTS: 235 patients were included in final analysis (n = 113 prospective, n = 122 baseline controls). High-risk patients were more likely to be readmitted at 60 and 90 days in the baseline cohort (9/38 vs 7/84, p = 0.04 and 11/38 vs 9/84, p = 0.02 respectively), with a trend towards increased readmissions at 30 days (5/38 vs 3/84, p = 0.11). Logistic regression identified the risk tool as an independent predictor of hospital readmission (IRR 1.18, p = 0.04), whereas age and Charlson comorbidity were not (p = 0.80 and 0.31 respectively). There was no significant difference between the new model (incorporating phone reviews) and the parent cohort (p = 0.25). CONCLUSION: Our risk score was able to identify those at highest risk of hospital readmission at 60 and 90 days. Utilising this risk score, a telephone HOMR for low-risk patients was a safe and efficient alternative to a traditional home review.

Detection and confirmation of serum lipid biomarkers for preeclampsia using direct infusion mass spectrometry.

Despite substantial research, the early diagnosis of preeclampsia remains elusive. Lipids are now recognized to be involved in regulation and pathophysiology of some disease. Shotgun lipidomic studies were undertaken to determine whether serum lipid biomarkers exist that predict preeclampsia later in the same in pregnancy. A discovery study was performed using sera collected at 12-14 weeks pregnancy from 27 controls with uncomplicated pregnancies and 29 cases that later developed preeclampsia. Lipids were extracted and analyzed by direct infusion into a TOF mass spectrometer. MS signals, demonstrating apparent differences were selected, their abundances determined, and statistical differences tested. Statistically significant lipid markers were reevaluated in a second confirmatory study having 43 controls and 37 preeclampsia cases. Multi-marker combinations were developed using those lipid biomarkers confirmed in the second study. The initial study detected 45 potential preeclampsia markers. Of these, 23 markers continued to be statistically significant in the second confirmatory set. Most of these markers, representing several lipid classes, were chemically characterized, typically providing lipid class and potential molecular components using MS(2) Several multi-marker panels with areas under the curve >0.85 and high predictive values were developed. Developed panels of serum lipidomic biomarkers appear to be able to identify most women at risk for preeclampsia in a given pregnancy at 12-14 weeks gestation.

Feasibility and impact of a post-discharge geriatric evaluation and management service for patients from residential care: the Residential Care Intervention Program in the Elderly (RECIPE).

BACKGROUND: Geriatric evaluation and management has become standard care for community dwelling older adults following an acute admission to hospital. It is unclear whether this approach is beneficial for the frailest older adults living in permanent residential care. This study was undertaken to evaluate (1) the feasibility and consumer satisfaction with a geriatrician-led supported discharge service for older adults living in residential care facilities (RCF) and (2) its impact on the uptake of Advanced Care Planning (ACP) and acute health care service utilisation. METHODS: In 2002-4 a randomised controlled trial was conducted in Melbourne, Australia comparing the geriatrician-led outreach service to usual care for RCF residents. Patients were recruited during their acute hospital stay and followed up at the RCF for six months. The intervention group received a post-discharge home visit within 96 hours, at which a comprehensive geriatric assessment was performed and a care plan developed. Participants and their families were also offered further meetings to discuss ACPs and document Advanced Directives (AD). Additional reviews were made available for assessment and management of intercurrent illness within the RCF. Consumer satisfaction was surveyed using a postal questionnaire. RESULTS: The study included 116 participants (57 intervention and 59 controls) with comparable baseline characteristics. The service was well received by consumers demonstrated by higher satisfaction with care in the intervention group compared to controls (95% versus 58%, p = 0.006).AD were completed by 67% of participants/proxy decision makers in the intervention group compared to 13% of RCF residents prior to service commencement. At six months there was a significant reduction in outpatient visits (intervention 21 (37%) versus controls 45 (76%), (p < 0.001), but no difference in readmissions rates (39% intervention versus 34% control, p = 0.6). There was a trend towards reduced hospital bed-day utilisation (intervention 271 versus controls 372 days). CONCLUSION: It is feasible to provide a supported discharge service that includes geriatrician assessment and care planning within a RCF. By expanding the service there is the potential for acute health care cost savings by decreasing the demand for outpatient consultation and further reducing acute care bed-days.

Forensic analysis of mtDNA haplotypes from two rural communities in Haiti reflects their population history.

Very little genetic data exist on Haitians, an estimated 1.2 million of whom, not including illegal immigrants, reside in the United States. The absence of genetic data on a population of this size reduces the discriminatory power of criminal and missing-person DNA databases in the United States and Caribbean. We present a forensic population study that provides the first genetic data set for Haiti. This study uses hypervariable segment one (HVS-1) mitochondrial DNA (mtDNA) nucleotide sequences from 291 subjects primarily from rural areas of northern and southern Haiti, where admixture would be minimal. Our results showed that the African maternal genetic component of Haitians had slightly higher West-Central African admixture than African-Americans and Dominicans, but considerably less than Afro-Brazilians. These results lay the foundation for further forensic genetics studies in the Haitian population and serve as a model for forensic mtDNA identification of individuals in other isolated or rural communities.

Exosome-associated tau is secreted in tauopathy models and is selectively phosphorylated in cerebrospinal fluid in early Alzheimer disease.

Recent demonstrations that the secretion, uptake, and interneuronal transfer of tau can be modulated by disease-associated tau modifications suggest that secretion may be an important element in tau-induced neurodegeneration. Here, we show that much of the tau secreted by M1C cells occurs via exosomal release, a widely characterized mechanism that mediates unconventional secretion of other aggregation-prone proteins (α-synuclein, prion protein, and ß-amyloid) in neurodegenerative disease. Exosome-associated tau is also present in human CSF samples and is phosphorylated at Thr-181 (AT270), an established phosphotau biomarker for Alzheimer disease (AD), in both M1C cells and in CSF samples from patients with mild (Braak stage 3) AD. A preliminary analysis of proteins co-purified with tau in secreted exosomes identified several that are known to be involved in disease-associated tau misprocessing. Our results suggest that exosome-mediated secretion of phosphorylated tau may play a significant role in the abnormal processing of tau and in the genesis of elevated CSF tau in early AD.

Pharmacist directed home medication reviews in patients with chronic heart failure: a randomised clinical trial.

BACKGROUND: Chronic heart failure (CHF) accounts for significant morbidity, mortality and health expenditure. Furthermore, patients with CHF are often on numerous pharmacological agents for their comorbidities. The objective of this study was to determine whether a pharmacist directed home medication review intervention had positive effects on CHF patient outcomes. METHODS: A total of 120 patients hospitalised for CHF were randomised to receive a pharmacist directed post-discharge home medication review (n = 64, 53.3%) or standard care (n = 56, 46.7%). Participants were followed for 6 months. Primary outcomes were death, CHF hospitalisation and length of hospital stay. RESULTS: There were no between group differences in mortality (hazard ratio = 1.41, 0.50 to 3.97; P = 0.514) or CHF hospitalizations (incidence rate ratio [IRR] = 1.74 95% CI: 0.85-3.60 P = 0.131) over the 6 month follow-up period. Days of hospital stay for CHF exacerbations in the 6 month follow-up were significantly greater in the intervention group (IRR = 2.34 95% CI: 1.80-3.05 P = 0.000). CONCLUSIONS: Post-discharge pharmacy directed home medication review appeared to have no effect on mortality and health care utilisation above that achieved with standard care. The post-acute management of CHF must be a collaborative multi-disciplinary effort by the health care team as it is the additive effect of interventions that are most effective.

A randomised trial of domiciliary, ambulatory oxygen in patients with COPD and dyspnoea but without resting hypoxaemia.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) who are not severely hypoxaemic at rest may experience significant breathlessness on exertion, and ambulatory oxygen is often prescribed in this circumstance despite a lack of conclusive evidence for benefit. This study aimed to determine whether such patients benefit from domiciliary ambulatory oxygen and, if so, which factors may be associated with benefit. METHODS: This was a 12 week, parallel, double-blinded, randomised, placebo-controlled trial of cylinder air versus cylinder oxygen, provided at 6 l/min intranasally, for use during any activity provoking breathlessness. Patients underwent baseline measurements of arterial blood gases and lung function. Outcome measures assessed dyspnoea, health-related quality of life, mood disturbance, functional status and cylinder utilisation. Data were analysed on an intention-to-treat basis, p≤0.05. RESULTS: 143 subjects (44 female), mean±SD age 71.8±9.8 years, forced expiratory volume in 1 s (FEV(1))1.16±0.51 litres, Pao(2) 9.5±1.1 kPa (71.4±8.5 mm Hg) were randomised, including 50 patients with exertional desaturation to ≤88%. No significant differences in any outcome were found between groups receiving air or oxygen. Statistically significant but clinically small improvements in dyspnoea and depression were observed in the whole study group over the 12 weeks of the study. CONCLUSION: In breathless patients with COPD who do not have severe resting hypoxaemia, domiciliary ambulatory oxygen confers no benefits in terms of dyspnoea, quality of life or function. Exertional desaturation is not predictive of outcome. Intranasal gas (either air or oxygen) may provide a placebo benefit. CLINICAL TRIAL NUMBER: ACTRN12605000457640.

Acute effects of hyperoxia on resting pattern of ventilation and dyspnoea in COPD.

BACKGROUND AND OBJECTIVE: Hyperoxia has been shown to reduce resting ventilation, hyperinflation and dyspnoea in patients with severely hypoxaemic COPD. This study assessed the effects of hyperoxia on these resting measures in patients with COPD of varying disease severity and characterized those patients who responded. METHODS: Measurements of dyspnoea (Borg score), oxyhaemoglobin saturation (SpO(2)), inspiratory capacity (IC), minute ventilation, tidal volume, breathing and cardiac frequency were performed at rest in 51 patients with COPD while they breathed air and 44% oxygen, in a randomized double-blinded fashion. RESULTS: Hyperoxia induced significant reductions in cardiac frequency and dyspnoea and a significant increase in SpO(2). No significant change was noted in IC for the group overall, and there was substantial inter-subject variation in this measurement. No significant changes were found in ventilation, and there was no correlation between change in dyspnoea and change in IC. In patients with moderate to severe airflow obstruction (FEV(1) < 70% predicted), a significant association was found between the degree of airflow obstruction and change in IC induced by hyperoxia. CONCLUSIONS: Hyperoxia improved dyspnoea but did not significantly alter resting pulmonary hyperinflation in a group of patients with COPD of varying severity. However, in a subset patients with moderate to severe airflow obstruction a relationship existed between the severity of airflow obstruction and volume response to hyperoxia.

Comparison of pedometer and activity diary for measurement of physical activity in chronic obstructive pulmonary disease.

PURPOSE: Precise, inexpensive tools for measuring physical activity levels are important for developing strategies to improve symptoms and enhance quality of life in chronic obstructive pulmonary disease (COPD). Self-report questionnaires and diaries have been used in many populations with variable results. The pedometer is widely recognized as a valid and reliable objective measurement tool, but it has not been well tested in COPD. This study aimed to determine the relationship between free-living physical activity recorded in a daily diary and that measured by using a pedometer in patients with COPD. METHODS: Participants with COPD (n = 80) recorded physical activity over 7 days. Cumulative pedometer readings and diary records of 4 activity categories for each 0.5 hour were compared. RESULTS: Participants (n = 76) with complete data sets were included in the analysis. The diary was more reliably completed. Mean pedometer reading per week was 23,129 (SD = 17,083) "step" counts (range, 1,725-66,454). Mean diary-recorded standing and walking time per week was 98.9 (SD = 10.4) hours (range, 73-119.5). The relationship between these measures was moderate and statistically significant (r = 0.37, P = .001). CONCLUSIONS: A daily diary record appears to offer more promise than the pedometer as a tool for measuring free-living physical activity in patients with COPD. Further research is required to assess the value of the 2 methods as discriminative, evaluative, and predictive tools in COPD populations.

Screening phosphatidylcholine biomarkers in mouse liver extracts from a hypercholesterolemia study using ESI-MS and chemometrics.

When fed a high-fat, high-cholesterol diet (HFD), homozygous LDL receptor knockout mice exhibit extremely high levels of plasma cholesterol that are expected to influence liver metabolism. One step in the investigation of potential hepatic alterations was the analysis of organic extracts of livers from these and control mice by electrospray mass spectrometry (ESI-MS). Chemometrics (bioinformatics) analysis shows that the sample spectra cluster into two groups: one from mice with plasma cholesterol levels in excess of 900 mg dL(-1) and one from animals with cholesterol levels of 60-250 mg dL(-1). The loadings plot of the first PC in the principal-components analysis (PCA) reveals the chemical basis for clustering, i.e., biomarkers present at different concentrations in the different groups. The exact masses of the key peaks in this loadings plot indicate these species are phosphatidylcholines (PtdChos). This assignment is confirmed by tandem MS. Partial least-squares (PLS) with variable selection shows that the spectra are well correlated with plasma total cholesterol, HDL cholesterol, and triglyceride (TG) levels.

Additional exercise does not change hospital or patient outcomes in older medical patients: a controlled clinical trial.

QUESTION: What are the effects of additional exercise on hospital and patient outcomes for acutely-hospitalised older medical patients? DESIGN: Controlled clinical trial. PARTICIPANTS: 236 Patients aged 65 or older admitted to an acute care hospital with a medical illness between October 2002 and July 2003. INTERVENTION: The experimental group received usual care plus an individually tailored exercise program administered twice daily from hospital admission to discharge. The control group received usual care only. OUTCOME MEASURES: The primary outcome was discharge destination. Secondary outcomes were measures of activity limitation (Barthel Index, Timed Up and Go, Functional Ambulation Classification), length of stay, and adverse events. RESULTS: There was no significant effect of the additional exercise program on any outcome. There were no significant differences between groups for the proportion of the patients discharged to home (RR 0.99, 95% CI 0.86 to 1.14) or inpatient rehabilitation (RR 0.76, 95% CI 0.30 to 1.51) or for measures of activity limitation at hospital discharge. A one day difference in length of stay was identified between groups but this difference was not significant (p = 0.45). There were no significant differences between groups for adverse events: 28-day readmission (RR 1.10, 95% CI 0.65 to 1.86), patient mortality (RR 1.15, 95% CI 0.16 to 8.0), intensive care admission (RR 0.16, 95% CI 0.01 to 3.13) and falls (RR 0.69, 95% CI 0.17 to 2.81). CONCLUSION: Additional physiotherapy intervention during hospitalisation did not significantly improve hospital or patient outcomes.

African-American mitochondrial DNAs often match mtDNAs found in multiple African ethnic groups.

BACKGROUND: Mitochondrial DNA (mtDNA) haplotypes have become popular tools for tracing maternal ancestry, and several companies offer this service to the general public. Numerous studies have demonstrated that human mtDNA haplotypes can be used with confidence to identify the continent where the haplotype originated. Ideally, mtDNA haplotypes could also be used to identify a particular country or ethnic group from which the maternal ancestor emanated. However, the geographic distribution of mtDNA haplotypes is greatly influenced by the movement of both individuals and population groups. Consequently, common mtDNA haplotypes are shared among multiple ethnic groups. We have studied the distribution of mtDNA haplotypes among West African ethnic groups to determine how often mtDNA haplotypes can be used to reconnect Americans of African descent to a country or ethnic group of a maternal African ancestor. The nucleotide sequence of the mtDNA hypervariable segment I (HVS-I) usually provides sufficient information to assign a particular mtDNA to the proper haplogroup, and it contains most of the variation that is available to distinguish a particular mtDNA haplotype from closely related haplotypes. In this study, samples of general African-American and specific Gullah/Geechee HVS-I haplotypes were compared with two databases of HVS-I haplotypes from sub-Saharan Africa, and the incidence of perfect matches recorded for each sample. RESULTS: When two independent African-American samples were analyzed, more than half of the sampled HVS-I mtDNA haplotypes exactly matched common haplotypes that were shared among multiple African ethnic groups. Another 40% did not match any sequence in the database, and fewer than 10% were an exact match to a sequence from a single African ethnic group. Differences in the regional distribution of haplotypes were observed in the African database, and the African-American haplotypes were more likely to match haplotypes found in ethnic groups from West or West Central Africa than those found in eastern or southern Africa. Fewer than 14% of the African-American mtDNA sequences matched sequences from only West Africa or only West Central Africa. CONCLUSION: Our database of sub-Saharan mtDNA sequences includes the most common haplotypes that are shared among ethnic groups from multiple regions of Africa. These common haplotypes have been found in half of all sub-Saharan Africans. More than 60% of the remaining haplotypes differ from the common haplotypes at a single nucleotide position in the HVS-I region, and they are likely to occur at varying frequencies within sub-Saharan Africa. However, the finding that 40% of the African-American mtDNAs analyzed had no match in the database indicates that only a small fraction of the total number of African haplotypes has been identified. In addition, the finding that fewer than 10% of African-American mtDNAs matched mtDNA sequences from a single African region suggests that few African Americans might be able to trace their mtDNA lineages to a particular region of Africa, and even fewer will be able to trace their mtDNA to a single ethnic group. However, no firm conclusions should be made until a much larger database is available. It is clear, however, that when identical mtDNA haplotypes are shared among many ethnic groups from different parts of Africa, it is impossible to determine which single ethnic group was the source of a particular maternal ancestor based on the mtDNA sequence.

The effect of a post acute respiratory outreach service for patients with chronic obstructive pulmonary disease on hospital readmission rates.

OBJECTIVE: The aim of this study was to investigate the effect of a Post Acute Respiratory Outreach Service (PAROS) for patients with chronic obstructive pulmonary disease (COPD), on hospital utilization. METHODS: A retrospective cohort of patients was examined, using a nested comparison, to test the hypothesis that PAROS would affect hospital utilization in the 12 months following the intervention. Patients admitted with COPD and subsequently enrolled in PAROS were compared with age, sex and diagnosis-matched controls admitted with COPD, who did not receive PAROS. RESULTS: Of 216 patients admitted with COPD during the 1-year study period, 28 were referred to PAROS. A total of 25 suitable controls were identified. Three cases that could not be matched were excluded from the analysis. There were no significant differences in lung function or prior hospitalization between the two groups at baseline. A significant increase in hospital bed days, in the 12 months following the index admission, was observed in the PAROS group (P = 0.046). There was no difference in the number of admissions or emergency department presentations between the groups. CONCLUSIONS: The PAROS program did not lead to a reduction in hospital utilization. This study supports previous findings that respiratory outreach services delivered immediately post discharge increase hospital utilization.

Mitochondrial DNA genetic diversity among four ethnic groups in Sierra Leone.

Although there are numerous ethnic groups in Sierra Leone, the Mende and Temne together account for approximately 60% of the total population. To see if genetic differences could be observed among ethnic groups in Sierra Leone, the nucleotide sequence of the hypervariable 1 (HV1) region of mitochondrial DNA (mtDNA) was determined from samples of the two major ethnic groups, the Mende (n=59) and Temne (n=121), and of two minor ethnic groups, the Loko (n=29) and Limba (n=67). Among these 276 HV1 sequences, 164 individual haplotypes were observed. An analysis of molecular variance indicated that the distribution of these haplotypes within the Limba sample was significantly different from that of the other ethnic groups. No significant genetic variation was seen between the Mende, Temne, and Loko. These results indicate that distinguishing genetic differences can be observed among ethnic groups residing in historically close proximity to one another. Furthermore, we observed some mitochondrial DNA haplotypes that are common among the Sierra Leone ethnic groups but that have not been observed in other published studies of West African ethnic groups. Therefore, we may have evidence for mtDNA lineages that are unique to this region of West Africa.

Clustering effects of chronic obstructive pulmonary disease specific quality of life in hospitalized patients.

OBJECTIVES: The primary aim of treatments for COPD is to improve health-related quality of life. However, little is known of the clustering effects related to health-related quality of life as an outcome measure. If clustering effects are observed, these have important implications for sample size estimates when cluster randomization is used in interventional studies. This study aimed to determine the intracluster correlation coefficient (ICC) of the quality of life, between hospitals for COPD patients. METHODOLOGY: The Dyspnoea Impact and Symptoms Questionnaire was administered to 100 COPD inpatients from four public hospitals (25 from each) around metropolitan Melbourne, selected on the basis that they had not had any major programs implemented within the last 2 years that aimed to improve the management of COPD. Data were collected concerning demographic and socioeconomic variables and comorbidities. RESULTS: The highest ICC value for a health-related quality of life subscale was 0.02 (psychological score), while the highest for a symptom-based subscale was 0.04. CONCLUSIONS: There is minimal clustering effect of quality of life in COPD patients between the hospitals studied. Despite this, when using a cluster randomised design the sample size needed to detect the same effect as a study using simple randomisation could be inflated by up to 183%. If cluster randomization is required, the average cluster size should be kept as small as possible to negate this effect.

Evaluation of a Fast Food Management Training Program: One Year Later.

This report summarizes an earlier short-term evaluation of a fast food restaurant manager training program and presents result from a re-evaluation approximately 1 year later. Thirty-one establishments in a single corporation were evaluated using criteria from the USPHS Food Service Sanitation Manual. Only 12 of the 31 original managers were still with the corporation 18 months after the start of the project. Those managers who participated in the training program tended to maintain or increase the sanitary quality in their establishments when compared with the short-term effects of training. The sanitary quality of the establishments with new managers that had joined the corporation after the training sessions were completed usually reverted to a quality similar to that before the start of the project which was generally unsatisfactory.