Biomedical subjects

Paul Miller

Publications and source records attributed to Paul Miller.

At least 37 records · Page 2Linked to original sources

PubMed2005

518A2 melanoma cells are protected by G3139 and other antineoplastic agents against the cytotoxic effects of DTIC.

G3139 is an antisense Bcl-2 phosphorothioate oligonucleotide that has been combined with DTIC in a phase III clinical trial in melanoma. However, its actual mechanism of action in melanoma is controversial. Treatment of 518A2 melanoma cells with either G3139 or G4126 (a two-base mismatch) and then with light-activated DTIC caused these cells (but not SK-Mel-30 or 346.1 cells) to be protected against the cytotoxic effects of DTIC. This cytoprotection was not recapitulated with a phosphodiester congener of G3139 nor with a small interfering RNA (siRNA) also targeted to the Bcl-2 mRNA. Administering the drugs in reverse order also did not produce cytoprotection, and an 18- mer phosphorothioate homopolymer of thymidine was also inactive. Subsequently, it was discovered that gemcitibine and cis-platinum also induced cytoprotection to DTIC in this cell line, suggesting that the cytoprotection is a stress response to chemical proapoptotic stress. Cytoprotection was completely inhibited by O(6)-benzylguanine, an inhibitor of O(6)-guanosine alkyltransferase (OGAT) activity. However, a direct assay of OGAT activity demonstrated that 518A2 melanoma cells are essentially completely devoid of it, either basally or induced. The cytoprotection may thus be caused by a chemical stress-induced increase in mismatch repair activity.

Antineoplastic Agents↗

PubMed2005

Naturally occurring proteasome inhibitors from mate tea (Ilex paraguayensis) serve as models for topical proteasome inhibitors.

Proteasome inhibitors have emerged as a clinically important therapy for neoplastic disease, with velcade, an organoboron compound used extensively in multiple myeloma. Recently, (-)-epigallocatechin gallate has been found to be a potent inhibitor of the proteasomal chymotrypsin-like activity. Other compounds that inhibit angiogenesis and are active as chemopreventive agents, such as curcumin, also inhibit proteasome activity. We have screened natural product extracts using ras-transformed endothelial cells (SVR cells) as a bioassay, and found that extracts of mate tea (Ilex paraguayensis) inhibit the growth of these endothelial cells. The extract was fractionated and found to have novel cinnamate esters that inhibit proteasome activity. Based upon the structures of the compounds isolated from mate tea, we examined synthetic analogs of these compounds for proteasome activity. Cinnamic acid amides had no inhibitory activity against proteasomes, whereas cinnamate esters displayed the activity. Based upon these findings, preclinical and clinical trials of topical cinnamate esters as proteasome inhibitors are warranted for psoriasis and other inflammatory disorders.

Cell Division↗

PubMed2005

Induction of apoptosis by G3139 in melanoma cells.

G3139 is an 18mer phosphorothioate oligonucleotide targeted to the initiation codon region of the Bcl-2 mRNA. Because of the ability of this antisense construct to downregulate the expression of Bcl-2 mRNA and protein, it has entered phase III clinical trials in a number of human cancers, including advanced melanoma. However, the actual mechanism of this agent is far from certain. In this work, we demonstrate that G3139 induces the relatively rapid release of cytochrome c into the cytoplasm of treated 518A2 melanoma cells. This release activates the intrinsic pathway of apoptosis, eventually leading to a mitochondrial permeability transition and cell death. By employing an siRNA strategy, we also show that this entire process appears to be Bcl-2 independent, as downregulation of Bcl-2 protein expression does not alter the induction of apoptosis by G3139. Furthermore, forced overexpression of Bcl-2 protein contributes relatively little to chemoresistance in this cell line. While these results may or may not be reflective of the in vivo situation, the value of Bcl-2 as a target in advanced melanoma must at least be questioned.

Animals↗

PubMed2005

Role of pharmacoeconomic analysis in R&D decision making: when, where, how?

Pharmacoeconomics is vitally important to drug manufacturers in terms of communicating to external decision-makers (payers, prescribers, patients) the value of their products, achieving regulatory and reimbursement approval and contributing to commercial success. Since development of new drugs is long, costly and risky, and decisions must be made how to allocate considerable research and development (R&D) resources, pharmacoeconomics also has an essential role informing internal decision-making (within a company) during drug development. The use of pharmacoeconomics in early development phases is likely to enhance the efficiency of R&D resource use and also provide a solid foundation for communicating product value to external decision-makers further downstream, increasing the likelihood of regulatory (reimbursement) approval and commercial success. This paper puts the case for use of pharmacoeconomic analyses earlier in the development process and outlines five techniques (clinical trial simulation [CTS], option pricing [OP], investment appraisal [IA], threshold analysis [TA] and value of information [VOI] analysis) that can provide useful input into the design of clinical development programmes, portfolio management and optimal pricing strategy. CTS can estimate efficacy and tolerability profiles before clinical data are available. OP can show the value of different clinical programme designs, sequencing of studies and stop decisions. IA can compare expected net present value (NPV) of different product profiles or study designs. TA can be used to understand development drug profile requirements given partial data. VOI can assist risk management by quantifying uncertainty and assessing the economic viability of gathering further information on the development drug. No amount of pharmacoeconomic data can make a bad drug good; what it can do is enhance the drug developers understanding of the characteristics of that drug. Decision-making, in light of this information, is likely to be better than that without it, whether it leads to faster termination of uneconomic projects or the allocation of more appropriate resources to attractive projects.

Decision Making, Organizational↗

PubMed2005

Reading experience and changes in the processing of letters, written words, and pseudohomophones: comparing fifth-grade students and university students.

In this study, the author elucidated whether reading experience continues to contribute to word recognition skills in readers with well-internalized reading skills. The participants performed consecutive same or different judgments regarding the identicalness of letters, words, and pseudohomophones. For a more detailed examination of how increased reading experience impacts particular stages of the processing of written stimuli, the author manipulated the identity dimension in each stimuli category. Twenty-five 5th-grade students and 22 university students participated in the study. Overall, findings indicated that a significant development occurs in the recognition of written stimuli after 5th grade because of a shift in the strategic allocation of mental resources (attention) within the recognition process. This change in strategy seems to prompt enhanced retrieval of knowledge relevant to the processing of written stimuli.

Child↗

PubMed2005

Phosphorothioate oligodeoxynucleotides and G3139 induce apoptosis in 518A2 melanoma cells.

In a previous study, we showed that G3139, an antisense phosphorothioate oligonucleotide that down-regulates the expression of Bcl-2 protein, did not cause chemosensitization of 518A2 melanoma cells. In this work, we show that G3139, and the 2-base mismatch, G4126, can initiate apoptosis in this and other melanoma cell lines as shown by increased cell surface Annexin V expression, typical nuclear phenotypic changes as assessed by 4',6-diamidino-2-phenylindole staining, activation of caspase-3 (but not caspase-8) and Bid, appearance of DEVDase (but not IETDase) activity, and cleavage of poly(ADP-ribose)-polymerase 1. Depolarization of the mitochondrial membrane occurs as a relatively late event. All of these processes seem to be substantially, but perhaps not totally, Bcl-2 independent as shown by experiments employing an anti-Bcl-2 small interfering RNA, which as shown previously down-regulated Bcl-2 protein expression but did not produce apoptosis or chemosensitization in melanoma cells. In fact, these G3139-induced molecular events were not dramatically altered in cells that forcibly overexpressed high levels of Bcl-2 protein. Addition of irreversible caspase inhibitors (e.g., the pan-caspase inhibitor zVAD-fmk) to G3139-treated cells almost completely blocked cytotoxicity. Examination of the time course of the appearance of caspase-3 and cleaved poly(ADP-ribose)-polymerase 1 showed that this could be correlated with the release of cytochrome c from the mitochondria, an event that begins only approximately 4 hours after the end of the oligonucleotide/LipofectAMINE 2000 5-hour transfection period. Thus, both G3139 and cytotoxic chemotherapy activate the intrinsic pathway of apoptosis in these cells, although Bcl-2 expression does not seem to contribute strongly to chemoresistance. These findings suggest that the attainment of G3139-induced chemosensitization in these cells will be difficult.

Antineoplastic Agents↗

PubMed2004

Relative Bcl-2 independence of drug-induced cytotoxicity and resistance in 518A2 melanoma cells.

PURPOSE: Inhibition of the function of Bcl-2 protein has been postulated to sensitize cells to cytotoxic chemotherapy. G3139 (Genasense) is a phosphorothioate anti-Bcl-2 antisense oligonucleotide, but its mechanism of action is uncertain. The aim of the present work is to investigate inhibition of Bcl-2 expression in 518A2 melanoma cells, the cell line on which recent phase II and phase III clinical trials employing this agent were based. EXPERIMENTAL DESIGN: We down-regulated the expression of Bcl-2 protein by two different strategies in these cells: one employing G3139 and controls, and the other using a small interfering RNA approach. Cell viability after treatment with oligonucleotides or small interfering RNA and cytotoxic agents including gemcitibine, DDP, docetaxel, and thapsigargin was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. A 518A2 melanoma cell line stably overexpressing Bcl-2 protein was constructed and treated with either these cytotoxic agents or G3139. RESULTS: The cytotoxic effects of either G3139 or small interfering RNA treatment of 518A2 melanoma cells are Bcl-2 independent. In addition, in the Bcl-2-overexpressing cells, only a modest increment in chemoresistance was observed, and treatment with G3139 not only did not down-regulate Bcl-2 expression but produced essentially identical toxicity as was observed in the wild-type or mock-transfected cells. CONCLUSIONS: Our results suggest that the mechanism whereby G3139 produces drug-induced cytotoxicity in the 518A2 melanoma line is not dependent on levels of Bcl-2. These findings emphasize the nonsequence specific effects of this phosphorothioate oligonucleotide and call into question the validity of Bcl-2 as a target in this cell line.

Antineoplastic Agents↗

PubMed2004

Treatment with once-weekly alendronate 70 mg compared with once-weekly risedronate 35 mg in women with postmenopausal osteoporosis: a randomized double-blind study.

UNLABELLED: Once-weekly alendronate 70 mg and once-weekly risedronate 35 mg are indicated for the treatment of postmenopausal osteoporosis. These two agents were compared in a 12-month head-to-head trial. Greater gains in BMD and greater reductions in markers of bone turnover were seen with alendronate compared with risedronate with similar tolerability. INTRODUCTION: The nitrogen-containing bisphosphonates, alendronate and risedronate, are available in once-weekly (OW) formulations for the treatment of postmenopausal osteoporosis. A 12-month, head-to-head study was performed to compare these agents in the treatment of postmenopausal women with low BMD. MATERIALS AND METHODS: A total of 1053 patients from 78 U.S. sites were randomized to OW alendronate 70 mg (N = 520) or risedronate 35 mg (N = 533), taken in the morning after fasting. Endpoints included BMD changes over 6 and 12 months at the hip trochanter, total hip, femoral neck, and lumbar spine (LS); percent of patients with predefined levels of change in trochanter and LS BMD at 12 months; and change in biochemical markers of bone turnover at 3, 6, and 12 months. Tolerability was evaluated by adverse experience (AE) reporting. RESULTS: Significantly greater increases in hip trochanter BMD were seen with alendronate (3.4%) than risedronate (2.1%) at 12 months (treatment difference, 1.4%; p < 0.001) as well as 6 months (treatment difference, 1.3%; p < 0.001). Significantly greater gains in BMD were seen with alendronate at all BMD sites measured (12-month difference: total hip, 1.0%; femoral neck, 0.7%; LS, 1.2%). Significant differences were seen as early as 6 months at all sites. A greater percentage of patients had > or =0% (p < 0.001) and > or =3% (p < 0.01) gain in trochanter and spine BMD at 12 months with alendronate than risedronate. Significantly greater (p < 0.001) reductions in all biochemical markers of bone turnover occurred with alendronate compared with risedronate by 3 months. No significant differences were seen between treatment groups in the incidence of upper gastrointestinal AEs or AEs causing discontinuation. CONCLUSIONS: In this 12-month, head-to-head trial of alendronate and risedronate, given in accordance with the approved OW regimens for treatment of osteoporosis in postmenopausal women, alendronate produced greater gains in BMD and greater reductions in markers of bone turnover than risedronate. The greater antiresorptive effect of alendronate was seen as early as 3 months, and the tolerability profiles were similar.

Aged↗

PubMed2004

Changes in gene expression induced by phosphorothioate oligodeoxynucleotides (including G3139) in PC3 prostate carcinoma cells are recapitulated at least in part by treatment with interferon-beta and -gamma.

PURPOSE: G3139 is an antisense bcl-2 phosphorothioate oligodeoxyribonucleotide that is currently being evaluated in Phase III clinical trials in several human cancers. The aim of the present work was to further identify the apparent non-bcl-2-dependent mechanism of this action of this compound in PC3 prostate cancer cells. EXPERIMENTAL DESIGN: We performed Affymetrix U95A oligonucleotide microarray studies on mRNA isolated from cells treated with G3139 and related oligonucleotides. RESULTS: Hierarchical clustering revealed the presence of a set of genes of which the expression was elevated on both 1 and 3 days after oligonucleotide treatment. Significantly, the persistence of expression of the up-regulation of these genes, many of which are members of the IFN cascade, was greater for G3139 than for any other oligomer evaluated. Furthermore, many of the genes with the greatest up-regulation of expression are also those of which the expression is up-regulated after treatment of cells with IFNs. Treatment of PC3 cells with either IFN-beta or -gamma recapitulated some of the aspects of the molecular and phenotypic changes observed after treatment with a G3139/Lipofectin complex. These include down-regulation of bcl-2 protein expression itself, down-regulation of protein kinase C alpha protein expression (but not that of other protein kinase C isoforms), alteration in p21/Waf1/Cip1 protein expression, up-regulation of MHC-I cell surface expression, and profound suppression of cell growth in the absence of a notable increase in cellular apoptosis. However, G3139 (when complexed with Lipofectin) did not induce the up-regulation of expression of either type I or type II IFNs, nor could IFNs be found in conditioned media from treated cells. CONCLUSIONS: Oligonucleotide microarray experiments demonstrated that G3139 could induce elements of the IFN cascade in PC3 cells in vitro. In addition, the cellular phenotype obtained after treatment with exogenous IFN could, at least in part, recapitulate that obtained after G3139 treatment. Nevertheless, the oligonucleotide microarray experiments we performed also demonstrated that there are extremely large qualitative and quantitative differences between the two treatments.

Algorithms↗

PubMed2004

A randomised controlled trial of a care home rehabilitation service to reduce long-term institutionalisation for elderly people.

OBJECTIVES: to evaluate the effect of a care home rehabilitation service on institutionalisation, health outcomes and service use. DESIGN: randomised controlled trial, stratified by Barthel ADL index, social service sector and whether living alone. The intervention was a rehabilitation service based in Social Services old people's homes in Nottingham, UK. The control group received usual health and social care. PARTICIPANTS: 165 elderly and disabled hospitalised patients who wished to go home but were at high risk of institutionalisation (81 intervention, 84 control). MAIN OUTCOME MEASURES: institutionalisation rates, Barthel ADL index, Nottingham Extended ADL score, General Health Questionnaire (12 item version) at 3 and 12 months, Health and Social Service resource use. RESULTS: the number of participants institutionalised was similar at 3 months (relative risk 1.04, 95% confidence intervals 0.65-1.65) and 12 months (relative risk 1.23, 95% confidence intervals 0.75-2.02). Barthel ADL Index, Nottingham Extended ADL score and General Health Questionnaire scores were similar at 3 and 12 months. The intervention group spent significantly fewer days in hospital over 3 and 12 months (mean reduction 12.1 and 27.6 days respectively, P < 0.01), but spent a mean of 36 days in a care home rehabilitation service facility. CONCLUSIONS: this service did not reduce institutionalisation, but diverted patients from the hospital to social services sector without major effects on activity levels or well-being.

Activities of Daily Living↗

PubMed2004

Antisense RNA down-regulation of bcl-2 expression in DU145 prostate cancer cells does not diminish the cytostatic effects of G3139 (Oblimersen).

PURPOSE: Inhibition of the function of the bcl-2 protein has been postulated to sensitize cells to cytotoxic chemotherapy, and thus provides an attractive target for investigative therapies. G3139, a phosphorothioate antisense oligonucleotide targeted to the initiation codon region of the bcl-2 mRNA, is currently being evaluated in several Phase II and Phase III clinical trials. However, the mechanism of action of this molecule appears to depend on a combination of antisense plus nonantisense events. Indeed, the very idea that bcl-2 is a critical target is, at least in part, an extrapolation from experiments in which intracellular bcl-2 protein concentrations have been dramatically increased, yielding chemoresistant cells. EXPERIMENTAL DESIGN: In this work, we down-regulated the expression of bcl-2 protein by 80-90% by two different antisense RNA strategies (antisense RNA and small interfering RNA) in DU145 prostate cancer cells. RESULTS: Even after down-regulation of bcl-2 protein expression by either one of these strategies, the cellular phenotype induced by subsequent G3139 treatment (inhibition of cellular growth and the generation of reactive oxygen species) was essentially identical to that induced in mock-infected or wild-type DU145 cells in which bcl-2 protein expression had not been down-regulated previously. CONCLUSIONS: These results strongly suggest that bcl-2 expression in DU145 cells is not strongly associated with the prolife phenotype and that the mechanism by which G3139 produces its cytostatic effects in this cell line is bcl-2 independent.

Apoptosis↗

PubMed2004

Modeling the atmospheric transport and deposition of mercury to the Great Lakes.

A special version of the NOAA HYSPLIT_4 model has been developed and used to estimate the atmospheric fate and transport of mercury in a North American modeling domain. Spatial and chemical interpolation procedures were used to expand the modeling results and provide estimates of the contribution of each source in a 1996 anthropogenic US/Canadian emissions inventory to atmospheric mercury deposition to the Great Lakes. While there are uncertainties in the emissions inventories and ambient data suitable for model evaluation are scarce, model results were found to be reasonably consistent with wet deposition measurements in the Great Lakes region and with independent measurement-based estimates of deposition to Lake Michigan. Sources up to 2000 km from the Great Lakes contributed significant amounts of mercury through atmospheric transport and deposition. While there were significant contributions from incineration and metallurgical sources, coal combustion was generally found to be the largest contributor to atmospheric mercury deposition to the Great Lakes.

Air Movements↗

PubMed2004

The influence of pulmonary artery morphology on the results of operations for major aortopulmonary collateral arteries and complex congenital heart defects.

OBJECTIVE: Congenital heart defects with major aortopulmonary collateral arteries show marked variability in the size and distribution of native pulmonary arteries. We sought to classify the size and distribution of native pulmonary arteries and to determine their influence on surgical outcome. METHODS: Between 1989 and 2002, 164 patients underwent surgical intervention for congenital heart defects with major aortopulmonary collateral arteries (median age, 10 months). Three patterns of native pulmonary arteries were identified: intrapericardial native pulmonary arteries present (group I); confluent intrapulmonary native pulmonary arteries without intrapericardial native pulmonary arteries (group II); and nonconfluent intrapulmonary native pulmonary arteries (group III). Thirty-seven (23%) patients had single-stage and 76 (47%) patients had multistage complete repair. Thirty (18%) patients await septation, and 8 (5.0%) patients are not septatable. Follow-up is 98% complete (median follow-up, 5.8 years). RESULTS: In the 164 patients there were 15 (9.1%) early and 12 (7.3%) late deaths. Early mortality after complete repair was 4.4% (n = 5). Actuarial survival was 90% +/- 3% and 85% +/- 4% at 1 and 10 years, respectively. Actuarial freedom from surgical or catheter reintervention in septated patients was 77% +/- 4% and 45% +/- 8% at 1 and 10 years, respectively. On multivariate analysis, the morphology of the native pulmonary arteries was the only factor that influenced actuarial survival after complete repair (P =.04). Group III had the highest risk of death after septation (P =.008). Group II fared better than group III after the initial operation (P <.05). CONCLUSIONS: Current classifications of congenital heart defects with major aortopulmonary collateral arteries are based on the presence or absence of intrapericardial pulmonary arteries. We have identified a subgroup without intrapericardial native pulmonary arteries but with confluent intrapulmonary native pulmonary arteries. This group has a better outcome than those with nonconfluent intrapulmonary native pulmonary arteries.

Abnormalities, Multiple↗

PubMed2004

Cooled transurethral microwave thermotherapy for intractable chronic prostatitis--results of a pilot study after 1 year.

OBJECTIVES: To evaluate the side effects, tolerability, and efficacy of transurethral microwave thermotherapy with urethral cooling (cooled TUMT) for chronic prostatitis/chronic pelvic pain syndrome in a prospective feasibility trial. Cooled TUMT, using the Targis system from Urologix, is an established treatment option for benign prostatic hyperplasia (BPH) with minimal side effects. METHODS: Patients with intractable chronic prostatitis/chronic pelvic pain syndrome and symptoms for more than 3 of the 6 months before treatment (National Institutes of Health-Chronic Prostatitis Symptom Index [NIH-CPSI] pain score of at least 8) were randomized to cooled TUMT at an intraprostatic temperature of either approximately 55 degrees C or approximately 70 degrees C. Tolerability, side effects, and efficacy were measured with standard diagnostic tests, including the NIH-CPSI. Subgroup analysis was performed to evaluate the effects with and without BPH comorbidity. RESULTS: A total of 42 patients were included in the study; 39 patients successfully completed treatment and 35 completed follow-up through 12 months. The baseline versus 12-month mean NIH-CPSI score was total score 23.4 +/- 6.4 versus 11.5 +/- 10.2 (improvement in mean value of 51%), pain score 11.5 +/- 2.8 versus 4.6 +/- 4.9 (improvement in mean value of 60%), quality-of-life impact score 7.2 +/- 2.9 versus 3.8 +/- 3.8 (improvement in mean value of 47%; all P <0.0001), and urinary score 4.7 +/- 2.8 versus 3.1 +/- 3.0 (improvement in mean value of 34%; P = 0.0079). Treatment discomfort was within the ranges reported for patients with Targis-treated BPH. Two patients had reduced sperm motility. Side effects were minimal and transient, resolved spontaneously or with medication, and were similar regardless of treatment temperature or BPH comorbidity. CONCLUSIONS: Cooled TUMT appears to be promising for intractable chronic prostatitis with or without BPH. Longer follow-up and a larger trial are required to evaluate the fertility impact and longer term durability further.

Chronic Disease↗

PubMed2004

Processing of written words by individuals with prelingual deafness.

The aim of this study was to elucidate how prelingual deafness affects the ability to process written words. An experiment designed to reveal possible differences in the word-processing strategies and efficiency of a sample of prelingually deafened students (n = 18; mean grade = 5.1) and a task-matched hearing control group (n = 28; mean grade = 4.9) was conducted. The experiment was based on a research paradigm demanding the same/different categorization of physically (perceptually) or conventionally identical word pairs. To elucidate the nature of the word-processing strategy adopted by each group, word pairs varying within their phonological information (monosyllabic, bisyllabic) were used for stimulation. Unexpectedly, findings revealed that the abilities of the 2 participant groups to process written words were remarkably similar. This was true whether or not the processing of the word pairs required the referencing of linguistic knowledge for the mediation of their identicalness. Furthermore, there was no evidence that either of the 2 participant groups relied on phonological information for processing the stimuli. In general, the findings support a conclusion that the difficulties of prelingually deafened individuals with reading are not rooted in a deficient ability to process written words per se but reflect the absence of crucial (probably general as well as linguistic) knowledge as the basis for their final interpretation. The results further suggest that the phonological decoding of written words may not be a prerequisite for their efficient processing in working memory.

Articulation Disorders↗

PubMed2004

Processing of written word and nonword visual information by individuals with prelingual deafness.

The objective of this study was to bring about a better understanding of the abilities of prelingually deafened individuals to process word and nonword visual information. Students with prelingual deafness (n = 18, mean grade = 5.1) and a task-matched hearing control group (n = 28, mean grade = 4.9) judged the identicalness of physically (perceptually) or conventionally identical words or drawings to learn about differences in their processing strategies as the phonological information contained in these stimuli was manipulated. Findings suggested that the information-processing skills of both groups of participants were similar regardless of stimulus material (i.e., words or drawings) and whether such processing required the referencing of conceptual knowledge. Evidence further indicated that both groups relied on similar strategies for processing the stimuli but that neither relied on a phonology-based strategy.

Case-Control Studies↗

PubMed2004

Sooner and healthier: a randomised controlled trial and interview study of an early discharge rehabilitation service for older people.

BACKGROUND: Hospitals are under pressure from admissions of increasing numbers of older people. Older people may suffer unnecessary activity limitation after acute illnesses through lack of appropriate rehabilitation. OBJECTIVE: To evaluate an early discharge and rehabilitation service for older people. DESIGN: A randomised controlled trial comparing an early discharge and rehabilitation with standard hospital aftercare. Outcome measures assessed at 3 and 12 months were the Barthel Index, Nottingham Extended Activities of Daily Living and EuroQol (for patients) the General Health Questionnaire (for patients and carers). Use of services over 12 months was recorded. An interview study of patients and staff was conducted. SETTING AND INTERVENTION: The early discharge and rehabilitation service offered a home-based rehabilitation and care programme for up to 4 weeks. PARTICIPANTS: 370 hospitalised older medical and surgical patients were included in the randomised controlled trial. Twenty patients and 11 staff were interviewed. RESULTS: Subjects in the early discharge rehabilitation service group used fewer days in hospital at 3 months (mean difference 9, median difference 4 days, 95% CI of median difference 2-8). At 3 months the early discharge and rehabilitation service patients had better Barthel scores (mean difference 1.2, 95% CI 0.4-1.9), Nottingham Extended Activities of Daily Living kitchen scores (mean difference 1.2, 95% CI 0.2-2.3), Nottingham Extended Activities of Daily Living domestic scores (mean difference 1.1, 95% CI 0.2-2.0) and General Health Questionnaire scores (mean difference 2.4, 95% CI 0.7-4.1). Significant Nottingham Extended Activities of Daily Living domestic and General Health Questionnaire benefits remained at 12 months. The early discharge and rehabilitation service carers had better General Health Questionnaire scores at 3 months (mean difference 2.0, 95% CI 0.1-3.8). The interviews suggested that the early discharge and rehabilitation service was patient-centred, set clear goals, worked as a team, and considered physical, psychological, social and environmental issues. It was found to be highly satisfactory. CONCLUSIONS: Some older people can be discharged from hospital sooner, with better health outcomes using a well-staffed and organised patient-centred early discharge service providing rehabilitation.

Activities of Daily Living↗

PubMed2004

Infant mortality and air pollution: modifying effect by social class.

UNLABELLED: Studies link air pollution with increased mortality; however, information on infants is scarce and inconclusive. OBJECTIVE: We studied short-term PM10 exposure, relating to increased respiratory-related infant mortality, and estimated for poor living conditions. METHODS: A case-crossover approach modeled the relationship between infant mortality (1 month-1 year of age), and ambient PM10 levels on days before death in Ciudad Juarez, Mexico (1997-2001). Socioeconomic level (SES) of the deceased was defined by residence location. RESULTS: Overall air pollutants did not affect infant mortality (odds ratio [OR] = 1.02, 95% confidence interval [CI] = 0.94-1.11 for PM10, lag1) but low SES increased risk. Each 20 microg/m3 in PM10 (24-hour average, lag1, cumulative over 2 previous days) increased respiratory-related mortality (OR = 1.61, 95% CI = 0.97-2.66; OR = 2.56; 95% CI = 1.06-6.17, respectively). Ozone levels did not affect infant mortality for any SES. CONCLUSIONS: Worse living conditions among lower SES concurred with increased mortality.

Air Pollutants↗