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Biomedical subjects

P Jacobs

Publications and source records attributed to P Jacobs.

At least 55 records · Page 3Linked to original sources

Responsiveness of the EuroQol in breast cancer patients undergoing high dose chemotherapy.

OBJECTIVE: To assess the responsiveness of the EuroQol (EQ-5D) by comparing it with the Functional Living Index-Cancer (FLIC) and a self-reported rating of health-related quality of life (HRQL). METHODS: HRQL was measured four times during the course of high dose chemotherapy (HDC) and bone marrow transplantation in 40 patients with stage II and III breast cancer. Measurements were at baseline (T1), pre-HDC (T2), 3 weeks post-HDC (T3), and 3 months post-HDC (T4). RESULTS: Effect size ranged from 1.16 (T1-T3) to 0.66 (T3-T4) for the EQ-5D and 0.85-0.91 respectively for the FLIC. No significant differences in effect sizes between the EQ-5D and the FLIC were found. Repeated measures ANOVA yielded a significant change for all measures, with HRQL decreasing post-HDC and returning to baseline levels by 3 m post-HDC. EQ-5D dimensions changed significantly over time for mobility, self-care, and usual activities. EQ-5D index scores at T3 had a bimodal distribution. Interpretation of psychological changes was facilitated by an analysis of FLIC items. CONCLUSIONS: The EQ-5D is responsive to the clinically large changes associated with HDC in breast cancer patients. The bimodal distribution of the EQ-5D index has implications for the interpretation of EQ-5D change scores.

Alberta↗

Descriptive patient data as an explanation for the variation in average daily costs in intensive care.

Intensive care patients require therapy that can vary considerably in type, duration and cost, so making it extremely difficult to predict patient resource use. Few studies measure actual costs; usually average daily costs are calculated and these do not reflect the variation in resource use between individual patients. The aim of this study was to analyse a data set of 193 critically ill adult patients to look for associations between routinely collected descriptive data and patient-specific costs. Regression analysis was used to explore any relationships between average daily patient-specific costs and the following variables: duration of intensive care unit stay, Acute Physiology and Chronic Health Evaluation II scores in the first 24 h, gender, age, mechanical ventilation at any point during the stay, postoperative status, emergency admission and mortality. Overall, this analysis explained 33.6% of the variation in average daily costs. The additional costs of an extra day of care, mechanical ventilation, an extra point on the Acute Physiology and Chronic Health Evaluation II score, and survival were obtained.

APACHE↗

Disruption of adhC reveals a large duplication in the Mycobacterium smegmatis mc(2)155 genome.

Disruption of the adhC gene of Mycobacterium smegmatis mc(2)155, by standard gene replacement methods, revealed that there are two copies of this gene within a large duplication of the M. smegmatis mc(2)155 genome. M. smegmatis AdhC(+/-) and M. smegmatis AdhC(-/-) mutants were obtained when one or two adhC copies, respectively, were disrupted by homologous recombination. Southern blot analysis of DraI restriction digests of the DNA from these mutants and from wild-type M. smegmatis mc(2)155, resolved by PFGE, showed that the duplication size may be at least approximately 250 kb. The single and double knockout mutants were characterized and compared with the M. smegmatis wild-type. A growth disadvantage and a different morphology were associated with the loss of expression of one or both of the adhC copies, but both mutants were still acid-fast. Findings in this study indicate that the process of chromosomal duplication in M. smegmatis is ongoing and remains a potent source of genome dynamics. Hence, the M. smegmatis mc(2)155 genome might be larger than previously thought.

Alcohol Dehydrogenase↗

Evaluation of a routine telepsychiatry service.

An assessment was undertaken of a routine telepsychiatry service in rural areas of a Canadian province as a follow-up to a pilot telepsychiatry project. Over two years, there were 546 consultations at the five participating general hospitals, although the level of use varied considerably between them. Health professionals expressed high satisfaction with the service. While there were equipment problems in 17% of all consultations in the second year, they did not seem to affect acceptance of the technique. A cost analysis comparing consultations provided by a visiting psychiatrist and telepsychiatry found a break-even point of 348 consultations a year. However, when use of the videoconferencing network for administrative meetings was considered, the break-even point was 224 consultations a year, substantially below the actual utilization of telepsychiatry. Telepsychiatry appeared to result in increased access to community mental health services, suggesting future increased demand for these. From the perspective of health authorities and health professionals, telepsychiatry proved to be a useful and sustainable addition to existing mental health services.

Adult↗

Telepsychiatry as a routine service--the perspective of the patient.

Patient perspectives were examined as part of an assessment of a routine telepsychiatry service in rural Alberta. Information was gathered through self-report questionnaires and telephone interviews. Of 379 questionnaires distributed to patients, 230 (61%) were returned. Of the patients who completed questionnaires, 89% reported being satisfied with the service and 96-99% were satisfied with the equipment and the room. Twenty-nine of 31 patients who were interviewed by telephone preferred telepsychiatry to waiting for a consultation, were willing to use the service again and would recommend telepsychiatry to a friend. While 25 of these 31 patients preferred telepsychiatry to travelling to a consultation, 15 indicated that they would prefer a face-to-face interview to telepsychiatry and a further seven were unsure. Twenty-three of the 31 patients interviewed would have had to miss time from work or pay for child care in order to travel to a conventional psychiatric consultation. The availability of telepsychiatry led to an estimated cost saving of $210 per consultation for patients who would otherwise have had to travel. From the patient's perspective, telepsychiatry was an acceptable technique in the management of mental health difficulties that both increased access to services and produced cost savings.

Adolescent↗

The cost of palliative care for hepatocellular carcinoma in Hong Kong.

BACKGROUND: Hepatocellular carcinoma (HCC) is endemic in parts of Asia and Africa and most patients are not suitable for treatment with a curative approach. Little is known about the cost of palliative care for HCC. OBJECTIVE: To determine: (i) patient-specific costs of palliative care of HCC; and (ii) individual factors that drive patient-specific costs and to develop a model of cost per case under alternative circumstances. METHODS: 204 patients with inoperable HCC were prospectively tracked from first hospitalisation until death for health service utilisation. A societal perspective of cost was taken, including costs of formal and informal services incurred by payers, caregivers and patients. Observational data from a large Hong Kong cancer care programme were used. A regression analysis was performed using formal costs only, with the cost per observed day as the dependent variable. RESULTS: The median survival was 95 days and the mean observation period was 153 days. The mean value per person for formal healthcare cost was 30 983 Hong Kong dollars [$HK] ($US3872, 1998 values). The distribution of cost values were positively skewed. The regression analysis showed that age, days of observation and survival were negatively related to cost per observed day, and the Child-Pugh grading of severity of liver cirrhosis was positively related to cost per observed day. A sensitivity analysis based on the regression equation indicated that nonsurvivorship doubles the cost per case, increased severity as measured by the Child-Pugh Index adds about 50% to the cost, and chemotherapy increases cost 2-fold. CONCLUSIONS: The relatively modest average cost per patient with HCC in Hong Kong reflects the short median survival and subsequently the limited use of inpatient care and chemotherapy.

Aged↗

Productivity losses associated with diabetes in the US.

OBJECTIVE: The objective of this study was to estimate the cost of productivity losses in the U.S. attributable to diabetes, with regard to specific demographic and disease-related characteristics in the U.S.. RESEARCH DESIGN AND METHODS: We used the 1989 National Health Interview Survey, a random survey of individuals in the U.S. that included a diabetes supplement. Data on individuals were obtained for labor force participation, hours of work, demographic and occupational characteristics, self-reported health status, and several variables that indicated the presence, duration, and severity (complications) of diabetes. Using multivariate regression analyses, we estimated the association of independent variables (e.g., demographics, health, and diabetes status) with labor force participation, hours of work lost, and the economic value of lost work attributable to diabetes and its complications and duration. RESULTS: In general, the presence of diabetes and complications were found to be related to workforce participation variables. The magnitude of the lost-productivity costs depended on personal characteristics and on the presence and status of diabetes. In general, the loss of yearly earnings amounted to about a one-third reduction in earnings and ranged from $3,700 to $8,700 per annum. CONCLUSIONS: Diabetes has a considerable net effect on earnings, and the complications and duration of diabetes have compound effects. Our findings have implications for the cost-effectiveness of diabetes control; the presence of complicating factors is the single most important predictive factor in lost productivity costs attributable to diabetes, and thus the avoidance or retardation of complications will have an impact on indirect health-related costs.

Adult↗

User fees, health staff incentives, and service utilization in Kabarole District, Uganda.

OBJECTIVE: To determine the impact of user fees on the utilization of health services in a community-based cost-sharing scheme in Kabarole District, western Uganda. METHODS: Of the 38 government health units that had introduced user-fee financing schemes, 11 were included in the study. Outpatient utilization was assessed as the median number of visits per month before and after cost sharing began. FINDINGS: After the introduction of cost sharing, overall utilization of general outpatient services, assessed by combining the data from all the participating units, dropped by 21.3%. Utilization increased, however, in facilities located in remote areas, while it decreased in those located in urban or semi-urban areas. The increased utilization in remote facilities was considered to be largely attributable to health workers' incentive payments derived from cost-sharing revenues. CONCLUSIONS: Incentive payments led the health workers to offer improved services. Other factors may also have been influential, such as an improved drug supply to health facilities and increased public identification with community projects in remote areas.

Attitude of Health Personnel↗

Cost effectiveness analysis of intravenous ketorolac and morphine for treating pain after limb injury: double blind randomised controlled trial.

OBJECTIVES: To investigate the cost effectiveness of intravenous ketorolac compared with intravenous morphine in relieving pain after blunt limb injury in an accident and emergency department. DESIGN: Double blind, randomised, controlled study and cost consequences analysis. SETTING: Emergency department of a university hospital in the New Territories of Hong Kong. PARTICIPANTS: 148 adult patients with painful isolated limb injuries (limb injuries without other injuries). MAIN OUTCOME MEASURES: Primary outcome measure was a cost consequences analysis comparing the use of ketorolac with morphine; secondary outcome measures were pain relief at rest and with limb movement, adverse events, patients' satisfaction, and time spent in the emergency department. RESULTS: No difference was found in the median time taken to achieve pain relief at rest between the group receiving ketorolac and the group receiving morphine, but with movement the median reduction in pain score in the ketorolac group was 1.09 per hour (95% confidence interval 1.05 to 2.02) compared with 0.87 (0.84 to 1.06) in the morphine group (P=0.003). The odds of experiencing adverse events was 144.2 (41.5 to 501.6) times more likely with morphine than with ketorolac. The median time from the initial delivery of analgesia to the participant leaving the department was 20 (4.0 to 39.0) minutes shorter in the ketorolac group than in the morphine group (P=0.02). The mean cost per person was $HK44 ( pound4; $5.6) in the ketorolac group and $HK229 in the morphine group (P<0.0001). The median score for patients' satisfaction was 6.0 for ketorolac and 5.0 for morphine (P<0.0001). CONCLUSION: Intravenous ketorolac is a more cost effective analgesic than intravenous morphine in the management of isolated limb injury in an emergency department in Hong Kong, and its use may be considered as the dominant strategy.

Adolescent↗

Expression and intracellular processing of chimeric and mutant CFTR molecules.

The cystic fibrosis transmembrane conductance regulator (CFTR) is a cyclic AMP-activated chloride channel comprising two membrane-spanning domains (MSDs), two nucleotide-binding domains (NBDs) and a unique regulatory (R) domain. The most frequent cystic fibrosis (CF) mutation, a deletion of Phe508 in NBD1, results in the retention of the DeltaF508 CFTR in the endoplasmic reticulum, as do many other natural or constructed mutations located within the first NBD. In order to further define the role of NBD1 in CFTR folding and to determine whether the higher frequency of mutations in NBD1 with respect to NBD2 results from its position in the molecule or is related to its primary sequence, we constructed and expressed chimeric CFTRs wherein NBD domains were either exchanged or deleted. Synthesis, maturation and activity of the chimeras were assessed by Western blotting and iodide efflux assay after transient or stable expression in COS-1 or CHO cells respectively. The data showed that deletion of NBD1 prevented transport of CFTR to the cytoplasmic membrane whereas deletion of NBD2 did not impair this process but resulted in an inactive chloride channel. On the other hand, substituting or inverting NBDs in the CFTR molecule impaired its processing. In addition, while the NBD1 R555K mutation is known to partially correct the processing of CFTR DeltaF508 and to increase activity of both wild-type and DeltaF508 individual channels, it showed no positive effect when introduced into the double NBD1 chimera. Taken together, these observations suggest that the proper folding process of CFTR results from complex interactions between NBDs and their surrounding domains (MSDs and/or R domain).

Animals↗

Age- and tissue-specific variation of X chromosome inactivation ratios in normal women.

The incidence of skewed X-inactivation in normal women is controversial, with up to 10-fold differences being reported by different authors. In order to clarify this issue, we have conducted a survey of the X-inactivation patterns in 270 informative females from various age groups, using the androgen receptor gene/polymerase chain reaction assay. Results obtained by using DNA extracted from blood samples show that the incidence of severe skewing (defined here as ratios > or = 90:10) is relatively common and increases with age (P<0.05), occurring in 7% of women under 25 years of age, and 16% of women over 60. In order to study tissue-specific patterns of X-inactivation, samples of both buccal and urinary epithelia were also obtained from 88 of the females studied. Although there was a significant association of the X-inactivation ratios between each tissue in most individuals, wide variations were apparent in some cases, making accurate extrapolations between tissues impossible. The degree of correlation between each tissue also fell markedly with age. Our data are consistent with the hypothesis that the major factors in the aetiology of skewed X-inactivation are secondary selection processes.

Adolescent↗

Cost-effectiveness analysis of case management versus a routine community care organization for patients with chronic schizophrenia.

This article reports the economic analysis of a study on the implementation of case management in the Community Psychiatric Nursing Service (CPNS) caring for chronic schizophrenic clients in Hong Kong. The purpose of the study was to compare the outcome of case management service with the conventional practice CPNS. Sixty-two subjects participated in the analysis. Cost-effectiveness analysis showed that case management costs more in Hong Kong $3,600 (US$450) per person and that over a 5-month period, case management was associated with improvements in psychological and functional outcomes and patient satisfaction. The results of this study will inform policy makers about resource allocation and policy development in the implementation of case management for the care of mentally ill clients.

Adult↗

The supply of blood products in 10 different systems or countries.

Countries vary greatly in their ability to produce their own blood products including albumin and IVIgG. Part of this variability depends on the supply of plasma within the country. As has been seen most recently in the UK, the quality of the plasma and its acceptability for plasma fractionation must also be considered. Therefore concerns regarding the quality of the plasma have been added to those regarding the quantity.Only a few countries are nationally self sufficient in plasma. This has a marked effect on blood product availability and therefore the ability to treat patients. Unlike most pharmaceuticals, the plasma fractionation industry must rely, for its raw products, on plasma obtained from blood donors. As such this puts it in a potentially compromised situation since neither the supply nor the quality of the raw material can be assured and both of those will vary with time. This paper reviews the processes through which blood products are made available in 10 different systems including: Canada, England, France, Italy, Norway Scotland, Sweden, Switzerland, South Africa and USA. A series of specific questions were posed and the responses received from the various coauthors and other respondents provide comparative data on blood product availability in different areas of the world.

Blood Banks↗

A comparative study of the photosensitizing characteristics of some cyanine dyes.

The present work has been carried out to explore the potential application of cyanines in photodynamic therapy. After photosensitization, the in vitro cytotoxic and antiproliferative activity on HeLa cells of a total of 35 cyanines belonging to several chemical subgroups is explored. Most of these cyanines have never been used before in similar experimental work. From a first set of experiments, it is found that none of the krypto-, oxa- and imidacyanines is photobiologically active on HeLa cells. Conversely, five thiacyanines (Thiacl-5), one rhodacyanine (Rhodac) and four indocyanines (Indoc2, Indoc4, Indoc5, Indoc7) show photodependent cytotoxicity or antiproliferative effects. A more detailed study shows that out of the ten selected compounds, eight cyanines feature significant photodependent cytotoxic and antiproliferative effects. All possess maximum absorption ranges between 545 and 824 nm. In particular, Rhodac, a tetramethinemeromonomethine rhodacyanine dye with an absorption maximum of 655 nm (ethanol) and a molar absorption coefficient epsilon = 108000 shows very promising photo-dependent biological activity. In general, the measured singlet oxygen quantum yield of the selected cyanines is low (< 0.08) and does not correlate with the degree of photosensitization. Furthermore, the present study shows that cyanines with a partition coefficient close to 1.5 accumulate to the highest extent in HeLa cells, while the more hydrophobic compounds (e.g., indocyanines) concentrate less intracellularly.

Cell Survival↗

A clinical, cytogenetic and molecular study of 47 females with r(X) chromosomes.

We studied 47 patients with a 45,X/46,X,r(X) karyotype to identify phenotypic differences between these patients and 45,X patients, and to determine whether these differences could be explained by the status of genes within the ring. Only 2 patients had the 'severe' r(X) phenotype, and both were consistent with this resulting from functional disomy of genes normally subject to X inactivation. A further 7 patients also carried active rings but these patients did not have a more severe phenotype than those whose rings were inactivated, probably because their rings were smaller and did not contain the (as yet unidentified) genes whose functional disomy is particularly damaging. Patients with a r(X) did not show clear physical differences when compared with a 45,X series, except for a possible reduction in the frequency of oedema in those whose r(X) had an Xq breakpoint distal to DXS128E, at Xq13.2. Thus some protection from oedema may be provided by the presence of two copies of Xq13.2.

Adolescent↗

Allogeneic stem cell transplantation. An economic comparison of bone marrow, peripheral blood, and cord blood technologies.

OBJECTIVES: To compare outcome attributes of three available technologies for stem cell transplantation--bone marrow transplantation (BM), peripheral blood cell transplantation (PB), and cord blood transplantation (CB). To compare the cost per recipient for the three technologies, incorporating all donor and antigen matching functions, as well as the transplantation procedures. METHODS: Review of relevant literature using the CancerLit and HealthSTAR databases (plus earlier searches of MEDLINE and Embase) to summarize outcome differences. Estimations of cost per transplant using models drawing on Canadian experience. RESULTS: The literature review indicated that PB may have a modest advantage over BM in terms of outcomes. The literature indicated that CB has longer engraftment times (although this may be due to inadequate controls). Our modeling exercise indicated that costs for PB and BM are similar. CB has a higher cost per recipient, due in large part to the higher testing costs for every donated unit. CONCLUSIONS: Current literature is inadequate to provide an outcomes comparison of CB, PB, and BM. Viewed from a system-wide perspective, CB is a higher cost technique. However, PB and CB are emerging as technologies, and so our results should be viewed alongside the notion that there may be a steep learning curve in these technologies.

Bone Marrow Transplantation↗

CD52 antibodies for prevention of graft-versus-host disease and graft rejection following transplantation of allogeneic peripheral blood stem cells.

Graft-versus-host disease (GVHD) is a major cause of mortality and morbidity after allogeneic bone marrow transplantation, but can be avoided by removing T lymphocytes from the donor bone marrow. However, T cell depletion increases the risk of graft rejection. In this study, two strategies are used to overcome rejection: (1) use of high doses of stem cells obtained from peripheral blood (PBSC), (2) admixture with a CD52 monoclonal antibody in order to deplete both donor and residual recipient lymphocytes. Two antibodies are compared: CAMPATH-1G (rat IgG2b) and its humanized equivalent CAMPATH-1H (human IgG1). A total of 187 consecutive patients at six centers received PBSC transplants from HLA-matched siblings between 1997 and 1999. A wide spectrum of diseases, both malignant and non-malignant, was included. The recovery of CD34+ cells after antibody treatment was close to 100%. The risk of acute GVHD (grade 2 to 4) was 11% in the CAMPATH-1G group and 4% in the CAMPATH-1H group (P = NS). The risk of chronic GVHD (any grade) was 11% in the CAMPATH-1G group and 24% in the CAMPATH-1H group (P = 0.03) but the risk of extensive chronic GVHD was only 2%. The overall risk of graft failure/rejection was 2%, not significantly different between the two antibodies. Antibody treatment was equally effective at concentrations between 10 microg/ml and 120 microg/ml and it made no significant difference to the outcome whether the patients received post-transplant immunosuppression or not (87% did not). Transplant-related mortality in this heterogenous group of patients (including high-risk and advanced disease) was 22% at 12 months. It is proposed that treatment of peripheral blood stem cells with CAMPATH-1H is a simple and effective method for depleting T cells which may be applicable to both autologous and allogeneic transplants from related or unrelated donors. Special advantages of this approach are the simultaneous depletion of donor B cells (which reduces the risk of EBV-associated lymphoproliferative disease) and the concomitant infusion of CAMPATH-1H to deplete residual recipient T cells and thus prevent graft rejection.

Alemtuzumab↗