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PubMed1994

The intelligent decision mapping patient record (IDMR).

IDMR explored in a representative group of diseases, the design of a European patient record, structured on the decisions made by the doctors in caring for patients throughout their hospitalisation in each country of the European Community. Over 350 patients involving 6000 decisions were entered in the database. Working programs in FoxPro and Windows, a demo Apple program and an expert system in Prolog were delivered. The approach worked well. The catalogue of decisions and costs was illuminating. The complexity of a telematics patient record and the clinical work needed to produce it may be underestimated.

Decision Support Techniques↗
PubMed2026

In vivo CAR-T therapy: The shift from ex vivo culturing to direct in situ immune reprogramming.

CAR T-cell therapy using chimeric antigen receptors (CARs) has provided a radical shift in the treatment of several hematological malignancies, producing high response rates and durable remissions. However, conventional ex vivo manufacturing is limited by complex processing steps, high costs, variability in product quality, and clinically relevant delays that restrict patient eligibility. In vivo manufacturing has emerged as a next-generation approach in which immune cells are reprogrammed directly within the patient, eliminating the need for exogenous handling and culture. This strategy uses viral and non-viral delivery platforms, including lentiviral vectors, adeno-associated viruses, lipid nanoparticles, and targeted polymer systems, together with DNA, mRNA, and genome editing tools such as CRISPR-based technologies. Early feasibility data are supported mainly by preclinical models and translational studies, while safety remains a central concern due to potential immunotoxicity, off-target transduction, and regulatory challenges. This review highlights key engineering strategies enabling in vivo CAR T-cell generation, summarizes emerging clinical research and development, and discusses future opportunities for expanding in vivo CAR T-cell therapies as scalable immunotherapy platforms.

Humans↗
PubMed2005

A cross-talk between RNA splicing and signaling pathway alters Fas gene expression at post-transcriptional level: alternative splicing of Fas mRNA in the leukemic U937 cells.

It is now widely accepted that alternative splicing is a mechanism that is responsible for generating protein complexity at low genetic cost. However, little is known about molecular mechanisms that govern alternative splicing of key apoptotic regulators. Here we investigate the effect of pro-apoptotic stimuli on alternative splicing of Fas mRNA by means of reverse transcription-polymerase chain reaction (RT-PCR). Exposure of U937 cells to etoposide, staurosporine, pacritaxel, or cyclohexamide promoted the appearance of the splice variant, which retained the 152-base-pair intron 5. Pretreatment with calyculin A, an inhibitor of protein phosphatase-1 (PP-1) as well as fumonisin B1, an inhibitor of ceramide synthase, prevented etoposide-induced alternative splicing of Fas mRNA. Our data demonstrate that cross-talk between RNA splicing and signaling pathways through endogenous ceramide synthesis and subsequent phosphatase activation is a mechanism that modifies Fas gene expression at the posttranscriptional level.

Alternative Splicing↗
PubMed1996

Clinical practice, ethics and economics: the physician at the crossroads.

In recent years health services have faced the challenge of increasingly complex services and rising costs, thus the consideration of costs is a key factor in health policy decisions. The introduction of an economic perspective has sometimes been viewed as conflicting with the ethics of the health care system, especially at the physician-patient level. this article explores the important role of the physician from the ethical and economic perspective in the distribution and allocation of services. An understanding of economic and ethical principles reveals that these two perspectives are compatible with good clinical practice: more efficient health care implies better care for the individual patient and makes it possible to increase the resources available to improve care for the population as a whole. Thus, being efficient is an ethical objective. The selective elimination of ineffective services would free resources to care for those who need effective diagnostic or therapeutic procedures. This requires a better understanding of the determinants and outcomes of clinical practice, physician motivation, the appropriate design and application of incentives, and the best use of limited resources. The physician can play a key role in increasing the efficiency, equity, and quality of the health system without restricting the provision of effective services.

Conflict of Interest↗
PubMed2002

Deposition and pharmacokinetics of budesonide from the Miat Monodose inhaler, a simple dry powder device.

Dry powder inhalers (DPIs) are used to deliver asthma drugs to patients, but lung deposition may depend upon the degree of inspiratory effort. The pulmonary deposition of the glucocorticosteroid budesonide (SMB-Galephar) has been assessed in 12 asthmatic patients when delivered by the Monodose inhaler (Miat, Milan, Italy); the Pulmicort Turbuhaler DPI (AstraZeneca, Lund, Sweden) was used as a comparator product. Patients inhaled from each device with maximal or sub-maximal inspiratory effort: Monodose inhaler 90 vs 45 l/min; Turbuhaler DPI 60 vs 30 l/min. The formulations were radiolabelled with (99m)Tc, and deposition of budesonide was quantified by gamma scintigraphy. Mean (SD) whole lung deposition for the Monodose inhaler (% capsule dose), was independent of inspiratory effort (maximal: 21.4 (4.3)%; sub-maximal: 21.4 (7.5)%), while lung deposition for the Turbuhaler DPI (% metered dose) fell significantly with decreasing inspiratory effort (maximal: 25.1 (6.1)%; sub-maximal: 18.5 (6.5)%; P<0.05). The plasma concentrations of budesonide showed the same trends as the whole lung deposition data. The Monodose inhaler showed inspiratory effort-independent drug delivery characteristics, and could prove be a valuable low-cost alternative to more complex devices such as the Turbuhaler DPI. The Monodose inhaler may be especially useful in groups of patients unable to inhale maximally through DPIs, including young children and adult patients with severe respiratory impairment.

Administration, Inhalation↗
PubMed2003

Development of an animal-human antibody complex for use as a control in ELISA.

In order to provide the equivalent of a human anti-human protein antibody as positive control in ELISAs, a goat-human antibody complex was created using chemical cross-linking. The resulting hybrid complex had a larger molecular size on HPLC and SDS-PAGE. In ELISA, the goat-human complex bound to human antigen and was detectable by a secondary anti-human conjugate. The method to make the hybrid complex is simple, cost-effective and can be used to make human-like antibodies to many human proteins.

Animals↗
PubMed2000

The future of orthopaedics in the United States: an analysis of the effects of managed care in the face of an excess supply of orthopaedic surgeons.

Recent technological advances in orthopaedic surgery have propelled both the volume of surgical cases and their complexity, resulting in increased costs, which should naturally result in higher incomes for surgeons. However, the transition from a fee-for-service model of physician compensation to a managed care model has resulted in major shifts in economic resource allocation. An economic model of this market based on imperfect competition shows that these changes have shifted market power from surgeons to the managed care organizations. Our model predicts that practicing surgeons will retire earlier, medical students will begin to select other specialties, and innovation will be slowed. Antitrust laws limit surgeons' ability to combat this trend through meaningful collective bargaining, creating the potential for future shortages as the baby boom generation reaches retirement age and the demand for orthopaedic services increases dramatically.

Education, Medical↗
PubMed1998

Monotherapy versus polytherapy in epilepsy: a framework for patient management.

The long-standing debate between proponents of monotherapy and those of polytherapy for treatment of epilepsy has been rekindled by the recent development of several new antiepileptic drugs. The likelihood of improved seizure control on polytherapy must be weighed against the risk of increased side effects, complex drug interactions and cost. Providing maximal seizure control while avoiding overtreatment is a challenge which requires an ongoing critical evaluation of each patient's management. This review provides a framework for decision-making by considering issues affecting the choice between monotherapy and polytherapy in five clinical situations: 1) newly diagnosed epilepsy; 2) seizures on monotherapy; 3) seizures controlled on polytherapy; 4) not controlled on polytherapy; 5) change in medical condition.

Anticonvulsants↗
PubMed2005

Uncommon dementia and the carer's perspective.

There is much caregiving literature describing factors that affect carer burden, and interventions that may be useful for carers of those with common dementias such as Alzheimer's disease (AD). By contrast, relatively little information and few data are available on potentially diverse issues facing carers of those with uncommon dementias, such as frontotemporal dementia (FTD), Huntington's disease (HD) and human immunodeficiency virus (HIV) dementia. This paper highlights particular characteristics of caregiving for those with uncommon dementias, and the unique needs that may arise for this group of carers who often "fall between the net" of services and supports available. Further research into this area is required.

AIDS Dementia Complex↗
PubMedDate not supplied

Disasters and development: Part 3: Assessing trade-offs in investing in vulnerability reduction.

This lesson describes how a government decides whether and how much it should spend on vulnerability reduction. There are techniques and methods by which decision-makers compare development alternatives. The differences between the risk that a potentially catastrophic event will occur and uncertainty are described, with uncertainty providing greater difficulty in economic analyses. There is a range of methods for identifying the complex mix of competing costs and benefits associated with any restructuring of investment priorities to accomplish disaster mitigation. The possibilities are described in terms of the opportunity costs and present value. Impact and consequent losses include: (1) direct monetary effects; (2) indirect monetary effects; (3) direct, non-monetary effects; (4) indirect, non-monetary effects; and (5) loss of non-renewable natural resources. The difficulties in assigning values to these effects are described, as well as the means of judging the cost-effectiveness of such interventions. An advantage of screening projects using a framework of analytical methods is that it can assist in focusing on a variety of possible outcomes and make the factors influencing these outcomes quite explicit.

Cost-Benefit Analysis↗
PubMedDate not supplied

Continuous beer fermentation using immobilized yeast cell bioreactor systems.

Traditional beer fermentation and maturation processes use open fermentation and lager tanks. Although these vessels had previously been considered indispensable, during the past decades they were in many breweries replaced by large production units (cylindroconical tanks). These have proved to be successful, both providing operating advantages and ensuring the quality of the final beer. Another promising contemporary technology, namely, continuous beer fermentation using immobilized brewing yeast, by contrast, has found only a limited number of industrial applications. Continuous fermentation systems based on immobilized cell technology, albeit initially successful, were condemned to failure for several reasons. These include engineering problems (excess biomass and problems with CO(2) removal, optimization of operating conditions, clogging and channeling of the reactor), unbalanced beer flavor (altered cell physiology, cell aging), and unrealized cost advantages (carrier price, complex and unstable operation). However, recent development in reactor design and understanding of immobilized cell physiology, together with application of novel carrier materials, could provide a new stimulus to both research and application of this promising technology.

Beer↗
PubMed2001

Executive control of cognitive processes in task switching.

In 4 experiments, participants alternated between different tasks or performed the same task repeatedly. The tasks for 2 of the experiments required responding to geometric objects in terms of alternative classification rules, and the tasks for the other 2 experiments required solving arithmetic problems in terms of alternative numerical operations. Performance was measured as a function of whether the tasks were familiar or unfamiliar, the rules were simple or complex, and visual cues were present or absent about which tasks should be performed. Task alternation yielded switching-time costs that increased with rule complexity but decreased with task cuing. These factor effects were additive, supporting a model of executive control that has goal-shifting and rule-activation stages for task switching. It appears that rule activation takes more time for switching from familiar to unfamiliar tasks than for switching in the opposite direction.

Cognition↗
PubMed2024

The importance of family-based sampling for biobanks.

Biobanks aim to improve our understanding of health and disease by collecting and analysing diverse biological and phenotypic information in large samples. So far, biobanks have largely pursued a population-based sampling strategy, where the individual is the unit of sampling, and familial relatedness occurs sporadically and by chance. This strategy has been remarkably efficient and successful, leading to thousands of scientific discoveries across multiple research domains, and plans for the next wave of biobanks are underway. In this Perspective, we discuss the strengths and limitations of a complementary sampling strategy for future biobanks based on oversampling of close genetic relatives. Such family-based samples facilitate research that clarifies causal relationships between putative risk factors and outcomes, particularly in estimates of genetic effects, because they enable analyses that reduce or eliminate confounding due to familial and demographic factors. Family-based biobank samples would also shed new light on fundamental questions across multiple fields that are often difficult to explore in population-based samples. Despite the potential for higher costs and greater analytical complexity, the many advantages of family-based samples should often outweigh their potential challenges.

Humans↗
PubMed1997

Clinical economics review: liver transplantation.

The economic assessment of liver transplantation is complex and involves the cost of the transplant procedure, the cost of alternative treatments and the positive economic contribution of successful outcomes. The one-year survival rates are currently in the order of 80-90% for elective transplants and 60-75% for emergency transplantation. The average cost of a liver transplant operation in the UK is between pounds 32,000 and pounds 45,000. Factors which have a major influence on costs are aetiology, patient status at the time of transplantation, retransplantation and duration of hospital stay. Rejection episodes, renal impairment and surgical complications are of intermediate importance. The cost of transplantation must be balanced against the cost of alternative treatments that would be required if the patient were not transplanted and the positive economic benefit derived from excellent rehabilitation in the majority of recipients.

Drug Costs↗
PubMed2000

Bacteriophages as indicators of enteric viruses and public health risk in groundwaters.

Low concentrations of all types of bacteriophages in groundwater limit their power to predict the presence of enteric viruses. There is little concordance in the literature regarding phage detection methods, thus making comparisons extremely difficult. Different authors have used different hosts, phage concentration methods, and end-point determinations. Also, markedly different volumes of sample have been employed, varying from 1 litre to 400 l. Bacteriophage concentration methods are not reproducible. There has been marked variability among groups in the natural substrates used (for example, beef extract), the type of adsorbing filter used, centrifugation instruments and conditions, and the delivery of the concentrate to the host cells. There is no consensus on the best bacterial host strain. Currently, several are employed with each showing differential sensitivities and specificities. In particular, host stability must be considered. Host stability has two components: the ability of the host to continue to be receptive to the bacteriophage after continued sub-culture, and the lack of lysogenic or temperate bacteriophage in the host cell line which may be randomly and unpredictably activated. There is a lack of consistent recovery of bacteriophages from individual faecal specimens. In particular, only approximately 3% of individual humans carry the FRNA phages. While there is some evidence to indicate that the phages multiply in sewage, it is not clear how they do so since the host pili should not be produced at lower temperatures. These ecological factors need to be understood. Of all the phages thus far studied, Bacteroides fragilis HSP40 has the highest recovery rate from individual people. However, Bacteroides, being an anaerobe, is a difficult host for routine laboratory analysis. Methods for the enumeration of F(+)-specific phages and Bacteroides phages are complex, time-consuming, costly and not reproducible. Conversely, somatic coliphage methods are simpler and results can be available in 4-6 h. The occurrence of phages and viruses in groundwater depends on physicochemical characteristics that control their fate and transport in the groundwater/aquifer environment. There are very little actual data taken from the field that allow an understanding of the ecology and life span of phages in their natural environment. Moreover, the ability of phages to serve as a source of food for other microbes needs to be understood. There has been a lack of association of bacteriophage recovery with gastroenteritis outbreaks due to enteric viruses. There is only a small epidemiological database concerning the occurrence of enteric viruses in groundwater.

Animals↗
PubMed2001

Does the interponat affect outcome after esophagectomy for cancer?

Clinical decision-making in esophageal cancer surgery is a process of balancing the risks of treatment against potential benefits, such as survival and quality of life. Various options are available for esophageal reconstruction. While these reconstructive options do not directly have an impact on cancer survival, they do affect operative morbidity and long-term quality of life. The affect of various interponats (reconstructive conduits) and routes of reconstruction on operative morbidity and foregut function is reviewed. Gastric interponats are preferred for esophageal reconstruction because of their reliable vascularity and the relative simplicity of the reconstructive operation. Colon interponats supposedly provide better long-term function as an esophageal substitute (unproven), but at the cost of increased operative complexity and morbidity. Colon interposition is therefore reserved for situations in which gastric transposition is not feasible. Both posterior and anterior mediastinal routes of gastric interponat reconstruction are acceptable (meta-analysis of randomized controlled trials). Posterior mediastinal reconstruction is usually preferred when a complete (R0) resection has been accomplished. Anterior mediastinal reconstruction may prevent secondary dysphagia after incomplete (R1, R2) resections.

Esophageal Neoplasms↗
PubMed2001

Is appendiceal CT scan overused for evaluating patients with right lower quadrant pain?

Reports citing excellent sensitivity, specificity, and predictive accuracy of focused appendiceal computed tomography (CT) and showing an overall reduction in resource use and nontherapeutic laparotomies have led to increasing use of that imaging modality. Diagnostic algorithms have begun to incorporate appendiceal CT for patients presenting to the emergency department with right lower quadrant pain. We present a series of 4 cases in which use of appendiceal CT ultimately led to increased cost, resource use, and complexity in patient care. The results of these cases support an argument against unbridled use of appendiceal CT scanning and reinforce the need for clinical evaluation by the operating surgeon before routine performance of appendiceal CT scan.

Abdominal Pain↗
PubMed1999

The intensity of physicians' work in patient visits--implications for the coding of patient evaluation and management services.

BACKGROUND: Clinicians use visit codes to bill for services involving the evaluation of patients and the management of their care. The existing guidelines for coding and documenting these services, as well as proposed revisions, have been criticized as complex, clinically irrelevant, and costly. We investigated whether easily measured characteristics of physician-patient visits accurately reflect differences in the amount of work performed. Such characteristics might provide the basis for a simple and equitable physician-payment scheme. METHODS: We collected information about the amount of physicians' work, the time spent in encounters with patients, and characteristics of patients and visits for 19,143 physician-patient visits in the practices of 339 urologists, rheumatologists, and general internists. Physicians recorded the actual time involved in evaluating the patient and managing his or her care during each visit and estimated the work involved in relation to a standardized, hypothetical visit. We used multivariate linear regression to identify factors related to differences in the total amount of work and to calculate work and work intensity (work per minute) for different types of visits. RESULTS: The duration of the face-to-face encounter with the patient or family (encounter time) was strongly predictive of the total amount of work. Total work, however, did not increase in direct proportion to encounter time. Visits with shorter encounter times were more intense than longer ones, in part because the work involved in providing fixed services, such as review of records and entry of information, did not vary in direct proportion to the length of the face-to-face encounter. Work intensity was greater for new patients than for established patients, for patients referred by other physicians than for those who were not, and for patients with new rather than previously existing problems. CONCLUSIONS: A simple coding scheme based on time spent by the physician in the face-to-face encounter and a limited set of characteristics of the visit would accurately reflect total work in actual practice. A fee structure based on these factors and the inverse relation between work per minute and the encounter time would provide equitable payment while encouraging efficiency and discouraging "upcoding" of services.

Data Collection↗