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Biomedical subjects

J Mason

Publications and source records attributed to J Mason.

At least 37 records · Page 2Linked to original sources
PubMed2002

The cost-effectiveness of population Helicobacter pylori screening and treatment: a Markov model using economic data from a randomized controlled trial.

BACKGROUND: Economic models have suggested that population Helicobacter pylori screening and treatment may be a cost-effective method of reducing mortality from gastric cancer. These models are conservative as they do not consider that the programme may reduce health service peptic ulcer and other dyspepsia costs. We have evaluated the economic impact of population H. pylori screening and treatment over 2 years in a randomized controlled trial and have incorporated the results into an economic model exploring the impact of H. pylori eradication on peptic ulcer disease and gastric cancer. METHODS: Subjects between the ages of 40 and 49 years were randomly invited to attend their local primary care centre. H. pylori status was evaluated by (13)C-urea breath test and infected individuals were randomized to receive omeprazole, 20 mg b.d., clarithromycin, 250 mg b.d., and tinidazole, 500 mg b.d., for 7 days or identical placebos. Economic data on health service costs for dyspepsia were obtained from a primary care note review for the 2 years following randomization. These data were incorporated into a Markov model comparing population H. pylori screening and treatment with no intervention. RESULTS: A total of 2329 of 8407 subjects were H. pylori positive: 1161 were randomized to receive eradication therapy and 1163 to receive placebo. The cost difference favoured the intervention group 2 years after randomization, but this did not reach statistical significance (11.42 ponds sterling per subject cost saving; 95% confidence interval, 30.04 ponds sterling to -7.19 pounds sterling; P=0.23). Analysis by gender suggested a statistically significant dyspepsia cost saving in men (27.17 ponds sterling per subject; 95% confidence interval, 50.01 pounds sterling to 4.32 pounds sterling; P=0.02), with no benefit in women (-4.46 per subject; 95% confidence interval, -33.85 pounds sterling to 24.93 pounds sterling). Modelling of these data suggested that population H. pylori screening and treatment for 1,000,000 45-year-olds would save over 6,000,000 pounds sterling and 1300 years of life. The programme would cost 14, 200 pounds sterling per life year saved if the health service dyspepsia cost savings were the lower limit of the 95% confidence intervals and H. pylori eradication had only a 10% efficacy in reducing mortality from distal gastric cancer and peptic ulcer disease. CONCLUSIONS: Modelling suggests that population H. pylori screening and treatment are likely to be cost-effective and could be the first cost-neutral screening programme. This provides a further mandate for clinical trials to evaluate the efficacy of population H. pylori screening and treatment in preventing mortality from gastric cancer and peptic ulcer disease.

Adult↗
PubMed2002

Topical preparations for the treatment of psoriasis: a systematic review.

BACKGROUND: There is clinical uncertainty about the appropriate use of first-line topical treatments for psoriasis. OBJECTIVES: To assess the relative effectiveness and tolerability of topical treatments for psoriasis suitable for use both in primary and secondary care. METHODS: All major medical databases of published literature were searched electronically; references of trial reports and recent reviews were searched; authors and companies were contacted for missing data from published reports. The study selection comprised: (1) randomized placebo-controlled trials of topical treatments for psoriasis; and (2) randomized head-to-head studies of the new vitamin D3 derivative treatments for psoriasis that reported clinical outcome using a Total Severity Score (TSS), Psoriasis Area Severity Index or Investigator Assessment of Global Improvement. Eligibility and validity were assessed and data extracted independently by two authors. Clinical outcomes were pooled using a random effect standardized weighted mean difference (SWMD) metric, including 3380 patients randomized in 41 placebo (vehicle)-controlled trials and 4898 patients randomized in 28 head-to-head studies. RESULTS: There was a significant benefit in favour of active treatments against vehicle, SWMD: -1.06 (95% confidence interval [CI]: -1.26 to -0.86), approximately a 2-point improvement on a 12-point TSS after 6-8 weeks of treatment. The only significantly different benefit was for very potent corticosteroids: SWMD: -1.51 (95% CI: -1.76 to -1.25), approximately a 3-point improvement on a 12-point TSS. Head-to-head studies support these findings, except that calcipotriol was estimated to be more effective than dithranol, coal tar and other vitamin D3 derivatives. Polytherapy, using a potent steroid and calcipotriol, was more effective than calcipotriol alone: SWMD 0.42 (95% CI: 0.12-0.72 ) approximately a 0.8-point improvement on a 12-point TSS. No important differences in withdrawal or reporting of adverse events were identified. CONCLUSIONS: Trials of short duration neither adequately inform the management of chronic disease nor describe the sequelae of treatment. The evidence base for long-term care, reflecting the disease pathway, should be improved. Combination therapy with topical vitamin D analogues and steroids, and maintenance therapy following treatment response merit further investigation.

Administration, Cutaneous↗
PubMed2002

The role of the trichologist.

The author seeks to establish both the specialty of clinincal trichology and its holistic nature. The myth that trichology is either an alternative therapy or a complimentary therapy is strongly refuted. Comparisons are drawn between the level of service which the trichologist can provide and that which is usually available through traditional medical channels. The training of trichologists is discussed in outline and its strong scientific base is emphasized. Whilst admitting that the majority of trichologists are not medically qualified, the author stresses that trichologists are taught medicine within the limits adequate for professional discharge of their restricted but specialized role. The article concludes by identifying a need for both the public and medical profession to learn how to differentiate between the properly trained and qualified trichologist and the many unqualified charlatans who monopolize publicity and proliferate in the high street. There would appear to be a clear case for better understanding of the profession and what it has to offer.

Allied Health Personnel↗
PubMed2002

Intellectual disability amongst people on probation: prevalence and outcome.

BACKGROUND: Previous research has suggested that people with intellectual disability (ID) can be found in the criminal justice system. However, little is currently known about those supervised in the community on probation orders. METHODS: Ninety people on probation in south-east England were screened using the Learning Disabilities in the Probation Service (LIPS) screening tool, which was designed to be used by probation officers to identify those with possible ID. The LIPS incorporates two measures of cognitive functioning: (1) the Quick Test (QT); and (2) the Clock Drawing Test (CDT). RESULTS: Seven per cent of participants were found to have QT IQs and CDT scores 1.6 SD below the mean. When compared to those who appeared to be functioning within the normal range, those with possible ID were found to be significantly younger. However, no differences were found between the two groups in terms of the final outcome of the probation order. CONCLUSIONS: It seems likely that the probation service contains a significant minority of people with ID. Despite the fact that no difference was found to exist in terms of outcome, people with ID or borderline ID are likely to have a number of support needs which could affect the success of their time on probation.

Adult↗
PubMed2002

Outcome of necrosectomy in acute pancreatitis: the case for continued vigilance.

BACKGROUND: Surgery for pancreatic necrosis complicating acute severe pancreatitis carries a high risk of mortality and may be influenced by a range of variables including patterns of referral, case selection and quality of care. METHODS: An observational study of a consecutive series of 54 patients undergoing pancreatic necrosectomy in a specialist Hepatobiliary unit over an 8-year study period. Principal outcomes were organ dysfunction and physiological derangement in relation to surgery, microbial colonization of necrosis and relation to outcome, re-operation rates, requirement for peri-operative nutritional support, trends in mortality and survival analysis. RESULTS: Necrosectomy was associated with statistically significant deterioration in immediate postoperative organ dysfunction scores (ANOVA P < 0.01). Infected necrosis was present in 36 (68%). Fungal colonization of necrosis was present in 5 (9%). Mortality in this subgroup was 80% (4 deaths). There was no association between bacterial colonization of necrosis and death in this study (P = 0.77; Fisher exact test; relative risk 0.9,95% confidence interval 0.54-1.54). Twenty patients (37%) required further surgical intervention with an average of 1.5 surgical procedures per patient. Twenty-three patients (43%) died. Patient survival to discharge was best predicted by admission APACHE-II score with relative risk of death increasing 14% for each unit increase in APACHE-II score at admission. CONCLUSIONS: The results of the present study illustrate that there is no place for complacency in the surgical management of patients with severe acute pancreatitis. A clinical governance approach would promote pre-defined protocols between admitting hospitals and tertiary referral centres. Future research should target new interventions in patients with high admission APACHE-II scores in whom prognosis is particularly poor and explore the role of infection of necrotic tissue.

APACHE↗
PubMed2002

Late referral for dialysis: improving the management of chronic renal disease.

BACKGROUND: Timely nephrological referral of patients with chronic renal failure (CRF) is important, but referral at a late stage of disease is common. AIM: To investigate whether late referral of patients is avoidable, and where the missed opportunities lie. DESIGN: Prospective ascertainment of new cases and comprehensive review of pre-end stage history. METHODS: Patients admitted to Bristol and Portsmouth renal units for chronic RRT between June 1997 and May 1998 were identified from computer databases. Data were collected from case notes and hospital records, and a self-administered patient questionnaire. Late referral, defined as dialysis within 4 months of first referral to a dialysing nephrologist, was categorized by algorithm as unavoidable or avoidable. RESULTS: Of 250 patients, 96 (38%) were referred late. Forty-three (45%) had definite avoidable reasons: 35 (37%) with raised serum creatinine for a median 3.7 years (IQR 1.5-8.2) before referral, and eight (8%) with risk factors for renal disease but scant assessment of renal function; 12/43 (31%) had a diagnosis of diabetic nephropathy. Late referred patients were less likely to receive standard renal therapies for chronic renal failure, were in a poorer clinical state at start of RRT, and more often required emergency dialysis, compared to patients referred early. Late referrals were as likely from a hospital as a primary care physician. DISCUSSION: A significant proportion of patients are avoidably referred to a dialysing renal unit at a very late stage. Guidelines on referral should be developed by nephrologists, primary and secondary care physicians, and patient groups, and further research is needed into the cost-effectiveness of early referral strategies.

Algorithms↗
PubMed2002

Clinical and economic consequences of dyspepsia in the community.

Dyspepsia is a common problem where many sufferers do not seek healthcare. The clinical impact of the condition in the community and the economic costs were assessed using data from a large cross sectional survey. Dyspepsia may be costing society 1 billion pounds each year in the UK. Thus dyspepsia is a huge clinical and economic burden and cost effective management strategies and treatments are urgently required.

Cost of Illness↗
PubMed2001

When is it cost-effective to change the behavior of health professionals?

Because of the workings of health care systems, new, important, and cost-effective treatments sometimes do not become routine care while well-marketed products of equivocal value achieve widespread adoption. Should policymakers attempt to influence clinical behavior and correct for these inefficiencies? Implementation methods achieve a certain level of behavioral change but cost money to enact. These factors can be combined with the cost-effectiveness of treatments to estimate an overall policy cost-effectiveness. In general, policy cost-effectiveness is always less attractive than treatment cost-effectiveness. Consequently trying to improve the uptake of underused cost-effective care or reduce the overuse of new and expensive treatments may not always make economic sense. In this article, we present a method for calculating policy cost-effectiveness and illustrate it with examples from a recent trial, conducted during 1997 and 1998, of educational outreach by community pharmacists to influence physician prescribing in England.

Cost-Benefit Analysis↗
PubMed2001

Psychiatric illness and mortality after hip fracture.

People with dementia or delirium have increased mortality in the 6 months after hip fracture, but depression might take longer to have an effect. We assessed the psychiatric status of 731 participants with hip fracture and analysed the effect of psychiatric illness on mortality during the next 2 years. We found that dementia, delirium, and depression all increased the risk of mortality (p<0.0001, p<0.0001, and p=0.0359, respectively), and that mortality differed significantly between hospitals (p=0.0003). We suggest that psychiatric interventions should be asssessed in hip-fracture patients with adequate follow up of outcome measures.

Aged↗
PubMed2001

Noninvasive control of stochastic resonance.

External feedback can enhance (or depress) the response of a noisy bistable system to monochromatic signals, significantly magnifying its natural stochastic resonance. We compare and contrast a variety of such feedback strategies, using both numerical simulations and analog electronic experiments. These noninvasive control techniques are especially valuable for noisy bistable systems that are difficult or impossible to modify internally.

Journal Article↗
PubMed2001

Lefty proteins exhibit unique processing and activate the MAPK pathway.

Lefty polypeptides, novel members of the transforming growth factor-beta (TGF-beta) superfamily, are involved in the formation of embryonic lateral patterning. Members of the TGF-beta superfamily require processing for their activation, suggesting cleavage to be an essential step for lefty activation. Transfection of different cell lines with lefty resulted in expression of a 42-kDa protein, which was proteolytically processed to release two polypeptides of 34 and 28 kDa. Since members of the proprotein convertase (PC) family cleave different TGF-beta factors and are involved in the establishment of embryonic laterality, we studied their role in lefty processing. Cotransfection analysis showed that PC5A processed the lefty precursor to the 34-kDa form in vivo, whereas furin, PACE4, PC5B, and PC7 had a limited activity. None of these PCs showed activity in the processing of the lefty polypeptide to the 28-kDa lefty form. The mutation of the consensus sequences for PC cleavage in the lefty protein allowed the lefty cleavage sites to be identified. Mutations of the sequence RGKR to GGKG (amino acids 74-77) and of RHGR to GHGR (amino acids 132-135) prevented the proteolytic processing of the lefty precursor to the 34- and 28-kDa forms, respectively. To identify the biologically active form of lefty, we studied the effect of lefty treatment on pluripotent P19 cells. Lefty did not induce Smad2 or Smad5 phosphorylation, Smad2/Smad4 heterodimerization, or nuclear translocation of Smad2 or Smad4, but activated the MAPK pathway in a time- and dose-dependent fashion. Further analysis showed the 28-kDa (but not the 34-kDa) polypeptide to induce MAPK activity. Surprisingly, the 42-kDa lefty protein was also capable of inducing MAPK activity, indicating that the lefty precursor is biologically active. The data support a molecular model of processing as a mechanism for regulation of lefty signaling.

3T3 Cells↗
PubMed2001

Vascular endothelial growth factor receptor-1 modulates vascular endothelial growth factor-mediated angiogenesis via nitric oxide.

The known responses of vascular endothelial growth factor (VEGF) are mediated through VEGF receptor-2 (VEGFR-2/KDR) in endothelial cells. However, it is unknown whether VEGFR-1 (Flt-1) is an inert decoy or a signaling receptor for VEGF during physiological or pathological angiogenesis. Here we report that VEGF-stimulated nitric oxide (NO) release is inhibited by blockade of VEGFR-1 and that VEGFR-1 via NO negatively regulates of VEGFR-2-mediated proliferation and promotes formation of capillary networks in human umbilical vein endothelial cells (HUVECs). Inhibition of VEGFR-1 in a murine Matrigel angiogenesis assay induced large aneurysm-like structures. VEGF-induced capillary growth over 14 days was inhibited by anti-VEGFR-2-blocking antibody as determined by reduced tube length between capillary connections (P < 0.0001) in an in vitro angiogenesis assay. In contrast, loss of VEGFR-1 activity with a neutralizing anti-VEGFR-1 antibody resulted in an increase in the accumulation of endothelial cells (P < 0.0001) and a dramatic decrease in the number of capillary connections that were restored by the addition of NO donor. Porcine aortic endothelial (PAE) cells expressing human VEGFR-1 but not VEGFR-2 plated on growth factor-reduced Matrigel rearranged into tube-like structures that were prevented by anti-VEGFR-1 antibody or a cGMP inhibitor. VEGF stimulated NO release from VEGFR-1- but not VEGFR-2-transfected endothelial cells and placenta growth factor-1 stimulated NO release in HUVECs. Blockade of VEGFR-1 increased VEGF-mediated HUVEC proliferation that was inhibited by NO donors, and potentiated by NO synthase inhibitors. These data indicate that VEGFR-1 is a signaling receptor that promotes endothelial cell differentiation into vascular tubes, in part by limiting VEGFR-2-mediated endothelial cell proliferation via NO, which seems to be a molecular switch for endothelial cell differentiation.

Cell Division↗
PubMed2001

Gene expression in the embryonic Xenopus liver.

In recent years, significant progress has been made in uncovering the molecular basis of endoderm specification in Xenopus. Much less is understood, however, about endodermal patterning and how endoderm-derived organs such as the liver are formed. Progress has been hampered by the lack of good molecular markers of presumptive liver tissue. Here, we have examined the embryonic expression of a number of marker genes during liver organogenesis, including the transcription factors hex, sox17alpha, and hnf3beta, as well as a number of proteins specific to the adult liver. Interestingly, sox17alpha appears to specifically mark the gall bladder precursors. At 7 days of development expression of the liver differentiation markers albumin, alpha1-microglobulin/bikunin precursor, fibrinogen, transferrin and transthyretin is restricted to the differentiating liver bud. Surprisingly, however, at 3 days of development most of these genes have a more widespread endodermal expression pattern. In addition to expression in the undifferentiated liver bud they were expressed extensively throughout the presumptive intestinal tissue, which may reflect some general feature of how the hepatic gene program is developmentally regulated.

Albumins↗
PubMed2001

TNF alpha promotes proliferation of oligodendrocyte progenitors and remyelination.

Here we used mice lacking tumor necrosis factor-alpha (TNF alpha) and its associated receptors to study a model of demyelination and remyelination in which these events could be carefully controlled using a toxin, cuprizone. Unexpectedly, the lack of TNF alpha led to a significant delay in remyelination as assessed by histology, immunohistochemistry for myelin proteins and electron microscopy coupled with morphometric analysis. Failure of repair correlated with a reduction in the pool of proliferating oligodendrocyte progenitors (bromodeoxyuridine-labeled NG2(+) cells) followed by a reduction in the number of mature oligodendrocytes. Analysis of mice lacking TNF receptor 1 (TNFR1) or TNFR2 indicated that TNFR2, not TNFR1, is critical to oligodendrocyte regeneration. This unexpected reparative role for TNF alpha in the CNS is important for understanding oligodendrocyte regeneration/proliferation, nerve remyelination and the design of new therapeutics for demyelinating diseases.

Animals↗
PubMed2001

Autotransplants for Hodgkin's disease in first relapse or second remission: a report from the autologous blood and marrow transplant registry (ABMTR).

Although patients with relapsed Hodgkin's disease have a poor prognosis with conventional therapies, high-dose chemotherapy and autologous hematopoietic stem cell transplantation (autotransplantation) may provide long-term progression-free survival. We reviewed data from the Autologous Blood and Marrow Transplant Registry (ABMTR) to determine relapse, disease-free survival, overall survival, and prognostic factors in this group of patients. Detailed records from the ABMTR on 414 patients with Hodgkin's disease in first relapse (n = 295) or second complete remission (CR) (n = 119) receiving an autotransplant from 1989 to 1995 were reviewed. Median age was 29 (range, 7-64) years. Median time from diagnosis to relapse was 18 (range, 6-219) months; median time from relapse to transplant was 5 (range, <1-215) months. Most patients received high-dose chemotherapy without total body irradiation for conditioning (n = 370). The most frequently used high-dose regimen was cyclophosphamide, BCNU, VP-16 (CBV) (n = 240). The graft consisted of bone marrow (n = 246), blood stem cells (n = 112), or both (n = 56). Median follow-up was 46 (range, 5-96) months. One hundred-day mortality (95% confidence interval) was 7 (5-9)%. One hundred and sixty-five of 295 patients (56%) transplanted in relapse achieved CR after autotransplantation. Of these, 61 (37%) recurred. Twenty-four of 119 patients (20%) transplanted in CR recurred. The probability of disease-free survival at 3 years was 46 (40-52)% for transplants in first relapse and 64 (53-72)% for those in second remission (P < 0.001). Overall survival at 3 years was 58 (52-64)% after transplantation in first relapse and 75 (66-83)% after transplantation in second CR (P < 0.001). In multivariate analysis, Karnofsky performance score <90% at transplant, abnormal serum LDH at transplant, and chemotherapy resistance were adverse prognostic factors for outcome. Progression of Hodgkin's disease accounted for 69% of all deaths. Autotransplantation should be considered for patients with Hodgkin's disease in first relapse or second remission. Future investigations should focus on strategies designed to decrease relapse after autotransplantation, particularly in patients at high risk for relapse.

Adolescent↗
PubMed2001

The use of primary, secondary, community and social care by families who frequently consult their general practitioner.

There have been very few studies that have examined either the use of other health and social services by patients who frequently consult their general practitioner, or the patterns of service use of frequently attending families. This study has three aims: to quantify the number of contacts to primary, secondary, community and social services of families who frequently attend their general practitioner; to examine the temporal patterns of these contacts and the patterns of use within families; and to determine the nature of these contacts and how they were valued by patients and health professionals. Thirty-five individuals in seven families completed diaries of health service use for 8 weeks; records from primary and community care records were analysed; health professionals and patients provided satisfaction scores for their contacts. The data were compared to standard datasets. The subjects made far more consultations with all health services than predicted, and less than half of these were with the general practitioner. Thirty-two per cent of the contacts with staff based within the health centre were not reported on the diary sheets. Temporal patterns of consulting were apparent within the families. The "index frequent attenders" within each family had most contacts. The differences between professional groups for the nature of the contact were marked, with over two-thirds of general practitioner contacts being for "specific symptoms or problems", and over two-thirds of health visitor contacts being for "weight problems". These findings show that patients who make high use of general practitioners' services also have a large number of contacts for health reasons with a range of other health and social services. These need to be considered as an outcome measure for trials of intervention for frequent attendance. More work is needed to explore why some individuals and their families make high use of health services.

Community Health Services↗
PubMed2001

Effect of aprotinin on endothelial cell activation.

BACKGROUND: Cardiopulmonary bypass surgery is often accompanied by a systemic inflammatory response, which can lead to postoperative complications in high-risk patients. This is mediated in part through a systemic rise in inflammatory cytokine levels and the sequestration of leukocytes within organs. Aprotinin has previously been shown to exert an anti-inflammatory effect by preventing the capacity of leukocytes to transmigrate through vascular endothelium. Here we have focused on whether aprotinin has an effect on endothelial cell activation and adhesion molecule expression in response to tumor necrosis factor-alpha, particularly with reference to whether aprotinin inhibits tumor necrosis factor-stimulated neutrophil transendothelial migration. METHODS AND RESULTS: Intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin expression was studied in tumor necrosis factor-alpha-activated human umbilical vein endothelial cells in the presence of aprotinin at 200, 800, and 1600 kIU/mL. Aprotinin inhibited tumor necrosis factor-alpha-stimulated expression of intercellular adhesion molecule-1 (P =.019 at 1600 kIU/mL) and vascular cell adhesion molecule-1 (P =.003 at 1600 kIU/mL) but not E-selectin. Similar results were obtained in the dermal microvascular endothelial cell line, HMEC-1, which exhibited diminished intercellular adhesion molecule-1 expression in the presence of aprotinin (P =.040 at 800 kIU/mL and P <.001 at 1600 kIU/mL). Aprotinin also significantly inhibited neutrophil transmigration across tumor necrosis factor-alpha-activated human umbilical vein endothelial cells (P =.046 at 1600 kIU/mL). CONCLUSIONS: We have demonstrated that aprotinin inhibits intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, but not E-selectin, expression on tumor necrosis factor-alpha-activated endothelial cells and that transendothelial migration by neutrophils is also specifically suppressed under these conditions. Our results indicate that endothelial cells can be specifically targeted by aprotinin, therefore adding to our understanding of the anti-inflammatory mechanism of action of aprotinin during cardiopulmonary bypass.

Aprotinin↗