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PubMed1998

Cost effectiveness of shortening screening interval or extending age range of NHS breast screening programme: computer simulation study.

OBJECTIVE: To compare the cost effectiveness of two possible modifications to the current UK screening programme: shortening the screening interval from three to two years and extending the age of invitation to a final screen from 64 to 69. DESIGN: Computer simulation model which first simulates life histories for women in the absence of a screening programme for breast cancer and then assesses how these life histories would be changed by introducing different screening policies. The model was informed by screening and cost data from the NHS breast screening programme. SETTING: North West region of England. MAIN OUTCOME MEASURES: Numbers of deaths prevented, life years gained, and costs. RESULTS: Compared with the current breast screening programme both modifications would increase the number of deaths prevented and the number of life years saved. The current screening policy costs 2522 pounds per life year gained; extending the age range of the programme would cost 2612 pounds and shortening the interval 2709 pounds per life year gained. The marginal cost per life year gained of extending the age range of the screening programme is 2990 pounds and of shortening the screening interval is 3545 pounds. CONCLUSIONS: If the budget for the NHS breast screening programme were to allow for two more invitations per woman, substantial mortality reductions would follow from extending the age range screened or reducing the screening interval. The difference between the two policies is so small that either could be chosen.

Age Factors↗

PubMed2003

Cost effectiveness of extended treatment with low molecular weight heparin (dalteparin) in unstable coronary artery disease: results from the FRISC II trial.

BACKGROUND: In unstable coronary artery disease short term treatment with low molecular weight heparin in addition to aspirin has been shown to be effective. OBJECTIVE: To assess the cost effectiveness of extended treatment with dalteparin in patients managed with a non-invasive treatment strategy. DESIGN: Prospective, randomised, multicentre study. SETTING: 58 centres in Sweden, Denmark, and Norway, of which 16 were interventional. PATIENTS: After at least five days' treatment with open label dalteparin, 2267 patients were randomised to continue double blind treatment with either subcutaneous dalteparin twice daily or placebo for three months. The patients' use of health service resources was recorded prospectively. MAIN OUTCOME MEASURE: Death/myocardial infarction. RESULTS: After one month into the double blind period there was a 47% relative reduction in death or myocardial infarction in the dalteparin group compared with the placebo group (p = 0.002). There was a non-significant mean cost difference, favouring the placebo group, of 849 Swedish crowns (SEK) per patient (equivalent to 58 pounds sterling). The incremental cost effectiveness ratio for giving dalteparin treatment for one month was SEK 30 300 (range -78 000 to 139 000) (2060 pounds sterling, range -5300 pounds sterling to pound 9400 pounds sterling) per avoided death or myocardial infarct. At three months, the decrease in death or myocardial infarction was not significant, precluding cost effectiveness analyses. CONCLUSIONS: There is a marginal and non-significant increase in costs for one month of extended dalteparin treatment compared with placebo. Extended dalteparin treatment lowers the risk of death or myocardial infarction in patients with unstable coronary artery disease. While in many countries the resources for early intervention are limited, extended dalteparin treatment up to one month is a cost effective bridge to invasive intervention.

Adult↗

PubMed1988

Corelease of amidated and glycine-extended antral gastrins after a meal.

Glycine-extended gastrin, the immediate precursor of bioactive (i.e., carboxyamidated) gastrin, was recently identified in antral tissue and in peripheral blood. Studies on pituitary cell lines have shown that although only bioactive peptides are released along the regulated pathway, i.e., stored at high concentrations in secretory granules and released upon appropriate stimulation, the release of precursors is constitutive, i.e., secreted continuously without secretagogue stimulation. To determine whether the secretion of glycine-extended gastrin from the antral G-cell is regulated, meal-induced release was examined. In anesthetized pigs (n = 8) the antral veins were catheterized and blood was collected continuously before and after intragastric instillation of meat extract. Surgical biopsies of antral mucosa were obtained from six animals. Glycine-extended and amidated gastrins were measured and characterized by radioimmunoanalysis and chromatography. The results demonstrate that glycine-extended gastrin is released in a regulated manner from antral G-cells and furthermore the component pattern is identical in mucosa and blood.

Amines↗

PubMed1999

COOH-terminally extended secretins are potent stimulants of pancreatic secretion.

Posttranslational processing of preprosecretin generates several COOH-terminally extended forms of secretin and alpha-carboxyl amidated secretin. We used synthetic canine secretin analogs with COOH-terminal -amide, -Gly, or -Gly-Lys-Arg to examine the effects of COOH-terminal extensions of secretin on bioactivity and detection in RIA. Synthetic products were purified by reverse-phase and ion-exchange HPLC and characterized by reverse-phase isocratic HPLC and amino acid, sequence, and mass spectral analyses. Secretin and secretin-Gly were noted to coelute during reverse-phase HPLC. In RIA using eight different antisera raised against amidated secretin, COOH-terminally extended secretins had little or no cross-reactivity. Bioactivity was assessed by measuring pancreatic responses in anesthetized rats. Amidated canine and porcine secretins were equipotent. Secretin-Gly and secretin-Gly-Lys-Arg had potencies of 81 +/- 9% (P > 0.05) and 176 +/- 13% (P < 0.01), respectively, compared with amidated secretin, and the response to secretin-Gly-Lys-Arg lasted significantly longer. These data demonstrate that 1) amidated secretin and secretin-Gly are not separable under some chromatographic conditions, 2) current RIA may not detect bioactive COOH-terminally extended forms of secretin in tissue extracts or blood, and 3) the secretin receptor mediating stimulation of pancreatic secretion recognizes both amidated and COOH-terminally extended secretins.

Amino Acid Sequence↗

PubMed2006

Hypothermia-induced cardioprotection using extended ischemia and early reperfusion cooling.

Optimal timing of therapeutic hypothermia for cardiac ischemia is unknown. Our prior work suggests that ischemia with rapid reperfusion (I/R) in cardiomyocytes can be more damaging than prolonged ischemia alone. Also, these cardiomyocytes demonstrate protein kinase C (PKC) activation and nitric oxide (NO) signaling that confer protection against I/R injury. Thus we hypothesized that hypothermia will protect most using extended ischemia and early reperfusion cooling and is mediated via PKC and NO synthase (NOS). Chick cardiomyocytes were exposed to an established model of 1-h ischemia/3-h reperfusion, and the same field of initially contracting cells was monitored for viability and NO generation. Normothermic I/R resulted in 49.7 +/- 3.4% cell death. Hypothermia induction to 25 degrees C was most protective (14.3 +/- 0.6% death, P < 0.001 vs. I/R control) when instituted during extended ischemia and early reperfusion, compared with induction after reperfusion (22.4 +/- 2.9% death). Protection was completely lost if onset of cooling was delayed by 15 min of reperfusion (45.0 +/- 8.2% death). Extended ischemia/early reperfusion cooling was associated with increased and sustained NO generation at reperfusion and decreased caspase-3 activation. The NOS inhibitor N(omega)-nitro-L-arginine methyl ester (200 microM) reversed these changes and abrogated hypothermia protection. In addition, the PKCepsilon inhibitor myr-PKCepsilon v1-2 (5 microM) also reversed NO production and hypothermia protection. In conclusion, therapeutic hypothermia initiated during extended ischemia/early reperfusion optimally protects cardiomyocytes from I/R injury. Such protection appears to be mediated by increased NO generation via activation of protein kinase Cepsilon; nitric oxide synthase.

Animals↗

PubMed1998

Extended radical Whipple resection for cancer of the pancreatic head: operative procedure and results.

Pancreatoduodenectomy is now the most fundamental operation for cancer of the pancreatic head. However, with the conventional operative procedure, the resection rate is low and long-term results are extremely poor. We introduced an extended radical Whipple operation in 1978 to improve surgical curability. Systemic dissection of extended lymph nodes and plexuses and en bloc resection of the portal vein was the basic concept. The resection rate for cancer of the pancreatic head has improved from 7-20 to 50%. The curative resection rate has also improved from 10 to 40-50%. The extended procedure did not increase the risk of the Whipple operation. When curative surgery was performed, good long-term survival was expected even in cases of extensive invasion to the portal vein. As a result, 11 patients who underwent curative surgery have survived for a long period of time. At present, however, the majority of patients are in an advanced stage at diagnosis and extended radical operation plays an important role in the curative therapy for this condition.

Aged↗

PubMed1999

Extended pancreatectomy and liver perfusion chemotherapy for resectable adenocarcinoma of the pancreas.

In order to increase the long-term survival after resection of pancreatic adenocarcinoma, it is essential to eradicate both locoregional recurrence and hepatic metastasis. We have added a wide range of lymphatic and connective tissue clearance to conventional pancreatectomy (extended pancreatectomy) and succeeded in improving the 5-year survival rate from 8 to 25% via decreasing the incidence of local failure. Among many procedures which together compose an extended pancreatectomy, connective tissue clearance seems to have played a more important role on patients' prognosis rather than wide range lymphadenectomy. Concomitant resection of the portal vein is recommended for selected patients, and it is important not to overlook a minute invasion even though it appears macroscopically intact. With regard to adjuvant therapy in combination with our extended pancreatectomy, the addition of preoperative irradiation failed to further improve the long-term survival rate because the cause of cancer deaths shifted from local recurrence to hepatic metastasis. When liver perfusion chemotherapy was added to this operation (without radiation), the 5-year survival rate was improved to 39% by decreasing the incidence of hepatic metastasis. In the future, a combination of extended pancreatectomy with chemoradiation plus liver perfusion chemotherapy is one of the promising approaches for this cancer.

Adenocarcinoma↗

PubMed2000

New insights into extended prophylaxis after orthopaedic surgery - the North American Fragmin Trial experience.

It is well-known that peri-operative and post-operative venous thrombosis are common. Trials in Europe have shown that extended out-of-hospital prophylaxis with a low-molecular-weight heparin reduces the rate of deep vein thrombosis in patients undergoing elective hip surgery. North American investigators of limited-outcome descriptive studies, however, have suggested that out-of-hospital prophylaxis is not necessary. To resolve this uncertainty, NAFT (North American Fragmin Trial) was conducted, the results of which are summarized in this paper. The findings of NAFT support the favourable findings of the European studies on extended prophylaxis. Furthermore, European data have shown extended out-of-hospital prophylaxis to be cost-effective. On the basis of the aggregate data, it is felt that the A2 recommendation made by the Fifth American College of Chest Physicians consensus conference for extended prophylaxis should be changed to an A1 recommendation.

Anticoagulants↗

PubMedDate not supplied

Extended liver resection and hepatic ischemia in pigs: a new, potentially reversible model to induce acute liver failure and study artificial liver support systems.

BACKGROUND: Extended hepatectomy is a valid model for the study of acute liver failure. Since the porcine liver is comparable in size, morphology and anatomy to the human liver, we describe a technique employing hepatic ischemia and extended liver resection to induce acute liver failure in a porcine model as a means of studying bioartificial liver support. METHOD: A subtotal (75-80% resection) extended left hepatectomy was performed in 7 pigs after 60 min warm ischemia of the future remnant liver. After resection, the animals were given the best supportive care and observed until death. RESULTS: All animals died within 18-48 h, none as a result of surgical complications. Gross appearance of the liver showed severe steatosis of the right lateral lobe, and histology revealed severe coagulative necrosis of the whole lobule. CONCLUSION: This technique of extended liver resection after hepatic ischemia in the porcine model may be useful for studies of potentially reversible acute liver failure and experimental bioartificial support.

Animals↗

PubMed2003

Pilot comparison of extended-release and standard preparations of divalproex sodium in patients with bipolar and schizoaffective disorders.

OBJECTIVE: The authors compared the new extended-release and standard preparations of divalproex sodium. METHOD: Twelve patients with DSM-IV bipolar disorder or schizoaffective disorder who were clinically stable while taking the standard form of divalproex participated in the study. These patients were given a single daily dose of the extended-release preparation of divalproex in an open 6-week trial. Clinical symptoms and adverse effects were rated weekly. Doses were adjusted to maintain steady serum valproate concentrations. RESULTS: The medication change was associated with negligible changes in clinical status and tolerability. To maintain serum drug levels, however, 21% higher doses of the extended-release preparation were required. CONCLUSIONS: Use of extended-release divalproex once a day was as well tolerated as the standard preparation, with no change in efficacy within 6 weeks, but the daily dose needed to maintain stable serum valproic acid concentration was 21% higher.

Ambulatory Care↗

PubMed2001

Assessing predictive factors for extended hospitalization at acute psychiatric admission.

OBJECTIVE: This study examined whether information obtained early in the hospitalization process can be used to assess a patient's need for extended care. METHODS: A sample of 2,430 inpatients who were admitted to a state psychiatric facility during a one-year index period (January through December 1997) were randomly assigned to a primary sample or a replication sample. Data were collected on demographic characteristics and history of previous hospitalization. The Brief Psychiatric Rating Scale-Anchored Version (BPRS-A) was administered to patients within 48 hours of admission, and four new subscales derived from ratings of newly admitted patients were calculated. Univariate and multivariate analyses were conducted to identify factors associated with whether a patient was discharged to the community or transported to another hospital for extended care. RESULTS: A discriminant analysis of the data correctly identified 70 percent of the patients who were referred for continued hospitalization and 80 percent of the patients who were discharged to the community. The main correlates of the need for extended inpatient services were, in descending order, scores on the BPRS-A resistance subscale, the number of previous referrals for extended hospitalizations, and scores on the BPRS-A positive symptoms and psychological discomfort scales. CONCLUSIONS: BPRS-A subscale scores should be considered to be at least as good as more traditional measures in predicting length of hospitalization.

Adult↗

PubMedDate not supplied

Extended supraglottic laryngectomy. Review of 84 cases.

Extended supraglottic laryngectomy is a surgical procedure by which the boundaries of standard supraglottic laryngectomy are extended to include the base of the tongue and/or pyriform sinus and/or one of the arytenoids, according to the extent of epilaryngeal or extralaryngeal invasion by vestibular cancer. We report the results of 84 extended supraglottic laryngectomies performed by our group from 1970 to 1980. Besides the highly favorable 5-year cure rate (75%), full functional rehabilitation followed in all but three patients, who were therefore submitted to secondary total laryngectomy. Rehabilitation time is often somewhat longer than in standard supraglottic laryngectomy, especially when an ample resection of the base of the tongue is required. Combined resection of the base of the tongue, aryepiglottic fold, and one of the arytenoids may further lengthen the rehabilitation period. We believe that extended supraglottic laryngectomy should be performed more often, not only for actual invasion, but also for suspected invasion of extralaryngeal structures.

Humans↗

PubMed1994

Influence of extended wakefulness on automatic and nonautomatic processing.

We investigated the influence of extended wakefulness on automatic and nonautomatic processes in memory and visual search tasks. Subjects were trained in consistently mapped and variably mapped versions of each task, attaining automatic performance in the consistently mapped versions. We then recorded performance measures and event-related brain potentials for a 14-h period that began during the evening of the last day of training. Overall performance declined with extended wakefulness, but the benefits of consistently mapped training were retained throughout the night. Performance decrements consisted of an increase in nonresponses, increased response latencies, and decreased accuracies. P300 latencies increased, and P300 amplitudes decreased with extended wakefulness. When viewed together, reaction time and event-related brain potentials measures suggest that the locus of extended wakefulness effects was during early perceptual processes.

Adult↗

PubMedDate not supplied

Microbiologic quality-control study for the purpose of extending the use of transfer sets on the automix 3 + 3 and micromix automated total nutrient admixture compounding pumps.

BACKGROUND: A quality-control study was undertaken by the departments of pharmacy and microbiology at St. Paul's Hospital (Vancouver, British Columbia, Canada) to evaluate the microbiologic safety of total nutrition admixtures (TNA) compounded by automated compounding pumps when the use of disposable transfer sets was extended from 1 day to 2 days. This study also evaluates the potential annual cost savings of this extended use. METHODS: Transfer sets and unused part containers of ingredients were left to sit overnight on the automated compounders after daily TNA manufacturing before a TNA sample was compounded for culturing. These TNA samples were cultured using a biphasic system consisting of a tryptic soy broth component and an agar slide component. Positive results were subcultured and isolates were identified by standard methods. Forty samples were collected and evaluated. RESULTS: Four bags grew Bacillus species, and 1 bag grew coagulase-negative staphylococci. The potential annual cost savings of this extended use was estimated to be approximately 35,000 Canadian dollars. CONCLUSIONS: The extended use of the disposable transfer sets cannot be instituted at the present time and should be reexamined when the cause(s) of the positive results are identified and corrected.

Bacillus↗

PubMedDate not supplied

Arthroscopic repair of meniscal tears extending into the avascular zone in patients younger than twenty years of age.

BACKGROUND: Limited data are available regarding repair results of meniscal tears extending into the central avascular region. HYPOTHESIS: Meniscal tears extending into the avascular region can be successfully repaired in patients less than 20 years old. STUDY DESIGN: Prospective cohort study. METHODS: We examined the results of 71 meniscal repairs (64 knees) for tears extending into the central avascular region in patients 19 years of age or younger; 67 were examined clinically (mean, 51 months after surgery) and 36, by follow-up arthroscopy (mean, 18 months). RESULTS: In 53 of 71 (75%) meniscal repairs patients had no tibiofemoral compartment symptoms and there were no clinical failures. In 18 (25%) meniscal repairs, patients showed tibiofemoral symptoms or a failed repair was detected on follow-up arthroscopy. In the subgroup of 45 knees with meniscal repair and anterior cruciate ligament reconstruction evaluated clinically, 39 (87%) patients rated their knee as normal or very good, 2 (4%) as good, 3 (7%) as fair, and 1 (2%) as poor. CONCLUSIONS: A stable repair of complex meniscal tears that extend into the avascular region can be obtained using a meticulous inside-out vertical divergent suture technique. We recommend repair, particularly in young active patients in whom removal of complex tears would result in major loss of meniscal function and the risk of future arthrosis.

Adolescent↗

PubMedDate not supplied

Improvements in breast cancer pathology practices among medicare patients undergoing unilateral extended simple mastectomy.

The information contained in pathology reports of breast cancer specimens is of critical importance to treating physicians for selection of local regional treatment, adjuvant therapy, evaluation of therapy, estimation of prognosis, and analysis of outcomes. This information is also of great importance to patients and their families. In 2000, a Breast Cancer Pathology Advisory Group was formed to advise on the design of a project to assess the quality of pathology reports on unilateral extended simple mastectomy (ICD-9-CM procedure code 85.43) specimens from Medicare patients in New York State. This group comprised clinical pathologists, breast surgeons, medical oncologists, clinical breast cancer specialists, and a radiation oncologist. The group suggested that the reports be examined for several elements (quality indicators) that are relevant to patient care and prognosis. Baseline random sample data assessing these elements were established from a random sample of all cases for the calendar year 1999. A random sample of 748 cases (43.5%) of unilateral extended simple mastectomy was chosen from among 1718 cases for the calendar year 1999. Of these, 555 (74.2%) were suitable for review. The remaining 193 (25.8%) cases did not satisfy the inclusion criteria. Aggregate performance on 7 quality indicators (presence of carcinoma, laterality of specimen, number of lymph nodes present, number of positive nodes, documentation of lymph nodes, histologic type, and largest dimension of the tumor) was 83.7% or better, whereas performance was 69.4% or less on 10 others (resection margin status, verification of tumor size, gross observation of the lesion, histologic grade, angiolymphatic invasion, nuclear grade, location of the tumor, mitotic rate, extent of tubule formation, and perineural invasion). The last, perineural invasion, was used as a control element and was not considered an evaluative quality indicator. Performance levels for New York State were significantly lower for histologic grade, resection margin status, and angiolymphatic invasion than in similar studies elsewhere. In addition, there were significant interhospital disparities in the performance levels for these quality indicators. Whereas some hospitals always recorded certain indicators, others never did. This in part reflects differing degrees of adoption of recommended specialty society protocols. The second phase of the project consisted of an educational feedback program involving the directors of pathology laboratories in New York State. The aggregate findings of the baseline study were shared with all the pathologists. In addition, each hospital that performed unilateral extended simple mastectomies during the study period received its own specific data so that it could compare its performance with the aggregate performance. The results of the baseline study also were shared with the New York Pathological Society and the New York State Society of Pathologists. The latter described the results in its newsletter. A postintervention review of the medical charts of a sample of 297 Medicare patients discharged from New York State acute care hospitals with an ICD-9-CM procedure code of 85.43 (unilateral extended simple mastectomy) was conducted for the 6-month period from December 1, 2001, through May 31, 2002. The 8 quality indicators, performance for which was below 84% in the baseline, were chosen for this remeasurement. Statistically significant improvements (P < .0001) occurred in all the 8 quality indicators, ranging from 12.6% to 19.9%. The results of this study indicate that the issues identified by breast cancer pathology reports are amenable to improvement. Such improvement can serve both the patients and the treating physicians better in making adjuvant treatment decisions, estimating prognosis, and evaluating outcomes. It also will be of help to patients and their families in making other life decisions.

Aged↗

PubMed2002

Effect of food on early drug exposure from extended-release stimulants: results from the Concerta, Adderall XR Food Evaluation (CAFE) Study.

Stimulant therapy is the mainstay of treatment for children, adolescents and adults with attention-deficit/hyperactivity disorder (ADHD). Once-daily, extended-release oral formulations offer long acting control of symptoms by modifying drug delivery and absorption. In particular, consistency in early drug exposure is important for symptom control during school or work hours. Because these once-daily formulations are usually taken in the morning, the timing of the doses with breakfast is important. This study compared the effect of a high-fat breakfast on early drug exposure from a morning dose of two extended-release stimulant formulations: the osmotic-controlled OROS tablet of methylphenidate HCI (CONCERTA) and the capsule containing extended-release beads of mixed amphetamine salts (ADDERALL XR). The study had a single-dose, open-label, randomised, four-treatment, crossover design in which healthy subjects received either 36 mg CONCERTA or 20 mg ADDERALL XR in the morning after an overnight fast or a high-fat breakfast. Serial blood samples were collected over 28h to determine plasma concentrations of methylphenidate and amphetamine. The food effect on early drug exposure and the pharmacokinetic profiles up to 8 h after dosing of the two extended-release stimulants were directly compared using partial area (AUC(p4h), AUC(p6h) and AUC(p8h)) fed/fasted ratios. Amphetamine concentrations were markedly lower when the subjects had eaten breakfast, resulting in lower early drug exposures (p < 0.0001). By contrast, methylphenidate concentrations over the same 8 h were unaffected by breakfast, providing consistent levels of early drug exposure. Therefore, as a child's or adult's eating pattern varies, methylphenidate exposure over the first 8 h would be expected to have less day-to-day variation compared with amphetamine exposure. The osmotic-controlled OROS tablet provides a reliable and consistent delivery of methylphenidate HCI, independent of food, for patients with ADHD.

Absorption↗

PubMed2001

Fibroblasts and monocyte macrophages contract and degrade three-dimensional collagen gels in extended co-culture.

BACKGROUND: Inflammatory cells are believed to play a prominent role during tissue repair and remodeling. Since repair processes develop and mature over extended time frames, the present study was designed to evaluate the effect of monocytes and fibroblasts in prolonged culture in three-dimensional collagen gels. METHODS: Blood monocytes from healthy donors and human fetal lung fibroblasts were cast into type I collagen gels and maintained in floating cultures for three weeks. RESULTS: Fibroblast-mediated gel contraction was initially inhibited by the presence of monocytes (P < 0.01). However, with extended co-culture, contraction of the collagen gels was greatly augmented (P < 0.01). In addition, with extended co-culture, degradation of collagen in the gels occurred. The addition of neutrophil elastase to the medium augmented both contraction and degradation (P < 0.01). Prostaglandin E2 production was significantly increased by co-culture and its presence attenuated collagen degradation. CONCLUSION: The current study, therefore, demonstrates that interaction between monocytes and fibroblasts can contract and degrade extracellular matrix in extended culture.

Cell Line↗