Strength of public preferences for endovascular or open aortic aneurysm repair.

BACKGROUND: This study evaluated public preferences for the treatment processes for abdominal aortic aneurysm repair in order to allow them to be incorporated into a cost-effectiveness analysis. METHODS: This was a telephone survey using a trade-off method in UK resident adults (aged at least 18 years) with no previous diagnosis of a vascular condition. RESULTS: Some 167 of 209 participants (79·9 per cent) stated that they would prefer endovascular aneurysm repair (EVAR), 40 (19·1 per cent) preferred open surgery and two (1·0 per cent) stated no preference. Participants preferred EVAR because of the less invasive nature of the intervention and quicker recovery. Participants preferring open surgery cited reasons such as having a single follow-up appointment, and a procedure that felt more permanent. When participants were asked to make a sacrifice in order to have their preferred treatment, 122 (58·4 per cent) favoured EVAR, 18 (8·6 per cent) favoured open surgery and 69 (33·0 per cent) had no preference. Those preferring EVAR were willing to give up a mean of 0·135 expected quality-adjusted life-years (QALYs) to have EVAR, compared with a willingness to give up 0·033 expected QALYs among those preferring open repair. CONCLUSION: These results indicate a clear preference for EVAR over open surgery for aortic aneurysm.

ANTECEDENTES: Este estudio evaluó las preferencias de la opinion pública en relación a las opciones de tratamiento para la reparación del aneurisma de aorta abdominal, con el objetivo de que dichas preferencias se puedan incorporar en un análisis de coste-efectividad. MÉTODOS: Se realizó una encuesta telefónica utilizando el método trade-off (solución de intercambio) en adultos residentes en el Reino Unido (mayores de 18 años) sin diagnóstico previo de enfermedad vascular. RESULTADOS: Un total de 167 (79,9%) de 209 participantes declararon que preferirían la reparación endovascular del aneurisma (endovascular aneurysm repair, EVAR), 40 (19,1%) prefirieron cirugía abierta y dos (1,0%) no tenían preferencia. Los participantes prefirieron el EVAR debido a la naturaleza menos invasiva de la intervención y a tiempos de recuperación más rápidos. Los participantes que preferían la cirugía abierta mencionaron como razones tener una única visita de seguimiento y consideraron que se trataba de un procedimiento más permanente. Cuando se pidió a los participantes que para recibir su tratamiento preferido hicieran un intercambio, 122 (58,4%) se decantaron por la EVAR, 18 (8,6%) por la cirugía abierta y 69 (33%) no tuvieron preferencia. Los que prefirieron EVAR estaban dispuestos a renunciar a una media de 0,135 años de vida ajustados por calidad (QALYs) esperados con tal de recibir una EVAR en comparación con la renuncia de 0,033 QALYs esperada entre quienes preferían la reparación abierta. CONCLUSIÓN: Estos resultados indican una clara preferencia por la EVAR sobre la cirugía abierta, lo que está en desacuerdo con la reciente recomendación de NICE de que la EVAR no debe recomendarse como una opción de tratamiento. Los hallazgos sugieren que se debe prestar mayor atención a las características del proceso de tratamiento. Al no incorporar explícitamente tales preferencias en el proceso de toma de decisiones, NICE corre el riesgo de recomendar opciones de tratamiento que son contrarias a las preferencias de la población del Reino Unido.

Efficacy of preoperative immunonutrition in locally advanced pancreatic cancer undergoing irreversible electroporation (IRE).

BACKGROUND: Improved preoperative immunonutrition has been shown to decrease the length of stay (LOS) and complications among patients undergoing elective gastrointestinal cancer surgeries. The purpose of this study was to determine whether preoperative immunonutrition supplementation decreases postoperative LOS, infectious complications, and morbidity in patients undergoing irreversible electroporation (IRE) surgery for locally advanced pancreatic cancer (LAPC). METHODS: At a regional hepatopancreatobiliary referral center within an academic medical center 71 patients receiving IRE treatment of LAPC were included in the study. The participants were divided into those receiving preoperative immunonutrition (n = 44) and those receiving no supplemental preoperative immunonutrition (n = 27). Main outcomes and measures were LOS, postoperative complications, nutritional risk index (NRI), and albumin levels. RESULTS: Patients in both groups were similar for preoperative nutrition parameters and operative therapy. Patients in the immunonutrition group experienced a statistically significant decrease in postoperative complications (p = 0.05) and LOS (10.7 vs. 17.4, p = 0.01), and less of a decrease in nutritional risk index (-12.6 vs. -16.2, p = 0.03) and albumin levels (-1.1 vs. -1.5, p < 0.01). CONCLUSION: Preoperative immunonutrition was clinically significant in decreasing postoperative complications, LOS, and improving post-surgery NRI and albumin levels in patients receiving elective IRE treatment of non-resectable pancreatic cancer. These results indicate that preoperative immunonutrition is effective and feasible in this subset of cancer patients.

Single-stage resection and microwave ablation for bilobar colorectal liver metastases.

BACKGROUND: Patients undergoing liver resection combined with microwave ablation (MWA) for bilobar colorectal metastasis may have similar overall survival to patients who undergo two-stage hepatectomy, but with less morbidity. METHODS: This was a multi-institutional evaluation of patients who underwent MWA between 2003 and 2012. Morbidity (90-day) and mortality were compared between patients who had MWA alone and those who underwent combined resection and MWA (CRA). Mortality and overall survival after CRA were compared with published data on two-stage resections. RESULTS: Some 201 patients with bilobar colorectal liver metastasis treated with MWA from four high-volume institutions were evaluated (100 MWA alone, 101 CRA). Patients who had MWA alone were older, but the groups were otherwise well matched demographically. The tumour burden was higher in the CRA group (mean number of lesions 3·9 versus 2·2; P = 0·003). Overall (31·7 versus 15·0 per cent; P = 0·006) and high-grade (13·9 versus 5·0 per cent; P = 0·030) complication rates were higher in the CRA group. Median overall survival was slightly shorter in the CRA group (38·4 versus 42·2 months; P = 0·132) but disease-free survival was similar (10·1 versus 9·3 months; P = 0·525). The morbidity and mortality of CRA compared favourably with rates in the existing literature on two-stage resection, and survival data were similar. CONCLUSION: Single-stage hepatectomy and MWA resulted in survival similar to that following two-stage hepatectomy, with less overall morbidity.

Phase I study of temozolomide in combination with thiotepa and carboplatin with autologous hematopoietic cell rescue in patients with malignant brain tumors with minimal residual disease.

Recurrence of malignant brain tumors results in a poor prognosis with limited treatment options. High-dose chemotherapy with autologous hematopoietic cell rescue (AHCR) has been used in patients with recurrent malignant brain tumors and has shown improved outcomes compared with standard chemotherapy. Temozolomide is standard therapy for glioblastoma and has also shown activity in patients with medulloblastoma/primitive neuro-ectodermal tumor (PNET), particularly those with recurrent disease. Temozolomide was administered twice daily on days -10 to -6, followed by thiotepa 300 mg/m(2) per day and carboplatin dosed using the Calvert formula or body surface area on days -5 to -3, with AHCR day 0. Twenty-seven patients aged 3-46 years were enrolled. Diagnoses included high-grade glioma (n=12); medulloblastoma/PNET (n=9); central nervous system (CNS) germ cell tumor (n=4); ependymoma (n=1) and spinal cord PNET (n=1). Temozolomide doses ranged from 100 mg/m(2) per day to 400 mg/m(2) per day. There were no toxic deaths. Prolonged survival was noted in several patients including those with recurrent high-grade glioma, medulloblastoma and CNS germ cell tumor. Increased doses of temozolomide are feasible with AHCR. A phase II study using temozolomide, carboplatin and thiotepa with AHCR for children with recurrent malignant brain tumors is being conducted through the Pediatric Blood and Marrow Transplant Consortium.

Evaluation of thermal injury to liver, pancreas and kidney during irreversible electroporation in an in vivo experimental model.

BACKGROUND: Irreversible electroporation (IRE) is a new technique for tumour cell ablation that is reported to involve non-thermal-based energy using high voltage at short microsecond pulse lengths. In vivo assessment of the thermal energy generated during IRE has not been performed. Thermal injury can be predicted using a critical temperature model. The aim of this study was to assess the potential for thermal injury during IRE in an in vivo porcine model. METHODS: In vivo continuous temperature assessments of 86 different IRE procedures were performed on porcine liver, pancreas, kidney and retroperitoneal tissue. Tissue temperature was measured continuously throughout IRE by means of two thermocouples placed at set distances (0·5 cm or less, and 1 cm) from the IRE probes within the treatment field. Thermal injury was defined as a tissue temperature of 54°C lasting at least 10 s. Tissue type, pulse length, probe exposure length, number of probes and retreatment were evaluated for associations with thermal injury. In addition, IRE ablation was performed with metal clips or metal stents within the ablation field to determine their effect on thermal injury. RESULTS: An increase in tissue temperature above the animals' baseline temperature (median 36·0°C) was generated during IRE in all tissues studied, with the greatest increase found at the thermocouple placed within 0·5 cm in all instances. On univariable and multivariable analysis, ablation in kidney tissue (maximum temperature 62·8°C), ablation with a pulse length setting of 100 µs (maximum 54·7°C), probe exposure of at least 3·0 cm (maximum 52·0°C) and ablation with metal within the ablation field (maximum 65·3°C) were all associated with a significant risk of thermal injury. CONCLUSION: IRE can generate thermal energy, and even thermal injury, based on tissue type, probe exposure lengths, pulse lengths and proximity to metal. Awareness of probe placement regarding proximity to critical structures as well as probe exposure length and pulse length are necessary to ensure safety and prevent thermal injury. A probe exposure of 2·5 cm or less for liver IRE, and 1·5 cm or less for pancreas, with maximum pulse length of 90 µs will result in safe and non-thermal energy delivery with spacing of 1·5-2·3 cm between probe pairs.

The association between demolition activity and children's blood lead levels.

Urban renewal efforts are a priority for many American cities. As efforts to reconstitute urban centers increase, the demolition of old, deteriorated structures has accelerated. Recent studies have identified demolitions as a potential source of environmental lead exposure. We conducted a study examining the relationship between demolition activity and blood lead levels of children residing in neighborhoods where demolition activity occurred. A retrospective cohort study was conducted in St. Louis City, Missouri. The study period was January 1, 2002 to December 31, 2002. Data were obtained from the Missouri Childhood Lead Poisoning Prevention Program's (CLPPP) lead surveillance system and St. Louis Demolition Permit Database. Children were considered exposed to a demolition if they had a blood lead test within 45 days of any demolition on a census block. Exposure was classified as both a dichotomous (yes/no) and a categorical (none/one/multiple) variable and was analyzed separately. Linear regression models were developed to determine effects of demolitions on blood lead levels. A total of 1196 children 6-72 months of age living in 395 census blocks were included. 314 (26.3%) were exposed and 882 (73.7%) were unexposed to a demolition. In an adjusted model, exposure to multiple demolitions was found to have significant effects on children blood lead levels (coefficient=0.281; 95% CI=0.069, 0.493; P-value=0.010). Age of the child, race, and age of housing where children's resided were also significant predictors. This study suggests that multiple demolitions within a census block may significantly increase children's blood lead levels. The findings may be useful to municipal planners in older cities where demolitions are being used as an urban renewal tool.

Laparoscopic total extraperitoneal (TEP) inguinal hernia repair under epidural anesthesia: a detailed evaluation.

BACKGROUND: Laparoscopic total extraperitoneal (TEP) inguinal hernia repair is as efficacious as the open Lichtenstein procedure, can be learned with proper training, and causes less postoperative pain, better cosmesis, and earlier return to work. The one major factor preventing the widespread acceptance of TEP is the requirement for general anesthesia (GA). In contrast, open hernia is performed using local or regional anesthesia, thereby having the advantage of quicker recovery, decreased postoperative nausea and vomiting (PONV), fewer hemodyanamic changes, reduced metabolic responses to surgical stress, and better muscle relaxation. This study attempted to evaluate whether laparoscopic TEP can be performed under less invasive anesthesia, such as regional anesthesia, and to determine its feasibility and limitations METHODS: All total of 22 male patients were studied between January 2002 and March 2003 in a tertiary care referral hospital. Epidural anesthesia with 2% lignocaine with adrenaline (Adr) was given via a lumbar epidural catheter, achieving a sensory level of T6. The standard technique for TEP was followed, using three midline infraumbilical ports. RESULTS: Twenty-two patients (20 unilateral, 2 bilateral) underwent operation. The mean operating time was 67.8 +/- 18 (range, 40-110) min. All 22 cases were started with epidural anesthesia, 7 of which (31.9%) were converted to GA; the other 15 (68.1%) were completed under epidural anesthesia. All cases were successfully completed laparoscopically, and there were no conversions. There were no intraoperative complications. There was no significant difference between the cases conducted under epidural anesthesia (67.6 +/- 23 min) and those converted to GA (69.3 +/- 7.3 min). There was no statistically significant difference between the conversion rates of smaller versus larger hernias in this study (p value 0.22). A significant association of success of the procedure was seen with a sensory level of T6 and above (2/15 conversions to GA; i.e., 13.3%) and cases with a sensory level below T6 (5/7 converted; i.e., 71.4%) and adequate epidural catheter length (p = 0.015). Prevention and management of pneumoperitoneum and subsequent shoulder-tip pain was the key to preventing conversions (6 of 9 converted to GA; i.e., 67%; p = 0.006). There were no significant postoperative complications, and no recurrences were noted during a mean follow-up period of 29 months (range, 20-36 months). CONCLUSIONS: From the present study it is clear that TEP is possible under epidural anesthesia provided a minimal sensory level of T6 is achieved. To achieve that level, an appropriate higher site for catheter insertion and/or adequate intraepidural catheter length needs specific attention. Pneumoperitoneum, shoulder-tip pain, intraoperative straining, and inadequate preperitoneal space are factors whose interplay leads to conversion to GA. The size of the hernia is not related to pneumoperitoneum or conversion to GA.

Time activity modelling of domestic exposures to radon.

Radon gas occurs naturally in the environment with a variable distribution. In some areas radon concentrates sufficiently within the built environment that it is considered as a public health risk. It is possible, successfully, to reduce radon levels in the built environment, and it has been shown that such remediation programmes can be justified in terms of the costs and benefits accruing. However, the estimated dose received by people in their homes depends on the time spent indoors. The research presented here uses data derived from time activity surveys in Northamptonshire, together with radon data from a representative home, to model potential exposures for different population sub-groups. Average home occupancy ranged from 14.8h (probable error 2.5h) for students to 17.7 (3.1) h for adults; schoolchildren spent an average of 14.9 (1.2) h at home. Over a quarter of adults, however, were in the home for 22 h on more. These differences in occupancy patterns lead to substantial differences in radon exposure. In a home with an average hourly ground floor radon concentration of 467 Bqm(-3), modelled hourly average exposures ranged from ca. 250 Bqm(-3) for students and school children, to over 340 Bqm(-3), for women based at home. Modelled exposures show a non-linear association with total time spent at home, suggesting that exposure estimates based on linear models may provide misleading estimates of health risks from radon and the potential benefits of radon remediation. Highest hourly exposures are likely to be experienced by people with highly occupancy, living in single-storey, ground floor accommodation (for example, the elderly the infirm and non-working young mothers). Since these may be least aware of radon risks, and least able to take up remediation measures, they should be specifically targeted for radon monitoring and for assistance in remediation schemes.

Characterization of adenylyl cyclase isoforms in rat peripheral pulmonary arteries.

Activation of adenylyl cyclase (AC), of which there are 10 diversely regulated isoforms, is important in regulating pulmonary vascular tone and remodeling. Immunohistochemistry in rat lungs demonstrated that AC2, AC3, and AC5/6 predominated in vascular and bronchial smooth muscle. Isoforms 1, 4, 7, and 8 localized to the bronchial epithelium. Exposure of animals to hypoxia did not change the pattern of isoform expression. RT-PCR confirmed mRNA expression of AC2, AC3, AC5, and AC6 and demonstrated AC7 and AC8 transcripts in smooth muscle. Western blotting confirmed the presence of AC2, AC3, and AC5/6 proteins. Functional studies provided evidence of cAMP regulation by Ca(2+) and protein kinase C-activated but not G(i)-inhibited pathways, supporting a role for AC2 and a Ca(2+)-stimulated isoform, AC8. However, NKH-477, an AC5-selective activator, was more potent than forskolin in elevating cAMP and inhibiting serum-stimulated [(3)H]thymidine incorporation, supporting the presence of AC5. These studies demonstrate differential expression of AC isoforms in rat lungs and provide evidence that AC2, AC5, and AC8 are functionally important in cAMP regulation and growth pathways in pulmonary artery myocytes.

Insulin and type 2 diabetes. Last resort or rational management?

BACKGROUND: Recent evidence indicates that lower glucose levels in people with type 2 diabetes result in fewer complications. People with diabetes generally have sub-optimal glycaemic control. The natural progression of diabetes is characterised by increasing glucose levels requiring increasing therapy. OBJECTIVE: This article explores the possible role of therapeutic insulin in the management of type 2 diabetes. Arguments for earlier use of insulin, illustrative cases and common dilemmas faced when introducing insulin are examined. DISCUSSION: Findings from the United Kingdom Prospective Diabetes Study (UKPDS) are reviewed. It suggests that active and aggressive management of type 2 diabetes in general practice can have a role to play in reducing complications from diabetes. It now appears that insulin has a role earlier in the management of type 2 diabetes.

International survey of radiotherapy practice for radical treatment of non-small cell lung cancer.

This postal survey was designed to assess the possible agreement or differences in staging, selection criteria and radiation volumes for a curative treatment of non-small cell lung cancer. The questionnaire was sent to 263 radiotherapists from 38 different countries; 114 responses (43%) were received. In this sample, some geographical differences, mainly for staging procedures (the use of brain CT scan or bone scan) and selection criteria (the role of positive mediastinal lymph nodes), were seen. There was a good agreement between radiotherapists in the choice of treatment volumes in the five different clinical scenarios. The clinical and radiobiological findings of the last decade have discredited the routine use of split course or hypofractionation schedules. Further studies are needed to improve the technical basis of thoracic radiotherapy.

Correction of neutropenia with rHuG-CSF after loss of response to rHuGM-CSF following autologous bone marrow transplant.

We describe a patient who presented with graft failure following autologous BMT, with an initial response of the neutrophil count to rHuGM-CSF but eventual loss of this response. Subsequently, this patient responded to rHuG-CSF. This could be explained by the fact that rHuG-CSF stimulates both early and late myeloid progenitor cells whereas rHuGM-CSF stimulates mainly the intermediate myeloid progenitor cells. This finding suggests that rHuG-CSF should be investigated for the treatment of patients with graft failure following ABMT.

Metabolic clearance of vasopressin and an analogue resistant to vasopressinase in human pregnancy.

The metabolic clearance rate (MCR) of arginine vasopressin (AVP) increases fourfold during human pregnancy. To explore whether circulating vasopressinase may play a role in this change, six women underwent a three-tier infusion clearance study, twice, in random order, to determine the MCRs of either AVP or 1-deamino-8-D-AVP (dDAVP, an analogue resistant to degradation by vasopressinase). Volunteers were tested in late pregnancy (LP), 24-48 h postdelivery (PD), and 5-6 (PP1) and 10-12 (PP2) wk postpartum, thus examining MCRs when vasopressinase levels were high, before and after removal of the placenta (LP and PD), and when plasma enzyme activity was becoming (PP1) and became (PP2) undetectable. Manipulation of infusate permitted comparison of MCRs at three plasma levels whose range was similar at each test period. PAVP and PdDAVP (2.2 and 10 pg/ml, respectively, during the initial infusion) increased to 8 and 31 pg/ml, stepwise increments that had no influence on respective MCRs (AVP: 3.4, 2.2, 0.77, and 0.67 l/min during LP, PD, PP1, and PP2 compared with 0.18, 0.21, 0.17, and 0.15 l/min for dDAVP). Comparison of similar and submaximal urinary osmolality revealed PdDAVP values three- to fourfold greater than PAVP. Von Willebrand factor (VWF) and factor VIIIc levels increased almost fourfold in response to dDAVP during pregnancy, but only doubled in the nonpregnant state; these differences did not reach significance. We conclude that although AVP disposal rates increase fourfold in pregnancy, those of dDAVP change little, suggesting a role of vasopressinase in the increased MCR of AVP in gestation (as well as in the genesis of certain polyuric disorders of pregnancy).(ABSTRACT TRUNCATED AT 250 WORDS)

A comparison of diagnosis related groups and ambulatory visit groups in day-case surgery.

Case-mix measurement is a basic requirement of clinical and resource management systems within health care organisations, and offers a potentially useful tool for the setting and monitoring of contracts. Ambulatory care has particular problems in the construction of appropriate case-mix measures, and day-case surgery provides an opportunity to test two existing measures, one inpatient (Diagnostic Related Groups) and one ambulatory (Ambulatory Visit Groups). These grouping systems were applies to the same data to compare the case-mix patterns that they produce. The findings show that the ambulatory visit group appear to have advantages over the diagnostic group with respect to their underlying assumptions and labelling of the groups; in particular, they assign greater weight to procedures. However, diagnostic groups are more developed, easier to use, more familiar and allow direct comparisons with inpatient care. Nevertheless, a proper evaluation of these issues requires further data collection and analysis, together with a fundamental examination of the uses of ambulatory case-mix.

A comparison of diagnosis related groups and ambulatory visit groups in day-case surgery.

Case-mix measurement is a basic requirement of clinical and resource management systems within health care organisations, and offers a potentially useful tool for the setting and monitoring of contracts. Ambulatory care has particular problems in the construction of appropriate case-mix measures, and day-case surgery provides an opportunity to test two existing measures, one inpatient (Diagnosis Related Groups) and one ambulatory (Ambulatory Visit Groups). These grouping systems were applied to the same data to compare the case-mix patterns that they produce. The findings show that Ambulatory Visit Groups appear to have advantages over the Diagnosis Related Groups with respect to their underlying assumptions and labelling of the groups; in particular, they assign greater weight to procedures. However, Diagnosis Related Groups are more developed, easier to use, more familiar and allow direct comparisons with inpatient care. Nevertheless, a proper evaluation of these issues requires further data collection and analysis, together with a fundamental examination of the uses of ambulatory case-mix.

Case mix measures for ambulatory care.

Resource management in Ambulatory Care is recognized as an increasingly important area for development by many countries, and there has been much interest in the part that Case Mix Measures (CMMs) can play in this. There are a number of possible approaches to case mix, and several measures already exist. However, these are at present mainly still at the development stage and all are North American in origin. This paper reviews the role and state of the art of ambulatory CMMs and reports on an initial evaluation of the Ambulatory Visit Group (AVG) methodology using European data. Although the AVG grouper works under limited conditions, important questions remain concerning its validity and usefulness.

Experience and preparation of community nursing staff for work associated with HIV infection and AIDS.

Some of the findings from a national survey of 3754 community nursing staff in England regarding their experience of and preparation for working with HIV infection and AIDS are reported. The current absence of confidence to deal with HIV infection is explained and suggestions made regarding the content of educational developments.