Electrolysis products, reactive oxygen species and ATP loss contribute to cell death following irreversible electroporation with microsecond-long pulsed electric fields.

Membrane permeabilization and thermal injury are the major cause of cell death during irreversible electroporation (IRE) performed using high electric field strength (EFS) and small number of pulses. In this study, we explored cell death under conditions of reduced EFS and prolonged pulse application, identifying the contributions of electrolysis, reactive oxygen species (ROS) and ATP loss. We performed ablations with conventional high-voltage low pulse (HV-LP) and low-voltage high pulse (LV-HP) conditions in a 3D tumor mimic, finding equivalent ablation volumes when using 2000 V/cm 90 pulses or 1000 V/cm 900 pulses respectively. These results were confirmed by performing ablations in swine liver. In LV-HP treatment, ablation volume was found to increase proportionally with pulse numbers, without the substantial temperature increase seen with HV-LP parameters. Peri-electrode pH changes, ATP loss and ROS production were seen in both conditions, but LV-HP treatments were more sensitive to blocking of these forms of cell injury. Increases in current drawn during HV-LP was not observed during LV-HP condition where the total ablation volume correlated to the charge delivered into the tissue which was greater than HV-LP treatment. LV-HP treatment provides a new paradigm in using pulsed electric fields for tissue ablation with clinically relevant volumes.

Non-Contact Irreversible Electroporation in the Esophagus With a Wet Electrode Approach.

Our objective was to develop a technique for performing irreversible electroporation (IRE) of esophageal tumors while mitigating thermal damage to the healthy lumen wall. We investigated noncontact IRE using a wet electrode approach for tumor ablation in a human esophagus with finite element models for electric field distribution, joule heating, thermal flux, and metabolic heat generation. Simulation results indicated the feasibility of tumor ablation in the esophagus using an catheter mounted electrode immersed in diluted saline. The ablation size was clinically relevant, with substantially lesser thermal damage to the healthy esophageal wall when compared to IRE performed by placing a monopolar electrode directly into the tumor. Additional simulations were used to estimate ablation size and penetration during noncontact wet-electrode IRE (wIRE) in the healthy swine esophagus. A novel catheter electrode was manufactured and wIRE evaluated in seven pigs. wIRE was performed by securing the device in the esophagus and using diluted saline to isolate the electrode from the esophageal wall while providing electric contact. Computed tomography and fluoroscopy were performed post-treatment to document acute lumen patency. Animals were sacrificed within four hours following treatment for histologic analysis of the treated esophagus. The procedure was safely completed in all animals; post-treatment imaging revealed intact esophageal lumen. The ablations were visually distinct on gross pathology, demonstrating full thickness, circumferential regions of cell death (3.52 ± 0.89 mm depth). Acute histologic changes were not evident in nerves or extracellular matrix architecture within the treatment site. Catheter directed noncontact IRE is feasible for performing penetrative ablations in the esophagus while avoiding thermal damage.

Use of Systematic Review and Meta-Analysis in Environmental Health Epidemiology: a Systematic Review and Comparison with Guidelines.

Systematic review (SR) and meta-analysis (MA) have potential to contribute substantially to environmental health (EH) risk assessment and policy-making, provided study questions are clear and methods sound. We undertook a systematic review of the published epidemiological literature for studies using both SR and MA examining associations between chronic low-dose chemical exposures and adverse health outcomes in general populations and compared actual methods and reporting with a checklist based on available published guidelines. We identified 48 EH SRMAs meeting these criteria. Associations were mainly positive and statistically significant, often involving large populations. A majority of studies followed most general SRMA guidance, although we identified weaknesses in problem formulation, study search, selection and data extraction, and integrating policy implications. Fewer studies followed EH-specific SRMA recommendations, particularly regarding exposure heterogeneity and other risks of bias. Development and adoption of EH-specific SRMA guidelines would contribute to strengthening these tools for public health decision-making.

Attitudes toward preventive services and lifestyle: the views of primary care patients in Europe. the EUROPREVIEW patient study.

BACKGROUND: For preventive interventions in general practice to succeed, patients' points of view must be taken into account in addition to those of GPs. OBJECTIVE: To explore patients' views and beliefs about the importance of lifestyle and preventive interventions, to assess their readiness to make changes to their lifestyle and their willingness to receive support from GPs. METHODS: Cross-sectional survey conducted by EUROPREV in primary care practices in 22 European countries. Patients were consecutively selected and interviewed from September 2008 to September 2009. RESULTS: Seven thousand nine hundred and forty-seven participants, 52.2% females. Only 30.5% of risky drinkers think they need to change, as opposed to 64% of smokers, 73.5% of patients with unhealthy eating habits and 73% with lack of physical activity. Risky drinkers reported that GPs initiated a discussion on alcohol consumption less often (42%) than on smoking (63%), eating habits (59%) or physical activity (55%). Seventy-five per cent, 66% and 63% of patients without hypertension, diabetes or hypercholesterolaemia, respectively, think blood pressure, blood sugar and serum cholesterol should be checked yearly. Women (80%) think they should be screened with the cervical smear test and 72.8% of women aged 30-49 years with mammography, yearly or every 2 years. CONCLUSIONS: A high proportion of patients attending primary care with unhealthy lifestyles (especially risky drinkers) do not perceive the need to change their habits, and about half the patients reported not having had any discussion on healthy lifestyles with their GPs. Patients overestimate their need to be screened for cardiovascular risk factors and for cancer.

Prevention and health promotion in clinical practice: the views of general practitioners in Europe.

BACKGROUND: Disease prevention and health promotion are important tasks in the daily practice of all general practitioners (GPs). The objective of this study was to explore the knowledge and attitudes of European GPs in implementing evidence-based health promotion and disease prevention recommendations in primary care, to describe GPs' perceived barriers to implementing these recommendations and to assess how GPs' own health behaviors affect their work with their patients. METHODS: A postal multinational survey was carried out from June to December 2000 in a random sample of GPs listed from national colleges of each country. RESULTS: Eleven European countries participated in the study, giving a total of 2082 GPs. Although GPs believe they should advise preventive and health promotion activities, in practice, they are less likely to do so. About 56.02% of the GPs answered that carrying-out prevention and health promotion activities are difficult. The two most important barriers reported were heavy workload/lack of time and no reimbursement. Associations between personal health behaviour and attitudes to health promotion or activities in prevention were found. GPs who smoked felt less effective in helping patients to reduce tobacco consumption than non-smoking GPs (39.34% versus 48.18%, P < 0.01). GPs who exercised felt that they were more effective in helping patients to practice regular physical exercise than sedentary GPs (59.14% versus 49.70%, P < 0.01). CONCLUSIONS: Significant gaps between GP's knowledge and practices persist in the use of evidence-based recommendations for health promotion and disease prevention in primary care.

Palliative care.

Palliative care represents a part of a whole philosophy and approach to patient care--it should not be an isolated service at the end of life. Whole person care does not have to be limited to those imminently dying. The Palliative Care Center and Hospice of the North Shore created a Palliative Care Consultation (PCC) service in 1999 to assist those patients needing help with pain and symptoms before they qualify for hospice care.