A comparison of the clinical and histological appearances after treatment of advanced stage ovarian cancer with PlasmaJet® device.

OBJECTIVE: To compare the clinical appearance of "no residual disease" to the histological assessment of the same tissue when treated with PlasmaJet®. To determine if the treated tissue with a clinical appearance of "no residual disease" demonstrated histologically apparent damage to underlying structures. AIM: The main aims of the study were to compare the clinical appearance of 'no residual disease' to the histological assessment of the same tissue and to assess whether treatment with PlasmaJet® to produce a clinical appearance of 'no residual disease' causes no histologically apparent damage to the underlying structures. METHOD: This prospective cohort study was conducted in Liverpool Women's NHS Foundation Trust between January 2019 and June 2020. Women with a diagnosis of advanced or presumed advanced stage ovarian cancer were approached and 20 women were recruited into the study. Tissue samples were collected from women with stage 3 or 4 ovarian cancer at either primary or interval debulking surgery. RESULTS: The clinical appearance of no residual disease was confirmed histologically in 84 % (n = 16) of cases. Fat was the only underlying tissue seen damaged in 21 % (n = 4) of cases. Bowel resection with stoma formation was needed in one case (5.26 %). CONCLUSION: PlasmaJet® ablated the malignant tissue in majority of the cases without causing any significant damage to the underlying tissue, it also reduced the need for stoma formation. This is a small study with encouraging results. PlasmaJet® could be a valuable tool in ovarian cancer surgery, it potentially could reduce the need for bowel surgery and allow treatment of significant mesenteric disease with reduced morbidity for the patient.

A novel experimental chamber for the characterization of free-falling particles in volcanic plumes.

Volcanic plumes pose a hazard to health and society and a particular risk for aviation. Hazard mitigation relies on forecasting plume dispersion within the atmosphere over time. The accuracy of forecasts depends on our understanding of particle dispersion and sedimentation processes, as well as on the accuracy of model input parameters, such as the initial particle size distribution and concentrations of volcanic particles (i.e., volcanic ash) in the atmosphere. However, our understating of these processes and the accurate quantification of input parameters remain the main sources of uncertainty in plume dispersion modeling. It is usually impractical to sample volcanic plumes directly, but particle sedimentation can be constrained in the laboratory. Here, we describe the design of a new experimental apparatus for investigating the dynamics of free-falling volcanic particles. The apparatus can produce a sustained column of falling particles with variable particle concentrations appropriate to a volcanic plume. Controllable experimental parameters include particle size distributions, types, and release rates. A laser-illuminated macrophotography system allows imaging of in-flight particles and their interactions. The mass of landing particles is logged to inform deposition rates. Quantitative measurements include particle morphology characterization, settling velocities, flow rates, and estimation of concentrations. Simultaneous observations of particle interaction processes and settling dynamics through direct control over a wide range of parameters will improve our parameterization of volcanic plume dynamics. Although the apparatus has been specifically designed for volcanological investigations, it can also be used to explore the characteristics of free-falling particle columns occurring in both environmental and industrial settings.

Predicting the factors influencing the inter- and intraspecific survival rates of riverine fishes implanted with acoustic transmitters.

Biotelemetry is a central tool for fisheries management, with the implantation of transmitters into animals requiring refined surgical techniques that maximize retention rates and fish welfare. Even following successful surgery, long-term post-release survival rates can vary considerably, although knowledge is limited for many species. The aim here was to investigate the post-tagging survival rates in the wild of two lowland river fish species, common bream Abramis brama and northern pike Esox lucius, following their intra-peritoneal double-tagging with acoustic transmitters and passive integrated transponder (PIT) tags. Survival over a 2-year period was assessed using acoustic transmitter data in Cox proportional hazards models. Post-tagging survival rates were lowest in the reproductive periods of both species, but in bream, fish tagged just prior to spawning actually had the highest subsequent survival rates. Pike survival was influenced by sex, with males generally surviving longer than females. PIT tag detections at fixed stations identified bream that remained active, despite loss of an acoustic transmitter signal. In these instances, loss of the acoustic signal occurred up to 215 days post-tagging and only during late spring or summer, indicating a role of elevated temperature, while PIT detections occurred between 18 and 359 days after the final acoustic detections. Biotelemetry studies must thus always consider the date of tagging as a fundamental component of study designs to avoid tagged fish having premature end points within telemetry studies.

Novel Single-Site Device for Conjoined Glucose Sensing and Insulin Infusion: Performance Evaluation in Diabetes Patients During Home-Use.

OBJECTIVE: This study evaluated a novel diabetes treatment device that combines commercially available continuous glucose monitoring and insulin infusion technology in such a way as to perform insulin delivery and glucose sensing through a single skin insertion site (single-port device). METHODS: Ten type 1 diabetes patients used the device for up to six days in their home/work environment for open-loop insulin delivery and glucose sensing. On an additional day, the device was used in combination with an algorithm to perform automated closed-loop glucose control under hospital settings. To assess the performance of the device, capillary blood glucose concentrations were frequently determined and a continuous glucose sensor was additionally worn by the patients. RESULTS: The average mean absolute relative deviation from blood glucose concentrations obtained for the sensor of the device was low (median, 13.0%; interquartile range, 10.5-16.7%; n = 10) and did not differ from that of the additionally worn glucose sensor (versus 13.9%; 11.9-15.3%; P = 0.922). Furthermore, insulin delivery with the single-port device was reliable and safe during home use and, when performed in combination with the control algorithm, was adequate to achieve and maintain near normoglycemia. CONCLUSION: Our data show the feasibility of open- and closed-loop glucose control in diabetes patients using a device that combines insulin delivery and glucose sensing at a single tissue site. SIGNIFICANCE: The reduction in device size and invasiveness achieved by this design may largely increase patient convenience and enhance acceptance of diabetes treatment with continuous glucose monitoring and insulin delivery technology.

To GP or not to GP: a natural experiment in children triaged to see a GP in a tertiary paediatric emergency department (ED).

OBJECTIVE: To evaluate the impact of integrating a general practitioner (GP) into a tertiary paediatric emergency department (ED) on admissions, waiting times and antibiotic prescriptions. DESIGN: Retrospective cohort study. SETTING: Alder Hey Children's NHS Foundation Trust, a tertiary paediatric hospital in Liverpool, UK. PARTICIPANTS: From October 2014, a GP was colocated within the ED, from 14:00 to 22:00 hours, 7 days a week. Children triaged green on the Manchester Triage System without any comorbidities were classed as 'GP appropriate'. The natural experiment compared patients triaged as 'GP appropriate' and able to be seen by a GP between 14:00 and 22:00 hours (GP group) to patients triaged as 'GP appropriate' seen outside of the hours when a GP was available (ED group). Intention-to-treat (ITT) analysis was used to assess the main outcomes. RESULTS: 5223 patients were designated as 'GP appropriate'-18.2% of the total attendances to the ED over the study period. There were 2821 (54%) in the GP group and 2402 (46%) in the ED group. The median duration of stay in the ED was 94 min (IQR 63-141) for the GP group compared with 113 min (IQR 70-167) for the ED group (p<0.0005). Using the ITT analysis equivalent, we demonstrated that the GP group were less likely to: be admitted to hospital (2.2% vs 6.5%, OR 0.32, 95% CI 0.24 to 0.44), wait longer than 4 hours (2.3% vs 5.1%, OR 0.45, 95% CI 0.33 to 0.61) or leave before being seen (3.1% vs 5.7%, OR 0.53, 95% CI 0.41 to 0.70), but more likely to receive antibiotics (26.1% vs 20.5%, OR 1.37, 95% CI 1.10 to 1.56). Sensitivity analyses yielded similar results. CONCLUSIONS: Introducing a GP to a paediatric ED service can significantly reduce waiting times and admissions, but may lead to more antibiotic prescribing. This study demonstrates a novel, potentially more efficient ED care pathway in the current context of rising demand for children's emergency services.

A randomised, double-blind, placebo-controlled trial of minocycline and/or omega-3 fatty acids added to treatment as usual for at-risk mental states (NAYAB): study protocol.

BACKGROUND: The at-risk mental state (ARMS) describes individuals at high risk of developing schizophrenia or psychosis. The use of antipsychotics in this population is not supported, because most individuals with ARMS are unlikely to develop psychosis. Anti-inflammatory treatments and polyunsaturated fatty acids (PUFAs) may have some beneficial effects in the treatment of ARMS. There have been no controlled clinical trials in which researchers have investigated the use of minocycline for ARMS and no trials involving PUFAs in combination with other proposed treatments. There is a need to find effective, tolerable and inexpensive interventions for individuals with ARMS that are available in high-, low- and middle-income countries. METHODS/DESIGN: A 6-month intervention study of minocycline and/or omega-3 fatty acids added to treatment as usual (TAU) in patients with ARMS will be conducted in Pakistan using a randomised, placebo-controlled, double-blind factorial design. A total of 320 consenting patients with capacity will be recruited from the community, general practitioner clinics and psychiatric units. Allowing for a 25% dropout rate, we will recruit 59 completing participants into each study arm, and in total 236 will complete the study. We will determine whether the addition of minocycline and/or omega-3 fatty acids to TAU attenuates the rate of transition from ARMS to first-episode psychosis and improves symptoms and/or level of functioning in ARMS. We will also investigate whether any candidate risk factors, such as negative symptoms, influence treatment response in the ARMS group. The primary efficacy endpoint is conversion to psychotic disorder at 12 months after study entry. Analysis will be done according to the intention to treat principle using analysis of variance, chi-square tests and adjusted ORs to assess between-group differences. Cox regression analysis will be used to evaluate potential between-group differences in time to onset of psychosis. DISCUSSION: The outcomes of this trial will provide evidence of the potential benefits of minocycline and PUFAs in the treatment of ARMS. Both minocycline and PUFAs are inexpensive, are readily available in low-/middle-income countries such as Pakistan, and if proven, may be safe and effective for treating individuals with ARMS. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02569307 . Registered on 3 October 2015.

Effect of pharmacist intervention on herpes zoster vaccination in community pharmacies.

OBJECTIVE: To evaluate the effectiveness of community pharmacy-based interventions in increasing vaccination rates for the herpes zoster vaccine. DESIGN: Prospective intervention study with a pre-post design. SETTING: Three independent community pharmacies in Tennessee, from December 2007 to June 2008. PATIENTS: Patients whose pharmacy profiles indicated that they were eligible for the vaccine and patients presenting to receive the vaccine at study sites. INTERVENTION: Pharmacists promoted the herpes zoster vaccine through a press release published in local newspapers, a flyer accompanying each prescription dispensed at participating pharmacies, and a personalized letter mailed to patients whose pharmacy profiles indicated that they were eligible for the vaccine. MAIN OUTCOME MEASURES: Comparison of vaccination rates for the herpes zoster vaccine during the control and intervention periods and patients' indication for their sources of education and influence in receiving the vaccine. RESULTS: Vaccination rates increased from 0.37% (n = 59 of 16,121) during the control period to 1.20% (n = 193 of 16,062) during the intervention period ( P < 0.0001). Cochran-Armitage trend analyses, including the months before and after the interventions, confirmed a significantly higher vaccination rate during the intervention month than other months analyzed. More patients indicated that they were educated about the herpes zoster vaccine by one of the pharmacist-driven interventions than by a physician, family/friend, or other source during the intervention period ( P < 0.0001 for all comparisons). Also, more patients were influenced to receive the vaccination as a result of one of the pharmacist-driven interventions than influenced by a physician ( P = 0.0260) or other source ( P < 0.0001). No difference in the effectiveness of patient influence was found when the pharmacy interventions were compared with family/friends ( P = 0.1025). CONCLUSION: Three pharmacist-driven interventions were effective in increasing vaccination rates for the herpes zoster vaccine.

Efficacy and safety of oral topotecan and bevacizumab combination as second-line treatment for relapsed small-cell lung cancer: an open-label multicenter single-arm phase II study.

BACKGROUND: Topotecan is currently the only US Federal Drug Administration (FDA)-approved drug for second-line treatment of relapsed small-cell lung cancer (SCLC). We investigated the efficacy and safety of a novel topotecan-bevacizumab combination in treating relapsed SCLC. PATIENTS AND METHODS: Each 21-day treatment cycle consisted of bevacizumab (15 mg/kg) administration on day 1 and oral topotecan (2.3 mg/m(2)/d) administration on days 1 to 5. Treatment was continued for 8 cycles or until disease progression/toxicity. The primary objective was evaluation of 3-month progression-free survival (PFS). Overall response rate (ORR), duration of response, time to response (TTR), and overall survival (OS) were secondary objectives. RESULTS: The study enrolled 50 patients between July 2008 and May 2010. The 3-month PFS was 65% (95% confidence interval [CI], 49.3%-76.9%), which was promising compared with the historical control of 50% (P = .017) but did not meet the predefined criteria for clinically meaningful improvement. Median PFS was 6.24 months for the sensitive subgroup (progression time from end of previous chemotherapy > 90 days; n = 27) and 2.91 months for the resistant subgroup (progression time ≤ 90 days; n = 23). No patient achieved complete response (CR), and the ORR was 16%. Twenty (40%) patients had stable disease (SD) and 13 (26%) had progressive disease (PD). Median OS, TTR, and duration of response were 7.4, 1.3, and 4.7 months, respectively. The worst reported adverse events (AEs) were grade 1/2 in 11 (22%) patients and grade 3/4/5 in 39 (78%) patients. CONCLUSION: Improvement in the 3-month PFS after treatment with topotecan-bevacizumab was promising compared with the historical control and justifies additional studies with this regimen.

Casopitant and ondansetron for postoperative nausea and vomiting prevention in women at high risk for emesis: a phase 3 study.

HYPOTHESIS: Postoperative nausea and vomiting (PONV) are associated with a variety of complications. Neurokinin subtype 1 receptor antagonists have antiemetic activity in the postoperative setting, and the neurokinin subtype 1 receptor antagonist casopitant mesylate (GW679769) was well tolerated and effective at reducing the incidence of PONV in phase 1 and phase 2 trials. DESIGN: A multicenter, randomized, double-blind, parallel-group, phase 3 analysis was designed to evaluate the safety and efficacy of casopitant in combination with a single intravenous dose of the serotonin subtype 3 receptor antagonist ondansetron hydrochloride for the prevention of PONV in the perioperative setting. SETTING: Forty-three centers in 11 countries. PATIENTS: We studied 484 women at high risk for developing PONV scheduled to undergo operations associated with high emetogenic risk. INTERVENTIONS: The women were randomized to receive a single dose of intravenous ondansetron, 4 mg, or oral casopitant, 50 mg, in combination with intravenous ondansetron, 4 mg. MAIN OUTCOME MEASURES: The primary end point was the proportion of patients who achieved a complete response, defined as no vomiting, retching, or rescue therapy. Patients received a balanced anesthetic regimen. RESULTS: Between March 20 and August 31, 2006, 484 patients were enrolled in the study. Patients in the casopitant plus ondansetron group had a 68.7% rate of complete response during the first 24 hours after surgery compared with 58.7% in the ondansetron-only group (P = .03). The difference between groups in complete response from 24 to 48 hours (63.4% with ondansetron only vs 70.0% with ondansetron plus casopitant) was not significant. No vomiting for 0 to 24 hours was observed in 89.7% of the casopitant plus ondansetron group compared with 74.9% of the ondansetron-only group (P < .001). Oral casopitant administered in combination with ondansetron was well tolerated. CONCLUSIONS: The results of this pivotal phase 3 study demonstrate that the combination of casopitant and ondansetron was superior to ondansetron only in patients at high risk for PONV. Trial Registration clinicaltrials.gov Identifier: NCT00326248.

Reducing dangerous nighttime events in persons with dementia by using a nighttime monitoring system.

BACKGROUND: Nighttime activity, a common occurrence in persons with dementia, increases the risk for injury and unattended home exits and impairs the sleep patterns of caregivers. Technology is needed that will alert caregivers of nighttime activity in persons with dementia to help prevent injuries and unattended exits. METHODS: As part of a product development grant, a controlled pilot study was conducted to test the effectiveness of a new night monitoring system designed for informal caregivers to use in the home. Data from 53 subjects were collected at nine points in time during a 12-month period regarding injuries and unattended home exits that occurred while the caregiver slept. Nighttime activity frequently resulted in nursing home placement. RESULTS: The night monitoring system proved a reliable adjunct to assist caregivers in managing nighttime activity. A total of nine events (injuries or unattended home exits) occurred during the study, with 6 events occurring in the control group. With intent-to-treat analysis, there was no difference between the groups. However, in a secondary analysis that was based on use of the intervention, experimental subjects were 85% less likely to sustain an event than control subjects. CONCLUSIONS: When nighttime activity occurred, it resulted in severe injuries sometimes associated with subsequent nursing home placement. The night monitoring system represents a new technology that caregivers can use to assist them in preventing nighttime injuries and unattended home exits in care recipients with dementia.

Toward single-calibrant quantification in HPLC. A comparison of three detection strategies: evaporative light scattering, chemiluminescent nitrogen, and proton NMR.

There is an urgent need for detection technologies that enable accurate and precise quantification of solutions containing small organic molecules in a manner that is rapid, cheap, non-labor-intensive, readily automated, and without a requirement for specific analyte standards. We provide a theoretical analysis that predicts that the logarithmic nature of the working domain of the evaporative light-scattering detector (ELSD) will normally bias toward underestimation of chromatographically resolved impurities, resulting in an overestimation of analyte purity. This analysis is confirmed by experiments with flow injection analysis (FIA) and gradient reversed-phase high performance liquid chromatography (RP-HPLC). Quantification is further compromised by the dependence of response parameters on the matrix composition and hence on the retention time of the analyte. Attempts were made to ameliorate these problems by using the response surface of a single compound to calibrate throughout the HPLC gradient. A chemiluminescent nitrogen detector (CLND) was also used in a similar manner, and the performance of the two techniques were compared against those of each other and that of a reference standard technique. A protocol for this purpose was developed using proton nuclear magnetic resonance (1H NMR) and the ERETIC method to enable quantification by integrating proton signals. The double-blind comparison exercise confirmed molar nitrogen CLND response to be sufficiently stable and robust across a methanol gradient to be used with a single external nitrogenous calibrant to quantify nitrogen-containing compounds of known molecular formula. The performance of HPLC-CLND was very similar to that of NMR, while that of HPLC-ELSD was seen to be significantly worse, showing it to be unsuitable for the purpose of single-calibrant quantification. We report details and experience of our use of RP-HPLC-CLND-MS to characterize and quantify small amounts of solutions of novel compounds at nominal levels of 10mM in microtiter plate (MTP) format.

Grid and slot scan scatter reduction in mammography: comparison by using Monte Carlo techniques.

PURPOSE: To evaluate a comprehensive array of scatter cleanup techniques in mammography by using a consistent methodology. MATERIALS AND METHODS: Monte Carlo techniques were used to evaluate the Bucky factor (BF) and the contrast improvement factor (CIF) for linear and cellular grids and for slot scan and scanning multiple-slot assembly (SMSA) systems. RESULTS: For a 28-kVp molybdenum anode-molybdenum filter spectrum with a standard detector and a 6-cm-thick 50% adipose-50% glandular breast phantom, slot scan techniques delivered an ideal BF. For slot widths greater than 4 mm, however, the CIF was lower than that achieved by the high-transmission cellular grid with a grid ratio of 3.8:1. A tungsten-septa air-interspaced cellular grid with a 4:1 grid ratio outperformed the high-transmission cellular grid in both BF and CIF. The SMSA was shown to be efficacious when 4-mm-wide slots were separated by at least 20 mm. In comparison with the literature, 3.6% agreement was achieved with other Monte Carlo studies, 3.3% with an experimental study that used a digital detector, and 13%-29% agreement was demonstrated in comparison to film-based experimental studies. CONCLUSION: With use of consistent methods for comparison, cellular grids were shown to substantially outperform linear grids but have slightly higher BFs compared with that of slot scan geometries at the same CIF.