Adjuvant Use of PlasmaJet Device During Cytoreductive Surgery for Advanced-Stage Ovarian Cancer: Results of the PlaComOv-study, a Randomized Controlled Trial in The Netherlands.

OBJECTIVE: Standard surgical treatment of advanced-stage ovarian carcinoma with electrosurgery cannot always result in complete cytoreductive surgery (CRS), especially when many small metastases are found on the mesentery and intestinal surface. We investigated whether adjuvant use of a neutral argon plasma device can help increase the complete cytoreduction rate. PATIENTS AND METHODS: 327 patients with FIGO stage IIIB-IV epithelial ovarian cancer (EOC) who underwent primary or interval CRS were randomized to either surgery with neutral argon plasma (PlasmaJet) (intervention) or without PlasmaJet (control group). The primary outcome was the percentage of complete CRS. The secondary outcomes were duration of surgery, blood loss, number of bowel resections and colostomies, hospitalization, 30-day morbidity, and quality of life (QoL). RESULTS: Complete CRS was achieved in 119 patients (75.8%) in the intervention group and 115 patients (67.6%) in the control group (risk difference (RD) 8.2%, 95% confidence interval (CI) -0.021 to 0.181; P = 0.131). In a per-protocol analysis excluding patients with unresectable disease, complete CRS was obtained in 85.6% in the intervention group and 71.5% in the control group (RD 14.1%, 95% CI 0.042 to 0.235; P = 0.005). Patient-reported QoL at 6 months after surgery differed between groups in favor of PlasmaJet surgery (95% CI 0.455-8.350; P = 0.029). Other secondary outcomes did not differ significantly. CONCLUSIONS: Adjuvant use of PlasmaJet during CRS for advanced-stage ovarian cancer resulted in a significantly higher proportion of complete CRS in patients with resectable disease and higher QoL at 6 months after surgery. (Funded by ZonMw, Trial Register NL62035.078.17.) TRIAL REGISTRATION: Approved by the Medical Ethics Review Board of the Erasmus University Medical Center Rotterdam, the Netherlands, NL62035.078.17 on 20-11-2017. Recruitment started on 30-1-2018.

Evaluation of effectiveness of the PlasmaJet surgical device in the treatment of advanced stage ovarian cancer (PlaComOv-study): study protocol of a randomized controlled trial in the Netherlands.

BACKGROUND: The most important goal for survival benefit of advanced stage ovarian cancer is to surgically remove all visible tumour, because complete cytoreductive surgery (CCS) has been shown to be associated with prolonged survival. In a remarkable number of women, CCS is very challenging. Especially in women with many small metastases on the peritoneum and intestinal surface, conventional CCS with electrosurgery is not able to be "complete" in removing safely all visible tumour. In this randomized controlled trail (RCT) we investigate whether the use of the PlasmaJet Surgical Device increases the rate of CCS, and whether this indeed leads to a longer progression free and overall survival. The main research question is: does the use of the PlasmaJet Surgical Device in surgery for advanced stage ovarian cancer result in an increased number of complete cytoreductive surgeries when compared with conventional surgical techniques. Secondary study objectives are: 30-day morbidity, duration of surgery, blood loss, length of hospitalisation, Quality of Life, disease-free survival, overall survival, percentage colostomy, cost-effectiveness. METHODS: The study design is a multicentre single-blinded superiority RCT in two university and nine non-university hospitals in The Netherlands. Three hundred and thirty women undergoing cytoreductive surgery for advanced stage ovarian carcinoma (FIGO Stage IIIB-IV) will be randomized into two arms: use of the PlasmaJet (intervention group) versus the use of standard surgical instruments combined with electrocoagulation (control group). The primary outcome is the rate of complete cytoreductive surgery in both groups. Secondary study objectives are: 30-day morbidity, duration of surgery, blood loss, length of hospitalisation, Quality of Life, disease-free survival, overall survival, percentage colostomy, cost-effectiveness. Quality of life will be evaluated using validated questionnaires at baseline, at 1 and 6 months after surgery and at 1, 2, 3 and 4 years after surgery. DISCUSSION: We hypothesize the additional value of the use of the PlasmaJet in CCS for advanced stage epithelial ovarian cancer. More knowledge about efficacy, side effects, recurrence rates, cost effectiveness and pathology findings after using the PlasmaJet Device is advocated. This RCT may aid in this void. TRIAL REGISTRATION: Dutch Trial Register NTR6624 . Registered 18 August 2017. Medical Ethical Committee approval number: NL62035.078.17 (Medical Ethical Committee Erasmus Medical Centre Rotterdam).

Can intravenous conscious sedation with midazolam be effective at facilitating surgical dentistry in adolescent orthodontic patients? A service evaluation.

Background Surgical dentistry during orthodontic care often occurs in adolescence and may involve surgical removal or exposure of teeth. The invasive nature of treatment, combined with dental anxiety, means care can often be provided under general anaesthesia (GA). Best-practice guidelines however endorse conscious sedation as an alternative, where appropriate. Although a limited number of studies have shown safe and effective use of intravenous conscious sedation (IVCS) with midazolam in this cohort, robust evidence to support routine use is lacking. Aim To assess whether IVCS with midazolam can effectively facilitate surgical dentistry in adolescent orthodontic patients in primary care.Method A retrospective service evaluation was undertaken reviewing clinical records of adolescents (aged 12-15 years) undergoing surgical exposure and/or surgical removal of teeth under IVCS with midazolam.Results A total of 174 adolescents (mean age 14.2 years) attended for treatment between 2009 and 2015. Of these adolescents, 98.9% (N = 172) allowed cannulation, with all surgical dentistry completed during a single visit. Midazolam dose ranged from 2-7 mg with 79.1% of patients having good or excellent cooperation and three minor adverse events occurring.Conclusion This service evaluation shows IVCS with midazolam can effectively facilitate surgical orthodontics in carefully selected adolescents. There is however a distinct need to further explore potential for this technique to provide a viable alternative to GA.

Investigation of inhalational conscious sedation as a tool for reducing anxiety in adults undergoing exodontia.

AIM: To determine whether adult patients' dental anxiety levels decrease following exodontia carried out under inhalational conscious sedation with nitrous oxide and oxygen (IHS) and local anaesthetic (LA). DESIGN: Retrospective analysis of pre- and post-operative modified dental anxiety score (MDAS) questionnaires completed by patients treated in a primary care oral surgery service between 21 July 2010 and 17 December 2010. METHODOLOGY: 138 patients who had undergone exodontia were divided into three groups: moderate to severe anxiety (MDAS scores 11-25) treated under IHS and LA (n = 60), mild anxiety (MDAS scores 5-10) treated under IHS and LA (n = 43) and mixed anxiety (MDAS scores 5-15) treated under LA only (n = 35). The mean pre- and post-operative MDAS scores were analysed by means of one-tailed, paired t-tests. RESULTS: The moderate to severely anxious group treated under IHS and LA showed a statistically significant decrease of 3.68 between the mean pre- and post-operative MDAS scores (p = 0.000). The IHS mildly anxious group showed a decrease of 0.07 (p = 0.392) and the LA group showed a decrease of 0.23 (p = 0.227). Neither of these results were statistically significant. CONCLUSION: These results support the use of IHS, to reduce anxiety of exodontia, in moderate to severely anxious adults undergoing minor oral surgery (MOS) procedures under LA in primary care oral surgery.

Improved search for Muon-neutrino to electron-neutrino oscillations in MINOS.

We report the results of a search for ν(e) appearance in a ν(µ) beam in the MINOS long-baseline neutrino experiment. With an improved analysis and an increased exposure of 8.2 × 10(20) protons on the NuMI target at Fermilab, we find that 2 sin(2) (θ(23))sin(2)(2θ(13))<0.12(0.20) at 90% confidence level for δ = 0 and the normal (inverted) neutrino mass hierarchy, with a best-fit of 2sin(2) (θ(23))sin(2)(2θ(13)) = 0.041(-0.031)(+0.047) (0.079(-0.053) (+0.071)). The θ(13) = 0 hypothesis is disfavored by the MINOS data at the 89% confidence level.

Active to sterile neutrino mixing limits from neutral-current interactions in MINOS.

Results are reported from a search for active to sterile neutrino oscillations in the MINOS long-baseline experiment, based on the observation of neutral-current neutrino interactions, from an exposure to the NuMI neutrino beam of 7.07×10(20) protons on target. A total of 802 neutral-current event candidates is observed in the Far Detector, compared to an expected number of 754 ± 28(stat) ± 37(syst) for oscillations among three active flavors. The fraction f(s) of disappearing ν(µ) that may transition to ν(s) is found to be less than 22% at the 90% C.L.

First direct observation of muon antineutrino disappearance.

This Letter reports the first direct observation of muon antineutrino disappearance. The MINOS experiment has taken data with an accelerator beam optimized for ν(µ) production, accumulating an exposure of 1.71 × 10²° protons on target. In the Far Detector, 97 charged current ν(µ) events are observed. The no-oscillation hypothesis predicts 156 events and is excluded at 6.3σ. The best fit to oscillation yields |Δm²| = [3.36(-0.40)(+0.46)(stat) ± 0.06(syst)] × 10⁻³ eV², sin²(2θ) = 0.86(-0.12)(+0.11)(stat) ± 0.01(syst). The MINOS ν(µ) and ν(µ) measurements are consistent at the 2.0% confidence level, assuming identical underlying oscillation parameters.

Measurement of the neutrino mass splitting and flavor mixing by MINOS.

Measurements of neutrino oscillations using the disappearance of muon neutrinos from the Fermilab NuMI neutrino beam as observed by the two MINOS detectors are reported. New analysis methods have been applied to an enlarged data sample from an exposure of 7.25×10(20) protons on target. A fit to neutrino oscillations yields values of |Δm(2)|=(2.32(-0.08)(+0.12))×10(-3) eV(2) for the atmospheric mass splitting and sin(2)(2θ)>0.90 (90% C.L.) for the mixing angle. Pure neutrino decay and quantum decoherence hypotheses are excluded at 7 and 9 standard deviations, respectively.

Search for Lorentz invariance and CPT violation with the MINOS far detector.

We searched for a sidereal modulation in the MINOS far detector neutrino rate. Such a signal would be a consequence of Lorentz and CPT violation as described by the standard-model extension framework. It also would be the first detection of a perturbative effect to conventional neutrino mass oscillations. We found no evidence for this sidereal signature, and the upper limits placed on the magnitudes of the Lorentz and CPT violating coefficients describing the theory are an improvement by factors of 20-510 over the current best limits found by using the MINOS near detector.

Search for muon-neutrino to electron-neutrino transitions in MINOS.

This Letter reports on a search for nu(mu) --> nu(e) transitions by the MINOS experiment based on a 3.14x10(20) protons-on-target exposure in the Fermilab NuMI beam. We observe 35 events in the Far Detector with a background of 27+/-5(stat)+/-2(syst) events predicted by the measurements in the Near Detector. If interpreted in terms of nu(mu) --> nu(e) oscillations, this 1.5sigma excess of events is consistent with sin2(2theta(13)) comparable to the CHOOZ limit when |Delta m2|=2.43x10(-3) eV2 and sin2(2theta(23))=1.0 are assumed.

Search for active neutrino disappearance using neutral-current interactions in the MINOS long-baseline experiment.

We report the first detailed comparisons of the rates and spectra of neutral-current neutrino interactions at two widely separated locations. A depletion in the rate at the far site would indicate mixing between nu(mu) and a sterile particle. No anomalous depletion in the reconstructed energy spectrum is observed. Assuming oscillations occur at a single mass-squared splitting, a fit to the neutral- and charged-current energy spectra limits the fraction of nu(mu) oscillating to a sterile neutrino to be below 0.68 at 90% confidence level. A less stringent limit due to a possible contribution to the measured neutral-current event rate at the far site from nu(e) appearance at the current experimental limit is also presented.

Testing Lorentz invariance and CPT conservation with NuMI neutrinos in the MINOS near detector.

A search for a sidereal modulation in the MINOS near detector neutrino data was performed. If present, this signature could be a consequence of Lorentz and CPT violation as predicted by the effective field theory called the standard-model extension. No evidence for a sidereal signal in the data set was found, implying that there is no significant change in neutrino propagation that depends on the direction of the neutrino beam in a sun-centered inertial frame. Upper limits on the magnitudes of the Lorentz and CPT violating terms in the standard-model extension lie between 10(-4) and 10(-2) of the maximum expected, assuming a suppression of these signatures by a factor of 10(-17).

Measurement of neutrino oscillations with the MINOS detectors in the NuMI beam.

This Letter reports new results from the MINOS experiment based on a two-year exposure to muon neutrinos from the Fermilab NuMI beam. Our data are consistent with quantum-mechanical oscillations of neutrino flavor with mass splitting |Deltam2| = (2.43+/-0.13) x 10(-3) eV2 (68% C.L.) and mixing angle sin2(2theta) > 0.90 (90% C.L.). Our data disfavor two alternative explanations for the disappearance of neutrinos in flight: namely, neutrino decays into lighter particles and quantum decoherence of neutrinos, at the 3.7 and 5.7 standard-deviation levels, respectively.

Is intravenous conscious sedation for surgical orthodontics in children a viable alternative to general anaesthesia?--a case review.

AIM: The aim of this case review was to describe the use of local anaesthesia (LA) and intravenous conscious sedation (IVCS) as a safe and effective means of managing patients requiring surgical orthodontic procedures as an alternative to general anaesthesia (GA) in children between the age of 11 and 15 years. MAIN OUTCOME MEASURES: 1) Whether treatment was completed, partially completed or not completed; 2) assessment of physiological parameters to verify safety profile of the technique. METHODS: Records were reviewed retrospectively for all patients included in the series undergoing planned surgical orthodontic procedures between January 2001 and January 2004 under IVCS. All patients had been pre-assessed and deemed to be of sufficient mental and physical maturity to be treated with IVCS. Written informed consent was gained from patients and their parents/guardians with full discussion of the alternative pain and anxiety control methods available including GA. All cases were undertaken by experienced SAS grade surgeons assisted by two dental nurses holding the certificate in dental sedation nursing and their recovery was supervised by registered general nurses. Patients were clinically monitored throughout together with continuous pulse oximetry and intermittent recording of non invasive blood pressure and pulse at 10-15 minute intervals. Patients were reviewed post operatively and any complications or comments noted. RESULTS: Over a three year period a total of 107 patients underwent surgical procedures to aid orthodontic treatment, 28 (26%) under IVCS and 79 (74%) under GA. Twenty-five out of 28 patients in the IVCS group successfully completed all of their planned treatment. CONCLUSIONS: Based on this case series, IVCS would appear to offer a safe and effective alternative to GA for this group of patients providing they are selected and managed by an appropriately trained team in a suitable setting. Further prospective evidence is needed if IVCS is to be recommended for general dental treatment in patients under the age of 16 years.

The use of an intra-oral injection of ketorolac in the treatment of irreversible pulpitis.

AIM: To examine whether an intra-oral injection of a nonsteroidal anti-inflammatory drug (ketorolac), in association with conventional local anaesthetic techniques, would improve the pulp extirpation rate in teeth with irreversible pulpitis. METHODOLOGY: A two group double-blind clinical trial was undertaken in the Dental Casualty Department of the University of Manchester School of Dentistry. Patients were randomly allocated to either the test or control group. The test group received an intra-oral injection of ketorolac (30 mg in 1 mL) in the buccal sulcus adjacent to the tooth being treated. After an interval of 15 min, they then received 2.2 mL of 2% lidocaine with 1 : 80 000 epinephrine by buccal infiltration in the maxilla or by inferior dental block in the mandible. The control group received an intra-oral injection of normal saline (1 mL) in the buccal sulcus adjacent to the tooth being treated, followed by the same local anaesthetic regime as the test group after the 15 min interval. Fifteen minutes after the local anaesthetic injections, pulp extirpation was attempted. All patients completed the short-form McGill pain questionnaire prior to treatment and completed identical questionnaires at 6 and 24 h after treatment. RESULTS: The study protocol set the number of patients to be treated at twenty. However, as the study progressed it became apparent that the intra-oral injection of ketorolac caused significant pain to four of the five patients who received it; therefore the study was terminated after ten patients had been treated. The results from the patients treated showed no significant difference in the pulp extirpation rate between the test and control groups. However, patients with higher pain scores at baseline were less likely to have the pulp completely extirpated, irrespective of whether they were in the test or control group. Pain scores for all patients decreased significantly from baseline to 24 h. CONCLUSION: An intra-oral injection of ketorolac did not improve the pulp extirpation rate in a small group of patients with irreversible pulpitis compared with a placebo. In addition, it was associated with such significant pain on injection that it cannot be recommended as a treatment in this situation.

Ectopic salivary gland tissue in the anterior mandible: a case report.

Ectopic salivary gland inclusions in the mandible are a rare phenomenon. Classically as described by Stafne they have been found in the posterior mandibular region. Cases affecting the anterior mandible are even more unusual. We report a case of ectopic salivary gland tissue in the anterior mandible. In our discussion we emphasise the need for a thorough history, examination and relevant investigations. Mandibular radiolucencies can prove a pitfall for the unwary.

Speech recognition by normal-hearing and cochlear implant listeners as a function of intensity resolution.

The importance of intensity resolution in terms of the number of intensity steps needed for speech recognition was assessed for normal-hearing and cochlear implant listeners. In experiment 1, the channel amplitudes extracted from a six-channel continuous interleaved sampling (CIS) processor were quantized into 2, 4, 8, 16, or 32 steps. Consonant recognition was assessed for five cochlear implant listeners, using the Med-El/CIS-link device, as a function of the number of steps in the electrical dynamic range. Results showed that eight steps within the dynamic range are sufficient for reaching asymptotic performance in consonant recognition. These results suggest that amplitude resolution is not a major factor in determining consonant identification. In experiment 2, the relationship between spectral resolution (number of channels) and intensity resolution (number of steps) in normal-hearing listeners was investigated. Speech was filtered through 4-20 frequency bands, synthesized as a linear combination of sine waves with amplitudes extracted from the envelopes of the bandpassed waveforms, and then quantized into 2-32 levels to produce stimuli with varying degrees of intensity resolution. Results showed that the number of steps needed to achieve asymptotic performance was a function of the number of channels and the speech material used. For vowels, asymptotic performance was obtained with four steps, while for consonants, eight steps were needed for most channel conditions, consistent with our findings in experiment 1. For sentences processed though 4 channels, 16 steps were needed to reach asymptotic performance, while for sentences processed through 16 channels, 4 steps were needed. The results with normal-hearing listeners on sentence recognition point to an inverse relationship between spectral resolution and intensity resolution. When spectral resolution is poor (i.e., a small number of channels is available) a relatively fine intensity resolution is needed to achieve high levels of understanding. Conversely, when the intensity resolution is poor, a high degree of spectral resolution is needed to achieve asymptotic performance. The results of this study, taken together with previous findings on the effect of reduced dynamic range, suggest that the performance of cochlear implant subjects is primarily limited by the small number (four to six) of channels received, and not by the small number of intensity steps or reduced dynamic range.

The effect of parametric variations of cochlear implant processors on speech understanding.

This study investigated the effect of five speech processing parameters, currently employed in cochlear implant processors, on speech understanding. Experiment 1 examined speech recognition as a function of stimulation rate in six Med-E1/CIS-Link cochlear implant listeners. Results showed that higher stimulation rates (2100 pulses/s) produced a significantly higher performance on word and consonant recognition than lower stimulation rates (<800 pulses/s). The effect of stimulation rate on consonant recognition was highly dependent on the vowel context. The largest benefit was noted for consonants in the /uCu/ and /iCi/ contexts, while the smallest benefit was noted for consonants in the /aCa/ context. This finding suggests that the /aCa/ consonant test, which is widely used today, is not sensitive enough to parametric variations of implant processors. Experiment 2 examined vowel and consonant recognition as a function of pulse width for low-rate (400 and 800 pps) implementations of the CIS strategy. For the 400-pps condition, wider pulse widths (208 micros/phase) produced significantly higher performance on consonant recognition than shorter pulse widths (40 micros/phase). Experiments 3-5 examined vowel and consonant recognition as a function of the filter overlap in the analysis filters, shape of the amplitude mapping function, and signal bandwidth. Results showed that the amount of filter overlap (ranging from -20 to -60 dB/oct) and the signal bandwidth (ranging from 6.7 to 9.9 kHz) had no effect on phoneme recognition. The shape of the amplitude mapping functions (ranging from strongly compressive to weakly compressive) had only a minor effect on performance, with the lowest performance obtained for nearly linear mapping functions. Of the five speech processing parameters examined in this study, the pulse rate and the pulse width had the largest (positive) effect on speech recognition. For a fixed pulse width, higher rates (2100 pps) of stimulation provided a significantly better performance on word recognition than lower rates (<800 pps) of stimulation. High performance was also achieved by jointly varying the pulse rate and pulse width. The above results indicate that audiologists can optimize the implant listener's performance either by increasing the pulse rate or by jointly varying the pulse rate and pulse width.

Neurophysiologic correlates of cross-language phonetic perception.

This study examined neurophysiologic correlates of the perception of native and nonnative phonetic categories. Behavioral and electrophysiologic responses were obtained from Hindi and English listeners in response to a stimulus continuum of naturally produced, bilabial CV stimuli that differed in VOT from -90 to 0 ms. These speech sounds constitute phonemically relevant categories in Hindi but not in English. As expected, the native Hindi listeners identified the stimuli as belonging to two distinct phonetic categories (/ba/ and /pa/) and were easily able to discriminate a stimulus pair across these categories. On the other hand, English listeners discriminated the same stimulus pair at a chance level. In the electrophysiologic experiment N1 and MMN cortical evoked potentials (considered neurophysiologic indices of stimulus processing) were measured. The changes in N1 latency which reflected the duration of pre-voicing across the stimulus continuum were not significantly different for Hindi and English listeners. On the other hand, in response to the /ba/-/pa/ stimulus contrast, a robust MMN was seen only in Hindi listeners and not in English listeners. These results suggest that neurophysiologic levels of stimulus processing reflected by the MMN and N1 are differentially altered by linguistic experience.

The effect of reduced dynamic range on speech understanding: implications for patients with cochlear implants.

OBJECTIVE: To determine the effect of reduced dynamic range on speech understanding when the speech signals are processed in a manner similar to a 6-channel cochlear implant speech processor. DESIGN: Signals were processed in a manner similar to a 6-channel cochlear implant processor and output as a sum of sine waves with frequencies equal to the center frequencies of the analysis filters. The amplitudes of the sine waves were compressed in a systematic fashion to simulate the effect of reduced dynamic range. The compressed signals were presented to 10 normal-hearing listeners for identification. RESULTS: There was a significant effect of compression for all test materials. The effect of the compression on speech understanding was different for the three test materials (vowels, consonants, and sentences). Vowel recognition was affected the most by the compression, and consonant recognition was affected the least by the compression. Feature analysis indicated that the reception of place information was affected the most. Sentence recognition was moderately affected by the compression. CONCLUSIONS: Dynamic range should affect the speech perception abilities of cochlear implant users. Our results suggest that a relatively wide dynamic range is needed for a high level of vowel recognition and a relatively small dynamic range is sufficient to maintain consonant recognition. We infer from this outcome that, if other factors were held equal, an implant patient with a small dynamic range could achieve moderately high scores on tests of consonant recognition but poor performance on vowel recognition, and that it is more likely for an implant patient with a large dynamic range to obtain high scores on vowel recognition than for an implant patient with a small dynamic range.