Implementing clinical supervision

To discover whether clinical supervision would be a useful tool, nurses must discuss their aims and expectations and, through workshops, create a system that reflects their needs. A co-ordinator well-versed in the literature could lead this project.     

Image registration of BANG gel dose maps for quantitative dosimetry verification

Background: The BANG® (product symbol SGEL, MGS Research Inc., Guilford, CT) polymer gel has been shown to be a valuable dosimeter for determining three-dimensional (3D) dose distributions. Because the proton relaxation rate (R2) of the gel changes as a function of absorbed dose, MR scans of the irradiated gel can be used to generate 3D dose maps. Previous work with the gel, however, has not relied on precise localization of the measured dose distribution. This has limited its quantitative use, as no precise correlation exists with the planned distribution. This paper reports on a technique for providing this correlation, thus providing a quality assurance tool that includes all of the steps of imaging, treatment planning, dose calculation, and treatment localization.

Methods and Materials: The BANG® gel formulation was prepared and poured into spherical flasks (15.3-cm inner diameter). A stereotactic head ring was attached to each flask. Three magnetic resonance imaging (MRI) and computed tomography (CT) compatible fiducial markers were placed on the flask, thus defining the central axial plane. A high-resolution CT scan was obtained of each flask. These images were transferred to a radiosurgery treatment-planning program, where treatment plans were developed. The gels were irradiated using our systems for stereotactic radiosurgery or fractionated stereotactic radiotherapy. The gels were MR imaged, and a relative 3D dose map was created from an R2 map of these images. The dose maps were transferred to an image-correlation program, and then fused to the treatment-planning CT scan through a rigid body match of the MRI/CT-compatible fiducial markers. The fused dose maps were imported into the treatment-planning system for quantitative comparison with the calculated treatment plans.

Results: Calculated and measured isodose surfaces agreed to within 2 mm at the worst points within the in-plane dose distributions. This agreement is excellent, considering that the pixel resolution of the MRI dose maps is 1.56 × 1.56 mm, and the treatment-planning dose distributions were calculated on a 1-mm dose grid. All points within the dose distribution were well within the tolerances set forth for commissioning and quality assurance of stereotactic treatment-planning systems. Moreover, the quantitative evaluation presented here tests the accuracy of the entire treatment-planning and delivery process, including stereotactic frame rigidity, CT localization, CT/MR correlation, dose calculation, and radiation delivery.

Conclusion: BANG® polymer gel dosimetry coupled with image correlation provides quantitative verification of the accuracy of 3D dose distributions. Such quantitative evaluation is imperative to ensure the high quality of the 3D dose distributions generated and delivered by stereotactic and other conformal irradiation systems.     

Long-term treatment of multiple sclerosis with interferon-beta may be cost effective

Multiple sclerosis (MS) is a devastating disease that can occur in early life, progressing to rapid disability and loss of physical, psychosocial and economic functioning, significantly affecting quality of life. The traditional treatment for MS has been symptomatic, treating acute relapses without affecting the underlying disease. The introduction of interferon-beta (IFN beta) has offered significant clinical benefits by reducing the frequency of relapses and slowing disease progression. Although the costs of this treatment are high, the costs to society of caring for a patient disabled by MS are greater, and if IFN beta can delay disease progression in the longer term, the economic impact would be substantial. Previous pharmacoeconomic studies of IFN beta have suggested that benefits can only be achieved at extremely high cost, with reported cost-effectiveness measures of up to 1 million pounds sterling (Pound) per quality-adjusted life year (QALY) [1995 values]. However, these studies have considered only the short term benefits of IFN beta treatment: over 2 to 3 years, the impact of treatment on patients' quality of life is relatively small, and cost-utility analyses that do not consider longer term benefits nor include societal costs may be misleading. The model reported here is based on the hypothesis that the delay in disease progression seen in short term clinical trials is likely to continue if treatment is continued. The model also assumes that the delay in disease progression, which represents a reduction in brain atrophy, will result in lasting clinical benefits even if treatment is stopped. These assumptions are strongly supported by clinical trial data and the treatment hypothesis itself. A delay in disease progression will result in a significant improvement in functioning and quality of life, and if the costs associated with increased disability can be postponed, even long term treatment of MS with IFN beta can be shown to be cost effective. Using resource utilisation costs derived from an economic evaluation of MS in the UK, it was possible to calculate the impact of delaying disease progression in terms of both health service and societal costs. An estimate of mean disease progression in patients with MS treated with IFN beta-1a compared with patients who did not receive disease-modifying agents suggested that significant cost savings would be realised after about 12 years' treatment with IFN beta-1a. The application of utility scores to the disease progression curves also facilitated estimates of cost effectiveness, with cost per QALY values ranging from 27,036 Pounds after 2 years' treatment with IFN beta-1a to 37,845 Pounds after 20 years' treatment (1995 values).     

Peri-operative outcomes of patients with stage IV endometriosis undergoing robotic-assisted laparoscopic surgery

We analyzed peri-operative outcomes of 80 patients who underwent robotic-assisted laparoscopic surgery and were diagnosed with stage IV endometriosis (revised American Society for Reproductive Medicine) between January 2007 and December 2010 at a tertiary gynecologic oncology referral center with a fellowship training program. Eligible women had a combination of one or more factors: pelvic mass, sub-acute or chronic pelvic pain, dysmenorrhea, dyspareunia, elevated serum CA-125, diagnosed with stage IV endometriosis at surgery with robotic-assisted gynecologic procedures using the da Vinci^? Surgical System. The mean age was 43.7?±?7.0?years, body mass index 27.5?±?7.4?kg/m², and 23 (28.9%) patients had prior endometriosis surgery. Presenting symptoms included: chronic pelvic pain (48.8%), dysmenorrhea (40.3%), and dyspareunia (33.8%). Sixty-nine (86%) patients had pelvic masses (43 unilateral and 26 bilateral). Thirty-seven (46.3%) had elevated CA-125 levels (mean 97.9?±?71.6 U/ml). Forty-eight (60%) underwent robotic-assisted laparoscopic hysterectomy (RALH)/bilateral salpingo-oophorectomy (BSO), 9 (11.3%) RALH/unilateral salpingo-oophorectomy (USO), 5 (6.3%) modified radical hysterectomy, and 10 (13%) USO or BSO only. Four (5%) had ovarian cystectomies with excision of endometriotic implants. Three (3.8%) underwent appendectomy and no patient required bowel resection. Four (5%) patients required conversion to laparotomy during the first 15 cases of this series [dense adhesions (3) and ureteral injury (1)]. Mean operative time was 115?±?46?min, blood loss 88?±?67?ml, and length of stay 1.0?±?0.4?days. There were four (5%) complications (ureteral injury, cuff abscess, cuff hematoma, re-admission for nausea and vomiting secondary to narcotics) and no transfusions. One (1.3%) patient underwent a second surgery for pain (dyspareunia). Robotic-assisted surgery for stage IV endometriosis resulted in excellent pain relief, with few laparotomy conversions or complications during a robotic learning-curve experience.     

Somatostatin release by glutamate in vivo is primarily regulated by AMPA receptors.

1. We have used in vivo microdialysis in anaesthetized rats to investigate whether levels of striatal somatostatin (SRIF) can be increased in response to application of the ionotropic glutamate receptor agonists AMPA and NMDA. 2. Application of both AMPA and NMDA (10, 50, 100 and 500 microM) for 20 min periods produced concentration-dependent increases in the extracellular levels of SRIF. A 500 microM dose of each compound was shown to be the most potent concentration tested, increasing levels of SRIF by 32 fold (NMDA) and 35 fold (AMPA). At lower concentrations (10 microM) NMDA failed to evoke significant amounts of SRIF while AMPA increased levels of the peptide 2.3 fold. 3. Application of the respective receptor antagonists APV (NMDA receptor) and DNQX (AMPA receptor) abolished the abilities of the agonists to evoke release of SRIF. Interestingly DNQX abolished the ability of NMDA to evoke release of the peptide as well. 4. The ability of both AMPA and NMDA to evoke increases in the levels of extracellular SRIF further illustrates the reciprocal relationship that exists between SRIF and glutamate in the striatum which impacts particularly on dopaminergic functioning in this region.     

Facilitation of learning by social-emotional feedback in humans is beta-noradrenergic-dependent

Adaptive behavior in dynamic environments critically depends on the ability to learn rapidly and flexibly from the outcomes of prior choices. In social environments, facial expressions of emotion often serve as performance feedback and thereby guide declarative learning. Abundant evidence implicates beta-noradrenergic signaling in the modulatory influence of emotion on declarative learning. It is currently unclear whether a similar mechanism also mediates a guidance of declarative learning by social-emotional feedback administered in the form of facial expressions. We therefore conducted a double-blind randomized placebo-controlled trial to test the effects of a 40-mg single oral dose of the nonspecific beta-noradrenergic antagonist propranolol in a behavioral task that required gradual declarative learning of item-category associations from either social-emotional (happy vs. angry faces) or nonsocial (green vs. red color signals) trial-by-trial feedback. As predicted on the basis of our previous experiments, learning from social-emotional feedback was more effective than learning from nonsocial feedback in placebo-treated subjects. This advantage of social-emotional over nonsocial feedback was abolished by propranolol treatment. Propranolol had no effect on learning during the nonsocial feedback condition. Our findings suggest that a facilitation of declarative learning by social-emotional feedback critically involves signaling via beta-noradrenergic receptors.     

Synthesis and evaluation of cryptolepine analogues for their potential as new antimalarial agents.

The indoloquinoline alkaloid cryptolepine 1 has potent in vitro antiplasmodial activity, but it is also a DNA intercalator with cytotoxic properties. We have shown that the antiplasmodial mechanism of 1 is likely to be due, at least in part, to a chloroquine-like action that does not depend on intercalation into DNA. A number of substituted analogues of 1 have been prepared that have potent activities against both chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum and also have in common with chloroquine the inhibition of beta-hematin formation in a cell-free system. Several compounds also displayed activity against Plasmodium berghei in mice, the most potent being 2,7-dibromocryptolepine 8, which suppressed parasitemia by 89% as compared to untreated infected controls at a dose of 12.5 mg kg(-1) day(-1) ip. No correlation was observed between in vitro cytotoxicity and the effect of compounds on the melting point of DNA (DeltaT(m) value) or toxicity in the mouse-malaria model.     

Low 25-hydroxyvitamin D level is independently associated with non-alcoholic fatty liver disease

Background and aimsWe sought to explore associations between serum 25-hydroxyvitamin D [25(OH)D] levels and non-alcoholic fatty liver disease [NAFLD] in an integrated healthcare delivery system in the U.S.Methods and resultsSix hundred and seven NAFLD cases were randomly matched 1:1 with controls for age, sex, race and season of measurement. Conditional logistic regression was used to evaluate if serum 25(OH)D levels were associated with increased odds of NAFLD (diagnosed by ultrasound) after adjusting for body mass index and history of diabetes, renal, peripheral vascular and liver diseases (model 1) and also for hypertension (model 2). Mean (SD) serum 25(OH)D level was significantly lower in the group with NAFLD as compared with that in the matched control group (75 ± 17 vs. 85 ± 20 nmol/L [30 ± 7 vs. 34 ± 8 ng/mL], P < 0.001). Inadequate 25(OH)D status progressively increased the odds of NAFLD when classified categorically as sufficient (25(OH)D 75 nmol/L [>30 ng/mL], reference group), insufficient (37–75 nmol/L [15–30 ng/mL]; adjusted odds ratio [OR]: 2.40, 95% confidence interval [CI]: 0.90–6.34) or deficient (<37 nmol/L [<15 ng/mL]; adjusted OR: 2.56, 95% CI: 1.27–5.19). When modeled as a continuous variable, increased log₁₀ 25(OH)D was inversely associated with the risk of prevalent NAFLD (adjusted OR: 0.25, 95% CI: 0.064–0.96, P = 0.02).ConclusionCompared with matched controls, patients with NAFLD have significantly decreased serum 25(OH)D levels, suggesting that low 25(OH)D status might play a role in the development and progression of NAFLD.