Entire Set Of Patients Research Articles

Are the rapid tranquilisation nice guidelines adhered to, in patients with agitated/aggressive behavior? a QIP

AimsTo explore whether the NICE guidelines for rapid tranquilisation are adhered to in the Psychiatric intensive care unit (PICU/ Tryweryn).MethodData were collected by core trainees. Standards were taken from NICE guidelines NG10. All patients who had received rapid tranquilisation, that were in PICU from August 2019 to February 2020 were considered in this a.ResultDuring the first PDSA, we discussed with the staff in the ward regarding the protocol. Prior to actually starting the second audit, the adherence was noted to be low. However following persistence and having created a protocol jointly with the ward manager, we could see the difference. The staff were appreciated for their efforts in maintaining 100% adherence. The same was intended to be continued with some positive reinforcement from the auditing team. Over the first 2 months, 12 patients received Rapid Tranquilisation. Out of these 12, we randomly selected 4 patients to find the adherence of the NICE guidelines to be 100 per cent. The predictions regarding the adherence to protocol showed that the PDSA was successful.During the second PDSA, the adherence was 100% again. The adherence to the protocol has been followed for not just the sample that was selected, but for the entire set of patients who received the Rapid Tranquilisation. Following this QIP, we formatted the proforma which included the services to be provided/ actions to be taken, Post Rapid Tranquilisation physical health monitoring and response to medication.ConclusionThe utilisation of de-escalation techniques and behavioural support plans that was person-centred in turn brought down the rate of Rapid Tranquilisation successfully. Thus placing our PICU as having the least restraints in the UK in 2019 (Second least 3/ month). Our PICU was awarded the prestigious Nursing Times Team of the Year Award for their pioneering work.Following this QIP, we then formatted the proforma for Rapid Tranquilisation which included the services to be provided/ actions to be taken, Post Rapid Tranquilisation physical health monitoring and patients response to medication. The PICU will continue to maintain this 100% standard and we would then consider extending the Audit to both Open wards and PICU in entire North Wales.

Variceal bleeding is aggravated by portal venous invasion of hepatocellular carcinoma: a matched nested case-control study

BackgroundWe hypothesized that portal vein tumor thrombosis (PVTT) in hepatocellular carcinoma (HCC) increases portal pressure and causes esophageal varices and variceal bleedings. We examined the incidence of high-risk varices and variceal bleeding and determined the indications for variceal screening and prophylaxis.MethodsThis study included 1709 asymptomatic patients without any prior history of variceal hemorrhage or endoscopic prophylaxis who underwent upper endoscopy within 30 days before or after initial anti-HCC treatment. Of these patients, 206 had PVTT, and after 1:2 individual matching, 161 of them were matched with 309 patients without PVTT. High-risk varices were defined as large/medium varices or small varices with red-color signs and variceal bleeding. Bleeding rates from the varices were compared between matched pairs. Risk factors for variceal bleeding in the entire set of patients with PVTT were also explored.ResultsIn the matched-pair analysis, the proportion of high-risk varices at screening (23.0% vs. 13.3%; P = 0.003) and the cumulative rate of variceal bleeding (4.5% vs. 0.4% at 1 year; P = 0.009) were significantly greater in the PVTT group. Prolonged prothrombin time, lower platelet count, presence of extrahepatic metastasis, and Vp4 PVTT were independent risk factors related to high-risk varices in the total set of 206 patients with PVTT (Adjusted odds ratios [95% CIs], 1.662 [1.151–2.401]; 0.985 [0.978–0.993]; 4.240 [1.783–10.084]; and 3.345 [1.457–7.680], respectively; Ps < 0.05). During a median follow-up of 43.2 months, 10 patients with PVTT experienced variceal bleeding episodes, 9 of whom (90%) had high-risk varices. Presence of high-risk varices and sorafenib use for HCC treatment were significant predictors of variceal bleeding in the complete set of patients with PVTT (Adjusted hazard ratios [95% CIs], 26.432 [3.230–216.289]; and 5.676 [1.273–25.300], respectively; Ps < 0.05).ConclusionsPVTT in HCC appears to increase the likelihood of high-risk varices and variceal bleeding. In HCC patients with PVTT, endoscopic prevention could be considered, at least in high-risk variceal carriers taking sorafenib.

Hypoglycemia Prevention via Personalized Glucose-Insulin Models Identified in Free-Living Conditions.

The objective of this research is to show the effectiveness of individualized hypoglycemia predictive alerts (IHPAs) based on patient-tailored glucose-insulin models (PTMs) for different subjects. Interpatient variability calls for PTMs that have been identified from data collected in free-living conditions during a one-month trial. A new impulse-response (IR) identification technique has been applied to free-living data in order to identify PTMs that are able to predict the future glucose trends and prevent hypoglycemia events. Impulse response has been applied to seven patients with type 1 diabetes (T1D) of the University of Amsterdam Medical Centre. Individualized hypoglycemia predictive alert has been designed for each patient thanks to the good prediction capabilities of PTMs. The PTMs performance is evaluated in terms of index of fitting (FIT), coefficient of determination, and Pearson's correlation coefficient with a population FIT of 63.74%. The IHPAs are evaluated on seven patients with T1D with the aim of predicting in advance (between 45 and 10 minutes) the unavoidable hypoglycemia events; these systems show better performance in terms of sensitivity, precision, and accuracy with respect to previously published results. The proposed work shows the successful results obtained applying the IR to an entire set of patients, participants of a one-month trial. Individualized hypoglycemia predictive alerts are evaluated in terms of hypoglycemia prevention: the use of a PTM allows to detect 84.67% of the hypoglycemia events occurred during a one-month trial on average with less than 0.4% of false alarms. The promising prediction capabilities of PTMs can be a key ingredient for new generations of individualized model predictive control for artificial pancreas.

Impact of first-line cancer treatment on the follicle quality in cryopreserved ovarian samples from girls and young women.

STUDY QUESTIONDoes first-line chemotherapy affect the quality of ovarian pre-antral follicles and stromal tissue in a population of young patients?SUMMARY ANSWERExposure to first-line chemotherapy significantly impacts follicle viability, size of residual intact follicles, steroid secretion in culture and quality of the stromal compartment.WHAT IS KNOWN ALREADYFirst-line chemotherapy is considered to have a low gonadotoxic potential, and as such, does not represent an indication for fertility preservation. Studies investigating the effects of chemotherapy on the quality of ovarian tissue stored for fertility preservation in young patients are limited and the results sometimes contradictory.STUDY DESIGN, SIZE, DURATIONWe conducted a retrospective cohort study including young patients referred to three centers (Helsinki, Oslo and Tampere) to perform ovarian tissue cryopreservation for fertility preservation between 2003 and 2018.PARTICIPANTS/MATERIALS, SETTING, METHODSA total of 43 patients (age 1–24 years) were included in the study. A total of 25 were exposed to first-line chemotherapy before cryopreservation, whereas 18 patients were not. Density and size of follicles divided by developmental stages, prevalence of atretic follicles, health of the stromal compartment and functionality of the tissue in culture were evaluated and related to age and chemotherapy exposure. Activation of dormant follicles and DNA damage were also assessed.MAIN RESULTS AND THE ROLE OF CHANCEPatients exposed to first-line chemotherapy showed a significantly higher density of atretic primordial and intermediary follicles than untreated patients. The intact primordial and intermediary follicles were significantly smaller in size in patients exposed to chemotherapy. Production of steroids in culture was also significantly impaired and a higher content of collagen and DNA damage was observed in the stromal compartment of treated patients. Collectively, these observations may indicate reduced quality and developmental capacity of follicles as a consequence of first-line chemotherapy exposure. Neither increased activation of dormant follicles nor elevated levels of DNA damage in oocyte nuclei were found in patients exposed to chemotherapy.LIMITATIONS, REASONS FOR CAUTIONThe two groups were not homogeneous in terms of age and the patients were exposed to different treatments, which did not allow us to distinguish the effect of specific agents. The limited material availability did not allow us to perform all the analyses on the entire set of patients.WIDER IMPLICATION OF THE FINDINGSThis study provides for the first time a comprehensive analysis of the effects of first-line chemotherapy on the health, density and functionality of follicles categorized according to the developmental stage in patients under 24 years of age. When exposed to these treatments, patients were considered at low/medium risk of infertility. Our data suggest a profound impact of these relatively safe therapies on ovarian health and encourages further exploration of this effect in follow-up studies in order to optimize fertility preservation for young cancer patients.STUDY FUNDING/COMPETING INTEREST(S)This study was funded by the Swedish Childhood Cancer Foundation, the Finnish Cancer Society, the Finnish Pediatric Research Foundation, the Väre Foundation for Pediatric Cancer Research, The Swedish Research Council, the Stockholm County Council (ALF project) and Karolinska Institutet. The authors have no conflict of interest to declare.

Rejoinder to “Statistical inference problems in sequential parallel comparison designs”

ABSTRACTIn this rejoinder the authors stipulate further for two challenging issues. First, if placebo non-responders are selected simply by their response meeting a threshold, this selection may have misclassification error and consequently the treatment effect estimate may be biased, regardless of whether the estimand at the second stage is the treatment effect in the entire population or placebo non-responders. Secondly, the weak null hypothesis considered in our article Statistical Inference Problems in Sequential Parallel Comparison Design (2019) is that the expected treatment effects in placebo non-responders and in the entire set of patients entering the trial are both zero, in contrast to the strong null hypothesis that the statistical distribution of the response variable is equal in the compared treatments. The impact of violating the assumption of equal moments other than the mean parameter on statistical operating characteristics in estimation and testing of treatment effect can be substantial. As an example, the ordinary least squares based test detects a treatment difference even if the expected treatment effects in placebo non-responders and the entire population are both zero.

Access to Initial Treatment Was Not the Driving Force of the Survival Disparity By Insurance Status in Follicular Lymphoma — an Analysis of the National Cancer Database (NCDB)

Background:Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma. The initial management varies from watchful waiting to a combination of chemoimmunotherapy (CT) and radiation therapy (RT). Goldstein et al. recently reported (Blood, pre-published online, July 24 2018) that FL patients with no insurance or Medicaid had worse OS. We examined whether the survival discrepancy was caused by access to initial treatment using the National Cancer Database (NCDB).Methods:FL cases diagnosed from year 2004-2015 in NCDB were included. Demographic characteristics were compared using Chi-square test for categorical variables and ANOVA for continuous variables. Use of CT and RT was analyzed in multivariate logistic regression including the following variables: age, gender, race, Hispanic ethnicity, stage, grade, primary site extranodal, facility type, urban/rural location, distance to facility, year period of diagnosis (2004-2010 vs 2011-2015), education, income and insurance status. Overall survival (OS) was analyzed using Cox proportional hazard model including the same covariates with addition of CT and RT.After Jan 2013, rituximab was captured as immunotherapy. To assess the use of rituximab, we compared immunotherapy in years 2014 and 2015 to avoid possible data entry error in 2013.The treatment modalities and OS were similar for uninsured and Medicaid patients, and for Private and Medicare patients after adjusting for covariates. We combined “uninsured” and “Medicaid” into “Less” insurance and “Private” and “Medicare” into “Increased” insurance.Results:A total of 94057 FL cases were included in the analysis with the following insurance status: Uninsured 2723 (2.9%), Medicaid 3804 (4.0%), Private insurance 43354 (46.1%), and Medicare 44176 (47.0%).Patients with no insurance or Medicaid were more likely to present at an advanced stage (Table 1).In the multivariate model, less insurance was associated with less initial use of radiation therapy (OR=0.87, p=0.003) and more use of CT (OR=1.28 p<0.0001). For patients diagnosed in years 2014 and 2015, initial use of immunotherapy (most likely rituximab) and the waiting time before starting immunotherapy did not differ by insurance status.Both less insurance and not-receiving radiation therapy were associated with worse OS after adjusting for covariates (HR=1.96 and 1.30, respectively, p<0.0001 for both, Table 3, Figure 1). Chemoimmunotherapy was not associated with OS. Lower education and income were both associated with worse OS after adjusting for insurance (Table 3).RT is recommended as frontline treatment for suitable patients with early stage (stage I/II) low grade (grade 1/2) FL. We analyzed the use of RT and survival outcome in this patient group. The results were similar to results for the entire patient set. Patients with less insurance received RT less often (21.7% vs 24.7%, p=0.02), and when they did receive radiation therapy, the waiting time before starting treatment was longer (89 days vs 79 days, respectively, p=0.02). Both less insurance and not-receiving RT were associated with worse OS (p<0.0001 for both, Table 4).Conclusion:Follicular lymphoma patients with no insurance or Medicaid had worse OS. Less insurance was associated with decreased access to initial radiation therapy but not chemoimmunotherapy. However the survival discrepancy cannot be solely explained by access to radiation therapy given the magnitude of difference. Moreover, insurance remains a significant predictor of survival after adjusting for initial treatment. The key drivers of the survival discrepancy by insurance status in FL patients need to be further defined. [Display omitted] DisclosuresFeldman:Portola: Research Funding; KITE: Speakers Bureau; Celgene: Speakers Bureau; Pharmacyclics: Speakers Bureau; Janssen: Speakers Bureau; Seattle Genetics: Research Funding, Speakers Bureau; Johnson and Johnson: Speakers Bureau. Chang:Incyte: Research Funding.

Spectral multi-energy CT texture analysis with machine learning for tissue classification: an investigation using classification of benign parotid tumours as a testing paradigm

There is a rich amount of quantitative information in spectral datasets generated from dual-energy CT (DECT). In this study, we compare the performance of texture analysis performed on multi-energy datasets to that of virtual monochromatic images (VMIs) at 65 keV only, using classification of the two most common benign parotid neoplasms as a testing paradigm. Forty-two patients with pathologically proven Warthin tumour (n = 25) or pleomorphic adenoma (n = 17) were evaluated. Texture analysis was performed on VMIs ranging from 40 to 140 keV in 5-keV increments (multi-energy analysis) or 65-keV VMIs only, which is typically considered equivalent to single-energy CT. Random forest (RF) models were constructed for outcome prediction using separate randomly selected training and testing sets or the entire patient set. Using multi-energy texture analysis, tumour classification in the independent testing set had accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of 92%, 86%, 100%, 100%, and 83%, compared to 75%, 57%, 100%, 100%, and 63%, respectively, for single-energy analysis. Multi-energy texture analysis demonstrates superior performance compared to single-energy texture analysis of VMIs at 65 keV for classification of benign parotid tumours. • We present and validate a paradigm for texture analysis of DECT scans. • Multi-energy dataset texture analysis is superior to single-energy dataset texture analysis. • DECT texture analysis has high accura\cy for diagnosis of benign parotid tumours. • DECT texture analysis with machine learning can enhance non-invasive diagnostic tumour evaluation.

A long non-coding RNA expression signature to predict survival of patients with colon adenocarcinoma.

Colon cancer is the most common type of gastrointestinal cancer and is still the leading cause of cancer-related mortality worldwide. Long non-coding RNAs (lncRNAs) have been proved to be superior biomarkers in cancer diagnosis and prognosis than miRNAs and protein-coding genes. In the current study, our objective was to detect novel lncRNA biomarkers by analyzing lncRNA expression profiles and clinical data in a large cohort of patients with colon patients from The Cancer Genome Atlas (TCGA). By using Cox regression analysis, we identified two lncRNAs (SNHG6 and CTD-2354A18.1) which could be independent prognostic factors for predicting clinical outcome in colon adenocarcinoma. Then a linear combination of these two lncRNA biomarkers (SNHG6 and CTD-2354A18.1), termed two-lncRNA signature, was developed in the training set as a predictor for OS in patients with colon adenocarcinoma, and validated in the testing set and the entire patient set. This two-lncRNA signature demonstrated significant prognostic performance in both the testing set and the entire patient set which classified the patients into two groups with significantly different OS. The multivariate and stratified analysis suggested that the prognostic value of the two-lncRNA signature was independent of other traditional clinical variables. Functional analysis suggested that these two lncRNA biomarkers might be mainly involved in transcription/translation-related or DNA repair-related biological processes. In summary, our results warrant further studies on these lncRNAs that will improve our understanding of the mechanisms associated with pathogenesis and progression of colon adenocarcinoma.

Inherited functional variants of the lymphocyte receptor CD5 influence melanoma survival.

Despite the recent progress in treatment options, malignant melanoma remains a deadly disease. Besides therapy, inherited factors might modulate clinical outcome, explaining in part widely varying survival rates. T-cell effector function regulators on antitumor immune responses could also influence survival. CD5, a T-cell receptor inhibitory molecule, contributes to the modulation of antimelanoma immune responses as deduced from genetically modified mouse models. The CD5 SNPs rs2241002 (NM_014207.3:c.671C > T, p.Pro224Leu) and rs2229177 (NM_014207.3:c.1412C > T, p.Ala471Val) constitute an ancestral haplotype (Pro224-Ala471) that confers T-cell hyper-responsiveness and worsens clinical autoimmune outcome. The assessment of these SNPs on survival impact from two melanoma patient cohorts (Barcelona, N = 493 and Essen, N = 215) reveals that p.Ala471 correlates with a better outcome (OR= 0.57, 95% CI = 0.33-0.99, Adj. p = 0.043, in Barcelona OR = 0.63, 95% CI = 0.40-1.01, Adj. p = 0.051, in Essen). While, p.Leu224 was associated with increased melanoma-associated mortality in both cohorts (OR = 1.87, 95% CI = 1.07-3.24, Adj. p = 0.030 in Barcelona and OR = 1.84, 95% CI = 1.04-3.26, Adj. p = 0.037, in Essen). Furthermore survival analyses showed that the Pro224-Ala471 haplotype in homozygosis improved melanoma survival in the entire set of patients (HR = 0.27, 95% CI 0.11-0.67, Adj. p = 0.005). These findings highlight the relevance of genetic variability in immune-related genes for clinical outcome in melanoma.

Tight glycemic control in acutely ill patients: low evidence of benefit, high evidence of harm!

In 1878 Claude Bernard described hyperglycemia during hemorrhagic shock [1]. It is now well known that acute illness or injury may result in hyperglycemia, insulin resistance, and glucose intolerance, collectively termed stress hyperglycemia [2]. Stress hyperglycemia is an evolutionarily preserved adaptive response which provides the nervous and immune system with an immediate source of energy at a time of crisis. Insects, worms, and all vertebrates develop stress hyperglycemia when exposed to stress [2]. Stress hyperglycemia is a component of the stereotypic and coordinated response to stress referred to by Hans Selye as the “general adaption syndrome” which until 2001 was believed to be a beneficial host response which enhanced the host’s chances of survival [3]. On 8 November 2001, Van den Berghe and colleagues published a study entitled “Intensive insulin therapy in critically ill patients” in which they randomized 1548 surgical ICU patients (63 % who had undergone cardiac surgery) to an intensive insulin therapy (IIT) protocol targeting a blood glucose of 80–110 mg/dl or a control arm in which patients only received insulin when the blood glucose exceeded 215 mg/dl with a target of 180–200 mg/ dl (Leuven I study) [4]. Hospital mortality was 7.2 % in the IIT group as compared to 10.9 % in the control group (p = 0.01); in addition IIT reduced length of stay and patient morbidities. This study was supported by retrospective cohort studies in acutely ill patients demonstrating an association between increasing hyperglycemia and poor clinical outcomes. The findings of the Leuven study were widely embraced and endorsed by the Institute for Health Care Improvement, the American College of Endocrinology as well as other national and international organizations and soon became considered the standard of care for ICU patients around the world. In 2006, Van den Berghe and colleagues repeated their study in medical ICU patients (Leuven II study) [5]. Although failing to reproduce the improvement in survival in the entire set of patients, this study demonstrated a reduction in morbidity in the patients randomized to IIT with a reduction in mortality in the subset of patients with an ICU stay of 3 days or more. Using a similar study design these authors repeated their study in a pediatric ICU (mostly cardiac surgery patients) and demonstrated an outcome very similar to the Leuven I study [6]. Following the Leuven I study, 14 randomized controlled trials in various patient populations including mixed ICUs, neurosurgical, neurological, coronary, trauma, and pediatric ICUs have been performed (see Table 1). Without exception all of these studies demonstrated no outcome benefit (NOB) from tight glycemic control in acutely ill patients. NICE-SUGAR, the largest trial to date (n = 6022), demonstrated a 2.6 % absolute increase in 90-day mortality in patients randomized to IIT (p = 0.02) [7]. Three of these studies demonstrated harm, with almost all of the studies demonstrating a significant increase in the risk of both moderate and severe hypoglycemia. Even mild hypoglycemia in ICU patients is associated with an increased risk of death [8]. The mechanism(s) by which hypoglycemia increases the risk of death in critically ill patients has (have) not been investigated. However, it is likely that hypoglycemia increases the risk of fatal arrhythmias [9]. Furthermore, cell death *Correspondence: marikpe@evms.edu 2 Eastern Virginia Medical School, 825 Fairfax Av, Suite 410, Norfolk, VA 23507, USA Full author information is available at the end of the article

A Novel Statistical Prognostic Score Model That Includes Serum CXCL5 Levels and Clinical Classification Predicts Risk of Disease Progression and Survival of Nasopharyngeal Carcinoma Patients

BackgroundAberrant expression of C-X-C motif chemokine 5 (CXCL5) contributes to the progression of various cancers. This study analyzed the clinical significance of serum CXCL5 (sCXCL5) levels of nasopharyngeal carcinoma (NPC) patients, with the goal of building a novel prognostic score model.Experimental DesignSerum samples were collected prior to treatment from 290 NPC patients for the detection of sCXCL5 with ELISA. Half of the patients (n = 145) were randomly assigned to the training set to generate the sCXCL5 cutoff point using receiver operator characteristic (ROC) analysis, while the other half (n = 145) were assigned to the testing set for validation. Associations between sCXCL5 levels and clinical characteristics were analyzed. A prognostic score model was built using independent predictors derived from multivariate analysis. A concordance index (C-Index) was used to evaluate prognostic ability.ResultsThe sCXCL5 cutoff point was 0.805 ng/ml. Sex, age, histology, T classification, clinical classification and local recurrence were not associated with sCXCL5 levels. However, sCXCL5 levels were positively associated with N classification, distant metastasis and disease progression (P<0.05). A high sCXCL5 level predicted poor 6-year overall survival (OS), poor 6-year distant metastasis-free survival (DMFS), and poor 6-year progression-free survival (PFS). A prognostic score model was subsequently constructed based on sCXCL5 levels and clinical classification (C-C model), which are independent predictors of OS, DMFS, and PFS, as confirmed by the multivariate analysis. Furthermore, this novel model successfully divided the patients into four risk subgroups in the training set, the testing set and the entire set of patients. The C-Indices were 0.751 and 0.762 for the training set and the testing set, respectively.ConclusionssCXCL5 level was determined to be an independent prognostic factor for NPC patients. The novel statistical C-C model, which includes sCXCL5 levels and clinical classification, could be helpful in predicting the prognosis of NPC patients.

Functional FCGR2B gene variants influence intravenous immunoglobulin response in patients with Kawasaki disease

In Kawasaki Disease patients, the authors show associations between high-dose intravenous immunoglobulin (IVIG) response and a polymorphism in the FCγRIIB. This provides basis for defining the IVIG regulatory mechanisms and pharmacogenomic approach to IVIG therapy.

A Ten-microRNA Expression Signature Predicts Survival in Glioblastoma

Glioblastoma (GBM) is the most common and aggressive primary brain tumor with very poor patient median survival. To identify a microRNA (miRNA) expression signature that can predict GBM patient survival, we analyzed the miRNA expression data of GBM patients (n = 222) derived from The Cancer Genome Atlas (TCGA) dataset. We divided the patients randomly into training and testing sets with equal number in each group. We identified 10 significant miRNAs using Cox regression analysis on the training set and formulated a risk score based on the expression signature of these miRNAs that segregated the patients into high and low risk groups with significantly different survival times (hazard ratio [HR] = 2.4; 95% CI = 1.4–3.8; p<0.0001). Of these 10 miRNAs, 7 were found to be risky miRNAs and 3 were found to be protective. This signature was independently validated in the testing set (HR = 1.7; 95% CI = 1.1–2.8; p = 0.002). GBM patients with high risk scores had overall poor survival compared to the patients with low risk scores. Overall survival among the entire patient set was 35.0% at 2 years, 21.5% at 3 years, 18.5% at 4 years and 11.8% at 5 years in the low risk group, versus 11.0%, 5.5%, 0.0 and 0.0% respectively in the high risk group (HR = 2.0; 95% CI = 1.4–2.8; p<0.0001). Cox multivariate analysis with patient age as a covariate on the entire patient set identified risk score based on the 10 miRNA expression signature to be an independent predictor of patient survival (HR = 1.120; 95% CI = 1.04–1.20; p = 0.003). Thus we have identified a miRNA expression signature that can predict GBM patient survival. These findings may have implications in the understanding of gliomagenesis, development of targeted therapy and selection of high risk cancer patients for adjuvant therapy.

Effects of direct-to-consumer advertising of hydroxymethylglutaryl coenzyme a reductase inhibitors on attainment of LDL-C goals

Background: Although highly controversial, directto-consumer (DTC) television advertising for prescription drugs is an established practice in the US health care industry. While the US Food and Drug Administration is currently reexamining its regulatory stance, little evidence exists regarding the impact of DTC advertising on patient health outcomes. Objective: The objective of this research was to study the relationship between heavy television promotion of 3 major hydroxymethylglutaryl coenzyme A reductase inhibitors (“statins”) and the frequency with which patients are able to attain low-density lipoprotein cholesterol (LDL-C) blood-level goals after treatment with any statin. Methods: We used logistic regression to determine achievement of LDL-C goals at 6 months after statin treatment, using electronic medical record extract data from patients from geographically dispersed primary care practices in the United States. We identified LDL-C blood levels as being at or less than goal, as defined by risk-adjusted guidelines published by the National Heart, Lung, and Blood Institute from the Adult Treatment Panel III (ATP III) data. A total of 50,741 patients, identified from 88 practices, were diagnosed with hyperlipidemia and had begun therapy with any statin medication during the 1998–2004 time period. In addition, total dollars spent each month on television advertising at the national and local levels for atorvastatin, pravastatin, and simvastatin were obtained. DTC advertising data were merged by local media market where the physician practice was located and by the month in which the patient was first prescribed a statin. The models were run for all patients who initiated therapy, and also on a subsample of patients who continued to receive prescriptions for the drugs for at least 6 months. Logistic regressions were used to predict the likelihood that each patient attained the ATP III LDL-C blood-level goals as a function of DTC advertising and other factors. Results: High levels of national DTC advertising when therapy was initiated were found to increase the likelihood that patients attained LDL-C goals at 6 months by 6% ( P < 0.001)—although the effect was concentrated among patients with the least-restrictive ATP III LDL-C goals (≤160 mg/dL). This result was found in both the entire set of patients as well as the restricted sample of patients who maintained therapy for at least 6 months. Conclusions: The results of this study suggest that higher levels of DTC television advertising of statin treatment were significantly associated with improvements in the likelihood of attaining cholesterol-management goals for at least some patients. While this paper does not address the impact of DTC advertising on the costs of care or on unnecessary switching between statin treatments, the results do suggest that DTC advertising can have beneficial effects, which should be a factor when additional restrictions on DTC advertising are considered. This result—that DTC ad vertising might have beneficial effects-should be weighed against existing studies that have found that patients' suggestions (conceptually which could be induced by DTC advertising) may be associated with overprescribing (eg, in the case of the use of antidepressants for adjustment disorder).

Endorectal diffusion-weighted imaging in prostate cancer to differentiate malignant and benign peripheral zone tissue.

To determine if the apparent diffusion coefficient (ADC) can discriminate benign from malignant peripheral zone (PZ) tissue in patients with biopsy-proven prostate cancer that have undergone endorectal diffusion-weighted imaging (DWI) of the prostate. Ten patients with prostate cancer underwent endorectal magnetic resonance imaging (MRI) in addition to DWI. A two-dimensional grid was placed over the axial images, and each voxel was graded by a 4-point rating scale to discriminate nonmalignant from malignant PZ tissue based on MR images alone. ADC was then determined for each voxel and plotted for nonmalignant and malignant voxels for the entire patient set. Second, with the radiologist aware of biopsy locations, any previously assigned voxel grade that was inconsistent with biopsy data was regrouped and ADCs were replotted. For the entire patient set, without and with knowledge of the biopsy data, the mean ADCs for nonmalignant and malignant tissue were 1.61 +/- 0.27 and 1.34 +/- 0.38 x 10(-3) mm2/second (P = 0.002) and 1.61 +/- 0.26 and 1.27 +/- 0.37 x 10(-3) mm2/second (P = 0.0005), respectively. DWI of the prostate is possible with an endorectal coil. The mean ADC for malignant PZ tissue is less than nonmalignant tissue, although there is overlap in individual values.

Dose response in prostate cancer with 8–12 years’ follow-up

Purpose: This communication reports the long-term results of the original group of prostate cancer patients who participated in the first prospective Fox Chase Cancer Center radiation dose escalation study for which 8–12 years of follow-up is now available.Methods and Materials: Between March 1, 1989 and October 31, 1992, 232 patients with clinically localized prostate cancer received three-dimensional conformal radiotherapy only at Fox Chase Cancer Center in a prospective dose-escalation study. Of these patients, 229 were assessable. The 8-, 10-, and 12-year actuarial rates of biochemical control (biochemically no evidence of disease [bNED]), freedom from distant metastasis (FDM), and morbidity were calculated. The Cox proportional hazards model was used to assess multivariately the predictors of bNED control and FDM, including pretreatment prostate-specific antigen (PSA) level (continuous), tumor stage (T1/T2a vs. T2b/T3), Gleason score (2–6 vs. 7–10), and radiation dose (continuous). The median total dose for all patients was 74 Gy (range 67–81). The median follow-up for living patients was 110 months (range 89–147). bNED control was defined using the American Society for Therapeutic Radiology and Oncology consensus definition.Results: The actuarial bNED control for all patients included in this series was 55% at 5 years, 48% at 10 years, and 48% at 12 years. Patients with pretreatment PSA levels of 10–20 ng/mL had statistically significant differences (19% vs. 31% vs. 84%, p = 0.0003) in bNED control when stratified by dose (<71.5, 71.5–75.6, and > 75.6 Gy, respectively) on univariate analysis. For the 229 patients with follow-up, 124 (54%) were clinically and biochemically without evidence of disease. Sixty-nine patients were alive at the time of last follow-up, and 55 patients were dead of intercurrent disease. On multivariate analysis, radiation dose was a statistically significant predictor of bNED control for all patients and for unfavorable patients with a pretreatment PSA <10 ng/mL. For the patients with a pretreatment PSA level of 10–20 ng/mL, the radiation dose was a statistically significant predictor across all groups. No radiation dose response was seen for those patients with a pretreatment PSA level >20 ng/mL, although large numbers of patients are required to demonstrate a difference. The radiation dose, Gleason score, and palpation T stage were significant predictors for the entire patient set, as well as for those with pretreatment PSA levels between 10 and 20 ng/mL. The FDM rate for all patients included in this series was 89%, 83%, and 83% at 5, 10, and 12 years, respectively. For patients with pretreatment PSA levels <10 ng/mL, all four covariates (radiation dose, Gleason score, pretreatment PSA, and palpation T stage) were significant predictors of distance metastasis. Using the Radiation Therapy Oncology Group morbidity scale, no difference was noted in the frequency of Grade 2 and 3 genitourinary and Grade 3 gastrointestinal morbidity when patients in this data set were stratified by radiation dose. However, a significant increase occurred in Grade 2 gastrointestinal complications as the radiation dose increased.Conclusion: The long-term results of the original Fox Chase radiation dose escalation study with >9 years of median follow-up confirm the existence of a dose response for both bNED control and FDM. The dose response in prostate cancer is real, and the absence of biochemical recurrence after 8 years demonstrates the lack of late failure and suggests cure.