Managing chemotherapy-induced nausea and vomiting in head and neck cancer patients receiving cisplatin chemotherapy with concurrent radiation.

BACKGROUND: The purpose was to retrospectively examine the anti-emetic regimens prescribed for prophylaxis of chemotherapy-induced nausea and vomiting (CINV) for head and neck cancer patients receiving moderate- or high-emetogenic chemotherapy (MEC/HEC) along with concurrent radiation treatment at an outpatient ambulatory care center to determine the efficacy of anti-emetics prescribed. METHODS: Consecutive patients with head and neck cancers who initiated cisplatin chemotherapy with concurrent radiation treatment between January 2013 and June 2015 were investigated. Patients' anti-emetic use and occurrence of CINV was extracted from available clinical documentation. Patients were divided into two cohorts: CISPL-HIGH (n=161), and CISPL-WEEKLY (n=38). RESULTS: A total of 199 head and neck cancer patients (158 male, 41 female) were included in the analysis (mean age =59 years). In the CISPL-HIGH cohort, 33 males (26%) and 16 females (49%) experienced CINV. In the CISPL-WEEKLY cohort, four males (13%) and two females (25%) experienced CINV. Nausea occurred in 71 patients (62 HEC and 9 MEC). The odds of achieving complete response (no nausea or vomiting) were 3.5 (P<0.0016) times more likely for patients receiving MEC. Overall, the complete response rate for the prophylaxis in MEC and HEC was 61% and 31%, respectively. Anti-emetic changes occurred in 34% and 11% of patients receiving HEC and MEC, respectively. CONCLUSIONS: In the current study CINV control for patients receiving HEC was sub-optimal. Changes to our prophylactic antiemetic regimens may help improve patient outcomes.

Penile necrosis secondary to purpura fulminans: a case report and review of literature.

We report the case of a 60-year-old Hispanic male with widespread necrotic purpuric lesions involving the penile, suprapubic, inguinal and hip dermis due to purpura fulminans. Purpura fulminans describes a rare syndrome involving intravascular thrombosis and hemorrhagic infarction of the skin; this rapidly progressing syndrome features vascular collapse and disseminated intravascular coagulation. This patient's penile necrosis involved the majority of the penile shaft and glans penis, and ultimately required partial glansectomy and repeated debridement for treatment. Subsequently, full thickness skin grafting was completed for reconstruction with good effect. While reports of penile necrosis secondary to various causes are documented in the literature, no prior reports describe penile necrosis secondary to purpura fulminans.

A definition of "uncomplicated bone metastases" based on previous bone metastases radiation trials comparing single-fraction and multi-fraction radiation therapy.

The most recent systematic review of randomized trials in patients with bone metastases has shown equal efficacy of single fraction (SF) and multiple fraction (MF) palliative radiation therapy in pain relief. It is important to determine the patient population to which the evidence applies. This study aims to examine the eligibility criteria of the studies included in the systematic review to define characteristics of "uncomplicated" bone metastases. Inclusion and exclusion criteria of 21 studies included in the systematic review were compared. Common eligibility criteria were documented in hopes of defining the specific features of a common patient population representative of those in the studies. More than half of the studies included patients with cytological or histological evidence of malignancy. Patients with impending and/or existing pathological fracture, spinal cord compression or cauda equina compression were excluded in most studies. Most studies also excluded patients receiving retreatment to the same site. "Uncomplicated" bone metastases can be defined as: presence of painful bone metastases unassociated with impending or existing pathologic fracture or existing spinal cord or cauda equina compression. Therefore, MF and SF have equal efficacy in patients with such bone metastases.

Retrospective review of the incidence of monitoring blood glucose levels in patients receiving corticosteroids with systemic anticancer therapy.

BACKGROUND: Corticosteroids are used adjuvant to certain chemotherapy regimens, either as an antiemetic, to reduce other side effects, or to enhance cancer treatment. Additionally, they are frequently used for symptom control in cancer patients with end stage disease. Corticosteroid use may induce hyperglycemia in approximately 20-50% of patients, which may negatively affect patient outcomes. OBJECTIVE: To determine the frequency of blood glucose monitoring in patients with and without diabetes receiving continuous corticosteroids with chemotherapy, and to determine the incidence of treatment-emergent abnormal blood glucose levels and steroid-induced diabetes mellitus (DM). METHODS: A retrospective review was conducted for 30 genitourinary (GU) cancer patients who were treated with continuous oral corticosteroids as part of their chemotherapy regimen. The Canadian Diabetes Association (CDA) criterion for diagnosis of diabetes was applied to categorize patients into two distinct groups, patients with diabetes and patients without diabetes. This categorization was made based on glucose measurements completed prior to commencement of corticosteroid therapy. Glucose monitoring was defined as receiving a laboratory blood glucose test before first chemotherapy administration along with a test within a week of each subsequent treatment cycle. The CDA criteria for diagnosis of pre-diabetes and diabetes was used to classify glucose levels as hyperglycemic. RESULTS: The mean incidence of blood glucose monitoring was 19% and 76% in patients with diabetes and patients without diabetes, respectively. Approximately, 40% of patients with diabetes required an adjustment to their diabetes management and a further 20% required hospitalization. Fifteen patients without diabetes received a fasting blood glucose test, of which 40% had abnormal blood glucose results; half of these fell into the pre-diabetic range and half in the diabetic range. Ten patients without diabetes were tested for diabetes using the CDA criteria for diabetes diagnosis during or after their chemotherapy, of which 30% developed diabetes. CONCLUSIONS: In order to optimize patient care, blood glucose levels should be monitored in all patients receiving continuous oral corticosteroids as part of their chemotherapy. Future studies should be conducted prospectively to determine the most effective manner of monitoring in order to implement screening guidelines and avoid unnecessary morbidity.

Minimal clinically important differences in the EORTC QLQ-BN20 in patients with brain metastases.

INTRODUCTION: Quality of life (QOL) is an important treatment endpoint in advanced cancer patients with brain metastases. In clinical trials, statistically significant changes can be reached in a large enough population; however, these changes may not be clinically relevant. OBJECTIVE: The objective of this study was to determine the minimal clinically important difference (MCID) for the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire brain module (EORTC QLQ-BN20) in patients with brain metastases. METHODS: Patients undergoing radiotherapy for brain metastases completed the EORTC QLQ-BN20 and QLQ-C30/C15-PAL at baseline and 1-month follow-up. MCIDs were calculated for both improvement and deterioration using anchor- and distribution-based approaches. The anchor of overall QOL (as assessed by question 30 or question 15 on the QLQ-C30 and QLQ-C15-PAL, respectively) was used to determine meaningful change. RESULTS: A total of 99 patients were included. The average age was 61 years, and the most common primary cancer sites were the lung and breast. Statistically significant meaningful differences were seen on two scales. A decrease of 6.1 (95 % confidence interval (CI) 0.8 to 11.4) units and 13.8 (0.2 to 27.4) units was required to represent clinically relevant deterioration of seizures and weakness of legs, respectively. Distribution-based MCID estimates tended to be closer to 0.5 SD on the EORTC QLQ-BN20. CONCLUSION: Understanding MCIDs allows physicians to determine the impact of treatment on patients' QOL and allows for determination of sample sizes for clinical trials. Future studies should be conducted to validate our findings in a larger population of patients with brain metastases.

Symptom clusters of gastrointestinal cancer patients undergoing radiotherapy using the Functional Living Index-Emesis (FLIE) quality-of-life tool.

OBJECTIVE: The Functional Living Index-Emesis (FLIE) instrument is a validated nausea and vomiting specific quality of life (QOL) tool originally created as a 3-day test of the impact of chemotherapy-induced nausea and vomiting on cancer patients' daily life. The primary objective of the present study was to retrospectively explore the use of the FLIE from data obtained in a previously published study of patients with gastrointestinal radiation-induced nausea and vomiting (RINV) and compare the extracted symptom clusters on a weekly basis for the entirety of gastrointestinal cancer patients' radiotherapy treatments. METHODS: QOL was assessed on a weekly basis using the 18-item FLIE questionnaire for patients' radiotherapy treatments. A principal component analysis with varimax rotation was performed at each visit. The internal consistency and reliability of the derived clusters was assessed with Cronbach's alpha. Robust relationship and correlation among symptoms was displayed with biplot graphics. RESULTS: A total of 460 FLIE assessments were completed for the 86 gastrointestinal patients who underwent radiotherapy. Two components were consistently identified except for week 5 where only one component was identified. Component 1 contained the items "Q10-Q18" which included all vomiting items. Component 2 included all nausea items from "Q1 to Q9". All the variables were well accounted for by two components for most weeks of treatment with excellent internal consistency. Biplots indicate that the two symptom clusters were evident at each week, with the exception of the first week of treatment. Strong correlations were seen between the effect of nausea on patients' ability to make meals, patients' ability to do tasks within the home, and patients' willingness to spend time with family and friends. CONCLUSION: The high internal consistency at all timepoints indicates that the FLIE QOL instrument is useful for the RINV population.

Inadequacy of Palliative Training in the Medical School Curriculum.

This report examines the literature on palliative training in the current medical school curriculum. A literature search was conducted to identify relevant articles. Physicians and medical students both report feeling that their training in end-of-life care and in palliative issues is lacking. The literature expresses concerns about the varied and non-uniform approach to palliative care training across medical schools. The authors recommend the development of more palliative training assessment tools in order to aid in the standardization of curriculum involving end-of-life care. In addition, increased exposure to dying patients will aid students in building comfort with palliative care issues. Such a goal may be accomplished through required clerkships or other similar programs.

Fatigue scores in patients receiving palliative radiotherapy for painful bone metastases.

INTRODUCTION: The purpose of this study was to examine changes in fatigue scores for patients receiving radiation therapy for bone metastases and its impact on quality of life (QOL). METHODS: Fatigue and QOL scores were prospectively collected in patients for up to 3 months following radiation therapy for bone metastases using three questionnaires: group 1, Edmonton Symptom Assessment System (ESAS) (0-10); group 2, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30); and Core 15 Palliative (EORTC QLQ-C15-PAL) (1-4). RESULTS: Average fatigue score in group 1 (399 patients) was 4.72 at baseline, 5.08 at month 1, 5.01 at month 2, and 4.95 at month 3, and was 2.40, 2.39, 2.56, and 2.70 in group 2 (482 patients), respectively. Thirty-five percent of patients in group 1 had fatigue score increase ≥2 points at month 1, 36% at month 2, and 36% at month 3. Twenty-one percent of patients in group 2 had fatigue score increase ≥1 at month 1, 27% at month 2, and 40% at month 3. There was a statistically significant increase in fatigue score from baseline to all 3 months in group 1 only. In both groups, there was a highly significant negative correlation between fatigue and overall QOL scores at baseline and any follow-up month. CONCLUSIONS: There was a statistically significant worsening in fatigue in group 1 only. Up to one third had increased fatigue of clinical significance. Patients with less fatigue symptoms reported better overall QOL.

Prognosis: the "missing link" within the CanMEDS competency framework.

BACKGROUND: The concept of prognosis dates back to antiquity. Quantum advances in diagnostics and therapeutics have relegated this once highly valued core competency to an almost negligible role in modern medical practice. Medical curricula are devoid of teaching opportunities focused on prognosis. This void is driven by a corresponding relative dearth within physician competency frameworks. This study aims to assess the level of content related to prognosis within CanMEDS (Canadian Medical Education Directives for Specialists), a leading and prototypical physician competency framework. METHODS: A quantitative content analysis of CanMEDS competency framework was carried out to measure the extent of this deficiency. Foxit Reader 5.1 (Foxit Corporation), a keyword scanning software, was used to assess the CanMEDS 2005 framework documents of 29 physician specialties and 37 subspecialties across the seven physician roles (medical expert, communicator, collaborator, manager, health advocate, scholar, and professional). The keywords used in the search included prognosis, prognostic, prognosticate, and prognostication. RESULTS: Of the 29 specialties six (20.7%) contained at least one citation of the keyword "prognosis", and one (3.4%) contained one citation of the keyword "prognostic". Of the 37 subspecialties, sixteen (43.2%) contained at least one citation of the keyword "prognosis", and three (8.1%) contained at least one citation of the keyword "prognostic". The terms "prognosticate" and "prognostication" were completely absent from all CanMEDS 2005 documents. Overall, the combined citations for "prognosis" and "prognostic" were linked with the following competency roles: Medical Expert (80.3%), Scholar (11.5%), and Communicator (8.2%). CONCLUSIONS: Given the fundamental and foundational importance of prognosis within medical practice, it is recommended that physicians develop appropriate attitudes, skills and knowledge related to the formulation and communication of prognosis. The deficiencies within CanMEDS, demonstrated by this study, should be addressed in advance of the launch of its updated version in 2015.

Performance of compulsive behavior in rats is not a unitary phenomenon - validation of separate functional components in compulsive checking behavior.

A previous analysis of the quinpirole sensitisation rat model of obsessive-compulsive disorder revealed that the behavioral phenotype of compulsive checking consists of three constitutive components - vigor of checking performance, focus on the task of checking, and satiety following a bout of checking. As confirmation of this analysis, the aim of the present study was to reconstitute, without quinpirole treatment, each of the putative components, with the expectation that these would self-assemble into compulsive checking. To reconstitute vigor and satiety, the employed treatment was a bilateral lesion of the nucleus accumbens core (NAc), as this treatment was shown previously to exaggerate these components. To reconstitute focus, the employed treatment was a low dose of the serotonin-1A receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin hydrochloride (DPAT) (0.0625 mg/kg), as high doses of this drug induce compulsive behavior and exacerbate focus. Results showed that injection of DPAT to NAc lesion rats did yield compulsive checking. Neither the drug alone nor the NAc lesion by itself produced compulsive checking. The demonstrated synthesis of compulsive checking by the combined treatment of low-dose DPAT and NAc lesion strengthened the previous fractionation of the model obsessive-compulsive disorder phenotype into three constitutive components, and suggested a role for serotonin-1A receptors outside the NAc in enhanced focus on the task of checking.

Separate mechanisms for development and performance of compulsive checking in the quinpirole sensitization rat model of obsessive-compulsive disorder (OCD).

RATIONALE: Acute administration of serotonergic agonist, meta-chlorophenylpiperazine (mCPP), attenuates performance of compulsive checking in an animal model of obsessive-compulsive disorder (OCD). It is not known whether mCPP has a similar effect on development of compulsive checking. OBJECTIVES: The objective of the study was to examine whether similar mechanisms mediate the development versus the performance of compulsive checking in the rat model. METHODS: Four groups of male rats (N = 14/group) were tested: two experimental groups co-injected with D2/D3 dopamine agonist quinpirole (0.25 mg/kg) and mCPP (0.625 mg/kg or 1.25 mg/kg), and two control groups, one co-injected with quinpirole and saline, the other receiving injections of saline. The time course of development of compulsive checking across injections 1 to 10 in quinpirole-treated rats was compared to rats co-injected with quinpirole and mCPP. RESULTS: Results showed that during the course of chronic treatment, mCPP (1.25 mg/kg) significantly attenuated performance of checking behavior. However, when these rats were retested for expression of compulsive checking (that is, with an injection of quinpirole only), their profile of compulsive checking was no different from the control rats treated throughout with quinpirole only. CONCLUSIONS: Findings show that mCPP inhibits performance of compulsive checking but does not block quinpirole from inducing the neural substrate underlying this compulsive behavior. Hence, a separate mechanism underlies the induction of compulsive checking and the performance of it. It is suggested that development of the OCD endophenotype reflects neuroplastic changes produced by repeated dopamine D2/D3 receptor stimulation, while stimulation of serotonergic receptors mediates a negative feedback signal that shuts down the motor performance of checking.

Effects of the serotonergic agonist mCPP on male rats in the quinpirole sensitization model of obsessive-compulsive disorder (OCD).

RATIONALE: The serotonergic agonist, meta-chlorophenylpiperazine (mCPP), produces inconsistent effects on obsessive-compulsive disorder (OCD) symptoms, perhaps because clinical studies have not utilized a homogenous OCD subgroup of patients. OBJECTIVES: This study aimed to evaluate mCPP effects on functional components of compulsive checking, using the quinpirole sensitization rat model of OCD. METHODS: In study 1, the effects of mCPP were evaluated in quinpirole rats with compulsive checking. Two experimental groups were co-injected with quinpirole (0.125 mg/kg) and mCPP (0.625 or 1.25 mg/kg), while one control group was co-injected with quinpirole (0.125 mg/kg) and saline and the other control group received co-injections of saline. In study 2, mCPP (0, 0.3125, 0.625, and 1.25 mg/kg) was administered repeatedly to naïve rats and induction of compulsive checking evaluated. RESULTS: mCPP significantly attenuated quinpirole-induced compulsive checking behavior by reducing vigor of checking (indexed by frequency of checking and length of check) and increasing rest after a bout of checking (indexed by time to the next checking bout), but it did not affect focus on the task of checking (indexed by recurrence time of checking and number of stops before returning to check). In naïve rats, mCPP did not induce compulsive behavior, but the highest dose reduced vigor of checking performance compared to saline controls. CONCLUSIONS: mCPP did not exacerbate or induce compulsive checking behavior. Instead, it ameliorated compulsive checking by reducing vigor of checking and increasing post-checking satiety, without affecting focus on checking. Ameliorative effects of mCPP may involve 5HT2A/2C receptors in substantia nigra pars reticulata that inhibit expression of motor vigor.