Marijuana toxicosis in 2 donkeys.

Marijuana toxicosis is typically seen by companion animal veterinarians. However, with increased marijuana availability, there is a greater potential for toxicosis in other species. Herein we describe a case of suspected marijuana toxicosis in a female and a male American Mammoth donkey, aged 8 y and 20 y, respectively, fed cannabis buds. Both cases were presented because of depression and lethargy. However, the jenny had ataxia, mild colic, tachycardia, tachypnea, and decreased tongue tone. Plasma samples from the jenny on presentation and 3 d following hospitalization were submitted to the Kansas State Veterinary Diagnostic Laboratory to be screened for cannabinoids using high-pressure liquid chromatography coupled with tandem mass spectroscopy (HPLC-MS/MS). A single serum sample from the jack was taken on presentation and submitted to the Animal Health Diagnostic Center at Cornell University for Δ9-tetrahydrocannabinol (THC) and cannabidiol analysis using HPLC-MS/MS. THC was detected in all samples. Clinical signs were noted 24-36 h after ingestion, which included mild-to-moderate neurologic deficits, mild colic, tachycardia, tachypnea, and decreased tongue tone. Both donkeys recovered uneventfully within 24 h of peak effects. Utilizing a cannabinoid screening assay in collaboration with a veterinary diagnostic laboratory may be useful when an equine practitioner suspects marijuana toxicosis in a patient.

Delirium in advanced cancer leading to distress in patients and family caregivers.

BACKGROUND: Information is limited about the experiences of delirium among patients with advanced cancer and their caregivers, which makes designing interventions to relieve delirium-related distress difficult. To better understand the experience and thus permit the design of effective interventions, we collected and analyzed data from patients with advanced cancer who had recovered from delirium and their family caregivers. METHOD: Phenomenological interviews were conducted separately with 37 caregivers and 34 patients. One investigator reviewed verbatim transcripts of the audio-taped interviews to identify themes, which the research team confirmed. RESULTS: Most patients and all caregivers had vivid memories of the experience; their descriptions were consistent. Most also attributed the confusion to pain medication. Caregivers had concerns about how best to help patients, patients' imminent deaths, and their own well-being. CONCLUSIONS: The main finding that delirium leads to distress for both patients and caregivers indicates the importance of recognizing, treating, and, if possible, preventing delirium in this population. Concerns about pain medications also indicate the need to educate patients and caregivers about symptom management. Caregivers also need emotional support.

Characteristics of family conferences in a palliative care unit at a comprehensive cancer center.

PURPOSE: Family conferences are used to facilitate communication concerning end-of-life issues with patients and their families. The purpose of our study was to obtain preliminary information on the characteristics of family conferences that take place in an inpatient palliative care unit (PCU). METHODS: A retrospective chart review was conducted during a 6-month period that identified 123 documented family conferences. Data including demographic information, type of cancer, and discharge disposition were collected. Timing, number of participants, expressions of emotional distress, conflict with health care providers, and topics discussed during the conference were collected. RESULTS: Sixty-one patients (50%) were female, 75 (61%) were white, 95 (77%) had solid tumors. Median age of patients was 61. In 74 of the 123 documented family meetings (60%), patients actively participated. Family conferences took place a median of 3 days prior to discharge. During the meetings, questions concerning advanced directives and withdrawal of care were found to be infrequent. Eighteen percent of patients expressed emotional distress, while 40% of families expressed distress which was higher at 47% when the patient was not present. CONCLUSIONS: Family conferences involved a high degree of patient participation and occurred at the end of a patients stay in our PCU. A trend toward greater expression of emotional distress displayed by family members was found when patients did not participate in the meetings. Further prospective studies that use validated tools to assess the content of the meetings and their impact on alleviating distress in patients and their family are needed.

Clinically important improvement in the intensity of fatigue in patients with advanced cancer.

Cancer-related fatigue (CRF) is the most common symptom experienced by patients with cancer. Clinically important improvement in the intensity of fatigue in palliative care patients has not been well established. We reviewed the data from 3 clinical trials of fatigue in 194 patients receiving palliative care treatment. Patients completed the Functional Assessment for Chronic Illness Therapy Fatigue (FACIT-F) and Edmonton Symptom Assessment System (ESAS) at baseline and day 8 and their global perception of fatigue improvement (Global benefit score [GBS]: 1 = not beneficial, 7 = greatly important] during day 8. A GBS of 4 or more (moderate improvement, consistently beneficial) was considered a clinically significant improvement. Change scores in the ESAS and FACIT-F from baseline to day 8 were compared to the GBS greater than 4. Receiver-operating characteristic curves were also derived for ESAS and FACIT-F change scores for a GBS greater than 4, greater than 5, and greater than 6. Results showed the mean patient age was 56 (+/-12) years, and 37% were men. A reduction of approximately 10 points in FACIT-F (sensitivity = 73%, specificity = 78%, area under the curve = 0.82) and 4 points in ESAS fatigue (sensitivity = 66%, specificity = 72%, area under the curve = 0.78) score was best able to predict a clinically important improvement (GBS >/= 4). We were able to characterize the relationship between FACIT-F and ESAS scores and patients' global perception of improvement but further studies are needed to validate our findings.

A randomized, controlled trial of physician postures when breaking bad news to cancer patients.

Medical training teaches physicians to sit when breaking bad news, though there have been no controlled studies to support this advice. We aimed to establish cancer patients' preference for physician posture when physicians break bad news using a randomized controlled crossover trial in a department of palliative care at a large US cancer center. Referred patients were blind to the hypothesis and watched video sequences of a sitting or standing physician breaking bad news to a cancer patient and 168 of 173 participants (88 female) completed the study. Sitting physicians were preferred and viewed as significantly more compassionate than standing physicians (P < 0.0001) but other physician attributes and behaviours were generally rated as of equal or more importance than posture. In summary, cancer patients, especially females, prefer physicians to sit when breaking bad news and rate physicians who adopt this posture as more compassionate. However, sitting posture alone is unlikely to compensate for poor communication skills and lack of other respectful gestures during a consultation.

Errors in symptom intensity self-assessment by patients receiving outpatient palliative care.

BACKGROUND: Patient-based symptom scores are the standard method for assessment in palliative care. There has been limited research on the frequency of errors upon using this approach. The Edmonton Symptom Assessment Scale (ESAS) is a reliable and valid assessment tool routinely used for symptom intensity assessment in our cancer center. OBJECTIVE: To determine if patients were scoring the symptoms on the ESAS in the way it was supposed to be scored. SETTINGS: The study was carried out at the outpatient palliative care center. DESIGN AND SUBJECTS: Retrospective review of 60 consecutive patient charts was done where the patient had initially scored the ESAS. The physician looked at this scoring on the ESAS and went back to the patient to do the scoring again to see if the patient had scored it in the way it was intended to be scored. The same physician did the assessment on all of the patients. OUTCOME MEASURES: Level of agreement (weighted kappa) before versus after the physician visit; Screening performance of patient completed ESAS for mild and moderate symptom intensity. RESULTS: Complete agreement ranged from 58% (sleep) to 82% (well-being); the weighted kappa ranged from 0.49 (drowsiness) to 0.78 (well-being). There was more agreement for symptoms such as dyspnea, nausea, anxiety, and depression and less agreement for symptoms such as lack of sleep and lack of appetite. The screening performance of the initial patient self assessment showed less sensitivity for nausea, drowsiness if the intensity was mild and less sensitivity for pain, nausea, anxiety, and drowsiness if the intensity was moderate. CONCLUSIONS: Vigilance needs to be maintained about the ESAS scores done by the patients particularly for symptoms of sleep, appetite, and pain. There is a likelihood of error if doctors or nurses do not routinely check the way patients have completed the assessment form. More research is needed to determine the best way to teach patients how to minimize errors in self-reporting of symptoms.

The Edmonton Symptom Assessment System as a screening tool for depression and anxiety.

PURPOSE: Mood disorders are among the most important psychiatric problems in patients with cancer. However, they are frequently underdiagnosed and therefore undertreated. This may lead to difficulties with symptom control, social withdrawal, and poor quality of life. This study was conducted to evaluate the screening performance of the Edmonton Symptom Assessment System (ESAS) for depression and anxiety, compared to Hospital Anxiety and Depression Scale (HADS). METHODS: We retrospectively reviewed and analyzed ESAS and HADS data collected from three previous clinical trials conducted by our group. The diagnosis of depression and/or anxiety, and moderate/severe depression and/or anxiety made when patients scored 8 or more, and 11 or more in HADS questionnaire, respectively. The sensitivity, specificity, positive, and negative predictive values for ESAS were calculated. RESULTS: Of 216 patients analyzed, the median (range) score for depression was 2 (0-10) and anxiety 3 (0-10) using ESAS, and 6 (0-16) and 7 (0-19) using HADS, respectively. A cut off of 2 out of 10 or more in the ESAS gave a sensitivity of 77% and 83% with a specificity of 55% and 47% for depression and moderate/severe depression, respectively. A cutoff of 2 out of 10 or more in the ESAS gave a sensitivity of 86% and 97%, and a specificity of 56% and 43% for anxiety and moderate/severe anxiety, respectively. CONCLUSION: Our data suggest that the ideal cutoff point of ESAS for the screening of depression and anxiety in palliative care is 2 out of 10 or more. More research is needed to define the ideal cutoff point for screening of severe depression and anxiety.

Objective evaluation of physical function in patients with advanced lung cancer: a preliminary report.

PURPOSE: This prospective study was designed in order to compare the most common subjective measurements of physical function in patients with advanced lung cancer with an objective physical functional test (Simmonds Functional Assessment Tool [SFA]). PATIENTS AND METHODS: One hundred patients agreed to participate and complete the study before or after their outpatient medical oncology appointment. Patients underwent assessment using the Karnofsky, the Brief fatigue Inventory, The Functional Assessment of Cancer Therapy-Lung patients (FACT-L) and the Edmonton Symptom Assessment Scale (ESAS). These results were compared to the SFA tool. The SFA consists of six tasks: tying a belt, putting coins in a cup, reaching above head, standing up/sitting down, reaching forward and walking 50 feet. RESULTS: Ninety-nine patients completed the study over 8 months: median Karnofsky performance status was 85 (70 to 100), Edmonton Symptom Assessment Scale (ESAS) score (0 to 10) was generally low (0.5 to 2.8). SFA scores were significantly different in patients compared to a control group. The correlation between the subscales of the SFA and the Karnofsky, the Brief Fatigue Inventory, The FACT-L and the ESAS was generally low to moderate (r values: 0.22 to 0.38). There was generally a moderate correlation between the different subjective scales (r values: 0.3 to 0.62). CONCLUSION: Adherence to the SFA tool was excellent. The low to moderate correlation between the abnormalities found in the objective SFA and the subjective fatigue tests suggest that objective evaluation of the functional capacity provides a potentially useful and independent end-point for clinical trials and therapeutic interventions. These assessment tools should be used complementary to each other to better assess the functional status of patients with advanced lung cancer. Large trials of objective functional assessment are justified.

A novel high-throughput automated chip-based nanoelectrospray tandem mass spectrometric method for PAMPA sample analysis.

Parallel artificial membrane permeability assay (PAMPA) has recently gained popularity as a novel, high-throughput assay capable of rapidly screening compounds for their permeability characteristics in early drug discovery. The analytical techniques typically used for PAMPA sample analysis are HPLC-UV, LC/MS or more recently UV-plate reader. The LC techniques, though sturdy and accurate, are often labor and time intensive and are not ideal for high-throughput. On the other hand, UV-plate reader technique is amenable to high-throughput but is not sensitive enough to detect the lower concentrations that are often encountered in early drug discovery work. This article investigates a novel analytical method, a chip-based automated nanoelectrospray mass spectrometric method for its ability to rapidly analyze PAMPA permeability samples. The utility and advantages of this novel analytical method is demonstrated by comparing PAMPA permeability values obtained from nanoelectrospray to those from conventional analytical methods. Ten marketed drugs having a broad range of structural space, physico-chemical properties and extent of intestinal absorption were selected as test compounds for this investigation. PAMPA permeability and recovery experiments were conducted with model compounds followed by analysis by UV-plate reader, UV-HPLC as well as the automated nanoelectrospray technique (nanoESI-MS/MS). There was a very good correlation (r(2) > 0.9) between the results obtained using nanoelectrospray and the other analytical techniques tested. Moreover, the nanoelectrospray approach presented several advantages over the standard techniques such as higher sensitivity and ability to detect individual compounds in cassette studies, making it an attractive high-throughput analytical technique. Thus, it has been demonstrated that nanoelectrospray analysis provides a highly efficient and accurate analytical methodology to analyze PAMPA samples generated in early drug discovery.

Quantitation of midazolam in human plasma by automated chip-based infusion nanoelectrospray tandem mass spectrometry.

An automated chip-based infusion nanoelectrospray ionization (nanoESI) platform was used to demonstrate reproducible quantitation of drug molecules from biological matrices. Three sample preparation strategies were explored including protein precipitation of plasma with acetonitrile, de-salting of the plasma, and a combination of protein precipitation with subsequent de-salting of the dried and reconstituted extract. The best results were obtained when fortified human plasma samples containing midazolam were precipitated with acetonitrile containing alprazolam as the internal standard (IS). The supernatant was concentrated to dryness, reconstituted in aqueous acid, and de-salted by automated reversed-phase solid-phase extraction (SPE) prior to infusion nanoESI-MS/MS. Analyses employed a triple quadrupole mass spectrometer operated in selected reaction monitoring (SRM) mode. Each sample was infused for approximately 10 s and the resulting ion current profiles were integrated. Area ratios were used for regression analysis of standard samples (1.5-500 ng/mL). Quality control samples (3, 250, and 400 ng/mL) in five replicates from three different analysis days demonstrated intra-assay precision (< or =16%), inter-assay precision (< or =5%), and overall accuracy (+/-9% deviation). Infusion reproducibility of the assay was established by analyzing extracts after storage for 24 h at ambient temperature. Control plasma samples from six different sources probed the potential utility of this technique for the analysis of clinical samples. At the lower limit of quantitation (LLQ), variability and mean overall accuracy were < or =13% CV and +/-3% deviation, respectively, while at the upper limit of quantitation (ULQ) variability and mean overall accuracy were < or =9% CV and +/-9% deviation, respectively. Inter-chip variability was established by determining standard sample extracts across five different chips (< or =12% CV). Throughput for the assay was 55 s per sample, although this time may be shortened to 40 s per sample with recent improvements in the automated nanoESI system. No contamination or carryover was observed using this promising automated nanoESI-MS/MS platform.