Impact of a workshop about aging on the empathy scores of pharmacy and medical students

Objective. To measure changes in pharmacy and medical students’ empathy scores after a 40-minute workshop during which students observed and discussed a theatrical performance about the challenges of aging.Methods. First-year pharmacy and medical students (n = 187 and n = 183, respectively) participating in the workshop observed and discussed a 10-minute performance in which students enacted problems and concerns faced by elderly patients. The Jefferson Scale of Empathy (JSE) was administered just prior to the workshop (pretest), immediately afterward (posttest 1), and 7 or 26 days afterward (posttest 2).Results. Empathy increased significantly from pretest to posttest 1 for students of each profession (p <0.01). Improvement in empathy scores declined by the time the JSE was readministered to pharmacy students 7 days later and to medical students 26 days later (posttest 2). Similar patterns of improved and declining empathy were found when the data were analyzed by gender and medical student specialty interest (ie, primary vs non-primary care specialties).Conclusion. Empathy scores increased but were not sustained for both pharmacy and medical students after a brief workshop on aging that required limited personnel resources.     

Discriminative-stimulus effects of triazolam in women and men

Benzodiazepines are among the most commonly prescribed therapeutics. Women seem to be more likely than men to be prescribed a benzodiazepine and to use benzodiazepines for nonmedical reasons; they also appear to be at higher risk for benzodiazepine dependence. The aim of the present investigation was to assess the acute behavioral effects of a benzodiazepine in women and men. To accomplish this, 13 volunteers (6 women, 7 men) first learned to discriminate 0.375-mg triazolam, a triazolobenzodiazepine hypnotic. After acquiring the discrimination, (i.e., >80% correct responding on 4 consecutive sessions) a range of doses of triazolam (0, 0.0625, 0.125, 0.25, and 0.375 mg) were tested in each participant. Triazolam dose dependently increased drug-appropriate responding and subject ratings of sedation and impaired performance (i.e., significant effect of dose). The women and men did not differ significantly on any measure. The results of the present experiment suggest that women and men are not differentially sensitive to the behavioral effects of triazolam.     

Pharmacokinetics,pharmacodynamics and toxicities of methotrexate in healthy and collagen‐induced arthritic rats

Methotrexate (MTX) is an anchor drug used to treat rheumatoid arthritis (RA), but responsiveness is variable in effectiveness and toxicity. Methotrexate and its polyglutamate conjugates (MTXPG_n) in red blood cells (RBC) have been associated with patient response. In the current study, 13 collagen‐induced arthritic (CIA) rats and 12 healthy rats were given subcutaneous doses of either saline or 0.3 or 1.5 mg/kg per 2 days of MTX from day 21 to 43 post‐induction. Blood samples were obtained at various times to measure MTX in plasma, and MTX and MTXPG_n in RBC. Effects on disease progression were indicated by body weight and paw size. After multiple‐doses, RBC MTX reached steady‐state (82.4 nm ) within 4 days. The MTXPG₂ and MTXPG₃ in RBC kept increasing until the end of the study, attaining 12.5 and 17.7 nm . Significant weight loss was observed after dosing with 1.5 mg/kg/2 days, whereas moderate effectiveness was observed after dosing with 0.3 mg/kg/2 days. A pharmacokinetic/pharmacodynamic/disease (PK/PD/DIS) model with indirect mechanisms and transduction components incorporating plasma MTX, RBC MTX and RBC MTXPG_n concentrations, and paw size was developed using naïve data pooling and ADAPT 5. The PK/PD in CIA rats dosed at 0.3 mg/kg/2 days were captured well by our proposed model. Methotrexate showed modest (I_maxd = 0.16) but sensitive (IC_50d = 0.712 nm ) effectiveness on paw edema. The higher dose produced toxicity. The proposed model offers improved understanding of the effects of methotrexate on rheumatoid arthritis. Copyright © 2013 John Wiley & Sons, Ltd.     

广西社区肝癌和鼻咽癌联合筛查研究

目的在社区建立动态的肝癌和鼻咽癌（简称“两癌”）高危人群队列,并通过定期复查以期早发现、早治疗肿瘤患者,从而提高“两癌”患者的生存率;评估在肝癌、鼻咽癌高发区实施联合筛检方案的可行性。方法在广西某社区对参与体检的自然人群采用“乙肝两对半”和“VCA—IgA抗体”的方法进行初筛。动员符合标准的肝癌、鼻咽癌高危人群参与每半年一次复查,对指定指标异常者做进一步的检测。结果目前建立了1546例肝癌高危人群和649例鼻咽癌高危人群队列,筛检出肝癌患者4例,总检出率为81．00／10万人年,规范化参加筛检的肝癌高危人群检出率为159．49／10万人年,中断检查的检出率为69．59／10万人年;筛检出鼻咽癌患者1例．总检出率为89．30／10万人年。结论按照规范化筛检的高危人群早中期肿瘤的检出率明显高于中断筛检者和普通人群,并随着复检次数的增加肿瘤检出率呈上升趋势。     

AD brain pathology: vascular origins? Results from the HAAS autopsy study

An increasing number of studies suggest a vascular contribution to Alzheimer's disease (AD). One major question these findings raise is whether vascular disease enhances the formation of AD-like lesions, or whether vascular disease just adds to clinical severity. We examined this question in a fully characterized autopsy sample based on the Honolulu Asia Aging Study. We found that AD markers of neurodegeneration (amyloid plaques, cerebral amyloid angiopathy and neurofibrillary tangles) were no more prevalent in those with neuropathologically defined vascular lesions compared to those without lesions. Our study suggests the burden of vascular and AD type lesions are independent of each other, and are consistent with an additive effect of the two types of lesions on cognitive impairment.     

Evaluation of Common Anesthetic and Analgesic Techniques for Tail Biopsy in Mice

Tail biopsy in mice is a common procedure in genetically modified mouse colonies. We evaluated the anesthetic and analgesic effects of various agents commonly used to mitigate pain after tail biopsy. We used a hot-water immersion assay to evaluate the analgesic effects of isoflurane, ice-cold ethanol, ethyl chloride, buprenorphine, and 2-point local nerve blocks before studying their effects on mice receiving tail biopsies. Mice treated with ethyl chloride spray, isoflurane and buprenorphine, and 2-point local nerve blocks demonstrated increased tail-flick latency compared with that of untreated mice. When we evaluated the behavior of adult and preweanling mice after tail biopsy, untreated mice demonstrated behavioral changes immediately after tail biopsy that lasted 30 to 60 min before returning to normal. The use of isoflurane, isoflurane and buprenorphine, buprenorphine, 2-point nerve block, or ethyl chloride spray in adult mice did not significantly improve their behavioral response to tail biopsy. Similarly, the use of buprenorphine and ethyl chloride spray in preweanling mice did not improve their behavioral response to tail biopsy compared with that of the untreated group. However, immersion in bupivacaine for 30 s after tail biopsy decreased tail grooming behavior during the first 30 min after tail biopsy. The anesthetic and analgesic regimens tested provide little benefit in adult and preweanling mice. Given that tail biopsy results in pain that lasts 30 to 60 min, investigators should carefully consider the appropriate anesthetic or analgesic regimen to incorporate into tail-biopsy procedures for mice.Abbreviation: HWI, Hot water immersionGenetically modified mice continue to advance the study of human disease. To obtain DNA for verification of genotype, mice may undergo tissues sample collection from multiple sites, including blood, saliva, hair, and stool. However, tail biopsy of the distal 5 mm continues to be the preferred location of obtaining sufficient DNA for genotyping.^14,19 Tail biopsy involves transecting multiple tissue types, including skin, nervous tissue, muscle, tendons, vasculature, cartilage, and bone,¹⁴ and this technique has the potential to cause short-term pain and distress. Several studies have demonstrated that tail biopsy without anesthesia causes short-term pain or distress that is greatest within the first 1 to 2 h but that may last as long as 5 h.^1,4,20,26 Similar physiologic changes associated with pain and distress were apparent and prolonged in anesthetized control mice.¹Analgesic protocols at the time of biopsy vary among institutions. IACUC policies from several institutions^{3,10,18,28,29} recommend but do not require anesthesia or analgesia for tail biopsy of mice 10 to 21 d old but do require anesthesia or analgesia for older mice. The anesthetic regimens to mitigate the temporary pain associated with tail biopsy at these institutions include immersion in ice-cold ethanol, topical ethyl chloride spray, and isoflurane inhalant anesthesia. Because of their short duration of action, we hypothesized that these agents provide poor management of the postprocedural pain associated with tail biopsy, and we decided to explore other practical options. The use of traditional drugs such as lidocaine, bupivacaine, or buprenorphine may provide more appropriate analgesia for tail biopsy. Here we examined the anesthetic and analgesic effects on mouse behavior after tail biopsy in adult and preweanling outbred NSA mice that had been treated with various analgesics and anesthetics.     

Citalopram for agitation in Alzheimer's disease: design and methods

BackgroundAgitation is one of the most common neuropsychiatric symptoms of Alzheimer’s disease (AD), and is associated with serious adverse consequences for patients and caregivers. Evidence-supported treatment options for agitation are limited. The citalopram for agitation in Alzheimer’s disease (CitAD) study was designed to evaluate the potential of citalopram to ameliorate these symptoms.MethodsCitAD is a randomized, double-masked, placebo-controlled multicenter clinical trial, with two parallel treatment groups assigned in a 1:1 ratio and randomization stratified by clinical center. The study included eight recruiting clinical centers, a chair’s office, and a coordinating center located in university settings in the United States and Canada. A total of 200 individuals having probable AD with clinically significant agitation and without major depression were recruited for this study. Patients were randomized to receive citalopram (target dose of 30 mg/d) or matching placebo. Caregivers of patients in both treatment groups received a structured psychosocial therapy. Agitation was compared between treatment groups using the NeuroBehavioral Rating Scale and the AD Cooperative Study- Clinical Global Impression of Change, which are the primary outcomes. Functional performance, cognition, caregiver distress, and rates of adverse and serious adverse events were also measured.ConclusionThe authors believe the design elements in CitAD are important features to be included in trials assessing the safety and efficacy of psychotropic medications for clinically significant agitation in AD.     

Ramucirumab as Second-Line Therapy in Metastatic Gastric Cancer: Real-World Data from the RAMoss Study

Background

Ramucirumab—alone or combined with paclitaxel—represents one of the main options for patients failing first-line treatment for advanced gastric cancer.

Objective

The RAMoss study aimed to evaluate the safety and efficacy profile of ramucirumab in the “real-life setting”.

Patients and Methods

Patients from 25 Italian hospitals started therapy consisting of ramucirumab 8 mg/kg i.v. d1,15q28 with or without paclitaxel 80 mg/m² i.v. d1,8,15q28. The primary endpoint was safety, and secondary endpoints were overall response rate (ORR), progression-free survival (PFS), and overall survival (OS).

Results

One hundred sixty-seven patients with disease progression on first-line therapy received ramucirumab as monotherapy (10%) or combined with paclitaxel (90%). Median treatment duration was 4 months (1–17 months). Global incidence of grade (G) 3–4 toxicity was 9.6%, and for neutropenia 5.4%; treatment was discontinued due to toxicity in 3% of patients. The most frequent adverse events (AE) were G1–2 fatigue (27.5%), G1–2 neuropathy (26.3%), and G1–2 neutropenia (14.9%). ORR was 20.2%. Stable disease was observed in 39.2% of patients, with a disease control rate of 59.4%. With a median follow-up of 11 months, median PFS was 4.3 months (95% confidence interval [CI] 4.1–4.7), whereas median OS was 8.0 months (95% CI: 7.09–8.9). In a multivariate analysis, ECOG performance status <1 or ≥1 (HR 1.13, 95% CI 1.0–1.27, p?=?0.04) and the presence versus absence of peritoneal metastases (HR 1.57, 95% CI 1.63–2.39, p?=?0.03) were independent poor prognostic factors.

Conclusions

These “real-life” efficacy data on ramucirumab treatment are in line with previous randomized trials. Ramucirumab is well tolerated in daily clinical practice.

     

Familial aggregation of endometriosis in a large pedigree of rhesus macaques

BACKGROUND: Endometriosis occurs in several non-human primate species that have menstrual cycles. This study investigated the prevalence and familial aggregation of endometriosis in one of those species, the rhesus macaque. METHODS: Between 1978 and 2001, 142 animals with endometriosis were identified from necropsy and surgical records and through the use of magnetic resonance imaging (MRI) at the Wisconsin National Primate Research Center, Madison, USA. All cases were used to build one large multigenerational pedigree and nine nuclear families comprising 1602 females in total. By 2002, the pedigrees contained 124 cases diagnosed at necropsy; 17 at surgery and three at MRI. Female animals that had died aged > or = 10 years without endometriosis, had both ovaries until at least 1 year prior to death, and had a full necropsy, were considered unaffected. RESULTS: The prevalence of endometriosis among necropsied animals aged > or = 10 years in the colony was 31.4% [95% confidence interval (CI) 26.9-35.9%]; prevalence increased with rising age and calendar age at death. Familial aggregation of endometriosis was strongly suggested by a significantly higher average kinship coefficient among affecteds compared with unaffecteds (P < 0.001) and a higher recurrence risk for full sibs (0.75; 95% CI 0.45-1.0) compared with maternal half sibs (0.26; 95% CI 0.10-0.41) and paternal half sibs (0.18; 95% CI 0.02-0.34). The segregation ratio among affected mothers (44.2%) was not significantly higher compared with unaffected mothers (36.6%). CONCLUSIONS: The results support familial aggregation of endometriosis in the rhesus macaque, and indicate that this is a promising animal model for the investigation of mode of inheritance, the location of potential genetic susceptibility loci and the influence of environmental factors.