The Practitioner Proposes a Treatment Change and the Patient Declines: What to do next?

Abstract Objective: This study describes how pain practitioners can elicit the beliefs that are responsible for patients’ judgments against considering a treatment change and activate collaborative decision making. Methods: Beliefs of 139 chronic pain patients who are in treatment but continue to experience significant pain were reduced to 7 items about the significance of pain on the patient’s life. The items were aggregated into 4 decision models that predict which patients are actually considering a change in their current treatment. Results: While only 34% of study participants were considering a treatment change overall, the percentage ranged from 20 to 70, depending on their ratings about current consequences of pain, emotional influence, and long‐term impact. Generalized linear model analysis confirmed that a simple additive model of these 3 beliefs is the best predictor. Conclusion: Initial opposition to a treatment change is a conditional judgment and subject to change as specific beliefs become incompatible with patients’ current conditions. These beliefs can be elicited through dialog by asking 3 questions.     

Branched chain and aromatic amino acids change acutely following two medical therapies for type 2 diabetes mellitus

ObjectiveElevated circulating levels of branched chain and aromatic amino acids (BCAA/AAAs) are associated with insulin resistance and incident type 2 diabetes (T2D). BCAA/AAAs decrease acutely during an oral glucose tolerance test (OGTT), a diagnostic test for T2D. It is unknown whether changes in BCAA/AAAs also signal an early response to commonly used medical therapies for T2D.Materials and MethodsA liquid chromatography–mass spectrometry approach was used to measure BCAA/AAAs in 30 insulin sensitive (IS) and 30 insulin resistant (IR) subjects before and after: 1) one dose of a sulfonylurea medication, glipizide, 5 mg orally; 2) two days of twice daily metformin 500 mg orally; and 3) a 75-g OGTT. Percent change in BCAA/AAAs was determined after each intervention.ResultsFollowing glipizide, which increased insulin and decreased glucose in both subject groups, BCAA/AAAs decreased in the IS subjects only (all P < 0.05). Following metformin, which decreased glucose and insulin in only the IR subjects, 4 BCAA/AAAs increased in the IR subjects at or below P = 0.05, and none changed in the IS subjects. Following OGTT, which increased glucose and insulin in all subjects, BCAA/AAAs decreased in all subjects (P < 0.05).ConclusionsBCAA/AAAs changed acutely during glipizide and metformin administration, and the magnitude and direction of change differed by the insulin resistance status of the individual and the intervention. These results indicate that BCAA/AAAs may be useful biomarkers for monitoring the early response to therapeutic interventions for T2D.     

Hb Hinwil [β38(C4)Thr→Asn,ACC>AAC] Associated with β0-Thalassemia in a Sicilian Child

Hemoglobins (Hbs) with high oxygen affinity play a well-known role among the causes of erythrocytosis. In 1996, a new Hb called Hb Hinwil or β38(C4)Thr→Asn was described. In carriers, it causes an increase in the number of red blood cells, total Hb, and hematocrit. Here we report the case of a patient, aged 10 months, whom we observed because of severe erythrocytosis. The family history of β-thalassemia (β-thal) inheritance, and the evidence in the patient of marked microcytosis, prompted us to perform molecular analysis to detect β gene mutations that revealed a codon 39 (C>T) (β⁰) mutation in the heterozygous state and the presence of the Hb Hinwil mutation on the other allele. We discuss diagnostic, clinical, prognostic, and therapeutic aspects of this rare condition, underlining the extreme difficulty in choosing therapeutic options because of a lack of similar reports in the literature.     

抗结核药品供应管理现状调查

目的 分析抗结核药品库存、缺货及过期破损等情况,了解抗结核药品供应管理现状。 方法 采用现况调查的方法,根据我国各地区免费抗结核药品的不同采购供应模式,选择河南省、重庆市、湖北省、吉林省、上海市及浙江省等6个省（直辖市）［包含6个省(直辖市)下属的4个地市及10个区（县）的20家结核病防治机构作为现场调查地区］,对全国和6个省(直辖市)2007年1-12月的季度末4种免费抗结核药品（HRZE、HRE、HR板式组合药和链霉素）库存情况,季度末药品缺货比率;以及20家结防机构的4种免费抗结核药品（HRZE、HRE、HR板式组合药和链霉素）库存率、药品过期破损率、账物相符率进行统计分析。 结果 全国免费抗结核药品季度末库存量平均可使用时间2.7～5.8个月,平均缺货比率12.9%～15.8%;6个省(直辖市)平均可使用时间1.4～18.1个月。20家调查机构的4种免费抗结核药品库存率为33.3%～100.0%,平均缺货比率1.0%～20.5%;7家机构存在药品过期破损,过期破损率为0.1%～2.4%;5家调查机构存在账物不符,账物相符率为50.0%～66.7%。 结论 应加强对药品供应管理的监控和评价,为完善我国抗结核药品的供应管理体系提供科学的依据。     

Zinc supplementation impairs monocyte function

Zinc has been shown to be involved in many functions of the immune system. This study was conducted to examine the effect of zinc supplementation on phagocytic, fungicidal and metabolic activity of blood monocytes of marasmic infants during nutritional rehabilitation. A controlled, double-blind design was used in which 19 infants fed a zinc-fortified formula were compared with 20 infants fed the same, unfortified formula. Evaluation of phagocytic-fungicidal capacity, growth, zinc, copper and iron status was performed in both groups on admission and after 60 and 105 days of nutritional rehabilitation. Although energy, copper and iron intakes were similar in the two groups, a decrease in the number of infants able to phagocytose one or more Candida buds was observed after 60 days of zinc supplementation compared to admission (p<0.03). No change in phagocytic ability was detected between admission and 60 days in the control group. The number of infants with depressed fungicidal activity increased significantly after 105 days of nutritional rehabilitation in the zinc-fortified group as compared to controls (p<0.04). The number and duration of impetigo episodes was significantly greater in the group fed the zinc-fortified formula. These results suggest that zinc supplements at the RDA level may impair monocyte function.     

Treatment of NSCLC patients with an EGF-based cancer vaccine: report of a Phase I trial

Epidermal Growth Factor (EGF) promotes tumor cell proliferation and survival upon binding to its receptor. We have developed a new active specific immunotherapy based on EGF deprivation. In the present paper, we show the results of a Phase I trial in 43 patients with advanced non-small cell lung cancer (NSCLC) who received the EGF vaccine. Patients who had already received first line therapy were randomized to receive a single or double dose of the EGF vaccine, weekly for four weeks and monthly thereafter. No significant toxicity was seen after vaccination. Adverse events consisted primarily of fever, chills, nausea, vomiting and flushing. Fifteen patients (39%) developed a good antibody response (GAR) against EGF. The geometric mean of the antibody titer was higher in the double dose group. EGF concentration was quantified in serum. An inverse correlation between anti-EGF antibody titers and EGF concentration was seen after immunization. Vaccinated patients achieved median survival times of 8.23 months from randomization. Patients who received the double dose of treatment showed a trend toward increased survival in comparison with patients who received the single dose. GAR and patients in whom the serum EGF decreased below the 168 pg/ml cut-off point had a significantly better survival when compared to poor responders or patients in which the EGF levels were not considerably reduced. Our results confirm the immunogenicity of the EGF vaccine in the treatment of patients with advanced stage NSCLC. Antibody titers and serum EGF levels appear to correlate with patient survival.     

Peripheral vision for perception and action

Anatomical and physiological evidence suggests that vision-for-perception and vision-for-action may be differently sensitive to increasingly peripheral stimuli, and to stimuli in the upper and lower visual fields (VF). We asked participants to fixate one of 24 randomly presented LED arranged radially in eight directions and at three eccentricities around a central target location. One of two (small, large) target objects was presented briefly, and participants responded in two ways. For the action task, they reached for and grasped the target. For the perception task, they estimated target height by adjusting thumb-finger separation. In a final set of trials for each task, participants knew that target size would remain constant. We found that peak aperture increased with eccentricity for grasping, but not for perceptual estimations of size. In addition, peak grip aperture, but not size-estimation aperture, was more variable when targets were viewed in the upper as opposed to the lower VF. A second experiment demonstrated that prior knowledge about object size significantly reduced the variability of perceptual estimates, but had no effect on the variability of grip aperture. Overall, these results support the claim that peripheral VF stimuli are processed differently for perception and action. Moreover, they support the idea that the lower VF is specialized for the control of manual prehension. Finally, the effect of prior knowledge about target size on performance substantiates claims that perception is more tightly linked to memory systems than action.     

Uncoupling between epidermal growth factor receptor and downstream signals defines resistance to the antiproliferative effect of Gefitinib in bladder cancer cells

Activation of the epidermal growth factor receptor (EGFR) and downstream signaling pathways, such as phosphatidylinositol-3 kinase/Akt and Ras/mitogen-activated protein kinase (MAPK), have been implicated in causing resistance to EGFR-targeted therapy in solid tumors, including the urogenital tumors. To investigate the mechanism of resistance to EGFR inhibition in bladder cancer, we compared EGFR tyrosine kinase inhibitor (Gefitinib, Iressa, ZD1839) with respect to its inhibitory effects on three kinases situated downstream of EGFR: MAPK, Akt, and glycogen synthase kinase-3beta (GSK-3beta). We found that the resistance to the antiproliferative effects of gefitinib, in vitro as well as in vivo in nude mice models, was associated with uncoupling between EGFR and MAPK inhibition, and that GSK-3beta activation and degradation of its target cyclin D1 were indicators of a high cell sensitivity to gefitinib. Further analysis of one phenotypic sensitive (253J B-V) and resistant (UM-UC13) cell lines revealed that platelet-derived growth factor receptor-beta (PDGFRbeta) activation was responsible for short circuiting the EGFR/MAPK pathway for mitogenic stimuli. However, invasion as well as actin dynamics were efficiently reduced by EGFR inhibition in UM-UC13. Chemical disruption of signaling pathways or of PDGFR kinase activity significantly reduced the inactive pool of cellular GSK-3beta in UM-UC13 cells. In conclusion, our data show that the uncoupling of EGFR with mitogenic pathways can cause resistance to EGFR inhibition in bladder cancer. Although this uncoupling may arise through different mechanisms, we suggest that the resistance of bladder cancer cells to EGFR blockade can be predicted early in the course of treatment by measuring the activation of GSK-3beta and of nuclear cyclin D1.