The experience of hopelessness in a population of Greek cancer patients receiving palliative care

BACKGROUND: Beck Hopelessness Scale (BHS) has been translated and validated in many languages. AiM: The validation of the English version of BHS in advanced cancer patients receiving palliative treatment in Greece. METHODS: The final sample was 112 advanced cancer patients. Internal consistency, item-total correlations, and test-retest using four different approaches were calculated for the assessment of the reliability. Construct validity was used by examining correlations between BHS, Hospital Anxiety and Depression Scale (HAD-Depression) and the Schedule of Attitudes toward Hastened Death (SAHD). Known-groups validity was also assessed by detecting group differences according to disease severity as measured by the Eastern Cooperative Oncology Group (ECOG) performance status. Univariate and multivariate analyses were constructed to explore the relationship between hopelessness, depression, hastened death and the patients' demographic and clinical characteristics. RESULTS: One factor solution was yielded accounted for 46.64% of the variance. The test-retest reliability was satisfactory (p < 0.0005). Validity as performed using known-group analysis showed good results. Most significant correlations were found between BHS, ECOG (p = 0.018) and gender (p = 0.08). The strongest predictors were gender (p = 0.050) and ECOG (p = 0.045). CONCLUSIONS: BHS seemed to be a useful instrument to assess pessimistic attitude and hopelessness in a Greek cancer population, with valid psychometric properties.     

Oral Transmucosal Fentanyl Citrate: Overview of Pharmacological and Clinical Characteristics

Oral transmucosal fentanyl citrate (OTFC; brand name Actiq®, Cephalon, UT) is a new opioid formulation that incorporates fentanyl into a lozenge and allows drug delivery through the buccal mucosa. This kind of absorption avoids first-pass metabolism, yielding a bioavailability substantially greater than oral administration. OTFC has a rapid onset of action and a short duration of effect. These characteristics, which resemble the course of a typical breakthrough pain episode, resulted in making OTFC the first opioid analgesic formulation specifically developed and approved for control of breakthrough pain in cancer patients. Apart from that, OTFC has been used in a variety of clinical situations of noncancer pain. This review article presents the synthesis; clinical pharmacology; pharmacokinetic and pharmacodynamic properties, toxicity, and clinical efficacy of this novel agent.     

Serum osteoprotegerin is markedly increased and may contribute to decreased blood T cell count in hemodialysis patients

Purpose

Acquired immunity is impaired in hemodialysis (HD) patients, and decreased T cell number may contribute. Receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG) are expressed in cells of the immune system and affect T cell development, homeostasis and proliferation. Serum levels of RANKL and OPG and their relation to blood T cell number were evaluated in HD patients.

Methods

Thirty-four HD patients and 20 healthy controls participated in the study. Serum RANKL and OPG were measured by ELISA and T cell number was assessed by flow cytometry.

Results

Median RANKL concentration did not differ between HD patients and healthy volunteers (300.00 pmol/L; range, 3,340.00 vs. 330.00 pmol/L; range, 440.00 pmol/L; p = 0.528). Median OPG was markedly higher in HD patients than in healthy volunteers (13.12 ± 4.71 vs. 4.71 ± 0.93 pmol/L, p < 0.001). The T cell count was significantly lower in HD patients than in healthy controls (1,177.00 ± 567.71 vs. 1,519.80 ± 594.96 cells/mm³, p = 0.044). In HD patients, blood T cell number was correlated positively with serum RANKL (ρ = 0.462, p = 0.007) and negatively to serum OPG (r = ?0.449, p = 0.008).

Conclusion

Serum OPG concentration is markedly increased in HD patients and may contribute to decreased blood T cell count and impaired acquired immunity that characterizes this population.     

New mutations in TK2 gene associated with mitochondrial DNA depletion

Mitochondrial deoxyribonucleic acid depletion syndromes are autosomal recessive disorders characterized by a reduction of the amount of mitochondrial deoxyribonucleic acid, which impairs the synthesis of respiratory chain complexes. Mutations in the deoxyguanosine kinase and polymerase gamma genes have been identified in hepatocerebral forms, whereas thymidine kinase 2 gene mutations have been found in patients with isolated myopathy, encephalomyopathy, or spinal muscular atrophy. Mutations in the gene encoding the beta subunit of the adenosine diphosphate-forming succinyl-coenzyme A synthetase have also been reported in a family. In this report, the clinical, molecular, morphologic, and biochemical features of five children from two independent families with an infantile encephalomyopathy are characterized. The affected children manifested muscle mitochondrial deoxyribonucleic acid depletion and three novel thymidine kinase 2 gene mutations. They consist of a homozygous substitution resulting in Ala to Val change at the highly conserved position 181 of thymidine kinase in the first family, and two heterozygous substitutions in the second family: a Cys to Trp change at residue 108 and a Leu to Pro change at residue 257 of the enzyme. Common clinical features associated with these TK2 mutations are a normal early developmental phase followed by psychomotor regression, encephalopathy often with epileptic seizures, and myopathy with features of a progressive dystrophic process.     

Substance P (SP)-neurokinin-1 receptor (NK-1R) alters adipose tissue responses to high-fat diet and insulin action

Peripheral administration of a specific neurokinin-1 receptor (NK-1R) antagonist to mice leads to reduced weight gain and circulating levels of insulin and leptin after high-fat diet (HFD). Here, we assessed the contribution of substance P (SP) and NK-1R in diet-induced obesity using NK-1R deficient [knockout (KO)] mice and extended our previous findings to show the effects of SP-NK-1R interactions on adipose tissue-associated insulin signaling and glucose metabolic responses. NK-1R KO and wild-type (WT) littermates were fed a HFD for 3 wk, and obesity-associated responses were determined. Compared with WT, NK-1 KO mice show reduced weight gain and circulating levels of leptin and insulin in response to HFD. Adiponectin receptor mRNA levels are higher in mesenteric fat and liver in NK-1 KO animals compared with WT, after HFD. Mesenteric fat from NK-1R KO mice fed with HFD has reduced stress-activated protein kinase/c-Jun N-terminal kinase and protein kinase C activation compared with WT mice. After glucose challenge, NK-1R KO mice remove glucose from the circulation more efficiently than WT and pair-fed controls, suggesting an additional peripheral effect of NK-1R-mediated signaling on glucose metabolism. Glucose uptake experiments in isolated rat adipocytes showed that SP directly inhibits insulin-mediated glucose uptake. Our results further establish a role for SP-NK-1R interactions in adipose tissue responses, specifically as they relate to obesity-associated pathologies such as glucose intolerance and insulin resistance. Our results highlight this pathway as an important therapeutic approach for type 2 diabetes.     

Investigating the effects of TTS-fentanyl for cancer pain on the psychological status of patients naïve to strong opioids: an open label study

Few studies have investigated the effect of fentanyl delivered via the transdermal route with regard to the patient's psychological status. Patients who were naive to strong opioids and were attending a palliative care unit for pain relief from advanced cancer participated in this study to determine the effect of transdermal therapeutic system fentanyl (TTS-F) on their psychological condition. Spielberger State-Trait Anxiety Inventory (STAI), Zung Self-Rating Depression Scale (SDS), the Karnofsky Performance Scale (100-0, optimum-death), and a Visual Analogue Scale (VAS) (0: no pain; 10: worst pain) were used to measure the level of pain. Data were collected at baseline (T0), on the 7th day (T1), and on the 14th day (T2) of TTS-F application in order to determine changes in correlation to TTS-F dose. Patients' status improved according to the Zung SDS questionnaire (P < .0005) and with each of its subscales (P < .05). A similar improvement was observed according to the Spielberger STAI questionnaire (P = .002). Moreover, VAS measures demonstrated that patients achieved significant pain relief (P < .0005), while patients' performance status did not alter significantly over the study period. Furthermore, the Zung SDS showed a statistically significant correlation when compared with the Spielberger STAI (P < .01). These data provide some evidence that the psychological status, as measured with respect to depression and anxiety in patients with advanced cancer, is improved in patients receiving TTS-fentanyl. Future research should use a broad range of psychological measurements in order to assist the development of practices, which are aimed at the improvement of quality of life in these patients.