HRQoL changes,mood disorders and satisfaction after treatment in an unselected population of patients with lung cancer

Objectives: This study intended to explore the impact of the first treatment modality on health‐related quality of life (HRQoL), mood disorders and mastery in an unselected population of patients with primary lung cancer and to judge patient satisfaction with treatment. Materials and Methods: An unselected group of 479 patients with newly diagnosed lung cancer in Southern Norway (Agder counties) were included prospectively from June 2002 to June 2005, collecting data on histology, treatment options, HRQoL, mood disorders and mastery at baseline as well as satisfaction with treatment, and changes in HRQoL and mood disorders after finishing the first treatment modality. Results: After finishing the first treatment modality, patients experienced a worsening of nine HRQoL parameters and an improvement in one. Patients in good performance status experienced reduced physical and role function, and if in reduced performance, improved emotional and role function. Patients with mood disorders experienced reduced anxiety and depression, anxious patients experienced reduced neuropathies, and depressed patients experienced improved social functioning and appetite. Half of the patients treated actively were definitely positive to repeat the same treatment again compared with only 15% in the best supportive care group. Surgery was associated with reduced role function and increased dyspnoea, radiation was associated with increased fatigue, and chemotherapy in small cell lung cancer (SCLC), to a larger extent, was associated with alopecia than in non‐SCLC (NSCLC). Conclusion: The development of many HRQoL parameters after the first treatment modality in an unselected population of patients with primary lung cancer seemed, at large, well correlated to general disease progression and to well‐known treatment side effects. However, reduced role function after lung surgery, and reduced anxiety and depression in patients with mood disorders at baseline might be surprising. Patient satisfaction with treatment was surprisingly good. Several findings in this study may help clinicians to improve their handling of patients with lung cancer. Please cite this paper as: Rolke HB, Bakke PS and Gallefoss F. HRQoL changes, mood disorders and satisfaction after treatment in an unselected population of patients with lung cancer. The Clinical Respiratory Journal 2010; 4: 168–175.     

Review: peroxisome proliferator-activated receptor-gamma and its role in the development and treatment of diabetes

Since its identification as the receptor for antidiabetic thiazolidinedione drugs, peroxisome proliferator-activated receptor-gamma (PPARgamma) has been the focus of pharmaceutical drug discovery programs directed toward finding better drugs for the treatment of diabetes, as well as the object of basic research aimed at understanding its role in the regulation of metabolism. We now understand a great deal about the crucial role that PPARgamma plays in adipocyte differentiation and development, and are rapidly gaining knowledge about the role of the receptor in the regulation of metabolism. However, many crucial aspects of the molecular mechanism by which modulation of PPARgamma activity affects insulin resistance and glucose homeostasis are still not clearly understood. Here the authors review the current status of PPARgamma research, with an emphasis on its role in the causes and treatment of type 2 diabetes.     

HLA and cytokine gene polymorphisms in relation to occurrence of palindromic rheumatism and its progression to rheumatoid arthritis

OBJECTIVE: Palindromic rheumatism (PR) is an episodic arthropathy that may precede typical rheumatoid arthritis (RA), although pathogenetic relationships between these disorders remain unclear. The predictive value for those immunogenetic risk factors implicated in RA for disease progression in PR remains to be established. A previous retrospective analysis from our group has implicated rheumatoid factor in disease progression. Our objective was to determine the contribution of HLA and cytokine gene polymorphisms implicated in RA to predisposition to PR and to progression of PR to chronic joint inflammation. METHODS: We studied 147 patients with PR seen in a tertiary referral center; 87 were selected retrospectively from the period 1986-96 using a structured selection process and 60 were selected prospectively in the period 1997-2001. Comparison groups included 149 patients with RA and 149 ethnically matched controls. Typing for HLA-DRB1 alleles and HLA-DRB1-04 subtypes was performed following polymerase chain reaction (PCR) amplification using sequence-specific primers (SSP). Cytokine genotypes were ascertained following PCR-SSP with and without digestion with restriction enzymes. Time-adjusted survival analysis (Kaplan-Meier) and multivariate logistic regression were used to assess the independent contribution of immunogenetic markers in assessing progression of PR to chronic joint inflammation. RESULTS: Thirty-one percent of patients progressed to connective tissue disease after a mean of 10.6 (retrospective group) and 3.9 (prospective group) years. A significantly increased prevalence of the shared epitope (SE) allele was noted in patients with PR (65%) versus controls (39%) (OR 2.9, 95% CI 1.8-4.6, p < 0.001). This primarily reflected increased prevalence of the DRB1-0401 and 0404 and not DRB1-01 alleles. A weak contribution to disease susceptibility was also noted with carriage of the IL4 promoter -590T (OR 1.8, 95% CI 1.1-3.0, p = 0.02) and IL4 intron 3 RP1 (OR 1.7, 95% CI 1.1-2.9, p = 0.03) alleles. The TNFa +489A allele was associated with RA (OR = 2.7, 95% CI 1.5-5.1, p = 0.001) in both SE+ and SE- patients, but not with PR. Time-adjusted and multivariate Cox regression analysis revealed that only homozygosity for SE alleles was a significant independent risk factor for disease progression to chronicity in PR (hazard ratio 2.9, 95% CI 1.2-6.9, p = 0.02). However, none of 8 patients homozygous for SE- DRB1 XP4n alleles developed chronic disease after 10 years of followup (p = 0.07). CONCLUSION: The immunogenetic risk profile for PR resembles that for RA, indicating that PR is likely not an independent entity. A significant gene dose effect for SE alleles is operative in determining risk for progression from PR to RA.     

The molecular and cellular basis of olfactory-driven behavior in Anopheles gambiae larvae

The mosquito Anopheles gambiae is the principal Afrotropical vector for human malaria. A central component of its vectorial capacity is the ability to maintain sufficient populations of adults. During both adult and preadult (larval) stages, the mosquitoes depend on the ability to recognize and respond to chemical cues that mediate feeding and survival. In this study, we used a behavioral assay to identify a range of odorant-specific responses of An. gambiae larvae that are dependent on the integrity of the larval antennae. Parallel molecular analyses have identified a subset of the An. gambiae odorant receptors (AgOrs) that are localized to discrete neurons within the larval antennae and facilitate odor-evoked responses in Xenopus oocytes that are consistent with the larval behavioral spectrum. These studies shed light on chemosensory-driven behaviors and represent molecular and cellular characterization of olfactory processes in mosquito larvae. These advances may ultimately enhance the development of vector control strategies, targeting olfactory pathways in larval-stage mosquitoes to reduce the catastrophic effects of malaria and other diseases.     

Osteoporosis and fractures in postmenopausal women using estrogen

BACKGROUND: Previous studies demonstrate that postmenopausal women who use estrogen are somewhat protected from bone loss and fractures compared with nonusers, but the extent to which estrogen users remain at risk for osteoporosis and fractures is uncertain. OBJECTIVE: To determine long-term probabilities for incident fractures among postmenopausal estrogen users. METHODS: We examined data from the Study of Osteoporotic Fractures, a prospective cohort study with 10 years of follow-up (1986-1999). This cohort includes 8816 women 65 years and older from community settings in 4 areas of the United States. MAIN OUTCOME MEASURES: Hip, wrist, vertebral, and nonvertebral fractures. RESULTS: At baseline, using criteria developed by the World Health Organization, 40% of continuous estrogen users were osteopenic and 13% were osteoporotic at the hip or spine. Although women currently using estrogen lost less bone density than past users or those who never used estrogen, all user groups on average lost bone from the hip and calcaneus. During 10 years of observation, the adjusted probability of nonvertebral fractures was 19.6% for continuous estrogen users, similar to current partial users and lower than past users and those who never used estrogen (P<.05). These comparisons were similar for hip, wrist, and vertebral fractures. CONCLUSIONS: Although estrogen use is associated with reduced prevalence of low bone density, less bone loss, and lower probabilities for fractures, osteoporosis and fractures are common in older women who used estrogen continuously since menopause. Estrogen users should be considered in strategies designed to detect, prevent, and treat osteoporosis.