A test of concordance between patient and psychiatrist valuations of multiple treatment goals for schizophrenia

Background While much discussion has been placed on the problem of poor compliance in the treatment of schizophrenia, there has been little discussion on the concordance between patients and psychiatrists, an important contributing factor to patient‐centred care. Objective To estimate the concordance between patients’ and psychiatrists’ (ordinal and cardinal) valuations of multiple goals for schizophrenia treatment and to illustrate the utility of the self‐explicated method in valuing a large number of treatment goals. Design Twenty treatment goals were identified during focus groups and literature review and were presented to patients and psychiatrists during structured interviews. Respondents were asked to rank the multiple treatment goals and rate them on a 5‐point Likert scale. Three scores were calculated based on the ranking (1–20), rating (Likert scale) (1–5) and a self‐explicated method estimated as the product of rating and ranking score (1–100). Concordance was tested using Spearman’s rho for overall ordinal rankings and via anova and F‐test for the cardinal values assigned to a specific treatment goal. Participants A total of 105 outpatients diagnosed with schizophrenia and 160 psychiatrists in Germany. Results Patient and psychiatrist values were concordant when the ordinal properties of their valuations were assessed by rating (ρ = 0.63; P = 0.002), ranking (ρ = 0.51; P = 0.02) and self‐explicated methods (ρ = 0.54; P = 0.01). Significant discordances were found when comparing the cardinal value placed on any given treatment goal using all three approaches, but the self‐explicated method produced a more discerning statistic. Relative to patients, psychiatrists significantly (P < 0.05) overvalued reduced lack of emotion, improved sexual pleasure and improved communication while undervaluing reuptake of activities of daily living, improved satisfaction and recovered capacity for work. Conclusions While there is an overall concordance between patients’ and psychiatrists’ valuation, significantly different valuations on specific goals can be identified. Here, psychiatrists tend to focus on ‘textbook’ outcomes, while patients are more concerned with functioning and living a normal life. This study also demonstrates the importance of comparing the concordance in treatment goals and the importance of preference‐based methods, such as the self‐explicated method, in the study of concordance.     

Fatigue performance of angle-stable tibial nail interlocking screws

Purpose

Tibial nail interlocking screw failure often occurs during delayed fracture consolidation or at early weight bearing of nailed unstable fractures, in general when high implant stress could not be reduced by other means. Is there a biomechanical improvement in long-term performance of angle stable locking screws compared to conventional locking screws for distal locking of intramedullary tibial nails?

Methods

Surrogate bones of human tibiae were cut in the distal third and distal locking of the 10 mm intramedullary tibial nail was performed with either two angle stable locking screws or two conventional locking screws in the mediolateral plane. Six specimens per group were mechanically tested under quasi-static and cyclic axial loading with constantly increasing force.

Results

Angle stable locking screw constructs exhibited significantly higher stiffness values (7,809 N/mm ± 647, mean ± SD) than conventional locking screw constructs (6,614 N/mm ± 859, p = 0.025). Angle stable locking screw constructs provided a longer fatigue life, expressed in a significantly higher number of cycles to failure (187,200 ± 18,100) compared to conventional locking screw constructs (128,700 ± 7,000, p = 0.004).

Conclusion

Fatigue performance of locking screws can be ameliorated by the use of angle stable locking screws, being especially important if the nail acts as load carrier and an improved stability during fracture healing is needed.     

Network centrality in the human functional connectome

The network architecture of functional connectivity within the human brain connectome is poorly understood at the voxel level. Here, using resting state functional magnetic resonance imaging data from 1003 healthy adults, we investigate a broad array of network centrality measures to provide novel insights into connectivity within the whole-brain functional network (i.e., the functional connectome). We first assemble and visualize the voxel-wise (4 mm) functional connectome as a functional network. We then demonstrate that each centrality measure captures different aspects of connectivity, highlighting the importance of considering both global and local connectivity properties of the functional connectome. Beyond "detecting functional hubs," we treat centrality as measures of functional connectivity within the brain connectome and demonstrate their reliability and phenotypic correlates (i.e., age and sex). Specifically, our analyses reveal age-related decreases in degree centrality, but not eigenvector centrality, within precuneus and posterior cingulate regions. This implies that while local or (direct) connectivity decreases with age, connections with hub-like regions within the brain remain stable with age at a global level. In sum, these findings demonstrate the nonredundancy of various centrality measures and raise questions regarding their underlying physiological mechanisms that may be relevant to the study of neurodegenerative and psychiatric disorders.     

Low-dose cyclosporine mediates donor hyporesponsiveness in a fully mismatched rat kidney transplant model

Tolerance induction protocols have been successfully tested in animal models, yet their compatibility with immunosuppressive drugs remains to be fully elucidated. Our own previous data have indicated that cyclosporine A (CsA) affects the balance of effector and regulatory mechanisms with low-dose CsA doses promoting hyporesponsiveness. Here, we present a fully mismatched rat kidney model in which low-dose CsA treatment induces donor hyporesponsiveness to secondary renal allografts. Lewis recipients of DA kidney grafts received low, medium or high doses of CsA × 10 days. By 30 days, the primary transplant was removed and a second transplant of donor origin was engrafted. Following low-dose CsA, but not high-dose CsA treatment of the primary recipient, secondary transplants were accepted long-term in the absence of immunosuppression. Regulatory T-cell function was unimpaired and independent of the CyA dosage. Of note, low-dose CsA significantly reduced alloantibody titers in primary recipients. Adoptive transfer of graft infiltrating cells or splenocytes from hyporesponsive recipients supported long-term acceptance of donor kidney allografts. These results demonstrate a dose-dependent and transferable "pro-tolerogenic" effect of low-dose CsA treatment. This model is of clinical relevance to test the interference of CsA with tolerance induction in the absence of additional immunosuppression.     

Association of circulating interleukin (IL)-12- and IL-10-producing dendritic cells with time posttransplant, dose of immunosuppression, and plasma cytokines in renal-transplant recipients

BACKGROUND: Interleukin (IL)-12-producing dendritic cells (IL-12+DC) polarize T helper (Th) differentiation toward Th1, whereas IL-10+DC induce Th differentiation toward Th2. We investigated DC and plasma cytokine patterns early and late after transplantation. METHODS: Twenty-five hospitalized renal-transplant recipients without acute rejection or infection early (<40 days) posttransplant, 32 symptom-free outpatients with long-term functioning transplants (2,762+/-2,423 days posttransplant), and 17 healthy controls were studied. The intracellular production of IL-12 and IL-10 in CD11c+ CD83+ CD40+ DC was measured in freshly obtained whole blood using four-color fluorescence flow cytometry. In addition, plasma cytokine levels were investigated. RESULTS: Early and late posttransplant patients had significantly lower proportions of IL-12+DC (early: P=0.001; late: P=0.034) and lower ratios of IL-12+/IL-10+DC (early: P=0.0001; late: P<0.0001) than healthy controls. IL-10+DC (P=0.0004) and IL-12+DC (P=0.002) increased with time posttransplant in association with dose reductions of cyclosporine (IL-10+DC: P=0.003; IL-12+DC: P=0.005), methylprednisolone (IL-10+DC: P<0.0001; IL-12+DC: P=0.001) and mycophenolate mofetil (IL-10+DC: P<0.0001; IL-12+DC: P=0.004). Both IL-10+DC and IL-12+DC were associated with low plasma IL-10 (IL-10+DC: P=0.010; IL-12+DC: P=0.011) and high plasma IL-6 (IL-10+DC: P=0.001; IL-12+DC: P=0.009). IL-10+DC were also associated with high plasma levels of IL-3 (P=0.003), interferon (IFN)-gamma (P=0.014), and IL-2 (P=0.058). CONCLUSION: IL-10+DC and IL-12+DC in peripheral blood are associated with time after transplantation and dosage of immunosuppression. IL-10+DC dominate late posttransplant in the presence of Th1 plasma cytokines (high IFN-gamma and IL-2), high IL-3, and low IL-10. These findings could be a reflection of immunoregulatory processes favoring long-term allograft acceptance.     

Surgical treatment of solitary adrenal metastasis from non-small cell lung cancer

BACKGROUND: Management of solitary adrenal metastasis from non-small cell lung cancer is still debated. Although classically considered incurable, various reports with small numbers of patients have shown that surgical treatment might improve long-term survival. The aim of this study was to review our experience and to identify factors that could affect survival. METHODS: From January 1989 through April 2003, 23 patients underwent complete resection of an isolated adrenal metastasis after surgical treatment of non-small cell lung cancer. There were 19 men and 4 women, with a mean age of 54 +/- 10 years. The diagnosis of adrenal metastasis was synchronous with the diagnosis of non-small cell lung cancer in 6 patients and metachronous in 17 patients. The median disease-free interval for patients with metachronous metastasis was 12.5 months (range, 4.5-60.1 months). RESULTS: The overall 5-year survival was 23.3%. Univariate and multivariate analysis demonstrated that a disease-free interval of greater than 6 months was an independent and significant predictor of increased survival in patients after adrenalectomy. All patients with a disease-free interval of less than 6 months died within 2 years of the operation. The 5-year survival was 38% after resection of an isolated adrenal metastasis that occurred more than 6 months after lung resection. Adjuvant therapy and pathologic staging of non-small cell lung cancer did not affect survival. CONCLUSIONS: Surgical resection of metachronous isolated adrenal metastasis with a disease-free interval of greater than 6 months can provide long-term survival in patients previously undergoing complete resection of the primary non-small cell lung cancer.     

Adjuvant endocrine therapy for perimenopausal women with early breast cancer

Adjuvant treatment with aromatase inhibitors (AIs) improves outcomes in postmenopausal women with hormone-sensitive early breast cancer compared with tamoxifen. However, AIs should not be used in premenopausal women because they can paradoxically increase estrogen secretion and may therefore stimulate tumor progression. In perimenopausal women undergoing treatment for breast cancer, it can be difficult to determine true menopausal status because adjuvant chemotherapy, tamoxifen, and gonadotropin-releasing hormone analogues can induce transient (or permanent) ovarian suppression. How can one determine whether these women are truly postmenopausal and therefore candidates for AI therapy? A panel of experts in the field of endocrine therapy in breast cancer met in Dubrovnik, Croatia, on October 23, 2006, to discuss this clinical dilemma. This report summarizes the conclusions and recommendations that arose from this discussion.