Cost-utility of a visiting service for older widowed individuals: Randomised trial

Background. Despite a growing understanding of the effectiveness of bereavement interventions and the groups that benefit most from them, we know little about the cost-effectiveness of bereavement interventions. Methods. We conducted a cost-utility analysis alongside a randomized clinical trial on a visiting service for older widowed individuals (n = 110) versus care as usual (CAU; n = 106). The visiting service is a selective bereavement intervention that offers social support to lonely widows and widowers by a trained volunteer. Participants were contacted 6-9 months post-loss. Eleven percent of all contacted persons responded and eight percent participated in the trial. The primary outcome measure was quality adjusted life years (QALYs) gained (assessed with the EQ-5D), which is a generic measure of health status. Costs were calculated from a societal perspective excluding costs arising from productivity losses. Using the bootstrap method, we obtained the incremental cost utility ratio (ICUR), projected these on a cost-utility plane and presented as an acceptability curve. Results. Overall, the experimental group demonstrated slightly better results against slightly higher costs. Whether the visiting service is acceptable depends on the willingness to pay: at a willingness to pay equal to zero per QALY gained, the visiting service has a probability of 31% of being acceptable; beyond €20,000, the visiting service has a probability of 70% of being more acceptable than CAU. Conclusion. Selective bereavement interventions like the visiting service will not produce large benefits from the health economic point of view, when targeted towards the entire population of all widowed individuals. We recommend that in depth analyses are conducted to identify who benefits most from this kind of interventions, and in what subgroups the incremental cost-utility is best. In the future bereavement interventions are then best directed to these groups. Trial registration. Controlled trials ISRCTN17508307. © 2008 Onrust et al; licensee BioMed Central Ltd

The Repertoire of Heterotrimeric G Proteins and RGS Proteins in Ciona intestinalis

BACKGROUND:Heterotrimeric G proteins and regulators of G protein signaling (RGS) proteins are key downstream interacting partners in the G protein coupled receptor (GPCR) signaling pathway. The highly versatile GPCR transmembrane signaling system is a consequence of the coupling of a diverse set of receptors to downstream partners that include multiple subforms of G proteins and regulatory proteins including RGS proteins, among others. While the GPCR repertoire of Ciona intestinalis, representing the basal chordate is known, the repertoire of the heterotrimeric G proteins and RGS proteins is unknown. METHODOLOGY/PRINCIPAL FINDINGS:In the present study, we performed an in-silico genome-wide search of C. intestinalis for its complement of G proteins and RGS proteins. The identification of several one-to-one orthologs of human G proteins at the levels of families, subfamilies and types and of homologs of the human RGS proteins suggests an evolutionarily conserved structure function relationship of the GPCR signaling mechanism in the chordates. CONCLUSIONS:The C. intestinalis genome encodes a highly conserved, albeit, limited repertoire of the heterotrimeric G protein complexes with the size of subunit types comparable with that in lower eukaryotes

Sub-lethal radiation enhances anti-tumor immunotherapy in a transgenic mouse model of pancreatic cancer

BACKGROUND: It is not uncommon to observe circulating tumor antigen-specific T lymphocytes in cancer patients despite a lack of significant infiltration and destruction of their tumors. Thus, an important goal for tumor immunotherapy is to identify ways to modulate in vivo anti-tumor immunity to achieve clinical efficacy. We investigate this proposition in a spontaneous mouse tumor model, Rip1-Tag2. METHODS: Experimental therapies were carried out in two distinctive trial designs, intended to either intervene in the explosive growth of small tumors, or regress bulky end-stage tumors. Rip1-Tag2 mice received a single transfer of splenocytes from Tag-specific, CD4(+) T cell receptor transgenic mice, a single sub-lethal radiation, or a combination therapy in which the lymphocyte transfer was preceded by the sub-lethal radiation. Tumor burden, the extent of lymphocyte infiltration into solid tumors and host survival were used to assess the efficacy of these therapeutic approaches. RESULTS: In either intervention or regression, the transfer of Tag-specific T cells alone did not result in significant lymphocyte infiltration into solid tumors, not did it affect tumor growth or host survival. In contrast, the combination therapy resulted in significant reduction in tumor burden, increase in lymphocyte infiltration into solid tumors, and extension of survival. CONCLUSIONS: The results indicate that certain types of solid tumors may be intrinsically resistant to infiltration and destruction by tumor-specific T lymphocytes. Our data suggest that such resistance can be disrupted by sub-lethal radiation. The combinatorial approach presented here merits consideration in the design of clinical trials aimed to achieve T cell-mediated anti-tumor immunity

Effectiveness of Triple P in the Netherlands: state of affairs and controversy

Objective: The Triple P – Positive Parenting Program is available in over 50% of the Dutch municipalities. In this article we summarize the effects of Triple P as found in international meta-analyses and Dutch research. We also discuss the controversy surrounding Triple P. Method: We systematically discuss international meta-analyses and Dutch studies with a control group. Results: According to international research, the effect of Triple P on child behavioural problems and parenting skills is greater than that of care-as-usual. In the Netherlands, Triple P levels 3 and 4 are not more effective than care-as-usual; other levels of Triple P have not been studied. Discussion: Conflict of interest among the developers of Triple P appears to influence the results of international research on Triple P in which they are often involved. Dutch research is performed independently of Triple P developers except for one study) and finds that Triple P is not more effective than care-as-usual

Prolonged Grief Disorder: Psychometric Validation of Criteria Proposed for DSM-V and ICD-11

BACKGROUND: Bereavement is a universal experience, and its association with excess morbidity and mortality is well established. Nevertheless, grief becomes a serious health concern for a relative few. For such individuals, intense grief persists, is distressing and disabling, and may meet criteria as a distinct mental disorder. At present, grief is not recognized as a mental disorder in the DSM-IV or ICD-10. The goal of this study was to determine the psychometric validity of criteria for prolonged grief disorder (PGD) to enhance the detection and potential treatment of bereaved individuals at heightened risk of persistent distress and dysfunction. METHODS AND FINDINGS: A total of 291 bereaved respondents were interviewed three times, grouped as 0-6, 6-12, and 12-24 mo post-loss. Item response theory (IRT) analyses derived the most informative, unbiased PGD symptoms. Combinatoric analyses identified the most sensitive and specific PGD algorithm that was then tested to evaluate its psychometric validity. Criteria require reactions to a significant loss that involve the experience of yearning (e.g., physical or emotional suffering as a result of the desired, but unfulfilled, reunion with the deceased) and at least five of the following nine symptoms experienced at least daily or to a disabling degree: feeling emotionally numb, stunned, or that life is meaningless; experiencing mistrust; bitterness over the loss; difficulty accepting the loss; identity confusion; avoidance of the reality of the loss; or difficulty moving on with life. Symptoms must be present at sufficiently high levels at least six mo from the death and be associated with functional impairment. CONCLUSIONS: The criteria set for PGD appear able to identify bereaved persons at heightened risk for enduring distress and dysfunction. The results support the psychometric validity of the criteria for PGD that we propose for inclusion in DSM-V and ICD-11. Please see later in the article for Editors' Summary