Course of alcohol problems in treated adolescents

Knowledge of the clinical course in treated adolescents is fundamental to determining the influence of treatment on long-term functioning and the factors associated with change in the severity of alcohol problems over time. This symposium, held at the 2002 annual Research Society on Alcoholism meeting and organized by Tammy Chung and Christopher S. Martin, presented research on the course of alcohol-related problems in treated adolescents who were followed prospectively for 1 to 8 years. Presentations included (1) Alcohol use outcomes at 1 year among adolescents in the drug abuse treatment outcomes studies (DATOS-A), by Christine E. Grella; (2) Pathways and predictors of the course of adolescent alcohol problems across 1- and 3-year follow-ups, by Tammy Chung; (3) Young adult outcomes of an adolescent clinical sample at 5-year follow-up, by Ken C. Winters; and (4) Trajectories of alcohol involvement following addiction treatment through 8-year follow-up in adolescents, by Ana M. Abrantes, Denis M. McCarthy, Gregory A. Aarons, and Sandra A. Brown. Sandra A. Brown, discussant, commented on the presentations. Results from these studies indicate multiple pathways of change, distinguished by fluctuations in the chronicity and severity of alcohol problems. Across studies, most adolescents showed reductions in alcohol use and problems after treatment, with concurrent improvements in psychosocial functioning. Findings highlight the influence of other drug use on posttreatment patterns of alcohol involvement and the need to consider the effect of normative developmental transitions on the course of adolescent-onset substance use disorders.     

Problems and hopes perceived by mothers,fathers and physicians of children receiving palliative care

Background

The quality of shared decision making for children with serious illness may depend on whether parents and physicians share similar perceptions of problems and hopes for the child.

Objective

(i) Describe the problems and hopes reported by mothers, fathers and physicians of children receiving palliative care; (ii) examine the observed concordance between participants; (iii) examine parental perceived agreement; and (iv) examine whether parents who identified specific problems also specified corresponding hopes, or whether the problems were left ‘hopeless’.

Method

Seventy‐one parents and 43 physicians were asked to report problems and hopes and perceived agreement for 50 children receiving palliative care. Problems and hopes were classified into eight domains. Observed concordance was calculated between parents and between each parent and the physicians.

Results

The most common problem domains were physical body (88%), quality of life (74%) and medical knowledge (48%). The most common hope domains were quality of life (88%), suffering (76%) and physical body (39%). Overall parental dyads demonstrated a high percentage of concordance (82%) regarding reported problem domains and a lower percentage of concordance on hopes (65%). Concordance between parents and physicians regarding specific children was lower on problem (65–66%) and hope domains (59–63%). Respondents who identified problems regarding a child's quality of life or suffering were likely to also report corresponding hopes in these domains (93 and 82%, respectively).

Conclusion

Asking parents and physicians to talk about problems and hopes may provide a straightforward means to improve the quality of shared decision making for critically ill children.     

Integrin β3 Haploinsufficiency Modulates Serotonin Transport and Antidepressant-Sensitive Behavior in Mice

Converging lines of evidence have identified genetic interactions between the serotonin transporter (SERT) gene and ITGB3, which encodes the β3 subunit that forms the αIIbβ3 and αvβ3 integrin receptor complexes. Here we examine the consequences of haploinsufficiency in the mouse integrin β3 subunit gene (Itgb3) on SERT function and selective 5-hydroxytryptamine (5-HT) reuptake inhibitor (SSRI) effectiveness in vivo. Biochemical fractionation studies and immunofluorescent staining of murine brain slices reveal that αvβ3 receptors and SERTs are enriched in presynaptic membranes from several brain regions and that αvβ3 colocalizes with a subpopulation of SERT-containing synapses in raphe nuclei. Notably, we establish that loss of a single allele of Itgb3 in murine neurons is sufficient to decrease 5-HT uptake by SERT in midbrain synaptosomes. Pharmacological assays to elucidate the αvβ3-mediated mechanism of reduced SERT function indicate that decreased integrin β3 subunit expression scales down the population size of active SERT molecules and, as a consequence, lowers the effective dose of SSRIs. These data are consistent with the existence of a subpopulation of SERTs that are tightly modulated by integrin αvβ3 and significantly contribute to global SERT function at 5-HT synapses in the midbrain. Importantly, our screen of a normal human population for single nucleotide polymorphisms in human ITGB3 identified a variant associated with reductions in integrin β3 expression levels that parallel our mouse findings. Thus, polymorphisms in human ITGB3 may contribute to the differential responsiveness of select patients to SSRIs.     

A locus on chromosome 9p predisposes to a specific disease manifestation, acute anterior uveitis, in ankylosing spondylitis, a genetically complex, multisystem, inflammatory disease

OBJECTIVE: Uveitis or intraocular inflammation is a major cause of visual loss. Acute anterior uveitis (AAU) affects approximately 40% of patients with ankylosing spondylitis (AS) but also affects patients with no evidence of spondylarthritis. We sought to determine whether a unique genetic region could be implicated in a specific manifestation-AAU-of a multisystem, inflammatory, genetically complex disease, AS. METHODS: Individuals from families multiplex for AAU were genotyped at 400 markers representing the ABI PRISM linkage map MD-10, and at the HLA-B, DRB1, DQA1, DQB1, and DPB1 alleles. Among the family members with AAU, 76 affected sibpairs were analyzed (6 without concomitant AS, 12 discordant for AS, and 58 concordant for AS). Two-point and multipoint nonparametric linkage analyses were performed, and 1-parameter allele-sharing model logarithm of odds (LOD) scores were determined. RESULTS: As previously reported for AS, linkage at the major histocompatibility complex region (chromosome 6p21) was evident, exhibiting the highest multipoint LOD score (4.96 at marker HLA-B). Strong linkage was seen at a region on chromosome 9p21-9p24, with a LOD score of 3.72 at marker D9S157. When compared with a companion cohort of AS families, the linkage at this region was found in association with AAU but not with AS. A third region on chromosome 1q23-1q31 was observed to have suggestive linkage (LOD 2.05 at marker D1S238), which overlaps with a region associated with AS. CONCLUSION: This is the first study in which a genetic region for AAU has been identified by genome-wide scan. Even though AS was highly prevalent in this cohort of families, a locus at chromosome 9p21-9p24 was identified that uniquely associates with AAU. Identifying the genetic perturbation at this region may advance our understanding of the mechanisms involved in tissue-specific pathology of complex inflammatory diseases.     

Clinical issues in renal transplantation in the elderly

Kidney transplantation is the best renal replacement therapy option and is superior to dialysis in elderly end‐stage renal disease (ESRD) patients. Furthermore, the outcome of transplantation in the elderly is comparable to younger patients in terms of allograft survival. The exact nature of this phenomenon is not completely clear. As the elderly population continues to grow, it becomes more important to identify specific issues associated with kidney transplantation. In particular, elderly transplant recipients might have a lower chance of acute rejection as their immune systems seem to be less reactive. This might predispose elderly recipients to greater risk of post‐transplant infectious complications or malignancies. Furthermore, due to differences in pharmacokinetics, elderly recipients might require lower doses of immunosuppressive medication. As the main cause of graft failure in the elderly is death with a functioning graft and also considering the scarcity of donor organs, it might make sense to recommend transplanting elderly recipients with extended criteria donor kidneys. This approach would balance shorter patient survival compared to younger recipients. In conclusion, old age should not preclude ESRD patients from kidney transplantation. However, specific differences that have to do with immunosuppression and other aspects of managing elderly transplant recipients should be considered.     

Hospital Elder Life Program in the Real World: The Many Uses of the Hospital Elder Life Program Website

The Hospital Elder Life Program (HELP) can prevent delirium, a common condition in older hospitalized adults associated with substantial morbidity, mortality, and healthcare costs. In 2011, HELP transitioned to a web‐based dissemination model to provide accessible resources, including implementation materials; information for healthcare professionals, patients, and families; and a searchable reference database. It was hypothesized that, although intended to assist sites to establish HELP, the resources that the HELP website offer might have broader applications. An e‐mail was sent to all HELP website registrants from September 10, 2012, to March 15, 2013, requesting participation in an online survey to examine uses of the resources on the website and to evaluate knowledge diffusion related to these resources. Of 102 responding sites, 73 (72%) completed the survey. Thirty‐nine (53%) had implemented and maintained an active HELP model. Twenty‐six (35%) sites had used the HELP website resources to plan for implementation of the HELP model and 35 (50%) sites to implement and support the program during and after launch. Sites also used the resources for the development of non‐HELP delirium prevention programs and guidelines. Forty‐five sites (61%) used the website resources for educational purposes, targeting healthcare professionals, patients, families, or volunteers. The results demonstrated that HELP resources were used for implementation of HELP and other delirium prevention programs and were also disseminated broadly in innovative educational efforts across the professional and lay communities.