Alefacept combined with tacrolimus, mycophenolate mofetil and steroids in de novo kidney transplantation: a randomized controlled trial.

Memory T cells play a central role in mediating allograft rejection and are a rational target for immunosuppressive therapy. Alefacept is a recombinant LFA3/IgG1 fusion protein that reduces the number of memory T cells in both psoriatic lesions and the peripheral circulation of psoriasis patients. This study evaluated the efficacy and safety of alefacept compared with placebo when combined with tacrolimus, mycophenolate mofetil and corticosteroids in de novo renal transplant recipients. Between December 2007 and March 2009 patients were randomized in a double-blind fashion to receive alefacept (n = 105) or placebo (n = 107) for 3 months and were then followed for a further 3 months. The primary efficacy endpoint was the incidence of biopsy-confirmed acute T cell mediated rejection (Banff grade ≥ 1) through Month 6. Memory T cell counts were significantly reduced in the alefacept group from Week 3 to study end compared with placebo. However, there was no significant difference between the alefacept and placebo groups for the primary efficacy endpoint (alefacept, 11.0% vs. placebo, 7.0%, p = 0.3). Patient and graft survival as well as renal function was similar between treatment groups. Safety and tolerability were generally similar between the treatment arms. Malignancy was higher in the alefacept treatment arm.

A phase 1, randomized ascending single-dose study of antagonist anti-human CD40 ASKP1240 in healthy subjects.

This first-in-human, phase I study evaluated the safety, tolerability, pharmacokinetic and pharmacodynamic profile of ASKP1240 in healthy subjects. Twelve sequential groups (each 6 active and 3 placebo) were randomly assigned to placebo or single ascending doses of intravenous ASKP1240 (0.00003-10 mg/kg). ASKP1240 exhibited nonlinear pharmacokinetics, with mean maximal serum concentrations and area under the serum concentration-time curves ranging from 0.7 to 251.6 µg/mL and 6.5 to 55409.6 h·µg/mL following doses 0.1 mg/kg-10 mg/kg, respectively. CD40 receptor occupancy by ASKP1240, which was dose-dependent, reached a maximum at doses above 0.01 mg/kg. ASKP1240 was well tolerated, with no evidence of cytokine release syndrome or thromboembolic events. Treatment emergent antibodies to ASKP1240 were detected in 5/70 (7.1%) ASKP1240 recipients. In conclusion, antagonism of the CD40/CD154 interaction with ASKP1240 was safe and well tolerated at the doses tested.

Tacrolimus with mycophenolate mofetil (MMF) or sirolimus vs. cyclosporine with MMF in cardiac transplant patients: 1-year report.

The most advantageous combination of immunosuppressive agents for cardiac transplant recipients has not yet been established. Between November 2001 and June 2003, 343 de novo cardiac transplant recipients were randomized to receive steroids and either tacrolimus (TAC) + sirolimus (SRL), TAC + mycophenolate mofetil (MMF) or cyclosporine (CYA) + MMF. Antilymphocyte induction therapy was allowed for up to 5 days. The primary endpoint of >/=3A rejection or hemodynamic compromise rejection requiring treatment showed no significant difference at 6 months (TAC/MMF 22.4%, TAC/SRL 24.3%, CYA/MMF 31.6%, p = 0.271) and 1 year (p = 0.056), but it was significantly lower in the TAC/MMF group when compared only to the CYA/MMF group at 1 year (23.4% vs. 36.8%; p = 0.029). Differences in the incidence of any treated rejection were significant (TAC/SRL = 35%, TAC/MMF = 42%, CYA/MMF = 59%; p < 0.001), as were median levels of serum creatinine (TAC/SRL = 1.5 mg/dL, TAC/MMF = 1.3 mg/dL, CYA/MMF = 1.5 mg/dL; p = 0.032) and triglycerides (TAC/SRL = 162 mg/dL, TAC/MMF = 126 mg/dL, CYA/MMF = 154 mg/dL; p = 0.028). The TAC/SRL group encountered fewer viral infections but more fungal infections and impaired wound healing. These secondary endpoints suggest that the TAC/MMF combination appears to offer more advantages than TAC/SRL or CYA/MMF in cardiac transplant patients, including fewer >/=3A rejections or hemodynamic compromise rejections and an improved side-effect profile.

Homelessness in rural areas: causes, patterns, and trends.

Although homelessness in urban areas has been examined extensively, little attention has been given to the problem of homelessness in rural areas. This article reports the findings from a 1990 statewide study of rural homelessness funded by the National Institute of Mental Health. During the six-month data collection period, 919 homeless adults were interviewed; 247 were heading family units, and 480 children were in these families. More than two-thirds of these families were headed by single parents. Implications of the findings for providing short-term emergency assistance and longer-term policy-making are presented.

Case management with homeless mentally ill people.

This article reports the findings of a National Institute of Mental Health (NIMH) services demonstration project that used a mobile case management team to serve homeless mentally ill clients. The project examined three issues: (1) factors associated with client engagement in case management, (2) clients' perceptions of how case management affected their quality of life, and (3) significant differences between clients who remained engaged in case management services and those who discontinued involvement. The results indicated that clients who received more frequent case management contact, had higher assessed independent living skills, were older, were less likely to be substance abusers, and had experienced fewer periods of homelessness and fewer prior psychiatric hospitalizations were more likely to remain engaged in case management services. After six months of case management, clients perceived significant improvement in their global well-being, living situation, use of leisure time, finances, and physical health. Implications for providing case management services to homeless mentally ill people are presented.

Discouraged older workers: an exploratory study.

The research literature has documented the social and psychological consequences of unemployment for individuals in our country. Unfortunately, few studies have examined the impact of unemployment on the older worker. This exploratory study examined the characteristics and experiences of seventy-three older unemployed workers, age fifty and above, who were discouraged and had stopped searching for a full-time job. The findings portray the discouraged older worker as potentially at risk of both economic and psychological difficulties. Participants reported feeling mildly depressed about their current unemployment situation, socially isolated and embarrassed, and were experiencing low life satisfaction generally. They also tended to use a low number of social and employment-related community services. Younger participants in the sample under age sixty, those with higher levels of education, and those suffering longer periods of unemployment tended to report having the greatest adjustment difficulties. These results reflect the challenges faced by the discouraged older worker and the need for targeted employment and supportive services to aid this population group.

Stress fracture of the clavicle after a radical neck dissection; Case report.

We report a case of a stress fracture occurring in the medial end of the clavicle, 15 months after a radical neck dissection.