Predictors of antipsychotic medication adherence in patients recovering from a first psychotic episode

BACKGROUND: Many patients recovering from a first psychotic episode will discontinue medication against medical advice, even before a 1-year treatment course is completed. Factors associated with treatment adherence in patients with chronic schizophrenia include beliefs about severity of illness and need for treatment, treatment with typical versus atypical antipsychotic and medication side effects. METHOD: In this 2-year prospective study of 254 patients recovering from a first episode of schizophrenia, schizophreniform, or schizoaffective disorder we examined the relationship between antipsychotic medication non-adherence and patient beliefs about: need for treatment, antipsychotic medication benefits, and negative aspects of antipsychotic medication treatment. We also examined the relationship between medication non-adherence and treatment with either haloperidol or olanzapine, and objective measures of symptom response and side effects. RESULTS: The likelihood of becoming medication non-adherent for 1 week or longer was greater in subjects whose belief in need for treatment was less (HR=1.75, 95% CI 1.16, 2.65, p=0.0077) or who believed medications were of low benefit (HR=2.88, 95 CI 1.79-4.65, p<0.0001). Subjects randomized to haloperidol were more likely to become medication non-adherent for >or=1 week than subjects randomized to olanzapine (HR-1.51, 95% CI 1.01, 2.27, p=0.045). CONCLUSION: Beliefs about need for treatment and the benefits of antipsychotic medication may be intervention targets to improve likelihood of long-term medication adherence in patients recovering from a first episode of schizophrenia, schizoaffective, or schizophreniform disorder.     

Machine perfusion versus cold storage for preservation of kidneys from expanded criteria donors after brain death

The purpose of this study was to analyze the possible effects of machine perfusion (MP) versus cold storage (CS) on delayed graft function (DGF) and early graft survival in expanded criteria donor kidneys (ECD). As part of the previously reported international randomized controlled trial 91 consecutive heart‐beating deceased ECDs – defined according to the United Network of Organ Sharing definition – were included in the study. From each donor one kidney was randomized to MP and the contralateral kidney to CS. All recipients were followed for 1 year. The primary endpoint was DGF. Secondary endpoints included primary nonfunction and graft survival. DGF occurred in 27 patients in the CS group (29.7%) and in 20 patients in the MP group (22%). Using the logistic regression model MP significantly reduced the risk of DGF compared with CS (OR 0.460, P = 0.047). The incidence of nonfunction in the CS group (12%) was four times higher than in the MP group (3%) (P = 0.04). One‐year graft survival was significantly higher in machine perfused kidneys compared with cold stored kidneys (92.3% vs. 80.2%, P = 0.02). In the present study, MP preservation clearly reduced the risk of DGF and improved 1‐year graft survival and function in ECD kidneys. (Current Controlled Trials number: ISRCTN83876362).     

Update on DCIS Outcomes from the American Society of Breast Surgeons Accelerated Partial Breast Irradiation Registry Trial

Background

Since the initial reports on use of MammoSite accelerated partial breast irradiation (APBI) for treatment of ductal carcinoma in situ (DCIS), additional follow-up data were collected. We hypothesized that APBI delivered via MammoSite would continue to be well tolerated, associated with a good cosmetic outcome, and carry a low risk for recurrence in patients with DCIS.

Materials and Methods

From 2002–2004, 194 patients with DCIS were enrolled in a registry trial to assess the MammoSite. Follow-up data were available for all 194 patients. Median follow-up was 54.4 months; 63 patients had at least 5 years of follow-up. Data obtained included patient-, tumor-, and treatment-related factors, and recurrence incidence.

Results

Of the 194 patients, 87 (45%) had the MammoSite placed at lumpectomy; 107 patients (55%) had the device placed postlumpectomy. In the first year of follow-up, 16 patients developed a breast infection, though the method of device placement was not associated with infection risk. Also, 46 patients developed a seroma that was associated with applicator placement at the time of lumpectomy (P = 0.001). For patients with at least 5 years of follow-up, 92% had favorable cosmetic results. There were 6 patients (3.1%) who had an ipsilateral breast recurrence, with 1 (0.5%) experiencing recurrence in the breast and axilla, for a 5-year actuarial local recurrence rate of 3.39%.

Conclusions

During an extended follow-up period, APBI delivered via MammoSite continued to be well tolerated for patients with DCIS. Use of this device may make lumpectomy possible for patients who would otherwise choose mastectomy because of barriers associated with standard radiation therapy.     

Diabetes and cancer: Looking at the multiligand/RAGE axis

The association between diabetes and hyperglycemia and the associated increased risk of several solid and hematologic malignancies has been the subject of investigation for many years.Although the association is not fully understood,current knowledge clearly indicates that diabetes may influence malignant cell transformation by several mechanisms,including hyperinsulinemia,hyperglycemia and chronic inflammation.In this context,the receptor for advanced glycation end-products (RAGE) has emerged as a focal point in its contribution to malignant transformation and tumor growth.We high-light how RAGE,once activated,as it manifests itself in conditions such as diabetes or hyperglycemia,is able to continuously bring about an inflammatory milieu,thus supporting the contribution of chronic inflammation to the development of malignancies.     

Incidence and risk factors for low trauma fractures in men with prostate cancer

BACKGROUND: Men with prostate cancer on androgen deprivation therapy (ADT) are at increased risk of bone loss. The present study sought to determine the incidence of low trauma fracture in men with prostate cancer (PC), and to characterize the association between potential risk factors and fracture risk in these men. METHODS: In the prospective, population-based Dubbo Osteoporosis Epidemiology Study, 43 men aged 60+ years reported a history of prostate cancer; among whom, 22 men received ADT, and 21 men did not. Low-trauma fractures were ascertained between 1989 and 2004. Bone mineral density at the femoral neck (FNBMD), postural instability and lifestyle factors were obtained at baseline. RESULTS: Men with prostate cancer had significantly higher lumbar spine BMD than those without cancer (p=0.013). During the follow-up period, 15 men with prostate cancer had sustained a fracture, yielding the age-adjusted incidence of fracture among this group was 31.6 per 1000 person-years, which was greater than those without cancer (22.1 per 1000 person-years). The age-adjusted incidence of fracture was more pronounced among those with prostate cancer on ADT (40.2 per 1000 person-years). After adjusting for age, the increase in fracture risk among prostate cancer patients was associated with lower femoral neck BMD (hazard ratio [HR] per SD=1.8, 95% CI: 1.0-3.4) and increased rate of bone loss (HR 2.3, 1.2-4.6). CONCLUSIONS: Men with prostate cancer, particularly those treated with ADT, had an increased fracture risk. Although the average BMD in men with prostate cancer was higher than men without cancer, a low BMD prior to treatment or increased rate of bone loss after initiating ADT treatment was each a significant predictor of fracture in these.     

Genetic variation, C-reactive protein levels, and incidence of diabetes

C-reactive protein (CRP) has been shown to be associated with type 2 diabetes, but whether CRP has a causal role is not yet clear. We examined the association in the Rotterdam Study, a population-based prospective cohort study. The association of baseline serum CRP and incident diabetes during follow-up was investigated, and a meta-analysis was conducted on the BMI-adjusted relation of CRP and diabetes. Furthermore, the association of CRP haplotypes with serum CRP and risk of diabetes was assessed. The age- and sex-adjusted hazard ratio for diabetes was 1.41 (95% CI 1.29-1.54) per 1 SD increase in natural logarithm of CRP, and it was 1.88, 2.16, and 2.83 for the second, third, and fourth quartiles of CRP, respectively, compared with the first quartile. The risk estimates attenuated but remained statistically significant after additional adjustment for obesity indexes, which agreed with the results of the meta-analysis. The most common genetic haplotype was associated with a significantly lower CRP level compared with the three other haplotypes. The risk of diabetes was significantly higher in the haplotype with the highest serum CRP level compared with the most common haplotype (OR 1.45, 95% CI 1.08-1.96). These findings support the hypothesis that serum CRP enhances the development of diabetes.     

A Process and Outcomes Evaluation of the International AIDS Conference: Who Attends? Who Benefits Most?

The objective of the study was to conduct a process and outcomes evaluation of the International AIDS Conference (IAC). Reaction evaluation data are presented from a delegate survey distributed at the 2004 IAC held in Thailand. Input and output data from the Thailand IAC are compared to data from previous IACs to ascertain attendance and reaction trends, which delegates benefit most, and host country effects. Outcomes effectiveness data were collected via a survey and intercept interviews. Data suggest that the host country may significantly affect the number and quality of basic science IAC presentations, who attends, and who benefits most. Intended and executed HIV work‐related behavior change was assessed under 9 classifications. Delegates who attended 1 previous IAC were more likely to report behavior changes than attendees who attended more than 1 previous IAC. The conference needs to be continually evaluated to elicit the required data to plan effective future IACs.     

Expression of galectin-3 and its regulation in the testes

Although spermatogenesis is a complex process under hormonal control, which includes mainly follicle stimulating hormone (FSH) and androgens, little is known about the intra-testicular mediators of these hormones. In the present study, galectin-3 (Gal-3) expression has been identified in human, rat and porcine testes where it is under hormonal control. Gal-3 is present in Sertoli cells and appears to be absent in human and (probably) in rat germ cells. Gal-3 expression was evidenced in the testes, in terms of both mRNA and protein (31 kDa). Gal-3 expression in cultured porcine Sertoli cells was shown to be under the positive control of FSH as well as of two cytokines epidermal growth factor (EGF) and tumour necrosis factor-alpha (TNF-alpha). Gal-3 expression in Sertoli cells is also potentially under the control of mature germ cells as an increased expression was observed in adult rat testes depleted in spermatocytes or spermatids. Although the function of testicular Gal-3 remains to be investigated, a potential role of Gal-3 in germ cell survival/regeneration is suggested based on its increased expression 1 month after a transient germ cell death process triggered by 10 days of treatment with the antiandrogen flutamide. Finally, although in the normal human testes, Gal-3 is exclusively located in the Sertoli cell cytoplasm, a nuclear localization is observed in the infertile testes. Together, the present findings have shown that (i) Gal-3 is expressed in the porcine, rat and human Sertoli cells; (ii) Gal-3 is under the positive control of FSH as well as of EGF and TNF-alpha and possibly of adult germ cells. These observations are compatible with a potential pro-survival role of Gal-3 in the testes.     

Reproductive failure in patients with various percentages of macronuclear spermatozoa: high level of aneuploid and polyploid spermatozoa

The aim of this study was to describe the association between various percentages of macronuclear spermatozoa (MNSs), sperm chromosomal abnormalities, and reproductive failure in 4 patients. One patient had a familial history of perinatal deaths. Patients were selected according to the coexistence of normal-sized spermatozoa and MNSs (19%, 22%, 29.5%, and 49.7%). Fluorescent in situ hybridization (FISH) on spermatozoa and semiautomated analysis of nuclear surface were assessed. All patients were characterized by an oligoasthenozoospermia. Three patients had a prevalence of irregular MNSs and prevalence of nondisjunction at the first meiotic division. One patient had a prevalence of regular MNSs and a prevalence of nondisjunction at the second meiotic division. FISH also showed a high rate of polyploidy and various rates of aneuploid sperm. The percentage of sperm with abnormal chromosome complements (25.6%, 43.6%, 51.4%, 71.7% with 3-color FISH) was higher than the percentage of MNSs. A population of apparently normal-sized spermatozoa that could be used for intracytoplasmic sperm injection (ICSI) was aneuploid. Sperm nuclear surface analysis revealed either a shift toward elevated values or distinguished 2 sperm subpopulations: normal and macronuclear. Patients underwent 7 ICSI cycles. The fertilization rate was low for 3 patients (50%, 40%, 50%) and normal for 1 patient (83.3%). Pregnancy rate per transfer was low (14.3%). The present study shows that the macronuclear phenotype can manifest a variety of clinical aspects. It is also shown that mild rates of MNSs impair fertility and constitute a risk of chromosomal abnormality for the embryos and a risk of perinatal death. We suggest conducting FISH on spermatozoa and genetic counseling for a couple when the percentage of MNSs reaches 20% in at least 1 spermiogram.     

Pediatric heart allocation and transplantation in Eurotransplant

Pediatric heart allocation in Eurotransplant (ET) has evolved over the past decades to better serve patients and improve utilization. Pediatric heart transplants (HT) account for 6% of the annual transplant volume in ET. Death rates on the pediatric heart transplant waiting list have decreased over the years, from 25% in 1997 to 18% in 2011. Within the first year after listing, 32% of all infants (<12 months), 20% of all children aged 1–10 years, and 15% of all children aged 11–15 years died without having received a heart transplant. Survival after transplantation improved over the years, and in almost a decade, the 1‐year survival went from 83% to 89%, and the 3‐year rates increased from 81% to 85%. Improved medical management of heart failure patients and the availability of mechanical support for children have significantly improved the prospects for children on the heart transplant waiting list.