Spirituality,Social Support,and Survival in Hemodialysis Patients

Background and objectives: No studies have evaluated the relationship among spirituality, social support, and survival in patients with ESRD. This study assessed whether spirituality was an independent predictor of survival in dialysis patients with ESRD after controlling for age, diabetes, albumin, and social support.Design, setting, participants, & measurements: A total of 166 patients who had ESRD and were treated with hemodialysis completed questionnaires on psychosocial variables, quality of life, and religious and spiritual beliefs. The religious variables were categorized into three scores on a 0 to 20 scale (low to high levels): Spirituality, religious involvement, and religion as coping. Social support was assessed using the Multidimensional Scale for Perceived Social Support. Analyses were also performed including and excluding patients with HIV infection. Religious variables were categorized on the basis of means, medians, and tertiles.Results: In analyses that used religious variables, only the responses on the spirituality scale split at the mean were associated with survival. The association of other religious variables with survival did not reach significance. Social support correlated with spirituality, religion as coping, and religious involvement measures. Only social support and age were associated with survival when controlling for diabetes, albumin concentration, HIV infection, and spirituality.Conclusions: These data suggest that the effects of spirituality may be mediated by social support. Larger, multicenter, prospective studies that use well-validated tools to measure religiosity and spirituality are needed to determine whether there is an independent association of spirituality variables with survival in patients with ESRD.Relationships between spirituality and mortality have been investigated in medical populations but remain controversial (1–13). Variable associations have been found depending on definitions of spirituality and patient populations studied (1–11). Miller and Thoreson (12) explored nine different hypotheses regarding the relationship among religious beliefs, spirituality, and mortality. The only hypothesis that they found to be supported by persuasive evidence stated that “church/service attendance protects [only] healthy people against death.” Studies supporting a similar link in patients with chronic illnesses have also shown mixed results. Koenig et al. (14) evaluated approximately 4000 elderly patients to determine whether attendance at religious services during a 6-yr period was associated with survival. In adjusted analyses, there was a significantly lower mortality in patients who frequently attended church services.Many researchers have suggested a publication bias, whereby only the studies that indicate a significant relationship are published (13). Most studies cited the need for more research on the relationship between spirituality and mortality before any firm conclusions can be reached. In addition, the health dimensions of lack of belief have not been well explored.There also exists considerable debate on how to operationalize religiosity and spirituality. Whereas the first term often is associated with participation in social institutions and adherence to specific beliefs and practices, the latter is a broader term that typically pertains to life''s vital qualities and an overall broad belief in the immaterial features of life (12). Spirituality relates to transcendent values and relationships and the way people find meaning, purpose, and hope in life and in the midst of suffering (15). A person may be spiritual and not religiously observant or observe rituals without a spiritual focus.Few studies have specifically evaluated the potential association between spirituality and survival in patients with ESRD (16,17). We (18) previously showed that religious and spiritual beliefs are associated with decreased perception of burden of illness, decreased depressive affect, increased perception of social support, and higher satisfaction with life and perception of quality of life in an urban, predominantly black ESRD population. We also found that a “spiritual beliefs scale” correlated with several quality-of-life measures in patients with ESRD (19). Even though many of these psychosocial measures have been shown to be related to survival independently, no study to our knowledge has demonstrated a link between spirituality and survival in this population.We determined whether three variables related to spirituality, religious beliefs, and practices and faith (spirituality, religious involvement, and religion as a coping measure) were independently associated with survival in hemodialysis patients with ESRD. We then assessed the relationship between social support and survival, regardless of whether the spiritual variables were included in analyses. We hypothesized that spiritual variables would be associated with survival in patients with ESRD.     

Corticobasal and ataxia syndromes widen the spectrum of C9ORF72 hexanucleotide expansion disease

Recently, a hexanucleotide (GGGGCC) repeat expansion in the first intron of C9ORF72 was reported as the cause of chromosome 9p21‐linked frontotemporal dementia‐amyotrophic lateral sclerosis (FTD‐ALS). We here report the prevalence of the expansion in a hospital‐based cohort and associated clinical features indicating a wider clinical spectrum of C9ORF72 disease than previously described. We studied 280 patients previously screened for mutations in genes involved in early onset autosomal dominant inherited dementia disorders. A repeat‐primed polymerase chain reaction amplification assay was used to identify pathogenic GGGGCC expansions. As a potential modifier, confirmed cases were further investigated for abnormal CAG expansions in ATXN2. A pathogenic GGGGCC expansion was identified in a total of 14 probands. Three of these presented with atypical clinical features and were previously diagnosed with clinical olivopontocerebellar degeneration (OPCD), atypical Parkinsonian syndrome (APS) and a corticobasal syndrome (CBS). Further, the pathogenic expansion was identified in six FTD patients, four patients with FTD‐ALS and one ALS patient. All confirmed cases had normal ATXN2 repeat sizes. Our study widens the clinical spectrum of C9ORF72related disease and confirms the hexanucleotide expansion as a prevalent cause of FTD‐ALS disorders. There was no indication of a modifying effect of the ATXN2 gene.     

Accuracy of supplementary serologic testing for human T-lymphotropic virus types I and II in US blood donors. Retrovirus Epidemiology Donor Study

Blood donations in the United States have been screened for antibody to human T-lymphotropic virus type I (HTLV-I) by HTLV-I enzyme immunoassay (EIA) since November 1988. Specimens repeatedly found to be reactive by EIA undergo confirmation by supplementary serologic tests. We assessed the accuracy of blood center testing of 994 HTLV-I EIA repeat-reactive specimens in five US blood centers between November 1988 and December 1991. Of 410 confirmed HTLV-I/II donations, 407 (99.3%) were infected with HTLV-I/II, as determined by polymerase chain reaction (PCR) (403 cases) and by repeat serologic testing (4 cases). The three false- positive results occurred in the first year of testing. Of 425 HTLV- indeterminate specimens, 6 (1.4%) were found to be infected by PCR (5 with HTLV-II and 1 with HTLV-I). None of 159 confirmatory test-negative donations was PCR positive. Of HTLV-I/II-seropositive specimens, 80.2% to 95.4% could be typed as HTLV-I or HTLV-II by type-specific serologic assays. These results support recommendations that HTLV-I/II- seropositive donors should be advised that they are infected with HTLV- I, HTLV-II, or HTLV-I/II (depending on results of type-specific assays). HTLV-indeterminate donors should be advised that their results only rarely indicate HTLV infection. HTLV confirmatory test-negative donors should be reassured that they are not infected with HTLV-I or HTLV-II.     

Copy number variants in patients with short stature

Height is a highly heritable and classic polygenic trait. Recent genome-wide association studies (GWAS) have revealed that at least 180 genetic variants influence adult height. However, these variants explain only about 10% of the phenotypic variation in height. Genetic analysis of short individuals can lead to the discovery of novel rare gene defects with a large effect on growth. In an effort to identify novel genes associated with short stature, genome-wide analysis for copy number variants (CNVs), using single-nucleotide polymorphism arrays, in 162 patients (149 families) with short stature was performed. Segregation analysis was performed if possible, and genes in CNVs were compared with information from GWAS, gene expression in rodents'' growth plates and published information. CNVs were detected in 40 families. In six families, a known cause of short stature was found (SHOX deletion or duplication, IGF1R deletion), in two combined with a de novo potentially pathogenic CNV. Thirty-three families had one or more potentially pathogenic CNVs (n=40). In 24 of these families, segregation analysis could be performed, identifying three de novo CNVs and nine CNVs segregating with short stature. Four were located near loci associated with height in GWAS (ADAMTS17, TULP4, PRKG2/BMP3 and PAPPA). Besides six CNVs known to be causative for short stature, 40 CNVs with possible pathogenicity were identified. Segregation studies and bioinformatics analysis suggested various potential candidate genes.     

CD44 enhances tumor formation and lung metastasis in experimental osteosarcoma and is an additional predictor for poor patient outcome

Formation of metastases in the lungs is the major cause of death in patients suffering from osteosarcoma (OS). Metastases at presentation and poor response to preoperative chemotherapy are strong predictors for poor patient outcome. The elucidation of molecular markers that promote metastasis formation and/or chemoresistance is therefore of importance. CD44 is a plasma membrane glycoprotein that binds to the extracellular matrix component hyaluronan (HA) and has been shown to be involved in metastasis formation in a variety of other tumors. Here we investigated the role of CD44 expression on OS tumor formation and metastasis. High CD44 expression, evaluated with a tissue microarray including samples from 53 OS patients and stained with a pan‐CD44 antibody (Hermes3), showed a tendency (p < 0.08) to shortened overall survival. However, nonresponders and patients with lung metastases and high CD44 expression had significantly poorer prognosis than patients with low CD44 expression. Overexpression of the standard CD44 isoform (CD44s) and its HA‐binding defective mutant R41A in osteoblastic SaOS‐2 cells resulted in HA‐independent higher migration rates and increased chemoresistance, partially dependent on HA. In an orthotopic mouse model of OS, overexpression of CD44s in SaOS‐2 cells resulted in an HA‐dependent increased primary tumor formation and increased numbers of micrometastases and macrometastases in the lungs. In conclusion, although CD44 failed to be an independent predictor for patient outcome in this limited cohort of OS patients, increased CD44 expression was associated with even worse survival in patients with chemoresistance and with lung metastases. CD44‐associated chemoresistance was also observed in vitro, and increased formation of lung metastases was found in vivo in SCID mice. © 2013 American Society for Bone and Mineral Research.     

Pacific Islands Families (PIF) Study: housing and psychological distress among Pacific mothers

Objective: In a sample of Pacific mothers living in New Zealand, we examined: 1) maternal reports about seven specific major housing problems (too small, difficult to get to from the street, in poor condition, damp, cold, presence of pests, too expensive); and 2) associations between these housing problems and maternal psychological distress, adjusting for some maternal sociodemographic characteristics. Methods: The Pacific Islands Families longitudinal study follows a cohort of Pacific children born in Auckland, New Zealand, in 2000 and their parents. At the 14‐year phase, mothers (n=844) were asked about housing conditions and psychological distress. Results: Mothers who reported having any major housing problem, particularly the presence of pests and poor housing conditions, were significantly more likely to report psychological distress after adjusting for sociodemographic confounders. Conclusions: The impact of housing on mental health is complex and may be influenced by social, health and sociodemographic characteristics of Pacific mothers. Implications for public health: The finding that housing problems are significantly associated with psychological distress among Pacific mothers in New Zealand is an important finding. However, more in‐depth qualitative research is needed to provide a clearer understanding of the way housing problems affect mental health and to guide strategies that minimise this outcome for Pacific mothers.     

Hair Mercury and Fish Consumption in Residents of O‘ahu,Hawai‘i

Recent studies have established that men are susceptible to cardiotoxicity from methylmercury exposure, which also poses risks to the pregnant woman. Hair samples were obtained and questionnaires for methylmercury exposure assessment were administered to 110 adults (57 men, 53 women) throughout O‘ahu, Hawai‘i during December 2010 to January 2011. Hair samples were analyzed for total mercury with a direct mercury analyzer. Men ≥ 46 years had a median of 2.0 µg/g, which was above the reference dose of 1 µg/g, as compared to younger men with a median 1.0 µg/g (P < 0.05). Hair concentrations from older women had a median of 1.2 µg/g of mercury compared to 0.6 µg/g for younger women. Additionally, 38% of women of childbearing age had a Hazard Index > 1.0. This indicates that both men and women were at risk for excessive methylmercury exposure. In the final regression model, male gender, age > 45 years, length of residency > 10 years in Hawai‘i, and fish consumption frequency > 1 meal per week were significant factors in increased hair mercury levels. Following safe fish consumption practices allows residents to reap health benefits of fish consumption without excessive toxicant exposure.     

Optimizing dose and scheduling of filgrastim (granulocyte colony- stimulating factor) for mobilization and collection of peripheral blood progenitor cells in normal volunteers [see comments]

To define an optimal regimen for mobilizing and collecting peripheral blood progenitor cells (PBPC) for use in allogeneic transplantation, we evaluated the kinetics of mobilization by filgrastim (recombinant met- human granulocyte colony-stimulating factor [r-metHuG-CSF]) in normal volunteers. Filgrastim was injected subcutaneously for up to 10 days at a dose of 3 (n = 10), 5 (n = 5), or 10 micrograms/kg/d (n = 15). A subset of volunteers from each dose cohort underwent a 7L leukapheresis on study day 6 (after 5 days of filgrastim). Granulocyte-macrophage colony-forming cell (GM-CFC) numbers in the blood were maximal after 5 days of filgrastim; a broader peak was evident for CD34+ cells between days 4 and 6. The 95% confidence intervals (CI) for mean number of PBPC per milliliter of blood in the three dose cohorts overlapped on each study day. However, on the peak day, CD34+ cells were significantly higher in the 10 micrograms/kg/d cohort than in a pool of the 3 and 5 micrograms/kg/d cohorts. Mobilization was not significantly influenced by volunteer age or sex. Leukapheresis products obtained at the 10 micrograms/kg/d dose level contained a median GM-CFC number of 93 x 10(4)/kg (range, 50 x 10(4)/kg to 172 x 10(4)/kg). Collections from volunteers receiving lower doses of filgrastim contained a median GM- CFC number of 36 x 10(4)/kg (range, 5 x 10(4)/kg to 204 x 10(4)/kg). The measurement of CD34+ cells per milliliter of blood on the day of leukapheresis predicted the total yield of PBPC in the leukapheresis product (r = .87, P < .0001). Assuming a minimum GM-CFC requirement of 50 x 10(4)/kg (based on our experience with autologous PBPC transplantation), all seven leukapheresis products obtained at the 10 micrograms/kg/d dose level were potentially sufficient for allogeneic transplantation purposes. We conclude that in normal donors, filgrastim 10 micrograms/kg/d for 5 days with a single leukapheresis on the following day is a highly effective regimen for PBPC mobilization and collection. Further studies are required to determine whether PBPC collected with this regimen reliably produce rapid and sustained engraftment in allogeneic recipients.