Diagnostic usefulness of five screening assays for HIV in an east African city where prevalence of infection is low

Five commercial screening assays for HIV-1, evaluated for their usefulness in detecting infection in high-risk groups in the East African country of Djibouti, produced varying degrees of performance when compared to Western blot and immunofluorescence confirmatory assays. In this population with a low prevalence of HIV infection (16/599), two enzyme-linked immunosorbent assays (ELISA; Abbott and Elavia) and two rapid assays (cambridge latex agglutination and Du Pont's HIV-CHEK) exhibited less than optimal sensitivities. However, with the exception of Elavia, these assays displayed excellent specificities. The fifth test (Serodia gelatin agglutination) produced the highest sensitivity (0.938) and negative predictive value but the lowest specificity and positive predictive value of all five tests. False positive reactions, which occurred only with the Elavia and Serodia tests, could not be explained on the basis of early infection in patients or cross-reactions with the related retroviruses HIV-2 and HTLV-I. We conclude that none of the five tests alone is sufficient in this testing situation, but that a combination of tests could satisfy most requirements for identifying HIV-1 reactive and non-reactive sera.     

Reduced breast cancer incidence in women treated with subcutaneous testosterone,or testosterone with anastrozole: A prospective,observational study

Objectives

There is evidence that androgens are breast protective and that testosterone therapy treats many symptoms of hormone deficiency in both pre and postmenopausal patients. However, unlike estrogen and progestins, there is a paucity of data regarding the incidence of breast cancer in women treated with testosterone therapy. This study was designed to investigate the incidence of breast cancer in women treated with subcutaneous testosterone therapy in the absence of systemic estrogen therapy.

Study design

This is a 5-year interim analysis of a 10-year, prospective, observational, IRB approved study investigating the incidence of breast cancer in women presenting with symptoms of hormone deficiency treated with subcutaneous testosterone (T) implants or, T combined with the aromatase inhibitor anastrozole (A), i.e., T + A implants. Breast cancer incidence was compared with that of historical controls reported in the literature, age specific Surveillance Epidemiology and End Results (SEER) incidence rates, and a representative, similar age group of our patients used as a ‘control’ group. The effect of adherence to T therapy was also evaluated.

Results

Since March 2008, 1268 pre and post menopausal women have been enrolled in the study and eligible for analysis. As of March 2013, there have been 8 cases of invasive breast cancer diagnosed in 5642 person-years of follow up for an incidence of 142 cases per 100 000 person-years, substantially less than the age-specific SEER incidence rates (293/100 000), placebo arm of Women's Health Initiative Study (300/100 000), never users of hormone therapy from the Million Women Study (325/100 000) and our control group (390/100 000). Unlike adherence to estrogen therapy, adherence to T therapy further decreased the incidence of breast cancer (73/100 000).

Conclusion

T and/or T + A, delivered subcutaneously as a pellet implant, reduced the incidence of breast cancer in pre and postmenopausal women. Evidence supports that breast cancer is preventable by maintaining a T to estrogen ratio in favor of T and, in particular, by the use of continuous T or, when indicated, T + A. This hormone therapy should be further investigated for the prevention and treatment of breast cancer.     

The impact of deep sternal wound infection on long-term survival after coronary artery bypass grafting

OBJECTIVES: To identify the impact of deep sternal wound infection (DSWI) on long-term survival after coronary artery bypass grafting (CABG). BACKGROUND: DSWI following CABG is an infrequent, yet devastating complication with increased morbidity and mortality. However, little has been published regarding the impact of DSWI on long-term mortality. METHODS: We studied 3,760 consecutive patients who underwent isolated CABG between 1992 and 2002. Patients with CABG and no DSWI were compared with those in whom DSWI developed. Long-term survival data (mean follow-up, 5.2 years) were obtained from the National Death Index. Groups were compared by Cox proportional hazard models and Kaplan-Meier survival plots. The propensity for DSWI was determined by logistic regression analysis, and each patient with DSWI was then matched to 10 patients without DSWI. RESULTS: DSWI developed in 40 of 3,760 patients (1.1%). Independent predictors for DSWI were diabetes (odds ratio [OR], 5.5; 95% confidence interval [CI], 2.7 to 11.6; p < 0.001), hemodynamic instability preoperatively (OR, 4.0; 95% CI, 1.2 to 13.9; p = 0.026), preoperative renal failure on dialysis (OR, 3.4; 95% CI, 1.0 to 13.6; p = 0.049), use of bilateral internal thoracic arteries (OR, 2.6; 95% CI, 1.3 to 5.3; p = 0.010), and sepsis and/or endocarditis after CABG (OR, 29.9; 95% CI, 11.7 to 76.4; p < 0.001). Patients with DSWI had prolonged length of stay (35.0 days vs 16.4 days; p < 0.001); however, there was no difference in early mortality between matched groups. After adjustment for preoperative, intraoperative, and postoperative factors, the adjusted hazard ratio of long-term mortality for patients with DSWI was 2.44 (95% CI, 1.51 to 3.92; p < 0.001). Patients without DSWI had a better 5-year survival rate (72.8 +/- 2.4% vs 50.8.6 +/- 8.5% [mean +/- SE]; p = 0.0007 between matched groups). CONCLUSIONS: We found that DSWI following CABG was associated with increased long-term mortality during a 10-year follow-up study.     

Informed consent for medical procedures: local and national practices

BACKGROUND: No studies have assessed whether clinicians obtain informed consent for invasive medical procedures, and there are no explicit national standards to guide the process. HYPOTHESIS: Informed consent practices are inconsistent for commonly performed invasive medical procedures. METHODS: A simple questionnaire was electronically mailed and/or faxed to training program directors of critical care medicine and internal medicine departments, and to ICU directors in the state of Connecticut. The questionnaire listed common invasive medical procedures and asked the respondents to check those for which practitioners routinely obtain informed consent in their hospital. RESULTS: The three samples, national intensivists (88 respondents), Connecticut intensivists (29 respondents), and national internists (56 respondents) demonstrated heterogeneity of consenting practices. The rate of obtaining consent for common vascular access procedures ranged from 20 to 90%. The rates of obtaining consent for Foley catheterization and nasogastric intubation were uniformly < 10%, and those for endoscopic procedures were > 90%. Separate consent (beyond the general consent to treat) was not uniformly obtained for the transfusion of blood products (range, 74 to 93%) and common diagnostic medical procedures (eg, thoracentesis, paracentesis, or lumbar puncture; range, 77 to 96%). Surgical intensivists reported that the obtaining of consent for invasive procedures was less routine compared to medical intensivists. Lower rates of consent were noted by those respondents who used a "blanket" consent form, which was signed at the time of hospital admission, to cover subsequent procedures. CONCLUSIONS: In this relatively small sample, there was no uniform practice of informed consent for commonly performed invasive medical procedures. Consent was routinely obtained for GI endoscopy, bronchoscopy, and medical research, and was not obtained for Foley catheterization and nasogastric intubation. The obtaining of consent for vascular cannulation and diagnostic procedures was not routine in the ICUs of a substantial number of respondents. Explicit standards that delineate specifically which procedures require consent may be required to assure more uniform practices.     

KiSS-1/G protein-coupled receptor 54 metastasis suppressor pathway increases myocyte-enriched calcineurin interacting protein 1 expression and chronically inhibits calcineurin activity

OBJECTIVE: Tumor metastasis is a critical determinant of death from cancer. Metastin, a product of the KiSS-1 gene, is an endogenously expressed metastasis suppressor that is the ligand for G protein-coupled receptor 54 (GPR54), a Gq/11-coupled receptor. In the present study, our goal was to define the basis of GPR54 action using thyroid cancer cells as a model. DESIGN AND RESULTS: We used GPR54-null thyroid cancer cells to create a stable GPR54 overexpression model. Cell growth and cell migration of the GPR54-expressing lines were inhibited by recombinant metastin, and metastin stimulated the protein kinase C, ERK, and phosphatidylinositol-3-kinase pathways. To identify metastin-regulated genes, we performed microarray analyses using RNA isolated from GPR54 stable transfectants before and after 1 and 24 h of metastin stimulation. Consistent increases in expression of the gene encoding myocyte-enriched calcineurin interacting protein 1 (MCIP-1), an inhibitor of calcineurin, were identified and confirmed using real-time RT-PCR and Western blot. Functionally, metastin treatment of GPR54-expressing cells initially increased calcineurin activity, followed by a prolonged reduction in calcineurin activity for 24 and 48 h, consistent with the pattern of MCIP-1 expression. In addition, treatment with cyclosporin A, a calcineurin inhibitor, blocked cell migration. Lymph node metastasis in papillary thyroid cancers demonstrated loss of MCIP-1 expression in comparison with primary tumors. CONCLUSIONS: These data suggest a role for MCIP-1 and calcineurin inhibition in GPR54-mediated metastasis suppression in human cancers.     

Incidence and prevalence of dementia in the Cardiovascular Health Study

OBJECTIVES: To estimate the incidence and prevalence of dementia, Alzheimer's disease (AD), and vascular dementia (VaD) in the Cardiovascular Health Study (CHS) cohort. DESIGN: Longitudinal cohort study using prospectively and retrospectively collected data to evaluate dementia. SETTING: Four U.S. communities. PARTICIPANTS: There were 3,602 CHS participants, including 2,865 white and 492 African-American participants free of dementia, who completed a cranial magnetic resonance image between 1992 and 1994 and were followed for an average of 5.4 years. MEASUREMENTS: Dementia was classified by neurologist/psychiatrist committee review using neuropsychological tests, neurological examinations, medical records, physician questionnaires, and proxy/informant interviews. Demographics and apolipoprotein E (APOE) genotype were collected at baseline. Incidence by type of dementia was determined using National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for AD and Alzheimer's Disease Diagnostic and Treatment Center's State of California criteria for VaD. RESULTS: Classification resulted in 227 persons with prevalent dementia at entry into the study and 480 incident cases during follow-up. Incidence rates of dementia scaled to age 80 were 34.7 per 1,000 person-years for white women, 35.3 for white men, 58.8 for African-American women, and 53.0 for African-American men. Sex differences were not significant within race. Adjusted for age and education, racial differences were only of borderline significance and may have been influenced by ascertainment methodology. Rates differed substantially by educational attainment but were only significant for whites. Those with the APOE epsilon4 allele had an incidence rate at age 80 of 56.4, compared with 29.6 for those without this allele (P<.001). In whites, type-specific incidence at age 80 was 19.2 for AD versus 14.6 for VaD. These rates were 34.7 and 27.2 for African Americans. At termination of observation, women had only a slightly higher prevalence of dementia (16.0%) than men (14.7%). CONCLUSION: Sex and racial differences were not found, and VaD was higher than reported in other studies. These data provide new estimates of dementia incidence in a community sample for projection of future burden.     

The association of neuropsychiatric symptoms and environment with quality of life in assisted living residents with dementia

PURPOSE: We conducted this study to determine whether neuropsychiatric symptoms and environmental characteristics are associated with quality of life in assisted living residents with dementia. DESIGN AND METHODS: We used a cross-sectional study of 134 residents from 22 facilities and employed the Alzheimer's Disease-Related Quality of Life Scale and the Neuropsychiatric Inventory. A scale was developed to capture the homelike climate of each facility. Linear regression analyses were used to estimate the relationship of neuropsychiatric symptoms and homelike climate with quality of life, controlling for sociodemographics, cognition, functional dependence, and physical health. Exploratory analyses and graphical techniques were employed to test for environmental-level moderating effects. RESULTS: Agitation, depression, apathy, and irritability were significant predictors of quality of life, explaining 29% of the variance. Neither facility size nor homelike environment was significantly associated with quality of life in univariate analyses. Size of facility moderated the relationship between agitation and quality of life. IMPLICATIONS: Neuropsychiatric symptoms impair quality of life in residents with dementia. Further research should investigate the role of other environmental aspects.