High rate of missed HIV infections in individuals with indeterminate or negative HIV western blots based on current HIV testing algorithm in China.

It remains unclear if China's current HIV antibody testing algorithm misses a substantial number of HIV infected individuals. Of 196 specimens with indeterminate or negative results on HIV western blot (WB) retrospectively examined by HIV-1 nucleic acid test (NAT), 67.57% (75/111) of indeterminate WB samples, and 16.47% (14/85) of negative WB samples were identified as NAT positive. HIV-1 loads in negative WB samples were significantly higher than those in indeterminate WB samples. Notably, 86.67% (13/15) of samples with negative WB and double positive immunoassay results were NAT positive. The rate of HIV-1 infections missed by China's current HIV testing algorithm is unacceptably high. Thus, China should consider using NAT or integrating fourth generation ELISA into current only antibodies-based HIV confirmation. J. Med. Virol. 88:1462-1466, 2016. © 2016 Wiley Periodicals, Inc.

Treatment adherence and health outcomes in MSM with HIV/AIDS: patients enrolled in "one-stop" and standard care clinics in Wuhan China.

BACKGROUND: Conducted in Wuhan China, this study examined follow-up and health markers in HIV patients receiving care in two treatment settings. Participants, all men who have sex with men, were followed for 18-24 months. METHOD: Patients in a "one-stop" service (ACC; N = 89) vs those in standard care clinics (CDC; N = 243) were compared on HIV treatment and retention in care outcomes. RESULTS: Among patients with CD4 cell count ≦350 cells/µL, the proportion receiving cART did not differ across clinic groups. The ACC was favored across five other indicators: proportion receiving tests for CD4 cell count at the six-month interval (98.2% vs. 79.4%, 95% CI 13.3-24.3, p = 0.000), proportion with HIV suppression for patients receiving cART for 6 months (86.5% vs. 57.1%, 95% CI 14.1-44.7, p = 0.000), proportion with CD4 cell recovery for patients receiving cART for 12 months (55.8% vs. 22.2%, 95% CI 18.5-48.6, p = 0.000), median time from HIV confirmation to first test for CD4 cell count (7 days, 95% CI 4-8 vs. 10 days, 95% CI 9-12, log-rank p = 0.000) and median time from first CD4 cell count ≦350 cells/µL to cART initiation (26 days, 95% CI 16-37 vs. 41.5 days, 95% CI 35-46, log-rank p = 0.031). Clinic groups did not differ on any biomedical indicator at baseline, and no baseline biomedical or demographic variables remained significant in the multivariate analysis. Nonetheless, post-hoc analyses suggest the possibility of self-selection bias. CONCLUSIONS: Study findings lend preliminary support to a one-stop patient-centered care model that may be useful across various HIV care settings.

Sex work and its associations with alcohol and methamphetamine use among female bar and spa workers in the Philippines.

To assess the prevalence of sex work and its associations with substance use among female bar/spa workers in the Philippines (N = 498), workers from 54 bar or spa venues in Metro Manila (2009-2010) were surveyed on demographics, drug/alcohol use, abuse history, and sex work. Their median age was 23 years and 35% engaged in sex work. Sex work was independently associated with methamphetamine use (19% vs 4%; adjusted odds ratio [AOR] =2.9, 95% confidence interval [CI] = 1.3-6.2), alcohol use with patrons (49% vs. 27%; AOR = 1.9, 95% CI = 1.1-3.4), and alcohol intoxication during sex (50% vs. 24%; AOR = 2.0, 95% CI = 1.2-3.5), but inversely associated with daily alcohol use (13% vs. 16%; AOR = 0.2, 95% CI = 0.1-0.5). Additional significant covariates included sexual abuse history, younger age, and not having a higher education. Findings suggest that interventions with sex workers in bars and spas should focus on methamphetamine use, alcohol use contexts, and violence victimization, to better meet the needs of this population.

CD4+ T cell count, HIV-1 viral loads and demographic variables of newly identified patients with HIV infection in Wuhan, China.

In China, the rate of human immunodeficiency virus (HIV) testing is increasing among men who have sex with men. The purpose of the present study was to describe HIV-related biomarkers and selected demographic variables of persons with newly diagnosed HIV/AIDS, among men who have sex with men in particular, in Wuhan China. Demographic indicators, and CD4+ T cell counts and HIV-1 viral load were collected from individuals newly identified as HIV-1 antibody positive during 2011. Of 176 enrolled patients, 132 (75.0%) were men who have sex with men. This group was significantly younger and had higher CD4+ T cell counts than patients who were likely infected through heterosexual contact. Most men who have sex with men (56.6%) were discovered by initiative investigation. Among heterosexual patients CD4+ T cell counts and HIV-1 viral load were significantly correlated; among the group of men who have sex with men, no such association was found.

Analytic performance studies and clinical reproducibility of a real-time PCR assay for the detection of epidermal growth factor receptor gene mutations in formalin-fixed paraffin-embedded tissue specimens of non-small cell lung cancer.

BACKGROUND: Epidermal growth factor receptor (EGFR) gene mutations identify patients with non-small cell lung cancer (NSCLC) who have a high likelihood of benefiting from treatment with anti-EGFR tyrosine kinase inhibitors. Sanger sequencing is widely used for mutation detection but can be technically challenging, resulting in longer turn-around-time, with limited sensitivity for low levels of mutations. This manuscript details the technical performance verification studies and external clinical reproducibility studies of the cobas EGFR Mutation Test, a rapid multiplex real-time PCR assay designed to detect 41 mutations in exons 18, 19, 20 and 21. METHODS: The assay's limit of detection was determined using 25 formalin-fixed paraffin-embedded tissue (FFPET)-derived and plasmid DNA blends. Assay performance for a panel of 201 specimens was compared against Sanger sequencing with resolution of discordant specimens by quantitative massively parallel pyrosequencing (MPP). Internal and external reproducibility was assessed using specimens tested in duplicate by different operators, using different reagent lots, instruments and at different sites. The effects on the performance of the cobas EGFR test of endogenous substances and nine therapeutic drugs were evaluated in ten FFPET specimens. Other tests included an evaluation of the effects of necrosis, micro-organisms and homologous DNA sequences on assay performance, and the inclusivity of the assay for less frequent mutations. RESULTS: A >95% hit rate was obtained in blends with >5% mutant alleles, as determined by MPP analysis, at a total DNA input of 150 ng. The overall percent agreement between Sanger sequencing and the cobas test was 96.7% (negative percent agreement 97.5%; positive percent agreement 95.8%). Assay repeatability was 98% when tested with two operators, instruments, and reagent lots. In the external reproducibility study, the agreement was > 99% across all sites, all operators and all reagent lots for 11/12 tumors tested. Test performance was not compromised by endogenous substances, therapeutic drugs, necrosis up to 85%, and common micro-organisms. All of the assessed less common mutations except one (exon 19 deletion mutation 2236_2248 > AGAC) were detected at a similar DNA input level as that for the corresponding predominant mutation. CONCLUSION: The cobas EGFR Mutation Test is a sensitive, accurate, rapid, and reproducible assay.

Multisite analytic performance studies of a real-time polymerase chain reaction assay for the detection of BRAF V600E mutations in formalin-fixed, paraffin-embedded tissue specimens of malignant melanoma.

CONTEXT: A polymerase chain reaction-based companion diagnostic (cobas 4800 BRAF V600 Mutation Test) was recently approved by the US Food and Drug Administration to select patients with BRAF-mutant metastatic melanoma for treatment with the BRAF inhibitor vemurafenib. OBJECTIVES: (1) To compare the analytic performance of the cobas test to Sanger sequencing by using screening specimens from phase II and phase III trials of vemurafenib, and (2) to assess the reproducibility of the cobas test at different testing sites. DESIGN: Specimens from 477 patients were used to determine positive and negative percent agreements between the cobas test and Sanger sequencing for detecting V600E (1799T>A) mutations. Specimens were evaluated with a massively parallel pyrosequencing method (454) to resolve discordances between polymerase chain reaction and Sanger results. Reproducibility of the cobas test was assessed at 3 sites by using 3 reagent lots and an 8-member panel of melanoma samples. RESULTS: A valid cobas result was obtained for all eligible patients. Sanger sequencing had a failure rate of 9.2% (44 of 477). For the remaining 433 specimens, positive percent agreement was 96.4% (215 of 223) and negative percent agreement, 80% (168 of 210). Among 42 cobas mutation-positive/Sanger V600E-negative specimens, 17 were V600E positive and 24 were V600K positive by 454. The cobas test detected 70% of V600K mutations. In the reproducibility study, a correct interpretation was made for 100% of wild-type specimens and specimens with greater than 5% mutant alleles; V600E mutations were detected in 90% of specimens with less than 5% mutant alleles. CONCLUSIONS: The cobas test (1) had a lower assay failure rate than that of Sanger, (2) was more sensitive in detecting V600E mutations, (3) detected most V600K mutations, and (4) was highly reproducible.

A phase-locked loop model of the response of the postural control system to periodic platform motion.

A phase-locked loop (PLL) model of the response of the postural control system to periodic platform motion is proposed. The PLL model is based on the hypothesis that quiet standing (QS) postural sway can be characterized as a weak sinusoidal oscillation corrupted with noise. Because the signal to noise ratio is quite low, the characteristics of the QS oscillator are not measured directly from the QS sway, instead they are inferred from the response of the oscillator to periodic motion of the platform. When a sinusoidal stimulus is applied, the QS oscillator changes speed as needed until its frequency matches that of the platform, thus achieving phase lock in a manner consistent with a PLL control mechanism. The PLL model is highly effective in representing the frequency, amplitude, and phase shift of the sinusoidal component of the phase-locked response over a range of platform frequencies and amplitudes. Qualitative analysis of the PLL control mechanism indicates that there is a finite range of frequencies over which phase lock is possible, and that the size of this capture range decreases with decreasing platform amplitude. The PLL model was tested experimentally using nine healthy subjects and the results reveal good agreement with a mean phase shift error of 13.7 degrees and a mean amplitude error of 0.8 mm.

Risks and benefits of splenectomy versus no splenectomy for hereditary spherocytosis--a personal view.

Splenectomy is indicated in hereditary spherocytosis to relieve symptoms due to anaemia or splenomegaly, reverse growth failure or skeletal changes due to over-robust erythropoiesis, and prevent recurrent gallstones. A life-long risk of bacterial infection has been recognised for many years as a concomitant cost of splenectomy. The scope of this risk has expanded to include a number of organisms beyond the triad of pneumococcus, meningococcus, and haemophilus influenzae. Recently, it has been demonstrated that splenectomy also confers a significant risk of delayed adverse vascular events in patients with hereditary spherocytosis, just as it does in patients undergoing splenectomy for other indications. Further, these same studies demonstrated a benefit of avoiding splenectomy: hereditary spherocytosis patients with a spleen have significantly fewer adverse vascular events than unaffected family members, probably because of the protective effect of chronic, mild anaemia. Accordingly, this review marshals the evidence favouring a conservative approach to splenectomy in spherocytosis.

A quiet standing index for testing the postural sway of healthy and diabetic adults across a range of ages.

A quiet standing index is developed for tracking the postural sway of healthy and diabetic adults over a range of ages. Several postural sway features are combined into a single composite feature C that increases with age a. Sway features are ranked based on the r(2)-values of their linear regression models, and the composite feature is a weighted sum of selected sway features with optimal weighting coefficients determined using principal component analysis. A performance index based on both reliability and sensitivity is used to determine the optimal number of features. The features used to form C include power and distance metrics. The quiet standing index is a scalar that compares the composite feature C to a linear regression model f(a) using C(')(a) = C/f(a). For a motionless subject, C(') = 0, and when the composite feature exactly matches the healthy control (HC) model, C(') = 1. Values of C(') >> 1 represent excessive postural sway and may indicate impaired postural control. Diabetic neurologically intact subjects, nondiabetic peripheral neuropathy subjects (PN), and diabetic PN subjects (DPN) were evaluated. The quiet standing indexes of the PN and DPN groups showed statistically significant increases over the HC group. Changes in the quiet standing index over time may be useful in identifying people with impaired balance who may be at an increased risk of falling.

Demographic trends in social work over a quarter-century in an increasingly female profession.

This article depicts the changing demographic portrait of social work education in the United States from 1974 through 2000 and considers the demographic shifts in the profession of social work. During this period, BSW and joint MSW-BSW programs increased from 150 to 404, MSW programs increased from 79 to 139, and social work doctoral programs increased from 29 to 67. BSW graduates increased by 24 percent to almost 12,000, MSW graduates grew by almost 90 percent to over 15,000, and doctoral graduates increased by 44 percent to only 229. From 1974 to 2000, people of color represented increasing proportions of social work graduates to almost 30 percent of BSW graduates, 26 percent of MSW graduates, and 19 percent of social work PhD graduates. By 2000, the proportion of women earning social work degrees had grown to 88 percent at the BSW, 85 percent at the MSW, and 73 percent at the PhD levels, and women accounted for almost two-thirds of social work faculty. The most dynamic trends within the composition of the profession are the substantial increases in the proportion of women faculty, and among MSW graduates, a decrease in the proportion of men from 43 percent in 1960 to 15 percent in 2000. Findings suggest that issues of racial, ethnic, and gender representation in particular merit discussion within the profession.

The 100% Condom Use Program: a demonstration in Wuhan, China.

The 100% Condom Use Program (100% CUP) was evaluated in Wuhan, China. The program sought to increase knowledge of STI/HIV transmission, increase condom use rates, and reduce the prevalence of sexually transmitted infections (STIs) among sex workers (commercial sex workers (CSWs)), via condom availability and use policies in entertainment establishments and STI services including education and counseling. Entertainment establishment owners and CSWs participated in educational sessions and multiple community sectors were involved in the program. At baseline, 170 female CSWs were assessed, and 102 CSWs were assessed at the final 21-month follow-up. At 6-month follow-up, 95% of entertainment establishments were in compliance with 100% CUP policies. At 15 months, condoms were readily available in retail outlets, and condom use rates rose by 94.5%. Refractive rates of chlamydia and methodological limitations of the evaluation leave unanswered questions about the effectiveness of the program. Nonetheless, outcomes suggest that the 100% CUP may be a promising approach to HIV prevention in China.

A biomechanical model of human ankle angle changes arising from short peri-threshold anterior translations of platform on which a subject stands.

This study modeled ankle angle changes during small forward perturbations of a standing platform. A two-dimensional biomechanical inverted pendulum model was developed that uses sway frequencies derived from quiet standing observations on a subject's Anterior Posterior Center of Pressure (APCoP) to track ankle angle changes during a 16 mm anterior displacement perturbation of a platform on which a subject stood. This model used the total torque generated at the ankle joint as one of the inputs, and calculated it assuming a PID controller. This feedback system generated a simulated ankle torque based on the angular position of the center of mass (CoM) with respect to vertical line passing through the ankle joint. This study also assumed that the internal components of the net torque were only a controller torque and a sway-pattern-generating torque. The final inputs to the model were the platform acceleration and anthropometric terms. This model of postural sway dynamics predicted sway angle and the trajectory of the center of mass. Knowing these relationships can advance an understanding of the ankle strategy employed in balance control.

Client factors associated with length of stay in methadone treatment among heroin users who inject drugs: quantitative analysis of state-level substance abuse treatment utilization data.

The objective of this study was to examine, for a population of 8,258 adult injection drug users (IDUs) who all had entered a Massachusetts licensed methadone maintenance treatment program (MMT) between 1996 and 2002, client factors associated with remaining in MMT for a minimum of 1 year after program entry. Two binomial logistic regression models were developed. The first model examined the association between age, sex, race/ethnicity, parental status, employment status, educational status, health insurance status, homelessness status, having injected drugs in the past month, residential treatment use, number of overall treatment admissions, and whether a client's longest consecutive stay in MMT had lasted for 1 year or more. Second, to examine the stability of the statistical relationships identified in the first logistic regression model, a second logistic regression model examined whether there were significant differences in client level characteristics between those who used MMT for 6 months or less compared with their counterparts. Those who were older, women, those who were not homeless, those who resided with their children, those who had public health insurance, and those who had not used residential treatment were significantly more likely to have stayed in MMT for at least 1 year or more. In contrast, those who were younger, males, homeless, did not live with children, had no insurance, and had used residential treatment were significantly more likely to have stayed in MMT for 6 months or less compared with their counterparts. Those who stayed in MMT for 1 year or more were more likely to have stable lives compared with those who dropped out of MMT before a year. Providing services to improve MMT clients' employment, housing, and family stability may help improve MMT retention rates. Second, clients with a history of having used residential substance abuse treatment were more likely to stay in MMT for a shorter time period compared with their counterparts. The extent to which treatment bifurcation is a matter of choice or related to other factors needs to be further explored.

Arteriosclerotic events are less frequent in persons with chronic anemia: evidence from families with hereditary spherocytosis.

Because anemic persons have lower cholesterol and whole blood viscosity than those who are not anemic, we hypothesized that subjects with hereditary spherocytosis who have not had the spleen removed should have fewer arteriosclerotic events than unaffected family members. We defined arteriosclerotic events as myocardial infarct, stroke, coronary artery surgery, and carotid artery surgery. We compared the rate of these events in affected-not splenectomized persons to the rate in unaffected family members. The relative risk of an arteriosclerotic event in hereditary spherocytosis patients with a spleen was one fifth that in unaffected family members. These data support the hypothesis that chronic anemia retards the development of arteriosclerosis. Spherocytosis is another example of an inherited condition that conveys an advantage in one system and a disadvantage in another.

Factors associated with emergency room use among injection drug users of African-American, Hispanic and White-European background.

This study examined the relationship between substance abuse treatment use, health services use, HIV status, and emergency room/hospital use for 507 injection drug users (IDUs). Logistic regression models showed that mental health status, severity of drug use and private health insurance were significantly associated with having used emergency room/hospital services in the past six months. History of substance abuse treatment use, positive HIV/AIDS diagnosis, mental health service use, ethnic/racial background, gender, age, education and homelessness were not significant at either the bivariate or the multivariate level. These results point to the need to improve mental health screening and referrals through emergency room medical systems.

Evidence-based drug treatment practice and the child welfare system: the example of methadone.

This article examined the extent to which methadone maintenance (MM) is considered a treatment alternative for drug-dependent parents, as reflected in the social work and child welfare literature and in child welfare policies. Findings were derived from a review of 15 social work journals published from 1996 through 2002 and from a review of child welfare policies in 27 states in regard to treatment recommendations for substance-abusing parents. These reviews found that 23 articles focused on child welfare-substance abuse issues; no article specifically discussed MM as a treatment option for heroin-using parents; and of the 27 states, only three included methadone as a treatment option in their child welfare policy recommendations. Practice and policy recommendations are discussed.