A Contextualization of Transgender Women and Condom Use Using the HIV Syndemic Framework: Scoping Review.

Objective: To contextualize condom use in the transgender women population utilizing the HIV syndemic framework. Methods: Studies reporting condom use frequency and syndemic factors associated with HIV risk in transgender women were systematically searched. We followed the Scoping Reviews (PRISMA-ScR) checklist. Results: Social factors have a proven relationship with using condoms and HIV among transgender women. Syndemic factors, defined as co-occurring adverse factors that interact to contribute to risk behaviors, deserve a specific analysis to develop strategies to face HIV among transgender women. Conclusions: A syndemic perspective allows to generate specific health intervention and prevention policies to protect transgender women.

[Discourses about condom use and non-use among gay, bisexual men, and other men who have sex with men in two colombian cities.] / Discursos identificados sobre el uso y no uso del condón en hombres gais, bisexuales y otros hombres que tienen sexo con hombres en dos ciudades de Colombia.

OBJECTIVE: The HIV increase cases raises concern worldwide. This phenomenon is related, among other things, to sexual practices where condom use is limited. To achieve the eradication of AIDS, international organizations have been interested in analyzing and understanding the sexual practices of certain population groups, within these men who have sex with other men. In this sense, the objective of this study was to analyze the discourses on the use and non-use of condoms held by a group of gay, bisexual and other men who have sex with men (GBHSH) men from two cities in Colombia. METHODS: A qualitative study was carried out with data analysis through the iterative process, from the interpretation of the Information, Motivation and Behavioral Skills (IMB) model. The collection of information was carried out between 2020 and 2021 through in-depth interviews, virtually and in person, with a sample of 20 GBHSH from Colombia from the cities of Cali and Medellín. RESULTS: In the Information component, it was identified that traditional sexual education had a negative impact and was very focused on a cisheterosexual and reproductive perspective. Regarding Motivational, it was highlighted that the majority were oriented towards not using condoms and that perceiving a low risk of contracting an STI was the main motivation for not using condoms. Regarding Behavioral Skills, it was analyzed that distrust towards the sexual partner promoted its use, but the intensification of pleasure, added to the consumption of alcohol and drugs, caused its use to decrease. It was also evidenced that the use of drugs such as PreP or PEP discouraged condom use in relationships. CONCLUSIONS: The information on condom use revolves around cisheteronormative practices, leaving aside the care related to STIs. The motivation for not using condoms revolves around misinformation, pleasure and trust in the couple, while the motivation for condom use revolves around health care. The behavior regarding the non-use of condoms is related to the previous points, while misinformation and pleasure in non-use predominate.

OBJETIVO: El aumento de casos de VIH suscita preocupación a nivel mundial. Este fenómeno se relaciona, entre otras cosas, con prácticas sexuales en donde se limita el uso del condón. Para lograr la erradicación del sida, organismos internacionales se han interesado en analizar y comprender las prácticas sexuales de ciertos grupos poblacionales, dentro de estos, los hombres que tienen relaciones sexuales con otros hombres. En este sentido, el objetivo de este estudio fue analizar los discursos sobre el uso y no uso del condón que tenía un grupo de hombres gais, bisexuales y otros hombres que tienen sexo con hombres (GBHSH) de dos ciudades de Colombia. METODOS: Se realizó un estudio cualitativo con análisis de datos por medio del proceso iterativo, desde la interpretación del modelo Información, Motivación y Habilidades conductuales (IMB, por sus siglas en inglés). La recolección de la información se realizó entre los años 2020 y 2021 por medio de entrevistas en profundidad, de manera virtual y presencial, con una muestra de 20 GBHSH de Colombia de las ciudades de Cali y Medellín. RESULTADOS: En el componente Información se identificó que la educación sexual tradicional tenía un impacto negativo y muy enfocado a una mirada cisheterosexual y reproductiva. Respecto a lo Motivacional, se destacó que la mayoría se orientaban al no uso del condón y que percibir un bajo riesgo de contraer una ITS era la principal motivación del no uso del condón. Con relación a las Habilidades Conductuales se analizó que la desconfianza hacia la pareja sexual promovía su uso, pero la intensificación del placer, sumado al consumo de alcohol y drogas, hacía que su uso disminuyera. También se evidenció que el uso de fármacos como el PreP o el PEP desestimulaban el uso del condón en las relaciones. CONCLUSIONES: La información sobre el uso del condón gira alrededor de prácticas cisheteronormativas, dejando de lado los cuidados relacionados con las ITS. La motivación sobre el no uso del condón gira alrededor de la desinformación, el placer y la confianza en la pareja, mientras que la motivación para el uso del condón gira alrededor del cuidado a la salud. El comportamiento sobre el no uso del condón se relaciona con los puntos anteriores, en tanto que predominan la desinformación y placer en el no uso.

Discursos identificados sobre el uso y no uso del condón en hombres gais, bisexuales y otros hombres que tienen sexo con hombres en dos ciudades de Colombia / Discourses about condom use and non-use among gay, bisexual men, and other men who have sex with men in two colombian cities

FUNDAMENTOS: El aumento de casos de VIH suscita preocupación a nivel mundial. Este fenómeno se relaciona, entre otrascosas, con prácticas sexuales en donde se limita el uso del condón. Para lograr la erradicación del sida, organismos internacionalesse han interesado en analizar y comprender las prácticas sexuales de ciertos grupos poblacionales, dentro de estos, los hombresque tienen relaciones sexuales con otros hombres. En este sentido, el objetivo de este estudio fue analizar los discursos sobre el usoy no uso del condón que tenía un grupo de hombres gais, bisexuales y otros hombres que tienen sexo con hombres (GBHSH) de dosciudades de Colombia. MÉTODOS: Se realizó un estudio cualitativo con análisis de datos por medio del proceso iterativo, desde la interpretación delmodelo Información, Motivación y Habilidades conductuales (IMB, por sus siglas en inglés). La recolección de la información se realizóentre los años 2020 y 2021 por medio de entrevistas en profundidad, de manera virtual y presencial, con una muestra de 20 GBHSHde Colombia de las ciudades de Cali y Medellín. RESULTADOS: En el componenteInformación se identificó que la educación sexual tradicional tenía un impacto negativo y muyenfocado a una mirada cisheterosexual y reproductiva. Respecto a loMotivacional, se destacó que la mayoría se orientaban al nouso del condón y que percibir un bajo riesgo de contraer una ITS era la principal motivación del no uso del condón. Con relación alasHabilidades Conductuales se analizó que la desconfianza hacia la pareja sexual promovía su uso, pero la intensificación del placer,sumado al consumo de alcohol y drogas, hacía que su uso disminuyera. También se evidenció que el uso de fármacos como el PrePo el PEP desestimulaban el uso del condón en las relaciones.CONCLUSIONES: Lainformación sobre el uso del condón gira alrededor de prácticas cisheteronormativas, dejando de ladolos cuidados relacionados con las ITS...(AU)

BACKGROUND: The HIV increase cases raises concern worldwide. This phenomenon is related, among other things, to sexual practices where condom use is limited. To achieve the eradication of AIDS, international organizations have been interested in analyzingand understanding the sexual practices of certain population groups, within these men who have sex with other men. In this sense,the objective of this study was to analyze the discourses on the use and non-use of condoms held by a group of gay, bisexual andother men who have sex with men (GBHSH) men from two cities in Colombia.METHODS: A qualitative study was carried out with data analysis through the iterative process, from the interpretation of the Information, Motivation and Behavioral Skills (IMB) model. The collection of information was carried out between 2020 and 2021 through in-depthinterviews, virtually and in person, with a sample of 20 GBHSH from Colombia from the cities of Cali and Medellín. RESULTS: In theInformation component, it was identified that traditional sexual education had a negative impact and was veryfocused on a cisheterosexual and reproductive perspective. RegardingMotivational, it was highlighted that the majority were orientedtowards not using condoms and that perceiving a low risk of contracting an STI was the main motivation for not using condoms. RegardingBehavioral Skills, it was analyzed that distrust towards the sexual partner promoted its use, but the intensification of pleasure,added to the consumption of alcohol and drugs, caused its use to decrease. It was also evidenced that the use of drugs such as PrePor PEP discouraged condom use in relationships. CONCLUSIONS: Theinformation on condom use revolves around cisheteronormative practices, leaving aside the care related toSTIs. Themotivation for not using condoms revolves around misinformation, pleasure and trust in the couple, while the motivationfor condom use revolves around health care...(AU)

Condom use and non-use among transgender women in Colombia: a qualitative analysis based on the IMB model.

OBJECTIVE: Review the reasons for condom use and non-use among transgender women in Colombia based on the information, motivation and behavioral skills (IMB) model. METHOD: Qualitative study in which an iterative process analysis was carried out. A focal group participated in person, and in-depth interviews were conducted virtually. RESULTS: First study carried out in Colombia on condom use among transgender women under the IMB model. The information component finds that traditional sexual education does not have a positive impact. Regarding motivational aspects, the importance of family support and follow-up and community-based organizations to motivate sexual health care and condom use is highlighted. Regarding behavioral skills, it was found that distrust towards sexual partners and the acquisition of condoms promote their use. CONCLUSIONS: It is important to create spaces for sexual education delivered by and for the LGBTIQ population, followed by the medical knowledge of health centers, to have positive impacts on the sexual health of transgender women; studies with sexual partners of transgender women are encouraged in order to know the reasons why they request the non-use of condoms.

Does food biodiversity protect against malnutrition and favour the resilience to climate change-related events in Amazon Indigenous communities? A protocol for a mixed methods study.

Background : Undernutrition is projected to be a major consequence of climate change. Biodiversity could enhance climate change resilience by improving nutritional outcomes and providing healthy food resources during and/or after climate-related events. For Indigenous populations who currently base their diet on local biodiversity, rapid climate changes may affect their ability to produce, access or gather food and consequently impact their nutritional status. There is a knowledge gap regarding whether nutritional status among Indigenous populations is better among those who consume a diet with greater biodiversity than those who have a diet with low biodiversity. Objective : This study aims to investigate the role of food biodiversity (FBD) in nutritional resilience to extreme flooding events of Shawi Amazon Indigenous adults living in Peruvian communities that have experienced extreme floods in the past five years. Methods : This study will use a mixed-method sequential explanatory design. The quantitative component includes a cross-sectional survey to assess the association between food biodiversity (FBD) and the prevalence of anaemia in adults aged 15 to 60 years old (n=365). Anaemia will be evaluated using blood hemoglobin and serum ferritin. FBD will be measured with a food frequency questionnaire and a 24-hour dietary recall. Soil-transmitted helminth infections, malaria, and inflammatory biomarkers will also be evaluated. The qualitative component will include a community-based participatory approach to investigate the role of FBD in the responses to extreme floods. Male (n=14) and female (n=14) participants, previously identified in the quantitative phase with high and low levels of FBD, will be invited to participate in a Photovoice activity and semi-structured interviews. A analytical framework for climate change resilience will be used to integrate the data. Discussion : Findings will be integrated to identify nutritional resilience indicators that can inform adaptative interventions to changing climatic conditions in the Amazon and that respect Indigenous worldviews.

Condom use and non-use among transgender women in Colombia: a qualitative analysis based on the IMB model / El uso y no uso del condón en mujeres trans de Colombia: un análisis cualitativo desde el modelo IMB

ABSTRACT OBJECTIVE Review the reasons for condom use and non-use among transgender women in Colombia based on the information, motivation and behavioral skills (IMB) model. METHOD Qualitative study in which an iterative process analysis was carried out. A focal group participated in person, and in-depth interviews were conducted virtually. RESULTS First study carried out in Colombia on condom use among transgender women under the IMB model. The information component finds that traditional sexual education does not have a positive impact. Regarding motivational aspects, the importance of family support and follow-up and community-based organizations to motivate sexual health care and condom use is highlighted. Regarding behavioral skills, it was found that distrust towards sexual partners and the acquisition of condoms promote their use. CONCLUSIONS It is important to create spaces for sexual education delivered by and for the LGBTIQ population, followed by the medical knowledge of health centers, to have positive impacts on the sexual health of transgender women; studies with sexual partners of transgender women are encouraged in order to know the reasons why they request the non-use of condoms.

RESUMEN OBJETIVO Analizar las razones del uso y no uso del condón que tienen las mujeres trans de Colombia desde el modelo de información, motivación y habilidades conductuales (IMB por sus siglas en inglés). MÉTODO Estudio cualitativo en el cual se llevó a cabo el análisis de proceso iterativo. Se realizó un grupo focal de manera presencial y entrevistas a profundidad de manera virtual. RESULTADOS Primer estudio llevado a cabo en Colombia sobre el uso del preservativo en mujeres trans bajo el modelo IMB. En el componente información se identifica que la educación sexual tradicional no tiene un impacto positivo. Respecto a lo motivacional, se destaca la importancia del apoyo y acompañamiento familiar y de las organizaciones de base comunitaria para motivar al cuidado de la salud sexual y el uso del preservativo. Con relación a las habilidades conductuales, se analiza que la desconfianza hacia la pareja sexual y la adquisición de los preservativos promueven su uso. CONCLUSIONES Se hace importante la creación de espacios de educación sexual realizados por y para la población LGBTIQ, acompañados por el saber médico de los centros de salud, para impactar de manera positiva la salud sexual de mujeres trans; se motiva a la realización de estudios con parejas sexuales de mujeres trans para conocer las razones por las cuales solicitan el no uso del preservativo.

Nicotinic receptor modulation of primary afferent excitability with selective regulation of Aδ-mediated spinal actions.

Somatosensory input strength can be modulated by primary afferent depolarization (PAD) generated predominantly via presynaptic GABAA receptors on afferent terminals. We investigated whether ionotropic nicotinic acetylcholine receptors (nAChRs) also provide modulatory actions, focusing on myelinated afferent excitability in in vitro murine spinal cord nerve-attached models. Primary afferent stimulation-evoked synaptic transmission was recorded in the deep dorsal horn as extracellular field potentials (EFPs), whereas concurrently recorded dorsal root potentials (DRPs) were used as an indirect measure of PAD. Changes in afferent membrane excitability were simultaneously measured as direct current (DC)-shifts in membrane polarization recorded in dorsal roots or peripheral nerves. The broad nAChR antagonist d-tubocurarine (d-TC) selectively and strongly depressed Aδ-evoked synaptic EFPs (36% of control) coincident with similarly depressed A-fiber DRP (43% of control), whereas afferent electrical excitability remained unchanged. In comparison, acetylcholine (ACh) and the nAChR agonists, epibatidine and nicotine, reduced afferent excitability by generating coincident depolarizing DC-shifts in peripheral axons and intraspinally. Progressive depolarization corresponded temporally with the emergence of spontaneous axonal spiking and reductions in the DRP and all afferent-evoked synaptic actions (31%-37% of control). Loss of evoked response was long-lasting, independent of DC repolarization, and likely due to mechanisms initiated by spontaneous C-fiber activity. DC-shifts were blocked with d-TC but not GABAA receptor blockers and retained after tetrodotoxin block of voltage-gated Na+ channels. Notably, actions tested were comparable between three mouse strains, in rat, and when performed in different labs. Thus, nAChRs can regulate afferent excitability via two distinct mechanisms: by central Aδ-afferent actions, and by transient extrasynaptic axonal activation of high-threshold primary afferents.NEW & NOTEWORTHY Primary afferents express many nicotinic ACh receptor (nAChR) subtypes but whether activation is linked to presynaptic inhibition, facilitation, or more complex and selective activity modulation is unknown. Recordings of afferent-evoked responses in the lumbar spinal cord identified two nAChR-mediated modulatory actions: 1) selective control of Aδ afferent transmission and 2) robust changes in axonal excitability initiated via extrasynaptic shifts in DC polarization. This work broadens the diversity of presynaptic modulation of primary afferents by nAChRs.

The activation of D2 and D3 receptor subtypes inhibits pathways mediating primary afferent depolarization (PAD) in the mouse spinal cord.

Somatosensory information can be modulated at the spinal cord level by primary afferent depolarization (PAD), known to produce presynaptic inhibition (PSI) by decreasing neurotransmitter release through the activation of presynaptic ionotropic receptors. Descending monoaminergic systems also modulate somatosensory processing. We investigated the role of D1-like and D2-like receptors on pathways mediating PAD in the hemisected spinal cord of neonatal mice. We recorded low-threshold evoked dorsal root potentials (DRPs) and population monosynaptic responses as extracellular field potentials (EFPs). We used a paired-pulse conditioning-test protocol to assess homosynaptic and heterosynaptic depression of evoked EFPs to discriminate between dopaminergic effects on afferent synaptic efficacy and/or on pathways mediating PAD, respectively. DA (10 µM) depressed low-threshold evoked DRPs by 43 %, with no effect on EFPs. These depressant effects on DRPs were mimicked by the D2-like receptor agonist quinpirole (35 %). Moreover, by using selective antagonists at D2-like receptors (encompassing the D2, D3, and D4 subtypes), we found that the D2 and D3 receptor subtypes participate in the quinpirole depressant inhibitory effects of pathways mediating PAD.

Activation of α-adrenoceptors depresses synaptic transmission of myelinated afferents and inhibits pathways mediating primary afferent depolarization (PAD) in the in vitro mouse spinal cord.

Somatosensory afferent transmission strength is controlled by several presynaptic mechanisms that reduce transmitter release at the spinal cord level. We focused this investigation on the role of α-adrenoceptors in modulating sensory transmission in low-threshold myelinated afferents and in pathways mediating primary afferent depolarization (PAD) of neonatal mouse spinal cord. We hypothesized that the activation of α-adrenoceptors depresses low threshold-evoked synaptic transmission and inhibits pathways mediating PAD. Extracellular field potentials (EFPs) recorded in the deep dorsal horn assessed adrenergic modulation of population monosynaptic transmission, while dorsal root potentials (DRPs) recorded at root entry zone assessed adrenergic modulation of PAD. We found that noradrenaline (NA) and the α1-adrenoceptor agonists phenylephrine and cirazoline depressed synaptic transmission (by 15, 14 and 22%, respectively). DRPs were also depressed by NA, phenylephrine and cirazoline (by 62, 30, and 64%, respectively), and by the α2-adrenoceptor agonist clonidine, although to a lower extent (20%). We conclude that NA depresses monosynaptic transmission of myelinated afferents onto deep dorsal horn neurons via α1-adrenoceptors and inhibits interneuronal pathways mediating PAD through the activation of α1- and α2-adrenoceptors. The functional significance of these modulatory actions in shaping cutaneous and muscle sensory information during motor behaviors requires further study.

Assessment of axonal recruitment using model-guided preclinical spinal cord stimulation in the ex vivo adult mouse spinal cord.

Spinal cord stimulation (SCS) is used clinically to limit chronic pain, but fundamental questions remain on the identity of axonal populations recruited. We developed an ex vivo adult mouse spinal cord preparation to assess recruitment following delivery of clinically analogous stimuli determined by downscaling a finite element model of clinical SCS. Analogous electric field distributions were generated with 300-µm × 300-µm electrodes positioned 200 µm above the dorsal column (DC) with stimulation between 50 and 200 µA. We compared axonal recruitment using electrodes of comparable size and stimulus amplitudes when contacting the caudal thoracic DC and at 200 or 600 µm above. Antidromic responses recorded distally from the DC, the adjacent Lissauer tract (LT), and in dorsal roots (DRs) were found to be amplitude and site dependent. Responses in the DC included a unique component not seen in DRs, having the lowest SCS recruitment amplitude and fastest conduction velocity. At 200 µm above, mean cathodic SCS recruitment threshold for axons in DRs and LT were 2.6 and 4.4 times higher, respectively, than DC threshold. SCS recruited primary afferents in all (up to 8) caudal segments sampled. Whereas A and C fibers could be recruited at nearby segments, only A fiber recruitment and synaptically mediated dorsal root reflexes were observed in more distant (lumbar) segments. In sum, clinically analogous SCS led to multisegmental recruitment of several somatosensory-encoding axonal populations. Most striking is the possibility that the lowest threshold recruitment of a nonprimary afferent population in the DC are postsynaptic dorsal column tract cells (PSDCs) projecting to gracile nuclei.NEW & NOTEWORTHY Spinal cord stimulation (SCS) is used clinically to control pain. To identify axonal populations recruited, finite element modeling identified scaling parameters to deliver clinically analogous SCS in an ex vivo adult mouse spinal cord preparation. Results showed that SCS first recruited an axonal population in the dorsal column at a threshold severalfold lower than primary afferents. These putative postsynaptic dorsal column tract cells may represent a previously unconsidered population responsible for SCS-induced paresthesias necessary for analgesia.

Correction to: Long-term safety and efficacy of vismodegib in patients with advanced basal cell carcinoma: final update of the pivotal ERIVANCE BCC study.

Following publication of the original article [1], it was reported that the legend for Fig. 1 was incomplete. The complete figure legend is.

Androgen Receptor Variant AR-V9 Is Coexpressed with AR-V7 in Prostate Cancer Metastases and Predicts Abiraterone Resistance.

Purpose: Androgen receptor (AR) variant AR-V7 is a ligand-independent transcription factor that promotes prostate cancer resistance to AR-targeted therapies. Accordingly, efforts are under way to develop strategies for monitoring and inhibiting AR-V7 in castration-resistant prostate cancer (CRPC). The purpose of this study was to understand whether other AR variants may be coexpressed with AR-V7 and promote resistance to AR-targeted therapies.Experimental Design: We utilized complementary short- and long-read sequencing of intact AR mRNA isoforms to characterize AR expression in CRPC models. Coexpression of AR-V7 and AR-V9 mRNA in CRPC metastases and circulating tumor cells was assessed by RNA-seq and RT-PCR, respectively. Expression of AR-V9 protein in CRPC models was evaluated with polyclonal antisera. Multivariate analysis was performed to test whether AR variant mRNA expression in metastatic tissues was associated with a 12-week progression-free survival endpoint in a prospective clinical trial of 78 CRPC-stage patients initiating therapy with the androgen synthesis inhibitor, abiraterone acetate.Results: AR-V9 was frequently coexpressed with AR-V7. Both AR variant species were found to share a common 3' terminal cryptic exon, which rendered AR-V9 susceptible to experimental manipulations that were previously thought to target AR-V7 uniquely. AR-V9 promoted ligand-independent growth of prostate cancer cells. High AR-V9 mRNA expression in CRPC metastases was predictive of primary resistance to abiraterone acetate (HR = 4.0; 95% confidence interval, 1.31-12.2; P = 0.02).Conclusions: AR-V9 may be an important component of therapeutic resistance in CRPC. Clin Cancer Res; 23(16); 4704-15. ©2017 AACR.

Long-term safety and efficacy of vismodegib in patients with advanced basal cell carcinoma: final update of the pivotal ERIVANCE BCC study.

BACKGROUND: In the primary analysis of the ERIVANCE BCC trial, vismodegib, the first US Food and Drug Administration-approved Hedgehog pathway inhibitor, showed objective response rates (ORRs) by independent review facility (IRF) of 30% and 43% in metastatic basal cell carcinoma (mBCC) and locally advanced BCC (laBCC), respectively. ORRs by investigator review were 45% (mBCC) and 60% (laBCC). Herein, we present long-term safety and final investigator-assessed efficacy results in patients with mBCC or laBCC. METHODS: One hundred four patients with measurable advanced BCC received oral vismodegib 150 mg once daily until disease progression or intolerable toxicity. The primary end point was IRF-assessed ORR. Secondary end points included ORR, duration of response (DOR), progression-free survival, overall survival (OS), and safety. RESULTS: At data cutoff (39 months after completion of accrual), 8 patients were receiving the study drug (69 patients in survival follow-up). Investigator-assessed ORR was 48.5% in the mBCC group (all partial responses) and 60.3% in the laBCC group (20 patients had complete response and 18 patients had partial response). ORRs were comparable across patient subgroups, including aggressive histologic subtypes (eg, infiltrative BCC). Median DOR was 14.8 months (mBCC) and 26.2 months (laBCC). Median OS was 33.4 months in the mBCC cohort and not estimable in the laBCC cohort. Adverse events remained consistent with clinical experience. Thirty-three deaths (31.7%) were reported; none were related to vismodegib. CONCLUSIONS: This long-term update of the ERIVANCE BCC trial demonstrated durability of response, efficacy across patient subgroups, and manageable long-term safety of vismodegib in patients with advanced BCC. TRIAL REGISTRATION: This study was registered prospectively with Clinicaltrials.gov , number NCT00833417 on January 30, 2009.

Point-Of-Care p24 Infant Testing for HIV May Increase Patient Identification despite Low Sensitivity.

The long delay in returning test results during early infant diagnosis of HIV (EID) often causes loss-to-follow-up prior to antiretroviral treatment (ART) initiation in resource-limited settings. A point-of-care (POC) test may help overcome these challenges. We evaluated the performance of the LYNX p24 Antigen POC test in Mozambique. 879 HIV-exposed infants under 18 months of age were enrolled consecutively at three primary healthcare clinics (PHC). Lancet heel-drawn blood was tested on-site by nurses using a prototype POC test for HIV Gag p24 antigen detection. Results of POC testing were compared to laboratory-based nucleic acid testing on dried blood spots. A comparison of the effect of sensitivity and timely test results return on successful diagnosis by POC and laboratory-based platforms was also calculated. The sensitivity and specificity of the LYNX p24 Ag test were 71.9%; (95% confidence interval [CI]: 58.5-83.0%) and 99.6% (95% CI: 98.9-99.9%), respectively. The predictive value of positive and negative tests were 93.2% (95% CI: 81.3-98.6%) and 97.9% (95% CI: 96.8-98.8%), respectively. Overall agreement was high (Cohen Kappa = 0.80; 95% CI: 0.71-0.89). Despite its lower sensitivity, the POC test had the potential to provide test results to up to 81% more patients compared to the laboratory-based test. This prototype POC p24 assay was feasible for use in PHCs but demonstrated low sensitivity for HIV detection. POC EID technologies that perform below standard recommendations may still be valuable diagnostic tools in settings with inefficient EID networks.

Relationship between physician-adjudicated adverse events and patient-reported health-related quality of life in a phase II clinical trial (NCT01143402) of patients with metastatic uveal melanoma.

PURPOSE: Clinical trials commonly use physician-adjudicated adverse event (AE) assessment via the common terminology criteria for adverse events (CTCAE) for decision-making. Patient-reported health-related quality of life (HRQoL) data are becoming more frequent in oncology; however, the relationship between physician-adjudicated AE assessment and HRQoL is understudied. METHODS: Data from a phase II trial (clinicaltrials.gov identifier: NCT01143402) where patients with metastatic uveal melanoma were randomized to receive selumetinib, an oral MEK inhibitor, or chemotherapy were analyzed. Patients reported HRQoL at baseline, after 1 month, and end of treatment (n = 118), whereas physicians adjudicated AEs via CTCAE. Mean HRQoL scores were compared between patient randomization arms, as well as between those patients who did/did not receive dose modifications. RESULTS: Ninety-four percent had a CTCAE grade ≥1 for at least one treatment-associated AE, with 18% undergoing dose modification due to toxicity. Mean HRQoL scores did not significantly differ at each of the three time points. Patient and physician-adjudicated reports of nausea were significantly correlated at the start (r = 0.31, p < 0.01) and end of treatment (r = 0.42, p < 0.05). There were no significant correlations between need for dose modification and HRQoL scores. CONCLUSIONS: Despite the high rate of physician-adjudicated AEs and need for dose modifications with selumetinib, patient-reported HRQoL was not impacted by treatment. Since HRQoL did not differ in the subgroup of patients who received dosage reductions due to AEs, patients may be willing to tolerate select AEs without dose modification (if medically appropriate). More research is needed to determine how to best integrate HRQoL data into clinical trial conduct.

Germline genetic variation in JAK2 as a prognostic marker in castration-resistant prostate cancer.

OBJECTIVES: To evaluate the prognostic significance of germline variation in candidate genes in patients with castration-resistant prostate cancer (CRPC). METHODS: Germline DNA was extracted from peripheral blood mononuclear cells of patients with CRPC enrolled in a clinically annotated registry. Fourteen candidate genes implicated in either initiation or progression of prostate cancer were tagged using single nucleotide polymorphisms (SNPs) from HapMap with a minor allele frequency of >5%. The primary endpoint was overall survival (OS), defined as time from development of CRPC to death. Principal component analysis was used for gene levels tests of significance. For SNP-level results the per allele hazard ratios (HRs) and 95% confidence intervals (CIs) under the additive allele model were estimated using Cox regression, adjusted for age at CRPC and Gleason score (GS). RESULTS: A total of 240 patients with CRPC were genotyped (14 genes; 84 SNPs). The median (range) age of the cohort was 69 (43-93) years. The GS distribution was 55% with GS ≥8, 32% with GS = 7 and 13% with GS <7 or unknown. The median (interquartile range) time from castration resistance to death for the cohort was 2.67 (1.6-4.07) years (144 deaths). At the gene level, a single gene, JAK2 was associated with OS (P < 0.01), and 11 of 18 JAK2 SNPs were individually associated with OS after adjustment for age and GS. A multivariate model consisting of age, GS, rs2149556 (HR 0.67; 95% CI 0.38-1.18) and rs4372063 (HR 2.17; 95% CI 1.25-3.76) was constructed to predict survival in patients with CRPC (concordance of 0.69, P < 3.2 × 10-9 ). CONCLUSIONS: Germline variation in the JAK2 gene was associated with survival in patients with CRPC and warrants further validation as a potential prognostic biomarker.

Evaluation of the Whole-Blood Alere Q NAT Point-of-Care RNA Assay for HIV-1 Viral Load Monitoring in a Primary Health Care Setting in Mozambique.

Viral load testing is the WHO-recommended monitoring assay for patients on HIV antiretroviral therapy (ART). Point-of-care (POC) assays may help improve access to viral load testing in resource-limited settings. We compared the performance of the Alere Q NAT POC viral load technology (Alere Technologies, Jena, Germany), measuring total HIV RNA using finger prick capillary whole-blood samples collected in a periurban health center, with that of a laboratory-based plasma RNA test (Roche Cobas Ampliprep/Cobas TaqMan v2) conducted on matched venous blood samples. The whole-blood Alere Q NAT POC assay produced results with a bias of 0.8593 log copy/ml compared to the laboratory-based plasma assay. However, at above 10,000 copies/ml, the bias was 0.07 log copy/ml. Using the WHO-recommended threshold to determine ART failure of 1,000 copies/ml, the sensitivity and specificity of the whole-blood Alere Q NAT POC assay were 96.83% and 47.80%, respectively. A cutoff of 10,000 copies/ml of whole blood with the Alere Q NAT POC assay appears to be a better predictor of ART failure threshold (1,000 copies/ml of plasma), with a sensitivity of 84.0% and specificity of 90.3%. The precision of the whole-blood Alere Q NAT POC assay was comparable to that observed with the laboratory technology (5.4% versus 7.5%) between detectable paired samples. HIV POC viral load testing is feasible at the primary health care level. Further research on the value of whole-blood viral load to monitor antiretroviral therapy is warranted.

Implementation and Operational Research: Expedited Results Delivery Systems Using GPRS Technology Significantly Reduce Early Infant Diagnosis Test Turnaround Times

The objective of this study was to quantify the impact of a new technology to communicate the results of an infant HIV diagnostic test on test turnaround time and to quantify the association between late delivery of test results and patient loss to follow-up. We used data collected during a pilot implementation of Global Package Radio Service (GPRS) printers for communicating results in the early infant diagnosis program in Mozambique from 2008 through 2010. Our dataset comprised 1757 patient records, of which 767 were from before implementation and 990 from after implementation of expedited results delivery system. We used multivariate logistic regression model to determine the association between late result delivery (more than 30 days between sample collection and result delivery to the health facility) and the probability of result collection by the infant's caregiver. We used a sample selection model to determine the association between late result delivery to the facility and further delay in collection of results by the caregiver. The mean test turnaround time reduced from 68.13 to 41.05 days post­expedited results delivery system. Caregivers collected only 665 (37.8%) of the 1757 results. After controlling for confounders, the late delivery of results was associated with a reduction of approximately 18% (0.44 vs. 0.36; P < 0.01) in the probability of results collected by the caregivers (odds ratio = 0.67, P < 0.05). Late delivery of results was also associated with a further average increase in 20.91 days of delay in collection of results (P < 0.01). Early infant diagnosis program managers should further evaluate the cost-effectiveness of operational interventions (eg, GPRS printers) that reduce delays.

Implementation and Operational Research: Expedited Results Delivery Systems Using GPRS Technology Significantly Reduce Early Infant Diagnosis Test Turnaround Times.

The objective of this study was to quantify the impact of a new technology to communicate the results of an infant HIV diagnostic test on test turnaround time and to quantify the association between late delivery of test results and patient loss to follow-up. We used data collected during a pilot implementation of Global Package Radio Service (GPRS) printers for communicating results in the early infant diagnosis program in Mozambique from 2008 through 2010. Our dataset comprised 1757 patient records, of which 767 were from before implementation and 990 from after implementation of expedited results delivery system. We used multivariate logistic regression model to determine the association between late result delivery (more than 30 days between sample collection and result delivery to the health facility) and the probability of result collection by the infant's caregiver. We used a sample selection model to determine the association between late result delivery to the facility and further delay in collection of results by the caregiver. The mean test turnaround time reduced from 68.13 to 41.05 days post-expedited results delivery system. Caregivers collected only 665 (37.8%) of the 1757 results. After controlling for confounders, the late delivery of results was associated with a reduction of approximately 18% (0.44 vs. 0.36; P < 0.01) in the probability of results collected by the caregivers (odds ratio = 0.67, P < 0.05). Late delivery of results was also associated with a further average increase in 20.91 days of delay in collection of results (P < 0.01). Early infant diagnosis program managers should further evaluate the cost-effectiveness of operational interventions (eg, GPRS printers) that reduce delays.