Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 124
Filtrar
1.
Anal Methods ; 14(13): 1361-1370, 2022 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-35297917

RESUMEN

Current HIV antiretroviral therapy (ART) or pre-exposure prophylaxis (PrEP) therapy adherence monitoring relies on either patient self-reported adherence or monitored drug dispensing, which are not reliable. We report a proof-of-concept adherence monitoring assay which directly measures nucleotide reverse transcriptase inhibitor (NRTI) concentration using a reverse transcription isothermal amplification inhibition assay. We measure the concentration of Tenofovir diphosphate (TFV-DP) - an NRTI that functions as a deoxyadenosine triphosphate (dATP) analog and long-term adherence marker for PrEP - by measuring the inhibition of the reverse transcription of an RNA template. The completion or inhibition of reverse transcription is evaluated by recombinase polymerase amplification (RPA), an isothermal nucleic acid amplification assay commonly used for point-of-care diagnostics. We present and validate a model that predicts the amplification probability as a function of dATP and TFV-DP concentrations, nucleotide insertion sites on the RNA template, and RNA template concentration. The model can be used to rationally design and optimize the assay to operate at clinically relevant TFV-DP concentrations. We provide statistical analysis that demonstrates how the assay may be used as a qualitative or semi-quantitative tool for measuring adherence to NRTI drugs and used to support patient compliance. Due to its simple instrumentation and short runtime (<1 hour), this assay has the potential for implementation in low-complexity laboratories or point-of-care settings, which may improve access to ART and PrEP adherence monitoring.


Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Profilaxis Pre-Exposición , Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/diagnóstico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/prevención & control , Humanos , Transcripción Reversa , Tenofovir/uso terapéutico
2.
Drug Alcohol Rev ; 41(2): 365-376, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34487593

RESUMEN

INTRODUCTION: The emergence of low-cost smartphone technology has coincided with major declines in adolescent smoking and other risk behaviours. This study explores the relationship between internet use and smoking in adolescents and investigates whether rising internet use contributed to the decline in smoking between 2012 and 2018. METHODS: Data were drawn from a nationally representative New Zealand survey of students aged 14-15 (N = 11 299), conducted biennially between 2012 and 2018. We used logistic regression to explore the association between internet use and smoking and test whether increasing time on the internet was associated with declining adolescent smoking over the study period. RESULTS: The proportion of students spending 5+ hours per day online increased from 15% to 35%. Heavy internet use was not a protective factor for smoking at the individual level. In 2016/2018, some types of past week internet use were associated with decreased risk of smoking (e.g. doing schoolwork, finding out about news), some were associated with increased risk (e.g. social media use) and others appeared to have no association with smoking (e.g. gaming, online shopping). The relative risk of smoking was lower in 2018 relative to 2012 (relative risk 0.68, 95% confidence interval 0.51, 0.90, after adjustment for demographic factors). Adding internet use to the model did not help to account for smoking decline. DISCUSSION AND CONCLUSIONS: We found no evidence that increasing time spent on the internet during the 2012-2018 period (during which smartphones became ubiquitous) contributed to the decline in adolescent smoking.


Asunto(s)
Uso de Internet , Teléfono Inteligente , Adolescente , Humanos , Internet , Fumar/epidemiología , Estudiantes , Fumar Tabaco
3.
BMJ Glob Health ; 6(12)2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34887304

RESUMEN

INTRODUCTION: Acute rheumatic fever (ARF) is usually considered a consequence of group A streptococcus (GAS) pharyngitis, with GAS skin infections not considered a major trigger. The aim was to quantify the risk of ARF following a GAS-positive skin or throat swab. METHODS: This retrospective analysis used pre-existing administrative data. Throat and skin swab data (1 866 981 swabs) from the Auckland region, New Zealand and antibiotic dispensing data were used (2010-2017). Incident ARF cases were identified using hospitalisation data (2010-2018). The risk ratio (RR) of ARF following swab collection was estimated across selected features and timeframes. Antibiotic dispensing data were linked to investigate whether this altered ARF risk following GAS detection. RESULTS: ARF risk increased following GAS detection in a throat or skin swab. Maori and Pacific Peoples had the highest ARF risk 8-90 days following a GAS-positive throat or skin swab, compared with a GAS-negative swab. During this period, the RR for Maori and Pacific Peoples following a GAS-positive throat swab was 4.8 (95% CI 3.6 to 6.4) and following a GAS-positive skin swab, the RR was 5.1 (95% CI 1.8 to 15.0). Antibiotic dispensing was not associated with a reduction in ARF risk following GAS detection in a throat swab (antibiotics not dispensed (RR: 4.1, 95% CI 2.7 to 6.2), antibiotics dispensed (RR: 4.3, 95% CI 2.5 to 7.4) or in a skin swab (antibiotics not dispensed (RR: 3.5, 95% CI 0.9 to 13.9), antibiotics dispensed (RR: 2.0, 95% CI 0.3 to 12.1). CONCLUSIONS: A GAS-positive throat or skin swab is strongly associated with subsequent ARF, particularly for Maori and Pacific Peoples. This study provides the first population-level evidence that GAS skin infection can trigger ARF.


Asunto(s)
Faringitis , Fiebre Reumática , Infecciones Estreptocócicas , Humanos , Nueva Zelanda/epidemiología , Faringitis/diagnóstico , Faringitis/epidemiología , Faringe , Estudios Retrospectivos , Fiebre Reumática/diagnóstico , Fiebre Reumática/epidemiología , Infecciones Estreptocócicas/diagnóstico , Infecciones Estreptocócicas/tratamiento farmacológico , Infecciones Estreptocócicas/epidemiología , Streptococcus pyogenes
5.
Cutis ; 108(1): E25-E27, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34397368

Asunto(s)
Neoplasias , Nalgas , Humanos
6.
Emerg Infect Dis ; 27(7)2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34153221

RESUMEN

We investigated outcomes for patients born after 1983 and hospitalized with initial acute rheumatic fever (ARF) in New Zealand during 1989-2012. We linked ARF progression outcome data (recurrent hospitalization for ARF, hospitalization for rheumatic heart disease [RHD], and death from circulatory causes) for 1989-2015. Retrospective analysis identified initial RHD patients <40 years of age who were hospitalized during 2010-2015 and previously hospitalized for ARF. Most (86.4%) of the 2,182 initial ARF patients did not experience disease progression by the end of 2015. Progression probability after 26.8 years of theoretical follow-up was 24.0%; probability of death, 1.0%. Progression was more rapid and ≈2 times more likely for indigenous Maori or Pacific Islander patients. Of 435 initial RHD patients, 82.2% had not been previously hospitalized for ARF. This young cohort demonstrated low mortality rates but considerable illness, especially among underserved populations. A national patient register could help monitor, prevent, and reduce ARF progression.


Asunto(s)
Fiebre Reumática , Cardiopatía Reumática , Progresión de la Enfermedad , Humanos , Nueva Zelanda , Estudios Retrospectivos
7.
Clin Trials ; 18(5): 622-629, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34154439

RESUMEN

INTRODUCTION: Clostridiodes difficile infection is the leading cause of infectious diarrhea in the United States, with substantial morbidity and mortality. Recurrent infection is especially challenging, with each recurrence increasing the likelihood of a successive recurrence, leading to cycles of prolonged symptoms, frequent antimicrobial use, and decreased quality of life. Fecal microbiota transplantation to prevent recurrent infection is a promising intervention with a large effect size in observational studies, but with conflicting results from randomized controlled trials. We are conducting a Veterans Affairs-wide randomized controlled trial utilizing centralized case identification, with enrollment and fecal microbiota transplant administration occurring at the participant's home. This type of trial design significantly improves trial efficiency, greatly decreases trial cost, increases consistency of trial administration, and most importantly makes nationwide clinical trials in less-common diseases possible. METHODS: This is a randomized comparison of capsule-delivered fecal microbiota transplant for the prevention of recurrent Clostridiodes difficile infection, administered after successful initial treatment of recurrent C. difficile infection with standard therapy. The primary endpoint is the incidence of recurrent C. difficile infection or death. Cases are identified by searching the Veterans Affairs Corporate Data Warehouse, with central study coordinators then reaching out to potential participants. Individuals meeting inclusion criteria and interested in participation are scheduled for in-home consent, randomization, and capsule administration, followed by telephone follow-up for 6 months. To mitigate risks of COVID-19, enrollment via video visits has been implemented. RESULTS: A total of 102 participants have been enrolled through January 2021. Centralized case identification and in-home enrollment has facilitated enrollment from 34 unique states, with 38% being from rural or highly rural areas. DISCUSSION: Centralized case identification and in-home enrollment is a feasible and innovative method of conducting randomized controlled trials in the Veterans Affairs system, improving access to clinical research for populations who may have difficulty engaging with the traditional model of clinical trials where enrollment is based at large hospitals in major metropolitan areas.


Asunto(s)
Antibacterianos , Clostridioides difficile , Infecciones por Clostridium/terapia , Trasplante de Microbiota Fecal , Antibacterianos/uso terapéutico , COVID-19 , Humanos , Microbiota , Calidad de Vida , Recurrencia , Resultado del Tratamiento
8.
Eur J Endocrinol ; 185(2): 333-342, 2021 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-34128826

RESUMEN

OBJECTIVE: GC/DBP effects on response to vitamin D supplementation have not been well-studied. Thus we assessed free and total 25-OHD after vitamin D treatment across the six common GC haplotypes. DESIGN: This double-blind, randomized study compared two vitamin D3 doses in healthy, urban-dwelling 6-month to 10-year-old children at-risk for vitamin D deficiency. Randomization was stratified by GC haplotype. METHODS: Children were randomized to receive 2800 or 7000 International Units of vitamin D3 weekly. 25-OHD and 1,25(OH)2D were sampled at baseline and after 1-6 months of supplementation. RESULTS AND CONCLUSIONS: One hundred ninety-two of 225 enrolled subjects completed the study. After one month, total 25-OHD increased with both doses and were higher with 7000 IU/week (85.5 ± 22.8 nmol/L) compared to 2800 IU/week (76.8 ± 18.0 nmol/L), despite equivalent baseline levels. No further significant increase occurred at 6 months (89.8 ± 35.5 and 74.3 ± 18.3 nmol/L, respectively). Free 25-OHD similarly changed. 25-OHD differed among GC groups at baseline. Although no significant effects of individual GC haplotypes on incremental changes were evident, a trend toward an effect of combined 'at risk' GC alleles on response was evident (P = 0.06). Total 1,25(OH)2D showed modest increases, moreso with the larger dose. In urban-dwelling children at-risk for vitamin D deficiency, 1 month of vitamin D3 2800 IU/week increased 25-OHD across all GC haplotype groups, and somewhat enhanced with 7000 IU/week with no further significant increases after 6 months of supplementation. Free 25-OHD measures offer no monitoring advantage over total 25-OHD.


Asunto(s)
25-Hidroxivitamina D 2/sangre , Colecalciferol/administración & dosificación , Colecalciferol/sangre , Haplotipos/fisiología , Deficiencia de Vitamina D/sangre , Deficiencia de Vitamina D/dietoterapia , Niño , Preescolar , Suplementos Dietéticos , Método Doble Ciego , Femenino , Humanos , Lactante , Masculino , Estudios Prospectivos , Deficiencia de Vitamina D/diagnóstico
9.
Analyst ; 146(9): 2851-2861, 2021 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-33949378

RESUMEN

The number of people living with HIV continues to increase with the current total near 38 million, of which about 26 million are receiving antiretroviral therapy (ART). These treatment regimens are highly effective when properly managed, requiring routine viral load monitoring to assess successful viral suppression. Efforts to expand access by decentralizing HIV nucleic acid testing in low- and middle-income countries (LMICs) has been hampered by the cost and complexity of current tests. Sample preparation of blood samples has traditionally relied on cumbersome RNA extraction methods, and it continues to be a key bottleneck for developing low-cost POC nucleic acid tests. We present a microfluidic paper-based analytical device (µPAD) for extracting RNA and detecting HIV in serum, leveraging low-cost materials, simple buffers, and an electric field. We detect HIV virions and MS2 bacteriophage internal control in human serum using a novel lysis and RNase inactivation method, paper-based isotachophoresis (ITP) for RNA extraction, and duplexed reverse transcription recombinase polymerase amplification (RT-RPA) for nucleic acid amplification. We design a specialized ITP system to extract and concentrate RNA, while excluding harsh reagents used for lysis and RNase inactivation. We found the ITP µPAD can extract and purify 5000 HIV RNA copies per mL of serum. We then demonstrate detection of HIV virions and MS2 bacteriophage in human serum within 45-minutes.


Asunto(s)
Infecciones por VIH , Isotacoforesis , Infecciones por VIH/diagnóstico , Humanos , Técnicas de Amplificación de Ácido Nucleico , ARN/genética , ARN Viral/genética , Recombinasas/genética , Recombinasas/metabolismo , Transcripción Reversa , Sensibilidad y Especificidad
10.
Analyst ; 146(8): 2449-2462, 2021 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-33899053

RESUMEN

The COVID-19 pandemic has put the spotlight on the urgent need for integrated nucleic acid tests (NATs) for infectious diseases, especially those that can be used near patient ("point-of-care", POC), with rapid results and low cost, but without sacrificing sensitivity or specificity of gold standard PCR tests. In the US, the Clinical Laboratory Improvement Amendments Certificate of Waiver (CLIA-waiver) is mandated by the Food and Drug Administration (FDA) and designated to any laboratory testing with high simplicity and low risk for error, suitable for application in the POC. Since the first issuance of CLIA-waiver to Abbot's ID NOW Influenza A&B in 2015, many more NAT systems have been developed, received the CLIA-waiver in the US or World Health Organization (WHO)'s pre-qualification, and deployed to the front line of infectious disease detection. This review highlights the regulatory process for FDA and WHO in evaluating these NATs and the technology innovation of existing CLIA-waived systems. Understanding the technical advancement and challenges, unmet needs, and the trends of commercialization facilitated through the regulatory processes will help pave the foundation for future development and technology transfer from research to the market place.


Asunto(s)
COVID-19 , Enfermedades Transmisibles , Ácidos Nucleicos , Enfermedades Transmisibles/diagnóstico , Humanos , Ácidos Nucleicos/genética , Pandemias , Sistemas de Atención de Punto , Pruebas en el Punto de Atención , SARS-CoV-2
12.
Artículo en Inglés | MEDLINE | ID: mdl-33401049

RESUMEN

Nucleic acid amplification tests (NAATs) are a crucial diagnostic and monitoring tool for infectious diseases. A key procedural step for NAATs is sample preparation: separating and purifying target nucleic acids from crude biological samples prior to nucleic acid amplification and detection. Traditionally, sample preparation has been performed with liquid- or solid-phase extraction, both of which require multiple trained user steps and significant laboratory equipment. The challenges associated with sample preparation have limited the dissemination of NAAT point-of-care diagnostics in low resource environments, including low- and middle-income countries. We report on a paper-based device for purification of nucleic acids from whole blood using isotachophoresis (ITP) for point-of-care NAATs. We show successful extraction and purification of target nucleic acids from large volumes (33 µL) of whole human blood samples with no moving parts and few user steps. Our device utilizes paper-based buffer reservoirs to fully contain the liquid ITP buffers and does not require complex filling procedures, instead relying on the natural wicking of integrated paper membranes. We perform on-device blood fractionation via filtration to remove leukocytes and erythrocytes from our sample, followed by integrated on-paper proteolytic digestion of endogenous plasma proteins to allow for successful isotachophoretic extraction. Paper-based isotachophoresis purifies and concentrates target nucleic acids that are added directly to recombinase polymerase amplification (RPA) reactions. We show consistent amplification of input copy concentrations of as low as 3 × 103 copies nucleic acid per mL input blood with extraction and purification taking only 30 min. By employing a paper architecture, we are able to incorporate these processes in a single, robust, low-cost design, enabling the direct processing of large volumes of blood, with the only intermediate user steps being the removal and addition of tape. Our device represents a step towards a simple, fully integrated sample preparation system for nucleic acid amplification tests at the point-of-care.


Asunto(s)
Isotacoforesis/instrumentación , Dispositivos Laboratorio en un Chip , Técnicas Analíticas Microfluídicas/instrumentación , Ácidos Nucleicos , Electroforesis en Gel de Poliacrilamida , Diseño de Equipo , Humanos , Isotacoforesis/métodos , Técnicas de Amplificación de Ácido Nucleico , Ácidos Nucleicos/sangre , Ácidos Nucleicos/química , Ácidos Nucleicos/aislamiento & purificación , Papel
13.
Emerg Infect Dis ; 27(1)2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33350929

RESUMEN

We describe trends in acute rheumatic fever (ARF), rheumatic heart disease (RHD), and RHD deaths among population groups in New Zealand. We analyzed initial primary ARF and RHD hospitalizations during 2000-2018 and RHD mortality rates during 2000-2016. We found elevated rates of initial ARF hospitalizations for persons of Maori (adjusted rate ratio [aRR] 11.8, 95% CI 10.0-14.0) and Pacific Islander (aRR 23.6, 95% CI 19.9-27.9) ethnicity compared with persons of European/other ethnicity. We also noted higher rates of initial RHD hospitalization for Maori (aRR 3.2, 95% CI 2.9-3.5) and Pacific Islander (aRR 4.6, 95% CI 4.2-5.1) groups and RHD deaths among these groups (Maori aRR 12.3, 95% CI 10.3-14.6, and Pacific Islanders aRR 11.2, 95% CI 9.1-13.8). Rates also were higher in socioeconomically disadvantaged neighborhoods. To curb high rates of ARF and RHD, New Zealand must address increasing social and ethnic inequalities.


Asunto(s)
Fiebre Reumática , Cardiopatía Reumática , Humanos , Nueva Zelanda/epidemiología , Fiebre Reumática/epidemiología , Cardiopatía Reumática/epidemiología
14.
J Prim Health Care ; 12(3): 199-206, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32988441

RESUMEN

INTRODUCTION Mass masking is emerging as a key non-pharmaceutical intervention for reducing community spread of COVID-19. However, although hand washing, social distancing and bubble living have been widely adopted by the 'team of 5 million', mass masking has not been socialised to the general population. AIM To identify factors associated with face masking in New Zealand during COVID-19 Alert Level 4 lockdown to inform strategies to socialise and support mass masking. METHODS A quantitative online survey conducted in New Zealand during April 2020 invited residents aged ≥18 years to complete a questionnaire. Questions about face masking were included in the survey. The sample was drawn from a commissioned research panel survey, with boosted sampling for Maori and Pacific participants. Responses were weighted to reflect the New Zealand population for all analyses. RESULTS A total of 1015 individuals participated. Self-reported beliefs were strongly related to behaviours, with respondents viewing face masking measures as 'somewhat' or 'very' effective in preventing them from contracting COVID-19 more likely to report having worn a face mask than respondents who viewed them as 'not at all' effective. The strongest barriers to face mask use included beliefs that there was a mask shortage and that the needs of others were greater than their own. DISCUSSION Highlighting the efficacy of and dispelling myths about the relative efficacy of mask types and socialising people to the purpose of mass masking will contribute to community protective actions of mask wearing in the New Zealand response to COVID-19.


Asunto(s)
COVID-19/prevención & control , Infecciones por Coronavirus/prevención & control , Conocimientos, Actitudes y Práctica en Salud , Máscaras , Pandemias/prevención & control , Neumonía Viral/prevención & control , Adulto , Betacoronavirus , COVID-19/epidemiología , Infecciones por Coronavirus/epidemiología , Femenino , Humanos , Masculino , Nueva Zelanda/epidemiología , Distanciamiento Físico , Neumonía Viral/epidemiología , SARS-CoV-2 , Autoinforme , Encuestas y Cuestionarios
15.
Ear Hear ; 42(2): 290-300, 2020 08 19.
Artículo en Inglés | MEDLINE | ID: mdl-32826512

RESUMEN

OBJECTIVES: To evaluate (1) the accuracy of the International Organization for Standardization (ISO) standard ISO 1999 [(2013), International Organization for Standardization, Geneva, Switzerland] predictions of noise-induced permanent threshold shift (NIPTS) in workers exposed to various types of high-intensity noise levels, and (2) the role of the kurtosis metric in assessing noise-induced hearing loss (NIHL). DESIGN: Audiometric and shift-long noise exposure data were acquired from a population (N = 2,333) of screened workers from 34 industries in China. The entire cohort was exclusively divided into subgroups based on four noise exposure levels (85 ≤ LAeq.8h < 88, 88 ≤ LAeq.8h < 91, 91 ≤ LAeq.8h < 94, and 94 ≤ LAeq.8h ≤ 100 dBA), two exposure durations (D ≤ 10 years and D > 10 years), and four kurtosis categories (Gaussian, low-, medium-, and high-kurtosis). Predicted NIPTS was calculated using the ISO 1999 model for each participant and the actual measured NIPTS was corrected for age and sex also using ISO 1999. The prediction accuracy of the ISO 1999 model was evaluated by comparing the NIPTS predicted by ISO 1999 with the actual NIPTS. The relation between kurtosis and NIPTS was also investigated. RESULTS: Overall, using the average NIPTS value across the four audiometric test frequencies (2, 3, 4, and 6 kHz), the ISO 1999 predictions significantly (p < 0.001) underestimated the NIPTS by 7.5 dB on average in participants exposed to Gaussian noise and by 13.6 dB on average in participants exposed to non-Gaussian noise with high kurtosis. The extent of the underestimation of NIPTS by ISO 1999 increased with an increase in noise kurtosis value. For a fixed range of noise exposure level and duration, the actual measured NIPTS increased as the kurtosis of the noise increased. The noise with kurtosis greater than 75 produced the highest NIPTS. CONCLUSIONS: The applicability of the ISO 1999 prediction model to different types of noise exposures needs to be carefully reexamined. A better understanding of the role of the kurtosis metric in NIHL may lead to its incorporation into a new and more accurate model of hearing loss due to noise exposure.


Asunto(s)
Pérdida Auditiva Provocada por Ruido , Ruido en el Ambiente de Trabajo , Umbral Auditivo , Benchmarking , China , Audición , Pérdida Auditiva Provocada por Ruido/diagnóstico , Pérdida Auditiva Provocada por Ruido/etiología , Humanos , Ruido en el Ambiente de Trabajo/efectos adversos
16.
Ophthalmology ; 127(12): 1627-1641, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32544560

RESUMEN

PURPOSE: To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of 10- and 15-µg bimatoprost implant in subjects with open-angle glaucoma (OAG) and ocular hypertension (OHT) after initial and repeated administrations. DESIGN: Randomized, 20-month, multicenter, subject- and efficacy evaluator-masked, parallel-group, phase 3 clinical study. PARTICIPANTS: Adults with OAG or OHT in each eye, open iridocorneal angle inferiorly in the study eye, and study eye baseline IOP (hour 0; 8 am) of 22-32 mmHg after washout. METHODS: Study eyes received bimatoprost implant 10 µg (n = 198) or 15 µg (n = 198) on day 1 with readministration at weeks 16 and 32, or twice-daily topical timolol maleate 0.5% (n = 198). Intraocular pressure was measured at hours 0 and 2 at each visit. MAIN OUTCOME MEASURES: Primary end points were IOP and change from baseline IOP through week 12. Safety measures included treatment-emergent adverse events (TEAEs) and corneal endothelial cell density (CECD). RESULTS: Both dose strengths of bimatoprost implant were noninferior to timolol in IOP lowering after each administration. Mean diurnal IOP was 24.0, 24.2, and 23.9 mmHg at baseline and from 16.5-17.2, 16.5-17.0, and 17.1-17.5 mmHg through week 12 in the 10-µg implant, 15-µg implant, and timolol groups, respectively. The incidence of corneal and inflammatory TEAEs of interest (e.g., corneal endothelial cell loss, iritis) was higher with bimatoprost implant than timolol and highest with the 15-µg dose strength. Incidence of corneal TEAEs increased after repeated treatment; with 3 administrations at fixed 16-week intervals, incidence of ≥20% CECD loss was 10.2% (10-µg implant) and 21.8% (15-µg implant). Mean best-corrected visual acuity (BCVA) was stable; 3 implant-treated subjects with corneal TEAEs had >2-line BCVA loss at their last visit. CONCLUSIONS: Both dose strengths of bimatoprost implant met the primary end point of noninferiority to timolol through week 12. One year after 3 administrations, IOP was controlled in most subjects without additional treatment. The risk-benefit assessment favored the 10-µg implant over the 15-µg implant. Ongoing studies are evaluating other administration regimens to reduce the potential for CECD loss. The bimatoprost implant has potential to improve adherence and reduce treatment burden in glaucoma.


Asunto(s)
Antihipertensivos/administración & dosificación , Bimatoprost/administración & dosificación , Glaucoma de Ángulo Abierto/tratamiento farmacológico , Presión Intraocular/efectos de los fármacos , Adulto , Anciano , Anciano de 80 o más Años , Método Doble Ciego , Implantes de Medicamentos , Femenino , Glaucoma de Ángulo Abierto/diagnóstico , Glaucoma de Ángulo Abierto/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Hipertensión Ocular/diagnóstico , Hipertensión Ocular/tratamiento farmacológico , Hipertensión Ocular/fisiopatología , Timolol/uso terapéutico , Tonometría Ocular , Cuerpo Vítreo/efectos de los fármacos , Adulto Joven
17.
ACS Sens ; 5(4): 952-959, 2020 04 24.
Artículo en Inglés | MEDLINE | ID: mdl-32248685

RESUMEN

Poor adherence to pre-exposure prophylaxis (PrEP) and antiretroviral therapy (ART) can lead to human immunodeficiency virus (HIV) acquisition and emergence of drug-resistant infections, respectively. Measurement of antiviral drug levels provides objective adherence information that may help prevent adverse health outcomes. Gold-standard drug-level measurement by liquid chromatography/mass spectrometry is centralized, heavily instrumented, and expensive and is thus unsuitable and unavailable for routine use in clinical settings. We developed the REverSe TRanscrIptase Chain Termination (RESTRICT) assay as a rapid and accessible measurement of drug levels indicative of long-term adherence to PrEP and ART. The assay uses designer single-stranded DNA templates and intercalating fluorescent dyes to measure complementary DNA (cDNA) formation by reverse transcriptase in the presence of nucleotide reverse transcriptase inhibitor drugs. We optimized the RESTRICT assay using aqueous solutions of tenofovir diphosphate (TFV-DP), a metabolite that indicates long-term adherence to ART and PrEP, at concentrations over 2 orders of magnitude above and below the clinically relevant range. We used dilution in water as a simple sample preparation strategy to detect TFV-DP spiked into whole blood and accurately distinguished TFV-DP drug levels corresponding to low and high PrEP adherences. The RESTRICT assay is a fast and accessible test that could be useful for patients and clinicians to measure and improve ART and PrEP adherence.


Asunto(s)
Antirretrovirales/uso terapéutico , Pruebas de Enzimas/métodos , Infecciones por VIH/tratamiento farmacológico , Humanos
18.
J Clin Endocrinol Metab ; 105(4)2020 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-31774125

RESUMEN

CONTEXT: Vitamin D status is usually assessed by serum total 25-hydroxyvitamin D (t25-OHD). Whether free 25-hydroxyvitamin D measures better correlate with various clinical outcomes is unclear. OBJECTIVE: To identify correlations between t25-OHD, calculated and direct measures of free 25-OHD, and to identify associations of these measures with other outcomes in children, across the 6 common GC haplotypes. DESIGN: Healthy urban-dwelling children underwent measurement of relevant variables. SETTING: Academic medical center. PARTICIPANTS: The study included 203 healthy, urban-dwelling children, aged 6 months to 10 years, predominantly of Hispanic background and representative of all common GC haplotypes. INTERVENTION: None. MAIN OUTCOME MEASURES: Total and free 25-OHD and 1,25(OH)2D, calcium, phosphate, parathyroid hormone (PTH), glucose, insulin, aldosterone, and renin. RESULTS: Mean t25-OHD [26.3 ±â€…6.7ng/ml; 65.8 ±â€…16.8nmol/L] were lowest in the GC2 genotype. Mean t1,25(OH)2D [57.6 ±â€…16.5pg/ml; 143.9 ±â€…41.3pmol/L], were lowest in GC1f/1f, GC1f/2, and GC2/2 groups. T25-OHD correlated strongly with calculated free 25-OHD (cf25-OHD) (r = 0.89) and moderately with directly measured free 25-OHD (dmf25-OHD) (r = 0.69). Cf25-OHD correlated with dmf25-OHD (r = 0.69) (P < 0.001 for all). t25-OHD inversely correlated with body mass index (BMI) (r=-0.191; P = 0.006), skin reflectometry, and systolic blood pressure. T25-OHD correlated with fasting insulin and the homeostatic model assessment for insulin resistance (HOMA-IR), however significance for these correlations was not evident after adjustment for BMI. PTH inversely correlated with all measures of 25-OHD, but most strongly with t25-OHD. CONCLUSIONS: Measures of circulating total and free 25-OHD are comparable measures of vitamin D status in heathy children. Correlations are similar with other outcome variables, however t25-OHD remains the strongest correlate of circulating PTH and other variables. These data argue against routine refinement of the t25-OHD measure using currently available assessments of free 25-OHD. CLINICAL TRIAL INFORMATION: Clinicaltrials.gov registration no: NCT01050387 (January 15, 2010).


Asunto(s)
Biomarcadores/sangre , Deficiencia de Vitamina D/diagnóstico , Vitamina D/análogos & derivados , Aldosterona/sangre , Glucemia/análisis , Calcio/sangre , Niño , Preescolar , Femenino , Hemoglobina A Glucada/análisis , Humanos , Lactante , Insulina/sangre , Masculino , Osteocalcina/sangre , Hormona Paratiroidea/sangre , Fosfatos/sangre , Pronóstico , Vitamina D/sangre , Deficiencia de Vitamina D/sangre
19.
Anal Methods ; 12(8): 1085-1093, 2020 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-35154421

RESUMEN

Estimated to be the most common non-viral sexually transmitted infection globally, Trichomonas vaginalis (TV) can lead to pelvic inflammatory disease, pregnancy complications, and increased risk of acquiring and transmitting HIV. Once diagnosed, TV infection can be treated with oral antibiotics; however, infected individuals are often asymptomatic and do not seek treatment. The WHO and others have identified a need for point-of-care tests to expand access to TV testing and screening; ideal test characteristics include high sensitivity and specificity and the ability to use urine as a sample type, rather than invasively collected swab samples. Here, we report on a proof-of-concept prototype for rapid, electrostatic enrichment of DNA from urine samples and demonstrate the use of large volumes of urine to increase sensitivity of downstream nucleic acid amplification testing. We developed an internally controlled thermophilic helicase-dependent amplification (tHDA) assay with lateral flow immunoassay readout and demonstrate that this tHDA assay can be performed directly on our DNA capture filter. We validated our method using clinical urine samples with qPCR-quantified TV loads. Using 62 clinical urine samples and a simple sample processing device, our tHDA assay displayed 96.6% sensitivity and 100% specificity. Our analytical limit of detection was found to be approximately 7 genomic equivalents of TV DNA per mL of sample when 1 mL of sample was tested, comparable to existing isothermal tests for TV. Using large-volume simulated samples (40 mL of buffered urine with spiked-in TV DNA), we also demonstrated that sensitivity could be improved 28-fold to 0.25 genomic equivalents of TV DNA per mL, with a sample processing time of only 2 minutes.

20.
Front Neurol ; 10: 1004, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31620075

RESUMEN

Objective: To investigate associations between peripheral innate immune activation and frontotemporal lobar degeneration (FTLD) in progranulin gene (GRN) haploinsufficiency. Methods: In this cross-sectional study, ELISA was used to measure six markers of innate immunity (sCD163, CCL18, LBP, sCD14, IL-18, and CRP) in plasma from 30 GRN mutation carriers (17 asymptomatic, 13 symptomatic) and 29 controls. Voxel based morphometry was used to model associations between marker levels and brain atrophy in mutation carriers relative to controls. Linear regression was used to model relationships between plasma marker levels with mean frontal white matter integrity [fractional anisotropy (FA)] and the FTLD modified Clinical Dementia Rating Scale sum of boxes score (FTLD-CDR SB). Results: Plasma sCD163 was higher in symptomatic GRN carriers [mean 321 ng/ml (SD 125)] compared to controls [mean 248 ng/ml (SD 58); p < 0.05]. Plasma CCL18 was higher in symptomatic GRN carriers [mean 56.9 pg/ml (SD 19)] compared to controls [mean 40.5 pg/ml (SD 14); p < 0.05]. Elevation of plasma LBP was associated with white matter atrophy in the right frontal pole and left inferior frontal gyrus (p FWE corrected <0.05) in all mutation carriers relative to controls. Plasma LBP levels inversely correlated with bilateral frontal white matter FA (R2 = 0.59, p = 0.009) in mutation carriers. Elevation in plasma was positively correlated with CDR-FTLD SB (b = 2.27 CDR units/µg LBP/ml plasma, R2 = 0.76, p = 0.003) in symptomatic carriers. Conclusion: FTLD-GRN is associated with elevations in peripheral biomarkers of macrophage-mediated innate immunity, including sCD163 and CCL18. Clinical disease severity and white matter integrity are correlated with blood LBP, suggesting a role for peripheral immune activation in FTLD-GRN.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...