Specialty Care Referral for Underrepresented Minorities Living with HIV in the United States: Experiences, Barriers, and Facilitators.

The increased incidence of chronic diseases among people with HIV (PWH) is poised to increase the need for specialty care outside of HIV treatment settings. To reduce outcome disparities for HIV-associated comorbidities in the United States, it is critical to optimize access to and the quality of specialty care for underrepresented racial and ethnic minority (URM) individuals with HIV. We explored the experiences of URM individuals with HIV and other comorbidities in the specialty care setting during their initial and follow-up appointments. We conducted qualitative interviews with participants at three large academic medical centers in the United States with comprehensive health care delivery systems between November 2019 and March 2020. The data were analyzed using applied thematic analysis. A total of 27 URM individuals with HIV were interviewed. The majority were Black or African American and were referred to cardiology specialty care. Most of the participants had positive experiences in the specialty care setting. Facilitators of the referral process included their motivation to stay healthy, referral assistance from HIV providers, access to reliable transportation, and proximity to the specialty care health center. Few participants faced individual, interpersonal, and structural barriers, including the perception of individual and facility stigma toward PWH, a lack of transportation, and a lack of rapport with providers. Future case studies are needed for those URM individuals with HIV who face barriers and negative experiences. Interventions that involve PWH and health care providers in specialty care settings with a focus on individual- and structural-level stigma can support the optimal use of specialty care.

Von Willebrand Factor (VWF) multiplex activity assay differentiation of type 1 von Willebrand Disease (VWD) and variant VWD.

INTRODUCTION: VWD diagnosis is challenging requiring multiple VWF activity tests using many individual assays. We have developed an ELISA-based VWF Multiplex Activity Assay (VWF-MAA) to address this concern; however, the ability of the VWF-MAA to discriminate between type 1 VWD, variant VWD, and normal subjects has not been evaluated. AIM: To evaluate the VWF-MAA and its ability to differentiate between type 1 VWD, variant VWD and normal subjects in individuals undergoing an initial laboratory evaluation for bleeding. METHODS: A total of 177 plasma samples from the Zimmerman Program: Comparative Effectiveness in the Diagnosis of VWD were evaluated from 11 centres across the US and Canada. The VWF-MAA was compared to Versiti Blood Research Institute (VBRI) and Local Center (LC) assigned VWD diagnosis. RESULTS: Overall, 129/177 (72.9%) were correctly assigned as normal (non-VWD), type 1, or variant VWD compared to the VBRI assigned diagnosis. VWF-MAA assigned non-VWD accurately in 29/57 (50.9%) samples, and type 1 VWD accurately in 93/110 (84.6%) samples. Considering LC diagnosis where there was agreement with VWF-MAA and not VBRI diagnosis, type 1 VWD was accurate in 105/110 (95.5%) samples. Bland-Altman analysis demonstrated good correlation between laboratory methods. VWD, types 2A, 2B, 1C VWD were also assigned by the VWF-MAA. CONCLUSIONS: We demonstrate that the VWF-MAA has utility in differentiating type 1 VWD, variant VWD and normal subjects in individuals undergoing an initial laboratory evaluation for bleeding.

Feasibility of Implementation of a Mobile Digital Personal Health Record to Coordinate Care for Children and Youth With Special Health Care Needs in Primary Care: Protocol for a Mixed Methods Study.

BACKGROUND: Electronic health record (EHR)-integrated digital personal health records (PHRs) via Fast Healthcare Interoperability Resources (FHIR) are promising digital health tools to support care coordination (CC) for children and youth with special health care needs but remain widely unadopted; as their adoption grows, mixed methods and implementation research could guide real-world implementation and evaluation. OBJECTIVE: This study (1) evaluates the feasibility of an FHIR-enabled digital PHR app for CC for children and youth with special health care needs, (2) characterizes determinants of implementation, and (3) explores associations between adoption and patient- or family-reported outcomes. METHODS: This nonrandomized, single-arm, prospective feasibility trial will test an FHIR-enabled digital PHR app's use among families of children and youth with special health care needs in primary care settings. Key app features are FHIR-enabled access to structured data from the child's medical record, families' abilities to longitudinally track patient- or family-centered care goals, and sharing progress toward care goals with the child's primary care provider via a clinician dashboard. We shall enroll 40 parents or caregivers of children and youth with special health care needs to use the app for 6 months. Inclusion criteria for children and youth with special health care needs are age 0-16 years; primary care at a participating site; complex needs benefiting from CC; high hospitalization risk in the next 6 months; English speaking; having requisite technology at home (internet access, Apple iOS mobile device); and an active web-based EHR patient portal account to which a parent or caregiver has full proxy access. Digital prescriptions will be used to disseminate study recruitment materials directly to eligible participants via their existing EHR patient portal accounts. We will apply an intervention mixed methods design to link quantitative and qualitative (semistructured interviews and family engagement panels with parents of children and youth with special health care needs) data and characterize implementation determinants. Two CC frameworks (Pediatric Care Coordination Framework; Patient-Centered Medical Home) and 2 evaluation frameworks (Consolidated Framework for Implementation Research; Technology Acceptance Model) provide theoretical foundations for this study. RESULTS: Participant recruitment began in fall 2022, before which we identified >300 potentially eligible patients in EHR data. A family engagement panel in fall 2021 generated formative feedback from family partners. Integrated analysis of pretrial quantitative and qualitative data informed family-centered enhancements to study procedures. CONCLUSIONS: Our findings will inform how to integrate an FHIR-enabled digital PHR app for children and youth with special health care needs into clinical care. Mixed methods and implementation research will help strengthen implementation in diverse clinical settings. The study is positioned to advance knowledge of how to use digital health innovations for improving care and outcomes for children and youth with special health care needs and their families. TRIAL REGISTRATION: ClinicalTrials.gov NCT05513235; https://clinicaltrials.gov/study/NCT05513235. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/46847.

Digital Medicine System in Veterans With Severe Mental Illness: Feasibility and Acceptability Study.

BACKGROUND: Suboptimal medication adherence is a significant problem for patients with serious mental illness. Measuring medication adherence through subjective and objective measures can be challenging, time-consuming, and inaccurate. OBJECTIVE: The primary purpose of this feasibility and acceptability study was to evaluate the impact of a digital medicine system (DMS) among Veterans (patients) with serious mental illness as compared with treatment as usual (TAU) on medication adherence. METHODS: This open-label, 2-site, provider-randomized trial assessed aripiprazole refill adherence in Veterans with schizophrenia, schizoaffective disorder, bipolar disorder, or major depressive disorder. We randomized 26 providers such that their patients either received TAU or DMS for a period of 90 days. Semistructured interviews with patients and providers were used to examine the feasibility and acceptability of using the DMS. RESULTS: We enrolled 46 patients across 2 Veterans Health Administration sites: 21 (46%) in DMS and 25 (54%) in TAU. There was no difference in the proportion of days covered by medication refill over 3 and 6 months (0.82, SD 0.24 and 0.75, SD 0.26 in DMS vs 0.86, SD 0.19 and 0.82, SD 0.21 in TAU, respectively). The DMS arm had 0.85 (SD 0.20) proportion of days covered during the period they were engaged with the DMS (mean 144, SD 100 days). Interviews with patients (n=14) and providers (n=5) elicited themes salient to using the DMS. Patient findings described the positive impact of the DMS on medication adherence, challenges with the DMS patch connectivity and skin irritation, and challenges with the DMS app that affected overall use. Providers described an overall interest in using a DMS as an objective measure to support medication adherence in their patients. However, providers described challenges with the DMS dashboard and integrating DMS data into their workflow, which decreased the usability of the DMS for providers. CONCLUSIONS: There was no observed difference in refill rates. Among those who engaged in the DMS arm, the proportion of days covered by refills were relatively high (mean 0.85, SD 0.20). The qualitative analyses highlighted areas for further refinement of the DMS. TRIAL REGISTRATION: ClinicalTrials.gov NCT03881449; https://clinicaltrials.gov/ct2/show/NCT03881449.

A Mixed-Methods Protocol to Identify Best Practices for Implementing Pharmacogenetic Testing in Clinical Settings.

Using a patient's genetic information to inform medication prescriptions can be clinically effective; however, the practice has not been widely implemented. Health systems need guidance on how to engage with providers to improve pharmacogenetic test utilization. Approaches from the field of implementation science may shed light on the complex factors affecting pharmacogenetic test use in real-world settings and areas to target to improve utilization. This paper presents an approach to studying the application of precision medicine that utilizes mixed qualitative and quantitative methods and implementation science frameworks to understand which factors or combinations consistently account for high versus low utilization of pharmocogenetic testing. This approach involves two phases: (1) collection of qualitative and quantitative data from providers-the cases-at four clinical institutions about their experiences with, and utilization of, pharmacogenetic testing to identify salient factors; and (2) analysis using a Configurational Comparative Method (CCM), using a mathematical algorithm to identify the minimally necessary and sufficient factors that distinguish providers who have higher utilization from those with low utilization. Advantages of this approach are that it can be used for small to moderate sample sizes, and it accounts for conditions found in real-world settings by demonstrating how they coincide to affect utilization.

Incorporating the patient voice and patient engagement in GOAL-Hem: Advancing patient-centric hemophilia care.

BACKGROUND: Goal Attainment Scaling for Hemophilia (GOAL-Hem) is a novel, hemophilia-specific, validated patient engagement tool and patient-reported outcome instrument. OBJECTIVE: We evaluated the degree to which the language of GOAL-Hem was patient-centric and the content valuable and relevant for people with hemophilia (PWH) and/or their caregivers. PATIENTS/METHODS: Patients and caregivers participated in one of three investigations: an online survey, one-on-one patient interviews, or a focus group. The survey and interviews assessed the clarity and relevance of the GOAL-Hem menu items. Interviews were semistructured, audio recorded, and transcribed verbatim. Feedback from interviews was coded as "clear," "unclear," "remove," or "add." The focus group explored participants' experience of GOAL-Hem and elicited recommendations for implementation. Quotations from focus group and interview transcripts were indexed and charted to emergent themes for analysis. RESULTS: Participants comprised 19 adults with hemophilia and 19 caregivers of children with hemophilia (survey, n = 20; interview, n = 12; focus group, n = 6). After their feedback, 32% (15/48) of goals were retained unchanged. Further feedback resulted in the removal of 45% (286/635) of the goal descriptors, and 30% (193/635) of the retained descriptors were modified. Three new (total = 38) goals and 42 descriptors (total = 368) were added to the menu. Thematic analysis indicated that participants were enthusiastic about patient-centric language, empowered through the goal-setting process, and recognized GOAL-Hem could measure clinically meaningful change. CONCLUSION: By listening closely to patients and caregivers, we refined GOAL-Hem to better capture the experiences of PWH, enhance content validity, and augment implementation strategies. Incorporating the patient voice is integral to developing patient-centered outcome measures.

Understanding constraints on integrated care for people with HIV and multimorbid cardiovascular conditions: an application of the Theoretical Domains Framework.

BACKGROUND: People with HIV (PWH) experience increased cardiovascular disease (CVD) risk. Many PWH in the USA receive their primary medical care from infectious disease specialists in HIV clinics. HIV care teams may not be fully prepared to provide evidence-based CVD care. We sought to describe local context for HIV clinics participating in an NIH-funded implementation trial and to identify facilitators and barriers to integrated CVD preventive care for PWH. METHODS: Data were collected in semi-structured interviews and focus groups with PWH and multidisciplinary healthcare providers at three academic medical centers. We used template analysis to identify barriers and facilitators of CVD preventive care in three HIV specialty clinics using the Theoretical Domains Framework (TDF). RESULTS: Six focus groups were conducted with 37 PWH. Individual interviews were conducted with 34 healthcare providers and 14 PWH. Major themes were captured in seven TDF domains. Within those themes, we identified nine facilitators and 11 barriers to CVD preventive care. Knowledge gaps contributed to inaccurate CVD risk perceptions and ineffective self-management practices in PWH. Exclusive prioritization of HIV over CVD-related conditions was common in PWH and their providers. HIV care providers assumed inconsistent roles in CVD prevention, including for PWH with primary care providers. HIV providers were knowledgeable of HIV-related CVD risks and co-located health resources were consistently available to support PWH with limited resources in health behavior change. However, infrequent medical visits, perceptions of CVD prevention as a primary care service, and multiple co-location of support programs introduced local challenges to engaging in CVD preventive care. CONCLUSIONS: Barriers to screening and treatment of cardiovascular conditions are common in HIV care settings and highlight a need for greater primary care integration. Improving long-term cardiovascular outcomes of PWH will likely require multi-level interventions supporting HIV providers to expand their scope of practice, addressing patient preferences for co-located CVD preventive care, changing clinic cultures that focus only on HIV to the exclusion of non-AIDS multimorbidity, and managing constraints associated with multiple services co-location. TRIAL REGISTRATION: ClinicalTrials.gov , NCT03643705.

Patients' Experiences With Staphylococcus aureus and Gram-negative Bacterial Bloodstream Infections: A Qualitative Descriptive Study and Concept Elicitation Phase To Inform Measurement of Patient-reported Quality of Life.

BACKGROUND: Although Staphylococcus aureus and gram-negative bacterial bloodstream infections (SAB/GNB) cause substantial morbidity, little is known regarding patient perceptions' of their impact on quality of life (QOL). Guidance for assessing QOL and disease-specific measures are lacking. We conducted a descriptive qualitative study to gain an in-depth understanding of patients' experiences with SAB/GNB and concept elicitation phase to inform a patient-reported QOL outcome measure. METHODS: We conducted prospective one-time, in-depth, semi-structured, individual, qualitative telephone interviews 6- 8 weeks following bloodstream infection with either SAB or GNB. Patients were enrolled in an institutional registry (tertiary academic medical center) for SAB or GNB. Interviews were audio-recorded, transcribed, and coded. Directed content analysis identified a priori and emergent themes. Theme matrix techniques were used to facilitate analysis and presentation. RESULTS: Interviews were completed with 30 patients with SAB and 31 patients with GNB. Most patients were at or near the end of intravenous antibiotic treatment when interviewed. We identified 3 primary high-level concepts: impact on QOL domains, time as a critical index, and sources of variability across patients. Across both types of bloodstream infection, the QOL domains most impacted were physical and functional, which was particularly evident among patients with SAB. CONCLUSIONS: SAB/GNB impact QOL among survivors. In particular, SAB had major impacts on multiple QOL domains. A combination of existing, generic measures that are purposefully selected and disease-specific items, if necessary, could best capture these impacts. Engaging patients as stakeholders and obtaining their feedback is crucial to conducting patient-centered clinical trials and providing patient-centered care.

Why Do People Living with HIV Adhere to Antiretroviral Therapy and Not Comorbid Cardiovascular Disease Medications? A Qualitative Inquiry.

BACKGROUND: After achieving viral suppression, it is critical for persons living with HIV (PLWH) to focus on prevention of non-AIDS comorbidities such as cardiovascular disease (CVD) in order to enhance their quality of life and longevity of life. Despite PLWH elevated risk of developing CVD compared to individuals without HIV, PLWH do not often meet evidence-based treatment goals for CVD prevention; the reasons for PLWH not meeting guideline recommendations are poorly understood. The objective of this study was to identify the factors associated with adherence to CVD medications for PLWH who have achieved viral suppression. METHODS: Qualitative data were obtained from formative research conducted to inform the adaptation of a nurse-led intervention trial to improve cardiovascular health at three large academic medical centers in the United States. Transcripts were analyzed using content analysis guided by principles drawn from grounded theory. RESULTS: Fifty-one individuals who had achieved viral suppression (<200 copies/mL) participated: 37 in 6 focus groups and 14 in individual semi-structured interviews. Mean age was 57 years (SD: 7.8); most were African Americans (n=31) and majority were male (n=34). Three main themes were observed. First, participants reported discordance between their healthcare providers' recommendations and their own preferred strategies to reduce CVD risk. Second, participants intentionally modified frequency of CVD medication taking which appeared to be related to low CVD risk perception and perceived or experienced side effects with treatment. Finally, participants discussed the impact of long-term experience with HIV care on adherence to CVD medication and motivational factors that enhanced adherence to heart healthy behaviors. CONCLUSION: Findings suggest that future research should focus on developing interventions to enhance patient-provider communication in order to elicit beliefs, concerns and preferences for CVD prevention strategies. Future research should seek to leverage and adapt established evidence-based practices in HIV care to support CVD medication adherence.

Rationale and design of a nurse-led intervention to extend the HIV treatment cascade for cardiovascular disease prevention trial (EXTRA-CVD).

Persons living with human immunodeficiency virus (PLHIV) are at increased risk of atherosclerotic cardiovascular disease (ASCVD). In spite of this, uptake of evidence-based clinical interventions for ASCVD risk reduction in the HIV clinic setting is sub-optimal. METHODS: EXTRA-CVD is a 12-month randomized clinical effectiveness trial that will assess the efficacy of a multi-component nurse-led intervention in reducing ASCVD risk among PLHIV. Three hundred high ASCVD risk PLHIV across three sites will be randomized 1:1 to usual care with generic prevention education or the study intervention. The study intervention will consist of four evidence-based components: (1) nurse-led care coordination, (2) nurse-managed medication protocols and adherence support (3) home BP monitoring, and (4) electronic health records support tools. The primary outcome will be change in systolic blood pressure and secondary outcome will be change in non-HDL cholesterol over the course of the intervention. Tertiary outcomes will include change in the proportion of participants in the following extended cascade categories: (1) appropriately diagnosed with hypertension and hyperlipidemia (2) appropriately managed; (3) at treatment goal (systolic blood pressure <130 mm Hg and non-HDL cholesterol < National Lipid Association targets). CONCLUSIONS: The EXTRA-CVD trial will provide evidence appraising the potential impact of nurse-led interventions in reducing ASCVD risk among PLHIV, an essential extension of the HIV care continuum beyond HIV viral suppression.

Bridging the integration gap between patient-generated blood glucose data and electronic health records.

Telemedicine can facilitate population health management by extending the reach of providers to efficiently care for high-risk, high-utilization populations. However, for telemedicine to be maximally useful, data collected using telemedicine technologies must be reliable and readily available to healthcare providers. To address current gaps in integration of patient-generated health data into the electronic health record (EHR), we examined 2 patient-facing platforms, Epic MyChart and Apple HealthKit, both of which facilitated the uploading of blood glucose data into the EHR as part of a diabetes telemedicine intervention. All patients were offered use of the MyChart platform; we subsequently invited a purposive sample of patients who used the MyChart platform effectively (n = 5) to also use the Apple HealthKit platform. Patients reported both platforms helped with diabetes self-management, and providers appreciated the convenience of the processes for obtaining patient data. Providers stated that the EHR data presentation format for Apple HealthKit was challenging to interpret; however, they also valued the greater perceived accuracy the Apple HealthKit data. Our findings indicate that patient-facing platforms can feasibly facilitate transmission of patient-generated health data into the EHR and support telemedicine-based care.

Using a geriatric oncology assessment to link with services (GOAL).

OBJECTIVE: Geriatric screening tools assess functional limitations and inform clinical decision-making for older adults with cancer. Our objective was to evaluate the feasibility and effectiveness of a screener in community-based oncology clinics. MATERIALS AND METHODS: Eligible patients were from two rural, underserved community-based cancer clinics; within 12 months of a cancer diagnosis (breast, lung, colorectal, pancreas, esophageal); aged ≥60 years; and not exclusively pursuing palliative care. We used a previously validated tool that was embedded in the electronic health record (EHR). Patient-reported responses identified memory impairment, depressive symptoms, deficits in activities of daily living, poor nutrition, and polypharmacy. At the discretion of the oncologist, responses prompted service referrals. From the EHR, we extracted information about referrals and completion of planned therapy. We present descriptive statistics. RESULTS: Enrolled patients (n = 44) had a mean age of 71.5 years (SD = 6.9). Most were non-white (61%), women (66%), with government-sponsored health insurance (80%). The most commonly identified geriatric syndromes: polypharmacy (89%), reduced quality of life (39%), and poor nutrition (39%). The screener triggered a referral in 98% of patients. Generated referrals were for depressive symptoms (52% needed, 39% received), nutrition (43% needed, 37% received), and polypharmacy (89% needed, 26% received). Patients were referred to social work (56%), nutrition (44%), and pharmacy (25%). Many patients completed planned radiation therapy (100%), surgery (70%), and chemotherapy (60%). CONCLUSIONS: Use of an EHR-embedded brief geriatric oncology assessment in rural oncology clinics identified geriatric syndromes that would benefit from provision of services in nearly all enrolled patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02906592.

The 30-second rule: the effects of prolonged intubation attempts on oxygen saturation and heart rate in preterm infants in the delivery room.

BACKGROUND: A duration of 30 seconds has been shown to improve the success rate of intubation attempts without any decompensation. There is limited data regarding the detrimental effects of prolonged intubation attempts in preterm infants. The aim was to determine the effect of prolonged intubation attempts on heart rate and oxygen saturation in preterm infants. METHODS: We retrospectively reviewed videos and physiologic data collected during delivery room (DR) resuscitations. Infants who had a functioning pulse oximeter at the time of intubation in the delivery room were analyzed using video and analog recordings. The duration of the intubation attempt was defined as the time the laryngoscope blade was in the infant's mouth. Prolonged intubations were defined as intubations over 30 seconds. Baseline heart rate and saturations were defined as the heart rate and saturation immediately prior to the intubation attempt. Video recording was used to determine time laryngoscope was in the mouth, what other procedures were performed, and whether there was recovery between attempts. Analog data including heart rate, airway pressure and saturation was also recorded. RESULTS: There were 52 intubation attempts in 28 infants. The median (IQR) birth weight and gestational age were 795 (705, 972) grams and 25 (25, 27) weeks. The duration of an intubation attempt was 35 (27, 46) seconds with number of attempts 2 (1, 2). There were 34 intubation attempts greater than 30 seconds (prolonged group) and 18 attempts less than or equal to 30 seconds (short group). Longer attempts did not affect intubation success (successful 34 [25,37] seconds vs. unsuccessful 41[29, 53] seconds; P=0.05). Infants in the prolonged group had a greater decrease in oxygen saturation percentage from baseline (5±8 percent, short intubation group and 13±27 prolonged intubation group; P=0.004). There was also a significant decrease in heart rate beats per minute between the two groups (6±9 in the short intubation group and 23±29 prolonged group; P=0.004). CONCLUSIONS: The currently recommended guideline by the Neonatal Resuscitation Program limiting intubation attempts to less than 30 seconds is supported by stable oxygen saturations and heart rate. Prolonging the intubation more than 30 seconds leads to greater hypoxia and may contribute to increased neonatal morbidity, with no effect on success rate.

Resistance of Colorimetric Carbon Dioxide Detectors Commonly Utilized in Neonates.

BACKGROUND: Colorimetric end-tidal carbon dioxide (ETCO2) detectors can identify airway obstruction during noninvasive ventilation and successful intubation during newborn resuscitation. The resistance of these devices is not well described, and the information provided by manufacturers is incomplete. METHODS: We compared the resistance of 3 colorimetric ETCO2 detectors (Neo-StatCO2, Pedi-Cap, and Mini StatCO2,) and 2 mainstream capnograph sensors (EMMA infant airway adapter 17449 and neonatal/infant airway adapter YG-213T). Endotracheal tubes, 2.5-4.0-mm inner diameter (Portex) were measured as a reference range. A differential pressure transducer was placed between the device and a T-piece resuscitator. The other side of the device was open to air. Resistance to flow was tested at 1-10 L/min. Resistance was calculated as the change in pressure over change in flow and expressed as cm H2O/L/s. RESULTS: There was a significantly higher mean resistance across all flows tested for the Neo-StatCO2 compared with the other ETCO2 devices (P < .001). There was a 6-fold difference between the least and most resistive colorimetric detectors. At the commonly utilized flow of 10 L/min, the resistance of the Neo-StatCO2 was 61.1 cm H2O/L/s, comparable with that of a 3.0 endotracheal tube, which we measured at 62.7 cm H2O/L/s. The resistance values of the Pedi-Cap and Mini StatCO2 were 9.9 and 8.4 cm H2O/L/s, respectively. Those of the EMMA and YG-213T were 7.1 and 2.6 cm H2O/L/s, respectively. CONCLUSIONS: We found significant differences in resistance between devices used to detect ETCO2 during resuscitation of premature infants. Future trials are needed to determine the effects of this resistance on work of breathing, particularly on very premature newborns receiving mask CPAP.

Evaluation of enhanced coagulation pretreatment to improve ozone oxidation efficiency in wastewater.

Enhanced coagulation (EC) using ferric chloride was evaluated as a pretreatment process to improve the efficiency of ozone (O3) for the oxidation of trace organic contaminants in wastewater. At the applied dosages (10-30 mg/L as Fe), EC pretreatment removed between 10 and 47% of the dissolved organic carbon (DOC) from the three wastewaters studied. Size exclusion chromatography (SEC) showed that EC preferentially removed higher apparent molecular weight (AMW) compounds. Subsequent O3 testing was performed using an O3:DOC ratio of 1. Results showed that O3 exposures were similar even though the required doses were reduced by 10-47% by the EC pretreatment process. Hydroxyl radical (HO·) exposure, measured by parachlorobenzoic acid (pCBA), showed 10% reduction when using a FeCl3 dose of 30 mg/L, likely due to the lower O3 dose and decreased production of HO· during the initial phase of O3 decomposition (t<30 s). The oxidation of 13 trace organic contaminants (including atenolol, carbamazepine, DEET, diclofenac, dilantin, gemfibrozil, ibuprofen, meprobamate, naproxen, primidone, sulfamethoxazole, triclosan, and trimethoprim) was evaluated after EC and O3 treatment. EC was ineffective at removing any of the contaminants, while O3 oxidation reduced the concentration of compounds according to their reaction rate constants with O3 and HO·.

A novel nucleoside analog, 1-beta-d-ribofuranosyl-3-ethynyl-[1,2,4]triazole (ETAR), exhibits efficacy against a broad range of flaviviruses in vitro.

Antiviral therapies are urgently needed to control emerging flaviviruses such as dengue, West Nile, and yellow fever. Ribavirin (RBV) has shown activity against flaviviruses in cultured cells, but efficacy in animal models has generally been poor. In a preliminary screen of novel, synthetic 1-beta-d-ribofuranosyl-azole analogs, two compounds, 1-beta-d-ribofuranosyl-3-ethynyl-[1,2,4]triazole (ETAR) and 1-beta-d-ribofuranosyl-4-ethynyl-[1,3]imidazole (IM18), significantly reduced the replication of dengue virus serotype 2 (DENV-2) in cultured Vero cells. In the current study we demonstrated that the effective concentration 50 (EC(50)) of ETAR for DENV-2 is substantially lower than both IM18 and RBV. Moreover, ETAR reduced the replication of five additional flaviviruses, including DENV serotypes 1, 3 and 4, Langat virus and Modoc virus, > or =1000-fold relative to untreated controls. Addition of exogenous guanosine to DENV-2 infected cells negated the antiviral effects of both RBV and ETAR, indicating that GTP depletion is a major mechanism of action for both drugs. ETAR represents a promising drug candidate for the treatment of flavivirus infections.