All You Can Do Is Try Your Best.

This essay describes the author's experience of losing her father while in medical school.

Examination of HIV Preexposure Prophylaxis Need, Availability, and Potential Pharmacy Integration in the Southeastern US.

Importance: Daily preexposure prophylaxis (PrEP) use can prevent up to 99% of HIV infections; however, PrEP uptake is low due to poor access to PrEP-prescribing locations for populations at increased risk for HIV, especially in the southeastern US. Pharmacies are a feasible option to increase PrEP access, but little is known about how they could complement current PrEP-prescribing locations. Objective: To examine geographic distributions of current PrEP-prescribing locations compared with pharmacies and the facility to need ratios (PFNRs) according to HIV risk in the Southeast and describe the potential reach of pharmacies to expand PrEP access. Design, Setting, and Participants: Data for this cross-sectional study of PrEP-prescribing locations and pharmacies were compiled from January 1 to December 31, 2021. States or specific counties in the Southeast included in this study were jurisdictions identified as high-priority areas for the Ending the HIV Epidemic in the US (EHE) initiative. Exposure: Expansion of HIV prevention services to pharmacies. Main Outcomes and Measures: Choropleth maps of 5-year HIV risk per 100 000 persons were developed for EHE jurisdictions in the southeastern US. PrEP-prescribing locations (obtained from a national database of PrEP prescribers) and pharmacies (obtained from state pharmacy boards) were overlayed on HIV risk maps. The PFNRs by state were calculated as number of facilities (PrEP-prescribing locations or pharmacies) divided by 5-year HIV risk per 100 000 persons. Lower PFNRs indicated lower geographic availability of locations to meet the needs of the population at risk for HIV. The PFNRs for current PrEP-prescribing locations vs pharmacies were compared. Results: Among the 2 southeastern states and 13 counties in 4 southeastern states included, PrEP-prescribing locations were unequally distributed across EHE areas, with substantially fewer in areas at high risk for HIV. Pharmacies were evenly dispersed across areas regardless of HIV risk. The mean PFNR across all states for current PrEP-prescribing locations was 0.008 (median, 0.000 [IQR, 0.000-0.003]); for pharmacies, it was 0.7 (median, 0.3 [IQR, 0.01-0.1]). The PFNRs were at least 20.3 times higher for pharmacies compared with PrEP-prescribing locations. States with the greatest potential increase in PFNRs with expansion to pharmacies included Kentucky, South Carolina, and Tennessee. Conclusions and Relevance: The findings of this cross-sectional study suggest that expanding HIV prevention services to pharmacies in EHE areas in the Southeast could significantly increase capacity to reach individuals at increased risk of HIV transmission. Legislation aimed at allowing pharmacists to prescribe PrEP and provide HIV prevention services may be an important next step in ending the HIV epidemic.

Psychosocial Correlates of Opioid Use Profiles among Young Adults in a Longitudinal Study across 6 US Metropolitan Areas.

Background: Examining opioid use profiles over time and related factors among young adults is crucial to informing prevention efforts. Objectives: This study analyzed baseline data (Fall 2018) and one-year follow-up data from a cohort of 2,975 US young adults (Mage=24.55, 42.1% male; 71.7% White; 11.4% Hispanic). Multinomial logistic regression was used to examine: 1) psychosocial correlates (i.e. adverse childhood experiences [ACEs], depressive symptoms, parental substance use) of lifetime opioid use (i.e. prescription use vs. nonuse, nonmedical prescription [NMPO] use, and heroin use, respectively); and 2) psychosocial correlates and baseline lifetime use in relation to past 6-month use at one-year follow-up (i.e. prescription use vs. nonuse and NMPO/heroin use, respectively). Results: At baseline, lifetime use prevalence was: 30.2% prescription, 9.7% NMPO, and 3.1% heroin; past 6-month use prevalence was: 7.6% prescription, 2.5% NMPO, and 0.9% heroin. Compared to prescription users, nonusers reported fewer ACEs and having parents more likely to use tobacco, but less likely alcohol; NMPO users did not differ; and heroin users reported more ACEs and having parents more likely to use cannabis but less likely alcohol. At one-year follow-up, past 6-month use prevalence was: 4.3% prescription, 1.3% NMPO, and 1.4% heroin; relative to prescription users, nonusers were less likely to report baseline lifetime opioid use and reported fewer ACEs, and NMPO/heroin users were less likely to report baseline prescription opioid use but more likely heroin use. Conclusions: Psychosocial factors differentially correlate with young adult opioid use profiles, and thus may inform targeted interventions addressing different use patterns and psychosocial risk factors.

Comparing open-ended question methods to vignette methods to explore willingness to obtain pre-exposure prophylaxis access in pharmacies among black men who have sex with men.

Black men who have sex with men (BMSM) are at higher risk of HIV transmission than any other group; however, their uptake of the highly effective HIV prevention medication, pre-exposure prophylaxis (PrEP), is low. In collaboration with a communitybased organization in Atlanta, Georgia, we explored ten HIV-negative BMSM's willingness to obtain PrEP in pharmacies using standard open-ended and vignette qualitative methods. Three overarching themes were identified: privacy, patient-pharmacist interactions, and HIV/STI screening. While open-ended questions allowed participants to provide broad answers on their willingness to receive prevention services at a pharmacy, the vignette drew out specific responses to facilitate in-pharmacy PrEP delivery. Using both openended questions and vignette data collection strategies, BMSM reported high willingness to screen for and uptake PrEP in pharmacies. However, the vignette method allowed for greater depth. Open-ended questions elicited responses that highlighted general barriers and facilitators of PrEP dispensing in pharmacies. However, the vignette allowed participants to customize a plan of action that would best fit their needs. Vignette methods are underutilized in HIV research and may be helpful in supplementing standard open-ended interview questions to uncovering unknown challenges about health behaviors and obtain more robust data on highly sensitive research topics in HIV research.

SARS-CoV-2 Antigenemia is Associated With Pneumonia in Children But Lacks Sensitivity to Diagnose Acute Infection.

BACKGROUND: Nucleocapsid antigenemia in adults has demonstrated high sensitivity and specificity for acute infection, and antigen burden is associated with disease severity. Data regarding SARS-CoV-2 antigenemia in children are limited. METHODS: We retrospectively analyzed blood plasma specimens from hospitalized children with COVID-19 or MIS-C. Nucleocapsid and spike were measured using ultrasensitive immunoassays. RESULTS: We detected nucleocapsid antigenemia in 62% (50/81) and spike antigenemia in 27% (21/79) of children with acute COVID-19 but 0% (0/26) and 15% (4/26) with MIS-C from March 2020-March 2021. Higher nucleocapsid levels were associated with radiographic infiltrates and respiratory symptoms in children with COVID-19. CONCLUSIONS: Antigenemia lacks the sensitivity to diagnose acute infection in children but is associated with signs and symptoms of lower respiratory tract involvement. Further study into the mechanism of antigenemia, its association with specific organ involvement, and the role of antigenemia in the pathogenesis of COVID-19 is warranted.

Examining Multilevel Correlates of Geographic Mobility in a Sample of US Young Adults Before and During the COVID-19 Pandemic.

Before the COVID-19 pandemic, geographic mobility, previously viewed as an indicator of economic stability, was declining among young adults. Yet, these trends shifted during the COVID-19 pandemic; young adults were more likely to move during COVID-19 for reasons related to reducing disease transmission and fewer educational and job opportunities. Few studies have documented the individual and neighborhood characteristics of young adults who moved before and during the pandemic. We used data from a cohort of young adults aged 18-34 in six metropolitan areas to examine individual- and neighborhood-level predictors of mobility before and during the COVID-19 pandemic. The sample was majority female, white, and educated with a bachelor's degree or more. Residents in neighborhoods they lived in were mostly White, US-born, employed, and lived above the poverty level. Before the pandemic, identifying as a sexual minority was significantly related to mobility. During the pandemic, being younger, single, and non-Hispanic were significantly related to mobility. Higher neighborhood poverty was significantly related to mobility before and during the COVID-19 pandemic. Future studies that examine young adult populations who moved during the pandemic are needed to determine whether COVID-19 related moves increase economic instability and subsequent health-related outcomes.

Examining pharmacies' ability to increase pre-exposure prophylaxis access for black men who have sex with men in the United States.

BACKGROUND: Pre-exposure prophylaxis (PrEP) has not effectively reached black men who have sex with men (BMSM). Using innovative, nontraditional health care settings-such as community pharmacies-may improve PrEP uptake among BMSM. OBJECTIVE: To examine correlates of patient willingness to be screened for PrEP (via human immunodeficiency virus [HIV] testing and risk assessment) in pharmacies among BMSM in the United States. METHODS: Data from the 2020 American Men's Internet Survey were analyzed. Using a modified Poisson regression method with robust variance estimates, we examined differences in willingness to screen for PrEP in pharmacies among BMSM. A 95% confidence interval (95% CI) was calculated for each estimated prevalence ratio (PR). RESULTS: Of 826 respondents, 637 (77%) were willing to be screened for PrEP in pharmacies. Having a high school degree (PR 0.76 [95% CI 0.62-0.95]), willingness to use PrEP (1.70 [1.41-2.05]), and comfort speaking with pharmacy staff about PrEP (2.5 [1.86-3.51]) were significantly associated with willingness to screen for PrEP in a pharmacy setting. Importantly, there were no observed differences in willingness by age, employment status, annual household income, or insurance status. CONCLUSION: Pharmacy-based PrEP access may be an effective strategy to end inequities in HIV, given that our results indicate that most BMSM are willing to be screened for PrEP in pharmacies. Future studies should examine whether willingness to use pharmacy-based HIV prevention services is associated with subsequent uptake of these services among BMSM.

A University-Led Contact Tracing Program Response to a COVID-19 Outbreak Among Students in Georgia, February-March 2021.

Few reports have described how university programs have controlled COVID-19 outbreaks. Emory University established a case investigation and contact tracing program in June 2020 to identify and mitigate transmission of SARS-CoV-2 in the Emory community. In February 2021, this program identified a surge in COVID-19 cases. In this case study, we present details of outbreak investigation, construction of transmission networks to assess clustering and identify groups for targeted testing, and program quality metrics demonstrating the efficiency of case investigation and contact tracing, which helped bring the surge under control. During February 10-March 5, 2021, Emory University identified 265 COVID-19 cases confirmed by nucleic acid testing in saliva or nasopharyngeal samples. Most students with COVID-19 were undergraduates (95%) and were affiliated with Greek life organizations (70%); 41% lived on campus. Network analysis identified 1 epidemiologically linked cluster of 198 people. Nearly all students diagnosed with COVID-19 (96%) were interviewed the same day as their positive test result. Of 340 close contacts, 90% were traced and 89% were tested. The median time from contact interview to first test was 2 days (interquartile range, 0-6 days); 43% received a positive test result during their quarantine. The surge was considered under control within 17 days, after which new cases were no longer epidemiologically linked. Early detection through systematic testing protocols and rapid and near-complete contact tracing, paired with isolation and quarantine measures, helped to contain the surge. Our approach emphasizes the importance of early preparation of adequate outbreak response infrastructure and staff to implement interventions appropriately and consistently during a pandemic.

Nucleocapsid Antigenemia Is a Marker of Acute SARS-CoV-2 Infection.

Detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is essential for diagnosis, treatment, and infection control. Polymerase chain reaction (PCR) fails to distinguish acute from resolved infections, as RNA is frequently detected after infectiousness. We hypothesized that nucleocapsid in blood marks acute infection with the potential to enhance isolation and treatment strategies. In a retrospective serosurvey of inpatient and outpatient encounters, we categorized samples along an infection timeline using timing of SARS-CoV-2 testing and symptomatology. Among 1860 specimens from 1607 patients, the highest levels and frequency of antigenemia were observed in samples from acute SARS-CoV-2 infection. Antigenemia was higher in seronegative individuals and in those with severe disease. In our analysis, antigenemia exhibited 85.8% sensitivity and 98.6% specificity as a biomarker for acute coronavirus disease 2019 (COVID-19). Thus, antigenemia sensitively and specifically marks acute SARS-CoV-2 infection. Further study is warranted to determine whether antigenemia may aid individualized assessment of active COVID-19.

Epidemiology beyond its limits.

In 1995, journalist Gary Taubes published an article in Science titled "Epidemiology faces its limits," which questioned the utility of nonrandomized epidemiologic research and has since been cited more than 1000 times. He highlighted numerous examples of research topics he viewed as having questionable merit. Studies have since accumulated for these associations. We systematically evaluated current evidence of 53 example associations discussed in the article. Approximately one-quarter of those presented as doubtful are now widely viewed as causal based on current evaluations of the public health consensus. They include associations between alcohol consumption and breast cancer, residential radon exposure and lung cancer, and the use of tanning devices and melanoma. This history should inform current debates about the reproducibility of epidemiologic research results.

Integrating and Disseminating Pre-Exposure Prophylaxis (PrEP) Screening and Dispensing for Black Men Who Have Sex With Men in Atlanta, Georgia: Protocol for Community Pharmacies.

BACKGROUND: Black men who have sex with men (BMSM) suffer from alarmingly high rates of HIV in the United States. Pre-exposure prophylaxis (PrEP) can reduce the risk of HIV infection by 99% among men who have sex with men, yet profound racial disparities in the uptake of PrEP persist. Low PrEP uptake in BMSM is driven by poor access to PrEP, including inconvenient locations of PrEP-prescribing physicians, distrust of physicians, and stigma, which limit communication about PrEP and its side effects. Previous work indicates that offering HIV prevention services in pharmacies located in low-income, underserved neighborhoods is feasible and can reduce stigma because pharmacies offer a host of less stigmatized health services (eg, vaccinations). We present a protocol for a pharmacy PrEP model that seeks to address challenges and barriers to pharmacy-based PrEP specifically for BMSM. OBJECTIVE: We aim to develop a sustainable pharmacy PrEP delivery model for BMSM that can be implemented to increase PrEP access in low-income, underserved neighborhoods. METHODS: This study design is a pilot intervention to test a pharmacy PrEP delivery model among pharmacy staff and BMSM. We will examine the PrEP delivery model's feasibility, acceptability, and safety and gather early evidence of its impact and cost with respect to PrEP uptake. A mixed-methods approach will be performed, including three study phases: (1) a completed formative phase with qualitative interviews from key stakeholders; (2) a completed transitional pilot phase to assess customer eligibility and willingness to receive PrEP in pharmacies during COVID-19; and (3) a planned pilot intervention phase which will test the delivery model in 2 Atlanta pharmacies in low-income, underserved neighborhoods. RESULTS: Data from the formative phase showed strong support of pharmacy-based PrEP delivery among BMSM, pharmacists, and pharmacy staff. Important factors were identified to facilitate the implementation of PrEP screening and dissemination in pharmacies. During the transitional pilot phase, we identified 81 individuals who would have been eligible for the pilot phase. CONCLUSIONS: Pharmacies have proven to be a feasible source for offering PrEP for White men who have sex with men but have failed to reach the most at-risk, vulnerable population (ie, BMSM). Increasing PrEP access and uptake will reduce HIV incidence and racial inequities in HIV. Translational studies are required to build further evidence and scale pharmacy-based PrEP services specifically for populations that are disconnected from HIV prevention resources. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/35590.

Trends in ICU Mortality From Coronavirus Disease 2019: A Tale of Three Surges.

OBJECTIVES: To determine the association between time period of hospitalization and hospital mortality among critically ill adults with coronavirus disease 2019. DESIGN: Observational cohort study from March 6, 2020, to January 31, 2021. SETTING: ICUs at four hospitals within an academic health center network in Atlanta, GA. PATIENTS: Adults greater than or equal to 18 years with coronavirus disease 2019 admitted to an ICU during the study period (i.e., Surge 1: March to April, Lull 1: May to June, Surge 2: July to August, Lull 2: September to November, Surge 3: December to January). MEASUREMENTS AND MAIN RESULTS: Among 1,686 patients with coronavirus disease 2019 admitted to an ICU during the study period, all-cause hospital mortality was 29.7%. Mortality differed significantly over time: 28.7% in Surge 1, 21.3% in Lull 1, 25.2% in Surge 2, 30.2% in Lull 2, 34.7% in Surge 3 (p = 0.007). Mortality was significantly associated with 1) preexisting risk factors (older age, race, ethnicity, lower body mass index, higher Elixhauser Comorbidity Index, admission from a nursing home); 2) clinical status at ICU admission (higher Sequential Organ Failure Assessment score, higher d-dimer, higher C-reactive protein); and 3) ICU interventions (receipt of mechanical ventilation, vasopressors, renal replacement therapy, inhaled vasodilators). After adjusting for baseline and clinical variables, there was a significantly increased risk of mortality associated with admission during Lull 2 (relative risk, 1.37 [95% CI = 1.03-1.81]) and Surge 3 (relative risk, 1.35 [95% CI = 1.04-1.77]) as compared to Surge 1. CONCLUSIONS: Despite increased experience and evidence-based treatments, the risk of death for patients admitted to the ICU with coronavirus disease 2019 was highest during the fall and winter of 2020. Reasons for this increased mortality are not clear.

Using the Think-Aloud Method to Assess the Feasibility and Acceptability of Network Canvas Among Black Men Who Have Sex With Men and Transgender Persons: Qualitative Analysis.

BACKGROUND: Characteristics of an individual's social network have been important factors in understanding infectious disease transmission patterns. Social network data collection is generally time and resource intensive, yet it is crucial to our understanding of the complex epidemiologic landscape of human behaviors among stigmatized social groups. OBJECTIVE: We sought to evaluate the feasibility and acceptability of a self-administered social network data collection tool, Network Canvas, among Black men who have sex with men (BMSM) and transgender persons using the think-aloud method, which is a robust and flexible research technique used to perform usability testing. METHODS: We piloted a self-administered network interview within the Network Canvas Software Suite. Participants aged 18 years and older were recruited through a community-based organization in Atlanta, GA, and were included based upon their willingness to share information on sexual behaviors and drug use for themselves and their social networks. A semistructured interview guide was used to document cognitive decision-making processes while using the tool. Recorded interviews were transcribed verbatim, and thematic analyses were performed. RESULTS: Among 7 BMSM and transgender participants, three main themes were identified from cognitive processes: (1) the utility, (2) navigation, and (3) intuitive design of Network Canvas. Overall, Network Canvas was described as "easy to use," with suggestions mainly directed toward improving navigation tools and implementing an initial tutorial on the program prior to use. Participants were willing to use Network Canvas to document their social networks and characteristics. In general, observed verbal responses from participants matched their behavior, although there were some discrepancies between verbal affirmations of use and understanding versus external observation. CONCLUSIONS: We found Network Canvas to be a useful new tool to capture social network data. Self-administration allowed participants the opportunity to provide sensitive information about themselves and their social networks. Furthermore, automated name generation and visualization of an individuals' social network in the app has the potential to reduce cognitive burden during data collection. More efficient methods of social network data collection have the potential to provide epidemiologic information to guide prevention efforts for populations with stigmatized health conditions or behaviors.

Diagnosis and Management of HIV-Associated Pulmonary Diseases in a Ryan White-Funded Primary Care Setting.

Despite widespread use of antiretroviral therapy (ART), people with HIV (PWH) continue to suffer substantial morbidity and mortality from pulmonary diseases. We sought to evaluate the prevalence of pulmonary symptoms, evaluations, and diagnoses (both infectious and noninfectious) among PWH receiving care at one of the largest HIV clinics in the United States. All PWH seen at the Infectious Disease Program in Atlanta, Georgia, from July 2013 to June 2018 were included. Multivariable logistic regression was used to assess the odds of all-cause mortality. Among 8387 patients, median age was 48 years, 35% had documented smoking, 74% were male, and the 47% with ≥1 pulmonary symptom or diagnosis were older and had higher rates of smoking compared to those without any symptoms or diagnoses (p-values <0.0001). Percent on ART was 97% and 81% for individuals with and without symptoms or diagnoses, respectively (p-value <0.0001). Patients with an infectious diagnosis were more likely to have a diagnostic test ordered than those with a noninfectious diagnosis (p-value <0.0001). After adjustment for demographic and clinical risk factors, odds of death were 2.1 times greater [95% confidence interval (CI) = 1.3-3.5] among those with a pulmonary symptom or diagnosis compared to those without. Despite a high prevalence of pulmonary symptoms and diagnoses in this large cohort of PWH, many did not have a complete diagnostic evaluation, particularly those with noninfectious diagnoses. Greater awareness of evaluation and treatment of noninfectious pulmonary diseases among HIV care providers will be critical to improving long-term outcomes for PWH.

Evaluation of a Cryptococcal Antigen Lateral Flow Assay and Cryptococcal Antigen Positivity at a Large Public Hospital in Atlanta, Georgia.

BACKGROUND: Cryptococcus neoformans is a major cause of morbidity and mortality among human immunodeficiency virus (HIV)-infected persons worldwide, and there are scarce recent data on cryptococcal antigen (CrAg) positivity in the United States We sought to determine the frequency of cryptococcal disease and compare the performance of a CrAg lateral flow assay (LFA) versus latex agglutination (LA) test. METHODS: All patients from Grady Health System in Atlanta who had a serum or cerebrospinal fluid (CSF) sample sent for CrAg testing as part of clinical care from November 2017 to July 2018 were included. Percentage positivity and test agreement were calculated. RESULTS: Among 467 patients, 557 diagnostic tests were performed; 413 on serum and 144 on CSF. The mean age was 44 years, and most were male (69%) and had HIV (79%). Twenty-four (6.4%, 95% confidence interval [CI] = 4.1-9.4) patients were serum CrAg positive, and 8 (5.8%, 95% CI = 2.6-11.2) individuals tested positive for CSF CrAg. Although overall agreement between the LA and LFA was substantial to high for CSF (κ = 0.71, 95% CI = 0.51-0.91) and serum (κ = 0.93, 95% CI = 0.86-1.00), respectively, there were important discrepancies. Five patients had false-positive CSF LA tests that affected clinical care, and 4 patients had discordant serum tests. CONCLUSIONS: We found a moderately high proportion of cryptococcal disease and important discrepancies between the LA test and LFA. Clinical implications of these findings include accurate detection of serum CrAg and averting unnecessary treatment of meningitis with costly medications associated with high rates of adverse events.

Silk Fibroin Microneedle Patches for the Sustained Release of Levonorgestrel.

The sustained release of levonorgestrel, a contraceptive, from silk-based microneedle patches was demonstrated for transdermal delivery. Modifications in the formulation of the silk protein and drug loading enabled the tuning of drug loading and release rates from the microneedle patches over time. Sustained drug release reached up to 100 days when the drug was loaded directly inside the microneedles, while release continued for more than a year when the drug was loaded inside microparticles prior to casting inside the microneedle patches. When coupled with the shelf-stable, refrigeration-less features of the silk protein matrix utilized in the microneedle fabrication, these findings suggest that long-acting contraception patches are feasible. This advance could provide practical options for women to have access to new options for protection against unwanted pregnancy.

Enhancing sustained-release local therapy: Single versus dual chemotherapy for the treatment of neuroblastoma.

BACKGROUND: Neuroblastoma is the most common pediatric extracranial solid malignancy with limited effective treatment. We have shown that sustained-release, single drugs delivered locally through a silk-based biomaterial are effective in decreasing orthotopic neuroblastoma xenograft growth. We further optimized this approach and hypothesized that increasing doses of local chemotherapy or delivering 2 chemotherapeutic agents simultaneously inhibit additional tumor growth. METHODS: MYCN-amplified and non-MYCN-amplified neuroblastoma cells were treated with combinations of cisplatin, vincristine, doxorubicin, and etoposide to determine cytotoxicity and synergy. Drug-loaded silk material was created, and the amounts of drug released from the material over time were recorded. Murine orthotopic neuroblastoma xenografts were generated; tumors were implanted with single- or dual-agent chemotherapy-loaded silk. Ultrasound was used to monitor tumor growth, and tumor histology was evaluated. RESULTS: In vitro, vincristine/cisplatin combination was synergistic and significantly decreased cell viability relative to other combinations. Both drugs loaded into silk could be released effectively for over 2 weeks. Locally implanted vincristine/cisplatin silk induced increased tumor growth suppression compared with either agent alone in MYCN-amplified tumors (P < .05). The dose-dependent effect seen in MYCN-amplified tumors treated with combination therapy diminished at higher doses in non-MYCN-amplified tumors, with little benefit with doses >50 µg to 500 µg for vincristine-cisplatin, respectively. Tumor histology demonstrated tumor cell necrosis adjacent to drug-loaded silk material and presence of large cell neuroblastoma. CONCLUSION: Local delivery of sustained release chemotherapy can suppress tumor growth especially at high doses or with 2 synergistic drugs. Locally delivered dual therapy is a promising approach for future clinical testing.

High Yield of Active Tuberculosis Case Finding Among HIV-Infected Patients Using Xpert MTB/RIF Testing.

OBJECTIVE: Conduct an active case finding study in Tbilisi, Georgia, for pulmonary tuberculosis (TB) among people living with HIV (PLWH). METHODS: Newly diagnosed HIV patients were assessed for symptoms and asked to submit sputum samples for smear microscopy, culture, and molecular diagnostic testing (Xpert MTB/RIF). RESULTS: Among 276 PLWH, 131 agreed to participate and 103 submitted sputum samples. Most participants were male (70%) and mean age of 43 years. There were high rates of a positive hepatitis C virus (HCV) antibody test (46%) and the median CD4 count was 122 cells/mm3. A total of 15 (11.5%) persons were diagnosed with pulmonary TB, including 1 each with multidrug-resistant and isoniazid-resistant disease. Twelve had a positive culture for Mycobacterium tuberculosis and Xpert TB/RIF assay, and 4 had positive smear microscopy. Patients with pulmonary TB were more likely to use injection drugs (67% vs 36%, P = .02) and have a positive HCV antibody (73% vs 42%, P = .02). The presence and absence of any TB symptom had a sensitivity and negative predictive value for TB of 93% and 98%, respectively. CONCLUSION: Our findings highlight the high prevalence of TB among newly diagnosed HIV-infected patients in an area with high rates of drug-resistant TB and the utility of an active case finding strategy for TB diagnosis.

Sustained release silk fibroin discs: Antibody and protein delivery for HIV prevention.

With almost 2 million new HIV infections worldwide each year, the prevention of HIV infection is critical for stopping the pandemic. The only approved form of pre-exposure prophylaxis is a costly daily pill, and it is recognized that several options will be needed to provide protection to the various affected communities around the world. In particular, many at-risk people would benefit from a prevention method that is simple to use and does not require medical intervention or a strict daily regimen. We show that silk fibroin protein can be formulated into insertable discs that encapsulate either an antibody (IgG) or the potent HIV inhibitor 5P12-RANTES. Several formulations were studied, including silk layering, water vapor annealing and methanol treatment to stabilize the protein cargo and impact the release kinetics over weeks. In the case of IgG, high concentrations were released over a short time using methanol treatment, with more sustained results with the use of water vapor annealing and layering during device fabrication. For 5P12-RANTES, sustained release was obtained for 31 days using water vapor annealing. Further, we show that the released inhibitor 5P12-RANTES was functional both in vitro and in ex vivo colorectal tissue. This work shows that silk fibroin discs can be developed into formidable tools to prevent HIV infection.

Silk Reservoirs for Local Delivery of Cisplatin for Neuroblastoma Treatment: In Vitro and In Vivo Evaluations.

Neuroblastoma is the most common extracranial childhood tumor, and current treatment requires surgical resection and multidrug chemotherapy. Local, perioperative delivery of chemotherapeutics is a promising treatment method for solid tumors that require surgical removal. In this study, we have aimed to develop a controlled-release implant system to deliver cisplatin in tumor or tumor resection area. Silk fibroin, a biodegradable, nonimmunogenic biopolymer was used to encapsulate different doses of cisplatin in a reservoir system. The physical integrity of the reservoirs was characterized by evaluating the crystalline structure of silk secondary structure using FTIR spectroscopy. The in vitro release of cisplatin was evaluated in phosphate-buffered saline at 37°C, and the reservoirs were able to release the drug up to 30 days. The cytotoxicity of cisplatin and cisplatin reservoirs were tested on KELLY cells. Cytotoxicity data showed 3.2 µg/mL cisplatin was required to kill 50% of the cell population, and the released cisplatin from the silk reservoirs showed significant cytotoxicity up to 21 days. Intratumoral implantation of silk reservoirs into an orthotopic neuroblastoma mouse model decreased tumor growth significantly when compared with control subjects. These results suggest that silk reservoirs are promising carriers for cisplatin delivery to the tumor site.