Factors Associated With Delays in Presentation and Treatment of Gonorrhea, Massachusetts 2015-2019.

BACKGROUND: Rates of gonorrhea are increasing across the United States. Understanding and addressing contributing factors associated with longer time to diagnosis and treatment may shorten the duration of infectiousness, which in turn may limit transmission. METHODS: We used Massachusetts data from the US Centers for Disease Control and Prevention Sexually Transmitted Disease Surveillance Network collected between July 2015 and September 2019, along with routinely reported surveillance data, to assess time from gonorrhea symptom onset to presentation to care, and time from presentation to care to receipt of treatment. Factors associated with longer time to presentation (TTP) and time to treatment (TTT) were assessed using Cox proportional hazard models with a constant time variable. RESULTS: Among symptomatic patients (n = 672), 31% did not receive medical care within 7 days of symptom onset. Longer TTP was associated with younger age, female gender, reporting cost as a barrier to care, and provider report of proctitis. Among patients with symptoms and/or known contact to gonorrhea (n = 827), 42% did not receive presumptive treatment. Longer TTT was associated with female gender, non-Hispanic other race/ethnicity, and clinics with less gonorrhea treatment experience. Among asymptomatic patients without known exposure to STI (n = 235), 26% did not receive treatment within 7 days. Longer TTT was associated with sexually transmitted disease clinic/family planning/reproductive health clinics and a test turnaround time of ≥3 days. CONCLUSIONS: Delays in presentation to care and receipt of treatment for gonorrhea are common. Factors associated with longer TTP and TTT highlight multiple opportunities for reducing the infectious period of patients with gonorrhea.

Swiping right on PrEP: a qualitative study of MSM preferences for PrEP public health messaging on dating apps.

Men who have sex with men (MSM) are disproportionately affected by HIV. Given that over 70% of MSM meet sexual partners via dating apps, such apps may be an effective platform for promoting HIV pre-exposure prophylaxis (PrEP) use. We aimed to describe preferences among MSM for PrEP advertisements displayed on dating apps. We conducted individual in-depth interviews with 16 MSM recruited from a mobile sexual health unit in Boston, Massachusetts. Two focus groups were also held: one with mobile unit staff (N = 3) and one with mobile unit users (N = 3). Content analysis was used to identify themes related to advertisement content and integration with app use. Mean participant age was 28 (SD 6.8); 37% identified as White and 63% as Latinx. 21% of interviews were conducted in Spanish. Preferences were organized around four themes: (1) relevant and relatable advertisements, (2) expansion of target audiences to promote access, (3) concise and captivating advertisements, and (4) PrEP advertisements and services as options, not obligations. MSM are supportive of receiving information about PrEP on dating apps, but feel that existing advertisements require modification to better engage viewers. Dating apps may be an underutilized tool for increasing PrEP awareness and knowledge among MSM.

Pre-exposure Prophylaxis Persistence at a Diverse Sexual Health Clinic: Comparison of the pre-COVID-19 era to the COVID-19 era.

The COVID-19 pandemic interrupted health care delivery and exacerbated disparities. Many sexual health clinics transitioned to telemedicine, including for pre-exposure prophylaxis (PrEP). We conducted a retrospective cohort study of patients at an urban sexual health clinic to assess the likelihood and predictors of PrEP persistence in the year following PrEP initiation. We compared patients starting PrEP in the four months preceding the first COVID surge to those starting PrEP one year prior. We found lower PrEP persistence in the COVID cohort compared to the pre-COVID cohort (50.8% vs. 68.9%, respectively). In both cohorts, most care was provided through in-person visits and telemedicine was rare. In the pre-COVID cohort, older patients and those identifying as non-Hispanic White were more likely to persist on PrEP. In the COVID cohort, these disparities in PrEP persistence were not observed. Flexible models of care may facilitate equitable care engagement and re-engagement.

Urban Sexual Health Clinic Patients With "Undetermined Risk" for HIV Are Less Likely to Receive Preexposure Prophylaxis.

BACKGROUND: New diagnoses of HIV increasingly occur among people who fall outside traditional transmission risk categories. This group remains poorly defined, and HIV prevention efforts for this group lag behind efforts for patients in other risk groups. METHODS: We conducted a retrospective review of patient visits at sexual health clinics in Boston, MA, over a 14-month period. Patients were classified into Centers for Disease Control and Prevention-defined HIV transmission risk categories. We compared frequencies of sexually transmitted infections (STIs), HIV, preexposure prophylaxis (PrEP) indications, and PrEP prescriptions. Predictors of HIV or STI among patients in the undetermined risk category were assessed with logistic regression. RESULTS: There were 4723 clinic visits during the study period. Patients in the undetermined risk group constituted the largest proportion (55.8%), followed by men who have sex with men (MSM; 42.7%). The proportion of visits by patients in the undetermined risk group with an indication for PrEP was low (28.0%) compared with MSM (91.3%) and MSM who also inject drugs (93.8%); however, the absolute number was high (737). Among patients with an indication for PrEP, those in the undetermined risk group were least likely to receive a prescription. Behavioral risk factors were poorly predictive of STI or HIV among patients in the undetermined risk group. CONCLUSIONS: Patients with undetermined risk for HIV constituted a large proportion of clinic visits and had a large volume of sexual health needs but rarely received PrEP when indicated. To end the HIV epidemic in the United States, prevention efforts must include people who fall outside traditional risk categories.

Outcomes of Early Liver Transplantation for Patients With Severe Alcoholic Hepatitis.

BACKGROUND & AIMS: The American Consortium of Early Liver Transplantation for Alcoholic Hepatitis comprises 12 centers from 8 United Network for Organ Sharing regions studying early liver transplantation (LT) (without mandated period of sobriety) for patients with severe alcoholic hepatitis (AH). We analyzed the outcomes of these patients. METHODS: We performed a retrospective study of consecutive patients with a diagnosis of severe AH and no prior diagnosis of liver disease or episodes of AH, who underwent LT before 6 months of abstinence from 2006 through 2017 at 12 centers. We collected data on baseline characteristics, psychosocial profiles, level of alcohol consumption before LT, disease course and treatment, and outcomes of LT. The interval of alcohol abstinence was defined as the time between last drink and the date of LT. The primary outcomes were survival and alcohol use after LT, defined as slip or sustained. RESULTS: Among 147 patients with AH who received liver transplants, the median duration of abstinence before LT was 55 days; 54% received corticosteroids for AH and the patients had a median Lille score of 0.82 and a median Sodium Model for End-Stage Liver Disease score of 39. Cumulative patient survival percentages after LT were 94% at 1 year (95% confidence interval [CI], 89%-97%) and 84% at 3 years (95% CI, 75%-90%). Following hospital discharge after LT, 72% were abstinent, 18% had slips, and 11% had sustained alcohol use. The cumulative incidence of any alcohol use was 25% at 1 year (95% CI, 18%-34%) and 34% at 3 years (95% CI, 25%-44%) after LT. The cumulative incidence of sustained alcohol use was 10% at 1 year (95% CI, 6%-18%) and 17% at 3 years (95% CI, 10%-27%) after LT. In multivariable analysis, only younger age was associated with alcohol following LT (P = .01). Sustained alcohol use after LT was associated with increased risk of death (hazard ratio, 4.59; P = .01). CONCLUSIONS: In a retrospective analysis of 147 patients who underwent early LT (before 6 months of abstinence) for severe AH, we found that most patients survive for 1 year (94%) and 3 years (84%), similar to patients receiving liver transplants for other indications. Sustained alcohol use after LT was infrequent but associated with increased mortality. Our findings support the selective use of LT as a treatment for severe AH. Prospective studies are needed to optimize selection criteria, management of patients after LT, and long-term outcomes.

The Development and Evaluation of an Online Healthcare Toolkit for Autistic Adults and their Primary Care Providers.

BACKGROUND: The healthcare system is ill-equipped to meet the needs of adults on the autism spectrum. OBJECTIVE: Our goal was to use a community-based participatory research (CBPR) approach to develop and evaluate tools to facilitate the primary healthcare of autistic adults. DESIGN: Toolkit development included cognitive interviewing and test-retest reliability studies. Evaluation consisted of a mixed-methods, single-arm pre/post-intervention comparison. PARTICIPANTS: A total of 259 autistic adults and 51 primary care providers (PCPs) residing in the United States. INTERVENTIONS: The AASPIRE Healthcare toolkit includes the Autism Healthcare Accommodations Tool (AHAT)-a tool that allows patients to create a personalized accommodations report for their PCP-and general healthcare- and autism-related information, worksheets, checklists, and resources for patients and healthcare providers. MAIN MEASURES: Satisfaction with patient-provider communication, healthcare self-efficacy, barriers to healthcare, and satisfaction with the toolkit's usability and utility; responses to open-ended questions. KEY RESULTS: Preliminary testing of the AHAT demonstrated strong content validity and adequate test-retest stability. Almost all patient participants (>94 %) felt that the AHAT and the toolkit were easy to use, important, and useful. In pre/post-intervention comparisons, the mean number of barriers decreased (from 4.07 to 2.82, p < 0.0001), healthcare self-efficacy increased (from 37.9 to 39.4, p = 0.02), and satisfaction with PCP communication improved (from 30.9 to 32.6, p = 0.03). Patients stated that the toolkit helped clarify their needs, enabled them to self-advocate and prepare for visits more effectively, and positively influenced provider behavior. Most of the PCPs surveyed read the AHAT (97 %), rated it as moderately or very useful (82 %), and would recommend it to other patients (87 %). CONCLUSIONS: The CBPR process resulted in a reliable healthcare accommodation tool and a highly accessible healthcare toolkit. Patients and providers indicated that the tools positively impacted healthcare interactions. The toolkit has the potential to reduce barriers to healthcare and improve healthcare self-efficacy and patient-provider communication.

Electronic Partner Notification for Sexually Transmitted Infections: A Qualitative Assessment of Patient, Clinical Staff, and State Field Epidemiologist Perspectives.

In Massachusetts (MA), partner notification is routinely offered for new HIV and infectious syphilis cases, but there are no formal partner notification services for gonorrhea and chlamydia. Electronic partner notification (ePN), which allows patients to anonymously notify their partners of sexually transmitted infection exposure, could fill this gap. We evaluated the acceptability of and ideal characteristics for a statewide ePN service in MA. We performed semistructured interviews with patients at a Boston area sexual health clinic and conducted focus groups with clinicians and Massachusetts Department of Public Health Field Epidemiologists (FEs). We developed a codebook and thematically analyzed interview and focus group data; 25% of interviews were double coded. We identified six main themes from our data: (1) partner notification is a relational process and (2) partner notification is situation dependent. There are three pairs of challenges and core values for an effective ePN system: (3) stigmatization versus inclusivity, (4) trust versus mistrust, and (5) privacy versus helpful information sharing. Therefore, (6) a statewide ePN platform must be customizable at each possible step. Although ePN was acceptable across all three groups, the likelihood of individual use was grounded in a patient's sociocultural context, interpersonal relationships, trust in the platform and health authorities, desire to avoid stigmatization, and privacy needs. These factors are best accommodated by a platform that adapts to users' preferences and needs. ePN presents an opportunity to link partners at risk for gonorrhea or chlamydia to clinical care that is complementary to the more labor-intensive FE role.

Evaluation of Hepatitis C Treatment Outcomes Among Patients Enrolled in Outpatient Parenteral Antibiotic Therapy-Boston, Massachusetts, 2016-2021.

In our Boston-based outpatient parenteral antibiotic therapy (OPAT) program between 2016 and 2021, we found that a low proportion of patients with active hepatitis C virus (HCV) were prescribed HCV treatment by their OPAT provider and few achieved sustained virologic response. Clinicians should consider concurrent HCV treatment during OPAT.

Curable sexually transmitted infections among women with HIV in sub-Saharan Africa.

OBJECTIVES: Sexually transmitted infections (STIs) cause significant morbidity among women with HIV and increase HIV transmission. We estimated the prevalence of four STIs among women with HIV in sub-Saharan Africa (SSA) and compared prevalence among women with and without HIV. DESIGN: Systematic review and meta-analysis. METHODS: We searched for studies published 1 January 1999 to 19 December 2019 reporting prevalence of gonorrhea, chlamydia, trichomoniasis, or Mycoplasma genitalium among women with HIV in SSA. We excluded studies conducted in high-risk groups (e.g. female sex workers). We extracted data on laboratory-confirmed STIs among women with HIV, and when included, among women without HIV. We estimated pooled prevalence for each STI among women with HIV using inverse variance heterogeneity meta-analysis, compared prevalence to women without HIV, and examined the influences of region, clinical setting, and pregnancy status in subgroup analyses. RESULTS: We identified 3756 unique records; 67 studies were included in the meta-analysis. Prevalence of gonorrhea, chlamydia, trichomoniasis, and M. genitalium was 3.5, 4, 15.6, and 10.2%, respectively. Chlamydia prevalence was lower in Eastern (2.8%) than in Southern (12.5%) and West/Central (19.1%) Africa combined. Prevalence of chlamydia and trichomoniasis was higher among pregnant (8.1%, 17.6%) than nonpregnant (1.7%, 12.3%) women. All STIs were more prevalent among women with than without HIV (relative risks ranging 1.54-1.89). CONCLUSION: STIs are common among women with HIV in SSA, and more common among women with than without HIV. Integrated STI and HIV care could substantially impact STI burden among women with HIV, with potential downstream impacts on HIV transmission.

Chlamydia Treatment Practices and Time to Treatment in Massachusetts: Directly Observed Therapy Versus Pharmacy Prescriptions.

BACKGROUND: Directly observed therapy (DOT) is recommended for the treatment of chlamydia, however pharmacy prescriptions are frequently used. Adherence to DOT and the association between treatment method and time to treatment is unknown. METHODS: We conducted a retrospective review of a randomized 2% of laboratory-confirmed chlamydia infections reported to the Massachusetts Department of Public Health from January 1, 2019 to May 31, 2019. Clinicians and pharmacies were contacted to ascertain treatment methods and timing. We assessed frequency of DOT and pharmacy prescriptions in the treatment of chlamydia infection in Massachusetts. We used log rank test to compare time to treatment initiation for patients receiving DOT versus pharmacy prescriptions. Data were stratified according to whether treatment was empiric or laboratory-driven. KEY RESULTS: We ascertained full outcomes for 199 patients. Eighty patients received DOT and 119 patients received pharmacy prescriptions. DOT was more common among those receiving empiric treatment and pharmacy prescriptions were more common among those receiving laboratory-driven treatment. The median time to treatment was 1.5 days for patients treated with DOT and 3 days for those treated with pharmacy prescriptions. For both groups, the median time to treatment for empiric therapy was 0 days and for laboratory-driven therapy was 4 days. The differences in time to treatment were not statistically significant. CONCLUSIONS: Pharmacy prescriptions are frequently used for the treatment of chlamydia in Massachusetts. We did not observe a significant difference in the time to treatment between DOT and pharmacy prescriptions.

Identifying and predicting longitudinal trajectories of care for people newly diagnosed with HIV in South Africa.

BACKGROUND: Predicting long-term care trajectories at the time of HIV diagnosis may allow targeted interventions. Our objective was to uncover distinct CD4-based trajectories and determine baseline demographic, clinical, and contextual factors associated with trajectory membership. METHODS: We used data from the Sizanani trial (NCT01188941), in which adults were enrolled prior to HIV testing in Durban, South Africa from August 2010-January 2013. We ascertained CD4 counts from the National Health Laboratory Service over 5y follow-up. We used group-based statistical modeling to identify groups with similar CD4 count trajectories and Bayesian information criteria to determine distinct CD4 trajectories. We evaluated baseline factors that predict membership in specific trajectories using multinomial logistic regression. We examined calendar year of participant enrollment, age, gender, cohabitation, TB positivity, self-identified barriers to care, and ART initiation within 3 months of diagnosis. RESULTS: 688 participants had longitudinal data available. Group-based trajectory modeling identified four distinct trajectories: one with consistently low CD4 counts (21%), one with low CD4 counts that increased over time (22%), one with moderate CD4 counts that remained stable (41%), and one with high CD4 counts that increased over time (16%). Those with higher CD4 counts at diagnosis were younger, less likely to have TB, and less likely to identify barriers to care. Those in the least favorable trajectory (consistently low CD4 count) were least likely to start ART within 3 months. CONCLUSIONS: One-fifth of people newly-diagnosed with HIV presented with low CD4 counts that failed to rise over time. Less than 40% were in a trajectory characterized by increasing CD4 counts. Patients in more favorable trajectories were younger, less likely to have TB, and less likely to report barriers to healthcare. Better understanding barriers to early care engagement and ART initiation will be necessary to improve long-term clinical outcomes.

Distributed Drug Discovery, Part 3: using D(3) methodology to synthesize analogs of an anti-melanoma compound.

For the successful implementation of Distributed Drug Discovery (D(3)) (outlined in the accompanying Perspective), students, in the course of their educational laboratories, must be able to reproducibly make new, high quality, molecules with potential for biological activity. This article reports the successful achievement of this goal. Using previously rehearsed alkylating agents, students in a second semester organic chemistry laboratory performed a solid-phase combinatorial chemistry experiment in which they made 38 new analogs of the most potent member of a class of antimelanoma compounds. All compounds were made in duplicate, purified by silica gel chromatography, and characterized by NMR and LC/MS. As a continuing part of the Distributed Drug Discovery program, a virtual D(3) catalog based on this work was then enumerated and is made freely available to the global scientific community.

The Role of Gender in Violence Experienced by Adults With Developmental Disabilities.

Violence against people with developmental disabilities is a highly prevalent yet understudied phenomenon. In particular, there is a paucity of literature surrounding the role of gender and the experiences of men. Using a cross-sectional study design, we surveyed 350 people with diverse developmental disabilities about experiences of abuse, perpetrators of abuse, and their physical and mental health status. These data were analyzed to determine whether gender influenced these domains. Statistical methods included chi-square, independent t tests, logistic regression, and hierarchical multiple regressions. Male and female participants reported abuse at high rates, with 61.9% of men and 58.2% of women reporting abuse as children and 63.7% of men and 68.2% of women reporting abuse as adults. More women than men reported adult sexual abuse, but there was no gender difference in the prevalence of any other form of abuse. Women were more likely than men to identify an intimate partner as their abuser, although intimate partners represented the minority of abusers for both men and women. Violence was associated with worse health status regardless of participant gender. These findings confirm that violence is an important issue for both men and women with developmental disabilities. Although some expected gender differences arose, such as higher rates of adult sexual abuse and intimate partner violence against women, these differences were less pronounced than they are in the general population, and the overall picture of abuse was one of gender similarities rather than differences.

Controlled delivery of cytokine growth factors mediated by core-shell particles with poly(acrylamidomethylpropane sulphonate) shells.

Core-shell particles have been prepared by surfactant-free emulsion polymerisations of butyl methacrylate in the presence of either linear or highly branched poly(acrylamidomethylpropane sulphonate)s (L-PAMPS or HB-PAMPS) with dithioate end groups: using a "shell-first" approach. In this method the water soluble PAMPS shells were anchored to the cores by polymerisation of BMA from the chain ends. The linear PAMPS produced non-crosslinked poly(AMPS-BMA) particles but the multiple chain ends of the highly branched PAMPS led to crosslinked particles. The particles were loaded with vascular endothelial growth factor or platelet derived growth factor, both of which are cytokines that are known to be important in the production of new blood vessels. The release of the growth factors was shown to be controlled by the architecture of the shell and we propose a mechanism that involves both ionic interaction of the PAMPS with the heparin-binding domains of the growth factors and size exclusion mediated diffusion.