Doxycycline post-exposure prophylaxis for sexually transmitted infections impacts the gut antimicrobial resistome.

Doxycycline post-exposure prophylaxis (doxy-PEP) reduces bacterial sexually transmitted infections (STIs) among men who have sex with men and transgender women. While poised for widespread clinical implementation, the impact of doxy-PEP on antimicrobial resistance remains a primary concern as its effects on the gut microbiome and resistome, or the antimicrobial resistance genes (ARGs) present in the gut microbiome, are unknown. To investigate these effects, we studied participants from a randomized clinical trial who either received doxy-PEP as a one-time doxycycline 200 mg taken after condomless sex (DP arm, n = 100) or standard of care treatment (SOC arm, n = 50). From self-collected rectal swabs at enrollment (day-0) and after 6 months (month-6), we performed metagenomic DNA sequencing (DNA-seq) or metatranscriptomic RNA sequencing (RNA-seq). DNA-seq data was analyzable from 127 samples derived from 89 participants, and RNA-seq data from 86 samples derived from 70 participants. We compared the bacterial microbiome and resistome between the two study arms and over time. Tetracycline ARGs were detected in all day-0 DNA-seq samples and 85% of day-0 RNA-seq samples. The proportional mass of tetracycline ARGs in the resistome increased between day-0 and month-6 in DP participants from 46-51% in the metagenome (p = 0.02) and 4-15% in the metatranscriptome (p < 0.01), but no changes in other ARG classes were observed. Exposure to a higher number of doxycycline doses correlated with proportional enrichment of tetracycline ARGs in the metagenome (Spearman's ρ = 0.23, p < 0.01) and metatranscriptome (Spearman's ρ = 0.55, p < 0.01). Bacterial microbiome alpha diversity, beta diversity, and total bacterial mass did not differ between day-0 and month-6 samples from DP participants when assessed by either DNA-seq or RNA-seq. In an abundance-based correlation analysis, we observed an increase over time in the strength of the correlation between tetracycline ARGs and specific bacterial taxa, including some common human pathogens. In sum, doxy-PEP use over a 6-month period was associated with an increase in the proportion of tetracycline ARGs comprising the gut resistome, and an increase in the expression of tetracycline ARGs. Notably, doxy-PEP did not significantly alter alpha diversity or taxonomic composition of the gut microbiome, and did not demonstrate significant increases in non-tetracycline ARG classes. Further studies and population level surveillance are needed to understand the implications of these findings as doxy-PEP is implemented as a public health strategy.

Rapid Biphasic Decay of Intact and Defective HIV DNA Reservoir During Acute Treated HIV Disease.

Antiretroviral therapy (ART) is not a cure. Upon ART cessation, virus rapidly rebounds from latently-infected cells ("the HIV reservoir"). The reservoir is largely stabilized at the time of ART initiation and then decays slowly. Here, leveraging >500 longitudinal samples from 67 people with HIV (PWH) treated during acute infection, we developed a novel mathematical model to predict reservoir decay using the intact proviral DNA assay (IPDA) from peripheral CD4+ T cells. Nonlinear generalized additive models adjusted for initial CD4+ T count, pre-ART viral load, and timing of ART initiation demonstrated rapid biphasic decay of intact DNA (week 0-5: t1/2 ~0.71 months; week 5-24: t1/2 ~3.9 months) that extended out to 1 year of ART, with similar trends for defective DNA. Predicted reservoir decay were faster for participants individuals with earlier timing of ART initiation, higher initial CD4+ T cell count, and lower pre-ART viral load. These estimates are ~5-fold faster than prior reservoir decay estimates among chronic-treated PWH. Thus, these data add to our limited understanding of host viral control at the earliest stages of HIV reservoir stabilization, potentially informing future HIV cure efforts aimed at diverse, global population of PWH initiating ART at varying stages of disease.

Doxycycline as Postsexual Exposure Prophylaxis: Use, Acceptability, and Associated Sexual Health Behaviors Among a Multi-Site Sample of Clinical Trial Participants.

Doxycycline postexposure prophylaxis (doxy-PEP) reduces sexually transmitted infections (STIs) in men who have sex with men (MSM) and transgender women (TGW). In a clinical trial of doxy-PEP, we sought to assess acceptability, impact, and meaning of doxy-PEP use among MSM/TGW. We conducted semistructured, in-depth 1:1 interviews with MSM and TGW enrolled in the intervention arm of the Doxy-PEP study. We queried motivations for and meaning of use, attitudes, beliefs, adherence, effect on sexual behaviors, and partner, community, and structural factors related to use. We coded interview transcripts into content areas, followed by thematic analysis. We interviewed 44 participants (median age 38), 2% were TGW, 17% Black, 61% White, 30% Hispanic, and 45% persons with HIV. We identified three overarching themes. First, participants found doxy-PEP acceptable, and believed it was effective based on their history of STIs, easy to adhere to, and acceptable to sex partners. Second, doxy-PEP benefited their quality of life and mental health, offering "peace of mind" by reducing their anxiety about acquisition or unwitting transmission of STIs. Participants reported feeling more "in control" of preventing STIs, and positive about supporting their personal, partner, and community health. Third, impact on sexual behavior was variable, with most reporting no change or a brief initial change. Participants in a multi-site clinical trial of doxycycline for STI prevention perceived it to be efficacious, and that it provided quality-of-life benefits, including reduced anxiety and sense of control over sexual health. Doxy-PEP had limited impact on sexual behavior. Clinicaltrials.gov: NCT03980223.

Comparison of in-person versus virtual ultrasound instruction for pediatric residents.

PURPOSE: Point-of-care ultrasound (POCUS) instruction is prevalent in medical schools but not in pediatric residency programs, even though the majority of pediatric residents desire POCUS instruction. Virtual ultrasound instruction with affordable handheld ultrasound devices may help remedy this deficiency by allowing qualified instructors to circumvent geographic and financial limitations to reach this population. This study sought to determine if virtual ultrasound instruction is an effective alternative to traditional in-person instruction in a cohort of pediatric residents for the extended Focused Assessment with Sonography in Trauma (eFAST) exam. METHODS: Pediatric residents were randomized to receive either in-person or virtual instruction to learn the eFAST exam using a Sonosite Edge (Sonosite, Inc., Bothell, WA) or Butterfly iQ (Butterfly Network, Inc., Guilford, CT), respectively. After the instructional session, the participants completed a timed assessment in which all required images for the eFAST exam were obtained on the same anatomic model. The content and quality of the images were then scored by expert faculty. RESULTS: There were no significant differences in assessment scores (65.8% and 61.8%, p = 0.349) and assessment duration (482.6 s and 432.6 s, p = 0.346) between pediatric residents who received in-person instruction and those who received virtual instruction. CONCLUSION: Virtual ultrasound instruction appears to be an effective alternative to traditional in-person instruction.

Prevalence of visual art education in medical school curricula: a national survey of US medical schools.

Background: The Association of American Medical Colleges (AAMC) has recommended integrating medically-relevant arts and humanities curricula into medical student education in order promote physician skills development. An analysis of the state of existing visual arts-based medical school pedagogies was conducted to inform future implementation strategies.Methodology: An electronic survey was distributed to representatives of US medical schools to describe the prevalence and characteristics of visual arts-based medical school curricula. Official courses, informal events, cross-registration opportunities, and established art museum partnerships were assessed.Results: Survey response rates were 65% for US allopathic medical schools and 56% for osteopathic medical schools. A majority (79%) of responding institutions incorporate or support medical student art experiences in some format. Thirty-one percent (n = 36) of schools offer stand-alone humanities courses using visual arts. These were primarily allopathic programs (n = 35; 37% of allopathic programs) and only one responding osteopathic program (n = 1; 5% of osteopathic programs). Schools without dedicated courses are less likely to report other curricular and extracurricular visual arts engagement. Most visual art medical courses are offered at medical schools located in the Northeastern United States.Conclusions: Many but not all medical schools are incorporating the visual arts into their medical education curriculum. Opportunities to promote increased uptake, more effective implementation, and collaboration strategies for the AAMC recommendations are proposed.

Prevalence of Undiagnosed Monkeypox Virus Infections during Global Mpox Outbreak, United States, June-September 2022.

Since May 2022, mpox has been identified in 108 countries without endemic disease; most cases have been in gay, bisexual, or other men who have sex with men. To determine number of missed cases, we conducted 2 studies during June-September 2022: a prospective serologic survey detecting orthopoxvirus antibodies among men who have sex with men in San Francisco, California, and a retrospective monkeypox virus PCR testing of swab specimens submitted for other infectious disease testing among all patients across the United States. The serosurvey of 225 participants (median age 34 years) detected 18 (8.0%) who were orthopoxvirus IgG positive and 3 (1.3%) who were also orthopoxvirus IgM positive. The retrospective PCR study of 1,196 patients (median age 30 years; 54.8% male) detected 67 (5.6%) specimens positive for monkeypox virus. There are likely few undiagnosed cases of mpox in regions where sexual healthcare is accessible and patient and clinician awareness about mpox is increased.

Use of 3-Dimensional Stereophotogrammetry to Detect Disease Progression in Craniofacial Morphea.

Importance: Objectively determining disease progression in craniofacial morphea (CM) is challenging, as clinical findings of disease activity are often lacking. Objective: To evaluate the utility of 3-dimensional (3D) stereophotogrammetry in detecting disease progression in CM over time. Design, Setting, and Participants: This prospective cohort study included 27 pediatric and adult patients with CM from 2 hospitals in Boston (Boston Children's Hospital and Brigham & Women's Hospital) consecutively enrolled from April 1, 2019, to March 1, 2023. Review of 3D stereophotogrammetry images and data analysis occurred from March 1 to April 1, 2023. Main Outcomes and Measures: Clinical and 3D stereophotogrammetry assessments were performed at 2- to 12-month intervals, depending on the clinical context. The 3D stereophotogrammetry images were then qualitatively rated as demonstrating no progression or definitive progression by an expert (board-certified plastic craniofacial surgeon) and nonexpert (board-certified dermatologist) in 3D stereophotogrammetry. In addition, κ coefficients were calculated for interrater reliability. Results: Of 27 patients with CM (19 female; median age, 14 [range, 5-40] years) and 3D stereophotogrammetry images obtained from a minimum of 2 time points (median, 4 [range, 2-10] images) spaced a median of 3 (range, 2-12) months apart, 10 experienced progression of their disease based on clinical assessments performed during the study period. In all cases in which clinical progression was favored, blinded qualitative assessment of 3D stereophotogrammetry images also favored progression with substantial interrater reliability (κ = 0.80 [95% CI, 0.61-0.99]). Furthermore, review of 3D stereophotogrammetry detected occult progression of asymmetry not noted on clinical examination in 3 additional patients. Conclusions and Relevance: In this prospective cohort study, blinded assessment of sequential 3D stereophotogrammetry images in patients with CM not only corroborated clinical assessment of disease progression but also detected occult progression of facial asymmetry not appreciable on clinical examination alone. Therefore, 3D stereophotogrammetry may serve as a useful adjunct to clinical examination of patients with CM over time. Future investigations are warranted to validate 3D stereophotogrammetry as an outcome measure in CM.

Disaster day: a simulation-based competition for educating emergency medicine residents and medical students on disaster medicine.

BACKGROUND: Disaster medicine is a growing field within the specialty of emergency medicine, but educational training typically focuses on hospital drills or other educational strategies, such as didactics, simulation, or tabletop exercises. With the success of gamification in other medical education applications, we sought to investigate if a novel gamified curricular innovation would lead to improved test performance and confidence in the ability to manage a real mass casualty incident (MCI). METHODS: This was a prospective observational study of medical students and emergency medicine residents who participated in a 4-h simulation-based competition consisting of 4 unique stations. Each station had learning objectives associated with the content taught. Learners completed a pre-event survey, followed by participation in the competitive gamification event, and subsequently completed a post-event survey. Differences between pre- and post-event responses were matched and analyzed using paired and unpaired t tests for medical knowledge assessments, the Mann-Whitney U test for perceptions of confidence in the ability to manage an MCI event, and descriptive statistics provided on perceptions of the effectiveness of this educational strategy. RESULTS: We analyzed data from 49 learners with matched (and unmatched) pre- and post-event survey responses. There was a statistically significant increase in medical knowledge assessment scores in both unmatched group means and available matched data (47 to 69%, p < 0.01, and 50 to 69%, p < 0.05). Self-reported confidence in the ability to handle an MCI scenario also significantly increased (p < 0.01). Finally, 100% of respondents indicated they "agreed" or "strongly agreed" that the event was an effective education tool for disaster preparedness and training. CONCLUSIONS: In this study, we found that learners perceived a novel gamification event as an effective educational tool, which led to improved learner knowledge and self-reported confidence in the ability to manage a real MCI.

Evaluating attributes of a collaborative model of service delivery for hereditary cancer risk assessment.

The purpose of this nonrandomized study was to compare several attributes of hereditary cancer risk assessment using a collaborative model of service delivery. Arm 1 included patients seen in-person by a board-certified genetic counselor (CGC), Arm 2 included high-complexity triaged patients from distant sites who received telegenetics with a CGC, and Arm 3 included low-complexity triaged patients from distant sites who had in-person risk assessment with a locally placed genetic counselor extender (GCE). A total of 152 patients consented and 98 had complete data available for analysis (35 in Arm 1, 33 in Arm 2, and 30 in Arm 3). The three groups were comparable in age, ethnicity, education, employment, and cancer status. There was no significant difference in median wait time or distance traveled to receive care across all three arms. However, if patients in Arms 2 and 3 had to access the CGC in-person, they would have had to travel significantly further (p < 0.0001). The time spent in a session was significantly longer in Arm 3 with a GCE than with a CGC in-person or by telegenetics (p < 0.01). There was no difference in the number of essential elements covered in the appointment, change in cancer worry, or appointment satisfaction across all three arms, although the sample size was small. Employing a collaborative model of service delivery with GCEs and telegenetics is feasible, satisfactory to patients and reduces the distance patients travel to access hereditary cancer genetic services.

Etiology, Diagnosis, and Modern Management of Chronic Pancreatitis: A Systematic Review.

Importance: The incidence of chronic pancreatitis is 5 to 12 per 100 000 adults in industrialized countries, and the incidence is increasing. Treatment is multimodal, and involves nutrition optimization, pain management, and when indicated, endoscopic and surgical intervention. Objectives: To summarize the most current published evidence on etiology, diagnosis, and management of chronic pancreatitis and its associated complications. Evidence Review: A literature search of Web of Science, Embase, Cochrane Library, and PubMed was conducted for publications between January 1, 1997, and July 30, 2022. Excluded from review were the following: case reports, editorials, study protocols, nonsystematic reviews, nonsurgical technical publications, studies pertaining to pharmacokinetics, drug efficacy, pilot studies, historical papers, correspondence, errata, animal and in vitro studies, and publications focused on pancreatic diseases other than chronic pancreatitis. Ultimately, the highest-level evidence publications were chosen for inclusion after analysis by 2 independent reviewers. Findings: A total of 75 publications were chosen for review. First-line imaging modalities for diagnosis of chronic pancreatitis included computed tomography and magnetic resonance imaging. More invasive techniques such as endoscopic ultrasonography allowed for tissue analysis, and endoscopic retrograde cholangiopancreatography provided access for dilation, sphincterotomy, and stenting. Nonsurgical options for pain control included behavior modification (smoking cessation, alcohol abstinence), celiac plexus block, splanchnicectomy, nonopioid pain medication, and opioids. Supplemental enzymes should be given to patients with exocrine insufficiency to avoid malnutrition. Surgery was superior to endoscopic interventions for long-term pain control, and early surgery (<3 years from symptom onset) had more superior outcomes than late surgery. Duodenal preserving strategies were preferred unless there was suspicion of cancer. Conclusions and Relevance: Results of this systematic review suggest that patients with chronic pancreatitis had high rates of disability. Strategies to improve pain control through behavioral modification, endoscopic measures, and surgery must also accompany management of the sequalae of complications that arise from endocrine and exocrine insufficiency.

Postexposure Doxycycline to Prevent Bacterial Sexually Transmitted Infections.

BACKGROUND: Interventions to reduce sexually transmitted infections (STIs) among men who have sex with men (MSM) are needed. METHODS: We conducted an open-label, randomized study involving MSM and transgender women who were taking preexposure prophylaxis (PrEP) against human immunodeficiency virus (HIV) infection (PrEP cohort) or living with HIV infection (persons living with HIV infection [PLWH] cohort) and who had had Neisseria gonorrhoeae (gonorrhea), Chlamydia trachomatis (chlamydia), or syphilis in the past year. Participants were randomly assigned in a 2:1 ratio to take 200 mg of doxycycline within 72 hours after condomless sex (doxycycline postexposure prophylaxis) or receive standard care without doxycycline. STI testing was performed quarterly. The primary end point was the incidence of at least one STI per follow-up quarter. RESULTS: Of 501 participants (327 in the PrEP cohort and 174 in the PLWH cohort), 67% were White, 7% Black, 11% Asian or Pacific Islander, and 30% Hispanic or Latino. In the PrEP cohort, an STI was diagnosed in 61 of 570 quarterly visits (10.7%) in the doxycycline group and 82 of 257 quarterly visits (31.9%) in the standard-care group, for an absolute difference of -21.2 percentage points and a relative risk of 0.34 (95% confidence interval [CI], 0.24 to 0.46; P<0.001). In the PLWH cohort, an STI was diagnosed in 36 of 305 quarterly visits (11.8%) in the doxycycline group and 39 of 128 quarterly visits (30.5%) in the standard-care group, for an absolute difference of -18.7 percentage points and a relative risk of 0.38 (95% CI, 0.24 to 0.60; P<0.001). The incidences of the three evaluated STIs were lower with doxycycline than with standard care; in the PrEP cohort, the relative risks were 0.45 (95% CI, 0.32 to 0.65) for gonorrhea, 0.12 (95% CI, 0.05 to 0.25) for chlamydia, and 0.13 (95% CI, 0.03 to 0.59) for syphilis, and in the PLWH cohort, the relative risks were 0.43 (95% CI, 0.26 to 0.71), 0.26 (95% CI, 0.12 to 0.57), and 0.23 (95% CI, 0.04 to 1.29), respectively. Five grade 3 adverse events and no serious adverse events were attributed to doxycycline. Of the participants with gonorrhea culture available, tetracycline-resistant gonorrhea occurred in 5 of 13 in the doxycycline groups and 2 of 16 in the standard-care groups. CONCLUSIONS: The combined incidence of gonorrhea, chlamydia, and syphilis was lower by two thirds with doxycycline postexposure prophylaxis than with standard care, a finding that supports its use among MSM with recent bacterial STIs. (Funded by the National Institutes of Health; DoxyPEP ClinicalTrials.gov number, NCT03980223.).

COVID-19-Induced Phlegmasia Cerulea Dolens.

A 44-year-old male with a history of deep venous thrombosis (DVT) and pulmonary embolism (PE) with the inferior vena cava (IVC) filter in place and peripheral vascular disease (PVD) status post lower extremity vascular stenting presented from a COVID-19 rehabilitation center with bilateral phlegmasia cerulea dolens and no palpable popliteal or dorsalis pedis pulses, at risk for venous gangrene and loss of limbs. The patient was anticoagulated and taken emergently to the operating room for vascular surgery where thrombolysis with alteplase and mechanical thrombectomy were performed. Bilateral thrombolysis infusion catheters were placed for two days. The patient had a return of arterial signals in the feet and decreasing clot burden. The patient is expected to make a full recovery.

Adding a genetic counseling assistant improves efficiency of hereditary cancer genetic counseling without impacting patient experience.

Improving efficiency of genetic counseling can allow genetic counselors to see more patients, increasing access to this valuable service. However, the patient experience should be carefully considered as changes are made, so that quality is not sacrificed. The primary outcome of this study was time in session with a board-certified genetic counselor at baseline (T0), after the addition of a genetic counseling assistant (GCA) (T1). The secondary outcome was the patient experience, which was collected from an electronic survey sent three days after the genetic counseling session. A total of 689 appointments were evaluated over 12 months; 291 in T0 by two genetic counselors (Jan-June 2019), 398 in T1 by two genetic counselors (August 2019-Jan 2020). The overall genetic counseling median appointment time decreased by 10 min in T1 (p < 0.001), and the median amount of time spent on post-session activities by the two genetic counselors decreased by 15 min (p < 0.001). There was an increase in the average number of patients seen per FTE per month from 24.3 in T0 to 33.2 in T1. There was no difference in overall patient experience from T0 to T1 (p = 0.3). There was high patient satisfaction, including with the amount of time spent in a session during both time periods (p = 0.63). This study found decreased appointment time with the addition of a GCA in a single clinic without impacting patient experience.

COVID-19, HIV, and Syphilis Contact Tracing: What Have We Learned and Where Are We Headed?

ABSTRACT: Contact tracing is a core public health intervention for a range of communicable diseases, in which the primary goal is to interrupt disease transmission and decrease morbidity. In this article, we present lessons learned from COVID-19, HIV, and syphilis in San Francisco to illustrate factors that shape the effectiveness of contact tracing programs and to highlight the value of investing in a robust disease intervention workforce with capacity to pivot rapidly in response to a range of emerging disease trends and outbreak response needs.

Using Geocoding to Identify COVID-19 Outbreaks in Congregate Residential Settings: San Francisco's Outbreak Response in Single-Room Occupancy Hotels.

More than 500 single-room occupancy hotels (SROs), a type of low-cost congregate housing with shared bathrooms and kitchens, are available in San Francisco. SRO residents include essential workers, people with disabilities, and multigenerational immigrant families. In March 2020, with increasing concerns about the potential for rapid transmission of COVID-19 among a population with disproportionate rates of comorbidity, poor access to care, and inability to self-isolate, the San Francisco Department of Public Health formed an SRO outbreak response team to identify and contain COVID-19 clusters in this congregate residential setting. Using address-matching geocoding, the team conducted active surveillance to identify new cases and outbreaks of COVID-19 at SROs. An outbreak was defined as 3 separate households in the SRO with a positive test result for COVID-19. From March 2020 through February 2021, the SRO outbreak response team conducted on-site mass testing of all residents at 52 SROs with outbreaks identified through geocoding. The rate of positive COVID-19 tests was significantly higher at SROs with outbreaks than at SROs without outbreaks (12.7% vs 6.4%; P < .001). From March through May 2020, the rate of COVID-19 cases among SRO residents was higher than among residents of other settings (ie, non-SRO residents), before decreasing and remaining at an equal level to non-SRO residents during later periods of 2020. The annual case fatality rate for SRO residents and non-SRO residents was similar (1.8% vs 1.5%). This approach identified outbreaks in a setting at high risk of COVID-19 and facilitated rapid deployment of resources. The geocoding surveillance approach could be used for other diseases and in any setting for which a list of addresses is available.