Ethical and practical considerations of pediatric refusal in clinical anesthesia: An educational review.

Children commonly refuse induction of anesthesia. Anesthesia providers must then decide whether to honor the child's dissent or to proceed over objection. In some circumstances, a forced induction involves restraining the child, incurring both practical and ethical harms to the patient-provider encounter. This educational review explores the practical dilemma encountered when a child dissents to induction of anesthesia. In the course of exploring this dilemma, dissent and associated terms are defined and compared, and the prominent ethical underpinnings regarding pediatric decision-making are described to clarify dissent as an ethical and practical concept. Important legal and professional standards are summarized, and practice trends are discussed to depict the current state of practice, including novel approaches to honoring pediatric dissent for elective surgeries. This information is then used to invite providers to consider where they ethically situate themselves within a legally and professionally defined space of acceptable practice. Finally, these considerations are synthesized to discuss important nuances regarding pediatric refusal, and some key questions are presented for clinicians to ponder as they consider their practice of choosing whether to honor pediatric dissent at induction.

The effects of grassland degradation on the genetic structure of a small mammal.

Grassland degradation is challenging the health of grassland ecosystems globally and causing biodiversity decline. Previous studies have demonstrated the impact of grassland degradation on the abundance and behavior of small mammals. Little is known about how it affects the genetic structure of gregarious mammals in the wild. This study explores the effects of grassland degradation on the genetic structure of a small burrowing mammal, plateau pika (Ochotona curzoniae). We used nine microsatellite loci to analyze the genetic diversity and genetic differentiation between colonies and genetic relatedness between individuals within the colony. We found that pikas in severely degraded grasslands had a significantly higher genetic diversity within colonies, a higher level of gene flow between colonies, and a lower genetic differentiation between colonies compared to pikas in less degraded grasslands. Individuals within colonies had a significantly lower genetic relatedness in severely degraded grasslands than in less degraded grasslands. This study has provided potential evidence of a significant impact of grassland degradation on the genetic structure of pikas, which has caused a breakdown of their kin-selected colony structure.

Pharmacokinetics of single dose doxycycline in the rectum, vagina, and urethra: implications for prevention of bacterial sexually transmitted infections.

BACKGROUND: Clinical trials showed a single oral dose of doxycycline taken after sex protects against STIs among men who have sex with men (MSM) but not women. Pharmacokinetic data at vaginal, rectal and penile sites of STI exposure are lacking. We examined vaginal, rectal and urethral doxycycline concentrations in men and women to better inform STI prevention. METHODS: Doxycycline pharmacokinetics in male and female participants 18-59 years of age were evaluated in blood and urine and on rectal and vaginal swabs collected at 1, 2, 4, 8, 24, 48, 72, 96 and 168 h after receiving a 200 mg oral doxycycline dose in a non-randomised single dose open label single centre study in Atlanta, Georgia. Rectal, vaginal, and cervical biopsies and male urethral swabs were collected 24 h after dosing (Trial registration: NCT04860505). Doxycycline was measured by liquid chromatography-mass spectrometry. FINDINGS: Eleven male and nine female participants participated in the study. Doxycycline concentrations on rectal and vaginal swabs collected up to 96 h after dosing were approximately twice those of plasma and remained above minimum inhibitory concentrations (MICs) for at least four, three, and two days for Chlamydia trachomatis, Treponema pallidum, and tetracycline-sensitive Neisseria gonorrhoeae, respectively. Geometric mean doxycycline concentrations in male urethral secretions (1.166 µg/mL; 95% CI 0.568-2.394 µg/mL), male rectal (0.596 µg/g; 0.442-0.803 µg/g), vaginal (0.261 µg/g; 0.098-0.696 µg/g) and cervical tissue (0.410 µg/g; 0.193-0.870 µg/g) in biopsies collected 24 h after dosing exceeded MICs. Plasma and urine doxycycline levels defined adherence markers up to four and seven days postdosing, respectively. No adverse events were reported in this study. INTERPRETATION: Doxycycline efficiently distributes to the rectum, vagina and urethra. Findings can help explain efficacy of STI prevention by doxycycline. FUNDING: Funded by CDC intramural funds, CDC contract HCVJCG-2020-45044 (to CFK).

Alpine grassland degradation intensifies the burrowing behavior of small mammals: evidence for a negative feedback loop.

Globally, grassland degradation is an acute ecological problem. In alpine grassland on the Tibetan Plateau, increased densities of various small mammals in degraded grassland are assumed to intensify the degradation process and these mammals are subject to lethal control. However, whether the negative impact of small mammals is solely a result of population size or also a result of activity and behavior has not been tested. In this study, we use plateau pika as a model to compare population size, core area of colony, and the number of burrow entrances and latrines between lightly and severely degraded grassland. We test whether the alleged contribution of pika to grassland degradation is a result of increased population size or increased burrowing activities of individuals in response to lower food abundance. We found that grassland degradation resulted in lower plant species richness, plant height, and biomass. Furthermore, the overall population size of pika was not significantly affected by location in lightly and severely degraded grassland. However, pika core areas in severely grassland degradation were significantly larger and had significantly higher densities of burrows and latrines. Our study provides convincing evidence that habitat-induced changes in the behavior of small, burrowing mammals, such as pika, can exacerbate grassland degradation. This finding has significant implications for managing small mammals and restoring degraded grassland ecosystems.

Experiences of junior doctors who shielded during the COVID-19 pandemic.

BACKGROUND: Shielding was introduced to protect clinically extremely vulnerable people during the COVID-19 pandemic. For junior doctors who had to shield, this meant pausing in-person clinical duties to protect their health. There is limited literature regarding this, and the available evidence is predominantly surveys or blogs that describe mainly negative experiences including guilt, isolation, inadequate support and Return To Work (RTW) concerns. Exploring the experiences of this group is valuable to understand the impact on them, and their support needs moving forward. METHODS: This was a qualitative study using individual semi-structured interviews. Three junior doctors were recruited using volunteer and snowball sampling. Interview transcripts were analysed using thematic analysis. FINDINGS: Seven themes were finalised: (1) Professional value, (2) Threatened autonomy, (3) Self-motivated, (4) Educational impact, (5) Mental health, (6) Inadequate support and (7) Return To Work concerns. DISCUSSION: Participant experiences largely reflected the evidence base including increased skill and knowledge acquisition, alongside guilt, isolation and inadequate support whilst shielding and upon RTW. These findings add valuable qualitative data to a scarcity of literature. However, caution should be applied when transferring these findings to other junior doctors, noting the small sample and regional setting. A small research grant has been secured for further research with a larger sample size incorporating the supervisor perspective. CONCLUSION: These findings demonstrate that shielding was a challenging experience for these junior doctors including impacts on mental health and insufficient support. This lack of support requires further attention to refine and strengthen available support structures.

Exploring the experiences of junior doctors who were shielding during the COVID-19 pandemic: a qualitative study of semi-structured interviews.

BACKGROUND: The term "Shielding" was introduced in the UK during the COVID-19 pandemic to protect approximately 4 million people at highest risk from infection. Shielding was characterised by extreme isolation and applied to those with certain illnesses, disabilities, and during pregnancy. For the estimated 1300 high-risk doctors, shielding meant abrupt departure from the clinical environment. We aimed to understand the impact of shielding on junior doctors (JDs) by interviewing them and their consultants. METHODS: This qualitative study used individual semi-structured interviews and reflexive thematic analysis. Virtual interviews were conducted between Sept 2, and Nov 30, 2022, using an interview guide, including open questions around impacts on training, career, and health. 11 JDs and 2 consultants were recruited via Scotland-wide purposive and snowball sampling. Written informed consent was obtained. 12 of 13 participants were women. Eight JDs were shielding because of health issues, and three because of pregnancy. Participant specialties included primary care, secondary care, and foundation and specialty training. Interview transcripts were coded by the lead author and the second author acted as a critical friend. FINDINGS: Despite making important contributions working from home, most JDs (73%, eight of 11) felt that their work was undervalued during shielding. They felt forgotten, feeling they had to "pester" supervisors to be allocated work. All participants reported inadequate support at Occupational Health and workplace levels, including limited supervision or information about training impacts. Negative attitudes towards JDs were experienced by 82% (nine of 11) of JDs, including being denied reasonable adjustments and threatened with dismissal if not following shielding advice. Consultants described supervisory challenges including not receiving guidance or resources and ongoing issues supporting disabled and pregnant JDs beyond the pandemic. INTERPRETATION: These findings offer novel qualitative insight into the impacts of shielding on JDs in Scotland. Findings indicated that support infrastructure was not fit for purpose. Given the significant number of JDs that take prolonged leave from the clinical environment, and the JDs working with disabilities and during pregnancy, these findings are of ongoing concern. Although the sample size was small and the study was set in a specific region, these findings suggest there is potential to improve support infrastructure and move towards a more inclusive clinical environment that recognises, celebrates, and benefits from the value of a diverse workforce. FUNDING: Scottish Medical Education Research Consortium.

ON LIVER FLUKE (FASCIOLA HEPATICA) IN CAPTIVE VICUÑAS (VICUGNA VICUGNA) AT KNOWSLEY SAFARI, PRESCOT, UNITED KINGDOM.

Knowsley Safari (KS), Prescot, United Kingdom houses a variety of captive exotic ungulates. As part of their animal welfare plan, a prospective coprological survey was undertaken for liver fluke. In June 2021, 330 fecal samples, representative of 18 exotic ungulate species, were processed by sedimentation and filtration, with examination by coproscopy. Finding fascioliasis in all five vicuña alone, with fecal egg counts ranging from one to eight eggs per gram, anthelminthic treatment was attempted twice, with three coprological reviews. While the first anthelminthic treatment (oxyclozanide) was equivocal, the second anthelminthic treatment (triclabendazole) was proven effective upon two later follow-ups. An initial malacological survey of 16 freshwater sites in KS, first found Galba truncatula at two sites in June 2021, then upon more extensive searching subsequently within the vicuña's enclosure. It appears that F. hepatica was locally acquired, being the first report of fascioliasis within captive vicuñas in the United Kingdom. To develop a better fluke-management plan, regular coprological and malacological surveillance is justified, perhaps with molecular xenomonitoring of snails, alongside prompt administration of appropriate flukicide as required.

Staged treatment of placenta accreta spectrum: A combined surgical and radiological approach.

BACKGROUND: Placenta accreta spectrum (PAS) is a rare but serious complication of pregnancy. AIMS: The aim of this study was to determine maternal and neonatal outcomes following a combined surgical and interventional radiology (IR) approach to managing PAS, and the risks associated with this technique. METHODS AND MATERIALS: Retrospective cohort study of all cases of PAS in a tertiary maternity centre between January 2001 and July 2020. Women who underwent caesarean hysterectomy for histologically confirmed PAS with a staged surgical and IR approach were compared with those who underwent caesarean hysterectomy without IR. Maternal, neonatal outcomes, surgical and radiological complications were assessed. RESULTS: Forty-six women were included in the study, and 30/46 (65.2%) underwent the staged surgical and IR approach. Women in the staged group had less overall blood loss (1794 mL vs 3713 mL; P < 0.001), less requirement for blood transfusion (40% vs 75%; P < 0.001), and a lower mean volume of packed red cells transfused (2.5 vs 6.1 units). Anaesthetic and operative times were longer for the staged group (468 vs 189 min: 272 vs 141 min P < 0.001), respectively. There were no differences in rates of neonatal or maternal complications between the two groups. CONCLUSION: This study demonstrates that a staged procedure combining surgery and IR for PAS results in a considerable reduction in blood loss, need for transfusion, and units of packed red cells transfused compared with surgery alone. The staged procedure required significantly longer anaesthetic and operative times; however, there were no differences in maternal and neonatal morbidity.

HIV Pre-exposure Prophylaxis Persistence and Adherence Among Men Who Have Sex With Men in Four US Cities.

BACKGROUND: HIV pre-exposure prophylaxis (PrEP) persistence and adherence are critical to ending the HIV epidemic in the United States. SETTING: In 2017 National HIV Behavioral Surveillance, HIV-negative men who have sex with men (MSM) in 4 US cities completed a survey, HIV testing, and dried blood spots at recruitment. METHODS: We assessed 3 PrEP outcomes: persistence (self-reported PrEP use at any time in the past 12 months and had tenofovir, emtricitabine, or tenofovir diphosphate detected in dried blood spots), adherence at ≥4 doses/week (self-reported past-month PrEP use and tenofovir diphosphate concentration ≥700 fmol/punch), and adherence at 7 doses/week (self-reported past-month PrEP use and tenofovir diphosphate concentration ≥1250 fmol/punch). Associations with key characteristics were examined using log-linked Poisson regression models with generalized estimating equations. RESULTS: Among 391 MSM who took PrEP in the past year, persistence was 80% and was lower among MSM who were younger, had lower education, and had fewer sex partners. Of 302 MSM who took PrEP in the past month, adherence at ≥4 doses/week was 80% and adherence at 7 doses/week was 66%. Adherence was lower among MSM who were younger, were Black, and had fewer sex partners. CONCLUSIONS: Although persistence and adherence among MSM were high, 1 in 5 past-year PrEP users were not persistent and 1 in 5 past-month PrEP users were not adherent at levels that would effectively protect them from acquiring HIV (ie, ≥4 doses/week). Efforts to support PrEP persistence and adherence should include MSM who are young, are Black, and have less education.

Participation in the CARES Act Provider Relief Fund policy by dentists in South Carolina's safety net.

OBJECTIVES: The Coronavirus Aid, Relief, and Economic Security (CARES) Act appropriated $100 billion to the Provider Relief Fund, allowing for direct payments to health care providers due to COVID-19. Few studies have evaluated participation in the Provider Relief Fund (PRF), and none have specifically looked at dental providers in the safety net. METHODS: We conducted a retrospective, secondary data analysis using a quasi-experimental cohort design of South Carolina dentists who received PRF payments, comparing those who did and did not participate in the safety net. Safety net practice was operationalized as those participating in Medicaid, and whether they provided care in dental health professional shortage areas, or rural communities. RESULTS: Of the 628 dental providers in South Carolina who received PRF payments, 34% were identified as Medicaid providers while 66% did not participate in Medicaid; we found no statistical difference between payments to Medicaid versus non-Medicaid dental providers. Of PRF payments to dental providers participating in South Carolina's Medicaid program, we found no difference between payments to rural and urban providers but did find that practices offering services in dental care shortage areas received less than providers practicing in counties not designated as a shortage area. CONCLUSIONS: The PRF achieved its goal of distributing financial support to providers affected by the COVID-19 pandemic. But without policy imperatives linked to need-based allocations or incentives for PRF recipients to serve safety net populations, we may later learn this was a missed opportunity for PRF.

Pharmacology of boosted and unboosted integrase strand transfer inhibitors for two-dose event-driven HIV prevention regimens among men.

BACKGROUND: Event-driven HIV prevention strategies are a priority for users who do not require daily pre-exposure prophylaxis (PrEP). Regimens containing integrase strand transfer inhibitors (INSTIs) are under evaluation as alternatives to daily PrEP. To better understand INSTI distribution and inform dosing selection we compared the pharmacology of two-dose boosted elvitegravir and unboosted bictegravir regimens in MSM. MATERIALS AND METHODS: Blood, rectal and penile secretions and rectal biopsies were collected from 63 HIV-negative MSM aged 18-49 years. Specimens were collected up to 96 h after two oral doses of tenofovir alafenamide and emtricitabine with elvitegravir boosted by cobicistat or unboosted bictegravir given 24 h apart. Antiretroviral drugs were measured by LC-MS. RESULTS: Mean bictegravir plasma concentrations remained above the 95% protein-adjusted effective concentration 96 h after dosing [273 (95% CI: 164-456) ng/mL] whereas elvitegravir plasma concentrations became undetectable 48 h after the second dose. Bictegravir and elvitegravir reached rectal tissues within 2 h after the first dose, and elvitegravir tissue concentrations [1.07 (0.38-13.51) ng/mg] were greater than bictegravir concentrations [0.27 (0.15-0.70) ng/mg]. Both INSTIs became undetectable in tissues within 96 h. Elvitegravir and bictegravir were not consistently detected in penile secretions. CONCLUSIONS: Whereas bictegravir plasma concentrations persist at least 4 days after a two-oral-dose HIV prophylaxis regimen, elvitegravir accumulates in mucosal tissues. Differing elvitegravir and bictegravir distribution may result in variable mucosal and systemic antiviral activity and can inform dosing strategies for event-driven HIV prevention.

Safe, supportive neighborhoods: Are they associated with childhood oral health?

OBJECTIVE: There has been limited examination of how community-level supports may influence oral health metrics among children. The purpose of our study is to examine the association between two types of community-level positive childhood experiences and oral healthcare and oral health outcomes among children ages 6 to 17 years of age. METHODS: This study uses a cross-sectional data set from the 2018-2019 National Survey of Children's Health. Two oral health metrics were used: preventive dental care, measured as one or more preventive dental visits in the past 12 months, and tooth decay, measured as tooth decay or cavities in the last 12 months. To quantify living in safe, stable, equitable environments, questions on residing in a safe and supportive neighborhood were used. Descriptive statistics and bivariate analyses were used to calculate frequencies, proportions, and unadjusted associations for each variable (n = 40,290). Multivariable logistic regression models were used. RESULTS: In an adjusted analysis, children who lived in a supportive neighborhood had a higher likelihood of receiving a preventive dental visit than children who did not live in a supportive neighborhood (aOR 1.41; 95% CI 1.21-1.65). Children who lived in a safe neighborhood were less likely to have tooth decay than children who did not live in a safe neighborhood (aOR 0.75; 95% CI 0.65-0.86). CONCLUSIONS: The findings from this study highlight the role of social structures in tightening the safety net for oral healthcare in children.

Artificial light at night correlates with seabird groundings: mapping city lights near a seabird breeding hotspot.

Artificial light at night (ALAN) is a growing conservation concern for seabirds, which can become disoriented and grounded by lights from buildings, bridges and boats. Many fledgling seabirds, especially Procellariiformes such as petrels and shearwaters, are susceptible to light pollution. The Hauraki Gulf, a seabird hotspot located near Tamaki Makaurau/Auckland, Aotearoa-New Zealand's largest urban city, with a considerable amount of light pollution and regularly documented events of seabird groundings. We aim to identify the characteristics of locations especially prone to seabird groundings. We used an online database of seabirds taken to a wildlife rescue facility by the public to map 3 years of seabird groundings and test for correlations between seabird groundings and the natural night sky brightness. We found that areas with lower amounts of natural night sky brightness and greater light pollution often had a higher number of seabirds grounded. Further, we identified important seasonal patterns and species differences in groundings. Such differences may be a by-product of species ecology, visual ecology and breeding locations, all of which may influence attraction to lights. In general, seabird groundings correlate with the brightness of the area and are species-specific. Groundings may not be indicative of human or seabird population abundance considering some areas have a lower human population with high light levels and had high amounts of seabird groundings. These findings can be applied worldwide to mitigate groundings by searching and targeting specific brightly lit anthropogenic structures. Those targeted structures and areas can then be the focus of light mitigation efforts to reduce seabird groundings. Finally, this study illustrates how a combination of community science, and a concern for seabirds grounded from light attraction, in addition to detailed animal welfare data and natural night sky brightness data can be a powerful, collaborative tool to aid global conservation efforts for highly-at-risk animals such as seabirds.

Differences in the Active Endometrial Microbiota across Body Weight and Cancer in Humans and Mice.

Obesity is a risk factor for endometrial cancer. The aim of this study was to determine whether actively replicating microbiota in the endometrium differ between obese vs. lean and cancer vs. benign states. We performed 16S rRNA amplicon sequencing on endometrial tissues from lean and obese women with and without endometrial cancer, and lean and obese mice. Results displayed human endometrial microbiota clustered into three community types (R = 0.363, p = 0.001). Lactobacillus was dominant in community type 1 (C1) while community type 2 (C2) had high levels of Proteobacteria and more cancer samples when compared to C1 (p = 0.007) and C3 (p = 0.0002). A significant increase in the prevalence of the C2 community type was observed across body mass index and cancer (χ2 = 14.24, p = 0.0002). The relative abundance of Lactobacillus was lower in cancer samples (p = 0.0043), and an OTU with 100% similarity to Lactobacillus iners was enriched in control samples (p = 0.0029). Mouse endometrial microbiota also clustered into three community types (R = 0.419, p = 0.001) which were not influenced by obesity. In conclusion, obesity and cancer are associated with community type prevalence in the human endometrium, and Lactobacillus abundance is associated with normal uterine histologies in humans and mice.

Pharmacokinetics of vaginally applied integrase inhibitors in macaques.

OBJECTIVES: We conducted a detailed pharmacokinetic assessment in macaques treated with vaginal gels formulated with HIV integrase strand transfer inhibitors (INSTIs) to better understand drug distribution and identify INSTI concentrations associated with previously demonstrated in vivo protection against vaginal simian HIV challenge. METHODS: Six macaques received vaginal gel containing 1% raltegravir (30 mg) once-weekly over 6 weeks. Following a washout period, five macaques received once-weekly gel containing 0.23% L-870,812 (7 mg). Drug concentrations were measured in plasma, mucosal fluids and vaginal tissues at baseline and 2, 5 and 24 h post-dosing. RESULTS: The median maximum concentration (Cmax) for raltegravir and L-870,812 in plasma was below the limit of quantification and 41.1 ng/mL, respectively. The Cmax in vaginal fluids (1441 and 1250 µg/mL) and tissues (266.7 and 368.4 µg/g) was achieved 2-5 h after dosing, respectively. A similar half-life was observed for raltegravir and L-870,812 in vaginal fluids (8-10 h) and remained 3-4 orders of magnitude above the protein-adjusted IC95 (0.016 and 0.106 µg/mL, respectively) at 24 h. Drug concentrations in vaginal fluids correlated well with those in vaginal tissues (Pearson r ≥ 0.788). Both drugs were consistently detected in rectal fluids 2 h after vaginal dosing, albeit at much lower levels (31-92-fold) than those in vaginal fluids. CONCLUSIONS: To the best of our knowledge, this study provides the first data on INSTI levels in vaginal tissues associated with in vivo protection and demonstrates rectal drug distribution of INSTIs after vaginal dosing. These findings may inform dose selection for topical products with INSTIs for HIV prevention.

Antiretroviral drug exposure in urethral and glans surface sampling of the penis.

BACKGROUND: HIV exposure to penile tissues provides a risk of acquisition among men, yet studies evaluating penile antiretroviral (ARV) drug distribution have been lacking. We measured ARVs on urethral and glans surface swabs collected following a dose of tenofovir alafenamide, emtricitabine, elvitegravir, darunavir and cobicistat. METHODS: Thirty-five HIV-negative male participants provided urethral swabs, glans swabs, rectal swabs, blood and urine up to 96 h following a single dose of tenofovir alafenamide/emtricitabine/elvitegravir/cobicistat and darunavir. ARVs were measured by liquid chromatography-mass spectrometry with a lower limit of detection (LOD) of 1 ng/swab for swabs and 10 ng/mL for plasma and urine. Concentrations are reported as median and range. RESULTS: Urethral swab emtricitabine and darunavir concentrations peaked at 4 h for emtricitabine (36 ng/swab; 3-307 ng/swab) and 8 h for darunavir (25 ng/swab; 2-52 ng/swab). Glans swab emtricitabine and darunavir concentrations peaked 24 h after dosing (emtricitabine 14 ng/swab,

A Technical Assistance Curriculum for Expanding Sustainable School-Based Oral Health Programs in the Carolinas' Dental Safety Net.

PURPOSE: School-based oral health programs (SBOHPs) provide opportunities to address oral health inequities by providing convenient access points for care. No published guidelines on SBOHP implementation existed. Our work describes how philanthropic, public, and academic organizations partnered to support dental safety net providers with designing comprehensive SBOHPs in North and South Carolina. DESCRIPTION: A multi-sector leadership team was established to manage a new SBOHP philanthropic-funded grant program organized into two phases, Readiness and Implementation, with the former a 6-month planning period in preparation of the latter. Readiness included technical assistance (TA) delivered through coaching and 15 online learning modules organized in four domains: operations, finance, enabling services, and impact. Organizations could apply for implementation grants after successful TA completion. Process evaluation was used including a Readiness Stoplight Report for tracking progression. ASSESSMENT: Ten Readiness grantees completed the TA. A variety of models resulted, including mobile, portable and fixed clinics. Descriptive analysis was conducted on the readiness stoplight reports. Components of the operation and finance domains required were the most time-intensive, specifically the development of policy manuals, production goals, and financial performance tracking. CONCLUSION: The program's structure resulted in (a) a two-state learning community, (b) SBOHP practice and policy alignment, and (c) coordinated program distribution. TA improvements are planned to account for COVID-19 threats, including school closures, space limitations, and transmission fears. Telehealth, non-aerosolizing procedures, and improved scheduling and communication can address concerns. Organizations considering SBOHPs should explore similar recommendations to navigate adverse circumstances.

The feasibility of modified HIV and antiretroviral drug testing using self-collected dried blood spots from men who have sex with men.

BACKGROUND: In the US, one in six men who have sex with men (MSM) with HIV are unaware of their HIV infection. In certain circumstances, access to HIV testing and viral load (VL) monitoring is challenging. The objective of this study was to evaluate the feasibility of conducting laboratory-based HIV and antiretroviral (ARV) drug testing, and VL monitoring as part of two studies on self-collected dried blood spots (DBS). METHODS: Participants were instructed to collect DBS by self-fingerstick in studies that enrolled MSM online. DBS from the first study (N = 1444) were tested with HIV serological assays approved by the Food and Drug Administration (FDA). A subset was further tested with laboratory-modified serological and VL assays, and ARV levels were measured by mass spectrometry. DBS from the second study (N = 74) were only tested to assess VL monitoring. RESULTS: In the first study, the mail back rate of self-collected DBS cards was 62.9%. Ninety percent of DBS cards were received at the laboratory within 2 weeks from the day of collection, and 98% of the cards had sufficient spots for one assay. Concordance between FDA-approved and laboratory-modified protocols was high. The samples with undetectable ARV had higher VL than samples with at least one ARV drug. In the second study, 70.3% participants returned self-collected DBS cards, and all had sufficient spots for VL assay. High VL was observed in samples from participants who reported low ARV adherence. CONCLUSIONS: In these studies, MSM were able to collect and provide adequate DBS for HIV testing. The FDA-approved and laboratory-modified testing algorithms performed similarly. DBS collected at home may be feasible for HIV testing, ARV measurement, and monitoring viral suppression.

Patients' and caregivers' maximum acceptable risk of death for non-curative gene therapy to treat Duchenne muscular dystrophy.

BACKGROUND: Gene therapy offers an etiologically targeted treatment for genetic disorders. Little is known about the acceptance of mortality risk among patients with progressive, fatal conditions. We assessed patients' and caregivers' maximum acceptable risk (MAR) of mortality for gene therapy when used to treat Duchenne muscular dystrophy (DMD). METHODS: The threshold technique was used to assess tolerance for mortality risks using a hypothetical vignette. Gene therapy was described as non-curative and resulting in a slowing of progression and with a 10-year benefit duration. MAR was analyzed using interval regression for gene therapy initiated "now"; in the last year of walking well; in the last year of being able to bring arms to mouth; and in newborns (for caregivers only). RESULTS: Two hundred eighty-five caregivers and 35 patients reported the greatest MAR for gene therapy initiated in last year of being able to lift arms (mean MAR 6.3%), followed by last year of walking well (mean MAR 4.4%), when used "now" (mean MAR 3.5%), and when used in the newborn period (mean MAR 2.1%, caregivers only). About 35% would accept ≥200/2000 risk in the last year of being able to lift arms. Non-ambulatory status predicted accepting 1.8 additional points in MAR "now" compared with ambulatory status (p = 0.010). Respondent type (caregiver or patient) did not predict MAR. CONCLUSION: In this first quantitative study to assess MAR associated with first-generation DMD gene therapy, we find relatively high tolerance for mortality risk in response to a non-curative treatment scenario. Risk tolerance increased with disease progression. Patients and caregivers did not have significantly different MAR. These results have implications for protocol development and shared decision making.