Topical Oral and Intranasal Antiviral Agents for Coronavirus Disease 2019 (COVID-19).

With the largest viral loads in both symptomatic and asymptomatic patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) present in the oral and nasal cavities, agents that act on these two areas have the potential for large therapeutic and prophylactic benefit. A literature review was conducted to elucidate the possible agents useful in treatment of SARS-CoV-2. These agents were evaluated for their current applications, adverse reactions, their current state of study, and any future considerations in their management of coronavirus disease 2019 (COVID-2019). Our review has found that, while there are many promising agents with proven efficacy in their in-vitro efficacy against SARS-CoV-2, more clinical trials and in-vivo studies, as well as safety trials, must be conducted before these agents can be effectively implemented.

DNA detection and seroprevalence of human papillomavirus in a cohort of adolescent women.

OBJECTIVES: Human papillomavirus (HPV) infections are common in adolescent women, while the rare cancerous sequelae of HPV infections do not generally occur until the 4th or 5th decades of life. This prospective study of a cohort of adolescent women was performed to further our knowledge of the natural history of incident and prevalent HPV infections. METHODS: Self-vaginal swabs collected from high-risk, unvaccinated adolescent women in a longitudinal study were analysed for HPV DNA. Sera were collected at enrolment and later tested for HPV antibodies. Statistical analysis was performed to determine the HPV genotype distribution and duration of detection, and to determine rates of seropositivity and seroconversion for HPV types represented in the assays. RESULTS: 146 subjects (mean enrolment age=15.4 years; mean duration of follow-up=5.8 years) had samples adequate for analysis of HPV detection, and 95 of these subjects had paired sera available. The cumulative prevalence for high-risk and low-risk HPV types was 95.9% and 91.1%, respectively. HPV types 6, 11, 16 and 18 (HPV types represented in the quadrivalent vaccine) were found at some point in 40.4%, 6.2%, 48% and 24% of participants, respectively. Serological data confirmed exposure to these vaccine-covered types, as well as to other high-risk HPV types. CONCLUSIONS: In this cohort of adolescent women, high- and low-risk HPV types were frequently detected, and serological data confirmed exposure in most subjects. The high-prevalence HPV types represented in the quadrivalent HPV vaccine further support vaccination of women at an age well before sexual debut.

High frequency of human papillomavirus detection in the vagina before first vaginal intercourse among females enrolled in a longitudinal cohort study.

BACKGROUND: Genital human papillomavirus (HPV) infection is believed to be primarily sexually transmitted. Few studies have documented the detection of HPV in the vagina before first vaginal intercourse. METHODS: We used a longitudinally followed cohort of adolescent females without prior vaginal intercourse to examine the frequency of detection of vaginal HPV and the association between first reported HPV detection and noncoital sexual behaviors. RESULTS: HPV was detected in 45.5% of subjects (10 of 22) before first vaginal sex. Seven of these 10 subjects reported noncoital behaviors that, in part, might have explained genital transmission. CONCLUSIONS: HPV can be detected in the vagina before first sexual intercourse, highlighting the need for early vaccination.

Association of Chlamydia trachomatis infection with redetection of human papillomavirus after apparent clearance.

BACKGROUND: Persistent infection with oncogenic human papillomavirus (HPV) is associated with an increased risk of cervical malignancy. Redetection of type-specific HPV after a period of nondetection may be caused by reactivation of a low-level persistent infection. Little is known about factors associated with type-specific HPV redetection. METHODS: For a longitudinal cohort of adolescent women with frequent behavioral and sexually transmitted infection (STI) information (every 3 months), Cox proportional hazard models were used to assess the influence of sexual behaviors and STIs on the redetection of oncogenic or high-risk HPV infections. RESULTS: A total of 210 type-specific high-risk HPV detection episode periods were identified in this longitudinal cohort; 71 (33.8%) were characterized by a period of nondetection followed by redetection. Chlamydia trachomatis (hazard ratio [HR], 3.14; 95% confidence interval [CI], 1.44-6.86) was associated with redetection; redetection was >2 times more likely with each additional self-reported sex partner in the past 3 months (HR, 2.26; 95% CI, 1.35-3.78). CONCLUSIONS: This study demonstrates the role of C. trachomatis and number of recent sexual partners in type-specific HPV redetection. Given that persistent oncogenic HPV infections are associated with cancer-related outcomes, understanding the potential role of such factors in the pathogenesis of HPV-related outcomes is important.

High Nonunion and Amputations Rates With Either Early Intramedullary Nail Removal or Retention for Tibial Shaft Fracture-Related Infections.

OBJECTIVES: To compare debridement, antibiotics, and implant retention (DAIR) and intramedullary nail (IMN) removal with subsequent strategy for fracture stabilization in the treatment of tibia fracture-related infections (FRIs) occurring within 90 days of initial IMN placement. DESIGN: Retrospective case-control. SETTING: Four academic, Level 1 trauma centers. PATIENTS: Sixty-six patients who subsequently received unplanned operative treatment for FRI diagnosed within 90 days of initial tibia IMN. INTERVENTION: DAIR versus IMN removal pathways. MAIN OUTCOME MEASUREMENTS: Fracture union. RESULTS: Twenty-eight patients (42.4%) were treated with DAIR and 38 (57.6%) via IMN removal with subsequent strategy for fracture stabilization. Mean follow-up was 16.3 months. At final follow-up, ultimate bone healing was achieved in 75.8% (47/62), whereas 24.2% (15/62) had persistent nonunion or amputation. No significant difference was observed in ultimate bone healing ( P = 0.216) comparing DAIR and IMN removal. Factors associated with persistent nonunion or amputation were time from injury to initial IMN ( P < 0.001), McPherson systemic host grade B ( P = 0.046), and increasing open-fracture grade, with Gustilo-Anderson IIIB/IIIC fractures being the worst ( P = 0.009). Fewer surgeries after initial FRI treatment were positively associated with ultimate bone healing ( P = 0.029). CONCLUSIONS: Treatment of FRI within 90 days of tibial IMN with DAIR or IMN removal with subsequent strategy for fracture stabilization results in a high rate, nearly 1 in 4, of persistent nonunion or amputation, with neither appearing superior for improving bone healing outcomes. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Poverty, Comorbidity, and Ethnicity: COVID-19 Outcomes in a Safety Net Health System.

Objective: To determine if race-ethnicity is correlated with case-fatality rates among low-income patients hospitalized for COVID-19. Research Design: Observational cohort study using electronic health record data. Patients: All patients assessed for COVID-19 from March 2020 to January 2021 at one safety net health system. Measures: Patient demographic and clinical characteristics, and hospital care processes and outcomes. Results: Among 25,253 patients assessed for COVID-19, 6,357 (25.2%) were COVID-19 positive: 1,480 (23.3%) hospitalized; 334 (22.6%) required intensive care; and 106 (7.3%) died. More Hispanic patients tested positive (51.8%) than non-Hispanic Black (31.4%) and White patients (16.7%, P<.001]. Hospitalized Hispanic patients were younger, more often uninsured, and less likely to have comorbid conditions. Non-Hispanic Black patients had significantly more diabetes, hypertension, obesity, chronic kidney disease, and asthma (P<.05). Non-Hispanic White patients were older and had more cigarette smoking history, COPD, and cancer. Non-Hispanic White patients were more likely to receive intensive care (29.6% vs 21.1% vs 20.8%, P=.007) and more likely to die (12% vs 7.3% vs 3.5%, P<.001) compared with non-Hispanic Black and Hispanic patients, respectively. Length of stay was similar for all groups. In logistic regression models, Medicaid insurance status independently correlated with hospitalization (OR 3.67, P<.001) while only age (OR 1.076, P<.001) and cerebrovascular disease independently correlated with in-hospital mortality (OR 2.887, P=.002). Conclusions: Observed COVID-19 in-hospital mortality rate was lower than most published rates. Age, but not race-ethnicity, was independently correlated with in-hospital mortality. Safety net health systems are foundational in the care of vulnerable patients suffering from COVID-19, including patients from under-represented and low-income groups.

The natural history of incident gonococcal infection in adolescent women.

BACKGROUND: The natural history of Neisseria gonorrhoeae (GC) infections is largely unknown. The objective of the current study was to use sequential weekly vaginal samples and molecular techniques to describe the natural history of incident gonorrhea infections in adolescent women. METHODS: A cohort of 387 adolescent women aged 14 to 17 were enrolled from urban, primary care clinics and followed longitudinally for a period of up to 8 years. Weekly vaginal swabs and daily diaries were provided during 12-week periods biannually, beginning and ending with a clinic visit, where all identified infections were treated. For this study, specimens and data from 16 women who became infected with GC during a weekly sampling period were analyzed. RESULTS: GC organism load was highly variable between subjects. The number of organisms did not significantly differ across the first 6 weeks of infection (P = 0.59). Organism load did not differ among women with a previously documented GC infection at week 1 (P = 0.43) or across the first 6 weeks of infection (P = 0.67). The association of concurrent chlamydial infection on gonorrhea organism load was borderline significant over the first 6 weeks of infection (P = 0.06). CONCLUSIONS: Individual shedding patterns varied widely, and GC organism load did not decline in women for at least several weeks and were not associated with genitourinary symptoms. Chlamydia coinfection is associated with higher GC organism loads, potentially increasing chances of transmission. This study utilized a standardized quantification technique to assess GC organism load.

Intranasal Antiviral Drug Delivery and Coronavirus Disease 2019 (COVID-19): A State of the Art Review.

OBJECTIVE: To provide a state of the art review of intranasal antiviral drug delivery and to discuss current applications, adverse reactions, and future considerations in the management of coronavirus disease 2019 (COVID-19). DATA SOURCES: PubMed, Embase, and Clinicaltrials.gov search engines. REVIEW METHODS: A structured search of the current literature was performed of dates up to and including April 2020. Search terms were queried as related to topics of antiviral agents and intranasal applications. A series of video conferences was convened among experts in otolaryngology, infectious diseases, public health, pharmacology, and virology to review the literature and discuss relevant findings. CONCLUSIONS: Intranasal drug delivery for antiviral agents has been studied for many years. Several agents have broad-spectrum antiviral activity, but they still require human safety and efficacy trials prior to implementation. Intranasal drug delivery has potential relevance for future clinical trials in the settings of disease spread prevention and treatment of SARS-CoV-2 and other viral diseases. IMPLICATIONS FOR PRACTICE: Intranasal drug delivery represents an important area of research for COVID-19 and other viral diseases. The consideration of any potential adverse reactions is paramount.

Necrotizing retinitis due to syphilis in a patient with AIDS.

The ocular manifestations of syphilis are varied. Ocular syphilis can occur during any stage of infection and involve virtually any part of the eye. In immunocompetent individuals, the most common etiologies include syphilitic uveitis. Although the clinical presentation of ocular syphilis in HIV-infected patients is also widespread, posterior segment involvement has been more commonly described particularly in patients with AIDS. The diagnosis of syphilitic retinitis is challenging since its clinical presentation mimics retinitis caused by other viral etiologies. In addition, HIV-infected individuals with syphilis are more likely to develop aberrant serologic responses. Recognition of syphilitic retinitis and prompt initiation of penicillin therapy is of critical importance since syphilitic retinitis generally responds well to treatment and loss of vision is reversible. In this report, we describe a 39-year-old female with advanced stages of AIDS who developed necrotizing retinitis due to syphilis. Prompt initiation of intravenous penicillin led to excellent visual outcome for this patient despite significantly decreased visual acuity on presentation.

Natural history of multiple human papillomavirus infections in female adolescents with prolonged follow-up.

PURPOSE: The aim of the study was to better characterize the natural history of human papillomavirus (HPV) infections in female adolescents. METHODS: Female adolescents were enrolled in a longitudinal study. Self-vaginal samples were obtained every 3 months and tested for HPV. No participants received HPV vaccination. The findings for 40 female adolescents with the longest follow-up are reported in this study. RESULTS: Average age at the time of enrollment was 15.2 years (range: 14-17; SD: .97). Mean duration of follow-up was 6.7 years (range: 4.4-9.2; SD: 1.2). In all, 32 participants (80%) reported being involved in sexual activity before their enrollment in the study; all reported being involved in sexual activity before enrollment; all reported being involved in sexual activity during follow-up. Baseline and cumulative prevalence of HPV among participants was 55% and 100%, respectively. During the study, each participant tested positive for a mean of 14 HPV types. Cumulatively, HPV 16 was detected in 29 of 40 participants (72.5%). Mean duration of high- and low-risk infections was 655.9 (median: 433) and 524.1 days (median: 334), respectively. CONCLUSION: With prolonged follow-up, HPV infections with multiple types were found in all participants. Most had infection with HPV-16 or HPV-18, the oncogenic types represented in current vaccines, as well as infection with other oncogenic types. These data reinforce the importance of vaccine and non-vaccine strategies for prevention of HPV infections.