Pilot label comprehension study for an over-the-counter combined oral contraceptive pill in the United States.

CONTEXT: A growing body of evidence supports over-the-counter access to oral contraceptives in the United States. An important consideration for over-the-counter approval is consumers' ability to understand key package label messages related to safety and effectiveness without clinician involvement. We developed a prototype over-the-counter Drug Facts Label for a combined oral contraceptive pill and conducted a pilot label comprehension study to evaluate consumer understanding of key messages for use. METHODS: In November-December 2020, we conducted interviews with 163 adults and teens in the United States who were aged 12-49 years and identified as female or another gender but had a uterus and the ability to become pregnant. We developed 11 primary endpoints based on assessment of clinical risks that could occur if consumers fail to heed them, including messages about contraindications and directions for use; 11 secondary endpoints represented additional important information but with lower potential for clinical consequences if not understood. We evaluated endpoint comprehension by computing frequencies, percentages, and 2-sided Exact (Clopper-Pearson) 95% confidence intervals for observed proportions. RESULTS: Ten of the 11 primary endpoints and 10 of the 11 secondary endpoints were each understood by ≥95% of participants. The remaining primary endpoint on use with prior blood clots was understood by 89% of participants. The remaining secondary endpoint on the product being designed for "people who have the ability to become pregnant" was understood by 83% of participants. CONCLUSION: Participants understood the key label information required for safe and effective combined oral contraceptive use without clinician involvement.

Adherence among a cohort taking progestin-only pills prescribed by a healthcare provider: Results of the BENCHMARK study.

OBJECTIVES: To measure adherence over six months of progestin-only pill (POP) use. STUDY DESIGN: Prospective observational cohort study measuring adherence to daily dosing and timing of dose in patients prescribed a POP, with up to six months of follow-up, conducted from January to October 2020. A pharmacy benefit manager identified potential participants with a newly prescribed POP and extended an invitation to participate. We enrolled qualified respondents by telephone, trained them to use an electronic diary to report daily whether they had taken their POP and at what time. We followed participants for up to six months. We calculated adherence to daily pill taking as the proportion of evaluable days in which a participant took a POP, and the proportion of participants reporting ≥85% adherence. We calculated adherence to same time each day as the proportion of doses taken no later than three hours after the previous dose time of day. RESULTS: The user population comprised 199 participants, 154 (77.4%) of whom completed six months of follow-up. The majority (n = 170, 85.4%) were taking norethindrone. Norethindrone users reported POP intake on 22,327 (96.4%) of 23,156 evaluable days, with 155 (91.2%) participants reporting ≥85% adherence; less than half (n = 73, 42.9%) reported 100% adherence. Participants reported adherence to same time each day on 21,698 of 22,157 (97.9%) evaluable days. CONCLUSIONS: Among participants taking a prescribed POP, participants demonstrated high adherence for daily pill taking and the same time of day, though the majority were not 100% adherent. IMPLICATIONS: This study reports data specific to adherence among those taking a progestin-only pill (POP) in the prescription setting. Clinicians who counsel patients about POP use should be aware that majority of patients were not 100% adherent, although most report ≥85% adherence.

Murine CMV-induced hearing loss is associated with inner ear inflammation and loss of spiral ganglia neurons.

Congenital human cytomegalovirus (HCMV) occurs in 0.5-1% of live births and approximately 10% of infected infants develop hearing loss. The mechanism(s) of hearing loss remain unknown. We developed a murine model of CMV induced hearing loss in which murine cytomegalovirus (MCMV) infection of newborn mice leads to hematogenous spread of virus to the inner ear, induction of inflammatory responses, and hearing loss. Characteristics of the hearing loss described in infants with congenital HCMV infection were observed including, delayed onset, progressive hearing loss, and unilateral hearing loss in this model and, these characteristics were viral inoculum dependent. Viral antigens were present in the inner ear as were CD(3+) mononuclear cells in the spiral ganglion and stria vascularis. Spiral ganglion neuron density was decreased after infection, thus providing a mechanism for hearing loss. The lack of significant inner ear histopathology and persistence of inflammation in cochlea of mice with hearing loss raised the possibility that inflammation was a major component of the mechanism(s) of hearing loss in MCMV infected mice.

Herpes simplex encephalitis during treatment with tumor necrosis factor-alpha inhibitors.

We report 3 cases of herpes simplex virus encephalitis in patients receiving tumor necrosis factor-alpha (TNF-alpha) inhibitors for rheumatologic disorders. Although TNF-alpha inhibitors have been reported to increase the risk of other infectious diseases, to our knowledge, an association between anti-TNF-alpha drugs and herpes simplex virus encephalitis has not been previously described.

Congenital cytomegalovirus infection: association between virus burden in infancy and hearing loss.

OBJECTIVE: To determine the relationship between the virus burden in infancy and hearing loss in congenital CMV infection. STUDY DESIGN: A cohort of 76 infants with congenital cytomegalovirus (CMV) infection identified by means of newborn virologic screening was monitored for outcome. The amount of infectious CMV was analyzed in urine specimens obtained during early infancy. Peripheral blood (PB) samples obtained during early infancy were available from 75 children and CMV DNA was quantitated with a real-time quantitative polymerase chain reaction. RESULTS: Infants with clinical abnormalities at birth (symptomatic congenital CMV infection) had higher amounts of CMV in urine (P = .005) and CMV DNA in PB (P = .001) than infants with no symptoms. Eight children with and 4 children without symptoms had hearing loss. Among children without symptoms, those with hearing loss had a significantly greater amount of CMV in urine (P = .03) and PB virus burden (P = .02) during infancy than those with normal hearing. Infants with < 5 x 10(3) pfu/mL of urine CMV and infants with < 1 x 10(4) copies/mL of viral DNA in PB were at a lower risk for hearing loss. CONCLUSION: In children with asymptomatic congenital CMV infection, hearing loss was associated with increased amounts of urine CMV and PB CMV DNA during early infancy.

Detection of cytomegalovirus (CMV) DNA by polymerase chain reaction is associated with hearing loss in newborns with symptomatic congenital CMV infection involving the central nervous system.

OBJECTIVE: The study sought to determine the relationship between cytomegalovirus (CMV) viremia during early infancy and clinical and laboratory outcome events, particularly hearing loss in infants with symptomatic congenital CMV infection involving the central nervous system (CNS). STUDY DESIGN: A total of 147 infant patients were enrolled prospectively in 2 clinical trials evaluating ganciclovir for the treatment of symptomatic congenital CMV infection involving the CNS. Aliquots of serum collected at enrollment in either of the 2 trials were available from 50 of the infants, and the degree of viremia was determined by real-time quantitative polymerase chain reaction. RESULTS: Of the 50 infants from whom serum samples were available, 37 had detectable CMV DNA in the serum sample collected at enrollment and were classified as viremic. Viremic infants were more likely to have (1) hearing loss both at enrollment (P = .045) and at the 6-month follow-up testing (P = .035) and (2) other indicators of active CMV disease, including elevated levels of alanine aminotransferase, petechial rash, and organomegaly. CONCLUSION: In children with symptomatic congenital CMV infection involving the CNS, viremia during early infancy is associated with hearing loss and systemic CMV disease.

Long-range mapping of the Streptococcus agalactiae phylogenetic lineage restriction digest pattern type III-3 reveals clustering of virulence genes.

Human isolates of serotype III Streptococcus agalactiae (group B streptococcus [GBS]) can be divided into three separate phylogenetic lineages based on analysis of the restriction digest patterns (RDPs) of chromosomal DNA. Nine DNA sequences that are present in all isolates of the RDP III-3 phylogenetic lineage, but not in the other lineages, were identified by genomic subtractive hybridization. A complete physical map of a III-3 chromosome was constructed. Six of the nine III-3-specific sequences mapped to a 340-kb Sse8387I fragment which contains or is located close to known GBS virulence genes. One of the III-3-specific probes, AW-10, encodes part of GBSi1, a group II intron that is inserted at two sites within the GBS genome. The second chromosomal site for GBSi1 was isolated, sequenced, and mapped to a location near the locus responsible for hemolysin production. These findings suggest that the genetic variation that distinguishes the RDP type III-3 strains from other serotype III strains occurs largely within localized areas of the genome containing known or putative virulence genes.