Human papillomavirus type 16 viral load is decreased following a therapeutic vaccination.

In the dose-escalation phase of a Phase I clinical trial in which six subjects each were vaccinated with PepCan at the 50, 100, 250, and 500 µg per peptide dose, the 50 µg dose showed the best histological regression rate. Ten additional subjects were vaccinated at this dose in the final dose phase. As with the dose-escalation phase, no dose-limiting toxicities were observed. Overall, the histological regression rates were 50% at the 50 µg dose (7 of 14) and 100 µg dose (3 of 6), and 45 % overall (14 of 31). Of subjects in whom HPV type 16 (HPV 16) was detected at entry, it became undetectable in three subjects after vaccination, and the viral loads significantly decreased in nine subjects in whom HPV 16 infection was detected at entry and exit (p = 0.008). Immune profiling revealed increased T-helper type 1 cells after vaccinations (p = 0.02 and 0.0004 after 2 and 4 vaccinations, respectively). T-helper type 2 cells initially increased after two vaccinations (p = 0.01), but decreased below the baseline level after four vaccinations although not significantly. Pre-vaccination regulatory T cell levels were significantly lower in histological responders compared to non-responders (p = 0.03). Feasibility of testing plasma for multiplex cytokine/chemokine analysis and of performing proteomic analysis of PBMCs was examined for potentially identifying biomarkers in the future. While these analyses are feasible to perform, attention needs to be given to how soon the blood samples would be processed after phlebotomy. As sufficient safety of PepCan has been demonstrated, enrollment for the Phase II clinical trial has been opened.

Application of a Telecolposcopy Program in Rural Settings.

BACKGROUND: Individuals in rural areas are often restricted by the amount of physicians' availability, thus limiting access to healthcare in those settings. INTRODUCTION: While Pap smear screening has increased across the United States, the rural South still reports high rates of cervical cancer and mortality. One solution to improve patient outcomes related to cervical cancer in rural settings is telecolposcopy. MATERIALS AND METHODS: Women with abnormal Pap results or an abnormal visual examination needing an evaluation by colposcopy were referred to a hospital-based telecolposcopy program. Descriptive data are provided that include patients' access to care based on travel time and transportation costs. RESULTS: Over a 15-month time period, 940 unique patients were seen using telecolposcopy. Telecolposcopy was done at eight spoke sites across Arkansas representing patients from 72 of the 75 counties. Data for risk factors that include smoking, first sexual experience, and number of sexual partners in past 12 months and in a lifetime are discussed. Pap results and impression are provided. In addition, avoided transportation costs and travel time have been calculated and included. DISCUSSION: Cervical cancer is important public health concern especially for women residing in rural areas. We were able to demonstrate that our telecolposcopy program has provided sustainability statewide since its inception and that patients are willing to participate. In addition to providing increased access to care, the program also reduced travel time and costs associated with a face-to-face visit. CONCLUSION: Telecolposcopy should be further explored and utilized in rural settings as a way to reduce patient costs and improve cervical cancer outcomes.

A novel use of a statewide telecolposcopy network for recruitment of participants in a Phase I clinical trial of a human papillomavirus therapeutic vaccine.

BACKGROUND: Historically, recruitment and retention of young women in intervention-based clinical trials have been challenging. In August 2012, enrollment for a clinical trial testing of an investigational human papillomavirus therapeutic vaccine called PepCan was opened at our institution. This study was an open-label, single-arm, single-institution, dose-escalation Phase I clinical trial. Women with recent Papanicolaou smear results showing high-grade squamous intraepithelial lesions or results that could not rule out high-grade squamous intraepithelial lesion were eligible to enroll. Patients with biopsy-confirmed high-grade squamous intraepithelial lesion were also eligible. Colposcopy was performed at the screening visit, and participants became eligible for vaccination when the diagnosis of high-grade squamous intraepithelial lesion was confirmed with biopsy and other inclusion criteria were met. The aim of this study was to identify strategies and factors effective in recruitment and retention of study participants. METHODS: Potential vaccine candidates were recruited through direct advertisement as well as referrals, including referrals through the Arkansas telecolposcopy network. The network is a federally funded program, administered by physicians and advanced practice nurses. The network telemedically links rural health sites and allows physician-guided colposcopy and biopsies to be conducted by advanced practice nurses. A variety of strategies were employed to assure good retention, including face-to-face contact with the study coordinator at the time of consent and most of study visits; frequent contact using text messaging, phone calls, and e-mails; and creation of a private Facebook page to improve communication among research staff and study participants. A questionnaire, inquiring about motivation for joining the study, occupation, education, household income, number of children, and number of sexual partners, was administered at the screening visit with the intent of identifying factor(s) associated with recruitment and retention. RESULTS: A total of 37 participants were enrolled between September 2012 and March 2014. The largest proportion of participants (46%) was enrolled from the telecolposcopy network. Others were enrolled through outside institutions (43%), in-house referrals (8%), or direct advertisement (3%). Most participants were motivated to join the study to take care of their health issues. Only two participants joined the Facebook private page. Of the 24 participants who qualified for vaccination, only 1 terminated early due to an unanticipated move. CONCLUSION: The availability of a large number of potential participants from the telecolposcopy network increased recruitment to this clinical trial by 85% over other traditional means of recruitment. The telecolposcopy network is not only a means of providing a gynecological service to women who otherwise would forego care but also a novel and valuable resource in recruiting participants for a clinical trial.

Optimizing appointment template and number of staff of an OB/GYN clinic--micro and macro simulation analyses.

BACKGROUND: The Department of Obstetrics and Gynecology (OB/GYN) at the University of Arkansas for Medical Sciences (UAMS) tested various, new system-restructuring ideas such as varying number of different types of nurses to reduce patient wait times for its outpatient clinic, often with little or no effect on waiting time. Witnessing little progress despite these time-intensive interventions, we sought an alternative way to intervene the clinic without affecting the normal clinic operations. AIM: The aim is to identify the optimal (1) time duration between appointments and (2) number of nurses to reduce wait time of patients in the clinic. METHODS: We developed a discrete-event computer simulation model for the OB/GYN clinic. By using the patient tracker (PT) data, appropriate probability distributions of service times of staff were fitted to model different variability in staff service times. These distributions were used to fine-tune the simulation model. We then validated the model by comparing the simulated wait times with the actual wait times calculated from the PT data. The validated model was then used to carry out "what-if" analyses. RESULTS: The best scenario yielded 16 min between morning appointments, 19 min between afternoon appointments, and addition of one medical assistant. Besides removing all peak wait times and bottlenecks around noon and late in the afternoon, the best scenario yielded 39.84 % (p<.001), 30.31 % (p<.001), and 15.12 % (p<.001) improvement in patients' average wait times for providers in the exam rooms, average total wait time at various locations and average total spent time in the clinic, respectively. This is achieved without any compromise in the utilization of the staff and in serving all patients by 5 pm. CONCLUSIONS: A discrete-event simulation model is developed, validated, and used to carry out "what-if" scenarios to identify the optimal time between appointments and number of nurses. Using the model, we achieved a significant improvement in wait time of patients in the clinic, which the clinic management initially had difficulty achieving through manual interventions. The model provides a tool for the clinic management to test new ideas to improve the performance of other UAMS OB/GYN clinics.

Telemedical cervical cancer screening to bridge medicaid service care gap for rural women.

BACKGROUND: The Arkansas Medicaid program for low-income women provides cervical cancer screening, in the form of Pap smears, and treatment but no diagnostic means of bridging the two, such as a procedure called "colposcopy." Telemedicine offers a viable means to bridging this gap. Previously telecolposcopy has been used in small demonstration projects as a means to deliver colposcopy services to at-risk rural populations at a comparable quality to in-person colposcopy. SUBJECTS AND METHODS: The University of Arkansas for Medical Sciences' Antenatal & Neonatal Guidelines, Education and Learning System Program and Center for Distance Health developed an innovative collaborative telemedicine pilot program with the Arkansas Department of Health that used both specialty physician oversight and nurse examiners. Underserved rural patients from the Department of Health were provided with colposcopy services via interactive telemedicine at four separate spoke sites. During each weekly 3-h clinic, an advanced practice nurse/nurse practitioner at each of the spoke sites performed the exams and collected biopsy specimens under the real-time, interactive supervision of an experienced faculty member at the hub site. RESULTS: Between January 1, 2010 and June 21, 2011, the program scheduled 1,812 visits, involving 1,504 unduplicated patient referrals from 68 of Arkansas's 75 counties, and performed 1,298 telecolposcopic exams. CONCLUSIONS: This project provides complex specialty gynecological services using telemedicine technology to overcome geographic barriers to care while producing results comparable to traditional examinations. It is cost-effective and well received by patients and can be used as a model for improving access to care among vulnerable populations.

Borderline or marginal amniotic fluid index and peripartum outcomes: a review of the literature.

The predictive accuracy of a borderline amniotic fluid index (AFI) for an adverse pregnancy outcome is uncertain. Pregnancy outcomes of a borderline versus normal AFI suggest an increased risk of meconium-stained fluid, intrauterine growth restriction, cesarean delivery for a nonreassuring fetal heart rate, low Apgar scores, and neonatal intensive care unit admission with borderline fluid. These results are inconclusive because of study design variations, the absence of receiver-operating characteristic curves, our inability to calculate likelihood ratios, and a lack of randomized trials. There is currently insufficient evidence to recommend additional antenatal testing delivery based on a borderline AFI. Sonography could be considered for evaluating fetal growth until a definitive association or lack of an association between a borderline AFI and intrauterine growth restriction/small size for gestational age can be determined.

Clinical Applications of Telemedicine in Gynecology and Women's Health.

Telemedicine and telehealth (TM/TH) are the 2 terms used interchangeably focusing on the delivery of health care services at a long distance using telecommunication technology. TM/TH has several gynecologic applications, including the well-woman visits, preventive care, preconception counseling, family planning including contraception and medical abortion, infertility workup, teleradiology, cervical cancer screening and colposcopy, mental health, and telesurgery. The goals of TM/TH are not only improving quality of health care in patients and building a virtual community of physicians but also increasing convenience, efficacy, and decreasing medical cost. In gynecology, TM/TH plays an important role, especially in well-woman care.

A phase I dose-escalation clinical trial of a peptide-based human papillomavirus therapeutic vaccine with Candida skin test reagent as a novel vaccine adjuvant for treating women with biopsy-proven cervical intraepithelial neoplasia 2/3.

PURPOSE: Non-surgical treatments for cervical intraepithelial neoplasia 2/3 (CIN2/3) are needed as surgical treatments have been shown to double preterm delivery rate. The goal of this study was to demonstrate safety of a human papillomavirus (HPV) therapeutic vaccine called PepCan, which consists of four current good-manufacturing production-grade peptides covering the HPV type 16 E6 protein and Candida skin test reagent as a novel adjuvant. PATIENTS AND METHODS: The study was a single-arm, single-institution, dose-escalation phase I clinical trial, and the patients (n = 24) were women with biopsy-proven CIN2/3. Four injections were administered intradermally every 3 weeks in limbs. Loop electrical excision procedure (LEEP) was performed 12 weeks after the last injection for treatment and histological analysis. Six subjects each were enrolled (50, 100, 250, and 500 µg per peptide). RESULTS: The most common adverse events (AEs) were injection site reactions, and none of the patients experienced dose-limiting toxicities. The best histological response was seen at the 50 µg dose level with a regression rate of 83% (n = 6), and the overall rate was 52% (n = 23). Vaccine-induced immune responses to E6 were detected in 65% of recipients (significantly in 43%). Systemic T-helper type 1 (Th1) cells were significantly increased after four vaccinations (P = 0.02). CONCLUSION: This study demonstrated that PepCan is safe. A significantly increased systemic level of Th1 cells suggests that Candida, which induces interleukin-12 (IL-12) in vitro, may have a Th1 promoting effect. A phase II clinical trial to assess the full effect of this vaccine is warranted.

The use of telemedicine in obstetrics: a review of the literature.

UNLABELLED: Telemedicine has been advertised for increasing efficiency, extending the scope of obstetric practice, improving pregnancy outcomes, and reducing costs in the healthcare system. The extent of telemedicine use in obstetrics was identified with a literature search. A total of 268 articles were identified of which 60 are the basis for this review. Telemedicine has been used to read ultrasounds, interpret nonstress tests, counsel patients, manage diabetes, manage postpartum depression, and support parents and children postpartum from remote sites. Reductions in time lost from work, transportation costs, more efficiency for the health care providers, and reducing medical costs all have been suggested as benefits of telemedicine. Despite the information published about telemedicine in obstetrics, this technology has not been shown to have adverse effects in obstetrics but neither has it demonstrated unequivocal benefits. Properly structured and powered investigations will be needed to determine the role of telemedicine in the future. TARGET AUDIENCE: Obstetricians & Gynecologists. LEARNING OBJECTIVES: After completing this CME activity, physicians should be better able to diagnose and treat diabetes using telemedicine techniques; assess the current scope of research in telemedicine in obstetrics; implement clinical telemedicine consultations based on the interaction and the needs of the participants; and the opportunities for further research in telemedicine in obstetrics.