Acceptability of human papillomavirus self-collection and the role of telehealth: a prospective, randomized study stratified by menopausal status.

OBJECTIVE: We investigated the utility of telehealth instruction versus mail-based written instruction in facilitating high-risk human papillomavirus (hrHPV) self-collection among post-menopausal patients compared with pre-menopausal patients, as well as the impact on acceptability and feasibility. METHODS: We conducted a prospective, randomized study of people eligible for cervical cancer screening, stratified by menopausal status, to undergo standard written or telehealth-based instructions for hrHPV self-collection. English speaking individuals residing in Oregon, with a cervix, eligible for primary hrHPV testing, and with access to a video-capable device were included. Patients with prior hysterectomy, trachelectomy, diagnosis of cervical cancer, or pelvic radiation for gynecologic cancer were excluded. We compared preference for and opinions about self-collection and hrHPV test results, by randomization group and stratified by menopausal status using descriptive statistics. RESULTS: Among 123 patients enrolled, 61 identified as post-menopausal with a median age of 57 years. While the majority of post-menopausal participants who received telehealth instructions found it helpful, only 6.1% considered telehealth instructions necessary to complete self-testing. There was no difference in opinion of telehealth by menopausal status. Overall, 88.5% of post-menopausal participants preferred self-collection to provider-collection. There were no significant differences between pre- and post-menopausal participants in terms of test preference, discomfort, ease of use, or perceptions of self-collection. CONCLUSION: Telehealth instruction did not add significant value to patients participating in hrHPV self-collection, nor did it alter the acceptability of hrHPV-self collection among an English-speaking cohort. Compared with prior experiences with provider-collected screening, hrHPV self-collection was preferred by both pre- and post-menopausal participants. There were no significant differences in preference for provider- versus self-collection when stratified by menopausal status.

HPV self-collection: what are we waiting for? Exploration of attitudes from frontline healthcare providers.

OBJECTIVE: Polymerase chain reaction based human papilloma virus (HPV) self-collection for cervical cancer screening is well established. It is utilized worldwide, accepted by patients, is cost-effective, has comparable sensitivity to provider-collected samples, and increases screening rates, however clinical practice in the United States has not shifted to include HPV self-collection. This study sought to examine provider knowledge and attitudes to better understand why HPV self-collection is not being utilized. METHODS: An observational, qualitative study was conducted. Data were collected with semi-structured focus groups and individual interviews with Oregon healthcare providers. Focus groups and interviews were continued until data saturation was achieved. A grounded theory method was used for analysis, a cyclical process of coding data, memo-writing, and theoretical sampling to the point of saturation. RESULTS: Eighteen healthcare providers participated in the focus group and interviews. They represented 14 of 36 counties across Oregon and 50% were physicians, 33% were nurse practitioners, and 94% worked within family medicine. All providers performed cervical cancer screening according to current American Society for Colposcopy and Cervical Pathology guidelines. Five overarching themes emerged: provider concerns, clinical and provider barriers, patient perspective and barriers, process-based themes, and barriers to cervical cancer screening. Nearly all providers stated they will offer HPV self-collection to most of their patients once available. CONCLUSION: While providers identified concerns and barriers for initiating HPV self-collection, there was a strong desire to implement HPV self-collection and acceptance within patient populations was assumed. Providers indicated the need for HPV self-collection to be incorporated into national screening guidelines along with best practices on how to successfully implement this modality to further increase cervical cancer screening rates.

Hysterectomy with a general gynecologist vs gynecologic-oncologist in the setting of endometrial intraepithelial neoplasia: a cost-effectiveness analysis.

BACKGROUND: Standard treatment for patients with endometrial intraepithelial neoplasia (EIN) is a hysterectomy, which has a 43% risk of concomitant endometrial cancer on final pathology. General gynecologists and gynecologic-oncologists perform hysterectomies; however, patients who have a hysterectomy for EIN with a general gynecologist and are found to have cancer may require a second surgery by a gynecologic-oncologist to complete staging. There is ongoing discussion regarding whether patients with EIN should be provided the option to receive the initial hysterectomy with a gynecologic-oncologist. OBJECTIVE: This study aimed to better understand if patients with EIN should be initially referred to a gynecologic-oncologist for treatment. We examined the cost-effectiveness of hysterectomy by general gynecologists vs gynecologic-oncologists for patients with EIN. STUDY DESIGN: We created a decision-analytical model using TreeAge Pro software to compare outcomes between hysterectomies by general gynecologists and those by gynecologic-oncologists in patients with EIN. Our theoretical cohort contained 200,000 patients, an estimate of the number of individuals diagnosed with EIN each year in the United States. Outcomes included costs, quality-adjusted life years, primary lymph node dissection, secondary lymph node dissection, surgical site infection, and perioperative mortality. We assumed that surgical morbidity and mortality were the same under generalist and specialist care and applied costs of travel and lost work for those seeing a gynecologic-oncologist. We performed univariable sensitivity analyses and multivariable probabilistic sensitivity analysis to assess the model's robustness given the uncertainty of model inputs. RESULTS: In our theoretical cohort of 200,000 patients with EIN, hysterectomy with a gynecologic-oncologist was associated with a decrease of 10,811 second surgeries for lymph node dissection, 87 surgical site infections, and 9 perioperative mortalities. When hysterectomy was performed by a general gynecologist, 9 fewer patients had a lymph node dissection because of perioperative mortalities that occurred before lymph node dissection with a gynecologic-oncologist. Hysterectomy with a gynecologic-oncologist was the dominant, cost-effective strategy because it saved $116 million and increased quality-adjusted life years by 180. In our univariable analyses, hysterectomy with a gynecologic-oncologist was cost-saving and increased quality-adjusted life years over a wide range of probabilities and costs for lymph node dissection, surgical site infection, and perioperative mortality. However, hysterectomy with a gynecologic-oncologist was only a cost-effective and cost-saving strategy in just over 50% of multivariable simulations, demonstrating that there is significant uncertainty in the model's cost-effectiveness. CONCLUSION: In our model, hysterectomy with a gynecologic-oncologist for patients with EIN was associated with cost savings and increased quality-adjusted life years. Our study supports that patients undergoing hysterectomy for EIN at institutions using Mayo criteria to determine need for lymphadenectomy may benefit from surgery with a gynecologic-oncologist rather than a general gynecologist to reduce costs and adverse events associated with a second surgery.

Effects of early daily alcohol exposure on placental function and fetal growth in a rhesus macaque model.

BACKGROUND: Prenatal alcohol exposure is the most common cause of birth defects and intellectual disabilities and can increase the risk of stillbirth and negatively impact fetal growth. OBJECTIVE: To determine the effect of early prenatal alcohol exposure on nonhuman primate placental function and fetal growth. We hypothesized that early chronic prenatal alcohol would alter placental perfusion and oxygen availability that adversely affects fetal growth. STUDY DESIGN: Rhesus macaques self-administered 1.5 g/kg/d of ethanol (n=12) or isocaloric maltose-dextrin (n=12) daily before conception through the first 60 days of gestation (term is approximately 168 days). All animals were serially imaged with Doppler ultrasound to measure fetal biometry, uterine artery volume blood flow, and placental volume blood flow. Following Doppler ultrasound, all animals underwent both blood oxygenation level-dependent magnetic resonance imaging to characterize placental blood oxygenation and dynamic contrast-enhanced magnetic resonance imaging to quantify maternal placental perfusion. Animals were delivered by cesarean delivery for placental collection and fetal necropsy at gestational days 85 (n=8), 110 (n=8), or 135 (n=8). Histologic and RNA-sequencing analyses were performed on collected placental tissue. RESULTS: Placental volume blood flow was decreased at all gestational time points in ethanol-exposed vs control animals, but most significantly at gestational day 110 by Doppler ultrasound (P<.05). A significant decrease in total volumetric blood flow occurred in ethanol-exposed vs control animals on dynamic contrast-enhanced magnetic resonance imaging at both gestation days 110 and 135 (P<.05); moreover, a global reduction in T2∗, high blood deoxyhemoglobin concentration, occurred throughout gestation (P<.05). Similarly, evidence of placental ischemic injury was notable by histologic analysis, which revealed a significant increase in microscopic infarctions in ethanol-exposed, not control, animals, largely present at middle to late gestation. Fetal biometry and weight were decreased in ethanol-exposed vs control animals, but the decrease was not significant. Analysis with RNA sequencing suggested the involvement of the inflammatory and extracellular matrix response pathways. CONCLUSION: Early chronic prenatal alcohol exposure significantly diminished placental perfusion at mid to late gestation and also significantly decreased the oxygen supply to the fetal vasculature throughout pregnancy, these findings were associated with the presence of microscopic placental infarctions in the nonhuman primate. Although placental adaptations may compensate for early environmental perturbations to fetal growth, placental blood flow and oxygenation were reduced, consistent with the evidence of placental ischemic injury.

Does obesity influence the preferred treatment approach for early-stage cervical cancer? A cost-effectiveness analysis.

OBJECTIVE: Abdominal radical hysterectomy in early-stage cervical cancer has higher rates of disease-free and overall survival compared with minimally invasive radical hysterectomy. Abdominal radical hysterectomy may be technically challenging at higher body mass index levels resulting in poorer surgical outcomes. This study sought to examine the influence of body mass index on outcomes and cost effectiveness between different treatments for early-stage cervical cancer. METHODS: A Markov decision-analytic model was designed using TreeAge Pro software to compare the outcomes and costs of primary chemoradiation versus surgery in women with early-stage cervical cancer. The study used a theoretical cohort of 6000 women who were treated with abdominal radical hysterectomy, minimally invasive radical hysterectomy, or primary chemoradiation therapy. We compared the results for three body mass index groups: less than 30 kg/m2, 30-39.9 kg/m2, and 40 kg/m2 or higher. Model inputs were derived from the literature. Outcomes included complications, recurrence, death, costs, and quality-adjusted life years. An incremental cost-effectiveness ratio of less than $100 000 per quality-adjusted life year was used as our willingness-to-pay threshold. Sensitivity analyses were performed broadly to determine the robustness of the results. RESULTS: Comparing abdominal radical hysterectomy with minimally invasive radical hysterectomy, abdominal radical hysterectomy was associated with 526 fewer recurrences and 382 fewer deaths compared with minimally invasive radical hysterectomy; however, abdominal radical hysterectomy resulted in more complications for each body mass index category. When the body mass index was 40 kg/m2 or higher, abdominal radical hysterectomy became the dominant strategy because it led to better outcomes with lower costs than minimally invasive radical hysterectomy. Comparing abdominal radical hysterectomy with primary chemoradiation therapy, recurrence rates were similar, with more deaths associated with surgery across each body mass index category. Chemoradiation therapy became cost effective when the body mass index was 40 kg/m2 or higher. CONCLUSION: When the body mass index is 40 kg/m2 or higher, abdominal radical hysterectomy is cost saving compared with minimally invasive radical hysterectomy and primary chemoradiation is cost effective compared with abdominal radical hysterectomy. Primary chemoradiation may be the optimal management strategy at higher body mass indexes.

Stepwise Approach to the Management of Endometriosis-Related Dysmenorrhea: A Cost-Effectiveness Analysis.

OBJECTIVE: To evaluate the cost effectiveness of sequential medical and surgical therapy for the treatment of endometriosis-related dysmenorrhea. METHODS: A cost-effectiveness model was created to compare three stepwise medical and surgical treatment strategies compared with immediate surgical management for dysmenorrhea using a health care payor perspective. A theoretical study cohort was derived from the estimated number of reproductive age (18-45) women in the United States with endometriosis-related dysmenorrhea. The treatment strategies modeled were: strategy 1) nonsteroidal antiinflammatory drugs (NSAIDs) followed by surgery; strategy 2) NSAIDs, then short-acting reversible contraceptives or long-acting reversible contraceptives (LARCs) followed by surgery; strategy 3) NSAIDs, then a short-acting reversible contraceptive or LARC, then a LARC or gonadotropin-releasing hormone modulator followed by surgery; strategy 4) proceeding directly to surgery. Probabilities, utilities, and costs were derived from the literature. Outcomes included cost, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios. Univariate, bivariate, and multivariate sensitivity analyses were performed. RESULTS: In this theoretical cohort of 4,817,894 women with endometriosis-related dysmenorrhea, all medical and surgical treatment strategies were cost effective at a standard willingness-to-pay threshold of $100,000 per QALY gained when compared with surgery alone. Strategy 2 was associated with the lowest cost per QALY gained ($1,155). Requiring a trial of a third medication before surgery would cost an additional $257 million, compared with proceeding to surgery after failing two medical treatments. The probability of improvement with surgery would need to exceed 83% for this to be the preferred first-line approach. CONCLUSION: All sequential medical and surgical management strategies for endometriosis-related dysmenorrhea were cost effective when compared with surgery alone. A trial of hormonal management after NSAIDs, before proceeding to surgery, may provide cost savings. Delaying surgical management in an individual with pain refractory to more than three medications may decrease quality of life and increase cost.

Trastuzumab with carboplatin/paclitaxel for treatment of advanced stage and recurrent uterine papillary serous carcinoma: A cost-effectiveness analysis.

OBJECTIVE: Uterine papillary serous carcinoma (UPSC) is a variant of endometrial cancer that is aggressive and associated with poor outcomes. We sought to evaluate the cost effectiveness of carboplatin/paclitaxel alone versus carboplatin/paclitaxel with trastuzumab among patients with Her2/neu-positive advanced or recurrent UPSC. METHODS: We designed a Markov model in TreeAge Pro 2019 software to simulate management of a theoretical cohort of 4000 patients with Her2/neu-positive advanced or recurrent uterine papillary serous carcinoma (UPSC) followed for four years. In the carboplatin/paclitaxel with trastuzumab strategy, we included the cost of testing for Her2/neu status. We obtained all model inputs from the literature and a societal perspective was assumed. Outcomes included progression-free survival, progression, UPSC-specific mortality, cost, and quality-adjusted life years (QALYs). The intervention was considered cost effective if the incremental cost-effectiveness ratio (ICER) was below the willingness-to-pay threshold of $100,000 per QALY. Sensitivity analyses were used to determine the robustness of the results. RESULTS: In our theoretical cohort of 4000 women, treatment with the addition of trastuzumab resulted in 637 fewer deaths and 627 fewer cases of progression compared with treatment with carboplatin/paclitaxel alone. Treatment with trastuzumab was associated with an additional cost of $144,335,895, but was associated with an increase of 2065 QALYs. The ICER was $69,903 per QALY, which was below our willingness-to-pay threshold. Sensitivity analysis demonstrated that this treatment strategy was cost-effective until the cost of 6 months of treatment surpassed $38,505 (baseline input: $27,562). CONCLUSION: We found that the addition of trastuzumab to carboplatin/paclitaxel was a cost-effective treatment strategy for patients with advanced/recurrent Her2/neu-positive UPSC.

Acute abdominal pain caused by hematometra in an adolescent female: a case report.

BACKGROUND: Hematometra is a pathologic collection of blood in the uterus. It is a rare condition that is most commonly associated with congenital anomalies or prior surgical procedures causing an obstruction of the genitourinary outflow tract. We present an unusual case of hematometra in a healthy and active adolescent female with no prior risk factors. This is a rare and important case report due to the complexity of diagnosis when a young female presents with an acute abdomen. In addition, for a patient who presents with no prior risk factors for hematometra, such as in our patient, the diagnosis and workup may become overly complicated, adding strain to patient care and health care cost. To the best of our knowledge and based on an extensive literature search, there has not been a reported case of hematometra in an adolescent female without any aforementioned risk factors. CASE PRESENTATION: Our patient is a healthy 18 year-old white woman with no significant prior medical or surgical history. Her only medication was depot medroxyprogesterone acetate use for contraception. She presented to a local emergency department with acute abdominal pain, accompanied by emesis and nausea. Workup with ultrasonography showed uterine distention most likely caused by hematometra, although no obvious cause was noted. She was treated with dilation and curettage; she was also advised to discontinue depot medroxyprogesterone acetate use. She was symptom free without recurrence of hematometra at 6-month follow-up. CONCLUSIONS: Due to the high prevalence of abdominal pain, this case report has a wide breadth of implications for health care providers ranging from general family practitioners to emergency room physicians and obstetricians/gynecologists. This case report provides potential future advancement in management and differential diagnosis in adolescent females presenting with acute abdominal pain. In addition, the use of depot medroxyprogesterone acetate contributing to or causing hematometra cannot be ruled out in our patient and warrants further investigation.

Perceived benefits of a transplant surgery experience to general surgery residency training.

OBJECTIVES: The benefit of a solid-organ transplant experience during general surgical training has been questioned recently. In 2008, in response to an American Board of Surgery (ABS) directive, a survey was conducted by the Association of Program Directors in Surgery (APDS) in coordination with the American Society of Transplant Surgeons (ASTS) to determine the perceived value of a transplant surgery rotation to program directors and residents. With the aim of providing additional insight, we conducted a separate study, independent of the ABS and ASTS, to ascertain resident perceptions regarding the specific skill sets that they acquire during their transplant surgery rotations and their applicability to other surgical subspecialties. METHODS: A preliminary, 51-item, web-based questionnaire was completed by 69.6% of residents in nationally accredited general surgery programs who accessed the survey. The results were examined using appropriate statistical methods to determine associations between answers. RESULTS: Although only 16.6% of participants responded that they were considering a career in transplantation, 63.4% answered that the skill sets acquired during this rotation would assist them in their surgical careers regardless of their chosen specialty. Most (65.5%) respondents answered that the techniques learned were directly applicable to other specialties, such as vascular, urologic, trauma, and hepatobiliary surgery. Free response questions indicated that the most common criticisms of this rotation were the limited amount of operative participation, lack of teaching by attendings, and lifestyle limitations. CONCLUSIONS: The results of this study indicate that surgery residents are conflicted regarding their transplant surgery experience but regard it as a beneficial addition to their training. Most respondents indicated also that these skills were transferable directly to other surgical specialties.

Biochemical study of recombinant PcrA from Staphylococcus aureus for the development of screening assays.

Helicases are ubiquitous enzymes, which utilize the energy liberated during nucleotide triphosphate hydrolysis to separate double-stranded nucleic acids into single strands. These enzymes are very attractive targets for the development of new antibacterial compounds. The PcrA DNA helicase from Staphylococcus aureus is a good candidate for drug discovery. This enzyme is unique in the genome of S. aureus and essential for this bacterium. Furthermore, it has recently been published that it is possible to identify inhibitors of DNA helicases such as PcrA. In this report, we study the properties of recombinant PcrA from S. aureus purified from Escherichia coli to develop ATPase and helicase assays to screen for inhibitors.