Clinical Trials That Have Changed Clinical Practice and Care of Pregnant People With HIV.

Over the last 4 decades, significant advances in the care of HIV during pregnancy have successfully reduced, and nearly eliminated, the risk of perinatal HIV transmission. The baseline risk of transmission without intervention (25% to 30%) is now <1% to 2% in the United States with contemporary antepartum, intrapartum, and postnatal interventions. In this review, we discuss 3 landmark clinical trials that substantially altered obstetric practice for pregnant individuals with HIV and contributed to this extraordinary achievement: 1) the Pediatric AIDS Clinical Trials Group 076 Trial determined that antepartum and intrapartum administration of antiretroviral drug zidovudine to the pregnant individual, and postnatally to the newborn, could reduce the risk of perinatal transmission by approximately two-thirds; 2) the European Mode of Delivery Collaboration Trial demonstrated performance of a prelabor cesarean birth before rupture of membranes among pregnant people with viremia reduced the risk of perinatal transmission compared with vaginal birth; and 3) the International Maternal Pediatric Adolescent AIDS Clinical Trials Network 2010 Trial identified that dolutegravir-containing, compared with efavirenz-containing, antiretroviral regimens during pregnancy achieved a significantly higher rate of viral suppression at delivery with shorter time to viral suppression, with fewer adverse pregnancy outcomes. Collectively, these trials not only advanced obstetric practice but also advanced scientific understanding of the timing, mechanisms, and determinants of perinatal HIV transmission. For each trial, we will describe key aspects of the study protocol and outcomes, insights gleaned about the dynamics of perinatal transmission, how each study changed clinical practice, and relevant updates to current practice since the trial's publication.

Peripartum interventions for people with class III obesity: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to identify evidence-based peripartum interventions for people with a body mass index ≥40 kg/m2. DATA SOURCES: PubMed, MEDLINE, EMBASE, Cochrane, CINAHL, and ClinicalTrials.gov were searched from inception to 2022 without date, publication type, or language restrictions. STUDY ELIGIBILITY CRITERIA: Cohort and randomized controlled trials that implemented an intervention and evaluated peripartum outcomes of people with a body mass index ≥40 kg/m2 were included. The primary outcome depended on the intervention but was commonly related to wound morbidity after cesarean delivery (ie, infection, separation, hematoma). METHODS: Meta-analysis was completed for interventions with at least 2 studies. Pooled risk ratios with 95% confidence intervals and heterogeneity (I2 statistics) were reported. RESULTS: Of 20,301 studies screened, 30 studies (17 cohort and 13 randomized controlled trials) encompassing 10 types of interventions were included. The interventions included delivery planning (induction of labor, planned cesarean delivery), antibiotics during labor induction or for surgical prophylaxis, 6 types of cesarean delivery techniques, and anticoagulation dosing after a cesarean delivery. Planned cesarean delivery compared with planned vaginal delivery did not improve outcomes according to 3 cohort studies. One cohort study compared 3 g with 2 g of cephazolin prophylaxis for cesarean delivery and found no differences in surgical site infections. According to 3 cohort studies and 2 randomized controlled trials, there was no improvement in outcomes with a non-low transverse skin incision. Ten studies (4 cohort and 6 randomized controlled trials) met the inclusion criteria for the meta-analysis. Two randomized controlled trials compared subcuticular closure with suture vs staples after cesarean delivery and found no differences in wound morbidity within 6 weeks of cesarean delivery (n=422; risk ratio, 1.09; 95% confidence interval, 0.75-1.59; I2=9%). Prophylactic negative-pressure wound therapy was compared with standard dressing in 4 cohort and 4 randomized controlled trials, which found no differences in wound morbidity (cohort n=2200; risk ratio, 1.19; 95% confidence interval, 0.88-1.63; I2=66.1%) or surgical site infections (randomized controlled trial n=1262; risk ratio, 0.90; 95% confidence interval, 0.63-1.29; I2=0). CONCLUSION: Few studies address interventions in people with a body mass index ≥40 kg/m2, and most studies did not demonstrate a benefit. Either staples or suture are recommended for subcuticular closure, but available data do not support prophylactic negative-pressure wound therapy after cesarean delivery for people with a body mass index ≥40 kg/m2.

Optimizing menstrual health and hygiene management in the U.S.: A mixed-methods study of the barriers and the role of healthcare professionals.

OBJECTIVE: Menstrual health (MH) practices have been understudied in the U.S. This study aimed to assess patient and medical staff views of MH. METHODS: The mixed-methods approach included medical staff and patient surveys, and patient interviews on MH experiences. Quantitative survey data generated descriptive statistics. Thematic content analysis (TCA) evaluated qualitative interviews. Convergent Parallel Triangulation Analysis (CPTA) evaluated both datasets in tandem. RESULTS: The medical staff survey's response rate was 72% (54 participants/75 invited staff). Only 7% (4/54) of staff consistently asked patients about menstrual products (MP), while 54% (29/54) were concerned about patients affording MP. The patient survey's response rate was 90% (186/207); 22% (40/186) of respondents showed MH insecurity, which was associated with annual income <$30,000 (p < 0.01); 45% (85/186) missed commitments during menses; 53% (98/186) never discussed MP with healthcare providers. To reach thematic saturation 10/17 invited patients were interviewed. Five themes were identified through TCA: menstruation as a social barrier; menstrual education comes from a variety of sources; MP choice is a balance of comfort, cost, and convenience; patients value relationships with their providers; adolescence is the window for establishing MH. Three threads were identified through CPTA: MH insecurity is common; MH screening and education are limited; menstruation impacts patients' ability to engage in daily activities. CONCLUSION: A holistic approach toward MH is needed; education and screening are inconsistent. Comprehensive MH can enhance a patient's understanding of and capacity to advocate for their health. These findings are specific to this population and may not be generalizable.

Menstrual Health and Hygiene among Adolescents in the United States.

STUDY OBJECTIVE: Menstrual health in adolescents has been understudied in the United States. We aimed to assess patient and provider perspectives surrounding menstrual health management and screening. DESIGN: Our mixed-methods approach consisted of provider surveys, patient surveys, and patient interviews. SETTING: Participants were recruited from a pediatric gynecology practice or an adolescent medicine clinic at an urban tertiary academic center. PARTICIPANTS: Providers were pediatrics faculty or residents. Patients aged 13-24 years were eligible. INTERVENTION: Participants completed an anonymous survey or semi-structured interview about their experiences with menstrual health. MAIN OUTCOME MEASURES: Descriptive statistics and thematic content analysis were used for quantitative and qualitative data, respectively. Convergent parallel analysis elucidated key findings in both data sets. RESULTS: The provider survey response rate was 65% (69/106); 15% (9/69) of providers consistently asked patients about menstrual products, whereas 44% (27/68) were concerned patients could not afford products. The patient survey response rate was 85% (101/119); 19% (19/101) of respondents reported menstrual hygiene insecurity, 55% (55/101) missed commitments during menses, and 45% (45/101) discussed menstrual products with providers. Fifteen patients were invited for qualitative interviews; 10 were conducted, and thematic saturation occurred. Interviews highlighted the importance of comprehensive early menstrual health education and providers' role in menstrual management. CONCLUSION: Adolescence is a crucial point of entry into health care. Because taboos surrounding menstruation could limit access to health care, menstrual health education must be emphasized. Menstrual health education is provided piecemeal by parents, schools, and providers. Current practice should be reevaluated to consider comprehensive educational approaches in which health care leads.

PI3K oncogenic mutations mediate resistance to afatinib in HER2/neu overexpressing gynecological cancers.

OBJECTIVE: Aberrant expression of HER2/neu and PIK3CA gene products secondary to amplification/mutations are common in high-grade-serous-endometrial (USC) and ovarian-cancers (HGSOC). Because scant information is currently available in the literature on the potential negative effect of PIK3CA mutations on the activity of afatinib, in this study we evaluate for the first time the role of oncogenic PIK3CA mutations as a potential mechanism of resistance to afatinib in HGSOC and USC overexpressing HER2/neu. METHODS: We used six whole-exome-sequenced primary HGSOC/USC cell-lines and three xenografts overexpressing HER2/neu and harboring mutated or wild-type PIK3CA/PIK3R1 genes to evaluate the role of PI3K-mutations as potential mechanism of resistance to afatinib, an FDA-approved pan-c-erb-inhibitor in clinical trials in USC. Primary-USC harboring wild-type-PIK3CA gene was transfected with plasmids encoding oncogenic PIK3CA-mutations (H1047R/E545K). The effect of afatinib on HER2/PI3K/AKT/mTOR pathway was evaluated by immunoblotting. RESULTS: We found PI3K wild-type cell-lines to be significantly more sensitive (lower IC50) than PI3K-mutated cell-lines p = 0.004). In vivo, xenografts of primary cell-line USC-ARK2, transfected with the PIK3CA-H1047R or E545K hotspot-mutations, exhibited significantly more rapid tumor growth when treated with afatinib, compared to mice harboring ARK2-tumors transfected with wild-type-PIK3CA (p = 0.041 and 0.001, respectively). By western-blot, afatinib effectively reduced total and phospho-HER2 proteins in all cell-lines. However, H1047R/E545K-PIK3CA-transfected-ARK2-cells demonstrated a greater compensatory increase in phosphorylated-AKT proteins after afatinib exposure when compared to controls ARK2. CONCLUSIONS: Oncogenic PI3K mutations may represent a major mechanism of resistance to afatinib. Combinations of c-erb with PIK3CA, AKT or mTOR inhibitors may be necessary to more efficiently block the PIK3CA/AKT/mTOR pathway.

Discharge Readiness after Robotic and Laparoscopic Hysterectomy.

STUDY OBJECTIVE: To evaluate which factors may be predictive of patient readiness of discharge after robotic and laparoscopic hysterectomy. DESIGN: A prospective cohort study (Canadian Task Force classification II-2). SETTING: A single tertiary care center in the United States. PATIENTS: All 230 patients undergoing robotic and laparoscopic hysterectomy between November 2015 and April 2017. INTERVENTIONS: The primary outcome measure was whether or not the patient felt ready for discharge when she was sent home, and this was assessed using a survey 4 to 6 weeks after surgery. Secondary outcomes included the number of postoperative phone calls, 30-day readmission, and also whether the patient felt knowledgeable about postoperative symptoms and restrictions (both assessed via a 4- to 6-week survey). Associations of baseline, operative, and postoperative characteristics with outcomes were evaluated using regression models appropriate for the nature of the given outcome measure. MEASUREMENTS AND MAIN RESULTS: Of the 230 patients, 207 (90%) reported they felt ready for discharge on the postoperative survey. The majority of patients strongly agreed that they felt knowledgeable about what symptoms to expect postoperatively (60%) and about postoperative restrictions (71%). The median number of postoperative phone calls was 1 (range, 0-11), with 104 patients (45%) having more than 1 postoperative call. The only factor that was significantly associated with a lack of readiness for discharge was a longer total operating room time (p = .011). Factors associated with more postoperative phone calls were a urogynecologic indication (p = .005), a cancer indication (p = .024), a longer total operative room time (p = .014), a postoperative complication (p <.001), and not seeing a patient education video (p = .018). Knowledge of postoperative restrictions was significantly worse for older patients (p = .004) and varied significantly according to surgeon (p = .038). No significant predictors of knowledge of postoperative symptoms were identified. CONCLUSIONS: Discharge readiness and knowledge of postoperative restrictions and symptoms were high in patients who underwent laparoscopic and robotic hysterectomies. The risk factors for outcomes that were identified highlight groups of patients who can be targeted for preemptive interventions both preoperatively and postoperatively.

Use of the Limbs and Things Hysterectomy Model to Describe the Process for Establishing Validity.

STUDY OBJECTIVE: To demonstrate the process for establishing or refuting validity for the Limbs and Things hysterectomy model. DESIGN: Prospective study using Kane's framework for establishing validity (Canadian Task Force classification: II-2). SETTING: Total laparoscopic hysterectomy (TLH) assessments completed in the operating room (OR) and simulation at 3 academic medical centers. PARTICIPANTS: Obstetrics and gynecology residents (n = 26 postgraduate years 3-4), a gynecologic oncology fellow (postgraduate year 5), and a gynecology oncology attending. INTERVENTIONS: Participants were rated with the myTIPreport feedback application by nonblinded faculty in the OR after TLH. In-person, simulation-based assessments were provided by 2 faculty members blinded to experience level using myTIPreport and Global Operative Assessment of Laparoscopic Skills (GOALS). Videos of simulated TLHs were rated by 2 minimally invasive gynecology fellows. MEASUREMENTS AND MAIN RESULTS: OR scores for TLH steps were significantly higher than simulation assessments (p < .001) with "competent" marked more frequently in the OR. Number of robotic + conventional TLHs performed as primary surgeon was not significantly correlated with OR myTIPreport rating (Spearman r = .30, p = .14) but was significantly correlated with myTIPreport and GOALS in-person simulation ratings (Spearman r = .39-.58, p = .001-.04). Agreement between in-person simulation rater 1 and 2 myTIPreport assessments was 71.4% (weighted κ, .68; 95% confidence interval, .45-.90), and intraclass correlation for the GOALS overall assessment was .71 (95% confidence interval, .46-.85), indicating substantial agreement. Blinded video reviews showed similar agreement (73.1%) between raters but less correlation with experience (Spearman r = .32-.42, p = .11-.03) than in-person reviews. Using area under the receiver operating characteristic curve, mean score for the individual components of GOALS that best differentiated myTIPreport noncompetent and competent levels of performance was 4.3. Feedback acceptability and model realism were rated highly. CONCLUSION: The scoring and generalization validity inferences for Limbs and Things and myTIPreport are supported when global assessments of performance are evaluated but not for individual components of the assessment instruments.

Robotic Placement of the FENIX Continence Restoration System in a Patient with Previous Radiation to the Pelvis: A Case Report.

Fecal incontinence (FI) is a disabling problem affecting women. Conservative treatment includes dietary modification, antimotility agents, and pelvic floor physical therapy. If conservative medical management is unsuccessful, surgical intervention may be required. Surgical options include rectal sphincteroplasty, bulking agent injection, radiofrequency anal sphincter remodeling, and sacral nerve stimulation therapy. Recently, a new therapy for FI, the FENIX Continence Restoration System (Torax Medical, Inc., Shoreview, MN), has become available. The FENIX device is placed through a perineal incision; however, pelvic radiation and previous anal carcinoma are both contraindications. We report the case of a 62-year-old woman with FI after anal carcinoma. Treatment included surgery, chemotherapy, and pelvic radiation. Initially, she was treated with conservative therapy and sacral nerve stimulation, which were only partially effective. A physical examination showed perineal skin changes consistent with previous radiation, which increased the patient's risk of infection and a nonhealing wound. Therefore, a robotic approach was used to place the FENIX device and improve the patient's quality of life. Our case sets a precedent for expanding the treatment options of FI in patients with previous pelvic radiation and using a robotic approach for the placement of the FENIX device.

Incumplimiento del protocolo de lavado de manos propuesto por la OMS en centros de salud de caracas / WHO's hand disinfection protocol breach in healthcare centers in Caracas

Objetivo: Los pacientes quirúrgicos constituyen una de las poblaciones más vulnerables para contraer infecciones nosocomiales (particularmente del sitio quirúrgico). La higiene de manos es fundamental para reducir la transmisión de infecciones, es por esto que nos parece necesario evaluar el cumplimiento del protocolo de higiene de manos (propuesto por la Organización Mundial de la Salud) en servicios quirúrgicos de un hospital modelo en Caracas. Métodos: Se llevó a cabo un estudio descriptivo, transversal, observacional, para evaluar el cumplimiento del protocolo y la disponibilidad de requisitos mínimos necesarios para llevarlo a cabo. Se utilizaron métodos de estadística descriptiva para el análisis de datos. Para la proporción de individuos que cumplieron el protocolo, se calcularon intervalos de confianza de 95% y al comparar el personal médico y el de enfermería se utilizó la prueba de chi-cuadrado. Resultados: Solo 4 habitaciones de pacientes (8,5%), contaban con los requisitos mínimos para un adecuado cumplimiento del protocolo. Por otra parte, solo el 2,3% de los participantes (pT = 0,0227. IC95%: 0,00 ; 0,0667) lo llevó a cabo. El personal de enfermería presentó una diferencia de riesgo de 0,033 (-0,097;0,031, p=0,51) con respecto al médico. Conclusión: La falta de prácticas de higiene de manos en la institución de salud (97,7%), es un problema que debe ser más estudiado. Es posible que se deba al hecho de que 91,5% de las habitaciones no cumple con los requisitos mínimos necesarios para el lavado de manos, sin embargo queda fuera de los alcances de este estudio explicar la causa(AU)

Objective: Surgical patients constitute one of the most vulnerable populations to nosocomial infections (particularly surgical site infections). Hand hygiene is fundamental to reduce infection transmission. This is the reason why we consider necessary to evaluate the fulfillment of the hand hygiene protocol (established by the World Health Organization) in surgical departments of a model healthcare center in Caracas. Methods: We carried out a crosssectional study in order to evaluate the fulfillment of the aforementioned protocol, as well as the availability of minimum requirements to perform it. We used descriptive statistics for data analysis, then constructed 95% confidence intervals for the proportion of individuals who carried out the protocol during daily activities, in order to compare nursing staff to medical staff we used the chisquare hypothesis test. Results: Only 4 patient rooms (8.5%) had the minimum requirements to fulfill an adequate hand hygiene protocol. On the other hand, only 2.3% of the individuals observed actually performed hand hygiene (pT= 0.0227. 95%CI: 0.00; 0.0667). Nursing staff had a non-statistically-significant risk difference of 0.033 (-0.097;0.031, p=0.51) when compared to medical staff. Conclusion: Absence of hand hygiene practices in the healthcare center (97.7%) is an issue that has to be studied more profoundly. It is indeed possible that this non adherence to the protocol is due to the fact that 91.5% of the patient rooms did not have the minimum requirements to perform adequate hand hygiene, it is however outside the scope of the study to establish any causal relations(AU)