Direct prostacyclin transition in pediatric patients with pulmonary hypertension.

Pediatric patients with pulmonary arterial hypertension (PAH) are commonly treated with the prostacyclin analog treprostinil in IV, SQ, inhaled or oral form, or the prostacyclin receptor agonist selexipag. Patients who transition between these medications often follow recommendations for gradual up- and down-titrations that take place over several days in the hospital or several weeks as an outpatient. However, hospital resources are limited, and long transitions are inconvenient for patients and families. We report a case series of eight pediatric patients with PAH transitioned directly between prostacyclins with no overlapping doses. Direct medication transitions occurred in the cardiac intensive care unit (CICU), at home and in cardiology clinic. Equivalent doses for selexipag were estimated using information extrapolated from experience, published materials and selexipag study guidelines. All patients completed direct transition as planned and remained on transition dose for at least 1 week. In most cases selexipag was up-titrated at home after establishing initial transition dose. In select patients, direct prostacyclin transition in pediatric patients with PAH is safe, effective, convenient for families and reduces the use of hospital resources.

Carbonate-Metal Reactions in the Lower Mantle.

Carbonates are important carbon-bearing phases in the mantle. While their role in upper mantle petrologic processes has been well studied, their effect on phase relations, melting, and transport properties in the lower mantle is less understood. The stability of carbonates in the mantle depends on a host of factors, including pressure, temperature, oxygen fugacity, and reactions with surrounding mantle phases. To understand the stability of carbonates in the presence of metal in the lower mantle, carbonate-metal reaction experiments on the Fe-Si-Ca-Mg-C-O system were conducted up to 124 GPa and 3200 K. We find that carbonates react with iron alloys to form silicates, iron carbides, and oxides. However, the temperature at which these reactions occur increases with pressure, indicating that along a geotherm in the lowermost mantle carbonates are the stable carbon-bearing phase. Carbon is found to be less siderophilic at high-pressure compared to silicon.

Depot medroxyprogesterone acetate concentrations in patients with and without the use of antiseizure medications.

OBJECTIVES: To measure plasma concentrations of medroxyprogesterone acetate (MPA) in users with epilepsy treated with antiseizure medications and compare these to MPA concentrations in those without epilepsy. STUDY DESIGN: For this multisite cross-sectional study, we obtained a single blood sample from those with epilepsy treated with various antiseizure medications (n = 18) within the week before their next depot medroxyprogesterone injection. Among the participants without epilepsy (n = 20), 10 similarly were scheduled within the week prior to the next injection, and 10 were scheduled at earlier intervals to attempt to balance the time intervals between groups. MPA concentrations were determined by a validated assay. RESULTS: MPA concentrations were similar among those with epilepsy and controls and between groups with and without the use of enzyme-inducing medications. The lowest MPA concentrations, under 0.07 ng/mL, were observed among two of eight using enzyme-inducing antiseizure medications, one of 10 using noninducing medications, and one of 19 controls had concentrations below 0.2 ng/mL. CONCLUSIONS: In this exploratory study, lower MPA concentrations in some participants using enzyme-inducing antiseizure medications suggest a potential interaction that could reduce depot medroxyprogesterone efficacy.

Dobbs Versus Jackson: Epilepsy, Reproductive Health, and Abortion.

On June 24, 2022, Dobbs vs Jackson Women's Health Organization was decided by the Supreme Court effectively overturning the former precedent of Roe v. Wade. This ruling has direct consequences for the care of persons with epilepsy of childbearing potential. Now more than ever we need to provide informed and comprehensive care to our patients with epilepsy who are particularly vulnerable to the impact of this legislation on their reproductive decision-making. Important areas to understand include (1) the current state of affairs on abortion in the United States; (2) contraception options, their effectiveness, and interactions with anti-seizure medications (ASM); (3) teratogenic effects and adverse neurocognitive outcomes of ASMs; (4) folic acid supplementation; (5) the effect on perinatal and pediatric care; and (6) unique issues related to people of color.

Catamenial epilepsy occurrence and patterns in a mixed population of women with epilepsy.

We evaluated the occurrence and distribution of patterns of catamenial epilepsy in a heterogenous cohort of women with epilepsy on no hormonal therapies, enrolled in a prospective, observational study. The primary aim of the study was pregnancy rate in women with epilepsy with no prior reproductive problems. In this analysis, we included women who recorded one or more menstrual cycles with one or more seizures. We measured progesterone concentrations for one to three cycles. We defined catamenial patterns as twofold or greater average daily seizure frequency around menstruation (C1), ovulation (C2), and for anovulatory cycles, from midcycle through menstruation (C3). Twenty-three of the 89 enrolled women with epilepsy were eligible for this analysis; 12 of 23 met criteria for catamenial epilepsy; five of 23 demonstrated only a C1 pattern, two of 23 only a C2 pattern, five of 23 a combined C1/C2 pattern, and the one woman with anovulatory cycles did not demonstrate a C3 pattern. There were no differences in likelihood of demonstrating a catamenial pattern between those who reported a prior catamenial pattern and those who did not (p = .855). This analysis demonstrates the utility of app-based tracking to determine a catamenial pattern. Larger prospective studies could confirm these findings and inform potential therapeutic trial designs for catamenial epilepsy.

Failure to tolerate continuous subcutaneous treprostinil in pediatric pulmonary hypertension patients.

Continuous subcutaneous (SubQ) treprostinil is an effective therapy for pediatric patients diagnosed with pulmonary hypertension (PH). To date, the clinical characteristics and factors associated with failure to tolerate this therapy have not been described. The purpose was to describe patient-reported factors contributing to SubQ treprostinil intolerance in pediatric patients with PH. A retrospective descriptive study was performed at 11 participating sites in the United States and Canada for patients younger than 21 years of age diagnosed with PH who failed treatment to tolerate SubQ treprostinil between January 1, 2009, and December 31, 2019. All data were summarized using descriptive statistics. Forty-one patients met the inclusion criteria. The average age at SQ treprostinil initiation, and length of treatment, was 8.6 years and 22.6 months, respectively. The average maximum dose, concentration, and rate were 95.8 ng/kg/min, 6.06 mg/mL, and 0.040 mL/h, respectively. The reasons for failure to tolerate SubQ treprostinil included intractable site pain (73.2%), frequent site changes (56.1%), severe site reactions (53.7%), infections (26.8%), and noncompliance/depression/anxiety (17.1%). Thirty-nine (95.1%) patients transitioned to a prostacyclin therapy with 23 patients transitioning to intravenous prostacyclin, 5 to inhaled prostacyclin, 5 to oral prostacyclin, and 7 to a prostacyclin receptor agonist. A subset of pediatric PH patients failed to tolerate SubQ treprostinil infusions despite advances in SubQ site maintenance and pain management strategies. Intractable site pain, frequent SubQ site changes, and severe localized skin reactions were the most common reasons for failure.

Anti-Müllerian Hormone Level Decline in Patients Undergoing Hysterectomy With and Without Oophorectomy Compared With Natural Menopause.

OBJECTIVE: To evaluate the relationship between hysterectomy with and without ovarian conservation and the onset of ovarian failure using anti-müllerian hormone (AMH) levels and imputed final menstrual period (FMP). METHODS: A total of 1,428 women with an observed FMP and 232 women who underwent hysterectomy (159 with bilateral salpingo-oophorectomy [BSO], 13 with one ovary conserved, and 60 with both ovaries conserved) and who had serial AMH measurements were included from SWAN (The Study of Women's Health Across the Nation), a multi-ethnic, multi-site, community-based study. Anti-müllerian hormone levels were sampled annually with at least one presurgery or pre-FMP measurement at least one postsurgery or post-FMP measurement. Surgery-related differences in patterns of AMH levels with respect to surgery date or FMP were estimated using piecewise linear mixed modeling; differences in age at first undetectable AMH level were estimated using survival analyses. RESULTS: Patients with conservation of one or both ovaries or natural menopause demonstrated similar patterns of decline in AMH levels when anchored to surgery or FMP. Patients with hysterectomy (all types) had a later counterfactual FMP (52.9±0.2 SEM) compared with the observed FMP in those with natural menopause (52.1±0.1 years, P =.002). Those undergoing BSO had an immediate reduction in AMH level to undetectable after surgery. CONCLUSION: Hysterectomy does not lead to a more rapid decline in AMH levels postoperatively compared with natural menopause. Patients undergoing BSO have a rapid loss of AMH, consistent with complete removal of the ovaries. These data suggest that hysterectomy as currently performed does not compromise ovarian reserve.

Improving the quality of head and neck radiotherapy CT images using a second image reconstruction set.

PURPOSE: To improve the quality of radiotherapy head and neck CT images through use of an additional image set reconstructed from the raw data of the primary scan, thus allowing parameters such as reconstruction field-of-view (FOV) and kernel to be optimised without impacting on the images used for treatment planning dose calculations. METHODS: Using a Catphan image quality phantom and a Toshiba Aquilion LB CT scanner, qualitative and quantitative measurements were made for different reconstruction kernels and FOV diameters. The preferred FOV diameter and kernels were selected. Clinical images from six patients were reconstructed using those kernels (FC13, FC41, FC44, FC64) and the chosen FOV, 200 mm. The images were ranked to choose the kernel which gave best image quality for organ delineation. The scanner workflow was adjusted to produce for every scan a second image set using the chosen kernel and FOV. Finally, for 10 patient scans, image quality was compared for the two reconstructed images. RESULTS: The second image set was produced using kernel FC44 and 200 mm FOV. The primary image set using 550 mm FOV and FC13 was unchanged and contours from the second image set merged onto the first. Oncologists reported increased confidence in contouring in all cases using the new procedure. CONCLUSION: Production of a second image set, using a reduced reconstruction FOV and a kernel which optimises contrast and sharpness, significantly improves the quality of head and neck CT images for contouring, and avoids any dose increase.

Development of a COVID-19 virtual community of practice in New South Wales: A qualitative study.

BACKGROUND AND OBJECTIVES: In April 2020, a group of general practice leaders in NSW, Australia, established a COVID-19 virtual community of practice (VCoP) to facilitate rapid transfer and implementation of clinical guidance into practice. This research aimed to gain an understanding of the experience and effectiveness of the VCoP from leaders and members. METHOD: The study used a qualitative participatory action research methodology. A framework analysis was applied to focus group discussion, semi-structured interview and open-text written response data. RESULTS: Thirty-six participants contributed data. In addition to a positive evaluation of the effectiveness of information transfer and support, a key finding was the importance of the role of the VCoP in professional advocacy. Areas for improvement included defining measures of success. DISCUSSION: This study has reinforced the potential for VCoPs to aid health crisis responses. In future crisis applications, we recommend purposefully structuring advocacy and success measures at VCoP establishment.

Preferences and experiences of women with epilepsy regarding sexual and reproductive healthcare provision.

RATIONALE: Women with epilepsy (WWE) have unique disease-specific considerations regarding their sexual and reproductive health (SRH), which impact decision-making around pregnancy and contraception. Understanding their perspectives, preferences, and experiences regarding SRH care contributes to optimizing patient-centered clinical practice. METHODS: We conducted individual semi-structured interviews with WWE aged 18-45 years, exploring their SRH care experiences and preferences. We audio-recorded and transcribed all interviews. Two coders used both inductive and deductive strategies to perform thematic analysis and identify key themes and representative quotes. RESULTS: Twenty WWE completed interviews (median age 23 years; range 18-43 years). Key themes included: 1) SRH counseling from neurologists often did not occur, was limited in scope, or contained misinformation, especially during adolescence and early adulthood. In particular, participants felt that they received poor counseling about contraception, fertility, folic acid, and teratogenic medications, which impacted their reproductive decision-making. 2) WWE report fragmented care between their neurologist and other SRH providers. 3) WWE prefer that their neurologists initiate routine comprehensive discussions about SRH. 4) Conversations about SRH should begin in adolescence and include private confidential discussions between neurologists and WWE. 5) Successful SRH conversations between neurologists and WWE involve detailed information, reassurance, and support for the patient's reproductive goals. CONCLUSION: WWE desire comprehensive, coordinated counseling and care regarding SRH and epilepsy, and often experience suboptimal SRH care. Better understanding of the SRH needs, preferences, and experiences of WWE will help inform interventions to optimize patient-centered SRH counseling and care by healthcare professionals, especially during adolescence.

Female permanent contraception trends and updates.

Permanent contraception remains one of the most popular methods of contraception worldwide. This article has reviewed recent literature related to demographic characteristics of users, prevalence of use and trends over time, surgical techniques, and barriers to obtain the procedure. We have emphasized the patient's perspective as a key element of choosing permanent contraception. This review has incorporated sections on salpingectomy, hysteroscopy, unmet need, impact of policies at religiously affiliated institutions, and reproductive coercion.

Analysis and results from a UK national dose audit of paediatric CT examinations.

OBJECTIVE: To present the results following a UK national patient dose audit of paediatric CT examinations, to propose updated UK national diagnostic reference levels (DRLs) and to analyse current practice to see if any recommendations can be made to assist with optimisation. METHODS: A UK national dose audit was undertaken in 2019 focussing on paediatric CT examinations of the head, chest, abdomen/pelvis and cervical spine using the methods proposed by the International Commission on Radiological Protection. The audit pro-forma contained mandatory fields, of which the post-examination dosimetry (volume CT dose index and dose-length product) and the patient weight (for body examinations) were the most important. RESULTS: Analysis of the data submitted indicates that it is appropriate to propose national DRLs for CT head examinations in the 0-<1, 1-<5, 5-<10 and 10-<15 year age ranges. This extends the number of age categories of national DRLs from those at present and revises the existing values downwards. For CT chest examinations, it is appropriate to propose national DRLs for the first time in the UK for the 5-<15, 15-<30, 30-<50 and 50-<80 kg weight ranges. There were insufficient data received to propose national DRLs for abdomen/pelvis or cervical spine examinations. Recommendations towards optimisation focus on the use of tube current (mA) modulation, iterative reconstruction and the selection of examination tube voltage (kVp). CONCLUSION: Updated UK national DRLs are proposed for paediatric CT examinations of the head and chest. ADVANCES IN KNOWLEDGE: A national patient dose audit of paediatric CT examinations has led to the proposal of updated national DRLs.

Maternal morbidity after preterm premature rupture of membranes at <24 weeks' gestation.

BACKGROUND: After preterm premature rupture of membranes at <24 weeks' gestation, pregnant women may choose continuation (expectant management) or termination of pregnancy, via either dilation and evacuation or labor induction. Neonatal outcomes after expectant management are well described. In contrast, limited research addresses maternal outcomes associated with expectant management compared to termination of pregnancy. OBJECTIVE: This study aimed to compare maternal morbidity after preterm premature rupture of membranes at <24 weeks' gestation in women who choose either expectant management or termination of pregnancy. STUDY DESIGN: This retrospective cohort study included women with preterm premature rupture of membranes between 14 0/7 and 23 6/7 weeks' gestation with singleton or twin pregnancies at 3 institutions from 2011 to 2018. We excluded pregnancies complicated by fetal anomalies, rupture of membranes immediately after obstetrical procedures (chorionic villus sampling, amniocentesis, cerclage placement, fetal reduction), spontaneous delivery <24 hours after membrane rupture, and contraindications to expectant management. Our primary outcome was the difference in composite maternal morbidity between women choosing expectant management and women choosing termination of pregnancy. We defined composite maternal morbidity as at least 1 of the following: chorioamnionitis, endometritis, sepsis, unplanned operative procedure after delivery (dilation and curettage, laparoscopy, or laparotomy), injury requiring repair, unplanned hysterectomy, unplanned hysterotomy (excluding cesarean delivery), uterine rupture, hemorrhage of >1000 mL, transfusion, admission to the maternal intensive care unit, acute renal insufficiency, venous thromboembolism, pulmonary embolism, and readmission to the hospital within 6 weeks. We compared the demographic and antenatal characteristics of women choosing expectant management with that of women choosing termination of pregnancy and used logistic regression to quantify the association between initial management decision and composite maternal morbidity. RESULTS: We identified 350 women with pregnancies complicated by preterm premature rupture of membranes at <24 weeks' gestation, and 208 women were eligible for the study. Of the 208 women, 108 (51.9%) chose expectant management as initial management, and 100 (48.1%) chose termination of pregnancy as initial management. Among women selecting termination of pregnancy, 67.0% underwent labor induction, and 33.0% underwent dilation and evacuation. Compared to women who chose termination of pregnancy, women who chose expectant management had 4.1 times the odds of developing chorioamnionitis (38.0% vs 13.0%; 95% confidence interval, 2.03-8.26) and 2.44 times the odds of postpartum hemorrhage (23.1% vs 11.0%; 95% confidence interval, 1.13-5.26). Admissions to the intensive care unit and unplanned hysterectomy only occurred after expectant management (2.8% vs 0.0% and 0.9% vs 0.0%). Of women who chose expectant management, 36.2% delivered via cesarean delivery with 56.4% non-low transverse uterine incisions. Composite maternal morbidity rates were 60.2% in the expectant management group and 33.0% in the termination of pregnancy group. After adjusting for gestational age at rupture, site, race and ethnicity, gestational age at entry to prenatal care, preterm premature rupture of membranes in a previous pregnancy, twin pregnancy, smoking, cerclage, and cervical examination at the time of presentation, expectant management was associated with 3.47 times the odds of composite maternal morbidity (95% confidence interval, 1.52-7.93), corresponding to an adjusted relative risk of 1.91 (95% confidence interval, 1.35-2.73). Among women who chose expectant management, 15.7% avoided morbidity and had a neonate who survived to discharge. CONCLUSION: Expectant management for preterm premature rupture of membranes at <24 weeks' gestation was associated with a significantly increased risk of maternal morbidity when compared to termination of pregnancy.

A baseline patch test series for New Zealand.

BACKGROUND: Patch testing is the gold standard diagnostic test for allergic contact dermatitis and needs to be relevant to the region and the population being tested. The aim of this study was to develop a specific New Zealand baseline series (NZBS). METHOD: We performed a retrospective case note review of patients attending four regional patch test centres between 2008 and 2020. Demographic and diagnostic information was collected for each patient along with results of patch testing. Using the results of this review, a group of 11 dermatologists with an interest in contact dermatitis agreed on a core group of allergens for inclusion in an NZBS, based on the frequency of positive reactions and allergens of interest. The remaining potential allergens were ranked by each dermatologist using an online questionnaire, with inclusion in the final NZBS by consensus. RESULTS: Results from 2402 patients (67% female, mean age 44 years) from Auckland, Wellington, Palmerston North and Christchurch were collated. The 10 most frequent positive (relevant and non-relevant) allergens were nickel sulfate (22.0%), fragrance mix I (8.6%), cobalt chloride (7.3%), Myroxylon pereirae (5.6%), colophonium (5.1%), p-phenylenediamine (4.9%), methylisothiazolinone/methylchloroisothiazolinone (4.1%), fragrance mix II (3.9%), potassium dichromate (3.5%) and methylisothiazolinone (3.4%). Based on these results, a core series of 30 allergens was developed, with an additional 30 allergens added to form the extended series (total 60 allergens). CONCLUSION: The baseline series of patch test allergens for routine use in New Zealand (NZBS) is based on national patch test data and expert consensus.

Diverse Approaches to Ovarian Tissue Cryopreservation Have Equivalent Outcomes in Markers of Tissue Viability.

Ovarian tissue cryopreservation (OTC) is an accepted method of fertility preservation. However, OTC is not standardized and many variations exist in the freezing strategy, tissue processing, and surgical approach. In this pilot study, we used a sheep model to compare slow freezing versus vitrification techniques, as well as the feasibility of processing ovarian tissue into a hyaluronan suspension of small ovarian units. Twelve ovaries were harvested from six female ewes. Paired tissues from each animal were assigned to different treatments and underwent freezing, thawing, autotransplantation, and second-look surgery, for a total of 18 surgical procedures and 3 measured time points. Treatments included whole tissue strips versus gel suspension and slow freezing versus vitrification. At each of the time points, tissue viability was measured by immunohistochemical analysis of CD31 and cleaved caspase-3 (CCASP3). CD31 and CCASP3 expression levels were equivalent between slow freezing and vitrification, and between whole ovarian tissue strips and gel suspension of fragmented ovarian tissue, at all time points. These preliminary data using a sheep model suggest that ovarian tissue is robust and likely to be minimally affected by aggressive fragmentation using a hyaluronan suspension. Furthermore, we provide evidence in support of vitrification as a viable option in OTC. Hyaluronan suspension of ovarian cortical fragments is novel and may represent a desirable method for reimplantation of frozen-thawed ovarian tissue in patients where occult malignant cells are a concern.

Retrospective phylogenetic analyses of formalin-fixed paraffin-embedded samples from the 2011 Rift Valley fever outbreak in South Africa, through sequencing of targeted regions.

The last major Rift Valley fever outbreak in South Africa was between 2008 and 2011. Viruses isolated between 2008 and 2010 were phylogenetically assigned to Lineage C, Lineage K and the novel lineage H. The 2011 outbreaks occurred primarily in the Eastern, Western and Northern Cape provinces, with no sequence data or phylogenetic relationship published. Samples from these outbreaks were submitted to the Faculty of Veterinary Sciences, University of Pretoria, for immunohistochemical confirmation of Rift Valley fever phlebovirus presence. These samples were formalin-fixed and paraffin-embedded (FFPE) and stored at the Pathology section for several years. This study describes a modified extraction method used to obtain RNA from the FFPE samples, as well as the primer combinations used to phylogenetically classify them as belonging to the novel lineage H.

Can different Catphan phantoms be used in a multi-centre audit of radiotherapy CT image quality?

PURPOSE: To determine the variation between Catphan image quality CT phantoms, specifically for use in a future multi-centre image quality audit. METHOD: 14 Catphan phantoms (models 503, 504 and 604) were scanned on a Canon Aquilion Prime CT scanner using a single scan protocol. Measurements were made of noise in the uniformity section, visibility of low contrast targets and contrast, x-ray attenuation and CT number for 5 materials in the sensitometry section. Scans were also acquired using one phantom and varying reconstruction field of view, image slice thickness, effective tube-current-time product and iterative reconstruction settings to determine how the degree of inter-phantom variability compared with the magnitude of changes from scan parameter alteration. RESULTS: Across all phantoms the mean CT value in the uniformity section was 7.0 (SD 0.9) range: 4.9-8.1 HU. For the different materials the CT numbers were air: -1004 ± 5, Polymethylpentene: -190 ± 2, Polystyrene: -42 ± 2, Delrin: 321 ± 5 and Teflon: 898 ± 8 HU. Consistency of low contrast targets through visual scoring was good. Measured contrast was lower (p < 0.001) with more variability for 504 versus 604 models. All phantoms produced identical tube current settings with x-ray tube current modulation, indicating no x-ray attenuation differences. The degree of change in image quality metrics between phantoms was small compared with results when scan parameters were varied. CONCLUSION: Catphan phantoms model 604 showed minimal differences and will be used for multi-centre inter-comparison work, with the consistency between phantoms appropriate for measuring possible variations in image quality.

Preparation and redeployment of house staff during a pandemic.

The COVID-19 pandemic created unique issues for house staff physicians. Gaps in surgical experience due to canceled cases, a focus on obstetrics over gynecology during the spring months when many senior residents and fellows are completing their case requirements and the stress of working with patients infected with a highly communicable disease all contributed to an unprecedented challenge facing residency and fellowship programs. Our objective is to describe how the Obstetrics and Gynecology residency and fellowship programs at Columbia University Irving Medical Center adapted to their changing landscape, redeployed their residents and fellows while assuring ongoing trainee education, wellness and scholarship during the peak of the pandemic.