bluuebunny/crossref_metadata_2025 huggingface dataset:
3D osteotomies—improved accuracy with patient-specific instruments (PSI)
Authors: Jörgens Maximilian , Keppler Alexander M. , Ahrens Philipp , Prall Wolf Christian , Bergstraesser Marcel , Bachmeier Andreas T. , Zeckey Christian , Cavalcanti Kußmaul Adrian , Böcker Wolfgang , Fürmetz Julian
Published: July 2022

Purpose

Three-dimensional (3D) printed patient-specific instruments (PSI) have been introduced to increase precision and simplify surgical procedures. Initial results in femoral and tibial osteotomies are promising, but validation studies on 3D planning, manufacturing of patient-specific cutting blocks and 3D evaluation of the attained results are lacking.

Methods

In this study, patient-specific cutting blocks and spacers were designed, fabricated, and used to perform a high tibial osteotomy (HTO). After segmentation of CT data sets from 13 human tibiae, 3D digital planning of the HTO was performed with a medial opening of 8 mm. These 3D models were used to fabricate patient-specific cutting blocks and spacers. After the surgical procedure, accuracy was evaluated measuring 3D joint angles and surface deviations.

Results

The lowest mean deviation was found to be 0.57° (SD ± 0.27) for the MPTA. Medial and lateral tibial slope deviated from the 3D planning by an average of 0.98° (SD ± 0.53) and 1.26° (SD ± 0.79), respectively, while tibial torsion deviated by an average of 5.74° (SD ± 3.24). Color analysis of surface deviations showed excellent and good agreement in 7 tibiae.

Conclusion

With 3D cutting blocks and spacers, the 3D planning of the HTO can be translated into reality with small deviations of the resulting joint angles. Within this study, the results of the individual steps are examined for errors and thus a critical evaluation of this new and promising method for performing patient-specific HTOs is presented.
Laparoscopic and robot-assisted suture versus mesh hysteropexy: a retrospective comparison
Authors: Gopinath Deepa , Yong Chin , Harding-Forrester Sam , McIntyre Felix , McKenzie Dean , Carey Marcus
Published: July 2022

Introduction and hypothesis

Our study was aimed at comparing the outcomes of laparoscopic and robot-assisted laparoscopic suture-based hysteropexy (SutureH) versus sacral hysteropexy using mesh (MeshH) for bothersome uterine prolapse. Our hypothesis is that MeshH is more successful and provides better uterine support than SutureH.

Methods

A retrospective cohort study of 228 consecutive women who underwent re-suspension of the uterus using uterosacral ligaments (SutureH n=97) or a “U-shaped” mesh from the sacral promontory (MeshH, n=132). Surgery was performed by laparoscopy or robot-assisted laparoscopy. Subjects were assessed at baseline, 1 year, and beyond 1 year. The null hypothesis, that SutureH and MeshH have similar success, was based on a composite outcome (“composite success”), and that they provide the same level of uterine support, was based on POP-Q point C at 1 year. “Composite success” was defined as: POP-Q point C above the hymen; absence of a vaginal bulge; no repeat uterine prolapse surgery or pessary placement. Other outcomes included improvement in symptomology using Patient Global Impression of Improvement, POP-Q point C change and complications.

Results

Follow-up data were available for 191 out of 228 women. “Composite success” was not significantly different between MeshH and SutureH groups (81.7% vs 84.5%, p=0.616). MeshH provided better elevation of the uterus than SutureH (point C change: −7.38cm vs −6.99cm; p<0.001). Similar symptom improvement and low complications occurred in both groups.

Conclusions

Laparoscopic and robot-assisted laparoscopic suture hysteropexy and mesh sacral hysteropexy provide women with minimally invasive, durable surgical options for uterine preservation. “Composite success” was similar in the two groups, but MeshH provided better uterine support than SutureH. However, SutureH gives women an effective mesh-free option.
Prognostic Value of Carcinoembryonic Antigen Changes Before and After Operation for Esophageal Squamous Cell Carcinoma
Authors: Hong Zhinuan , Huang Zhixin , Chen Zhen , Kang Mingqiang
Published: July 2022

Background

To study the prognostic significance of changes in the level of carcinoembryonic antigen (CEA) before and after surgery on the long‐term prognosis of patients with esophageal squamous cell carcinoma (ESCC).

Methods

Patients with ESCC who underwent radical esophagectomy (between 2010 and 2017) were divided into three groups as follows: normal group (preoperative CEA≦1.6 ng/ml), normalized group (preoperative CEA > 1.6 ng/ml and postoperative CEA≦1.6 ng/ml) and non‐normalized group (preoperative CEA > 1.6 ng/ml and postoperative CEA > 1.6 ng/ml). The Kaplan–Meier analysis was used to construct survival curves. Cox proportional hazards regression models was used to determine the independent prognostic factors for ESCC. Variables with P < 0.1 in univariable analysis were included in the multivariable model used to determine the independent risk factors.

Results

A total of 394 patients were included. The 5‐OS rate of ESCC patients in normalized group (n = 36) and non‐normalized group (n = 161) were significantly shorter than normal group (n =197) patients (57.3% vs 58.3% vs 82.0%, P < 0.001). The difference in survival time distribution between normal group and normalized/non‐normalized group is statistically significant, P < 0.001. However, there was no statistically significant variation in survival time distribution between the normalized and non‐normalized groups, P = 0.289. In multivariate analysis, older age (> 65 years old), advanced pT‐stage, advanced pN‐stage, normalized group and non‐normalized group were independent prognostic risk factors of worse overall survival.

Conclusions

ESCC patients with high preoperative CEA level had poorer prognosis regardless of the changes of postoperative CEA level.
Inter-model variability of the CMIP5 future projection of Baiu, Meiyu, and Changma precipitation
Authors: Horinouchi Takeshi , Kawatani Yoshio , Sato Naoki
Published: July 2022

Many studies have suggested that mean precipitation associated with the East Asian Summer Monsoon (EASM) will be increased by the ongoing global warming, but its quantitative projection by climate models has large variability, with some models suggesting even decreases. We investigate the inter-model variability of projected centennial changes of the EASM separately for Baiu over Japan, Meiyu over eastern China, and Changma over Korea by using monthly-mean model outputs provided by the Coupled Model Intercomparison Project Phase 5 (CMIP5) project. Results with the Representative Concentration Pathway 4.5 and 8.5 scenarios (RCP4.5 and RCP8.5) are consolidated by normalizing with the global-mean near-surface air temperature changes. For all the three EASM land regions, inter-model differences in the mean precipitation changes are positively correlated with the southerly moisture flux changes to the south of the regions. The correlation is highest in June among the June-to-August months, whose reason may be because precipitation in early summer relies on large-scale southerly moisture transport. These changes are localized and nearly independent among the three regions where Baiu, Meiyu and Changma occur. The low-level southerly change to the south of Japan, which affects the Baiu precipitation change, is positively correlated with upper-tropospheric meridional wind to its north; it further exhibits a stationary Rossby-wave feature associated with the Silk-Road teleconnection. This study suggests that future changes in the EASM mean precipitation depend on circulation changes and more-or-less localized.
Nonlocal Harnack inequalities in the Heisenberg group
Authors: Palatucci Giampiero , Piccinini Mirco
Published: July 2022

We deal with a wide class of nonlinear integro-differential problems in the Heisenberg-Weyl group $$\mathbb {H}^n$$Hn, whose prototype is the Dirichlet problem for thep-fractional subLaplace equation. These problems arise in many different contexts in quantum mechanics, in ferromagnetic analysis, in phase transition problems, in image segmentations models, and so on, when non-Euclidean geometry frameworks and nonlocal long-range interactions do naturally occur. We prove general Harnack inequalities for the related weak solutions. Also, in the case when the growth exponent is$$p=2$$p=2, we investigate the asymptotic behavior of the fractional subLaplacian operator, and the robustness of the aforementioned Harnack estimates as the differentiability exponentsgoes to 1.
Deterioration of anterior resin composite restorations in moderate to severe tooth wear patients: 3-year results
Authors: Lima Verônica P. , Crins Luuk A. M. J. , Opdam Niek J. M. , Moraes Rafael R. , Bronkhorst Ewald M. , Huysmans Marie-Charlotte D. N. J. M. , Loomans Bas A. C.
Published: July 2022

Objectives

Deterioration in anterior resin composite restorations placed in tooth wear patients was investigated after 36 months.

Materials and methods

Data collected prospectively for 47 participants of the Radboud Tooth Wear Project were used (41 ± 8 years, 90% male, n = 270 restorations). Restorations were individually evaluated using intraoral photographs and 3D scans to rate modified FDI scores and to record the presence of degradation features. Four groups with distinct combinations of composites and techniques were assessed, and multivariable logistic regression models were used to analyze the data (p < 0.05).

Results

For all groups together, early degradation signs were present at 1 month: irregularities (41.5%) and ditching (7.4%) were observed at the surface and adhesive interfaces. The frequency of irregularities decreased in the 36-month evaluation (37%), but ditching (12.2%) and fractures (10.7%) were more common. The most frequent deterioration (based on photographs) was observed for staining (44%) and loss of luster (31%). In 3D scans, the most frequent were for wear (25%), marginal adaptation (24%), and the presence of irregularities (19%). Canines had 5.5 times more chances of deterioration by ditching than incisors (p < 0.001). The differences between composites and restorative techniques were minor.

Conclusions

A continuous degradation process of restorations placed in tooth wear patients was observed in anterior teeth restored with different composites, with a progression of the deterioration over 36 months.

Clinical relevance

When placing anterior resin composite restorations in tooth wear patients, it could be important to establish realistic expectations and the need for checkup appointments.
Block avoiding point sequencings of partial Steiner systems
Authors: Horsley Daniel , Ó Catháin Padraig
Published: July 2022

A partial$$(n,k,t)_\lambda $$

(
n
,
k
,
t
)

λ

-system is a pair $$(X,{\mathcal {B}})$$

(
X
,
B
)

where X is an n-set of vertices and $${\mathcal {B}}$$
B
is a collection of k-subsets of X called blocks such that each t-set of vertices is a subset of at most $$\lambda $$
λ
blocks. A sequencing of such a system is a labelling of its vertices with distinct elements of $$\{0,\ldots ,n-1\}$$

{
0
,
…
,
n
-
1
}

. A sequencing is $$\ell $$
ℓ
-block avoiding or, more briefly, $$\ell $$
ℓ
-good if no block is contained in a set of $$\ell $$
ℓ
vertices with consecutive labels. Here we give a short proof that, for fixed k, t and $$\lambda $$
λ
, any partial $$(n,k,t)_\lambda $$

(
n
,
k
,
t
)

λ

-system has an $$\ell $$
ℓ
-good sequencing for some $$\ell =\Theta (n^{1/t})$$

ℓ
=
Θ
(

n

1
/
t

)

as n becomes large. This improves on results of Blackburn and Etzion, and of Stinson and Veitch. Our result is perhaps of most interest in the case $$k=t+1$$

k
=
t
+
1

where results of Kostochka, Mubayi and Verstraëte show that the value of $$\ell $$
ℓ
cannot be increased beyond $$\Theta ((n \log n)^{1/t})$$

Θ
(

(
n
log
n
)

1
/
t

)

. A special case of our result shows that every partial Steiner triple system (partial $$(n,3,2)_1$$

(
n
,
3
,
2
)

1

-system) has an $$\ell $$
ℓ
-good sequencing for each positive integer $$\ell \leqslant 0.0908\,n^{1/2}$$

ℓ
⩽
0.0908

n

1
/
2

.
What can we learn about credit risk from debt valuation adjustments?
Authors: Lin Wen , Panaretou Argyro , Pawlina Grzegorz , Shakespeare Catherine
Published: July 2022

Motivated by the debate about the introduction of the fair value option for (financial) liabilities (FVOL) and the requirement to recognize and separately disclose in financial statements debt valuation adjustments (DVAs), this study explores what we can learn about a firm’s credit risk from DVAs. Using a sample of US bank holding companies that elect the FVOL, we show that DVAs generally cannot be explained by the same factors that explain contemporaneous changes in bank’s credit quality. We further find that DVAs can explain future changes in credit risk when the fair value of liabilities is based on managerial inputs (Level 3). Overall our results suggest that managers have an information advantage in estimating credit risk and that DVAs provide inside information to the market.
Automated geometric analysis of metallic components through picture recognition models for manufacturing technology assessments
Authors: Buechler Tobias , Schulz Martin , Zaeh Michael F.
Published: July 2022

The selection and interaction of various manufacturing technologies are key difficulties in product development and production processes. A component’s geometry is one of the most important factors to consider when choosing the best technology. This article presents a method for an automated geometry analysis of metallic components. The goal is to analyze manufacturing technology alternatives regarding their capability to create required geometries. It also aims at short computing times since the outcome of this geometric analysis supplements a part screening methodology for the selection of the most suitable manufacturing technology for each component. To achieve a successful classification, artificial intelligence (AI) approaches are trained with images of the components that are labeled with suitable manufacturing technologies. The AI models hence learn how components of different manufacturing technologies look like and which characteristics they embody. To support the classification model, object recognition models are tested to automatically extract component features such as holes, coinages, or profile compositions. After training and comparing different AI approaches, the best performers are selected and implemented to analyze unseen image data of upcoming projects. In summary, this article’s research unifies existing AI approaches for image analyses with the field of production technology and product development. It provides a general methodology for applying image classification and object detection approaches in development processes of metallic components.
Antihypertensive Deprescribing in Older Adults: a Practical Guide
Authors: Sheppard James P. , Benetos Athanase , McManus Richard J.
Published: July 2022

Purpose of Review

To summarise evidence on both appropriate and inappropriate antihypertensive drug withdrawal.

Recent Findings

Deprescribing should be attempted in the following steps: (1) identify patients with several comorbidities and significant functional decline, i.e. people at higher risk for negative outcomes related to polypharmacy and lower blood pressure; (2) check blood pressure; (3) identify candidate drugs for deprescribing; (4) withdraw medications at 4-week intervals; (5) monitor blood pressure and check for adverse events. Although evidence is accumulating regarding short-term outcomes of antihypertensive deprescribing, long-term effects remain unclear.

The limited evidence for antihypertensive deprescribing means that it should not be routinely attempted, unless in response to specific adverse events or following discussions between physicians and patients about the uncertain benefits and harms of the treatment.

Perspectives

Clinical controlled trials are needed to examine the long-term effects of deprescribing in older subjects, especially in those with comorbidities, and significant functional decline.
Environmental Impacts of Ecofriendly Iron Oxide Nanoparticles on Dyes Removal and Antibacterial Activity
Authors: Hammad Eman N. , Salem Salem S. , Mohamed Asem A. , El-Dougdoug Wagdi
Published: July 2022

Biosynthesized nanoparticles have a promising future since they are a more environmentally friendly, cost-effective, repeatable, and energy-efficient technique than physical or chemical synthesis. In this work, Purpureocillium lilacinum was used to synthesize iron oxide nanoparticles (Fe2O3-NPs). Characterization of mycosynthesized Fe2O3-NPs was done by using UV–vis spectroscopy, transmission electron microscope (TEM), dynamic light scattering (DLS), and X-ray diffraction (XRD) analysis. UV–vis gave characteristic surface plasmon resonance (SPR) peak for Fe2O3-NPs at 380 nm. TEM image reveals that the morphology of biosynthesized Fe2O3-NPs was hexagonal, and their size range between 13.13 and 24.93 nm. From the XRD analysis, it was confirmed the crystalline nature of Fe2O3 with average size 57.9 nm. Further comparative study of photocatalytic decolorization of navy blue (NB) and safranin (S) using Fe2O3-NPs was done. Fe2O3-NPs exhibited potential catalytic activity with a reduction of 49.3% and 66% of navy blue and safranin, respectively. Further, the antimicrobial activity of Fe2O3-NPs was analyzed against pathogenic bacteria (Pseudomonas aeruginosa, Escherichia coli, Bacillus subtilis, and Staphylococcus aureus). The Fe2O3-NPs were clearly more effective on gram-positive bacteria (S. aureus and B. subtilis) than gram-negative bacteria (E. coli and P. aeruginosa). Thus, the mycosynthesized Fe2O3-NPs exhibited an ecofriendly, sustainable, and effective route for decolorization of navy blue and safranin dyes and antibacterial activity.
A combined GIS and remote sensing approach for monitoring climate change-related land degradation to support landscape preservation and planning tools: the Basilicata case study
Authors: Gabriele Marzia , Brumana Raffaella , Previtali Mattia , Cazzani Alberta
Published: July 2022

Monitoring landscapes in times of climate change patterns is a crucial issue, moreover, in the analyzed Mediterranean area, one of the major global candidates to develop land degradation stresses and consequential desertification phenomena. The research presented here is developed in the Mediterranean Basin, specifically in the Basilicata Region (southern Italy). The region is characterized by a very long history of intensive anthropization endowed by the high diversity of relatively geologically young soil types that consequentially created a vastity of spatial mosaics, which contributed to the composition of its archeolandscapes and endorsed some specific characteristics of the Mediterranean region, that evolved to respond to the human impact, including grazing, cultivation, and fires. Those key elements lead to the crucial issues of the region investigated here as soil erosion, salinization, loss of organic carbon, loss of biodiversity, and landslides, which together with deforestations, depopulation, and wildfires, define the exact framework of degradation and marginality. The evaluation of the sensitivity to degradation was performed (i) firstly at the regional scale, through a MEDALUS (Kosmas et al. 1999) approach, by implementing 6 main indicators (Soil Quality Index, Climate Quality Index, Vegetation Quality Index, Management Quality Index, Landslide Risk Index, Water Availability Index), and (ii) secondly at the mid-regional scale, through remote sensing by evaluation of the NDVI differencing thresholds in time intervals, covering a 20 years’ time span going from 2000 to 2020. The study helped to define the in-progress land degradation trends and scenarios of the region, which must be the evidence-based foundation of integrated landscape planning strategies in marginal territories, implemented through a Decision Support System (DSS) based both on ecological, climate-adaptive, and environmental indicators, and on social, cultural, and economic development co-creation strategies.
La prevenzione del diabete mellito di tipo 1
Authors: Nigi Laura , Formichi Caterina , Dotta Francesco
Published: July 2022

Sommario

Il trattamento del diabete di tipo 1 (DM1) prevede la somministrazione di insulina che tuttavia non rappresenta, com’è noto, una vera e propria “cura” per questa malattia. Negli ultimi decenni stiamo assistendo allo sviluppo di strategie preventive per il DM1 articolate su tre livelli: una prevenzione primaria finalizzata a prevenire lo sviluppo del processo autoimmune responsabile della distruzione $\beta $
β
-cellulare che caratterizza la malattia; una prevenzione secondaria per arrestare il processo autoimmunitario e impedire l’esordio clinico del diabete; una prevenzione terziaria per preservare la massa $\beta $
β
-cellulare residua e per ridurre il rischio di sviluppo delle complicanze croniche. Fra i molteplici approcci terapeutici sviluppati per impedire, ritardare o arrestare la distruzione $\beta $
β
-cellulare l’immunoterapia, in particolare, è stata ed è tutt’oggi oggetto di innumerevoli ricerche. I risultati sono tutt’altro che semplici da raggiungere, in quanto i meccanismi eziopatogenetici alla base del DM1 sono complessi e non ancora del tutto noti. Per il raggiungimento di un’efficacia preventiva è importante, inoltre, tenere in considerazione l’eterogeneità del DM1, la quale indubbiamente ha influenzato i risultati dei trattamenti finora sperimentati, così come validare nuovi biomarcatori che ci permettano di selezionare al meglio i pazienti da indirizzare a un determinato trattamento.
Adaptive Fuzzy Fault-Tolerant Control of Flexible Spacecraft with Rotating Appendages
Authors: Zhang Gaowang , Qiu Shi , Wang Feng
Published: July 2022

This paper focuses on the attitude control problems of spacecraft with external interference and platform actuator failure. The Lagrange method is used to establish dynamic models of complex spacecraft composed of rotating appendages and platform, and the quaternion is used to describe spacecraft attitude kinematics. Second, a fault-tolerant control algorithm that combined adaptive fuzzy control with finite time sliding mode is proposed for the spacecraft platform, and fixed-time control schemes are proposed for rotating parts to achieve stable rotation of the spacecraft components relative to the platform. Finally, a numerical simulation is performed to verify the superiority and effectiveness of the proposed control laws, and comparisons with other control methods are presented.
A Semi-Empirical Damage Evaluation Criterion for Thin Composite Impact Analysis
Authors: Colamartino I. , Bassi S. M. , Benetton D. , Anghileri M.
Published: July 2022

The present work aimed to develop a semi-empirical criterion able to describe impact events on GFRP and CFRP (glass and carbon fiber reinforced polymers) composite thin laminates: these events are able to generate large damages involving multiple mechanisms such as matrix cracking, fiber failure and, above all, delamination. Main purpose of this research was to obtain an accurate numerical description of the impact region in terms of damage extension and depth without the modelization of the adhesive layers. Starting from an experimental campaign of drop-weight impact tests on representative specimens and the implementation of related numerical Ansys LS-DYNA models exploiting equivalent shell approach, a damage criterion was developed and calibrated and a numerical tool was written and implemented within the LsPrePost, evaluating its reliability by means of correlation with the drop tests.
Fungi Functions: Cross-Species Imaginaries in Tade Thompson’s Wormwood Trilogy
Authors: Crane Kylie
Published: July 2022

Science fiction (SF), through its various generic conventions, provides a stage for exploring many dimensions of the Anthropocene: It enables challenges to time, to species, to causalities, to space-time coherences, and also to singularity. Tade Thompson’s-Wormwood trilogy engages several non-linear metaphors in engendering a nonhuman other, most specifically internet networks and fungi becoming. The alien sentience rendered in the trilogy offers an – amorphous and yet simultaneously very concrete – other against which humans must rally, themselves at the brink of the threat of extinction. Wormwood’s xenosphere – an atmosphere permeated with ›xenoforms‹, a kind of alien fungi which can interact with humans – constitutes only one of the many ways in which this SF world challenges the modes with which we organise our knowledges of our world.
Characteristics of effective entrepreneurship education post-COVID-19 in New Zealand primary and secondary schools: a Delphi study
Authors: Hardie Bethany , Lee Kerry , Highfield Camilla
Published: July 2022

This study was designed to investigate the perceptions of experts regarding the characteristics of effective entrepreneurship education in New Zealand primary and secondary schools. The aim of the study was to inform future policies, curriculum review and decision-making regarding entrepreneurial projects that were effective in the mainstream compulsory schooling sector. Using snowball sampling, 28 local entrepreneurship experts were recruited to participate in a Delphi Study. Through successive rounds, these participants established consensus on current and relevant characteristics of an effective entrepreneurship education primary and secondary school. The collective consensus determined seven characteristics for effective entrepreneurship education, centred around student learning approaches. Findings support curriculum planning focussed on creating authentic, action orientated projects or problem solving, strategies to foster entrepreneurship knowledge, skills and capabilities, seeking mentors or role models from the community, and the incorporation of financial literacy and business activities. These findings provide a basis for the successful development of New Zealand’s curricula for entrepreneurship education and enhanced entrepreneurship projects.
In-Season Estimation of Wheat Response to Nitrogen Using Normalized Difference Vegetation Index
Authors: Ali Ali M. , Ibrahim Sherif M. , Salem Emad M. M. , El-Sadek Ashraf N. , Salem Haytham M.
Published: July 2022

Applying fertilizer nitrogen (N) only when a crop response is predicted may enhance use efficiency and profitability while protecting the environment. The crop response index at harvest (RI-harvest, the ratio of the maximum grain yield and that of the plot in question) indicates the actual crop response to applied fertilizer N, although it is calculated after harvest. The objective of this study was to predict RI-harvest of wheat using normalized difference vegetation index (NDVI) response index (RI-NDVI, defined as the ratio of the NDVI in an N-sufficient plot and that in the field in question) captured at Feekes 6 stage. Field experiments were carried out across seven site-years (2017/18 to 2020/21) on wheat. In the first three seasons, the relationships between RI-harvest and RI-NDVI were established by applying a range of fertilizer N levels (0–320 kg N ha− 1), whereas the fourth season was used for validation. The results indicated that RI-NDVI could explain 79% of the variation in RI-harvest using the linear relationship: RI-harvest = 7.077 × RI-NDVI – 6.4885. This model was satisfactorly validated in the fourth season using an independent data set in which a range of fertilizer N doses was applied before the Feekes 6 growth stage. Validation was also carried out by applying a fertilizer N dose corresponding to the predicted RI-harvest. In comparison to the general recommendation, the application of appropriate prescriptive fertilizer N dose along with a fertilizer N dose based on the predicted RI-harvest resulted in an 11% increase in fertilizer N recovery efficiency. It suggests that estimation of in-season RI-NDVI is a viable method for identifying fields that are likely to respond to additional fertilizer N.
Improving Development of Drug Treatments for Pregnant Women and the Fetus
Authors: David Anna L. , Ahmadzia Homa , Ashcroft Richard , Bucci-Rechtweg Christina , Spencer Rebecca N. , Thornton Steve
Published: July 2022

The exclusion of pregnant populations, women of reproductive age, and the fetus from clinical trials of therapeutics is a major global public health issue. It is also a problem of inequity in medicines development, as pregnancy is a protected characteristic. The current regulatory requirements for drugs in pregnancy are being analyzed by a number of agencies worldwide. There has been considerable investment in developing expertise in pregnancy clinical trials (for the pregnant person and the fetus) such as the Obstetric-Fetal Pharmacology Research Centers funded by the National Institute of Child Health and Human Development. Progress has also been made in how to define and grade clinical trial safety in pregnant women, the fetus, and neonate. Innovative methods to model human pregnancy physiology and pharmacology using computer simulations are also gaining interest. Novel ways to assess fetal well-being and placental function using magnetic resonance imaging, computerized cardiotocography, serum circulating fetoplacental proteins, and mRNA may permit better assessment of the safety and efficacy of interventions in the mother and fetus. The core outcomes in women’s and newborn health initiative is facilitating the consistent reporting of data from pregnancy trials. Electronic medical records integrated with pharmacy services should improve the strength of pharmacoepidemiologic and pharmacovigilance studies. Incentives such as investigational plans and orphan disease designation have been taken up for obstetric, fetal, and neonatal diseases. This review describes the progress that is being made to better understand the extent of the problem and to develop applicable solutions.
Relationship Between Adverse Childhood Experiences and Vulvodynia Pain Scores
Authors: Phipps D , Southworth E , Welch K , Carey E
Published: July 2022

Introduction

Vulvodynia is a chronic vulvar pain disorder that has a significant impact on physical and mental health. As with other chronic pain disorders, vulvodynia appears to have a link with childhood exposure to physical and sexual abuse and poor family support.

Objective

To assess the relationship between adverse childhood experiences (ACEs) and vulvodynia pain scores using the standardized McGill Pain Scale.

Methods

This study is a retrospective review of intake questionnaire data for patients presenting to a multispecialty vulvar diseases clinic. Demographic information, ACEs-related questions and McGill pain scale portions of the intake questionnaire were included. Exclusion criteria included age less than 18, cancer diagnosis, or presenting postoperatively in initial consultation. A control group was randomly selected using 2:1 age-matching from patients within our database without a coexisting diagnosis of vulvodynia. The primary outcome, McGill pain score, was calculated as the sum across all 20 pain elements. Group differences across demographic characteristics, ACE responses, and McGill scores were assessed using simple linear regressions for continuous measures, and logistic regressions for binary measures.

Results

A total of 1,245 patients, 415 vulvodynia and 830 age-matched controls were analyzed. Patients with vulvodynia differed significantly across self-reported race/ethnicity, marital status, and income level. Overall, patients with a diagnosis of vulvodynia had higher median McGill pain scores compared to controls (22.0 vs 20.0, p<0.001). Among patients with vulvodynia, patients who reported ACEs exposure had higher McGill pain scores compared to patients without disclosed ACEs exposure (26.0 vs 22.0, p<0.001). Similarly, among patients in the control group, patients who reported ACE exposure had higher McGill pain scores compared to those without (24.0 vs 17.0, p<0.001).

Conclusions

Our findings indicate a relationship between exposure to ACEs and increased pain in patients with vulvodynia and controls. These findings suggest exposure to ACEs alone may contribute to increased perception of pain and result in higher McGill Pain Scores.

Disclosure

No
Vaginal Estrogen Therapy for Vulvovaginal Atrophy in Women with a Personal History of Breast Cancer – A Claims Database Analysis
Authors: Dumas K , Singh S , Kohn J , Kohn T , Clifton M
Published: July 2022

Introduction

Systemic therapies for breast cancer – selective estrogen receptor modulators (SERM), aromatase inhibitors (AI), oophorectomy, and chemotherapies – often result in vulvovaginal atrophy (VVA or atrophic vaginitis), in up to 70% of postmenopausal breast cancer survivors. While systemic estrogen therapy is often avoided in these patients, vaginal estrogen therapy is a safe treatment option that can be used to treat VVA symptoms in breast cancer survivors.

Objective

Our objective is to assess the use of vaginal estrogen for women with a diagnosis of VVA and a personal history of breast cancer using a large US claims database.

Methods

The TriNetX Diamond network database was queried: a US health research network of 190 million patients, encompassing healthcare encounters and prescriptions between 2009-2021. Females with a diagnosis of postmenopausal atrophic vaginitis or atrophy of the vulva (ICD-10 N95.2, N90.5) were included. Of these, women with breast cancer (C50 or Z86.000) were included if the diagnosis was at least 1 month prior to VVA diagnosis. Estrogen receptor status was collected when available (ICD-10 Z17.0, Z17.1). Prescriptions for treatment of VVA were included if prescribed within 1 year of VVA diagnosis. Incidence of vaginal estrogen use in patients with a history of breast cancer was determined for 2013-2015, 2016-2018, and 2019 to present.

Results

A total of 2,159,766 women with VVA were identified; of whom, 4.8% (n=104,327) had a personal history of breast cancer.Vaginal estrogen prescriptions were less frequent prescribed to women with history of breast cancer compared to women without (11% vs 22%, p<0.01, Table 1). Incidence rate of vaginal estrogen prescriptions for women with VVA and history of breast cancer remained stable around 10-11% from 2013 to present. 25,410 women with VVA and history of breast cancer had positive estrogen receptor status (ER+) and 4,893 had negative estrogen receptor status (ER-). There was no difference in vaginal estrogen prescribing between ER+ and ER- patients (7.4% vs 8.4%).

Conclusions

While vaginal estrogen can be safely used in women with VVA and personal history of breast cancer, it is prescribed for few eligible patients. Barriers to prescribing and using vaginal estrogen in this population should be explored, in order to significantly improve quality of life for those living with vulvovaginal atrophy.

Disclosure

No
Value of Next Generation Microbial DNA Sequencing in Sexually Related Infections in Heterosexual Dyads
Authors: Hlavinka T
Published: July 2022

Introduction

Sexually related infections, including cystitis and vaginitides in the female, and cystitis, urethritis and prostatitis in the male, as well as infections of the external genitalia in both genders were previously thought to be uncommonly transmitted from member to member of a dyad. Newer microbial detection techniques have allowed for more rapid identification of potential pathogens. However, persistence of an infection in a partner remains a perplexing diagnostic and therapeutic dilemma, raising the question of transmission of an infectious organism from a potentially asymptomatic partner.

Objective

To evaluate the benefit of mutual, synchronous microbial detection assays in dyads in whom at least one partner has a persistent, symptomatic infection that could be transmitted by sexual activity.

Methods

Twenty-six (26) heterosexual, monogamous couples underwent synchronous microbial testing including traditional laboratory culture techniques and polymerase chain reaction (PCR) and next generation sequencing (NGS) with a urine specimen, superficial and deep vaginal swab specimens in the female and urine and semen specimens in the male. Both genders had swab specimens of the external genitalia. The female member was symptomatic in 17 of the couples, the male in 4, and both were symptomatic in 5 couples. Results from all assays were tabulated and comorbid pathogens were treated with concurrent appropriate antimicrobials, using guidelines for therapeutic choices and duration of antimicrobial course. Sexual abstinence was required for the duration of the antimicrobial therapy. To assess efficacy, repeat assays were done after a time frame sufficient to allow for relapse/recurrence of the infection.

Results

Traditional culture techniques failed to demonstrate the significant pathogen(s) in at least one member of the dyad in all but 3 couples. This failure emerged from two primary foci: one methodological, in which automated techniques discarded specimens with low microbial growth or multiple organisms. The other was failure to identify the organism entirely. PCR identified the pathogen in at least one member in 11 of the 26 dyads, but NGS detected pathogens in both members in all the couples. Novel pathogens were detected, organisms previously thought to be commensal or contaminants. Multiple pathogen detection was common, occurring in 17 couples.

Conclusions

A frequent concern of patients and clinicians for those patients who have persistent, potentially sexually related infections is the underlying contribution from a partner. Limitations in accurate microbial detection often complicate eradication of the infection. Only NGS found significant pathogens on synchronous assays of all dyads tested, allowing organism specific concurrent antimicrobial therapy of both members. These results suggest a new algorithm for detection and therapy in patients whose persistent infection may involve the contribution of a partner.

Disclosure

No
Rate of Prior Invasive Pelvic Procedures, Co-Diagnoses, and Treatment Choices in Women Presenting with Dyspareunia – A United States Claims Database Analysis
Authors: Dumas K , Kohn J , Kohn T , Clifton M
Published: July 2022

Introduction

The International Continence Society defines dyspareunia as “persistent or recurrent pain or discomfort associated with attempted or complete vaginal penetration.” As the incidence of dyspareunia depends on the definition used and the population studied, dyspareunia is inadequately characterized in the current literature.

Objective

The objective of this study was to identify incidence, baseline characteristics, and subsequent treatments for women receiving a diagnosis of dyspareunia utilizing a large US claims database.

Methods

The TriNetX Diamond network database was queried: a US health research network consisting of 190 million patients and encompassing health care encounters between 2009-2021. Incidence of dyspareunia (ICD10 N94.1) in women over the age of 18 was calculated for 2009-2012, 2013-2016, and 2017-2021. Co-morbidities and pelvic procedures were identified prior to the date of dyspareunia diagnosis. Subsequent therapies were identified within 60 days after the initial diagnosis of dyspareunia.

Results

A total of 1,089,728 unique patients had a diagnosis of dyspareunia with an average age of 41.3±14.8 years. There was a high rate of reported prior invasive pelvic procedures at 30.7% (Table 1). Women also had high rates of co-diagnoses of chronic back pain (48.4%), anxiety (37.1%), sleep disorders (21.7%), migraines (18.4%), vascular headaches (18.1%), and constipation (18.9%). In the initial 60 days after initial diagnosis of dyspareunia, only 766 women (0.07%) were prescribed pelvic floor therapy (CPT 90901 or 90911). Only 6.8% were prescribed vaginal estrogen (4.5% of women with dyspareunia age 18-54 and 15.1% of women with dyspareunia age >54), while 1.7% were prescribed gabapentin, 0.8% venlafaxine, and 0.5% ospemifene. Notably, 9.7% were prescribed opioids and 5.1% were prescribed benzodiazepines with 3.9% receiving both an opioid prescription and benzodiazepine prescription within 60 days of index diagnosis of dyspareunia.

Conclusions

Dyspareunia is an increasingly identified diagnosis and often associated with prior invasive pelvic procedures. Rates of prescribing vaginal estrogen and pelvic floor therapy are low while prescribing of benzodiazepines and opioids initially after diagnosis are relatively elevated.

Disclosure

No
“O” No: A Reddit Analysis of Orgasmic Dysfunction
Authors: Belcher R , Sim D , Meykler M , Owens-Walton J , Hassan N , Rubin R , Malik R
Published: July 2022

Introduction

Orgasmic dysfunction includes reduced orgasmic intensity, decreased orgasm frequency and inability to achieve orgasm. Issues with orgasming are often multi-factorial in origin and can cause significant distress to patients.

Objective

We aimed to evaluate the experience of women with orgasmic dysfunction on Reddit, an anonymous forum-based platform that allows users to interact with a global audience.

Methods

The subreddit “TwoXChromosomes” was queried using the Reddit Application Programming Interface (API) for posts using the keywords “orgasm” and “climax”. Posts that were deleted, archived or unrelated to themes of orgasm were excluded. Threads were qualitatively analyzed using the grounded theory approach. Five independent researchers read and coded each thread identifying dominant themes and emergent concepts.

Results

Qualitative analysis of 108 threads and approximately 6,300 comments resulted in 5 major categories: psychological aspect of orgasms, difficulty orgasming with partners, partners’ response to orgasmic dysfunction, types of orgasms, and treatments for orgasmic dysfunction. Preliminary themes included (1) the presence of an emotional component or history of trauma resulting in orgasmic difficulty, (2) difficulty orgasming with a partner regardless of ability to orgasm during masturbation, and mixed partner responses to orgasmic dysfunction, with approximately half of posters reporting a supportive sexual partner who was interested in their sexual satisfaction while the remainder of posters reported partner dissatisfaction. (3) variety of stimulation required to orgasm, (4) the definition of a “normal orgasm and (5) self-motivated treatment for orgasmic dysfunction, including clitoral stimulation devices and masturbation techniques, with few posters discussing their orgasmic dysfunction with health care providers.

Conclusions

Overall, Reddit provides a medium for individuals with orgasmic dysfunction to discuss their experiences. Posts addressed users’ inability to orgasm, the interplay with their mental health and relationships, types of stimulation and treatments. Interestingly, very few posts discussed seeking out medical care for orgasmic dysfunction, potentially suggesting that women do not classify their orgasmic dysfunction as a health issue. The obvious prevalence of orgasmic dysfunction with little discussion surrounding healthcare reveals a large gap in sexual health counseling, indicating the need for expanded sexual health screening and detailed clinician-patient counseling.

Disclosure

Any of the authors act as a consultant, employee or shareholder of an industry for: Sprout (Raliegh, NC), Absorption Pharmaceuticals, Urovant Sciences, Inc.
The Role of Anxiety and Depression in Heart Rate Variability During Sexual Activity
Authors: McMahon L , Freihart B , Meston C
Published: July 2022

Introduction

Individuals with depression and anxiety demonstrate lower levels of heart rate variability (HRV) as a function of sympathetic and parasympathetic dominance respectively. Low HRV is also implicated in sexual concerns which, in turn, are closely associated with mood disorders. Given that HRV is an autonomic marker of responsivity to exogenous and endogenous demands, a blunted response to environmental cues may lead to decreased sexual satisfaction among individuals with low HRV during sex. This pattern might contribute to the decrements in sexual satisfaction often observed among individuals experiencing depression and anxiety.

Objective

The goal of the current study is to examine HRV differences during sexual activity among individuals above and below the clinical cutoffs on measures of anxiety and depression, while controlling for baseline HRV differences. A secondary goal is to determine if HRV differences correspond to individual variation in satisfaction with the observed sexual encounter.

Methods

Participants will complete validated measures of depression (PHQ-9) and anxiety (GAD-7). Using impedance cardiography, participants will measure baseline HRV and HRV during sexual activity in the comfort and privacy of their homes. Subsequently, participants will rate their level of satisfaction with the sexual encounter.

Results

Data collection is ongoing with an anticipated completion date of December 2021. Results will be updated with an addendum upon data analysis.

Conclusions

The discussion will focus on the interplay between mood symptoms and sexual satisfaction via the autonomic nervous system. Implications for the treatment of comorbid sexual and mood concerns will be highlighted.

Disclosure

No
“We Are Not Gays”: Regime Preservation and the Politicization of Identity in Mugabe’s Zimbabwe
Authors: Frossard de Saugy Yolaine
Published: July 2022

Politicized homophobia has become a dominant theme in the study of regime preservation tactics in southern Africa. However, a consensus on the potency of this tool has prevented researchers from fully exploring the conditions of its general success and occasional failure. Frossard de Saugy fills this gap with a thorough examination of the strategies of politicized homophobia deployed by the Robert Mugabe regime, their connection to hegemonic masculinity, the liberation war, and land questions, and the conditions which led them to lose their potency and ultimately fail to save Mugabe from mounting domestic challenges.
Information effects on parental choices for early childhood education and care
Authors: Burns Samantha , Davidson Adrienne , White Linda , Hampton Delaine , Perlman Michal
Published: July 2022

Existing research demonstrates that parents are poorly informed consumers of early childhood education and care (ECEC) services. Choosing such services is a complex process shaped by a combination of logistical limitations (e.g., cost/location), informational barriers and ideas about what the goal of care should be (e.g., education of young children or provision of an environment that feels like home). Experimental studies have also demonstrated that when study participants are informed of the importance of a specific decision, they engage in more complex decision-making. In this article, we test whether providing parents with information about the regulatory stringency of ECEC options available influences their choices regarding ECEC. A conjoint survey designed to capture quasi-behavioural choices for ECEC services was completed by 682 parents. Before engaging with the survey, participants were randomly assigned into either a control group or a treatment group that informed them about the stringency of oversight regarding ECEC options available in the province of Ontario, Canada. Receiving information did not meaningfully change the choices of the entire sample. However, a subgroup analysis revealed an important information effect on parent decisions for lower income/lower-education parents.