Untangling the stranglehold through mathematical modelling of Streptococcus equi subspecies equi transmission.

Strangles, a disease caused by infection with Streptococccus equi subspecies equi (S. equi), is endemic worldwide and one of the most frequently diagnosed infectious diseases of horses. Recent work has improved our knowledge of key parameters of transmission dynamics, but important knowledge gaps remain. Our aim was to apply mathematical modelling of S. equi transmission dynamics to prioritise future research areas, and add precision to estimates of transmission parameters thereby improving understanding of S. equi epidemiology and quantifying the control effort required. A compartmental deterministic model was constructed. Parameter values were estimated from current literature wherever possible. We assessed the sensitivity of estimates for the basic reproduction number on the population scale to varying assumptions for the unknown or uncertain parameters of: (mean) duration of carriership (1∕γC), relative infectiousness of carriers (f), proportion of infections that result in carriership (p), and (mean) duration of immunity after natural infection (1∕γR). Available incidence and (sero-)prevalence data were compared to model outputs to improve point estimates and ranges for these currently unknown or uncertain transmission-related parameters. The required vaccination coverage of an ideal vaccine to prevent major outbreaks under a range of control scenarios was estimated, and compared available data on existing vaccines. The relative infectiousness of carriers (as compared to acutely ill horses) and the duration of carriership were identified as key knowledge gaps. Deterministic compartmental simulations, combined with seroprevalence data, suggest that 0.05

Setting clinically relevant thresholds for the notification of canine disease outbreaks to veterinary practitioners: an exploratory qualitative interview study.

Introduction: The Small Animal Veterinary Surveillance Network (SAVSNET) has developed mathematical models to analyse the veterinary practice and diagnostic laboratory data to detect genuine outbreaks of canine disease in the United Kingdom. There are, however, no validated methods available to establish the clinical relevance of these genuine statistical outbreaks before their formal investigation is conducted. This study aimed to gain an actionable understanding of a veterinary practitioner's preferences regarding which outbreak scenarios have a substantial impact on veterinary practice for six priority canine diseases in the United Kingdom. Methodology: An intensity sampling approach was followed to recruit veterinary practitioners according to their years of experience and the size of their practice. In-depth semi-structured and structured interviews were conducted to describe an outbreak notification and outbreak response thresholds for six canine endemic diseases, exotic diseases, and syndromes. These thresholds reflected participants' preferred balance between the levels of excess case incidence and predictive certainty of the detection system. Interviews were transcribed, and a thematic analysis was performed using NVivo 12. Results: Seven interviews were completed. The findings indicate higher preferred levels of predictive certainty for endemic diseases than for exotic diseases, ranging from 95 to 99% and 80 to 90%, respectively. The levels of excess case incidence were considered clinically relevant at values representing an increase of two to four times in the normal case incidence expectancy for endemic agents, such as parvovirus, and where they indicated a single case in the practice's catchment area for exotic diseases such as leishmaniosis and babesiosis. Conclusion: This study's innovative methodology uses veterinary practitioners' opinions to inform the selection of a notification threshold value in real-world applications of stochastic canine outbreak detection models. The clinically relevant thresholds derived from participants' needs will be used by SAVSNET to inform its outbreak detection system and to improve its response to canine disease outbreaks in the United Kingdom.

The association between edentulism and progress of multimorbidity over 12 years among older American adults.

OBJECTIVES: To examine the relationship between edentulism and the progress of multimorbidity, and the role of nutritional intake and behaviours among older Americans. METHODS: We used 7 waves (2006-2018) of the Health and Retirement Study, a longitudinal survey of older Americans (number included in analysis 2,224). Edentulism was assessed in 2006 and 2012. Multimorbidity was indicated by 5 self-reported conditions: diabetes, heart conditions, lung diseases, cancer, and stroke. Behavioural factors were smoking, excessive alcohol consumption, physical activity, and body mass index. Nutritional intake was calculated by summing 10 nutrients (Protein, Vitamins C, D, B12, E, Calcium, Zinc, Polyunsaturated fatty acids, Folate and ß- carotene). Multilevel models for analysis of longitudinal data were used to assess the association between change in repeated measures of multimorbidity (between 2006 and 2018) and edentulism (2006) adjusting for nutritional intake, behavioural and socioeconomic factors. RESULTS: Participants who were edentate in 2006 and 2012 had higher rate-ratios (RR) for change in multimorbidity between 2006 to 2018 (RR: 1.29 and 1.28, respectively). After adjusting for socioeconomic factors, total nutrients and behavioural factors, these RR attenuated to 1.12 (95%CI: 1.06, 1.18) and 1.10 (95%CI: 1.05, 1.16), respectively. Total nutrition was negatively associated with progress of multimorbidity, but after adjusting for socioeconomic and behavioural factors the association became insignificant. Total nutrients rates in 2013 were significantly lower among those who were edentate in 2006 and 2012. CONCLUSION: There was a longitudinal association between edentulism and progress of multimorbidity. The relationship appeared to be mediated be behaviours and nutrition.

Placenta accreta spectrum care infrastructure: an evidence-based review of needed resources supporting placenta accreta spectrum care.

The incidence of placenta accreta spectrum, the deeply adherent placenta with associated increased risk of maternal morbidity and mortality, has seen a significant rise in recent years. Therefore, there has been a rise in clinical and research focus on this complex diagnosis. There is international consensus that a multidisciplinary coordinated approach optimizes outcomes. The composition of the team will vary from center to center; however, central themes of complex surgical experts, specialists in prenatal diagnosis, critical care specialists, neonatology specialists, obstetrics anesthesiology specialists, blood bank specialists, and dedicated mental health experts are universal throughout. Regionalization of care is a growing trend for complex medical needs, but the location of care alone is just a starting point. The goal of this article is to provide an evidence-based framework for the crucial infrastructure needed to address the unique antepartum, delivery, and postpartum needs of the patient with placenta accreta spectrum. Rather than a clinical checklist, we describe the personnel, clinical unit characteristics, and breadth of contributing clinical roles that make up a team. Screening protocols, diagnostic imaging, surgical and potential need for critical care, and trauma-informed interaction are the basis for comprehensive care. The vision from the author group is that this publication provides a semblance of infrastructure standardization as a means to ensure proper preparation and readiness.

Delivery outcomes in the subsequent pregnancy following the conservative management of placenta accreta spectrum disorder: a systematic review and meta-analysis.

OBJECTIVE: Cesarean hysterectomy is generally presumed to decrease maternal morbidity and mortality secondary to placenta accreta spectrum disorder. Recently, uterine-sparing techniques have been introduced in conservative management of placenta accreta spectrum disorder to preserve fertility and potentially reduce surgical complications. However, despite patients often expressing the intention for future conception, few data are available regarding the subsequent pregnancy outcomes after conservative management of placenta accreta spectrum disorder. Thus, we aimed to perform a systematic review and meta-analysis to assess these outcomes. DATA SOURCES: PubMed, Scopus, and Web of Science databases were searched from inception to September 2022. STUDY ELIGIBILITY CRITERIA: We included all studies, with the exception of case studies, that reported the first subsequent pregnancy outcomes in individuals with a history of placenta accreta spectrum disorder who underwent any type of conservative management. METHODS: The R programming language with the "meta" package was used. The random-effects model and inverse variance method were used to pool the proportion of pregnancy outcomes. RESULTS: We identified 5 studies involving 1458 participants that were eligible for quantitative synthesis. The type of conservative management included placenta left in situ (n=1) and resection surgery (n=1), and was not reported in 3 studies. The rate of placenta accreta spectrum disorder recurrence in the subsequent pregnancy was 11.8% (95% confidence interval, 1.1-60.3; I2=86.4%), and 1.9% (95% confidence interval, 0.0-34.1; I2=82.4%) of participants underwent cesarean hysterectomy. Postpartum hemorrhage occurred in 10.3% (95% confidence interval, 0.3-81.4; I2=96.7%). A composite adverse maternal outcome was reported in 22.7% of participants (95% confidence interval, 0.0-99.4; I2=56.3%). CONCLUSION: Favorable pregnancy outcome is possible following successful conservation of the uterus in a placenta accreta spectrum disorder pregnancy. Approximately 1 out of 4 subsequent pregnancies following conservative management of placenta accreta spectrum disorder had considerable adverse maternal outcomes. Given such high incidence of adverse outcomes and morbidity, patient and provider preparation is vital when managing this population.

Effect of speed and water depth on limb and back kinematics in Thoroughbred horses walking on a water treadmill.

Water treadmill (WT) exercise may induce limb and back kinematics that meet specific training and rehabilitation goals. The study aimed to investigate the effects of walk speed, at different water depths (WDs), on limb and back kinematics of six Thoroughbreds exercising on a WT. Horses walked at 2.8/4.3/5.5/6.0 km/h (i.e. 0.8/1.2/1.5/1.7 m/s) at dry, metacarpophalangeal and carpal WD. Videography captured limb movement in the sagittal plane. Motion-capture measured thoracolumbosacral flexion-extension (FE), and lateral bend (LB) ranges of movement (ROM) using skin surface markers on the sixth, tenth, thirteenth, eighteenth thoracic, third and fifth lumbar, and third sacral spinous processes. Inertial-motion-sensors measured poll, withers and pelvic displacements. Following preliminary univariable analyses, multivariable mixed-effects linear-regression analyses were used to examine the relationship between speed, WD and each outcome variable (P < 0.05). Peak metacarpophalangeal, carpal and tarsal joint flexion increased with speed (P ≤ 0.002) and depth combined (P 0.001) while peak metatarsophalangeal flexion increased with WD only (P 0.001). Thoracolumbar FE-ROM between T10 and L3 and hindlimb retraction was increased by speed and WD combined (P 0.001). Hindlimb protraction was increased by speed (P 0.001) while hindlimb retraction was increased by speed and WD combined (P 0.001). Dorsoventral poll displacement was increased by speed (P 0.001) and carpal WD (P = 0.013), craniocaudal poll displacement was increased by speed and WD combined (P 0.001). Pelvic (tubera coxae and sacrum) dorsoventral displacements increased with speed and WD combined (P 0.001). Understanding the effects of speed and WD on limb, back and pelvic kinematics will improve decision making relating to dry and WT exercise within training.

Arrest of mouse preterm labor until term delivery by combination therapy with atosiban and mundulone, a natural product with tocolytic efficacy.

There is a lack of FDA-approved tocolytics for the management of preterm labor (PL). In prior drug discovery efforts, we identified mundulone and mundulone acetate (MA) as inhibitors of in vitro intracellular Ca2+-regulated myometrial contractility. In this study, we probed the tocolytic potential of these compounds using human myometrial samples and a mouse model of preterm birth. In a phenotypic assay, mundulone displayed greater efficacy, while MA showed greater potency and uterine-selectivity in the inhibition of intracellular-Ca2+ mobilization. Cell viability assays revealed that MA was significantly less cytotoxic. Organ bath and vessel myography studies showed that only mundulone exerted inhibition of myometrial contractions and that neither compounds affected vasoreactivity of ductus arteriosus. A high-throughput combination screen identified that mundulone exhibits synergism with two clinical-tocolytics (atosiban and nifedipine), and MA displayed synergistic efficacy with nifedipine. Of these combinations, mundulone+atosiban demonstrated a significant improvement in the in vitro therapeutic index compared to mundulone alone. The ex vivo and in vivo synergism of mundulone+atosiban was substantiated, yielding greater tocolytic efficacy and potency on myometrial tissue and reduced preterm birth rates in a mouse model of PL compared to each single agent. Treatment with mundulone after mifepristone administration dose-dependently delayed the timing of delivery. Importantly, mundulone+atosiban permitted long-term management of PL, allowing 71% dams to deliver viable pups at term (>day 19, 4-5 days post-mifepristone exposure) without visible maternal and fetal consequences. Collectively, these studies provide a strong foundation for the development of mundulone as a single or combination tocolytic for management of PL.

Stakeholder opinion-led study to identify canine priority diseases for surveillance and control in the UK.

BACKGROUND: Many pathogens cause disease in dogs; however, meaningful surveillance in small companion animals is often only possible for the most impactful diseases. We describe the first stakeholder opinion-led approach to identify which canine infectious diseases should be prioritised for inclusion in surveillance and control strategies in the UK. METHODS: Participants were identified through a stakeholder analysis. A multicriteria decision analysis was undertaken to establish and weight epidemiological criteria for evaluating diseases, and a Delphi technique was employed to achieve a consensus among participants on the top-priority canine diseases. RESULTS: Nineteen stakeholders from multiple backgrounds participated in this study. Leptospirosis and parvovirus were identified as the top two endemic diseases of concern, while leishmaniosis and babesiosis were the top two exotic diseases. Respiratory and gastrointestinal diseases were identified as the top two syndromes of concern. LIMITATIONS: Due to the COVID-19 pandemic, the number of participants was reduced. Despite this, a representative multidisciplinary sample of relevant stakeholders contributed to the present study. CONCLUSIONS: Findings from this study are being used to inform the development of a future UK-wide epidemic response strategy. This methodology could provide a blueprint for other countries.

Arrest of mouse preterm labor until term delivery by combination therapy with atosiban and mundulone, a natural product with tocolytic efficacy.

Currently, there is a lack of FDA-approved tocolytics for the management of preterm labor (PL). In prior drug discovery efforts, we identified mundulone and its analog mundulone acetate (MA) as inhibitors of in vitro intracellular Ca 2+ -regulated myometrial contractility. In this study, we probed the tocolytic and therapeutic potential of these small molecules using myometrial cells and tissues obtained from patients receiving cesarean deliveries, as well as a mouse model of PL resulting in preterm birth. In a phenotypic assay, mundulone displayed greater efficacy in the inhibition of intracellular-Ca 2+ from myometrial cells; however, MA showed greater potency and uterine-selectivity, based IC 50 and E max values between myometrial cells compared to aorta vascular smooth muscle cells, a major maternal off-target site of current tocolytics. Cell viability assays revealed that MA was significantly less cytotoxic. Organ bath and vessel myography studies showed that only mundulone exerted concentration-dependent inhibition of ex vivo myometrial contractions and that neither mundulone or MA affected vasoreactivity of ductus arteriosus, a major fetal off-target of current tocolytics. A high-throughput combination screen of in vitro intracellular Ca 2+ -mobilization identified that mundulone exhibits synergism with two clinical-tocolytics (atosiban and nifedipine), and MA displayed synergistic efficacy with nifedipine. Of these synergistic combinations, mundulone + atosiban demonstrated a favorable in vitro therapeutic index (TI)=10, a substantial improvement compared to TI=0.8 for mundulone alone. The ex vivo and in vivo synergism of mundulone and atosiban was substantiated, yielding greater tocolytic efficacy and potency on isolated mouse and human myometrial tissue and reduced preterm birth rates in a mouse model of PL compared to each single agent. Treatment with mundulone 5hrs after mifepristone administration (and PL induction) dose-dependently delayed the timing of delivery. Importantly, mundulone in combination with atosiban (FR 3.7:1, 6.5mg/kg + 1.75mg/kg) permitted long-term management of PL after induction with 30 µg mifepristone, allowing 71% dams to deliver viable pups at term (> day 19, 4-5 days post-mifepristone exposure) without any visible maternal and fetal consequences. Collectively, these studies provide a strong foundation for the future development of mundulone as a stand-alone single- and/or combination-tocolytic therapy for management of PL.

Knowledge Gaps in Placenta Accreta Spectrum.

Since its first description early in the 20th Century, placenta accreta and its variants have changed substantially in incidence, risk factor profile, clinical presentation, diagnosis and management. While systematic use of diagnostic tools and a multidisciplinary team care approach has begun to improve patient outcomes, the condition's pathophysiology, epidemiology, and best practices for diagnosis and management remain poorly understood. The use of large databases with broadly accepted terminology and diagnostic criteria should accelerate research in this area. Future work should focus on non-traditional phenotypes, such as those without placenta previa-preventive strategies, and long term medical and emotional support for patients facing this diagnosis. KEY POINTS: · Placenta accreta spectrum research may be improved with standardized terminology and use of large databases.. · Placenta accreta prediction should move beyond ultrasound with the addition of biomarkers, and needs to extend to those without traditional risk factors.. · Future research should identify practices that can prevent future accreta development..

Surgical Techniques for the Management of Placenta Accreta Spectrum.

The surgical management of placenta accreta spectrum (PAS) is often challenging. There are a variety of techniques and management options described in the literature ranging from uterine sparing to cesarean hysterectomy. Following the inaugural meeting of the Pan-American Society for Placenta Accreta Spectrum a multidisciplinary group collaborated to describe collective recommendations for the surgical management of PAS. In this manuscript, we outline individual components of the procedure and provide suggested direction at key points of a cesarean hysterectomy in the setting of PAS. KEY POINTS: · The surgical management of PAS requires careful planning and expertise.. · Multidisciplinary team care for pregnancies complicated by PAS can decrease morbidity and mortality.. · Careful surgical techniques can minimize risk of significant hemorrhage by avoiding pitfalls..

General Management Considerations for Placenta Accreta Spectrum.

The ideal management of a patient with placenta accreta spectrum (PAS) includes close antepartum management culminating in a planned and coordinated delivery by an experienced multidisciplinary PAS team. Coordinated team management has been shown to optimize outcomes for mother and infant. This section provides a consensus overview from the Pan-American Society for the Placenta Accreta Spectrum regarding general management of PAS.

Over a decade of an eating disorders treatment program: Where to from here?

OBJECTIVE: Currently available treatments for eating disorders lack efficacy resulting in poor outcomes for patients. In this paper, we describe a number of issues that we have identified in our clinical service, which are not unique to our treatment program. CONCLUSIONS: The issues described are common among eating disorder services worldwide and need to be addressed in order to move the field forward. We provide a number of solutions and research areas that need greater focus so that we are able to improve the efficacy of eating disorder treatment services.

Social support and pre-operative anxiety in patients undergoing elective surgical procedures: A systematic review and meta-analysis.

Pre-operative anxiety may adversely affect post-operative recovery and treatment satisfaction. This systematic review assessed the impact of social support on pre-operative anxiety in elective surgery patients. MEDLINE via Ovid, Embase, PsycINFO, Web of Science, CINAHL Plus, Emcare and LILACS were searched for publications (1950-2021). Fourteen studies were included for descriptive analysis and five for meta-analysis. The pooled estimate in the meta-analysis was r = -0.372 (95% CI: -0.578 to -0.122). Stronger social support was weakly associated with reduced pre-operative anxiety, but the quality of available evidence was low. The findings suggest potential benefit in enhancing utilisation of support networks before elective surgery.

Intrauterine closure of myelomeningocele defects with primary linear repair versus bipedicle fasciocutaneous flaps: a post-MOMS cohort study with long-term follow-up.

OBJECTIVE: The objective of this study was to determine the effects of in utero bipedicle flaps on maternal-fetal morbidity/mortality, the need for CSF diversion, and long-term functional outcomes. METHODS: Eighty-six patients who underwent fetal myelomeningocele repair from 2011 to 2021 at a single institution were reviewed. Primary outcomes included intrauterine fetal demise, postnatal death, postnatal myelomeningocele repair dehiscence, and CSF diversion by final follow-up. RESULTS: The cohorts were no different with regard to race, ethnicity, maternal age at fetal surgery, body mass index, gravidity, parity, gestational age at fetal surgery, estimated fetal weight at fetal surgery, or fetal lesion level. Of the 86 patients, 64 underwent primary linear repair and 22 underwent bipedicle flap repair. There were no significant differences in rates of intrauterine fetal demise, postnatal mortality, midline repair site dehiscence, or the need for CSF diversion by final follow-up. Operative times were longer (32.5 vs 18.7 minutes, p < 0.001) and gestational age at delivery was lower (232 vs 241 days, p = 0.01) in the bipedicle flap cohort, but long-term functional outcomes were not different. CONCLUSIONS: Analysis of the total cohort affirms the long-term benefits of fetal myelomeningocele repair. In utero bipedicle flaps are safe and can be used for high-tension lesions without increasing perioperative risks to the mother or fetus. In utero flaps preserve the long-term benefits seen with primary linear repair and may expand inclusion criteria for fetal repair, providing life-changing care for more patients.

Transcatheter Arterial Chemoembolization Imaging Features in MR-Linac Radiation Therapy Planning for the Liver.

For MR-guided radiation therapy treatment planning, an MRI and CT of the intended treatment site are typically acquired. Patients' prior treatments or procedures can cause image artifacts in one or both scans, which may impact treatment planning or the radiation dose calculation. In this case report, a patient with several previous transcatheter arterial chemoembolization (TACE) procedures was planned for radiation therapy on a low-field MR-linac, and the impact of residual iodinated oil on the radiation dose calculation and MR-guided adaptive workflow was evaluated.

Seroprevalence of Equine Influenza and Its Associated Risk Factors in Northwest Nigeria.

Equine influenza (EI) is a fast-spreading respiratory disease of equids caused by equine influenza A virus (EIV), often resulting in high morbidity and a huge economic impact on the equine industry globally. In this cross-sectional study to determine the seroprevalence of EI and its associated risk factors, sera from 830 horses bled on a single occasion in Northwest Nigeria between October 2019 and January 2020 were screened for antibodies to A/equine/Richmond/1/2007 (H3N8) using the single radial haemolysis (SRH) assay. Antibodies were detected in 71.3% (592/830, 95% CI: 68−74%) of horses (SRH area ≥ 0.5 mm2). Although there were statistically significant univariable associations between seropositivity and age, sex, breed, purpose and coat colour, only age remained significant when included with each of the other variables in bivariable analyses. There was a clear trend for increasing odds of seropositivity with increasing age: OR 1.6, 95% CI: 1.05−2.40 (p = 0.03) for 5−14-year-olds and OR 8.13, 95% CI: 2.75−24.1 (p < 0.001) for ≥15-year-olds compared to horses <5 years old. The mean SRH value was 78.2 mm2 (median = 88 mm2, interquartile range = 0−121 mm2) with only 9% of the horses having an SRH value > 150 mm2, considered sufficient to protect against clinical disease and virus shedding. Comparative screening of a subset of the horses (n = 118) with a 2019 H3N8 virus (A/equine/Worcestershire/2019) revealed a significantly greater seropositivity (p = 0.0001) than A/equine/Richmond/1/2007 consistent with exposure of the population during a widespread outbreak of EI in the region in 2019. In conclusion, there was an insufficient level of protection against EI in the region and introduction of a vaccination programme with vaccines containing recently circulating virus is recommended to mitigate against further outbreaks of EI in Nigeria.

Dentists' Perceptions of Personal Infection Control Measurements in Response to COVID-19.

OBJECTIVE: To explore through focus groups (FGs) the perceptions of dental practitioners (DPs) from different countries of the challenges of implementing coronavirus disease 2019 (COVID-19) related biosafety measures, especially personal protection equipment (PPE), during the COVID-19 pandemic period. METHODS: DPs from Colombia, Germany, the United Kingdom, and the United States were invited to participate in country-based FGs. These were facilitated by an experienced moderator who explored the factors that guided the implementation of COVID-19 related biosafety measures and PPE use. Data were analyzed through thematic analysis on the basis of categories defined by the researchers deductively and inductively. RESULTS: A total of 25 DPs participated in 3 FGs (Colombia:n = 8; United Kingdom: n = 7; United States: n = 9) and 1 in an in-depth interview (Germany). DPs described using several processes to judge which guidance document to adopt and which aspects of the guidance were important in their practice. These included making judgments concerning the views of any indemnity organization to which the DPs were responsible, the staff's views in the practice, and the views of patients. In the absence of a single overarching guidance document, DPs filtered the available information through several considerations to find a level of PPE that they deemed "implementable" in local practice. CONCLUSIONS: The findings suggest that the implementation of evidence-based practice is subject to modification through a lens of what is "feasible" in practice. KNOWLEDGE TRANSFER STATEMENT: Clinicians, educators, and policy makers can use the results of this study to understand the process through which guidance is transformed into implementable patient care pathways in the dental practice.