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Objective To report the 30-day outcomes of patients with perioperative SARS-CoV-2 infection undergoing surgery in the USA. Summary background data Uncertainty regarding the postoperative risks of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exists. Methods As part of the COVIDSurg multicenter study, all patients aged ≥17 years undergoing surgery between January 1 and June 30, 2020 with perioperative SARS-CoV-2 infection in 70 hospitals across 27 states were included. The primary outcomes were 30-day mortality and pulmonary complications. Multivariable analyses (adjusting for demographics, comorbidities, and procedure characteristics) were performed to identify predictors of mortality. Results A total of 1,581 patients were included; more than half of them were males (n= 822, 52.0%) and older than 50 years (n=835, 52.8%). Most procedures (n=1,261, 79.8%) were emergent, and laparotomies (n= 538, 34.1%). The mortality and pulmonary complication rates were 11.0 and 39.5%, respectively. Independent predictors of mortality included age ≥70 years (OR 2.46, 95% CI [1.65-3.69]), male sex (2.26 [1.53-3.35]), ASA grades 3-5 (3.08 [1.60-5.95]), emergent surgery (2.44 [1.31-4.54]), malignancy (2.97 [1.58-5.57]), respiratory comorbidities (2.08 [1.30-3.32]), and higher Revised Cardiac Risk Index (1.20 [1.02-1.41]). While statewide elective cancelation orders were not associated with a lower mortality, a sub-analysis showed it to be associated with lower mortality in those who underwent elective surgery (0.14 [0.03-0.61]). Conclusions Patients with perioperative SARS-CoV-2 infection have a significantly high risk for postoperative complications, especially elderly males. Postponing elective surgery and adopting non-operative management, when reasonable, should be considered in the USA during the pandemic peaks.

Diagnostic evaluation for infertility in women should be conducted in a systematic, expeditious, and cost-effective manner to identify all the relevant factors with an initial emphasis on the least invasive methods for detecting the most common causes of infertility. The purpose of this committee opinion is to provide a critical review of the current methods and procedures for the evaluation of in fertile women, and it replaces the document of the same name, last published in 2015 (Fertil Steril 2015;103:e44-50). This guidance is intended for any provider evaluating women for infertility.

RationalePulmonary rehabilitation is an effective treatment for people with chronic respiratory disease but is delivered to MethodsA multicentre randomised controlled trial with assessor blinding, powered for equivalence was undertaken. Individuals with a chronic respiratory disease referred to pulmonary rehabilitation at four participating sites (one rural) were eligible and randomised using concealed allocation to pulmonary rehabilitation or telerehabilitation. Both programmes were two times per week for 8 weeks. The primary outcome was change in Chronic Respiratory Disease Questionnaire Dyspnoea (CRQ-D) domain at end-rehabilitation, with a prespecified equivalence margin of 2.5 points. Follow-up was at 12 months. Secondary outcomes included exercise capacity, health-related quality of life, symptoms, self-efficacy and psychological well-being.Results142 participants were randomised to pulmonary rehabilitation or telerehabilitation with 96% and 97% included in the intention-to-treat analysis, respectively. There were no significant differences between groups for any outcome at either time point. Both groups achieved meaningful improvement in dyspnoea and exercise capacity at end-rehabilitation. However, we were unable to confirm equivalence of telerehabilitation for the primary outcome ΔCRQ-D at end-rehabilitation (mean difference (MD) (95% CI) −1 point (−3 to 1)), and inferiority of telerehabilitation could not be excluded at either time point (12-month follow-up: MD −1 point (95% CI −4 to 1)). At end-rehabilitation, telerehabilitation demonstrated equivalence for 6-minute walk distance (MD −6 m, 95% CI −26 to 15) with possibly superiority of telerehabilitation at 12 months (MD 14 m, 95% CI −10 to 38).Conclusiontelerehabilitation may not be equivalent to centre-based pulmonary rehabilitation for all outcomes, but is safe and achieves clinically meaningful benefits. When centre-based pulmonary rehabilitation is not available, telerehabilitation may provide an alternative programme model.Trial registration numberACtelerehabilitationN12616000360415.

Pre-exposure prophylaxis (PrEP) is an effective HIV prevention method, but it has been underutilized by women. Anticipated stigma regarding use of PrEP is a contributing factor in the underutilization of this prevention strategy. The current study explored the relationships among PrEP stigma, sex risk (i.e., inconsistent condom use, condomless sex with persons of unknown serostatus, or sex in exchange for money or drugs), substance use, attitudes toward HIV testing, and medical mistrust. Participants were 106 primarily ethnic-minority women who reported recent substance use and agreed to participate in a study exploring HIV prevention attitudes. Within this sample, the majority of participants had one or more CDC-defined PrEP indications. Findings indicate that medical mistrust was associated with perceived PrEP stereotypes and HIV testing attitudes. These results provide some insight into reasons for low PrEP uptake among women at risk for HIV. Implications for HIV prevention with women are discussed.

OBJECTIVES/HYPOTHESIS Tonsillectomy is one of the most common ambulatory surgeries performed in the United States, yet the incidence of post-tonsillectomy hemorrhage (PTH) in adults remains unclear. In addition, any association between non-steroidal anti-inflammatory drugs (NSAIDs) and PTH in adults is currently unknown. The aim of this study is to examine the incidence and management of adult PTH at a single academic center and to assess for any association between NSAID use and PTH in adults. STUDY DESIGN Retrospective chart review. METHODS We conducted a retrospective chart review of adult tonsillectomies performed at our institution between January 1, 2012, and December 30, 2019. Demographics, past medical history, medications, NSAID use, surgical indication, bleeding events, and interventions were documented. The rate of PTH was calculated, logistic regression was performed to assess for any predictive factors, and odds ratios were calculated for NSAID use and PTH. RESULTS A total of 1,057 adult tonsillectomies were performed within the aforementioned time period. A total of 126 patients experienced 163 bleeding events for a postoperative hemorrhage rate of 11.9%. Most were controlled with bedside interventions, while 29 (23%) bled more than once. The hemorrhage rate for those who were not prescribed NSAIDs postoperatively (n = 625) was 11.7%, compared to 12.6% for those who did receive NSAIDs postoperatively (n = 432), which was not significantly different (adjusted odds ratio 1.01, 95% confidence interval 0.69-1.49; P = .95). CONCLUSIONS This retrospective cohort study of 1,057 adult patients found the incidence of PTH to be 11.9%. This study found no association between the use of NSAIDs and the rate of PTH, although a higher-powered study is needed. LEVEL OF EVIDENCE Level 3 Laryngoscope, 2021.

BACKGROUND: Prioritized research agendas are viewed internationally as an important method for ensuring that health research meets actual areas of clinical need. There is growing evidence for speech-language therapy-prioritized research agendas, particularly in disorder-specific areas. However, there are few general research priority agendas to guide speech-language therapy research. AIMS: To collaboratively develop a prioritized research agenda for an Australian public health context with clinical speech-language therapists (SLTs), academic SLTs and consumers of speech-language therapy services. METHODS & PROCEDURES: An initial stimulus list of potential research areas for prioritization was collected from SLTs via an online survey. Two categories (service delivery and expanded scope of practice) were selected from this list for prioritization due to their relevance across multiple health services. The Nominal Group Technique (NGT) was used to develop a prioritized research agenda for each of the two categories. One NGT session was conducted with each of the three participant groups (clinical SLTs, academic SLTs, consumers) for each category (total NGT sessions = six). The prioritization data for each group within each category were summed to give a single, ranked prioritized research agenda for each category. OUTCOMES & RESULTS: Two prioritized research agendas were developed. Within each agenda, SLTs and consumers prioritized a need for more research in areas related to specific practice areas (e.g., Alternative and Augmentative Communication, Communication Partner Training), as well as broader professional issues (e.g., telehealth, working with culturally and linguistically diverse families). CONCLUSIONS & IMPLICATIONS: The current findings support the need for funding proposals and targeted projects that address these identified areas of need. WHAT THIS PAPER ADDS: What is already known on this subject Evidence-based practice is a critical component of SLT practice. There is often a disconnect between the research evidence generated and areas of clinical need, and in some areas a lack of evidence. Prioritized research agendas can help drive research in areas of clinical need. What this paper adds to existing knowledge A collaborative, prioritized SLT research agenda was developed using the NGT according to the views of clinical SLTs, academic SLTs and consumers of speech-language therapy services in a conglomerate of public health services. SLTs and consumers identified a need for further research in specific areas of SLT practice as well as broader emerging professional issues What are the potential or actual clinical implications of this work? Targeted research projects funded on a large scale are required to address these identified areas of need. Other health services around the world could replicate this prioritization process to drive research in areas of clinical need.

The purported goals of commercial sex work criminalization policies in the United States have shifted over the past two decades as local jurisdictions have adopted End Demand reforms. These reforms aim to refocus arrest from individuals who sell sexual services to buyers and facilitators, representing a departure from the quality-of-life, nuisance-focused approach of the late twentieth century. This article presents a case study examining enforcement of commercial sex laws in Chicago, a city that has been heralded as a leader in End Demand reforms. Our case study utilized annualized arrest statistics from 1998 to 2017 and individual arrest reports (n = 575) from 2015 to 2017. Commercial sex arrests by the Chicago Police Department have declined substantially over the past two decades, falling 98.4% from its peak. However, our analysis suggests that sellers of sexual services continue to face the heaviest burden of arrest (80.5%) and officers generally continue to approach commercial sex as a quality-of-life issue. We argue that this divergence between the goals and implementation of End Demand are the result of three institutional factors: street-level bureaucracy, logics of spatial governmentality, and participatory security. Our results suggest that the ideals of End Demand may be incompatible with the institutional realties of urban policing.

Objective To determine whether follicle flushing during oocyte retrieval improves live birth or secondary outcomes in assisted reproductive technology (ART). Design Systematic review and meta-analysis. Setting Not applicable. Patient(s) Women undergoing ART using autologous gametes. Intervention(s) A systematic search of PubMed, EMBASE, Cochrane Database, and Web of Science for randomized controlled trials comparing follicle flushing to direct aspiration during oocyte retrieval published in English between 1989 to 2020. Main Outcome Measure(s) Live birth as primary outcome, and clinical and ongoing pregnancy, total and mature metaphase II (MII) oocytes retrieved, and operating time as secondary outcomes. Result(s) Eleven studies were included totaling 1,178 cases. No difference in live birth was demonstrated between follicle flushing and direct aspiration. Clinical pregnancy and ongoing pregnancy were not improved with flushing. Total oocyte and MII yield were lower with flushing compared with direct aspiration. Procedure time was increased with flushing by 2 minutes in poor responders and 9 minutes in normal responders. Other sensitivity analyses did not demonstrate any changes, except the difference in MII yield was no longer statistically significant. Conclusion(s) Follicle flushing during oocyte retrieval increases procedure time and does not improve live birth or secondary ART outcomes. Randomized data do not support the use of follicle flushing as an intervention in ART.

We have based parts of the Methods, as well as Appendix 1, Appendix 2 and Appendix 3 of this Cochrane Protocol on a standard template established by the CMED Group. EDITORIAL NOTE: This protocol will not be progressed to a review because the topic is no longer considered a priority. See https://doi.org/10.1002/14651858.cd012651, https://doi.org/10.1002/14651858.cd012691.

People with brain cancer and their support persons (SPs) are critical sources of information on the components of care that contribute to psychosocial outcomes. To determine the proportion of studies that examined (1) at least one of 14 nominated components of psychosocial cancer care and (2) more than one component of care. Medline, The Cochrane Library, PsycINFO and Embase were electronically searched for publications from January 1999 to December 2019. Publications that met the inclusion criteria were coded according to the number and type of psychosocial care components assessed from 14 listed components, and whether patient and/or SPs’ views about care were elicited. Of the 113 included publications, 61 publications included patient-reported data only (54%), 27 included both patient and SP-reported data (24%) and 25 included SP-reported data only (22%). Most assessed a single component of care (77% of patient-reported and 71% of SP-reported). No publications assessed all 14 components. The “Psychosocial” component was the most frequently assessed component of care for patient-reported (n = 80/88, 91%) and SP-reported publications (n = 46/52, 88%). Publications reporting on psychosocial care in brain cancer present a relatively narrow view of patient and support person experiences. The inclusion of both patient and support person perspectives and the assessment of multiple components of care are required in future research to optimize psychosocial outcomes in brain cancer.

To compare clinical and ongoing pregnancy after natural cycle (NC) intrauterine insemination (IUI) versus ovarian stimulation (OS) IUI in ovulatory women undergoing therapeutic donor insemination (TDI).Retrospective cohort.Single infertility center.A total of 76,643 IUI cycles in patients treated with intrauterine insemination were examined. Women undergoing TDI in the absence of diagnosed female factor infertility were included.NC TDI or OS TDI with either clomiphene citrate or letrozole.Clinical and ongoing pregnancies were analyzed by generalized estimating equations adjusting for age, body mass index, total motile sperm at time of insemination and cycle number. Ongoing multiple gestations were examined as a secondary outcome.Six thousand one hundred ninety-two TDI cycles from 2,343 patients (711 patients without repeated IUI cycles) met inclusion criteria and were available for analysis (3,837 NC and 2,355 OS). There was no difference in mean age between the two groups (NC, 34.2 years vs. OS, 34.3 years). Probability of clinical and ongoing pregnancy was higher in the OS cohort compared with the NC cohort (OS, 22.4% vs. NC, 18.7% and OS, 15.4% vs. NC, 14.9%, respectively). However, OS significantly increased ongoing multiple gestations (OS, 10.8% vs. NC, 2.4%).Ovarian stimulation in TDI cycles resulted in a4% increase in clinical and1% increase in ongoing pregnancy, and more than fourfold increase in ongoing multiple gestations. Natural cycle IUI should be considered as a first-line treatment for ovulatory women who need donor insemination.

Background/objectives Obese pregnant women are at high risk of developing gestational diabetes mellitus (GDM), which might be reduced by sufficient physical activity (PA) and reduced sedentary time (ST). We assessed whether PA and ST are longitudinally associated with the glucose-insulin axis in obese pregnant women. Subjects/methods In this secondary analysis of the DALI (vitamin D And Lifestyle Intervention for gestational diabetes mellitus prevention) study, pregnant women, 2, without GDM on entry were included. Time spent in moderate-to-vigorous PA (MVPA) and ST were measured objectively with accelerometers at <20 weeks, 24–28 weeks and 35–37 weeks of gestation. Fasting glucose (mmol/l) and insulin (mU/l), insulin resistance (HOMA-IR) and first-phase and second-phase insulin release (Stumvoll first and second phase) were assessed at the same time. Linear mixed regression models were used to calculate between-participant differences and within-participant changes over time. Analyses were adjusted for gestational age, randomisation, pre-pregnancy BMI, education and age. MVPA, Insulin, HOMA-IR and Stumvoll first and second phase were log-transformed for analyses due to skewness. Results 232 women were included in the analysis. Concerning differences between participants, more ST was associated with higher fasting glucose (Estimate: 0.008; 95% CI: 0.002, 0.014), fasting insulin (0.011; 0.002, 0.019), HOMA-IR (0.012; 0.004, 0.021) and Stumvoll first and second phase (0.008; 0.001, 0.014 and 0.007; 0.001, 0.014). Participants with more MVPA had lower Stumvoll first and second phase (−0.137; −0.210, −0.064 and −0.133; −0.202, −0.063). Concerning changes over time, an increase in ST during gestation was associated with elevated Stumvoll first and second phase (0.006; 0.000, 0.011). Conclusions As the glucose-insulin axis is more strongly associated with ST than MVPA in our obese population, pregnant women could be advised to reduce ST in addition to increasing MVPA. Moreover, our findings suggest that behaviour change interventions aiming at GDM risk reduction should start in early or pre-pregnancy.

The COVID-19 pandemic has the potential to disrupt HIV prevention services. We conducted an electronic health record analysis of PrEP, HIV, and STI visits at eight sexual health clinics in Arkansas, Missouri, and Oklahoma during the onset of the pandemic (March 1, 2020 to June 30, 2020) and compared the data with pre-pandemic (March 1, 2019 to June 30, 2019) volumes. Our data revealed a significant increase in the proportion of male PrEP visits during the pandemic compared to the pre-pandemic period, with the majority provided via telehealth/telePrEP. Overall, HIV and STI testing significantly decreased during the pandemic period.La pandemia del COVID-19 tiene el potencial de interrumpir los servicios de prevención del VIH. Conducimos un análisis electrónico de expedientes de salud sobre visitas para la PrEP, el VIH, e ITS en ocho diferentes clínicas de salud sexual en Arkansas, Misuri y Oklahoma durante el inicio de la pandemia (1 de marzo de 2020 hasta 30 de junio de 2020) y comparamos esos datos con los índices previos a la pandemia (1 de marzo de 2019 hasta 30 de junio de 2019). Nuestros datos revelaron un aumento significativo en la proporción de visitas para la PrEP por personas masculinas durante la pandemia, comparado al periodo previo a la pandemia, con la mayoría de citas conducidas mediante la telemedicina/telePrEP. En general, las pruebas de VIH e ITS disminuyeron significativamente durante el periodo de la pandemia.

Sample selectivity is a recurrent problem in public health programmes and poses serious challenges to their evaluation. Traditional approaches to handle sample selection tend to rely on restrictive assumptions. The aim of this paper is to illustrate a copula-based selection model to handle sample selection in the evaluation of public health programmes. Motivated by a public health programme to promote physical activity in Leeds (England), we describe the assumptions underlying the copula selection, and its relative advantages compared with commonly used approaches to handle sample selection, such as inverse probability weighting and Heckman’s selection model. We illustrate the methods in the Leeds Let’s Get Active programme and show the implications of method choice for estimating the effect on individual’s physical activity. The programme was associated with increased physical activity overall, but the magnitude of its effect differed according to adjustment method. The copula selection model led to a similar effect to the Heckman’s approach but with relatively narrower 95% confidence intervals. These results remained relatively similar when different model specifications and alternative distributional assumptions were considered. The copula selection model can address important limitations of traditional approaches to address sample selection, such as the Heckman model, and should be considered in the evaluation of public health programmes, where sample selection is likely to be present.

Supplemental Digital Content is Available in the Text., Objectives: We tested preliminary efficacy of a peer change agent type I network intervention to increase pre-exposure prophylaxis (PrEP) linkage to care among network members connected to young Black men who have sex with men. Design: Parent study is a pragmatic randomized controlled trial with 110 weeks of total follow-up. Interim midpoint analyses are performed here using participant data before crossover assignment at 55 weeks. Methods: We randomly assigned 423 participants in Chicago to receive the network intervention, an opinion leader workshop with telephonic booster sessions, versus a time-matched control from 2016 to 2018. The consolidated surrogate outcome was PrEP referral and linkage to clinical care among network members connected to study participants and was collected from independent administrative data. Results: Each study participant in the trial (n = 423) had on average 1822 network contacts who could be eligible for PrEP referral and linkage. During the 55-week observation period, PrEP referral was most likely to occur within 3 days of an intervention session compared to control [odds ratio (OR) 0.07 (0.02–0.013); P = 0.007] resulting in 1–2 referrals of network members per session. Network members with referral or linkage were more likely to be connected to study participants in the intervention arm than the control condition [aOR 1.50 (1.09–2.06); P = 0.012]. Conclusions: A peer change agent type I network intervention is preliminarily effective at diffusing PrEP through a network of individuals highly susceptible to HIV over 55 weeks. This low-intensity intervention demonstrated network-level impact among populations that have experienced limited PrEP care engagement in the United States.

TP53 mutations are implicated in the progression of mucinous borderline tumors (MBOT) to mucinous ovarian carcinomas (MOC). Optimized immunohistochemistry (IHC) for TP53 has been established as a proxy for the TP53 mutation status in other ovarian tumor types. We aimed to confirm the ability of TP53 IHC to predict TP53 mutation status in ovarian mucinous tumors and to evaluate the association of TP53 mutation status with survival among patients with MBOT and MOC. Tumor tissue from an initial cohort of 113 women with MBOT/MOC was stained with optimized IHC for TP53 using tissue microarrays (75.2%) or full sections (24.8%) and interpreted using established criteria as normal or abnormal (overexpression, complete absence, or cytoplasmic). Cases were considered concordant if abnormal IHC staining predicted deleterious TP53 mutations. Discordant tissue microarray cases were re-evaluated on full sections and interpretational criteria were refined. The initial cohort was expanded to a total of 165 MBOT and 424 MOC for the examination of the association of survival with TP53 mutation status, assessed either by TP53 IHC and/or sequencing. Initially, 82/113 (72.6%) cases were concordant using the established criteria. Refined criteria for overexpression to account for intratumoral heterogeneity and terminal differentiation improved concordance to 93.8% (106/113). In the expanded cohort, 19.4% (32/165) of MBOT showed evidence for TP53 mutation and this was associated with a higher risk of recurrence, disease-specific death, and all-cause mortality (overall survival: HR = 4.6, 95% CI 1.5-14.3, p = 0.0087). Within MOC, 61.1% (259/424) harbored a TP53 mutation, but this was not associated with survival (overall survival, p = 0.77). TP53 IHC is an accurate proxy for TP53 mutation status with refined interpretation criteria accounting for intratumoral heterogeneity and terminal differentiation in ovarian mucinous tumors. TP53 mutation status is an important biomarker to identify MBOT with a higher risk of mortality.

Background: Physical activity levels are low in people with chronic obstructive pulmonary disease, and there is limited knowledge about how pulmonary rehabilitation transforms movement behaviors. This study analyzed data from a pulmonary rehabilitation trial and identified determinants of movement behaviors.Methods: Objectively assessed time in daily movement behaviors (sleep, sedentary, light-intensity physical activity, and moderate- to vigorous-intensity physical activity) from a randomized controlled trial (n = 73 participants) comparing home- and center-based pulmonary rehabilitation was analyzed using conventional and compositional analytical approaches. Regression analysis was used to assess relationships between movement behaviors, participant features, and response to the interventions.Results: Compositional analysis revealed no significant differences in movement profiles between the home- and center-based groups. At end rehabilitation, conventional analyses identified positive relationships between exercise capacity (6-min walk distance), light-intensity physical activity, and moderate- to vigorous-intensity physical activity time. Compositional analyses identified positive relationships between a 6-minute walk distance and moderate- to vigorous-intensity physical activity time, accompanied by negative relationships with sleep and sedentary time (relative to other time components) and novel relationships between body mass index and light-intensity physical activity/sedentary time.Conclusion: Compositional analyses following pulmonary rehabilitation identified unique associations between movement behaviors that were not evident in conventional analyses.

Normal pregnancy is associated with increased insulin resistance as a metabolic adaptation to the nutritional demands of the placenta and fetus, and this is amplified in obese mothers. Insulin resistance is normally compensated for by an adaptive increase in pancreatic β-cell mass together with enhanced glucose-stimulated insulin release. Placentally-derived hormones and growth factors are central to the altered pancreatic morphology and function. A failure of β-cells to undergo adaptive change after the first trimester has been linked with gestational diabetes. In the pregnant mouse, an increase in β-cell replication contributes to a 2-3-fold increase in mass peaking in late gestation, depending on the proliferation of existing β-cells, the differentiation of resident progenitor β-cells, or islet cell transdifferentiation. Using mouse models and human studies placenta- and islet of Langerhans-derived molecules have been identified that are likely to contribute to the metabolic adaptations to pregnancy and whose physiology is altered in the obese, glucose-intolerant mother. Maternal obesity during pregnancy can create a pro-inflammatory environment that can disrupt the response of the β-cells to the endocrine signals of pregnancy and limit the adaptive changes in β-cell mass and function, resulting in an increased risk of gestational diabetes.

HIV incidence and prevalence rates in emergency departments (EDs) around the nation warrant strategies to protect and sustain the HIV negative status of persons who are at risk for HIV. The ED provides a rare opportunity to serve as a vehicle for connecting pre‐exposure prophylaxis (PrEP)‐eligible patients with clinical settings such as an ED that are knowledgeable and well informed about PrEP. PrEP has established efficacy at preventing HIV acquisition. The greatest challenge is access to PrEP and uptake thereof among vulnerable populations. We propose recommendations to improve the functionality of EDs as access points for PrEP referrals as an HIV prevention strategy to increase PrEP availability and uptake.

Introduction Geographical barriers and impaired physical mobility among people with Parkinson’s disease (PD) hinder their timely access to speech pathology services. We compared the costs of delivering a speech treatment via in-person consultation versus telerehabilitation. Methods We used data from a non-inferiority randomised controlled trial delivering the Lee Silverman Voice Treatment (LSVT LOUD®), where patients with dysarthria associated with PD were assigned to either the urban in-person group ( N = 16) or the urban online group ( N = 15), supplemented with a non-randomised group (regional online; N = 21). We compared costs over a one-month treatment period from a health-system perspective and a patient perspective. Results The mean treatment costs of both urban online ($1076) and regional ($1206) treatments tended to be slightly higher than urban in-person ($1020) from a health-system perspective. From a patient perspective, the mean treatment cost was $831 in the urban in-person group, $247 in the urban online group and $200 in the regional group. Discussion LSVT LOUD® may be delivered via telerehabilitation at a slightly higher cost than in-person delivery from a health-system perspective, but it is cost saving from a patient perspective. Telerehabilitation is an economically beneficial alternative for the delivery of the LSVT LOUD® programme in PD patients with speech disorders.

Objectives The emergency department provides opportunities for identifying undiagnosed HIV cases. We sought to describe the racial and sex epidemiology of HIV through ED screening in Harris County, Texas, one of the most diverse and populous metropolitan cities in the Southern United States. Methods We used a descriptive secondary analysis of a universal HIV screening program (2010–2017) to quantify demographic differences in HIV incidence. We applied a validated codebook to a dataset by the local health department containing 894,387 records of ED visits with 62 variables to assess race/ethnicity and sex differences. Results Of 885,199 (98.9%) patients screened for HIV during an ED visit, 1795 tested positive (incidence rate = 0.2%). Of those tested for HIV, most were White (66.3%), followed by racial minorities (African Americans (29.9%), Asians (3.6%), and American Indian, Alaska Native, Native Hawaiian or Pacific Islanders (natives) (0.1%). Half of those tested were Hispanic. Conversely, of patients testing positive (n = 1782, 99.3% of positive cases), most were African American (52.6%) followed by Whites (46.6%), Asians (0.7%), and natives (0.1%). Less than half (35.5%) of positives were Hispanic. A racial disparity in HIV incidence was discovered among African American females. This group represented 16.8% of the tested population; yet accounted for 65.8% of females who tested positive for HIV and 20.3% of all HIV‐positive test results. Conclusion Descriptive findings of the racial and sex epidemiology of HIV revealed that African American females had the largest disparity between the population tested and those who tested positive for HIV.

Combination of ischemia and β-amyloid (Aβ) toxicity has been shown to simultaneously increase neuro-inflammation, endogenous Aβ deposition, and neurodegeneration. However, studies on the evolution of infarct and panorama of cellular degeneration as a synergistic or overlapping mechanism between ischemia and Aβ toxicity are lacking. Here, we compared fluorojade B (FJB) and hematoxylin and eosin (H&E) stains primarily to examine the chronology of infarct, and the viability and morphological changes in neuroglia and neurons located in different brain regions on d1, d7, and d28 post Aβ toxicity and endothelin-1 induced ischemia (ET1) in rats. We demonstrated a regional difference in cellular degeneration between cortex, corpus callosum, striatum, globus pallidus, and thalamus after cerebral injury. Glial cells in the cortex and corpus callosum underwent delayed FJB staining from d7 to d28, but neurons in cortex disappeared within the first week of cerebral injury. Striatal lesion core and globus pallidus of Aβ + ET1 rats showed extensive degeneration of neuronal cells compared with ET1 rats alone starting from d1. Differential and exacerbated expressions of cyclooxygenase-2 might be the cause of excessive neuronal demise in the striatum of Aβ + ET1 rats. Such an investigation may improve our understanding to identify and manipulate a critical therapeutic window post comorbid injury.

Background Complete heart block (CHB) is a frequent cause for acute admission in older patients with significant cardiac conduction disease. Common presenting symptoms are syncope and dyspnoea. Some patients may exhibit clinical and radiological signs of left ventricular (LV) decompensation, despite preserved LV ejection fraction on transthoracic echocardiography (TTE) and absent pre-existing LV dysfunction. Case summary In this clinical report, we present a case of CHB associated with transient but severe elevation in pulmonary artery systolic pressure, measured as the equivalent right ventricular systolic pressure (RVSP = 99 mmHg) by TTE in the absence of right ventricular outflow tract obstruction, that subsequently ‘normalized’ after implantation of a permanent pacemaker. After searching our echocardiogram database, we did find other cases with similar findings. Discussion There is limited literature describing transient acute elevation in estimated pulmonary pressures in the setting of new CHB that is subsequently reversed by permanent pacing. The true prevalence and mechanism of transient estimated pulmonary pressure as a result of CHB remains unknown. Based on our limited assessment, we postulate that the acute elevation in estimated pulmonary pressures is predominantly related to a compensatory augmentation of RV stroke volume and is caused by the underlying bradycardia and need to maintain forward cardiac output. This phenomenon may require further investigation and validation in future studies.

Background The cornea is innervated with a rich supply of sensory nerves that play important roles in ocular surface health. Any injury or pathology of the corneal nerves increases the risk of dry eye disease and infection. This study aims to evaluate the therapeutic potential of topical decorin to improve corneal nerve regeneration in a mouse model of sterile epithelial abrasion injury. Methods Bilateral central corneal epithelial abrasions (2-mm, Alger Brush) were performed on young C57BL/6 J mice to remove the corneal sensory nerves. Decorin, or vehicle, was applied topically, three times per day for 1 week or every 2 h for 6 h. Spectral-domain optical coherence tomography was performed to measure the abrasion area and corneal thickness. Wholemount immunofluorescence staining was used to assess sensory nerve regeneration (β-tubulin III) and immune cell density (CD45, Iba1, CD11c). To investigate the specific role of dendritic cells (DCs), Cx3cr1gfp/gfp mice, which spontaneously lack resident corneal epithelial DCs, were also investigated. The effect of prophylactic topical administration of recombinant human decorin (applied prior to the abrasion) was also investigated. Nerve tracing (NeuronJ software) was performed to compare recovery of basal nerve axons and superficial nerve terminals in the central and peripheral cornea. Results At 6 h after injury, topical decorin application was associated with greater intraepithelial DC recruitment but no change in re-epithelialisation or corneal thickness, compared to the vehicle control. One week after injury, sub-basal nerve plexus and superficial nerve terminal density were significantly higher in the central cornea in the decorin-treated eyes. The density of corneal stromal macrophages in the decorin-treated eyes and their contralateral eyes was significantly lower compared to saline-treated corneas. No significant improvement in corneal nerve regeneration was observed in Cx3cr1gfp/gfp mice treated with decorin. Conclusions Decorin promotes corneal epithelial nerve regeneration after injury. The neuroregenerative effect of topical decorin was associated with a higher corneal DC density during the acute phase, and fewer macrophages at the study endpoint. The corneal neuroregenerative effects of decorin were absent in mice lacking intraepithelial DCs. Together, these findings support a role for decorin in DC-mediated neuroregeneration following corneal abrasion injury.

Background Following concerns regarding the emergence of Clostridium difficile infection in 2010, we changed antibiotic prophylaxis in patients undergoing primary hip and knee arthroplasty from cefuroxime to flucloxacillin and single-dose (SD) gentamicin. A subsequent perceived increase in the incidence of post-operative acute kidney injury (AKI) led us to evaluate the AKI incidence between different prophylactic antibiotic regimes used at our centre. Methods We examined the incidence of AKI as defined by Kidney Disease: Improving Global Outcomes criteria in 1588 patients undergoing primary hip or knee arthroplasty from January 2010 to January 2015. Patients received the following prophylactic antibiotic regimes: 8 g flucloxacillin in four divided doses and SD gentamicin 1.5 mg/kg ideal body weight (IBW; maximum dose 120 mg; n = 400), 8 g flucloxacillin alone in four divided doses (n = 400), SD cefuroxime (n = 400), triple-dose (TD) cefuroxime (n = 188) and teicoplanin with SD gentamicin 1.5 mg/kg IBW (n = 200). Results The incidence of AKI was as follows: flucloxacillin and gentamicin (13%); flucloxacillin alone (8.5%); SD cefuroxime (2%); TD cefuroxime (0.5%); and teicoplanin and gentamicin (3%). Of the six patients who developed Stage 3 AKI, all were in the flucloxacillin and gentamicin group. The odds ratio for the development of AKI derived from a binary logistic regression model was highest in the flucloxacillin and gentamicin group [7.79 (95% confidence interval 3.54–17.14), P Conclusions Our findings suggest that the use of prophylactic high-dose flucloxacillin and gentamicin should be used with caution in patients undergoing primary hip or knee arthroplasty without a clear advantage in reducing surgical site infections given the association with increased rates of AKI.

To investigate people with Parkinson's disease (PwPD): 1) self-reported communication and swallowing difficulties due to Parkinson's disease (PD), 2) participation and psychosocial impacts of these difficulties and 3) experience with and access to speech-language pathology (SLP) services.A cross-sectional mix-methods survey was conducted using nonprobability, purposive sampling for recruitment. An inclusion criterion was that participants needed to have self-reported communication and/or swallowing changes due to PD. Descriptive statistics and thematic analysis were utilised.All of the 78 PwPD who participated reported changes to their communication (97%) and/or swallowing (93%). A diverse range of participation restrictions was found in social, recreational, vocational and everyday living activities. Adverse emotional impacts including frustration, loss of self-confidence, depression and isolation were reported due to these changes. Only 59% of our sample had accessed SLP services. The most common reason for PwPD not accessing services was that neither their general practitioner nor neurologist had referred them to SLP. The majority of PwPD wanted to access SLP at some point in the future. Wide variability in the SLP services provided was evident. Most of the PwPD who had received SLP support wanted further ongoing management.This study provided insight into the everyday impacts of communication and swallowing changes experienced by PwPD, and the gap between service supply and demand.

Mounting evidence suggests hyperoxia therapy may be harmful. We describe injury characteristics and survival outcomes for pediatric trauma casualties in Iraq and Afghanistan, stratified by partial pressure of arterial oxygen (PaO2). Secondarily, we performed subgroup analyses for severe traumatic brain injury (TBI) and massive transfusion of blood products (MT).We utilized Department of Defense Trauma Registry data. We included subjects18 years. We excluded subjects without an arterial blood gas (ABG). We stratified subjects as hyperoxemia (PaO2 100-300 mmHg) and extreme hyperoxemia (PaO2300 mmHg).January 2007-January 2016, 3439 pediatric encounters were in the database. Of those, 1323 had an ABG, with 291 (22%) demonstrating hyperoxemia and 43 (3.3%) extreme hyperoxemia. The median age was 8, most were male (76%) in Afghanistan (69%), and injured by explosive (42%). There were no significant differences in survival between subjects with no hyperoxemia, hyperoxemia, and extreme hyperoxemia (92% vs 87% vs 86%; p = 0.078). Also, there were no significant differences in survival between groups among TBI and MT subjects, and there were no increased odds of survival between groups on multivariable regression analyses.Hyperoxemia was common among hospitalized, wartime pediatric trauma casualties in Iraq and Afghanistan that underwent ABG analysis. Survival to hospital discharge rates were not significantly different between subjects with hyperoxemia and subjects without hyperoxemia.

Sociodemographics and travel among patients receiving abortion care differed during the pandemic, suggesting coronavirus disease 2019 (COVID-19)–related restrictions may have negatively affected abortion access, particularly for patients of color.

The incidence of kidney stones in the United States is currently unknown. Here, we assessed the incidence of kidney stones using recent, nationally representative data.We used the National Health and Nutrition Examination Survey (NHANES) from 2015 to 2018. During this time participants were asked, "Have you ever had a kidney stone?" and "In the past 12 months, have you passed a kidney stone?" Demographics analyzed include age, race, gender, body mass index, history of smoking, diabetes, hypertension, hypercholesterolemia and gout. Multivariable models were used to assess the independent impact of subject characteristics on kidney stone prevalence and incidence.Data were available on 10,521 participants older than age 20. The prevalence of kidney stones was 11.0% (95% CI 10.1-12.0). The 12-month incidence of kidney stones was 2.1% (95% CI 1.5-2.7), or 2,054 stones per 100,000 adults. We identified significant relationships between stone incidence and subject age, body mass index, race and history of hypertension.Here we find a substantially higher 12-month incidence of kidney stones than previous reports. We also validate known risk factors for stone prevalence as associated with incidence. The remarkable incidence and prevalence of stones is concerning and has implications for disease prevention and allocation of medical resources.

The apelin receptor (Aplnr) and its ligands, Apelin and Apela, contribute to metabolic control. The insulin resistance associated with pregnancy is accommodated by an expansion of pancreatic β-cell mass (BCM) and increased insulin secretion, involving the proliferation of insulin-expressing, glucose transporter 2-low (Ins+Glut2LO) progenitor cells. We examined changes in the apelinergic system during normal mouse pregnancy and in pregnancies complicated by glucose intolerance with reduced BCM. Expression of Aplnr, Apelin and Apela was quantified in Ins+Glut2LO cells isolated from mouse pancreata and found to be significantly higher than in mature β-cells by DNA microarray and qPCR. Apelin was localized to most β-cells by immunohistochemistry although Aplnr was predominantly associated with Ins+Glut2LO cells. Aplnr-staining cells increased three- to four-fold during pregnancy being maximal at gestational days (GD) 9–12 but were significantly reduced in glucose intolerant mice. Apelin-13 increased β-cell proliferation in isolated mouse islets and INS1E cells, but not glucose-stimulated insulin secretion. Glucose intolerant pregnant mice had significantly elevated serum Apelin levels at GD 9 associated with an increased presence of placental IL-6. Placental expression of the apelinergic axis remained unaltered, however. Results show that the apelinergic system is highly expressed in pancreatic β-cell progenitors and may contribute to β-cell proliferation in pregnancy.

Endometriosis is a common, chronic inflammatory condition, thought to have a higher incidence in symptomatic women, yet, commonly associated symptoms do not always correlate with the presence or severity of disease and diagnosis requires surgery. We prospectively collected data and assessed symptomology and NMR spectroscopy-based metabolomics of 102 women undergoing laparoscopic sterilisation at a tertiary referral centre in a cross-sectional study. Twelve women were incidentally diagnosed with endometriosis (11.7%). According to the pre-operative questionnaire, presence and absence of many symptoms usually attributed to endometriosis were declared at similar frequencies in women with or without endometriosis. Women with endometriosis reported apparently more persistent heavy periods (50% vs 18.9%), prolonged periods (25% versus 7.8%) and problems conceiving (27.3% versus 9%) than those without endometriosis. NMR could not discern any distinguishable differences in the serum metabolome between those with and without endometriosis. Our paper highlights the complex symptomology experienced by women, regardless of a surgical diagnosis of endometriosis. Previous literature and the current study failed to identify clear, distinguishable symptoms or biomarkers pertinent to surgically confirmed endometriosis in the general population. Therefore, development of effective, non-invasive tests for identifying this heterogenous benign condition, endometriosis, is likely to be challenging. Supplementary Information The online version contains supplementary material available at 10.1007/s43032-021-00725-w.

We present the case of an acute onset ANCA positive vasculitis in an asymptomatic COVID-19 infected teenager, resulting in significant colonic damage. The patient was initially diagnosed with Henoch-Schönlein purpura and presented with worsening symptoms with significant necrosis of her perineum and rectum requiring surgical debridement and diverting colostomy. As a part of her work-up, she tested positive for COVID-19 total IgG/IgM antibodies and ANCA antibodies. This case complements previously reported cases of COVID-19 induced autoimmune disease in children but is novel in describing extensive intestinal disease as a result of an autoimmune vasculitis in a child.

Background and ObjectivesGenetic variants impact both Parkinson’s disease (PD) risk and manifestations. While genetic information is of potential interest to patients and clinicians, genetic testing is rarely performed during routine PD clinical care. The goal of this study was to perform genome sequencing and examine patient interest in comprehensive genetic testing for PD in 2 academic movement disorder clinics.MethodsIn 208 subjects with PD (age=63 years, 67% male), genome sequencing was performed and filtered using a custom panel, including 49 genes associated with PD, parkinsonism, or related disorders, as well as a 90-variant PD genetic risk score. Separately, 231 patients (age=67 years, 63% male) were surveyed on interest in genetic testing at baseline and in response to vignettes covering (i) familial risk of PD (LRRK2); (ii) risk of PD dementia (GBA); (iii) PD genetic risk score; and (iv) secondary, medically-actionable variants (BRCA1).ResultsGenome sequencing revealed a LRRK2 variant in 3.4% and a GBA risk variant in 10.1% of our clinical sample. The genetic risk score was normally distributed, identifying 42 subjects with high risk of PD. Medically-actionable findings were discovered in 2 subjects (1%). In our survey, the majority (82%) responded they would share a LRRK2 variant with relatives. Most registered unchanged or increased interest in testing when confronted with potential risk for dementia or medically- actionable findings, and most (75%) expressed interest in learning their PD genetic risk score.DiscussionOur results highlight broad interest in comprehensive genetic testing among patients with PD and may facilitate integration of genome sequencing in clinical practice.

BackgroundInterstitial lung disease is a debilitating condition associated with significant dyspnoea, fatigue, and poor exercise tolerance. Pulmonary rehabilitation is an effective and key intervention in people with interstitial lung disease. However, despite the best efforts of patients and clinicians, many of those who participate are not achieving clinically meaningful benefits. This assessor-blinded, multi-centre, randomised controlled trial aims to compare the clinical benefits of high intensity interval exercise training versus the standard pulmonary rehabilitation method of continuous training at moderate intensity in people with fibrotic interstitial lung disease.MethodsEligible participants will be randomised to either a standard pulmonary rehabilitation group using moderate intensity continuous exercise training or high intensity interval exercise training. Participants in both groups will undertake an 8-week pulmonary rehabilitation program of twice-weekly supervised exercise training including aerobic (cycling) and strengthening exercises. In addition, participants in both groups will be prescribed a home exercise program.Outcomes will be assessed at baseline, upon completion of the intervention and at six months following the intervention by a blinded assessor. The primary outcome is endurance time on a constant work rate test. Secondary outcomes are functional capacity (6-min walk distance), health-related quality of life (Chronic Respiratory Disease Questionnaire (CRQ), St George’s Respiratory Questionnaire idiopathic pulmonary fibrosis specific version (SGRQ-I), breathlessness (Dyspnoea 12, Modified Medical Research Council Dyspnoea Scale), fatigue (fatigue severity scale), anxiety (Hospital Anxiety and Depression Scale), physical activity level (GeneActiv), skeletal muscle changes (ultrasonography) and completion and adherence to pulmonary rehabilitation.DiscussionThe standard exercise training strategies used in pulmonary rehabilitation may not provide an optimal exercise training stimulus for people with interstitial lung disease. This study will determine whether high intensity interval training can produce equivalent or even superior changes in exercise performance and symptoms. If high intensity interval training proves effective, it will provide an exercise training strategy that can readily be implemented into clinical practice for people with interstitial lung disease.Trial registrationClinicalTrials.gov Registry (NCT03800914). Registered 11 January 2019,https://clinicaltrials.gov/ct2/show/NCT03800914Australian New Zealand Clinical Trials Registry ACTRN12619000019101. Registered 9 January 2019,https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=376050&isReview=true

Gestational diabetes mellitus results, in part, from a sub-optimal β-cell mass (BCM) during pregnancy. Artemisinins were reported to increase BCM in models of diabetes by α- to β-cell conversion leading to enhanced glucose tolerance. We used a mouse model of gestational glucose intolerance to compare the effects of an artemisinin (artesunate) on glycemia of pregnant mice with vehicle treatment (acetone) or no treatment. Animals were treated daily from gestational days (GD) 0.5 to 6.5. An intraperitoneal glucose tolerance test was performed prior to euthanasia at GD18.5 or post-partum. Glucose tolerance was significantly improved in both pregnant and non-pregnant mice with both artesunate and vehicle-alone treatment, suggesting the outcome was primarily due to the acetone vehicle. In non-pregnant, acetone-treated animals, improved glucose tolerance was associated with a higher BCM and a significant increase in bihormonal insulin and glucagon-containing pancreatic islet cells, suggesting α- to β-cell conversion. BCM did not differ with treatment during pregnancy or post-partum. However, placental weight was higher in acetone-treated animals and was associated with an upregulation of apelinergic genes. Acetone-treated animals had reduced weight gain during treatment despite comparable food consumption to non-treated mice, suggesting transient effects on nutrient uptake. The mean duodenal and ileum villus height was reduced following exposure to acetone. We conclude that acetone treatment may mimic transient fasting, resulting in a subsequent improvement in glucose tolerance during pregnancy.

Objective To evaluate similarities and differences in clinical and laboratory practices among high-performing fertility clinics. Design Cross-sectional questionnaire study of selected programs. Setting Academic and private fertility practices performing in vitro fertilization (IVF). Patient(s) Not applicable. Intervention(s) A comprehensive survey was conducted of 13 IVF programs performing at least 100 cycles a year and having high cumulative singleton delivery rates for 2 years. Main Outcome Measure(s) Clinical and laboratory IVF practices. Result(s) Although many areas of clinical practice varied among top programs, some commonalities were observed. All programs used a combination of follicle-stimulating hormone and luteinizing hormone for IVF stimulation, intramuscular progesterone in frozen embryo transfer cycles, ultrasound-guided embryo transfers, and a required semen analysis before starting the IVF cycle. Common laboratory practices included vitrification of embryos at the blastocyst stage, air quality control with positive air pressure and high-efficiency particulate air filtration, use of incubator gas filters, working on heated microscope stages, and incubating embryos in a low-oxygen environment, most often in benchtop incubators. Conclusion(s) Some areas of consistency in clinical and laboratory practices were noted among high-performing IVF programs that are likely contributing to their success. High-performing programs focused on singleton deliveries. As the field of IVF is rapidly evolving, it is imperative that we share best practices in an effort to improve outcomes from all clinics for the good of our patients.

Foreign body objects could be a cause of prepatellar bursitis. This is the only reported case in the literature describing prepatellar bursitis caused by a glass foreign body and the use of endoscopy to retrieve it. During an endoscopic bursectomy to alleviate symptoms of prepatellar bursitis, glass was discovered. The glass was removed and the prepatellar space irrigated and debrided to removed inflamed tissue. This case highlights the only case report of prepatellar bursitis caused by a retained foreign body and the use of endoscopy to remove it. Endoscopic bursectomy is a viable alternative to open bursectomy to minimize wound complications and allow faster recovery.

Objectives To determine if a saline-filled cuff seen at the suprasternal notch on ultrasound corresponds to correct endotracheal tube depth on a chest radiograph (tip at/below clavicle AND ≥ 1 cm above carina). Design Prospective observational study. Setting Tertiary Care Pediatric hospital. Patients Patients between the ages of 0-18 years requiring nonemergent cardiac catheterizations and endotracheal intubation with a cuffed endotracheal tube were included in the study. Children with anticipated or known difficult airways were excluded. Interventions Ultrasound evaluation of the neck following saline inflation of the endotracheal tube cuff. Measurements and main results Ultrasonography of the patient's neck was performed following intubation by a pediatric anesthesiologist. A linear probe was used in transverse axis to identify the saline-filled cuff starting at the suprasternal notch and moving cephalad. A cine-fluoroscopic image, similar to a chest radiograph, was obtained to ascertain the endotracheal tube depth after the cuff was identified sonographically. Endotracheal tube cuffs seen on ultrasound at the suprasternal notch were compared with the endotracheal tube depth on the cine-fluoroscopic image. A total of 75 children were enrolled in the study. The endotracheal tube was seen sonographically at the suprasternal notch in 70 patients of which 60 had complete data (an adequate chest radiograph available for review). Patient ages ranged from 2 months to 18 years with a median age of 4 years. The median endotracheal tube tip to carina distance was 2.4 cm (interquartile range, 1.75-3.3 cm.) The endotracheal tube tip to carina distance was greater than or equal to 1 cm in 57 out of the 60 patients. Endotracheal tube cuff at the suprasternal notch on ultrasound corresponded with correct endotracheal tube depth on chest radiograph with an accuracy of 95% (CI, 86-98%). Conclusions Visualization of the cuff at the suprasternal notch by ultrasound demonstrates potential as a means of confirming correct depth of the endotracheal tube following endotracheal intubation.

Background Inflammation and elevated blood lipids are associated with infertility. Aspirin and statin therapy may improve infertility treatment outcomes among overweight and obese women with systemic inflammation, but little is known about the short-term effects of statins in this population. We conducted a pilot study of aspirin, pravastatin, or combined treatment among a group of overweight and obese, reproductive-aged women. Our goal was to characterize short-term changes in inflammatory and lipid biomarkers during and after treatment. Methods In this open-label trial, women aged 18–40 years with a body mass index ≥25 kg/m2 were randomized to receive either 162 mg aspirin, 40 mg pravastatin, or both. The study medication was taken daily for 2 weeks, and participants were then followed for a two-week washout period. Participants provided blood samples at baseline, after the intervention period, and after the washout period. The outcomes were changes in biomarkers of inflammation and lipids measured in blood components at each timepoint. Results Nine, 8, and 8 women were randomized to the aspirin, pravastatin, and combined arms, respectively. Analyses were conducted among 8, 7, and 7 women in the aspirin, pravastatin, and combined arms for whom biomarker data was available at baseline. High-sensitivity C-reactive protein (hsCRP) levels were lower after treatment in all arms and continued to decrease after washout in the pravastatin and combined arms. Results were consistent between the whole sample and women with baseline hsCRP between 2 and 10 mg/L. Low-density lipoprotein (LDL) cholesterol was lower after treatment in the pravastatin and combined arms and rose slightly after washout. Conclusions Our results provide preliminary evidence that short-term aspirin and pravastatin therapy reduces hsCRP and LDL cholesterol among overweight and obese women of reproductive age, including those with low-grade inflammation. Because of these short-term effects, these drugs may improve infertility treatment outcomes in this population, which we will assess in a future randomized trial.

Large cerebral infarctions are major predictors of death and severe disability from stroke. Conversely, data concerning these types of infarctions and the affected adjacent brain circuits are scarce. It remains to be determined if the co-morbid concurrence of large infarct and β-amyloid (Aβ) toxicity can precipitate the early development of dementia. Here, we described a dose-dependent effect of a unilateral striatal injection of vasoconstrictive endothelin-1 (ET-1) along with Aβ toxicity on CNS pathogenesis; driven by the anatomical and functional networks within a brain circuit. After 21 days of treatment, a high dose (60 pmol) of ET-1 (E60) alone caused the greatest increase in neuroinflammation, mainly in the ipsilateral striatum and distant regions with synaptic links to the striatal lesion such as white matter (subcortical white matter, corpus callosum, internal capsule, anterior commissure), gray matter (globus pallidus, thalamus), and cortices (cingulate, motor, somatosensory, entorhinal). The combined E60 + Aβ treatment also extended perturbation in the contralateral hemisphere of these rats, such as increased deposition of amyloid precursor protein fragments associated with the appearance of degenerating cells and the leakage of laminin from the basement membrane across a compromised blood-brain barrier. However, the cerebral damage induced by the 6 pmol ET-1 (E6), Aβ and E6 + Aβ rats was not detrimental enough to injure the complete network. The appreciation of the causal interactions among distinct anatomical units in the brain after ischemia and Aβ toxicity will help in the design of effective and alternative therapeutics that may disassociate the synergistic or additive association between the infarcts and Aβ toxicity.

Key points: Pancreatic β-cell dysfunction is hypothesized to be the significant determinant of gestational diabetes pathogenesis, however pancreatic samples from patients are scarce. This study reports a novel mouse model of gestational glucose intolerance in pregnancy, originating from previous nutrition restriction in utero, in which glucose intolerance was restricted to late gestation as is seen in human gestational diabetes. Glucose intolerance was attributed to reduced β-cell proliferation, leading to impaired gestational β-cell mass expansion in maternal endocrine pancreas, in addition to reduced glucose-stimulated insulin secretion. This model reproduces some of the features of gestational diabetes and is suitable for testing safe therapeutic interventions that increase β-cell mass during pregnancy and prevent or reverse gestational glucose intolerance. Abstract: Gestational diabetes mellitus (GDM) is an increasingly prevalent form of diabetes that appears during pregnancy. Pathological studies link a failure to adaptively increase maternal pancreatic β-cell mass (BCM) in pregnancy to GDM. Due to the scarcity of pancreatic samples from GDM patients, we sought to develop a novel mouse model for impaired gestational glucose tolerance. Mature female C57Bl/6 mouse offspring (F1) born to dams fed either a control (C) or low-protein (LP) diet during gestation and lactation were randomly allocated into two subsequent study groups: pregnant (CP, LPP) or non-pregnant (CNP, LPNP). Glucose tolerance tests were performed at gestational day (GD) 9, 12 and 18. Subsequently, pancreata were removed for fluorescence immunohistochemistry to assess α-cell mass (ACM), BCM and β-cell proliferation. An additional group of animals was used to measure insulin secretion from isolated islets at GD18. LPP females displayed glucose intolerance compared to CP females at GD18 (P < 0.001). BCM increased threefold at GD18 in CP females. However, LPP females had reduced BCM expansion (P < 0.01) concurrent with reduced β-cell proliferation at GD12 (P < 0.05). LPP females also had reduced ACM expansion at GD18 (P < 0.01). LPP islets had impaired glucose-stimulated insulin secretion in vitro compared to CP islets (P < 0.01). Therefore, impaired glucose tolerance during pregnancy is associated with a failure to adequately adapt BCM, as a result of reduced β-cell proliferation, in addition to lower glucose-stimulated insulin secretion. This model could be used to evaluate novel interventions during pregnancy to increase BCM or function as a strategy to prevent/reverse GDM.

The terminology applied to autoimmune hemolytic anemia (AIHA) seems inconsistent. We aimed to evaluate the consistency of definitions used for diagnosis and treatment. In this systematic review of literature from January 2006 to December 2015, we assessed heterogeneity in the definition of AIHA and its subtypes, refractory disease, disease phase, severity, criteria for treatment response, and response durability. A Medline search for anemia, hemolytic, autoimmune was supplemented with keyword searches. Main exclusions were conference abstracts, animal and non-English studies, and studies with

Optical coherence tomography (OCT) provides non-invasive, high-resolution in vivo imaging of the ocular surface and anterior segment. Over the years, it has become an essential tool for evaluating the anterior segment of the eye to monitor ocular development and ocular pathologies in both the clinical and research fields of ophthalmology and optometry. In this review, the clinical applications relating to the use of anterior segment OCT for imaging and quantifying normal and pathological features of the ocular surface, cornea, anterior chamber, and aqueous outflow system are summarised in a range of human ocular diseases. Applications of anterior segment OCT technology that have improved imaging and quantitation of ocular inflammation in experimental animal models of ocular diseases, such as anterior uveitis, microbial keratitis and glaucoma, are also described. The capacity to longitudinally evaluate anterior segment anatomical changes during development, and inflammation facilitates the understanding of the dynamics of tissue responses, and further enhances the intra-operative in vivo imaging during procedures, such as corneal transplantation and drug delivery. Future developments including in vivo ultrahigh-resolution anterior segment OCT, automated analyses of anterior segment OCT images and functional extensions of the technique, may revolutionise the clinical evaluation of anterior segment, corneal and ocular surface diseases.

SummarySARS-CoV-2 (CoV-2), which surfaced in late 2019 in Wuhan City, China, most likely originated in bats and rapidly spread among humans globally, harming and disrupting livelihoods worldwide. Early into the pandemic, reports of CoV-2 diagnoses in pets and other animals emerged, including dogs, cats, farmed mink and some large felids (tigers and lions) from various countries. While most CoV-2 positive animals were confirmed to have been in close contact with CoV-2 positive humans, there has been a paucity of published evidence to-date describing risk factors associated with CoV-2 transmission among humans and domestic and wild animals. The COVID-19 Human-Animal Interactions Survey (CHAIS) was developed through a cross-CEIRS Center collaboration to provide a standardized survey describing human-animal interaction during the pandemic and to evaluate behavioral, spatiotemporal, and biological risk factors associated with bi-directional zoonotic transmission of CoV-2 within households and other shared environments. CHAIS measures four broad domains of transmission risk; 1) intensity and risk of infection among human hosts, 2) spatial characteristics of shared environments, 3) behaviors and human-animal interactions, and 4) animal susceptibility to infection and propensity for onward spread. Following the development of CHAIS, with a One Health approach, a multidisciplinary group of experts (n=20) was invited to review and provide feedback on the survey for content validity. Expert feedback was incorporated into two final survey formats-a long-form and an abridged version for which specific core questions addressing zoonotic and reverse zoonotic transmission were identified. Both forms are modularized, with each section having the capacity to serve as independent instruments, allowing researchers to customize the survey based on context and research-specific needs. Further adaptations for studies seeking to investigate other zoonotic pathogens with similar routes of transmission (i.e. respiratory, direct contact) are also possible. The CHAIS instrument is a standardized human-animal interaction survey developed to provide important data on risk factors that guide transmission of CoV-2 from humans to animals, with great utility in capturing information of zoonotic transmission risk factors for CoV-2 and other similar pathogens.ImpactsWe present a standardized survey instrument for evaluating risk factors associated with bi-directional zoonotic transmission of SARS-CoV-2 and other similarly transmitted pathogens in household and other settings where humans and animals share close contact.The CHAIS instrument evaluates behavioral, spatiotemporal, and host determinants of transmission risk of SARS-CoV-2 and is highly adaptable for use in studies seeking to investigate other zoonotic pathogens such as influenza viruses.This standardized instrument will enable pooling of data across studies for meta-analyses to improve predictive models of bi-directional transmission of SARS-CoV-2 among humans and animals and will inform public health prevention and mitigation measures.

Gestational diabetes mellitus increases the risk of dysglycemia postpartum, in part, due to pancreatic β-cell dysfunction. However, no histological evidence exists comparing endocrine pancreas after healthy and glucose-intolerant pregnancies. This study sought to address this knowledge gap, in addition to exploring the contribution of an inflammatory environment to changes in endocrine pancreas after parturition. We used a previously established mouse model of gestational glucose intolerance induced by dietary low protein insult from conception until weaning. Pancreas and adipose samples were collected at 7, 30 and 90 days postpartum for histomorphometric and cytokine analyses, respectively. Glucose tolerance tests were performed prior to euthanasia and blood was collected via cardiac puncture. Pregnant female mice born to dams fed a low protein diet previously shown to develop glucose intolerance at late gestation relative to controls continued to be glucose intolerant until 1 month postpartum. However, glucose tolerance normalized by 3 months postpartum. Glucose intolerance at 7 days postpartum was associated with lower beta- and alpha-cell fractional areas and higher adipose levels of pro-inflammatory cytokine, interleukin-6. By 3 months postpartum, a compensatory increase in the number of small islets and a higher insulin to glucagon ratio likely enabled euglycemia to be attained in the previously glucose-intolerant mice. The results show that impairments in endocrine pancreas compensation in hyperglycemic pregnancy persist after parturition and contribute to prolonged glucose intolerance. These impairments may increase the susceptibility to development of future type 2 diabetes.

Purpose Recent evidence supports the benefit of intensive aphasia intervention programs for people with chronic aphasia, yet it is unclear if all participants can expect positive outcomes and for how long therapeutic gains last. Methods We systematically searched for studies investigating intensive interventions in chronic aphasia. To explore individual response rates and maintenance of therapeutic gains we carried out meta-synthesis by calculating and analysing the Standard Error of Measurement and Minimal Detectable Change metrics of six common outcome measures. Results Forty-four studies comprising 24 experimental (13 group, 11 single-subject) and 20 non-experimental studies met our inclusion criteria (n = 670). Whereas most group studies reported statistically significant post-therapy improvement and maintenance, analysis of individual participant data (IPD, n = 393) from these studies revealed that only about a third of participants were classified as "immediate responders," of which more than a third had lost their initial immediate gains at follow-up. This pattern did not change when IPD from single-subject studies (n = 49) was added to the analysis. Thus, only 22% of all IPD receiving an intensive intervention improved significantly and maintained their therapy gains. Conclusions Intensive aphasia therapy is effective when measured at the group-level, but many individuals do not respond significantly to the intervention, and even fewer individuals preserve their initial gains. Group study results do not allow prediction of an individual's response to the intervention. Future research should elucidate which factors mediate positive treatment response and maintenance for an individual.Implications for rehabilitationOnly a small proportion (about one fifth in this review) of intensive aphasia treatment program participants respond and maintain their therapy gains, a fact that is obscured by traditional p-value group analysis.A simple clinical decision-making method is presented for evaluating individual therapy gains and their maintenance.For some immediate treatment responders (about one third in this review), gains from intensive therapy programs are unlikely to be maintained in the long-term without additional, ongoing practice.Clinicians should consider the possibility of individual clients losing some of their therapy gains and take proactive steps to support long-term maintenance.

Background Chronic obstructive pulmonary disease (COPD) presents with physical, emotional and social difficulties that affect quality of life. Multimodal management includes both pharmacological and non-pharmacological strategies, and pulmonary rehabilitation (PR) plays an important role. Recent research has suggested that manual therapies may improve perceptions of dyspnea for people with COPD. Methods Focus group interviews were conducted as part of a mixed methods study to assess the feasibility of implementing a manual therapy technique—muscle energy technique (MET)—as an adjunct to PR for people with moderate to severe COPD. Focus group interviews were conducted to examine trial participants views of the intervention and the trial design. A thematic analysis was undertaken to explore the data. Results Twelve participants with moderate to severe COPD participated in three focus groups. Participants were motivated to participate in the trial to be proactive about their health. They perceived MET to be a gentle, comfortable form of stretching that allowed them to ‘breathe easier’ and prepared them for PR. A small number of participants reported mild muscular discomfort during MET, but this was short-lasting and was not bothersome. Participants enjoyed the one-on-one contact with researchers and learned more about their breathing while performing spirometric testing. Most participants wanted longer and more frequent MET sessions, and some requested ‘homework’ stretching exercises. Conclusions The findings of this study show that a manual therapy intervention was received well by participants in a clinical trial setting. A small number of participants reported mild musculoskeletal discomfort in relation to the MET treatment. Participant preferences for additional and longer treatment sessions should be carefully considered against available resources in future clinical trials. Trial registration ANZCTR, ACTRN12618000801213. Registered 11 May 2018 - Retrospectively registered. http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374643&isReview=true