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Background There is a need for evidence-based guidance on complementary medicines and therapies (CMT) use during pregnancy due to high prevalence of use and lack of guidance on the balance of benefit and harms. Aim Evaluate the extent to which current clinical practice guidelines relevant to Australian healthcare professionals make clear and unambiguous recommendations about CMT use in pregnancy, and synthesise these recommendations. Methods The search included EMBASE, PubMed, the National Health and Medical Research Council’s Clinical Practice Guidelines Portal, and websites of Australian maternity hospitals and professional/not-for-profit organisations for published guidelines on pregnancy care. Data were synthesised narratively. Guidelines were appraised by two independent reviewers using the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument. Findings A total of 48 guidelines were found, of which 41% provided recommendations that were not limited to routine vitamin and mineral supplementation. There were wide variations in recommendations, particularly for vitamin D and calcium. There was some consensus on recommending ginger and vitamin B6 for nausea and vomiting, and additional supplementation for women with obesity. Guidelines generally scored poorly in the domains of editorial independence and rigour of development. Discussion There is a lack of guidance with regard to appropriate CMT use during pregnancy, which may result in less-than-optimal care. Inconsistency between guidelines may lead to variations in care. Conclusion Guidelines should include clear and unambiguous guidance on appropriate CMT use during pregnancy, be based on a structured search of the evidence and informed by stakeholder engagement.

Compared to US university students, far less is known about the scale of unwanted and non-consensual sexual experiences [USEs] faced by UK university students, particularly those in Northern Ireland [NI]. The Sexual Experiences Survey (Short Form [SEF-SFV]) is considered a popular tool for measuring USEs but has not been updated since 2007; there is some indication that additional perpetrator tactics may be more inclusive of students' experiences and that certain scoring strategies may impact our understanding of data. This paper examines the USEs reported by 1033 students attending either of NI's traditional universities. Participants completed a modified version of the SES-SFV that included two additional perpetration tactics: "ignorance of refusal" and "taken by surprise." Sixty-three percent ( n = 650) reported experiencing at least one USE, but this reduced to 53% ( n = 546) without the new perpetrator tactics. Female and non-heterosexual students reported significantly more USEs than male and heterosexual students, respectively. "Taken by surprise" was highly endorsed (81%, n = 525) and the most commonly endorsed tactic. Whilst dichotomous scoring is the most straightforward, continuous scoring affords greater analytical opportunities whilst still retaining frequency of USEs. "Taken by surprise" may be a relevant addition but further mixed-methodological research is required to assess its validity among larger and more diverse samples. SES-SFV scoring options should be also validated using male and mixed-gender samples, particularly categorical scoring to ensure current construction is reflective of the wider student experience.

Background No effective pharmacological or non-pharmacological interventions exist for patients with long COVID. We aimed to describe recovery 1 year after hospital discharge for COVID-19, identify factors associated with patient-perceived recovery, and identify potential therapeutic targets by describing the underlying inflammatory profiles of the previously described recovery clusters at 5 months after hospital discharge. Methods The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a prospective, longitudinal cohort study recruiting adults (aged ≥18 years) discharged from hospital with COVID-19 across the UK. Recovery was assessed using patient-reported outcome measures, physical performance, and organ function at 5 months and 1 year after hospital discharge, and stratified by both patient-perceived recovery and recovery cluster. Hierarchical logistic regression modelling was performed for patient-perceived recovery at 1 year. Cluster analysis was done using the clustering large applications k-medoids approach using clinical outcomes at 5 months. Inflammatory protein profiling was analysed from plasma at the 5-month visit. This study is registered on the ISRCTN Registry, ISRCTN10980107, and recruitment is ongoing. Findings 2320 participants discharged from hospital between March 7, 2020, and April 18, 2021, were assessed at 5 months after discharge and 807 (32·7%) participants completed both the 5-month and 1-year visits. 279 (35·6%) of these 807 patients were women and 505 (64·4%) were men, with a mean age of 58·7 (SD 12·5) years, and 224 (27·8%) had received invasive mechanical ventilation (WHO class 7–9). The proportion of patients reporting full recovery was unchanged between 5 months (501 [25·5%] of 1965) and 1 year (232 [28·9%] of 804). Factors associated with being less likely to report full recovery at 1 year were female sex (odds ratio 0·68 [95% CI 0·46–0·99]), obesity (0·50 [0·34–0·74]) and invasive mechanical ventilation (0·42 [0·23–0·76]). Cluster analysis (n=1636) corroborated the previously reported four clusters: very severe, severe, moderate with cognitive impairment, and mild, relating to the severity of physical health, mental health, and cognitive impairment at 5 months. We found increased inflammatory mediators of tissue damage and repair in both the very severe and the moderate with cognitive impairment clusters compared with the mild cluster, including IL-6 concentration, which was increased in both comparisons (n=626 participants). We found a substantial deficit in median EQ-5D-5L utility index from before COVID-19 (retrospective assessment; 0·88 [IQR 0·74–1·00]), at 5 months (0·74 [0·64–0·88]) to 1 year (0·75 [0·62–0·88]), with minimal improvements across all outcome measures at 1 year after discharge in the whole cohort and within each of the four clusters. Interpretation The sequelae of a hospital admission with COVID-19 were substantial 1 year after discharge across a range of health domains, with the minority in our cohort feeling fully recovered. Patient-perceived health-related quality of life was reduced at 1 year compared with before hospital admission. Systematic inflammation and obesity are potential treatable traits that warrant further investigation in clinical trials. Funding UK Research and Innovation and National Institute for Health Research.

Background: Torus (buckle) fractures of the wrist are the most common fractures in children, involving the distal radius and/or ulna. It is unclear if children require rigid immobilisation and follow-up, or would equally recover by being discharged without any immobilisation or a bandage. Given the large number of these injuries, identifying the optimal treatment strategy could have important effects on the child, school absences and NHS costs. Objectives: To establish whether treating children with a distal radius torus fracture with the offer of a soft bandage and immediate discharge (“offer of bandage”), provides the same recovery, in terms of pain, function, complications, acceptability, school absence and resource use, as treatment with rigid immobilisation and follow-up as per usual practice (“rigid immobilisation”). Design: A pragmatic, multicentre, randomised controlled equivalence trial. Setting: 23 UK Emergency Departments. Participants: 965 children (4-15 years) with a distal radius torus fracture were randomised from January 2019 to July 2020 using a secure, centralised, online encrypted randomisation service. Exclusion criteria included presentation >36 hours after injury, multiple injuries and inability to complete follow-up. Interventions: Offer of bandage (n= 489) of whom the bandage was applied in 458, versus rigid immobilisation (n= 476). Participants and clinicians were not blinded to the treatment allocation. Main outcome measures: Pain at 3-days post-randomisation measured using the WongBaker FACES Pain Rating Scale. Secondary outcomes were the PROMIS Upper Extremity score for children, health related quality of life (QoL), complications, school absence, analgesia use and resource use collected up to 6 weeks post-randomisation. Results: 94% of participants provided primary outcome data. Pain was equivalent at the 3 day primary outcome for both groups. With reference to the pre-specified equivalence margin of 1.0, the adjusted difference in the intention-to-treat population was -0.10; 95% CI -0.37 to 0.17 and the per-protocol population was -0.06; 95% CI -0.34 to 0.21. There was equivalence in pain for both age subgroups (4-7 and 8–15 years). There was no difference in the rate of complications, with five (1.0%) in the offer of bandage group and three (0.6%) in the rigid immobilisation group. There were no differences between treatment groups in functional recovery, QoL or school absence at any point during follow-up. Analgesia use was marginally higher at Day 1 in the offer of bandage group (83% vs 78% participants), though was no different at other times. The offer of bandage significantly reduced the cost of treatment, and had a high probability of cost-effectiveness. Limitations: Families had a strong pre-existing preference for rigid immobilisation. Given this, and the inability to blind families to the treatment allocation, observer bias was a concern. However, there was clear evidence of equivalence. Conclusions: The study findings support the offer of bandage in children with a distal radius torus fracture.

Graphical abstract Abstract Endometriosis is a common yet under-recognised chronic disease with one in nine (more than 830,000) women and those assigned female at birth diagnosed with endometriosis by the age of 44 years in Australia. In 2018, Australia was the first country to develop a roadmap and blueprint to tackle endometriosis in a nationwide, coordinated manner. This blueprint is outlined in the National Action Plan for Endometriosis (NAPE), created from a partnership between government, endometriosis experts and advocacy groups. The NAPE aims to improve patient outcomes in the areas of awareness and education, clinical management and care and research. As researchers and clinicians are working to improve the lives of those with endometriosis, we discuss our experiences since the launch of the plan to highlight areas of consideration by other countries when developing research priorities and clinical plans. Historically, major barriers for those with endometriosis have been twofold; first, obtaining a diagnosis and secondly, effective symptom management post-diagnosis. In recent years, there have been calls to move away from the historically accepted ‘gold-standard’ surgical diagnosis and single-provider specialist care. As there are currently no reliable biomarkers for endometriosis diagnosis, specialist endometriosis scans and MRI incorporating artificial intelligence offer a novel method of visualisation and promising affordable non-invasive diagnostic tool incorporating well-established technologies. The recognised challenges of ongoing pain and symptom management, a holistic interdisciplinary care approach and access to a chronic disease management plan, could lead to improved patient outcomes while reducing healthcare costs. Lay summary Endometriosis is a chronic disease where tissue like the lining of the uterus is found in other locations around the body. For the 830,000 people living with endometriosis in Australia, this often results in an immense burden on all aspects of daily life. In 2018, Australia was the first country to introduce a roadmap and blueprint to tackle endometriosis in a nationwide coordinated manner with the National Action Plan for Endometriosis. This plan was created as a partnership between government, endometriosis experts and advocacy groups. There are several other countries who are now considering similar plans to address the burden of endometriosis. As researchers and clinicians are working to improve the lives of those with endometriosis, we share our experiences and discuss areas that should be considered when developing these national plans, including diagnostic pathways without the need for surgery, and building new centres of expertise in Endometriosis and Pelvic Pain.

BACKGROUND: Black women have greater than a three-fold risk of pregnancy-associated death compared to White women; cardiomyopathy is a leading cause of maternal mortality. OBJECTIVES: This study examined racial disparities in health outcomes among women with peripartum cardiomyopathy. STUDY DESIGN: Retrospective cohort of women with peripartum cardiomyopathy per the National Heart, Lung, and Blood Institute definition from January 2000–November 2017 from a single referral center. Selected health outcomes among Black and White women were compared; primary outcome was ejection fraction at diagnosis. Secondary outcomes included cardiovascular outcomes, markers of maternal morbidity, resource utilization, and subsequent pregnancy outcomes. RESULTS: Ninety-five women met inclusion criteria: 48% Black, 52% White. Nearly all peripartum cardiomyopathy diagnoses were postpartum (95.4% Black, 93% White, p=0.11). Ejection fraction at diagnosis was not different between Black and White women (26.8% ± 12.5 vs 28.7% ± 9.9, p=0.41). Though non-significant, fewer Black women had myocardial recovery to EF ≥ 55% (35% vs 53%, p = 0.07); however, 11 (24%) of Black women vs 1 (2%) White woman had an ejection fraction ≤ 35% at 6 – 12 months postpartum (p < 0.01). More Black women underwent implantable cardioverter defibrillator placement: n = 15 (33%) vs n = 7 (14%), p=0.03. Eight women (8.4%) died in the study period, not different by race (p = 0.48). Black women had higher rates of healthcare utilization. In the subsequent pregnancy, Black women had a lower initial ejection fraction (40% vs 55%, p = 0.007) and were less likely to recover postpartum (37.5% vs 55%, p = 0.02). CONCLUSIONS: Black and White women have similar mean ejection fraction at diagnosis of peripartum cardiomyopathy, but Black women have more severe left ventricular systolic dysfunction leading to worse outcomes, increased resource use, and lower ejection fraction entering the subsequent pregnancy.

Background Chronic pelvic pain (CPP) causes non-cyclical pelvic pain, period pain, fatigue and other painful symptoms. Current medical and surgical management strategies are often not sufficient to manage these symptoms and may lead to uptake of other therapies. Aims To determine the prevalence of allied health (AH) and complementary therapy (CM) use, the cost burden of these therapies and explore predictive factors for using allied health or complementary medicines. Materials and methods An online cross-sectional questionnaire using the WERF EndoCost tool was undertaken between February to April 2017. People were eligible to participate in the survey if they were aged 18–45, living in Australia and had chronic pelvic pain. Results From 409 responses, 340/409 (83%) of respondents reported a diagnosis of endometriosis. One hundred and five (30%) women with self-reported endometriosis, and thirteen (18%) women with other forms of CPP saw at least one AH or CM practitioner in the previous two months, with physiotherapists and acupuncturists the most common. Women who accessed CM or AH services spent an average of $480.32 AUD in the previous two months. A positive correlation was found between education and number of AH or CM therapies accessed in the past two months (p p = 0.028). Conclusions Women with CPP commonly access AH and CM therapies, with a high out of pocket cost. The high cost and associations with income and education levels may warrant a change to policy to improve equitable access to these services.

Half of out-of-hospital cardiac arrests (OHCA) are deemed inappropriate for resuscitation by emergency medical services (EMS). We investigated patient characteristics and reasons for non-treatment of OHCAs, and determined the proportion involving illicit drug use.We reviewed consecutive EMS-untreated OHCA from the British Columbia Cardiac Arrest Registry (2019-2020). We abstracted patient characteristics and categorized reasons for EMS non-treatment: (1) prolonged interval from the OHCA to EMS arrival ("non-recent OHCA") with or without signs of "obvious death"; (2) do-not-resuscitate (DNR) order; (3) terminal disease; (4) verbal directive; and (5) unspecified. We abstracted clinical details regarding a history of, or evidence at the scene of, illicit drug use.Of 13 331 cases, 5959 (45%) were not treated by EMS. The median age was 67 (IQR 54-81) and 1903 (32%) were female. EMS withheld resuscitation due to: non-recent OHCA, with and without signs of "obvious death" in 4749 (80%) and 108 (1.8%), respectively; DNR order in 952 (16%); terminal disease in 77 (1.3%); family directive in 41 (0.69%); and unspecified in 32 (0.54%). Overall and among those with non-recent OHCA, 695/5959 (12%) and 691/4857 (14%) had either a history of or evidence of recent illicit drug use, respectively.A prolonged interval from the OHCA until EMS assessment was the predominant reason for withholding treatment. Innovative solutions to decrease this interval may increase the proportion of OHCA that are treated by EMS and overall outcomes. Targeted interventions for illicit-drug use-related OHCAs may add additional benefit.

Objective: To determine the acceptability and feasibility of acupuncture for the treatment of endometriosis-related chronic pelvic pain. Design: A prospective, randomized controlled feasibility study. Setting: Outpatient setting in Sydney, Australia. Subjects: Participants who were aged 18-45 years, had a confirmed laparoscopic diagnosis of endometriosis in the past 5 years, and had regular menstrual periods and mean pelvic pain scores ≥4/10. Interventions: Sixteen acupuncture treatments delivered by registered acupuncturists using a standardized point protocol over 8 weeks, twice per week plus usual care compared with usual care alone. Outcome measures: Primary outcome measures were feasibility, safety, and acceptability of the acupuncture intervention. Secondary outcomes were changes in self-reported pelvic pain scores, changes in quality of life as measured by the Endometriosis Health Profile (EHP-30), changes in descending pain modulation, and changes in systemic inflammation (plasma interleukin [IL-6] concentrations). Results: Twenty-nine participants were eligible to participate, with 19 participants completing the trial. There was unequal withdrawals between groups; the acupuncture group had a withdrawal rate of 14% compared with 53% in usual care. Adverse events were uncommon (6.7%) and generally mild. A 1.9 point decrease in median nonmenstrual pain scores and a 2.0 decrease in median menstrual pain scores between baseline and end of trial were observed in the acupuncture group only. Improvements in all domains of the EHP-30 were seen in the acupuncture group, with no changes seen in usual care. There was no difference between baseline and end of treatment in IL-6 concentrations for either group. Conclusions: Acupuncture was an acceptable, well-tolerated treatment and it may reduce pelvic pain and improve quality of life; however, usual care was not an acceptable control group. Trial Registration: anzctr.org.au: ACTRN12617000053325. Prospectively registered January 11, 2017.

AZD1222 (ChAdOx1 nCoV-19) is a COVID-19 vaccine that is not yet licensed for use during pregnancy. To support the inclusion of pregnant and breastfeeding people in AZD1222 clinical studies, a non-clinical developmental and reproductive toxicity study was performed to evaluate its effects on fertility and reproductive processes of female CD-1 mice during the embryofetal development phase, and postnatal outcomes during the littering phase. Immunogenicity assessments were also made in dams, fetuses, and pups. There were no vaccine-related unscheduled deaths throughout the study. Furthermore, there were no vaccine-related effects on female reproduction, fetal or pup survival, fetal external, visceral, or skeletal findings, pup physical development, and no abnormal gross pathology findings in pups or dams. Antibody responses raised in dams were maintained throughout gestation and postnatal periods, and seroconversion in fetuses and pups indicate placental and lactational transfer of immunoglobulins. Together with clinical data from non-pregnant people, these results support the inclusion of pregnant and breastfeeding people in AZD1222 clinical studies.

Study Objective To explore the prevalence and impact of dysmenorrhea, pelvic pain and menstrual symptoms on young women at school or in tertiary education. Design and Setting Cross-sectional online survey in Australia. Participants A total of 4202 adolescent and young women (13-25 years of age; median age 17 years), having reached menarche, living in Australia and currently attending school (n = 2421) or tertiary education (n = 1781). Interventions Online survey hosted by Qualtrics between November 2017 to January 2018. Data were collected on sociodemographic data, menstrual cycle characteristics, dysmenorrhea, pelvic pain, and educational and social impact. Main Outcome Measures Information on menstrual and pelvic pain impact, academic absenteeism and presenteeism, impact on non-academic activities and interactions with teaching staff. Results and Conclusions Dysmenorrhea was reported by 92% of respondents. Dysmenorrhea was moderate (median 6.0 on a 0-10 numeric rating scale) and pain severity stayed relatively constant with age [rs(3804) = 0.012, P = .477]. Noncyclical pelvic pain at least once a month was reported by 55%. Both absenteeism and presenteeism related to menstruation were common. Just under half of women reported missing at least one class/lecture in the previous three menstrual cycles. The majority of young women at school (77%) and in tertiary education (70%) reported problems with classroom concentration during menstruation. Higher menstrual pain scores were strongly correlated with increased absenteeism and reduced classroom performance at both school and in tertiary education. Despite the negative impact on academic performance the majority of young women at school (60%) or tertiary education (83%) would not speak to teaching staff about menstruation.

Contains fulltext : 220431.pdf (Publisher’s version ) (Closed access) BACKGROUND: Disordered thyroid hormone transport, due to mutations in the SLC16A2 gene encoding monocarboxylate transporter 8 (MCT8), is characterised by intellectual and motor disability resulting from cerebral hypothyroidism and chronic peripheral thyrotoxicosis. We sought to systematically assess the phenotypic characteristics and natural history of patients with MCT8 deficiency. METHODS: We did an international, multicentre, cohort study, analysing retrospective data from Jan 1, 2003, to Dec 31, 2019, from patients with MCT8 deficiency followed up in 47 hospitals in 22 countries globally. The key inclusion criterion was genetically confirmed MCT8 deficiency. There were no exclusion criteria. Our primary objective was to analyse the overall survival of patients with MCT8 deficiency and document causes of death. We also compared survival between patients who did or did not attain full head control by age 1.5 years and between patients who were or were not underweight by age 1-3 years (defined as a bodyweight-for-age Z score

OBJECTIVES: To (i) quantify relationships between LBP symptoms, physical activity, and psychosocial characteristics in young adults and (ii) identify sub-classes of young adults with distinct pain trajectories. DESIGN: Prospective cohort study with 12 months follow-up METHODS: 120 adults (age 20.8±2.6 years, 99 women) participated. Participants completed a baseline survey that measured anxiety, depression, fear avoidance, quality of life, and history and impact of any LBP. Participants completed follow up surveys every 3 months for one year. Sub-classes based on pain trajectories over time were identified using latent class analysis and predictors of class membership at baseline were assessed. RESULTS: Individuals with LBP at baseline had lower physical quality of life scores than back-healthy participants (P = 0.01). Sub-class 1 (25% of individuals with LBP) had persistent moderate/high intensity of pain over the 1-year study period. Sub-class 2 (75%) had significantly improving pain over the 1-year study period. Higher fear avoidance (physical subscale) and pain interference at baseline were associated with greater odds of membership of sub-class 1 (odds ratios 1.2 (95% CI 1.01– 0.1.32) and 1.4, (95% CI 1.15 – 1.64) respectively). CONCLUSION: Most young adults with LBP had symptoms that improved over time. Levels of fear avoidance and pain interference may help to identify individuals at risk of persistent pain early in the lifespan.

Background Lipedema is a loose connective tissue disease predominantly in women identified by increased nodular and fibrotic adipose tissue on the buttocks, hips and limbs that develops at times of hormone, weight and shape change including puberty, pregnancy, and menopause. Lipedema tissue may be very painful and can severely impair mobility. Non-lipedema obesity, lymphedema, venous disease, and hypermobile joints are comorbidities. Lipedema tissue is difficult to reduce by diet, exercise, or bariatric surgery. Methods This paper is a consensus guideline on lipedema written by a US committee following the Delphi Method. Consensus statements are rated for strength using the GRADE system. Results Eighty-five consensus statements outline lipedema pathophysiology, and medical, surgical, vascular, and other therapeutic recommendations. Future research topics are suggested. Conclusion These guidelines improve the understanding of the loose connective tissue disease, lipedema, to advance our understanding towards early diagnosis, treatments, and ultimately a cure for affected individuals.

Study Objective To explore key aspects of menstrual health literacy and menstrual management in young women at school or in tertiary education. Design Cross-sectional online survey. Setting Australia-wide. Participants A total of 4202 adolescent and young women (13-25 years of age; median age 17 years), having reached menarche, living in Australia and currently attending school (n = 2421) or tertiary education (n = 1781). Interventions Online survey hosted by Qualtrics between November 2017 and January 2018. Data were collected on contraceptive use, management strategies, sources of information, and knowledge of menstruation. Main Outcome Measures Information on prevalence and effectiveness of different management strategies, health-seeking behavior, knowledge about menstruation, and common menstrual disorders such as endometriosis. Results The majority of young women did not seek medical advice for their menstrual symptoms, but used information from the Internet (50%) and engaged in self-management, most commonly with over-the-counter medications such as paracetamol (51%) or ibuprofen (52%). Oral contraceptive use was relatively common (35%), and mostly for reduction of menstrual pain (58%). Despite having significant dysmenorrhea, approximately one-half of the participants (51%) thought that their period was normal. Women with higher pain scores were more likely to rate their period as “abnormal” (P Conclusion Self-management of menstrual symptoms is common, but a significant minority of women are underdosing or choosing ineffective methods. Most women do not seek medical advice even when symptoms are severe, and cannot identify symptoms suggestive of secondary dysmenorrhea. Improved education on menstruation is vital.

BACKGROUND: Hand-held dynamometry is considered an efficient, effective, and portable means of objectively measuring lower extremity strength; however, it has yet to be studied specific to dance-relevant muscle performance. Also, dynamometry is often criticized for variability in results based on tester strength and sex. Use of an external stabilizing device has been suggested to minimize differences in outcomes between male and female testers by reducing variability associated with tester strength limitations. Therefore, this study used a barre-mounted, portable dynamometer stabilizing device to improve consistency of results among different testers for assessing hip and lower extremity muscle performance in dance-relevant positions. OBJECTIVE: To assess the intra and inter-rater reliability of a barre-mounted dynamometer stabilizing device in measuring muscle performance in common dance maneuvers. METHODS: Two testers assessed muscle performance of three common dance maneuvers-—développé en avant, à la secondé, and arabesque-—on 11 pre-professional and professional dancers on two separate occasions to establish intra- and inter-rater reliability of the barre-mounted dynamometer stabilizing device. RESULTS: Intra-rater reliability was moderate to high and inter-rater reliability of the device was excellent, with intraclass correlation coefficients ranging from 0.527–0.851 and 0.834–0.953, respectively, for all positions. CONCLUSIONS: The barre-mounted stabilizing device shows promise in mitigating tester strength or fatigue in assessing muscle performance of dancers. Initial assessment of the device suggests further study may be indicated to improve generalizability to applications of larger-scale muscle performance screening and assessment in dancers or other athletic populations who engage in movements that require extensive hip range of motion and multi-joint stability. CLINICAL RELEVANCE: Using a portable, barre-mounted stabilizing device in assessing multi-joint lower extremity muscle performance in dancers improves consistency of testing results. Application of this testing device into wider scale screenings could assist in developing normative data for a population that is lacking.

Background Some people produce specific body odours that make them more attractive than others to mosquitoes, and consequently are at higher risk of contracting vector-borne diseases. The skin microbiome can break down carbohydrates, fatty acids and peptides on the skin into volatiles that mosquitoes can differentiate. Results Here, we examined how skin microbiome composition of women differs in relation to level of attractiveness to Anopheles coluzzii mosquitoes, to identify volatiles in body odour and metabolic pathways associated with individuals that tend to be poorly-attractive to mosquitoes. We used behavioural assays to measure attractiveness of participants to An. coluzzii mosquitoes, 16S rRNA amplicon sequencing of the bacteria sampled from the skin and gas chromatography of volatiles in body odour. We found differences in skin microbiome composition between the poorly- and highly-attractive groups, particularly eight Amplicon Sequence Variants (ASVs) belonging to the Proteobacteria, Actinobacteria and Firmicutes phyla. Staphylococcus 2 ASVs are four times as abundant in the highly-attractive compared to poorly-attractive group. Associations were found between these ASVs and volatiles known to be attractive to Anopheles mosquitoes. Propanoic pathways are enriched in the poorly-attractive participants compared to those found to be highly-attractive. Conclusions Our findings suggest that variation in attractiveness of people to mosquitoes is related to the composition of the skin microbiota, knowledge that could improve odour-baited traps or other next generation vector control tools.

Introduction Asthma has substantial and increasing health and economic burden worldwide. This study aimed to estimate healthcare expenditure and determine the factors that increase expenditure in Australians with poorly controlled asthma. Methods Individuals ≥18 years of age with poorly controlled asthma, as determined by a score ≥1.5 on the Asthma Control Questionnaire, were included in the study. Healthcare utilization costs from medical services and medications were estimated over an average follow-up of 12 months from administratively linked data: the Medicare Benefits Schedule and Pharmaceutical Benefits Scheme. A generalized linear model with gamma distribution and log link was used to predict participants’ key baseline characteristics associated with variations in healthcare costs. Results A total of 341 participants recruited through community pharmacies were included. The mean (standard deviation, SD) age of participants was 56.6 (SD 17.6) years, and approximately 71% were females. The adjusted average monthly healthcare expenditure per participant was $AU386 (95% CI: 336, 436). On top of the average monthly costs, an incremental expenditure was found for each year increase in age ($AU4; 95% CI: 0.78, 7), being unemployed ($AU201; 95% CI: 91, 311), one unit change in worsening quality of life ($AU35; 95% CI: 9, 61) and being diagnosed with depression and anxiety ($AU171; 95% CI: 36, 306). Conclusions In a cohort of Australian patients, characterized by poor asthma control and co-morbidities individuals impose substantial economic burden in terms of Medicare funded medical services and medications. Programs addressing strategies to improve the quality of life and manage co-morbid anxiety and depression and encourage asthma patients’ engagement in clinically tolerable jobs, may result in significant cost savings to the health system.

Background Acupuncture is a popular treatment for women’s health. Several trials and meta-analysis have been published in recent years on key women’s health conditions but it is unclear if this has led to any changes in clinical practice or referrals from other health professionals. The aim of this survey was to explore if, how, and why, aspects of acupuncture practice have changed since our survey in 2013. Method An online cross-sectional survey of registered acupuncturists and Chinese Medicine practitioners in Australia and New Zealand. Questions covered the practitioner demographics and training, women’s health conditions commonly treated, modalities used, sources of information and continuing education (CE) (e.g. webinars), changes in clinical practice, and referral networks. Results One hundred and seventy registered practitioners responded to this survey, with 93% reporting treating women’s health in the last 12 months. The majority of respondents were from Australia (60%), held a bachelors level qualification (60%), and used a traditional Chinese medicine framework (86%). Most practitioners incorporated other modalities in addition to acupuncture. Most practitioners’ referral networks were predominantly based on word of mouth for menstrual, fertility and pregnancy related conditions, with referrals from medical practitioners being much less common. More than half (57%) reported having changed their women’s health practice in the past 12 months; just over a quarter of those who changed treatment (27%) reported it was due to research findings. The most commonly used sources of information/CE used to inform treatment were webinars and conferences, while peer-reviewed journal articles were the least commonly used source. Conclusion Acupuncture practitioners in Australia and New Zealand commonly treat women’s health conditions, but this is usually the result of women seeking them out, rather than being referred from a medical practitioner. The majority of practitioners did report changing their women’s health practice, but peer reviewed academic articles alone are not an ideal medium to convey this information since practitioners favour knowledge obtained from webinars and conferences. Academics and other clinician researchers should consider alternative means of disseminating knowledge beyond traditional academic publications and conferences, special interest groups may assist in this and also help improve research literacy.

Objective: Menstrual cycle-related conditions, such as dysmenorrhea and heavy bleeding, are common amongst those under 25 years. Despite having significant impact on work, education, and social activities, most do not seek medical advice, preferring to self-manage their symptoms. We aimed to determine if access to a web-based resource could improve health literacy, reduce menstrual symptoms, and encourage health-seeking behavior in those at risk of conditions, such as endometriosis. Methods: People were eligible to participate if they were currently living in Australia, aged 14-25 years, and had menstruated for at least 12 months. Access to the resource, comprising evidence-based information on the menstrual cycle, the Period ImPact and Pain Assessment (PIPPA) tool, and guidance on self-care options, was provided for three menstrual cycles. Results: Seventy-five participants with a mean age of 20.4 years enrolled to use the web-based resource. Forty-three percent visited their doctor regarding their menstrual symptoms during the study period, with 84% indicating that they made the appointment due to the resource; over half (56%) who visited their doctor received a referral to a gynecologist. There were clinically relevant improvements in health literacy reflecting improved confidence of participants regarding having both adequate information and skills to manage their symptoms. Almost half (48.8%) said the resource had changed what they thought was a ‘normal’ period, and 94% could now identify symptoms of endometriosis. Conclusion: A low-cost, web-based resource can improve health literacy, provide effective options for self-management of menstrual cycle-related conditions, and motivate young people to seek medical advice.

Hydroxocobalamin (vitamin B12a) is an emerging treatment for vasoplegic syndrome (VS) associated with cardiopulmonary bypass (CPB). Given its cost and scarcity, an institutional guideline for its use as a rescue treatment in cases of suspected VS was developed. Hemodynamic variables and vasopressor requirements were reviewed for a series of 24 post-CPB patients who received B12a. Favorable changes in hemodynamic parameters and vasopressor requirements were seen after B12a administration although guideline criteria for VS were inconsistently met. These findings support the continued study of B12a in patients with CPB-associated VS.

Introduction Youth cigarette smoking decreased significantly over the last two decades in the United States. This study provides estimates and trends from 2011 to 2018 and factors associated with youth menthol and non-menthol smoking from 2016 to 2018. Methods Using data from the 2011–2018 National Youth Tobacco Surveys, past 30-day (current) menthol and non-menthol cigarette smoking were estimated for all youth (prevalence) and youth smokers (proportions). Trends were examined using Joinpoint regression, calculating the annual percent change (APC). Multivariate logistic regression analyses identified factors associated with menthol smoking. Results From 2011 to 2018, menthol cigarette smoking among current youth cigarette smokers significantly decreased from 57.3% to 45.7% (APC: −3.0%), while non-menthol (38.2% to 47.3% [APC: 2.9%]) and unknown menthol status (not sure\missing) (4.5% to 7.0% [APC: 7.1%]) significantly increased. Menthol cigarette smoking among high school, male, female, and non-Hispanic white current cigarette smokers decreased, but remained unchanged among middle school, non-Hispanic black, and Hispanic smokers. Significantly higher proportions of menthol cigarette smokers smoked on ≥20 days, ≥2 cigarettes per day, and ≥100 cigarettes in their lifetime compared to non-menthol smokers. Among current cigarette smokers, non-Hispanic blacks, Hispanics, flavored non-cigarette tobacco users, frequent smokers (≥20 days), those smoking 2–5 cigarettes per day, and those living with someone who uses tobacco had higher odds of menthol cigarette smoking. Conclusions In 2018, nearly half of current youth cigarette smokers smoked menthol cigarettes. While menthol cigarette smoking declined from 2011 to 2018 among all youth and among youth smokers, there was no change in menthol cigarette smoking among non-Hispanic black, Hispanic, and middle school cigarette smokers. Implications This study finds that overall cigarette and menthol cigarette smoking declined in youth from 2011 to 2018. However, menthol cigarette smoking among non-Hispanic black, Hispanic, and middle school youth cigarette smokers did not change. Information from this study can help inform efforts to reduce menthol cigarette smoking among US youth, particularly racial/ethnic minority populations.

There is a growing need to understand the potential neurotoxicity of organophosphate flame retardants (OPFRs) and plasticizers because use and, consequently, human exposure, is rapidly expanding. We have previously shown in rats that developmental exposure to the commercial flame retardant mixture Firemaster 550 (FM 550), which contains OPFRs, results in sex-specific behavioral effects, and identified the placenta as a potential target of toxicity. The placenta is a critical coordinator of fetal growth and neurodevelopment, and a source of neurotransmitters for the developing brain. We have shown in rats and humans that flame retardants accumulate in placental tissue, and induce functional changes, including altered neurotransmitter production. Here, we sought to establish if OPFRs (triphenyl phosphate and a mixture of isopropylated triarylphosphate isomers) alter placental function and fetal forebrain development, with disruption of tryptophan metabolism as a primary pathway of interest. Wistar rat dams were orally exposed to OPFRs (0, 500, 1000, or 2000 μg/day) or a serotonin (5-HT) agonist 5-methoxytryptamine for 14 days during gestation and placenta and fetal forebrain tissues collected for analysis by transcriptomics and metabolomics. Relative abundance of genes responsible for the transport and synthesis of placental 5-HT were disrupted, and multiple neuroactive metabolites in the 5-HT and kynurenine metabolic pathways were upregulated. In addition, 5-HTergic projections were significantly longer in the fetal forebrains of exposed males. These findings suggest that OPFRs have the potential to impact the 5-HTergic system in the fetal forebrain by disrupting placental tryptophan metabolism.

A major challenge in modern biology is to understand how naturally occurring variation in DNA sequences affects complex organismal traits through networks of intermediate molecular phenotypes. This question is best addressed in a genetic mapping population in which all molecular polymorphisms are known and for which molecular endophenotypes and complex traits are assessed on the same genotypes. Here, we performed deep RNA sequencing of 200 Drosophila Genetic Reference Panel inbred lines with complete genome sequences and for which phenotypes of many quantitative traits have been evaluated. We mapped expression quantitative trait loci for annotated genes, novel transcribed regions, transposable elements, and microbial species. We identified host variants that affect expression of transposable elements, independent of their copy number, as well as microbiome composition. We constructed sex-specific expression quantitative trait locus regulatory networks. These networks are enriched for novel transcribed regions and target genes in heterochromatin and euchromatic regions of reduced recombination, as well as genes regulating transposable element expression. This study provides new insights regarding the role of natural genetic variation in regulating gene expression and generates testable hypotheses for future functional analyses.

The purpose of this study was to determine the association between corticomotor excitability (CME) of gluteus maximus (GM) and hip biomechanics during a single-leg drop-jump task. Thirty-two healthy individuals participated. The slope of the input-output curve (IOC) obtained from transcranial magnetic stimulation was used to assess CME of GM. The average hip extensor moment and peak hip flexion angle during the stance phase of the drop jump task was calculated. The slope of the IOC of GM was found to be a predictor of the average hip extensor moment (r

The purpose of this study was to compare gait kinematics, kinetics, and muscle activation between pregnant females with high and low scores for low back and/or pelvic girdle pain during and after pregnancy.Twenty participants tested during second trimester, third trimester, and again post-partum. At each session, motion capture, force plates, and surface electromyography data were captured during self-selected velocity over-ground walking. Participants completed the Quebec Back Pain Disability Scale (QBPDS) and were assigned to high (QBPDS ≥15) or low pain groups (QBPDS15) based on third trimester scores. Two-way mixed model ANOVAs were used to compare high and low pain groups over time.Nine participants met the high pain group criteria and 11 were low pain. During second trimester the high pain group compared to the low pain group demonstrated smaller peak hip flexor moments, total hip work, percent hip contribution to work, and larger percent ankle contribution to work. Pregnant females demonstrated greater hip, knee, and ankle moments, ankle work, and gluteus maximus muscle activation third trimester than second trimester.Reduced hip and greater ankle contribution to work in the high pain group during second trimester could indicate decreased hip utilization early in pregnancy and may contribute to disability as pregnancy progresses. It is also possible kinetic differences during second trimester reflect an early strategy to reduce pain by avoiding hip joint loading. Increased moments and work during third trimester indicate a clinical imperative to better prepare pregnant females to accommodate increased joint loading and muscular demand.

Autosomal-recessive renal tubular dysgenesis (AR-RTD) is a rare genetic disorder caused by defects in the renin-angiotensin system that manifests as fetal anuria leading to oligohydramnios and Potter sequence. Although the most common outcome is neonatal death from renal failure, pulmonary hypoplasia, and/or refractory arterial hypotension; several cases have been reported that describe survival past the neonatal period.Herein, we report the first family with biallelic ACE variants and more than one affected child surviving past the neonatal period, as well as provide a review of the previously reported 18 cases with better outcomes.While both siblings with identical compound heterozygous ACE variants have received different treatments, neither required renal replacement therapy. We show that both vasopressin and fludrocortisone in the neonatal period may provide survival advantages, though outcomes may also be dependent on the type of gene variant, as well as other factors.While AR-RTD is most often a lethal disease in the neonatal period, it is not universally so. A better understanding of the factors affecting survival will help to guide prognostication and medical decision-making.

Chronic pelvic pain (CPP) causes important negative effects on quality of life. Endometriosis is the most common cause of CPP in females, and diagnostic delay is over six years internationally. Data remain scarce for CPP impact or diagnostic delay in Aotearoa New Zealand. This study used an online survey to explore the impact of CPP on various life domains for those aged over 18. Additionally, for those with an endometriosis diagnosis, diagnostic delay and factors affecting this over time were explored. There were 800 respondent (620 with self-reported endometriosis). CPP symptoms, irrespective of final diagnosis, started prior to age 20 and negatively impacted multiple life domains including employment, education, and relationships. Mean diagnostic delay for those with endometriosis was 8.7 years, including 2.9 years between symptom onset and first presentation and 5.8 years between first presentation and diagnosis. Five doctors on average were seen prior to diagnosis. However, there was a reduction in the interval between first presentation and diagnosis over time, from 8.4 years for those presenting before 2005, to two years for those presenting after 2012. While diagnostic delay is decreasing, CPP, irrespective of aetiology, continues to have a significant negative impact on the lives of those affected.

Objective To examine how insertion and presence of intramuscular fine-wire electromyography electrodes (IFWEs) in lumbar multifidus affect paraspinal muscle strength, endurance, and activation in persons with and without recurrent lower back pain (RLBP) during activities that require high levels of muscle contraction. Design Case-control with randomization of conditions. Setting Clinical research laboratory. Participants Forty participants age 18 to 40 years were recruited (18 female; mean age = 25.5 years); 20 with a history of RLBP were compared to a matching control group of 20 without RLBP. Interventions Each participant was tested under three conditions over three sessions. On Session 1, the baseline condition, we assessed muscle performance without IFWE insertion. On Sessions 2 and 3, participants were randomly alternated between two experimental conditions: (1) wire-in, in which the IFWE was inserted and remained within the muscle during testing; and (2) wire-out, in which the IFWE was inserted and immediately removed. Main outcome measurements Lumbar spinal extensor peak strength, endurance, and normalized electromyography (EMG) amplitude during the endurance test. Results Individuals with RLBP showed a significant decrease in peak strength during conditions that involved IFWE insertion and tend to experience more pain during muscle testing. Both groups exhibited similar levels of performance and muscle activation during the endurance test. Conclusion Our findings indicate that individuals with RLBP exhibited reduced lumbar extensor strength in response to IFWE insertion to the deep paraspinal muscles. This behavior is different from those without RLBP. Researchers should carefully consider the use of IFWE in individuals with RLBP during high exertion activities.

Background: chronic pelvic pain (CPP) is a common gynaecological condition accounting for 20% of all gynaecological referrals. There are wide ranges of causes with overlapping symptomatology, therefore the management of the condition is a formidable challenge for clinicians. The aetiology of CPP is heterogeneous and in many cases, no clear diagnosis can be reached. It is in this scenario that the label of chronic pelvic pain syndrome (CPPS) can be applied. We defined women with CPPS as having a minimum duration of pain of at least 6 months, including with a diagnosis of pelvic congestion syndrome, but excluding pain caused by a condition such as endometriosis. Many surgical interventions have been tried in isolation or in conjunction with non-surgical interventions in the management with variable results. Surgical interventions are invasive and carry operative risks. Surgical interventions must be evaluated for their effectiveness prior to their prevalent use in the management of women with CPPS.Objectives: to review the effectiveness and safety of surgical interventions in the management of women with CPPS.Search methods: we searched the Cochrane Gynaecology and Fertility Group (CGF) Specialised Register of Controlled Trials, CENTRAL, MEDLINE, Embase and PsycINFO, on 23 April 2021 for any randomised controlled trials (RCT) for surgical interventions in women with CPPS. We also searched the citation lists of relevant publications, two trial registries, relevant journals, abstracts, conference proceedings and several key grey literature sources.Selection criteria: RCTs with women who had CPPS. The review authors were prepared to consider studies of any surgical intervention used for the management of CPPS. Outcome measures were pain rating scales, adverse events, psychological outcomes, quality of life (QoL) measures and requirement for analgesia.Data collection and analysis: Two review authors independently evaluated studies for inclusion and extracted data using the forms designed according to Cochrane guidelines. For each included trial, we collected information regarding the method of randomisation, allocation concealment, blinding, data reporting and analyses. We reported pooled results as mean difference (MDs) or odds ratios (OR) and 95% confidence interval (CI) by the Mantel-Haenszel method. If similar outcomes were reported on different scales, we calculated the standardised mean difference (SMD). We applied GRADE criteria to judge the overall certainty of the evidence.Main results: our studies met our inclusion criteria involving 216 women with CPP and no identifiable cause. Adhesiolysis compared to no surgery or diagnostic laparoscopy We are uncertain of the effect of adhesiolysis on pelvic pain scores postoperatively at three months (MD -7.3, 95% CI -29.9 to 15.3; 1 study, 43 participants; low-certainty evidence), six months (MD -14.3, 95% CI -35.9 to 7.3; 1 study, 43 participants; low-certainty evidence) and 12 months postsurgery (MD 0.00, 95% CI -4.60; 1 study, 43 participants; very low-certainty evidence). Adhesiolysis may improve both the emotional wellbeing (MD 24.90, 95% CI 7.92 to 41.88; 1 study, 43 participants; low-certainty evidence) and social support (MD 23.90, 95% CI -1.77 to 49.57; 1 study, 43 participants; low-certainty evidence) components of the Endometriosis Health Profile-30, and both the emotional component (MD 32.30, 95% CI 13.16 to 51.44; 1 study, 43 participants; low-certainty evidence) and the physical component of the 12-item Short Form (MD 22.90, 95% CI 10.97 to 34.83; 1 study, 43 participants; low-certainty evidence) when compared to diagnostic laparoscopy. We are uncertain of the safety of adhesiolysis compared to comparator groups due to low-certainty evidence and lack of structured adverse event reporting. No studies reported on psychological outcomes or requirements for analgesia. Laparoscopic uterosacral ligament ablation or resection compared to diagnostic laparoscopy/other treatment We are uncertain of the effect of laparoscopic uterosacral ligament/nerve ablation (LUNA) or resection compared to other treatments postoperatively at three months (OR 1.26, 95% CI 0.40 to 3.93; 1 study, 51 participants; low-certainty evidence) and six months (MD -2.10, 95% CI -4.38 to 0.18; 1 study, 74 participants; very low-certainty evidence). At 12 months post-surgery, we are uncertain of the effect of LUNA on the rate of successful treatment compared to diagnostic laparoscopy. One study of 56 participants found no difference in the effect of LUNA on non-cyclical pain (P = 0.854) or dyspareunia (P = 0.41); however, there was a difference favouring LUNA on dysmenorrhea (P = 0.045) and dyschezia (P = 0.05). We are also uncertain of the effect of LUNA compared to vaginal uterosacral ligament resection on pelvic pain at 12 months (MD 2.00, 95% CI 0.47 to 3.53; 1 study, 74 participants; very low-certainty evidence). We are uncertain of the safety of LUNA or resection compared to comparator groups due to the lack of structured adverse event reporting. Women undergoing LUNA may require more analgesia postoperatively than those undergoing other treatments (P < 0.001; 1 study, 74 participants). No studies reported psychological outcomes or QoL.Authors' conclusions: we are uncertain about the benefit of adhesiolysis or LUNA in management of pain in women with CPPS based on the current literature. There may be a QoL benefit to adhesiolysis in improving both emotional wellbeing and social support, as measured by the validated QoL tools. It was not possible to synthesis evidence on adverse events as these were only reported narratively in some studies, in which none were observed. With the inadequate objective assessment of adverse events, especially long-term adverse events, associated with adhesiolysis or LUNA for CPPS, there is currently little to support these interventions for CPPS.

Objective To determine the population-level impact of COVID-19 pandemic–related obstetric practice changes on maternal and newborn outcomes. Methods Segmented regression analysis examined changes that occurred 240 weeks pre-pandemic through the first 32 weeks of the pandemic using data from Ontario’s Better Outcomes Registry & Network. Outcomes included birth location, length of stay, labour analgesia, mode of delivery, preterm birth, and stillbirth. Immediate and gradual effects were modelled with terms representing changes in intercepts and slopes, corresponding to the start of the pandemic. Results There were 799 893 eligible pregnant individuals included in the analysis; 705 767 delivered in the pre-pandemic period and 94,126 during the pandemic wave 1 period. Significant immediate decreases were observed for hospital births (relative risk [RR] 0.99; 95% CI 0.98–0.99), length of stay (median change –3.29 h; 95% CI –3.81 to –2.77), use of nitrous oxide (RR 0.11; 95% CI 0.09–0.13) and general anesthesia (RR 0.69; 95% CI 0.58– 0.81), and trial of labour after cesarean (RR 0.89; 95% CI 0.83–0.96). Conversely, there were significant immediate increases in home births (RR 1.35; 95% CI 1.21–1.51), and use of epidural (RR 1.02; 95% CI 1.01–1.04) and regional anesthesia (RR 1.01; 95% CI 1.01–1.02). There were no significant immediate changes for any other outcomes, including preterm birth (RR 0.99; 95% CI 0.93–1.05) and stillbirth (RR 1.11; 95% CI 0.87–1.42). Conclusion Provincial health system changes implemented at the start of the pandemic resulted in immediate clinical practice changes but no significant increases in adverse outcomes.

Background: Surveys of acupuncture practitioners worldwide have shown an increase in the use of acupuncture to treat women&rsquo, s health conditions over the last ten years. Published studies have explored the effectiveness of acupuncture for various conditions such as period pain, fertility, and labor induction. However, it is unclear what role, if any, peer-reviewed research plays in guiding practice. Methods: Acupuncturists with a significant women&rsquo, s health caseload were interviewed online in three small groups to explore factors that contribute to acupuncturists&rsquo, clinical decision made around treatment approaches and research. Results: Eleven practitioners participated in the focus groups. The overarching theme that emerged was one of &lsquo, Not mainstream but a stream.&rsquo, This captured two themes relating to acupuncture as a distinct practice: &lsquo, working with what you&rsquo, ve got&rsquo, as well as &lsquo, finding the right lens&rsquo, illustrating practitioners&rsquo, perception of research needing to be more relevant to clinical practice. Conclusions: Acupuncture practitioners treating women&rsquo, s health conditions reported a disconnect between their clinical practice and the design of clinical trials, predominantly due to what they perceived as a lack of individualization of treatment. Case histories were popular as a learning tool and could be used to support increasing research literacy.

Pompe disease (PD) is a severe neuromuscular disorder caused by deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA). PD is currently treated with enzyme replacement therapy (ERT) with intravenous infusions of recombinant human GAA (rhGAA). Although the introduction of ERT represents a breakthrough in the management of PD, the approach suffers from several shortcomings. Here, we developed a mouse model of PD to compare the efficacy of hepatic gene transfer with adeno-associated virus (AAV) vectors expressing secretable GAA with long-term ERT. Liver expression of GAA results in enhanced pharmacokinetics and uptake of the enzyme in peripheral tissues compared to ERT. Combination of gene transfer with pharmacological chaperones boosts GAA bioavailability, resulting in improved rescue of the PD phenotype. Scale-up of hepatic gene transfer to non-human primates also successfully results in enzyme secretion in blood and uptake in key target tissues, supporting the ongoing clinical translation of the approach., Pompe disease is currently treated with enzyme replacement therapy (ERT) with recombinant human acid alpha-glucosidase (GAA). Here, the authors show hepatic-directed gene therapy with AAV vectors enhances GAA bioavailability compared with ERT, resulting in improved rescue of the disease phenotype in mice and broad enzyme distribution in mice and non-human primates.

Endometriosis is known to impact work productivity. The COVID-19 pandemic resulted in a shift in working practices for many, with an increase in working from home and/or flexible working hours. The aim of this online cross-sectional study was to determine if these changes resulted in changes in symptom management and productivity in Australian people with endometriosis. Three hundred and eighty-nine people responded to the survey. The majority of respondents found that their endometriosis symptoms were much easier to manage, and they were more productive. A key factor was flexibility in work hours and the increased ability to self-manage their time.

Background The impact of COVID-19 on physical and mental health and employment after hospitalisation with acute disease is not well understood. The aim of this study was to determine the effects of COVID-19-related hospitalisation on health and employment, to identify factors associated with recovery, and to describe recovery phenotypes. Methods The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a multicentre, long-term follow-up study of adults (aged ≥18 years) discharged from hospital in the UK with a clinical diagnosis of COVID-19, involving an assessment between 2 and 7 months after discharge, including detailed recording of symptoms, and physiological and biochemical testing. Multivariable logistic regression was done for the primary outcome of patient-perceived recovery, with age, sex, ethnicity, body-mass index, comorbidities, and severity of acute illness as covariates. A post-hoc cluster analysis of outcomes for breathlessness, fatigue, mental health, cognitive impairment, and physical performance was done using the clustering large applications k-medoids approach. The study is registered on the ISRCTN Registry (ISRCTN10980107). Findings We report findings for 1077 patients discharged from hospital between March 5 and Nov 30, 2020, who underwent assessment at a median of 5·9 months (IQR 4·9–6·5) after discharge. Participants had a mean age of 58 years (SD 13); 384 (36%) were female, 710 (69%) were of white ethnicity, 288 (27%) had received mechanical ventilation, and 540 (50%) had at least two comorbidities. At follow-up, only 239 (29%) of 830 participants felt fully recovered, 158 (20%) of 806 had a new disability (assessed by the Washington Group Short Set on Functioning), and 124 (19%) of 641 experienced a health-related change in occupation. Factors associated with not recovering were female sex, middle age (40–59 years), two or more comorbidities, and more severe acute illness. The magnitude of the persistent health burden was substantial but only weakly associated with the severity of acute illness. Four clusters were identified with different severities of mental and physical health impairment (n=767): very severe (131 patients, 17%), severe (159, 21%), moderate along with cognitive impairment (127, 17%), and mild (350, 46%). Of the outcomes used in the cluster analysis, all were closely related except for cognitive impairment. Three (3%) of 113 patients in the very severe cluster, nine (7%) of 129 in the severe cluster, 36 (36%) of 99 in the moderate cluster, and 114 (43%) of 267 in the mild cluster reported feeling fully recovered. Persistently elevated serum C-reactive protein was positively associated with cluster severity. Interpretation We identified factors related to not recovering after hospital admission with COVID-19 at 6 months after discharge (eg, female sex, middle age, two or more comorbidities, and more acute severe illness), and four different recovery phenotypes. The severity of physical and mental health impairments were closely related, whereas cognitive health impairments were independent. In clinical care, a proactive approach is needed across the acute severity spectrum, with interdisciplinary working, wide access to COVID-19 holistic clinical services, and the potential to stratify care. Funding UK Research and Innovation and National Institute for Health Research.

Myocardial infarction causes pathological changes in the autonomic nervous system, which exacerbate heart failure and predispose to fatal ventricular arrhythmias and sudden death. These changes are characterized by sympathetic activation and parasympathetic dysfunction (reduced vagal tone). Reasons for the central vagal withdrawal and, specifically, whether myocardial infarction causes changes in cardiac vagal afferent neurotransmission that then affect efferent tone, remain unknown. The objective of this study was to evaluate whether myocardial infarction causes changes in vagal neuronal afferent signaling. Using in vivo neural recordings from the inferior vagal (nodose) ganglia and immunohistochemical analyses, structural and functional alterations in vagal sensory neurons were characterized in a chronic porcine infarct model and compared with normal animals. Myocardial infarction caused an increase in the number of nociceptive neurons but a paradoxical decrease in functional nociceptive signaling. No changes in mechanosensitive neurons were observed. Notably, nociceptive neurons demonstrated an increase in GABAergic expression. Given that nociceptive signaling through the vagal ganglia increases efferent vagal tone, the results of this study suggest that a decrease in functional nociception, possibly due to an increase in expression of inhibitory neurotransmitters, may contribute to vagal withdrawal after myocardial infarction.

Background\udGeneralized anxiety and depression are extremely prevalent and debilitating. There is evidence for age and sex variability in symptoms of depression, but despite comorbidity it is unclear whether this extends to anxiety symptomatology. Studies using questionnaire sum scores typically fail to address this phenotypic complexity.\ud\udMethod\udWe conducted exploratory and confirmatory factor analyses on Generalized Anxiety Disorder (GAD-7) and Patient Health Questionnaire (PHQ-9) items to identify latent factors of anxiety and depression in participants from the Genetic Links to Anxiety and Depression Study (N = 35,637; 16–93 years). We assessed age- and sex-related variability in latent factors and individual symptoms using multiple logistic regression.\ud\udResults\udFour factors of mood, worry, motor, and somatic symptoms were identified (comparative fit index [CFI] = 0.99, Tucker–Lewis Index [TLI] = 0.99, root mean square error of approximation [RMSEA] = 0.07, standardized root mean square residuals [SRMR] = 0.04). Symptoms of irritability (odds ratio [OR] = 0.81) were most strongly associated with younger age, and sleep change (OR = 1.14) with older age. Males were more likely to report mood and motor symptoms (p

Endometriosis is known to impact work productivity. The COVID-19 pandemic resulted in a shift in working practices for many, with an increase in working from home and/or flexible working hours. The aim of this online cross-sectional study was to determine if these changes resulted in changes in symptom management and productivity in Australian people with endometriosis. Three hundred and eighty-nine people responded to the survey. The majority of respondents found that their endometriosis symptoms were much easier to manage, and they were more productive. A key factor was flexibility in work hours and the increased ability to self-manage their time.

OBJECTIVE To assess the general population's knowledge regarding the utility and availability of tools to diagnosis endometriosis, with a focus on ultrasound. DESIGN An international cross-sectional online survey study was performed between August and October 2019. SETTING AND POPULATION 5301 respondents, representing 73 countries. METHODS In all, 23 questions survey focused on knowledge of endometriosis diagnosis distributed globally via patient- and community-endometriosis groups using social media. MAIN OUTCOMES AND MEASURES Descriptive data of the knowledge of diagnostic tools for diagnosing endometriosis, including details about diagnosis using ultrasound. RESULTS In all, 84.0% of respondents had been previously diagnosed with endometriosis, 71.5% of whom had been diagnosed at the time of surgery. Ultrasound and MRI were the methods of diagnosis in 6.5% and 1.8%, respectively. A total of 91.8%, 28.8% and 16.6% of respondents believed surgery, ultrasound and MRI could diagnose endometriosis, respectively (more than one answer allowed). In those diagnosed by surgery, 21.7% knew about ultrasound as a diagnosis method, whereas in those diagnosed non-surgically, 51.5% knew (P

Background Chronic pelvic pain (CPP) in women is persistent, intermittent cyclical and non-cyclical lower abdominal pain, lasting for more than 6 months. Traditional Chinese Medicine (TCM) is a popular treatment option for women’s health conditions, but little is known about how treatment for CPP is delivered by TCM practitioners. The aim of this survey was to explore practitioners understanding and treatment of women with CPP, and how they integrate their management and care into the health care system. Method An online cross-sectional survey of registered TCM practitioners in Australia and New Zealand between May and October 2018. Survey domains included treatment characteristics (e.g. frequency), evaluation of treatment efficacy, referral networks, and sources of information that informed clinical decision making. Results One hundred and twenty-two registered TCM practitioners responded to this survey, 91.7% reported regular treatment of women with CPP. Treatment decisions were most-often guided by a combination of biomedical and TCM diagnosis (77.6%), and once per week was the most common treatment frequency (66.7%) for acupuncture. Meditation (63.7%) and dietary changes (57.8%) were other commonly used approaches to management. The effectiveness of treatment was assessed using multiple approaches, most commonly pain scales, (such as the numeric rating scale) and any change in use of analgesic medications. Limitations to TCM treatment were reported by over three quarters (83.7%) of practitioners, most commonly due to cost (56.5%) and inconvenience (40.2%) rather than safety or lack of efficacy. Sources informing practice were most often Integration within the wider healthcare system was common with over two thirds (67.9%) receiving referrals from health care providers. Conclusion TCM practitioners seeing women with various CPP symptoms, commonly incorporate both traditional and modern diagnostic methods to inform their treatment plan, monitor treatment progress using commonly accepted approaches and measures and often as a part of multidisciplinary healthcare for women with CPP.

Background: Complex Posttraumatic Stress Disorder (C-PTSD) was recently included in the revised International Classification of Diseases (ICD-11) by the World Health Organization (WHO, 2018). C-PTSD is a new trauma related disorder which may develop after prolonged and multiple exposures to trauma. It is a sister disorder of PTSD and is further characterized by symptomatology of disorganized self-organization (DSO). To qualify for the diagnosis, individuals must first meet the diagnostic criteria for PTSD, then report DSO symptoms and functional impairment. A body of work is emerging which has focused on the underlying dimensionality of C-PTSD across both adult and more recently adolescent populations from differing index trauma groups and from across several nations and cultures. However, few studies have been conducted in populations exposed to combat trauma despite the obvious prolonged and multiple nature of their trauma histories. Objective: To contribute to emerging evidence of the factor structure of ICD-11 C-PTSD in a novel population. Methods: This is the first factor analytic study to explore C-PTSD in a sample of UK Armed Forces veterans residing in Northern Ireland (N = 732). C-PTSD was measured via the ITQ and we utilized CFA to assess the fit of 7 competing models. Results: Based on established CFA fit indices, a correlated, first order, 6-factor model of C-PTSD, representing 3 PTSD and 3 DSO symptom groupings, was deemed to provide superior fit to the data compared to 6 alternative C-PTSD models. The superiority of the model was further supported by statistical comparisons of competing C-PTSD models. All factor loadings (0.866–0.998) and inter-factor correlations (.746-.975) of the optimally fitting model were statistically significant and high. Conclusion: These results provide support for the construct validity of ICD-11 C-PTSD in a unique sample of Armed Forces veterans residing in Northern Ireland., HIGHLIGHTS This is the first factor analytic study to explore C-PTSD in a sample of UK Armed Forces veterans residing in Northern Ireland.A correlated, first order, 6-factor model of C-PTSD, was deemed to provide superior fit to the data compared to 6 alternative C-PTSD models.These results provide support for the construct validity of ICD-11 C-PTSD.

We performed a systematic review and meta-analysis with the aim to answer whether operative laparoscopy is an effective treatment in a woman with demonstrated endometriosis compared with alternative treatments. Moreover, we aimed to assess the risks of operative laparoscopy compared with those of alternatives. In addition, we aimed to systematically review the literature on the impact of patient preference on decision making around surgery.We searched MEDLINE, Embase, PsycINFO, ClinicalTrials.gov, CINAHL, Scopus, OpenGrey, and Web of Science from inception through May 2019. In addition, a manual search of reference lists of relevant studies was conducted.Published and unpublished randomized controlled trials (RCTs) in any language describing a comparison between surgery and any other intervention were included, with particular reference to timing and its impact on pain and fertility. Studies reporting on keywords including, but not limited to, endometriosis, laparoscopy, pelvic pain, and infertility were included. In the anticipated absence of RCTs on patient preference, all original research on this topic was considered eligible.In total, 1990 studies were reviewed. Twelve studies were identified as being eligible for inclusion to assess outcomes of pain (n = 6), fertility (n = 7), quality of life (n = 1), and disease progression (n = 3). Seven studies of interest were identified to evaluate patient preferences. There is evidence that operative laparoscopy may improve overall pain levels at 6 months compared with diagnostic laparoscopy (risk ratio [RR], 2.65; 95% confidence interval [CI], 1.61-4.34; p.001; 2 RCTs, 102 participants; low-quality evidence). Because the quality of the evidence was very low, it is uncertain if operative laparoscopy improves live birth rates. Operative laparoscopy probably yields little or no difference regarding clinical pregnancy rates compared with diagnostic laparoscopy (RR, 1.29; 95% CI, 0.99-1.92; p = .06; 4 RCTs, 624 participants; moderate-quality evidence). It is uncertain if operative laparoscopy yields a difference in adverse outcomes when compared with diagnostic laparoscopy (RR, 1.98; 95% CI, 0.84-4.65; p = .12; 5 RCTs, 554 participants; very-low-quality evidence). No studies reported on the progression of endometriosis to a symptomatic state or progression of extent of disease in terms of volume of lesions and locations in asymptomatic women with endometriosis. We found no studies that reported on the timing of surgery. No quantitative or qualitative studies specifically aimed at elucidating the factors informing a woman's choice for surgery were identified.Operative laparoscopy may improve overall pain levels but may have little or no difference with respect to fertility-related or adverse outcomes when compared with diagnostic laparoscopy. Additional high-quality RCTs, including comparing surgery to medical management, are needed, and these should report adverse events as an outcome. Studies on patient preference in surgical decision making are needed (International Prospective Register of Systematic Review registration number: CRD42019135167).

Aberrant afferent signaling drives adverse remodeling of the cardiac nervous system in ischemic heart disease. The study objective was to determine whether thoracic spinal dorsal column stimulation (SCS) modulates cardiac afferent sensory transduction of the ischemic ventricle. In anesthetized canines ( n = 16), extracellular activity generated by 62 dorsal root ganglia (DRG) soma (T1-T3), with verified myocardial ischemic (MI) sensitivity, were evaluated with and without 20-min preemptive SCS (T1-T3 spinal level; 50 Hz, 90% motor threshold). Transient MI was induced by 1-min coronary artery occlusion (CAO) of the left anterior descending (LAD) or circumflex (LCX) artery, randomized as to sequence. LAD and LCX CAO activated cardiac-related DRG neurons (LAD: 0.15 ± 0.04–1.05 ± 0.20 Hz, P < 0.00002; LCX: 0.08 ± 0.02–1.90 ± 0.45 Hz, P < 0.0003). SCS decreased basal neuronal activity of neurons that responded to LAD (0.15 ± 0.04 to 0.02 ± 0.01 Hz, P < 0.006) and LCX (0.08 ± 0.02 to 0.02 ± 0.01 Hz, P < 0.003). SCS suppressed responsiveness to transient MI (LAD: 1.05 ± 0.20–0.03 ± 0.01 Hz; P < 0.0001; LCX: 1.90 ± 0.45–0.03 ± 0.01 Hz; P < 0.001). Suprathreshold SCS (1 Hz) did not activate DRG neurons antidromically ( n = 10 animals). Ventricular fibrillation (VF) was associated with a rapid increase in DRG activity to a maximum of 4.39 ± 1.07 Hz at 20 s after VF induction and a return to 90% of baseline within 10 s thereafter. SCS obtunds the capacity of DRG ventricular neurites to transduce the ischemic myocardium to second-order spinal neurons, a mechanism that would blunt reflex sympathoexcitation to myocardial ischemic stress, thereby contributing to its capacity to cardioprotect. NEW & NOTEWORTHY Aberrant afferent signaling drives adverse remodeling of the cardiac nervous system in ischemic heart disease. This study determined that thoracic spinal column stimulation (SCS) obtunds the capacity of dorsal root ganglia ventricular afferent neurons to transduce the ischemic myocardium to second-order spinal neurons, a mechanism that would blunt reflex sympathoexcitation to myocardial ischemic stress. This modulation does not reflect antidromic actions of SCS but likely reflects efferent-mediated changes at the myocyte-sensory neurite interface. Listen to this article’s corresponding podcast at https://ajpheart.podbean.com/e/spinal-cord-stimulation-blunts-dorsal-root-transduction-of-the-ischemic-ventricle/ .

Due to the higher incidence of hormone responsive tumours in women >50, the safety of hormone replacement therapy (HRT) in older breast cancer survivors may differ from younger age groups. The primary outcome in this review was the risk of tumour recurrence and secondary outcome the relationship with breast cancer-related mortality. Medline, CINAHL, Cochrane, Google Scholar and EMBASE databases were searched through August 2018 for studies reporting exposure to HRT in survivors ≥50 at primary diagnosis. Random effects models were used to estimate the combined relative risk (RR) of tumour recurrence and breast cancer-related mortality using the Mantel-Haenszel method and the quality of evidence determined for the primary outcome. Overall, nine studies (four cohort, one case-control, four RCTs; n = 16,002) were included. Very low quality evidence from observational studies demonstrated no adverse effect on tumour recurrence with HRT use (RR 0.80, 95% CI 0.53 to 1.19; I2 = 66%; n = 11,984), while moderate quality evidence from RCTS demonstrated an adverse effect (RR 1.46, 95% CI 1.20 to 1.77; I2 = 17%; n = 4108). Similarly, observational studies demonstrated no adverse effect on breast cancer-related mortality (RR 0.32, 95% CI 0.21 to 1.49; I2 = 0%, n = 2182), while RCTs demonstrated a non-significant higher risk (RR 1.07, 95% CI 0.77 to 1.49; I2 = 0%; n = 3918). Ultimately, despite conflicting findings, evidence of sufficient quality suggests that HRT may increase the risk of tumour recurrence in older survivors. However, adverse effect on mortality is unlikely. Caution with HRT use in survivors is further advised.

Nontruncating sequence variants represent a major challenge in variant interpretation and classification. Here, we report a patient with features of Kabuki syndrome who carries two rare heterozygous variants in KMT2D: c.12935C>T, p.(Ser4312Phe) and c.15785-10T>G. The clinical significance of these variants were discordantly interpreted by different diagnostic laboratories. Parental testing showed that the missense variant was inherited from the father with a mild Kabuki phenotype and the intronic variant from the mother with mosaic status. Through genome-wide DNA methylation analysis of peripheral blood, we confirmed that the proband exhibited a previously described episignature of Kabuki syndrome. Parental samples had normal DNA methylation profiles, thus ruling out the involvement of the paternally inherited missense variant. RNA analysis revealed that the intronic change resulted in exon 49 skipping and frameshift, thereby providing a molecular diagnosis of Kabuki syndrome. This study demonstrates the utility of epigenomic and RNA analyses in resolving ambiguous clinical cases.