Differential effects of high-fat diet on endocrine, metabolic and depressive-like behaviors in male and female rats.

The complications of obesity extend beyond the periphery to the central nervous system (CNS) and include an increased risk of developing neuropsychiatric co-morbidities like depressive illness. Preclinical studies support this concept, including studies that have examined the effects of a high-fat diet (HFD) on depressive-like behaviors. Although women are approximately two-fold more likely to develop depressive illness compared to men, most preclinical studies have focused on the effects of HFD in male rodents. Accordingly, the goal of this study was to examine depressive-like behaviors in male and female rats provided access to a HFD. In agreement with prior studies, male and female rats provided a HFD segregate into an obesity phenotype (i.e., diet-induced obesity; DIO) or a diet resistant (DR) phenotype. Upon confirmation of the DR and DIO phenotypes, behavioral assays were performed in control chow, DR, and DIO rats. In the sucrose preference test, male DIO rats exhibited significant decreases in sucrose consumption (i.e., anhedonia) compared to male DR and male control rats. In the forced swim test (FST), male DIO rats exhibited increases in immobility and decreases in climbing behaviors in the pre-test sessions. Interestingly, male DR rats exhibited these same changes in both the pre-test and test sessions of the FST, suggesting that consumption of a HFD, even in the absence of the development of an obesity phenotype, has behavioral consequences. Female rats did not exhibit differences in sucrose preference, but female DIO rats exhibited increases in immobility exclusively in the test session of the FST, behavioral changes that were not affected by the stage of the estrous cycle. Collectively, these studies demonstrate that access to a HFD elicits different behavioral outcomes in male and female rats.

Daily artificial gravity partially mitigates vestibular processing changes associated with head-down tilt bedrest.

Microgravity alters vestibular signaling and reduces body loading, driving sensory reweighting. The unloading effects can be modelled using head-down tilt bedrest (HDT). Artificial gravity (AG) has been hypothesized to serve as an integrated countermeasure for the declines associated with HDT and spaceflight. Here, we examined the efficacy of 30 min of daily AG to counteract brain and behavior changes from 60 days of HDT. Two groups received 30 min of AG delivered via short-arm centrifuge daily (n = 8 per condition), either in one continuous bout, or in 6 bouts of 5 min. To improve statistical power, we combined these groups (AG; n = 16). Another group served as controls in HDT with no AG (CTRL; n = 8). We examined how HDT and AG affect vestibular processing by collecting fMRI scans during vestibular stimulation. We collected these data prior to, during, and post-HDT. We assessed brain activation initially in 12 regions of interest (ROIs) and then conducted an exploratory whole brain analysis. The AG group showed no changes in activation during vestibular stimulation in a cerebellar ROI, whereas the CTRL group showed decreased activation specific to HDT. Those that received AG and showed little pre- to post-HDT changes in left vestibular cortex activation had better post-HDT balance performance. Whole brain analyses identified increased pre- to during-HDT activation in CTRLs in the right precentral gyrus and right inferior frontal gyrus, whereas AG maintained pre-HDT activation levels. These results indicate that AG could mitigate activation changes in vestibular processing that is associated with better balance performance.

Co-delivery of HIV pre-exposure prophylaxis (PrEP) and HIV testing among publicly insured adolescents and young adults (AYA) receiving medication for opioid use disorder (MOUD).

BACKGROUND: Low rates of HIV pre-exposure prophylaxis (PrEP) prescribing contribute to the disproportionate burden of HIV in the United States. Among adolescent and young adults (AYA) with opioid use disorder, HIV testing and PrEP co-prescription rates are poorly characterized. METHODS: We performed a retrospective analysis involving deidentified data from Philadelphia's Medicaid beneficiaries ages 16-29 years who were prescribed medication for opioid use disorder (MOUD) from 2015 to 2020 and continuously Medicaid-enrolled for ≥6 months prior to that prescription. After identifying the presence of a qualifying diagnosis signifying a PrEP indication, we examined the outcome of appropriate PrEP co-prescriptions and HIV testing using generalized estimating equations (GEE) modeling. RESULTS: We identified 795 AYA Medicaid beneficiaries with 1269 qualified treatment episodes. We calculated a PrEP prescribing rate of 29.47 per 1000 person-years among AYA receiving MOUD. The HIV testing rate was 63.47 per 1000 person-years among AYA receiving MOUD. GEE modeling revealed that individuals receiving methadone were more likely (aOR=2.62, 95% CI=1.06-6.49) to receive HIV testing within 6 months after a PrEP-qualifying diagnosis compared to those receiving other MOUD medications. Those who only saw outpatient behavioral health providers were less likely (aOR=0.48, 95% CI=0.24-0.99) to have received an HIV test within 6 months after the PrEP-qualifying diagnosis compared to those receiving inpatient behavioral health services. CONCLUSIONS: Co-prescription of PrEP and HIV testing among AYA receiving MOUD was rare in this large urban publicly insured population. Interventions are needed to increase HIV prevention services for this key population of AYA at risk for HIV infection.

Post-acute COVID-19 complications in UK doctors: results of a cross-sectional survey.

BACKGROUND: As a consequence of their occupation, doctors and other healthcare workers were at higher risk of contracting coronavirus disease 2019 (COVID-19), and more likely to experience severe disease compared to the general population. However, systematic information on post-acute COVID complications in doctors is very limited. AIMS: This study aimed to determine the symptoms, perceived determinants, health and occupational impact, and consequent needs relating to post-acute COVID complications in UK doctors. METHODS: An online cross-sectional survey was distributed to UK doctors self-identifying as having Long COVID or other post-acute COVID complications. RESULTS: Of 795 responses, 603 fulfilled the inclusion criteria of being a UK-based medical doctor experiencing one or more post-acute COVID complications. Twenty-eight per cent reported a lack of adequate Respiratory Protective Equipment at the time of contracting COVID-19. Eighteen per cent of eligible respondents reported that they had been unable to return to work since acquiring COVID. CONCLUSIONS: Post-acute COVID (Long COVID) in UK doctors is a substantial burden for respondents to our questionnaire. The results indicated that insufficient respiratory protection could have contributed to occupational disease, with COVID-19 being contracted in the workplace, and resultant post-COVID complications. Although it may be too late to address the perceived determinants of inadequate protection for those already suffering with Long COVID, more investment is needed in rehabilitation and support of those afflicted.

The relationship between subjective sleep disturbance and attenuated psychotic symptoms after accounting for anxiety and depressive symptoms.

BACKGROUND AND HYPOTHESES: Sleep disturbances are increasingly recognized as cooccurring with psychotic symptoms. The potential importance of this relationship is complicated when considering the effects of anxiety and depressive symptoms which commonly present in early-stage illness states. This study aimed to investigate the relationship between self-reported sleep disturbance on the development of attenuated psychotic symptoms (APS) cross-sectionally and longitudinally while adjusting for roles of anxiety and depressive symptoms. DESIGN: Eight-hundred and two help-seeking young people aged 12 to 25 years who engaged with our Australian early intervention services were included in the study (the "Transitions" cohort). Cross sectional mediation and cross-lagged longitudinal (12-month) mediation models were developed with outcomes being different APS domains. RESULTS: Only baseline excessive daytime sleepiness predicted later APS when accounting for previous APS, anxiety and depressive symptomatology. Cross sectionally, self-reported sleep disturbance showed both direct and indirect predictive relationships with all APS domains. Partial mediation through anxiety and depression was shown for unusual thought content, perceptual abnormalities, and disorganised speech, while full mediation through depression was shown for non-bizarre ideas. CONCLUSIONS: The specificity of the relationship between self-reported sleep disturbance on APS highlights the potential for different roles in mechanistic models of psychotic symptom expression. This further indicates the need for further experimental research to illuminate potential causal pathways. Future research should continue to use continuous, symptom level approaches across a range of timeframes to more accurately model the complex dynamics present in the sleep-psychosis relationship.

Using network analysis to detect associations between suspected painful health conditions and behaviour in dogs.

Pain associated with chronic health conditions in non-human animals is an important animal welfare issue. To identify animals in pain and develop an understanding of the mechanisms by which pain affects behaviour, it is therefore important to establish the direct behavioural effects of painful health conditions. We reanalyse data from a cross-sectional survey that considered the presence or absence of a painful condition in dogs and quantified their affective predispositions using the Positive and Negative Activation Scale (PANAS). By applying ideas from network theory, we conceptualise pain as a stressor that exerts direct effects on a network of interacting behavioural variables, and subsequently estimated a network model of conditional dependence relations. Painful health conditions were positively conditionally associated with age (posterior mean partial correlation, ρ = 0.34; standard deviation [SD]=0.05), and negatively conditionally associated with the item 'your dog is full of energy' (ρ = -0.14; SD=0.06). In turn, the energy item was conditionally associated with other PANAS items which were marginally associated with pain, such as items representing ease of excitability and persistence in play. This suggests these marginal effects might be indirectly mediated via the energy item. Further, utilising the posterior predictive distribution we estimated that the median conditional probability (95% credible interval) of a painful health condition given an answer of 'strongly agree' on the energy item was 0.08 (0.05, 0.11), which increased to 0.32 (0.09, 0.58), given a response of 'strongly disagree'. This provides a potentially clinically useful interpretation of the conditional dependencies detected in the network.

Musculoskeletal injuries in UK Service Personnel and the impact of in-theatre rehabilitation during Cold Weather Warfare training: Exercise CETUS 2020.

INTRODUCTION: The Royal Marines provide the lead Service for UK Defence Mountain and Cold Weather Warfare capability. This is the first prospective study addressing musculoskeletal injury rates sustained during Cold Weather Warfare training, with the aim of informing injury mitigation interventions and assist military medical planning with respect to delivering primary care rehabilitation in theatre. METHODS: All musculoskeletal injuries were surveyed by the Forward Rehabilitation Team (Nov 2019-Mar 2020) during a Cold Weather Deployment to Norway (Ex CETUS 2019/20). The frequency, nature of injury (new or recurrent), onset (sudden or gradual), cause, location and exercise/treatment outcome were recorded. RESULTS: Eleven per cent (n=136 cases) of the deployed population (n=1179) reported a musculoskeletal injury, which were mainly 'new' (62%), and with a 'sudden' onset (64%). Injury rate was 17.8 injuries per 10 000 personnel days. The majority of injuries occurred due to military training (88%), specifically during ski-related (61%) and load carriage (10%) activities.The average Service Person treated by the Forward Rehabilitation Team improved from 'injured with restricted duties' to 'fully fit', and with an improvement in their self-reported Musculoskeletal Health Questionnaire from 33 to 45 over an average of two rehabilitation sessions. One hundred and seventeen Service Personnel were able to continue on Ex CETUS with rehabilitation in theatre, thus negating the requirement for aeromedical evacuation for continuation of rehabilitation in the UK. Nineteen patients were unable to continue their Cold Weather Deployment due to the nature of their musculoskeletal injury and returned to the UK for continued care in firm base rehabilitation centres. CONCLUSION: This study identifies the nature, causation and injury location. It demonstrates the effectiveness of in-theatre rehabilitation and the ability to treat patients when deployed. Recommendations are presented to support strategies to mitigate musculoskeletal injury risk during future Cold Weather Warfare deployments to Norway.

Trends in sexually transmitted infection screening during COVID-19 and missed cases among adolescents.

OBJECTIVE: The COVID-19 pandemic disrupted sexual health services for young people, with potential consequences of decreasing preventive screening and increasing undiagnosed sexually transmitted infections (STIs). This study aimed to assess trends in asymptomatic screening among patients receiving STI testing and to estimate the number of STI cases that were missed during the early months of the pandemic. STUDY DESIGN: A cross-sectional study of electronic health records for chlamydia, gonorrhea, and trichomonas testing encounters from six pediatric primary care clinics in Philadelphia, July 2014 to November 2020. METHODS: A total of 35,548 testing encounters were analyzed, including 2958 during the pandemic. We assessed whether testing at each encounter was performed as asymptomatic screening, risk-based testing, or symptomatic testing. We evaluated screening trends over time and estimated the number of missed STI cases during the pandemic. RESULTS: The mean monthly testing encounters decreased from 479 per month prepandemic to 329 per month during the pandemic. The percent of tests performed as asymptomatic screening dropped from 72.5% prepandemic to a nadir of 54.5% in April 2020. We estimate that this decrease in asymptomatic screening would represent 159 missed cases (23.8% of expected cases) based on patient volume from the previous year. CONCLUSIONS: During the pandemic, the total volume of STI testing encounters and the proportion of tests performed as asymptomatic screening decreased, potentially resulting in missed diagnoses. Undiagnosed STIs can result in severe sequelae and contribute to community transmission of STIs. Efforts are needed to re-establish and sustain access to STI services for adolescents in response to disruptions caused by the pandemic.

ctDNA as a biomarker of progression in oesophageal adenocarcinoma.

BACKGROUND: The incidence of oesophageal adenocarcinoma (OAC) is rapidly increasing and despite improvements in treatment, the 5-year survival rate remains poor. Prognostic biomarkers that address the genomic heterogeneity in this highly complex disease will aid the development of precision therapeutics and improve patient survival. The aim of this study was to determine whether circulating tumour DNA (ctDNA) has prognostic significance as a biomarker in OAC patients. PATIENTS AND METHODS: We profiled 209 blood and tumour samples from 57 OAC patients. Using a panel of 77 cancer genes, we sequenced ctDNA in plasma samples (n = 127) which were taken at multiple time points before and after therapy. In parallel, we sequenced matched tumour samples from 39 patients using the same gene panel. To assess whether the ctDNA profile reflected the tumour heterogeneity, we sequenced additional multi-region primary tumour samples in 17 patients. In addition, we analysed whole-genome and whole-exome sequencing data from primary tumours for a subset of 18 patients. RESULTS: Using a tumour-agnostic approach, we found that detectable ctDNA variants in post-treatment plasma samples were associated with worse disease-specific survival. To evaluate whether the ctDNA originated from the primary tumour, we carried out a tumour-informed analysis which confirmed post-treatment ctDNA variants were associated with worse survival. To determine whether ctDNA could be used as a clinical follow-up test, we assessed blood samples from multiple time points before and after treatment, in a subset of patients. Results showed that the variant allele frequency of ctDNA variants increased with disease recurrence. CONCLUSION: This study demonstrates that ctDNA variants can be detected in patients with OAC and this has potential clinical utility as a prognostic biomarker for survival.

Comparison of actionable events detected in cancer genomes by whole-genome sequencing, in silico whole-exome and mutation panels.

BACKGROUND: Next-generation sequencing is used in cancer research to identify somatic and germline mutations, which can predict sensitivity or resistance to therapies, and may be a useful tool to reveal drug repurposing opportunities between tumour types. Multigene panels are used in clinical practice for detecting targetable mutations. However, the value of clinical whole-exome sequencing (WES) and whole-genome sequencing (WGS) for cancer care is less defined, specifically as the majority of variants found using these technologies are of uncertain significance. PATIENTS AND METHODS: We used the Cancer Genome Interpreter and WGS in 726 tumours spanning 10 cancer types to identify drug repurposing opportunities. We compare the ability of WGS to detect actionable variants, tumour mutation burden (TMB) and microsatellite instability (MSI) by using in silico down-sampled data to mimic WES, a comprehensive sequencing panel and a hotspot mutation panel. RESULTS: We reveal drug repurposing opportunities as numerous biomarkers are shared across many solid tumour types. Comprehensive panels identify the majority of approved actionable mutations, with WGS detecting more candidate actionable mutations for biomarkers currently in clinical trials. Moreover, estimated values for TMB and MSI vary when calculated from WGS, WES and panel data, and are dependent on whether all mutations or only non-synonymous mutations were used. Our results suggest that TMB and MSI thresholds should not only be tumour-dependent, but also be sequencing platform-dependent. CONCLUSIONS: There is a large opportunity to repurpose cancer drugs, and these data suggest that comprehensive sequencing is an invaluable source of information to guide clinical decisions by facilitating precision medicine and may provide a wealth of information for future studies. Furthermore, the sequencing and analysis approach used to estimate TMB may have clinical implications if a hard threshold is used to indicate which patients may respond to immunotherapy.

Opportunities to improve the impact of two national clinical audit programmes: a theory-guided analysis.

BACKGROUND: Audit and feedback is widely used in healthcare improvement, with evidence of modest yet potentially important effects upon professional practice. There are approximately 60 national clinical audit programmes in the UK. These programmes often develop and adapt new ways of delivering feedback to optimise impacts on clinical practice. Two such programmes, the National Diabetes Audit (NDA) and the Trauma Audit Research Network (TARN), recently introduced changes to their delivery of feedback. We assessed the extent to which the design of these audit programmes and their recent changes were consistent with best practice according to the Clinical Performance Feedback Intervention Theory (CP-FIT). This comprehensive framework specifies how variables related to the feedback itself, the recipient, and the context operate via explanatory mechanisms to influence feedback success. METHODS: We interviewed 19 individuals with interests in audit and feedback, including researchers, audit managers, healthcare staff, and patient and public representatives. This range of expert perspectives enabled a detailed exploration of feedback from the audit programmes. We structured interviews around the CP-FIT feedback cycle and its component processes (e.g. Data collection and analysis, Interaction). Our rapid analytic approach explored the extent to which both audits applied features consistent with CP-FIT. RESULTS: Changes introduced by the audit programmes were consistent with CP-FIT. Specifically, the NDA's increased frequency of feedback augmented existing strengths, such as automated processes (CP-FIT component: Data collection and analysis) and being a credible source of feedback (Acceptance). TARN's new analytic tool allowed greater interactivity, enabling recipients to interrogate their data (Verification; Acceptance). We also identified scope for improvement in feedback cycles, such as targeting of feedback recipients (Interaction) and feedback complexity (Perception) for the NDA and specifying recommendations (Intention) and demonstrating impact (Clinical performance improvement) for TARN. CONCLUSIONS: The changes made by the two audit programmes appear consistent with suggested best practice, making clinical improvement more likely. However, observed weaknesses in the feedback cycle may limit the benefits of these changes. Applying CP-FIT via a rapid analysis approach helps identify strengths and remediable weaknesses in the design of audit programmes that can be shared with them in a timely manner.

Commercial weight management programmes for patients living with overweight or obesity prior to elective orthopaedic surgery: an evidence review.

BACKGROUND: Increased body mass index is associated with increased operative risk during elective joint replacement surgery. Commercial weight management programmes are designed to achieve weight loss. It is not known whether commercial weight management programmes are effective at achieving weight loss in patients awaiting planned hip or knee replacement surgery, or whether achieving significant planned weight loss prior to surgery is associated with changes in surgical outcome. METHODS: A systematic literature search of seven databases was conducted. Reference lists and grey literature were searched, including commercial weight management programme and medical association websites. Four relevant primary interventional studies were identified. RESULTS: There is weak, low-quality evidence from four small studies, of which three demonstrated that commercial weight management programmes initiated between 3 and 6 months prior to elective joint replacement surgery are associated with a statistically significant weight loss and body mass index reduction. There is a weak evidence from two studies that peri- and post-operative complications are similar between control and commercial weight management programme groups. CONCLUSION: There is a paucity of studies investigating commercial weight management programmes aiming to reduce weight in patients living with overweight or obesity awaiting total joint replacement. Further, high-quality research is urgently needed.

Comparison of the survival of different isolates of SARS-CoV-2 in evaporating aerosols.

Numerous variants of SARS-CoV-2 with increased transmissibility have emerged over the course of the pandemic. Potential explanations for the increased transmissibility of these variants include increased shedding from infected individuals, increased environmental stability, and/or a lower infectious dose. Upon exhalation of a respiratory particle into the environment, water present in the particle is rapidly lost through evaporation, resulting in a decrease in particle size. The aim of the present study was to compare the losses of infectivity of different isolates of SARS-CoV-2 during the rapid evaporation of aerosol particles that occurs immediately post-generation to assess if there are differences suggestive of increased survival, and ultimately greater transmissibility, for more recent variants. Losses of infectivity of several isolates of SARS-CoV-2 suspended in viral culture media were assessed following aerosolization and evaporation in a flowing chamber. The results demonstrate that losses of infectivity measured post-evaporation were similar for three different isolates of SARS-CoV-2, including isolates from the more recent Delta and Omicron lineages. The average loss in infectivity across all three isolates was 61 ± 15% (-0.46 ± 0.17 log10 TCID50/L-air) at a relative humidity <30%. These results, together with those from several previous studies, suggest that it is unlikely that an increase in environmental stability contributes to the observed increases in transmissibility observed with more recent variants of SARS-CoV-2.

The phenomenology of auditory verbal hallucinations in emotionally unstable personality disorder and post-traumatic stress disorder.

OBJECTIVE: To explore the phenomenology of auditory verbal hallucinations (AVHs) in a clinical sample of young people who have a 'non-psychotic' diagnosis. METHODS: Ten participants aged 17-31 years with presentation of emotionally unstable personality disorder or post-traumatic stress disorder and frequent AVHs were recruited and participated in a qualitative study exploring their subjective experience of hearing voices. Photo-elicitation and ethnographic diaries were used to stimulate discussion in an otherwise unstructured walking interview. RESULTS: 'Non-psychotic' voices comprised auditory qualities such as volume and clarity. Participants commonly personified their voices, viewing them as distinct characters with which they could interact and form relationships. There appeared to be an intimate and unstable relationship between participant and voice, whereby voices changed according to the participants' mood, insecurities, distress and circumstance. Equally, participants reacted to provocation by the voice, leading to changes in mood and circumstance through emotional and physical disturbances. In contrast to our previous qualitative work in psychosis, voice hearing was not experienced with a sense of imposition or control. CONCLUSIONS: This phenomenological research yielded in-depth and novel accounts of 'non-psychotic' voices which were intimately linked to emotional experience. In contrast to standard reports of voices in disorders such as schizophrenia, participants described a complex and bi-directional relationship with their voices. Many other features were in common with voice hearing in psychosis. Knowledge of the phenomenology of hallucinations in non-psychotic disorders has the potential to inform future more successful management strategies. This report gives preliminary evidence for future research.

Has improved treatment contributed to the declining rate of transition to psychosis in ultra-high-risk cohorts?

BACKGROUND: The factors contributing to declining psychotic disorder transition rates in ultra-high-risk populations remain unclear. We examined the contribution of longitudinal changes in standard clinical treatment ('treatment as usual') to this decline. METHOD: An audit was conducted on 105 clinical files of patients who received standard care at a specialised ultra-high-risk service. The session notes of these files were quantified, allowing examination of treatment quantity, targets, psychotherapy, and medication. Differences in these aspects across patients' year of clinic entry were assessed. Variables with significant differences across years were examined using cox regression to assess their contribution to psychosis transition rates. RESULTS: Findings were that, as a function of patients' year of clinic entry, there were increases in: patients' number of sessions, cognitive behavioural therapy (CBT), problem and solving therapy. There was a relationship between baseline year cohort and psychosis transition rate, with lower rates observed in more recent cohorts. When changes in treatment between cohorts were adjusted for, the relationship between baseline year cohort and transition rate disappeared. The relationship between baseline year and transition rate was attenuated most by increases in CBT. CONCLUSION: Changes in standard treatment, particularly increases in CBT, may have contributed to the decline in psychosis risk observed in recent ultra-high-risk cohorts, although these variables do not fully explain this trend. Implications for clinical practice, prediction and intervention research are discussed. Future ultra-high-risk research should investigate the impact of other treatment factors, such as therapeutic alliance.

Brain and Behavioral Evidence for Reweighting of Vestibular Inputs with Long-Duration Spaceflight.

Microgravity alters vestibular signaling. In-flight adaptation to altered vestibular afferents is reflected in post-spaceflight aftereffects, evidenced by declines in vestibularly mediated behaviors (e.g., walking/standing balance), until readaptation to Earth's 1G environment occurs. Here we examine how spaceflight affects neural processing of applied vestibular stimulation. We used fMRI to measure brain activity in response to vestibular stimulation in 15 astronauts pre- and post-spaceflight. We also measured vestibularly-mediated behaviors, including balance, mobility, and rod-and-frame test performance. Data were collected twice preflight and four times postflight. As expected, vestibular stimulation at the preflight sessions elicited activation of the parietal opercular area ("vestibular cortex") and deactivation of somatosensory and visual cortices. Pre- to postflight, we found widespread reductions in this somatosensory and visual cortical deactivation, supporting sensory compensation and reweighting with spaceflight. These pre- to postflight changes in brain activity correlated with changes in eyes closed standing balance, and greater pre- to postflight reductions in deactivation of the visual cortices associated with less postflight balance decline. The observed brain changes recovered to baseline values by 3 months postflight. Together, these findings provide evidence for sensory reweighting and adaptive cortical neuroplasticity with spaceflight. These results have implications for better understanding compensation and adaptation to vestibular functional disruption.

Quantifying changes in ultrasound tongue-shape pre- and post-intervention in speakers with submucous cleft palate: an illustrative case study.

Ultrasound Tongue Imaging is increasingly used during assessment and treatment of speech sound disorders. Recent literature has shown that ultrasound is also useful for the quantitative analysis of a wide range of speech errors. So far, the compensatory articulations of speakers with cleft palate have only been analysed qualitatively. This study provides a pilot quantitative ultrasound analysis, drawing on longitudinal intervention data from a child with submucous cleft palate. Two key ultrasound metrics were used: 1. articulatory t-tests were used to compare tongue-shapes for perceptually collapsed phonemes on a radial measurement grid and 2. the Mean Radial Difference was reported to quantify the extent to which the two tongue shapes differ, overall. This articulatory analysis supplemented impressionistic phonetic transcriptions and identified covert contrasts. Articulatory errors identified in this study using ultrasound were in line with errors identified in the speech of children with cleft palate in previous literature. While compensatory error patterns commonly found in speakers with cleft palate have been argued to facilitate functional phonological development, the nature of our findings suggest that the compensatory articulations uncovered are articulatory in nature.

Impact of Age, Frailty, and Dementia on Prescribing for Type 2 Diabetes at Hospital Discharge 2012-2016.

BACKGROUND: The risks of intensive blood glucose lowering may outweigh the benefits in vulnerable older people. OBJECTIVES: Our primary aim was to determine whether age, frailty, or dementia predict discharge treatment types for patients with type 2 diabetes (T2D) and related complications. Secondly, we aimed to determine the association between prior hypoglycemia and discharge treatment types. DESIGN, SETTING AND PARTICIPANTS: We conducted a cohort study involving 3,067 patients aged 65-99 years with T2D and related complications, discharged from Melbourne's Eastern Health Hospital Network between 2012 and 2016. MEASUREMENTS: Multinomial logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CI) for the association between age, frailty, dementia and hypoglycemia, and being prescribed insulin-only, non-insulin glucose-lowering drugs (GLDs) or combined insulin and non-insulin GLDs compared to no GLD. International Classification of Diseases-10 codes were used to identify dementia status and prior hypoglycemia; frailty was quantified using the Hospital Frailty Risk Score. RESULTS: Insulin-only, non-insulin GLDs, combined insulin and non-insulin GLDs, and no GLDs were prescribed to 19%, 39%, 20%, and 23% of patients, respectively. Patients >80 years were less likely than patients aged 65-80 to be prescribed any of the GLD therapies, (eg. non-insulin GLDs [OR 0.67; 95%CI 0.55-0.82]), compared to no GLD. Similarly, high vs. low frailty scores were associated with not being prescribed any of the three GLD therapies, (eg. non-insulin GLDs [OR 0.63; 95%CI 0.45-0.87]). However, dementia was not associated with discharge prescribing of GLD therapies. Patients with a hypoglycemia-related admission were more likely than those not hospitalized with hypoglycemia to receive insulin-only (OR 4.28; 95%CI 2.89-6.31). CONCLUSIONS: Clinicians consider age and frailty when tailoring diabetes treatment regimens for patients discharged from hospital with T2D and related complications. There is scope to optimize prescribing for patients with dementia and for those admitted with hypoglycemia.

Toxoplasma gondii, Herpesviridae and long-term risk of transition to first-episode psychosis in an ultra high-risk sample.

BACKGROUND: Ultra high-risk (UHR) criteria were introduced to identify people at imminent risk of developing psychosis. To improve prognostic accuracy, additional clinical and biological risk factors have been researched. Associations between psychotic disorders and infections with Toxoplasma gondii and Herpesviridae have been found. It is unknown if exposure to those pathogens increases the risk of transition to psychosis in UHR cohorts. METHODS: We conducted a long-term follow-up of 96 people meeting UHR criteria, previously seen at the Personal Assessment and Crisis Evaluation (PACE) clinic, a specialized service in Melbourne, Australia. Transition to psychosis was assessed using the Comprehensive Assessment of the At-Risk Mental State (CAARMS) and state public mental health records. The relationship between IgG antibodies to Herpesviridae (HSV-1, HSV-2, CMV, EBV, VZV) and Toxoplasma gondii and risk for transition was examined with Cox regression models. RESULTS: Mean follow-up duration was 6.46 (±3.65) years. Participants who transitioned to psychosis (n = 14) had significantly higher antibody titers for Toxoplasma gondii compared to those who did not develop psychosis (p = 0.03). After adjusting for age, gender and year of baseline assessment, seropositivity for Toxoplasma gondii was associated with a 3.6-fold increase in transition hazard in multivariate Cox regression models (HR = 3.6; p = 0.036). No significant association was found between serostatus for Herpesviridae and risk of transition. CONCLUSIONS: Exposure to Toxoplasma gondii may contribute to the manifestation of positive psychotic symptoms and increase the risk of transitioning to psychosis in UHR individuals.

Management of bone metastasis and cancer treatment-induced bone loss during the COVID-19 pandemic: An international perspective and recommendations.

Optimum management of patients with cancer during the COVID-19 pandemic has proved extremely challenging. Patients, clinicians and hospital authorities have had to balance the risks to patients of attending hospital, many of whom are especially vulnerable, with the risks of delaying or modifying cancer treatment. Those whose care has been significantly impacted include patients suffering from the effects of cancer on bone, where delivering the usual standard of care for bone support has often not been possible and clinicians have been forced to seek alternative options for adequate management. At a virtual meeting of the Cancer and Bone Society in July 2020, an expert group shared experiences and solutions to this challenge, following which a questionnaire was sent internationally to the symposium's participants, to explore the issues faced and solutions offered. 70 respondents, from 9 countries (majority USA, 39%, followed by UK, 19%) included 50 clinicians, spread across a diverse range of specialties (but with a high proportion, 64%, of medical oncologists) and 20 who classified themselves as non-clinical (solely lab-based). Spread of clinician specialty across tumour types was breast (65%), prostate (27%), followed by renal, myeloma and melanoma. Analysis showed that management of metastatic bone disease in all solid tumour types and myeloma, adjuvant bisphosphonate breast cancer therapy and cancer treatment induced bone loss, was substantially impacted. Respondents reported delays to routine CT scans (58%), standard bone scans (48%) and MRI scans (46%), though emergency scans were less affected. Delays in palliative radiotherapy for bone pain were reported by 31% of respondents with treatments often involving only a single dose without fractionation. Delays to, or cancellation of, prophylactic surgery for bone pain were reported by 35% of respondents. Access to treatments with intravenous bisphosphonates and subcutaneous denosumab was a major problem, mitigated by provision of drug administration at home or in a local clinic, reduced frequency of administration or switching to oral bisphosphonates taken at home. The questionnaire also revealed damaging delays or complete stopping of both clinical and laboratory research. In addition to an analysis of the questionnaire, this paper presents a rationale and recommendations for adaptation of the normal guidelines for protection of bone health during the pandemic.