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Groups 4 Health (G4H) is a group psychotherapy program that targets social group disconnection. An emerging evidence base supports its efficacy in reducing loneliness, depression, and social anxiety. However, to date there has been no formal analysis of its acceptability to clients and therapists, nor an investigation of its feasibility for wider implementation. This input from end users is crucial to ensure the program's wider suitability and to contribute to its improvement. This study drew data from three clinical trials, including 266 G4H clients and 68 G4H therapists. From the Phase III trial only, additional data were available from 90 clients in a dose-controlled cognitive-behavioral therapy (CBT) comparison group, and focus groups/interviews with 6 therapists and 13 clients. Client satisfaction was high, with all average ratingsgt;7/10, significantly exceeding the CBT comparison group. Therapist satisfaction with each module wasgt;5/7. Retention wasgt;80%. Homework completion was high, withlt;10% of clients saying that they had not attempted the homework. Therapists and clients both emphasized the benefits arising from G4H, and the contribution of the group context itself as a vehicle to achieve positive outcomes.

PTEN is one of the most commonly inactivated tumour suppressor genes in sporadic cancer. Germline heterozygous PTEN gene alterations also underlie PTEN hamartoma tumour syndrome (PHTS), a rare human cancer-predisposition condition. A key feature of systemic PTEN deregulation is the inability to adequately dampen PI3-kinase (PI3K)/mTORC1 signalling. PI3K/mTORC1 pathway inhibitors such as rapamycin are therefore expected to neutralise the impact of PTEN loss, rendering this a more druggable context compared with those of other tumour suppressor pathways such as loss of TP53. However, this has not been explored in cancer prevention in a model of germline cancer predisposition, such as PHTS. Clinical trials of short-term treatment with rapamycin have recently been initiated for PHTS, focusing on cognition and colon polyposis. Here, we administered a low dose of rapamycin from the age of 6 weeks onwards to mice with heterozygous germline Pten loss, a mouse model that recapitulates most characteristics of human PHTS. Rapamycin was well tolerated and led to a highly significant improvement of survival in both male and female mice. This was accompanied by a delay in, but not full blockade of, the development of a range of proliferative lesions, including gastro-intestinal and thyroid tumours and endometrial hyperplasia, with no impact on mammary and prostate tumours, and no effect on brain overgrowth. Our data indicate that rapamycin may have cancer prevention potential in human PHTS. This might also be the case for sporadic cancers in which genetic PI3K pathway activation is an early event in tumour development, such as endometrial cancer and some breast cancers. To the best of our knowledge, this is the first report of a long-term treatment of a germline cancer predisposition model with a PI3K/mTOR pathway inhibitor. © 2022 The Authors. The Journal of Pathology published by John WileySons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Neurons have highlighted the needs for decentralized gene expression and specific RNA function in somato-dendritic and axonal compartments, as well as in intercellular communication via extracellular vesicles (EVs). Despite advances in miRNA biology, the identity and regulatory capacity of other small non-coding RNAs (sncRNAs) in neuronal models and local subdomains has been largely unexplored.We identified a highly complex and differentially localized content of sncRNAs in axons and EVs during early neuronal development of cortical primary neurons and in adult axons invivo. This content goes far beyond miRNAs and includes most known sncRNAs and precisely processed fragments from tRNAs, sno/snRNAs, Y RNAs and vtRNAs. Although miRNAs are the major sncRNA biotype in whole-cell samples, their relative abundance is significantly decreased in axons and neuronal EVs, where specific tRNA fragments (tRFs and tRHs/tiRNAs) mainly derived from tRNAs Gly-GCC, Val-CAC and Val-AAC predominate. Notably, although 5'-tRHs compose the great majority of tRNA-derived fragments observed invitro, a shift to 3'-tRNAs is observed in mature axons invivo.The existence of these complex sncRNA populations that are specific to distinct neuronal subdomains and selectively incorporated into EVs, equip neurons with key molecular tools for spatiotemporal functional control and cell-to-cell communication. ispartof: RNA BIOLOGY vol:18 issue:sup2 pages:832-855 ispartof: location:United States status: published

The present research applied the social identity approach to examine how the perceived legitimacy of weight-based discrimination among ingroup members influences their experience of their higher-weight identity and their well-being, and the conditions under which this occurs. Specifically, we investigated whether portraying weight-based discrimination as legitimate, as opposed to illegitimate, influenced higher-weight individuals' group identification, intentions to engage in collective action on behalf of their group, and their body satisfaction and self-esteem. The moderating role of group boundary permeability and the mediating role of group identification were also examined. North American adults with a self-reported BMI of or above 30 (N = 327) were randomly assigned to one of two experimental conditions: weight-based discrimination that was portrayed as legitimate or illegitimate by other ingroup members. Results revealed that portraying weight-based discrimination as being perceived as legitimate (versus illegitimate) among ingroup members significantly reduced group identification, but only among those who perceived their group's boundaries to be more permeable. For this particular group, reduced identification predicted, in turn, lower collective action intentions, body satisfaction, and self-esteem. This study highlights the damaging effect of legitimized discrimination for ingroup identification and the downstream consequences for collective action and well-being.

Current research evidence suggests that people with schizophrenia have sensory processing difficulties. Sensory modulation has growing evidence for use in this population. This study aimed to evaluate the extent to which health, social, cognitive, and occupational functioning outcomes were impacted by sensory modulation interventions for people with schizophrenia.A prospective observational cohort study using a waitlist control design was used in two large hospital and health services in Queensland, Australia. The study recruited patients who used sensory modulation (n = 30) across the two hospitals and those who did not use sensory modulation interventions as a control (n = 11). Results were analysed using a series of planned comparisons including independent and paired t-tests, and mixed ANOVA was used whenever statistically indicated. The analysed measures were pre- and post-intervention scores.This study found no statically significant differences between the control and intervention groups at both pre- and post-intervention. However, analysis of results from within the intervention group showed statistically significant improvements between pre- and post-test scores on distress, occupational functioning, and health and social functioning but not on sensory processing and global cognitive processing. Further analysis of results from this study, compared with those from an earlier study on the general population showed significant differences in Low Registration and Sensation Avoiding, as measured by the Adult/Adolescent Sensory Profile, between participants with schizophrenia and those without schizophrenia.This study provides evidence to suggest that sensory modulation interventions can be complementary to standard care when utilised appropriately in clinical settings. Findings also suggest that the sensory profile of people with schizophrenia is different to that of the general population and this may have clinical implications. Further longitudinal research is needed with larger and randomised samples, using more targeted measures to better explore effectiveness of sensory modulation interventions.

Background According to published meta-analyses, cervical total disc replacement (CTDR) seems to be superior to anterior cervical decompression and fusion (ACDF) in most clinical parameters. Despite short-term clinical success of CTDR, there are concerns regarding long-term durability of these prostheses. Methods This prospective study involved 382 patients who received standalone CTDR or a hybrid procedure (ACDF/CTDR). A retrospective comparison between different CTDR devices was conducted regarding patient-reported outcome measures (PROMs), failure scenarios, and revision surgeries. The M6-C™ Artificial Cervical Disc (Orthofix, Lewisville, Texas) cohort was compared to the other CTDR devices clinically. Etiological reasons for revision, and the surgical technique of the revision was investigated. Results Fifty-three patients received M6-C CTDR. Eighteen patients (34%) were revised at an average of 67 months postoperatively for wear-induced osteolysis. There were three additional cases of pending revision. The PROMs of the two groups were similar, indicating that the failure mode (wear-induced osteolysis) is often asymptomatic. The demographics of the two groups were also similar, with more women undergoing revision surgery than men. There were three one-level CTDR, four two-level hybrids, seven three-level hybrids, and three four-level hybrids revised anteriorly. Sixteen patients underwent removal of the prosthesis and were treated according to the extent of osteolysis. There were four vertebrectomies, six revisions to ACDF, and six revisions to another CTDR. One patient underwent supplemental fixation using a posterior approach. The other CTDR cohort had an incidence of 3.3% at the equivalent time, and none of these were due to osteolysis or wear-related events. Conclusions There is a concerning midterm failure rate related to ultra-high-molecular-weight-polyethylene wear-induced osteolysis in the M6-C. Patients implanted with the M6-C prosthesis should be contacted, informed, and clinically and radiologically assessed.

Background Decades of research indicate that when social connectedness is threatened, mental health is at risk. However, extant interventions to tackle loneliness have had only modest success, and none have been trialled under conditions of such threat. Method 174 young people with depression and loneliness were randomised to one of two evidence-based treatments: cognitive behaviour therapy (CBT) or Groups 4 Health ( G4H ), an intervention designed to increase social group belonging. Depression, loneliness, and well-being outcomes were evaluated at one-year follow-up; COVID-19 lockdown restrictions were imposed partway through follow-up assessments. This provided a quasi-experimental test of the utility of each intervention in the presence (lockdown group) and absence (control group) of a threat to social connectedness. Results At one-year follow-up, participants in lockdown reported significantly poorer wellbeing than controls who completed follow-up before lockdown, t(152)=2.41, p=.017. Although both CBT and G4H led to symptom improvement, the benefits of G4H were more robust following an unanticipated threat to social connectedness for depression (χ2(16)=31.35, p=.001), loneliness (χ2(8)=21.622, p=.006), and wellbeing (χ2(8)=22.938, p=.003). Limitations Because the COVID-19 lockdown was unanticipated, this analysis represents an opportunistic use of available data. As a result, we could not measure the specific impact of restrictions on participants, such as reduced income, degree of isolation, or health-related anxieties. Conclusions G4H delivered one year prior to COVID-19 lockdown offered greater protection than CBT against relapse of loneliness and depression symptoms. Implications are discussed with a focus on how these benefits might be extended to other life stressors and transitions.

BackgroundDepression treatments are typically less effective for young people than for adults. However, treatments rarely target loneliness, which is a key risk factor in the onset, maintenance and development of depression.AimsThis study evaluated the efficacy of a novel loneliness intervention, Groups 4 Health (G4H), relative to the best-practice treatment of cognitive–behavioural therapy (CBT) in reducing loneliness and depression over a 12-month period (Australian New Zealand Clinical Trial Registry: ACTRN12618000440224).MethodThe study was a phase 3 randomised non-inferiority trial comparing G4H with dose-controlled group CBT. Participants were 174 people aged 15–25 years experiencing loneliness and clinically significant symptoms of depression, who were not in receipt of adjunct treatment. Participants were recruited from mental health services in Southeast Queensland, Australia. Randomisation was conducted using computer software. Follow-up assessments and statistical analyses were masked to allocation. Both interventions consisted of five 75 min group-based psychotherapy sessions. The primary outcomes were depression and loneliness, with a non-inferiority margin of 2.20 for depression.ResultsThe trial enrolled 174 participants between 24 April 2018 and 25 May 2019, with 84 in the G4H condition and 90 in the CBT condition. All randomised participants were included in the intention-to-treat analyses (n = 174). The pre–post effect sizes for depression were dG4H = −0.71 and dCBT = −0.91. For loneliness, they were dG4H = −1.07 and dCBT = −0.89. At 12-month follow-up, the absolute difference between groups on depression was 1.176 (95% CI −1.94 to 4.29) and on loneliness it was −0.679 (95% CI −1.43 to 0.07). No adverse effects were observed.ConclusionsG4H was non-inferior to CBT for depression and showed a slight advantage over CBT for loneliness that emerged after treatment completion.

Objective assessment of grit and its association with burnout in obstetrics and gynaecology (OG) training is underexplored.This study utilises the Short Grit Scale and the Oldenburg Burnout Inventory to investigate the association of grit with burnout, thriving and career progression among OG trainees and Fellows in Australia/New Zealand.A cross-sectional survey of the RANZCOG (Royal Australian and New Zealand College of Obstetricians and Gynaecologists) members was conducted. Participants were categorised by seniority level (core trainees, advanced trainees and Fellows). Mean grit and burnout scores were compared with one-way analyses of variance. Correlation between grit and burnout was estimated using Pearson's correlation coefficient. Logistic regression models were used to determine factors associated with high vs low burnout. Grit was categorised as low/medium/high for regression models.A total of 751 (26%) participants completed the survey. Fellows reported higher mean grit than core (P = 0.02) and advanced trainees (P = 0.03), and lower mean burnout than core trainees (P 0.001). Moderate negative correlation was demonstrated between grit and burnout scores (r = -0.34). In the multivariable model, only seniority (adjusted adds ratio (OR): 0.40 for Fellows vs core trainees, P = 0.008) and grit levels (adjusted OR:4.52 for low versus high, P 0.001; 2.32 for low vs medium, P = 0.001) were significantly associated with burnout.This study demonstrates the protective role of grit in combating burnout among RANZCOG trainees and Fellows. While further well-designed studies are warranted, findings from our study are expected to help the College in developing targeted interventions and subsequently minimise burnout-related adverse outcomes in high-risk groups.

Critical illness-associated weakness (CIAW) is an umbrella term used to describe a group of neuromuscular disorders caused by severe illness. It can be subdivided into three major classifications based on the component of the neuromuscular system (i.e. peripheral nerves or skeletal muscle or both) that are affected. This includes critical illness polyneuropathy (CIP), critical illness myopathy (CIM), and an overlap syndrome, critical illness polyneuromyopathy (CIPNM). It is a common complication observed in people with critical illness requiring intensive care unit (ICU) admission. Given CIAW is found in individuals experiencing grave illness, it can be challenging to study from a practical standpoint. However, over the past 2 decades, many insights into the pathophysiology of this condition have been made. Results from studies in both humans and animal models have found that a profound systemic inflammatory response and factors related to bioenergetic failure as well as microvascular, metabolic, and electrophysiological alterations underlie the development of CIAW. Current management strategies focus on early mobilization, achieving euglycemia, and nutritional optimization. Other interventions lack sufficient evidence, mainly due to a dearth of large trials. The goal of this Physiology in Medicine article is to highlight important aspects of the pathophysiology of these enigmatic conditions. It is hoped that improved understanding of the mechanisms underlying these disorders will lead to further study and new investigations for novel pharmacologic, nutritional, and exercise-based interventions to optimize patient outcomes.

Objectives Student-led clinics offer a work-based learning (WBL) opportunity for undergraduate healthcare students to engage with professional activities in a real-life setting. Participation is posited to provide experiential learning and prepare students for clinical practice. This study aims to assess the feasibility of establishing and engaging undergraduate students in one such initiative through the collaboration between one School of Pharmacy and local authority. Methods The clinic was developed using a logic model and delivered in 2019–2020. A service specification and training were developed and provided to volunteering undergraduate pharmacy students. Anonymised service data were collected and process outcomes around student and public engagement were recorded to assess feasibility for longer-term embedding into the undergraduate programme. Key findings The clinic was operational for 20 days from November 2019 to February 2020. Student volunteers (n = 43, 36.7%) were trained and provided blood pressure screening and healthy living advice to 131 members of the public. Student drop-out occurred due to the voluntary nature of the initiative. Conclusions Collaborative working with the local authority facilitated this WBL experience outside conventional clinical environments. The study demonstrated the potential for students to participate in service provision. This offers value to the local population through a health prevention service when a structured approach to the design and delivery of the educational experience is undertaken. The study provides insight into how the WBL can work, what it requires (e.g. resource, preparation), and learning to inform the wider implementation of this WBL into the undergraduate curriculum.

This project investigated how alternative non-stigmatising public health messages influence people’s health behaviours and well-being, relative to traditional stigmatising weight-loss messages. We conducted three experimental studies (total N = 1281) that compared traditional weight-loss messages to weight-neutral messages (Study 1), weight-inclusive messages (Study 2) and size acceptance messages (Study 3). Results revealed that public health messages have differential effects on health behaviours and well-being, depending on the audience’s BMI or perceived weight. However, campaigns that challenge weight stigma and promote body positivity have positive effects on some psychological indicators of health and well-being for people of all body sizes.

Objective Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is an essential tool in the diagnosis of pancreatic lesions. The aim of this study was to evaluate the diagnostic accuracy of cytology from EUS-FNA, to correlate the results with the corresponding histopathological diagnoses and to analyse the impact of retrospective assignment of the Papanicolaou Society of Cytopathology (PSC) reporting system categories. Methods All pancreatic FNA specimens reported at the Royal Free Hospital during a 2-year period were retrospectively collected and assigned to the PSC system categories. Any available corresponding histological samples were assessed for concordance. Results In total, 236 cytology specimens from 223 patients were identified, of which 108 (45.8%) had corresponding histology samples. The main reason for cyto-histological discrepancy was sampling error. Interpretive error was identified in one case. Overall, sensitivity was 92.5%, specificity was 100%, diagnostic accuracy of cytology was 95%, false-positive rate was 0% and false-negative rate was 7.5%. The implementation of the new reporting system reduced the number of cases in the atypical category. All cases previously categorised as suspicious or malignant remained in the same category. Conclusions EUS-FNA is an accurate method for evaluating pancreatobiliary lesions. The implementation of the Papanicolaou Society of Cytopathology diagnostic system enhances standardisation of the reporting terminology and reduces the number of samples in the non-standardised and equivocal atypical category.

Background The role of inpatient rehabilitation after total knee arthroplasty (TKA) remains uncertain, with evidence suggesting no better functional outcomes for those who discharge to rehabilitation to those who discharge home. The aim of this study is to develop and implement a pre-operative predictive tool, ARISE (Arthroplasty Rehabilitation Initial Screening Evaluation), that incorporated psychological, functional, and socio-demographic factors to determine discharge destination. Methods One week prior to TKA, the ARISE tool was administered to 100 patients, in addition to an EQ-5D-5L survey and other demographic data being recorded. The primary outcome was discharge destination. An enhanced recovery pathway, which included an anesthetic protocol designed to optimize early mobilization, was utilized. Univariable and multivariable logistic regression analysis was performed to determine the likelihood of discharge destination. Results Patients in the rehabilitation group were, on average, 4.5 years older than the home group (P = .036). After multivariable regression, ARISE questions were predictive of discharge destination related to beliefs around the superiority of inpatient rehabilitation (odds ratio = 9.9 [2.6-37.9]) and post-discharge level of support (odds ratio = 6.3 [1.5-26.8]). No question around self-reported physical function was predictive. Conclusion Pre-operative patient beliefs regarding rehabilitation and future home support are highly predictive of discharge destination after primary TKA. Pre-operative patient-reported functional status and demographic variables, with the exception of increasing age, were not shown to be predictive. Predicting those that are most likely to discharge to rehabilitation allows for early, targeted interventions to optimize resources and increase likelihood of home discharge.

Acceptance and commitment therapy, mindfulness-based cognitive therapy, and problem-solving therapy are types of cognitive-behavioural therapy (CBT) group that improve physical and mental health in chronic pain or cancer. However, dropout is high due to group demands alongside physical impairments. Motivational interviewing (MI) is a well-evidenced means of enhancing treatment adherence. Few studies have investigated MI as an adjunct to CBT in cancer or chronic pain, and none have established the minimum MI duration required for adherence improvement. This study evaluated minimal-duration MI to improve adherence in three CBT group types for cancer and chronic pain.In a cohort study of 99 cancer and chronic pain patients, 47 were given a 10- to 15-min structured MI telephone intervention (MI-call) after the first session. The remaining 52 received a CBT group without MI (no-MI).Odds of completing group CBTs were five times greater for patients in the MI-call cohort versus no-MI. Effects remained when controlling for age, gender, diagnosis, group type, and baseline quality of life. The MI-call cohort attended one extra session per patient compared to no-MI, controlling for age, gender, and diagnosis.A brief MI telephone intervention may improve adherence to group CBTs in cancer and chronic pain.A brief motivational interviewing (MI) telephone intervention may reduce dropout from group cognitive-behavioural therapies (CBTs) for cancer and chronic pain patients when administered after the first group session in routine care. Recipients of this intervention were five times more likely to complete a group CBT programme than those who did not receive it. Therefore, a minimal-dose MI intervention can have clinically important effects on dropout in group CBTs for patients with long-term conditions. It is unclear whether this intervention would also result in greater outcome improvements.

Background WhatsApp is an instant messaging application that has grown in popularity over the last decade. The literature has focused on the use of WhatsApp in medical, surgical and nursing disciplines, with little work exploring pharmacists’ experiences of using WhatsApp to provide services. Objective(s): The aim of this research was to explore pharmacists’ experiences of using WhatsApp to support delivery of out-of-hours pharmacy services. Methods A qualitative design was underpinned by a phenomenological philosophy. Focus groups and an extract of the WhatsApp transcript were thematically analysed using NVivo. Results Over three hundred communication events (1580 messages) were analysed in the WhatsApp transcript. Message type was classified as follows; handover (26%, n = 410), procedural queries (26%, n = 410), laptop location (18%, n = 284), whole staff communication (24%, n = 379), clinical queries (5%, n = 79), and administrative communications (1%, n = 16). A total of five focus groups were conducted between October and November 2017 with 27 participants that included pharmacists with different levels of experience. The findings suggest that WhatsApp improved communication between junior and senior pharmacists, particularly during the global cyber crisis, and provided an opportunity to share best practice. Concerns were raised regarding the encroachment of work activities into personal time. Additionally, the tacit approval by senior pharmacists to group information sharing and solution development, despite the potential for non-active participation, highlighted the issue of collective complicity. Conclusions WhatsApp can be a useful platform to support the delivery of out-of-hours services through professional development, improving communication and supporting relationships. This paper demonstrates that service managers must consider multiple ethico-legal and social frameworks when developing or allowing the organic development of such communication methods within healthcare provider organisations.

We hypothesized that exposure to weight stigma simultaneously increases motivation to lose or avoid gaining weight to avoid future stigma and decreases perceived capacity to do so, by heightening concerns about experiencing stigma and negative affect. Study 1 showed that more frequently experiencing weight-based discrimination was associated with greater concerns about being a victim of weight stigma, which predicted increased motivation to lose weight but decreased perceived capacity for weight control. Study 2 showed that participants randomly assigned to view a weight-stigmatizing (vs. control) message showed increased concerns about being a target of weight stigma, which indirectly increased motivation to lose weight and decreased state self-control. These, in turn, predicted increased willingness to engage in unhealthy weight-loss behaviors and decreased perceived capacity for weight control, respectively. Study 3 showed that increased motivation to avoid stigma and increased negative affect mediate these effects of exposure to weight stigma.

Advances in the engineering of comprehensive skeletal muscle models in vitro will improve drug screening platforms and can lead to better therapeutic approaches for the treatment of skeletal muscle injuries. To this end, a vascularized tissue-engineered skeletal muscle (TE-SkM) model that includes adipocytes was developed to better emulate the intramuscular adipose tissue that is observed in skeletal muscles of patients with diseases such as diabetes. Muscle precursor cells cultured with and without microvessels derived from adipose tissue (microvascular fragments) were used to generate TE-SkM constructs, with and without a microvasculature, respectively. TE-SkM constructs were treated with adipogenic induction media to induce varying levels of adipogenesis. With a delayed addition of induction media to allow for angiogenesis, a robust microvasculature in conjunction with an increased content of adipocytes was achieved. The augmentation of vascularized TE-SkM constructs with adipocytes caused a reduction in maturation (compaction), mechanical integrity (Young's modulus), and myotube and vessel alignment. An increase in basal glucose uptake was observed in both levels of adipogenic induction, and a diminished insulin-stimulated glucose uptake was associated with the higher level of adipogenic differentiation and the greater number of adipocytes. IMPACT STATEMENT: The findings of the current study represent the effectiveness of employing a combinatorial approach involving muscle precursor cells and microvascular fragments to create a vascularized tissue-engineered skeletal muscle model with adipocytes that induce structural and metabolic changes. This model is a platform to support the discovery of mechanisms underlying the phenomena of intramuscular adipose tissue that is characteristic of the skeletal muscles of patients with diseases.

The impact of memory loss on the self in Alzheimer's disease (AD) is poorly understood. Previous research is mixed on whether episodic or semantic memories are most important for supporting identity. The present study examined autobiographical memories cued by self-images (e.g., I am a father) and non-self-related cues in 16 AD patients and 29 healthy older adults. The AD group generated fewer self-images and memories compared to controls, but demonstrated similar temporal organization of self-cued memories. In both groups, self-images were supported by semantic memories that were temporally clustered around times of identity-formation. These self-supporting memories are proposed to form a scaffold to support the self and may persist the longest in AD, as opposed to memories from early adulthood per se. In both AD and control groups, self-images cued more semantic memories than non-self-relevant cues, further suggesting that semantic autobiographical memories play a fundamental role in supporting the self. These findings demonstrate that the self remains largely intact in AD, in spite of severe episodic memory deficits and global cognitive decline. In later stages of the disease, these self-supporting memories could provide effective tools for reminiscence therapy.

Our breast screening unit was identified as high outlier for B3 lesions with a low positive predictive value (PPV) compared to the England average. This prompted a detailed internal audit and review of B3 lesions and their outcomes to identify causes and address any variation in practice.The B3 rate was calculated in 4168 breast core biopsies from 2019, using the subsequent excision to determine the PPV. Atypical intraductal epithelial proliferation (AIDEP) cases were subject to microscopic review to reassess the presence of atypia against published criteria. The B3 rate was re-audited in 2021, and the results compared.Screening cases had a high B3 rate of 12.4% (30% above the national average), and a PPV of 7.7% (9.7% with atypia). AIDEP was identified as a possible cause of this outlier status. On review and by consensus, AIDEP was confirmed in only 66% of cases reported as such, 17% were downgraded, and 16% did not reach consensus, the latter highlighting the difficulty and subjectivity in diagnosis of these lesions. Repeat audit of B3 rates after this extended review revealed a reduction from 12.4% to 9.11%, which is more in line with national standards.Benchmarking against national reporting standards is critical for service improvement. Through a supportive environment, team working, rigorous internal review and adherence to guidelines, interobserver variation and outlier status in breast pathology screening outliers can both be addressed. This study can serve as a model to other outlier units to identify and tackle underlying causes.

Purpose\ud Idea density has been shown to influence comprehension time for text in various populations. This study aims to explore the influence of spoken idea density on attainment in young, healthy subjects using demographic characteristics.\ud \ud Methods\ud Students watched two online lectures and answered 10 multiple choice questions on them. Students received one more idea dense (MID) and one less idea dense (LID) lecture on two different subjects.\ud \ud Results\ud Seventy-five students completed the study achieving a higher median score after a less idea-dense lecture (LID = 7(3), MID = 6(3), p = 0.04). Artificial neural network models revealed the first language as the main predictor of exam performance. The odds ratio (OR) of obtaining ≥70% after a more idea-dense lecture was six-time higher for the first language versus second language English speakers (OR = 5.963, 95% CI 1.080–32.911, p = 0.041). The odds ratio was not significant when receiving a less dense lecture (OR = 2.298, 95% CI 0.635–8.315, p = 0.205). Second-language speakers benefited from receiving a lower idea density, achieving a 10.8% score increase from high to low density, versus a 3.2% increase obtained by first language speakers.\ud \ud Conclusions\ud The propositional idea density of lectures directly influences students’ comprehension, and disproportionately for second language speakers; revealing the possibility of reduced spoken idea density in levelling the attainment differential between first and second language speakers.

STUDY DESIGN Prospective Cohort Study. OBJECTIVE The aim of this paper is to compare the mid- to long-term patient-reported outcome measures (PROMs) between single-level total disc arthroplasty (TDA), multi-level TDA, and hybrid constructs (combination of TDA and anterior lumbar interbody fusion (ALIF) across multiple levels) for symptomatic degenerative disc disease (DDD). SUMMARY OF BACKGROUND DATA The treatment of single-level DDD is well documented using TDA. However, there is still a paucity of published evidence regarding long-term outcomes on multi-level TDA and hybrid constructs for the treatment of multi-level DDD, as well as lack of long-term comparisons regarding treatment of single-level DDD and multi-level DDD. METHODS 950 patients underwent surgery for single-level or multi-level DDD between July 1998 and February 2012 with single-level TDA (n = 211), multi-level TDA (n = 122) or hybrid construct (n = 617). Visual Analog Score for the back (VAS-B) and leg (VAS-L) were recorded, along with the Oswestry Disability Index (ODI) and Roland Morris Disability Questionnaire (RMDQ). RESULTS All PROMs in all groups showed statistically and clinically significant improvements (p

The Ballistic Exercise of the Lower Limb (BELL) trial examined the efficacy and safety of a pragmatic hardstyle kettlebell training program in older adults. Insufficiently active men and women aged 59–79 years, were recruited to a 6-month repeated measures study, involving 3-months usual activity and 3-months progressive hardstyle kettlebell training. Health-related physical fitness outcomes included: grip strength [GS], 6-min walk distance [6MWD], resting heart rate [HR], stair-climb [SC], leg extensor strength [LES], hip extensor strength [HES], Sit-To-Stand [STS], vertical jump [CMVJ], five-times floor transfer [5xFT], 1RM deadlift, body composition (DXA), attendance, and adverse events. Sixteen males (68.8 ± 4.6 yrs, 176.2 ± 7.8 cm, 90.7 ± 11.0 kg, 29.2 ± 2.6 kg/m2) and sixteen females (68.6 ± 4.7 yrs, 163.9 ± 5.4 cm, 70.4 ± 12.7 kg, 26.3 ± 4.9 kg/m2) were recruited. Compliance with the supervised exercise program was very high (91.5%). Kettlebell training increased GS (R: MD = 7.1 kg 95% CI [4.9, 9.3], L: MD = 6.3 kg 95% CI [4.1, 8.4]), 6MWD (41.7 m, 95% CI [17.9, 65.5]), 1RM (16.2 kg, 95% CI [2.4, 30.0]), 30 s STS (3.3 reps, 95% CI [0.9, 5.7]), LES (R: MD = 61.6 N, 95% CI [4.4, 118.8]), HES (L: MD = 21.0 N,95% CI [4.2,37.8]), appendicular skeletal lean mass (MD = 0.65 kg, 95% CI [0.08, 1.22]), self-reported health change (17.1%, 95% CI [4.4, 29.8]) and decreased SC time (2.7 s, 95% CI [0.2, 5.2]), 5xFT time (6.0 s, 95% CI [2.2, 9.8]) and resting HR (7.4 bpm, 95% CI [0.7, 14.1]). There were four non-serious adverse events. Mean individual training load for group training sessions during the trial was 100,977 ± 9,050 kg. High-intensity hardstyle kettlebell training was well tolerated and improved grip strength and measures of health-related physical fitness in insufficiently active older adults.Trial registration: Prospectively registered: 20/08/2019, Australian New Zealand Clinical Trials Registry (ACTRN12619001177145).

Mass gathering events often involve high levels of substance use, yet the psychological predictors of substance use in these contexts have received minimal attention. This study examined the relationship between social norms and mass gathering attendees' anticipated substance use. We (a) tested this relationship while controlling for established predictors of substance use, (b) assessed longitudinally the impact of intraindividual changes in perceived substance use norms on intraindividual changes in participants' anticipated substance use, and (c) compared the relative impact of two normative referents (friends and typical mass gathering attendees).Data were collected in situ at Schoolies (Australia's largest youth mass gathering). On Days 1, 3, and 5 of the 7-day festival, participants (N = 427; ages 16-19, 66% female) reported normative perceptions of drinking and drug taking among friends and other attendees, and indicated their own anticipated drinking and drug taking.Friend norms were associated with anticipated drinking and drug taking at each corresponding time point, with particularly strong relationships observed for anticipated drinking. Changes in friend norms also predicted changes in anticipated drinking and drug taking. Conversely, the effects of norms for typical attendees were weak.People's substance use at mass gatherings is particularly influenced by perceptions of friends' substance use. Friend norm perceptions change over time and dynamically influence young people's anticipated substance use in these high-risk settings. Interventions to reduce substance use at mass gatherings may be enhanced by correcting misperceptions of the normative behaviors of friends.

Skeletal muscle is a tissue that is directly involved in the progression and persistence of type 2 diabetes (T2D), a disease that is becoming increasingly common. Gaining better insight into the mechanisms that are affecting skeletal muscle dysfunction in the context of T2D has the potential to lead to novel treatments for a large number of patients. Through its ability to emulate skeletal muscle architecture while also incorporating aspects of disease, tissue-engineered skeletal muscle (TE-SkM) has the potential to provide a means for rapid high-throughput discovery of therapies to treat skeletal muscle dysfunction, to include that which occurs with T2D. Muscle precursor cells isolated from lean or obese male Zucker diabetic fatty rats were used to generate TE-SkM constructs. Some constructs were treated with adipogenic induction media to accentuate the presence of adipocytes that is a characteristic feature of T2D skeletal muscle. The maturity (compaction and creatine kinase activity), mechanical integrity (Young's modulus), organization (myotube orientation), and metabolic capacity (insulin-stimulated glucose uptake) were all reduced by diabetes. Treating constructs with adipogenic induction media increased the quantity of lipid within the diabetic TE-SkM constructs, and caused changes in construct compaction, cell orientation, and insulin-stimulated glucose uptake in both lean and diabetic samples. Collectively, the findings herein suggest that the recapitulation of structural and metabolic aspects of T2D can be accomplished by engineering skeletal muscle in vitro. IMPACT STATEMENT: The tissue engineering of skeletal muscle to model disease and injury has great promise to provide a tool to develop and/or improve therapeutic approaches for improved health care. A tissue-engineered skeletal muscle model of one of the most common and debilitating diseases, type 2 diabetes, has been developed in vitro as evidenced by the structural and metabolic alterations that are consistent with the disease phenotype in vivo.

Background and objective: Despite consistent evidence that bisexual people have poorer mental health than heterosexual people, gay men or lesbians, the reasons for this remain largely unknown. The 'Who I Am' study aims to address this current knowledge gap. Methods: A cross-sectional survey was completed by 2651 adults living in Australia who had bisexual attraction, identity and/or experience. Ordinal regression identified significant ('P' Results: Higher levels of internalised biphobia, being in a heterosexual relationship and having a less supportive partner significantly ('P' Discussion: While there has been an increased focus on lesbian and gay health in recent years, general practitioners may be less familiar with the specific health needs of bisexual people. This is the largest study of bisexual Australians to date and provides detailed information about the relationships between bisexual life experiences and poor mental health.

Background Mesenchymal stromal cell (MSC)-derived extracellular vesicles (EVs) have great potential as a cell-free therapy in wound healing applications. Because EV populations are not equivalent, rigorous characterization is needed before clinical use. Although there has been much focus on their RNA composition and regenerative capabilities, relatively less is known regarding the effects of MSC cell type (adipose tissue [Ad-MSCs] or bone marrow [BM-MSCs]) and culture condition (monolayer or spheroid) on MSC-EV performance, including characteristics related to their ability to promote coagulation, which could determine EV safety if administered intravenously. Methods The successful isolation of EVs derived from Ad-MSCs or BM-MSCs cultured in either monolayer or spheroid cultures was confirmed by NanoSight (particle size distribution) and Western blot (surface marker expression). Extracellular vesicle surface expression of procoagulant molecules (tissue factor and phosphatidylserine) was evaluated by flow cytometry. Extracellular vesicle thrombogenicity was tested using calibrated thrombogram, and clotting parameters were assessed using thromboelastography and a flow-based adhesion model simulating blood flow over a collagen-expressing surface. Results The MSC cell type and culture condition did not impact EV size distribution. Extracellular vesicles from all groups expressed phosphatidylserine and tissue factor on their surfaces were functionally thrombogenic and tended to increase clotting rates compared to the negative control of serum-free media without EVs. On average, EVs did not form significantly larger or stronger clots than the negative control, regardless of cell source or culture condition. Additionally, EVs interfered with platelet adhesion in an in vitro flow-based assay. Conclusion Adipose-derived EVs were more thrombogenic and expressed higher amounts of phosphatidylserine. Our findings suggest that, like intact MSCs, source variability among EVs is an important factor when considering EVs for potential therapeutic purposes. Level of evidence Therapeutic care management, level II.

ObjectiveAs mass gathering events resume in the wake of the COVID-19 pandemic, there is a pressing need to understand (a) engagement in COVID-safe behaviour at these events and (b) how attending a mass gathering impacts subsequent behaviours. This study examined anticipated COVID-safe behaviour before, during, and after a youth mass gathering event.DesignLongitudinal cohort study.SettingSelf-report data were collected online at five timepoints from secondary-school graduates participating in celebrations linked to an annual week-long youth mass gathering event in Australia.ParticipantsAustralian secondary-school graduates completed surveys before the event (N=397), on days 1 (N=183), 3 (N=158) and 5 (N=163) of the event, and 3 weeks after the event (N=140). Of those who completed the first survey, 72 indicated they would attend a primary mass gathering site where the largest mass gathering of graduates in Australia occurs in a typical (non-pandemic) year; 325 indicated they would be celebrating at other locations (ie, secondary sites).Primary outcome measuresAnticipated COVID-safe behaviour: physical distancing from friends and strangers and additional protective behaviours (hand hygiene and mask wearing).ResultsAt all timepoints, participants anticipated maintaining appropriate (>1.5 m) physical distance from strangers, but not from friends (2(4)=16.89, p=0.002. Physical distancing from strangers, χ2(4)=26.93, p2(4)=221.23, pConclusionIt is critical that public health messaging and interventions emphasise the risks of disease transmission arising from other attendees who are known to us during mass gathering events, and that such messaging is sustained during and following the event to combat reductions in COVID-safe behaviour.

What is known: Medication non‐adherence leads to negative health outcomes. Medication adherence is predicted if patients understand the necessity of medication use to control disease symptoms and progression. It could be expected then, that patients with diseases with symptoms which are managed with medications, such as chronic obstructive pulmonary disorder or gout, or diseases with high‐mortality rates, such as cancer, would have higher adherence rates than asymptomatic diseases, such as hypertension. However, poor medication adherence remains problematic in both symptomatic and asymptomatic diseases. Further work is needed to explore patient experiences of medication adherence to understand the link between adherence and symptom control. Objective: To explore patients' lived experiences of medication adherence. Methods: Participants were recruited from community pharmacies and general practices. Forty‐one semi‐structured interviews and three focus groups were used to collect data from patients with disease states that had different symptomatic and asymptomatic profiles. Inductive thematic analysis was used to identify key parts of the experience of using medications. Results: Participants reported similar experiences of medication adherence despite having different disease symptoms. Participants said that they used medications because it was an expected part of everyday life and that medications ‘must be needed’ because they had been supplied, rather than being used for a particular symptom. Participants reported short‐term episodes of non‐adherence were unlikely to lead to negative health outcomes but may result in negative social consequences. Discussion: The findings broaden our understanding of patient experiences of medication use by indicating patients with symptomatic and asymptomatic diseases share similar experiences of medication use. The necessity to use medications appeared to come from ‘the system’ of healthcare professionals, family and friends that supply and recommend medications. What is new: There were key similarities in experiences of medication adherence in patients with different disease states. The negative consequences of short‐term episodes of non‐adherence were normalized by healthcare professionals. Conclusion: Patients with symptomatic and asymptomatic diseases share similar experiences of medication adherence.

COVID-19 has become a global pandemic of the highest priority. Multiple treatment protocols have been proposed worldwide with no definitive answer for acure. A prior retrospective study showed association between bitter taste receptor 38 (T2R38) phenotypes and the severity of COVID-19. Based on this, we proposed assessing the different T2R38 phenotypes response towards a targeted treatment protocol. Starting July 2020 till December 2020, we tested subjects for T2R38 phenotypic expression (supertasters, tasters, and nontasters). Subjects who were subsequently infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (diagnosed via PCR) were included. Based on their taster status, supertasters were given dexamethasone for 4 days, tasters were given azithromycin and dexamethasone +/− hydroxychloroquine for 7 days, and nontasters were given azithromycin and dexamethasone for 12 days. Subjects were followed prospectively and their outcomes were documented. Seven hundred forty-seven COVID-19 patients were included, with 184 (24.7%) supertasters, 371 (49.6%) tasters, and192 (25.7%) nontasters. The average duration of symptoms with the treatment protocol was 5 days for supertasters, 8.1 days for tasters, and 16.2 days for nontasters. Only three subjects (0.4%) required hospitalization (3/3 nontasters). Targeted treatment protocol showed significant correlation (p &lt, 0.05) based on patients’ T2R38 phenotypic expression. Assessing treatment protocols for COVID-19 patients according to their T2R38 phenotype could provide insight into the inconsistent results obtained from the different studies worldwide. Further study is warranted on the categorization of patients based on their T2R38 phenotype.

Introduction Qualitative research is a well-established branch of scientific enquiry that draws insights from experiences.1, 2Within social and administrative pharmacy research, interview and focus group methods are a mainstay of collecting data. However, other disciplines such as sociology, psychology and anthropology, use existing data that is routinely to provide a substance for qualitative inquiry. Drawing on our experiences of using interdisciplinary research methods, this paper presents three case studies where textual data was qualitatively analysed and critically examines the strengths and weaknesses of these method in relation to pharmacy practice. Methods Three case studies were selected that access different types of existing, routinely collected data from pharmacy practice. This included 1) a study utilising boardroom meeting minutes, 2) a study using incident reports and 3) a study using WhatsApp messages as data. Each case study is described and critically examined. The strengths and weaknesses of this approach are based on our own reflections of completing the studies. Results Relationships between people, products and organisations can be examined in documents, records and text that is routinely collected. Existing data can also provide insights into culture, working patterns, education and errors. Practical advantages of using existing data include faster data collection and access to first-hand, accounts of experiences of human relationship with pharmaceutical products and practice. Drawbacks of using existing data are that some data may be missing, participants may no longer be accessible for participant checking and the context of language may have changed. Conclusion This paper critically examined the use of methods rarely used in pharmacy practice research which draw on existing, routinely collected data. Adopting a wider range of data collection methods may will provide new understanding and insights into social and clinical pharmacy practice.

Objectives To investigate patient-reported rehabilitation characteristics and barriers to and facilitators of ACL reconstruction rehabilitation. Design Survey-based study. Setting Online survey platform. Participants Adults 1–20 years post ACL reconstruction (n = 304). Main outcome measures 1) rehabilitation characteristics, 2) barriers to and facilitators of rehabilitation. Results Fear of re-injury (43.8%) was the highest rating barrier to rehabilitation adherence, while a good relationship with your rehabilitation provider was regarded as the most important factor (83.6%) in facilitating rehabilitation. Rehabilitation frequency reduced across the duration of rehabilitation from most commonly 1 x week (38.2%) in the first three months to once every month (26%) from 6 to 9 months. Almost all participants (95.7%) consulted a rehabilitation provider for the first six months. Only 43.4% of respondents returned to their previous level of sport. The exploratory analysis identified that low barriers to rehabilitation and a longer duration of supervised rehabilitation are associated with a faster return to sport, greater likelihood of return to previous level of sport and fewer reported ongoing problems with the knee. Conclusions This cross-sectional survey provides insight into the patient’s experience of rehabilitation practices and a patient’s perspective on the key barriers to and facilitators of ACL rehabilitation adherence and participation.

Objective:To critically review the literature regarding workplace breast-feeding interventions and to assess their impact on breast-feeding indicators.Design:A systematic review and meta-analysis was conducted. Electronic searches for workplace intervention studies to support breast-feeding, without restriction on language or study design, were performed in PubMed, CENTRAL, CINAHL, Embase, Web of Science, Business Source Complete, ProQuest-Sociology and ProQuest-Social Science to 13 April 2020. A meta-analysis of the pooled effect of the programmes on breast-feeding indicators was conducted.Results:The search identified 10 215 articles; fourteen studies across eighteen publications met eligibility criteria. Programmes were delivered in the USA (n 10), Turkey (n 2), Thailand (n 1) or Taiwan (n 1). There were no randomised controlled trials. The pooled OR for exclusive breast-feeding at 3 or 6 months for participants v. non-participants of three non-randomised controlled studies was 3·21 (95 % CI 1·70, 6·06, I2 = 22 %). Despite high heterogeneity, other pooled outcomes were consistently in a positive direction with acceptable CI. Pooled mean duration of breast-feeding for five single-arm studies was 9·16 months (95 % CI 8·25, 10·07). Pooled proportion of breast-feeding at 6 months for six single-arm studies was 0·76 (95 % CI 0·66, 0·84) and breast-feeding at 12 months for three single-arm studies was 0·41 (95 % CI 0·22, 0·62). Most programmes were targeted at mothers; two were targeted at expectant fathers.Conclusions:Workplace programmes may be effective in promoting breast-feeding among employed mothers and partners of employed fathers. However, no randomised controlled trials were identified, and better-quality research on workplace interventions to improve breast-feeding is needed.

Objectives Iterative reflective practice is recognised to support learners’ formation of humanism and resilience, facilitating the healthy development of professional identity. In one undergraduate pharmacy programme, students experience a series of seminars to develop their understanding and skills in the practice of reflection and its articulation. In Stage (year) 4, students engage in a reflection conference where they present a reflective account of a ‘Significant Learning Event’ or their journey ‘From Student to Professional’. Student abstracts from this conference were investigated to explore the nature of the reflective practice. Methods The student abstracts submitted for the reflection conference in the academic years 2017–2018 and 2018–2019 were subjected to manifest and latent content analysis to investigate what and how students chose to reflect. This was supplemented by the ethnographic approach of the researchers, who attended, observed and engaged with students at the event. Key findings 107 abstracts were submitted across the cohorts. Students reflected mainly upon experiences across a range of extra- and co-curricular activities, and reported significant learning, according to Fink’s taxonomy, mainly in the human dimension, caring and learning to learn. Conclusions At the culmination of the reflection educational strand within this programme, students demonstrated purposeful, deliberate introspection and metacognition in their abstracts for the reflection conference. These skills are fundamental to support transformative learning, whereby students have the ability to self-regulate and critique their frames of reference with autonomy and flexibility that will enable them to most effectively engage and benefit from lifelong learning within the profession.

Background and objectives People who identify as bisexual, transgender or gender diverse report poorer mental health than their homosexual and cisgender counterparts. The aim of this article is to shed light on the mental health experiences of gender diverse bisexual people and the reasons for poor mental health in this group. Method This article reports on a subset of a large cross-sectional survey of bisexual Australians (n = 2651), examining predictors of poor mental health among the 19% (n = 474) of respondents who identified as transgender or gender diverse. Results Very high rates of psychological distress, mental illness and suicidality were reported by participants who identified as transgender and gender diverse. Higher levels of internalised biphobia and less participation in lesbian, gay, bisexual, transgender and intersex community events predicted higher psychological distress (P Discussion The high rates of mental health problems among transgender and gender diverse bisexual Australians mean it is essential that general practitioners and those on the frontline of mental healthcare provision recognise the need to engage with these groups. This research provides new insights to support and inform this engagement.

Risk taking is typically viewed through a lens of individual deficits (e.g., impulsivity) or normative influence (e.g., peer pressure). An unexplored possibility is that shared group membership, and the trust that flows from it, may play a role in reducing risk perceptions and promoting risky behavior. We propose and test a Social Identity Model of Risk Taking in eight studies (total N = 4,708) that use multiple methods including minimal group paradigms, correlational, longitudinal, and experimental designs to investigate the effect of shared social identity across diverse risk contexts. Studies 1 and 2 provided evidence for the basic premise of the model, showing that ingroup members were perceived as posing lower risk and inspired greater risk taking behavior than outgroup members. Study 3 found that social identification was a moderator, such that effect of shared group membership was strongest among high identifiers. Studies 4 and 5 among festival attendees showed correlational and longitudinal evidence for the model and further that risk-taking was mediated by trust, not disgust. Study 6 manipulated the mediator and found that untrustworthy faces were trusted more and perceived as less risky when they were ingroup compared with outgroup members. Studies 7 and 8 identified integrity as the subcomponent of trust that consistently promotes greater risk taking in the presence of ingroup members. The findings reveal that a potent source of risk discounting is the group memberships we share with others. Ironically, this means the people we trust the most may sometimes pose the greatest risk. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Objective: To evaluate the effectiveness of a postnatal dynamic elastomeric fabric orthoses to manage postpartum pain, improve functional capacity and enhance the quality of life arising from postnatal ailments immediately to an 8-week postpartum, compared with patients who did not wear dynamic elastomeric fabric orthoses. Method: A total of 51 postpartum women were recruited (day 0 to 10 days post-delivery) from hospitals and community-based health clinics to participate in a prospective quasi-experimental controlled study using parallel groups without random allocation. The subgroup of the compression shorts group wore SRC recovery shorts and received standard postnatal care. The comparison group received standard postnatal care alone. Wear compliance was monitored throughout the study. Primary outcome measure, Numeric Pain Rating Scale, and secondary outcome measures, Roland Morris Disability Questionnaire, Pelvic Floor Impact Questionnaire–7, and Short Form (SF-36) were assessed fortnightly over 8 weeks for both groups. Results: The compression shorts group reported a larger reduction in mean (SD) Numeric Pain Rating Scale score (−3.09 (2.20)) from baseline to 8 weeks, compared to the comparison group (−2.00 (1.41)). However, there was insufficient evidence of a statistical difference in Numeric Pain Rating Scale score at 8 weeks when comparing the compression shorts group and comparison group (−1.17; 95%CI: (−2.35, −0.01), R2 = .19, p = .050). The compression shorts group met the wear compliance of the dynamic elastomeric fabric orthoses and reported an average wear of the dynamic elastomeric fabric orthoses as 9 out of 14 days for 11 h per day (SD 4.8 h) between the fortnightly timepoints. Conclusion: The use of dynamic elastomeric fabric orthoses may be considered during postnatal care as a non-pharmacological therapeutic intervention to manage pain resulting from common postpartum ailments. While the dynamic elastomeric fabric orthoses was clinically well accepted by participants with high wearing compliance, future research with larger population samples are needed to enable statistical conclusions on the effectiveness of a dynamic elastomeric fabric orthoses in postnatal care to be made. Registration: Trial registration was not required as per the Australian Government Department of Health, Therapeutic Goods Administration.

Introduction SARS-CoV-2 has been identified as the pathogen causing the outbreak of Coronavirus Disease 2019 (COVID-19) that started in Wuhan, China, in December 2019. SARS-CoV-2 has human-to-human transmission ability and universally contagious to all populations. The main transmission patterns are respiratory droplets transmission and contact transmission. The purpose of this study is to propose a protocol that may be used as a guide to reduce the incidence of COVID-19 infections among otolaryngology care teams. Methods A prospective cohort study was conducted to show the efficacy of our protocol to prevent transmission to health-care providers from March 11, 2020 through April 14, 2020. The protocol consisted of a series of protective measures that we applied to all health-care providers, then testing of our providers for COVID-19 using reverse transcription polymerase chain reaction along with immunoglobulin M (IgM) and immunoglobulin G (IgG) testing at the end of the study period to ensure effectiveness. Results Our protocol resulted in zero transmissions to our health-care providers during the duration of the initial study. We were involved in greater than 150 sinonasal, skull base, open airway, and endoscopy procedures during this study. At the conclusion of the initial 5 weeks, we had no health-care providers test positive for SARS-CoV-2. Conclusion According to our proposed protocol, we were able to provide care for all patients in clinic, hospital, emergent, intensive, and surgical settings with no transmission of SARS-CoV-2 by symptomatology and post evaluation testing.

Objectives: This project explored the deployment of pharmacy assistants to inpatient wards in a new role as ‘medicines assistants’ (MA). Methods: Ward-based MAs were introduced to six wards across two UK hospitals to support medicines administration. Each 30-bed ward delivered acute inpatient services with MAs supporting typical nursing medication administration rounds to 15 patients. Data were collected using activity diaries, observations, clinical audit and semistructured interviews with pharmacy assistants, pharmacy technicians, clinical pharmacists, nurses, ward managers and pharmacy managers. Thematic analysis, descriptive statistics and the Mann-Whitney U test were used to analyse qualitative and quantitative data, respectively. Results: MAs were able to act as a point of contact between the ward and the pharmacy department and were perceived to save nursing time. A statistically significant reduction in the length of time to complete morning medication administration to 15 patients was observed (mean 74.5 vs 60.8 min per round, p

BACKGROUND Mesenchymal stem/stromal cell (MSC)-derived extracellular vesicles (EVs) are a possible cell-free alternative to MSCs because they retain the regenerative potential of MSCs, while still mitigating some of their limitations (such as the possible elicitation of host immune responses). The promotion and restoration of angiogenesis, however, is an important component in treating trauma-related injuries, and has not been fully explored with EVs. Herein, we describe the effects of monolayer adipose-derived EVs, spheroid adipose-derived EVs (SAd-EVs), monolayer bone marrow-derived EVs (MBM-EVs), and spheroid bone marrow-derived EVs (SBM-EVs) on human umbilical vein endothelial cell (HUVEC) tube formation and mitochondrial respiration. METHODS The successful isolation of EVs derived from adipose MSCs or bone marrow MSCs in monolayer or spheroid cultures was confirmed by NanoSight (particle size distribution) and Western blot (surface marker expression). The EV angiogenic potential was measured using a 24-hour HUVEC tube formation assay. The EV effects on HUVEC mitochondrial function were evaluated using the Seahorse respirometer machine. RESULTS The number of junctions, branches, and the average length of branches formed at 24 hours of tube formation were significantly affected by cell and culture type; overall adipose-derived EVs outperformed bone marrow-derived EVs, and spheroid-derived EVs outperformed monolayer-derived EVs. Additionally, adipose-derived EVs resulted in significantly increased HUVEC mitochondrial maximal respiration and adenosine triphosphate (ATP) production, while only MBM-EVs negatively impacted HUVEC proton leak. CONCLUSION Adipose-derived EVs promoted HUVEC tube formation significantly more than bone marrow-derived EVs, while also maximizing HUVEC mitochondria function. Results demonstrate that, as with MSC therapies, it is possible to tailor EV culture and production to optimize therapeutic potential. LEVEL OF EVIDENCE Basic or Foundational Research.

Background There are an overwhelming number of patients suffering from low back pain (LBP) resulting from disc pathology. Although several strategies are being developed pre-clinically, simple strategies to treat the large number of patients currently affected is still needed. One option is to use concentrated bone marrow aspirate (cBMA), which may be effective due to its intrinsic stem cells and growth factors. Methods Thirty-three patients who received intradiscal injections of cBMA to relieve LBP were followed up based on Numeric Rating Scale (NRS), Oswestry Low Back Pain Disability Index (ODI), and Short Form-36 Health Survey (SF-36) scores. Patients were also subdivided into those with a pre-injection NRS > 5 and pre-injection NRS ≤ 5. The proportion of patients demonstrating at least 50% improvement (and 95% confidence intervals) from baseline at five follow-up visits for each outcome was evaluated. Results At least 50% improvement in NRS was observed for 13.8, 45.8, 41.1, 23.5, and 38.9% of patients across five follow-up visits, out to 1 year. When stratified by high (> 5) versus low (≤ 5) baseline NRS scores, the values were 14.3, 45.5, 71.4, 22.2, and 44.4% among those with high baseline pain, and 13.3, 46.2, 20.0, 25.0, and 33.3% among those with low baseline pain. The 50% improvement rates across visits were 4.3, 28.6, 30.0, 22.2, and 30.8% for SF-36, and 4.2, 26.7, 36.4, 55.6, and 30.8% for ODI. Conclusions Intradiscal cBMA injections may be effective to reduce pain and improve function. Patients with relatively higher initial pain may have potential for greatest improvement.

Purpose: To compare the effect of 12-weeks of cycling training and competition versus recreational cycling on successful aging across physical, psychological, cognitive, and social functioning doma...

Introduction: Thymoquinone (TQ), 2-isopropyl-5-methylbenzo-1, 4-quinone, the main active constituent of Nigella sativa (NS) plant, has been proven to be of great therapeutic aid in various in vitro and in vivo conditions. Despite the promising therapeutic activities of TQ, this molecule is not yet in the clinical trials, restricted by its poor biopharmaceutical properties including photo-instability.Area covered: This review compiles the different types of polymeric and lipidic nanocarriers (NCs), encapsulating TQ for their improved oral bioavailability, and augmented in vitro and in vivo efficacy, evidenced on various pathologies. Furthermore, we provide a comprehensive overview of TQ in relation to its encapsulation approaches advancing the delivery and improving the efficacy of TQ.Expert opinion: TQ was first identified in the essential oil of Nigella sativa L. black seed. TQ has not been used in formulations because it is a highly hydrophobic drug having poor aqueous solubility. To deal with the poor physicochemical problems associated with TQ, various NCs encapsulating TQ have been tried in the past. Nevertheless, these NCs could be impending in bringing forth this potential molecule to clinical reality. This will also be beneficial for a large research community including pharmaceutical & biological sciences and translational researchers.

Background Total Knee Arthroplasty (TKA) reduces pain and improves function in those suffering from severe osteoarthritis. A significant cost of TKA is post-acute care, however, current evidence suggests that discharge to an Inpatient Rehabilitation Facility (IRF) has inferior outcomes to home discharge, with no greater benefit in physical function. Only individual studies have investigated TKA patient characteristics predictive of discharge destination, therefore, the aim is to systematically review the literature and meta-analyse intrinsic patient factors predictive of IRF discharge. If predictive factors are known, then early discharge planning and intervention strategies could be implemented. Methods Databases PubMed, CINAHL, Embase, Cochrane, and Pedro were searched up to October 2019 for all studies investigating pre-operative intrinsic patient factors predictive of IRF discharge. For assessing the methodological quality of included studies, the Quality In Prognosis Studies (QUIPS) tool was used. Statistical analysis and graphical reporting were conducted in R statistical software. To assess the effect of predictors of discharge destination, odds ratios with the corresponding 95%CI were extracted from the results of univariate and multivariable analyses. Results A total of 9 articles published between 2011 to 2018 with 218,151 TKA patients were included. Of the 13 intrinsic patient factors reported, 6 met the criteria for synthesised review: age, obesity, comorbidity, gender, SF-12/VR-12 survey, and smoking. Due to the heterogeneity of statistical analysis and reporting 2 variables could undergo meta-analysis, gender and smoking. Female gender increased the likelihood of IRF discharge by 78% (OR = 1.78; 95%CI = 1.43–2.20; I2 = 33.3%), however, the relationship between smoking status and discharge destination was less certain (OR = 0.80; 95%CI = 0.42–1.50; I2 = 68.5%). Conclusion In this systematic literature review and meta-analysis female gender was shown to be predictive of IRF discharge after total knee arthroplasty. There was also a trend for those of older age and increased comorbidity, as measured by the Charlson Comorbidity Index, or the severely obese to have an increased likelihood of IRF discharge. The marked heterogeneity of statistical methods and reporting in existing literature made pooled analysis challenging for intrinsic patient factors predictive of IRF discharge after TKA. Further, high quality studies of prospective design on predictive factors are warranted, to enable early discharge planning and optimise resource allocation on post-acute care following TKA. Trial registration This review was registered with PROSPERO (CRD42019134422).

Background A substantial proportion of breast cancer patients develop metastatic disease, with over 450,000 deaths globally per year. Bone is the most common first site of metastatic disease accounting for 40% of all first recurrence and 70% of patients with advanced disease develop skeletal involvement. Treatment of bone metastases currently focusses on symptom relief and prevention and treatment of skeletal complications. However, there remains a need for further treatment options for patients with bone metastases. Combining systemic therapy with a bone-targeted agent, such as radium-223, may provide an effective treatment with minimal additional side effects. Methods/design CARBON is a UK-based, open-label, multi-centre study which comprises an initial safety phase to establish the feasibility and safety of combining radium-223 given on a 6-weekly schedule in combination with orally administered capecitabine followed by a randomised extension phase to further characterise the safety profile and provide preliminary estimation of efficacy. Discussion The CARBON study is important as the results will be the first to assess radium-223 with chemotherapy in advanced breast cancer. If the results find acceptable rates of toxicity with a decrease in bone turnover markers, further work will be necessary in a phase II/III setting to assess the efficacy and clinical benefit. Trial registration ISRCTN, ISRCTN92755158, Registered on 17 February 2016.

ObjectivesTo assess the effectiveness and reporting standards of psychological interventions for improving outcomes after total knee replacement (TKR).DesignMedline, Embase, and PsycINFO were searched from inception to up to 9 May 2019 with no language restrictions applied. Randomised controlled trials (RCTs) assessing the effectiveness of psychological interventions for short-term and long-term postoperative pain after TKR were included. Screening, data extraction, and assessment of methodological quality were performed in duplicate by two reviewers. The primary effectiveness outcome was postoperative pain severity and the primary harm outcome was serious adverse events. Secondary outcomes included function, quality of life, and psychological well-being. Reporting standards were assessed using the Template for Intervention Description and Replication (TIDieR) checklist for intervention reporting.Results12 RCTs were included, with a total of 1299 participants. Psychological interventions comprised music therapy (five studies), guided imagery and music (one study), hypnosis (one study), progressive muscle relaxation with biofeedback (one study), pain coping skills programme (one study), cognitive–behavioural therapy (two studies), and a postoperative management programme (one study). Due to the high heterogeneity of interventions and poor reporting of harms data, it was not possible to make any definitive statements about the overall effectiveness or safety of psychology interventions for pain outcomes after TKR.ConclusionFurther evidence about the effectiveness of psychological interventions for improving pain outcomes after TKR is needed. The reporting of harm outcomes and intervention fidelity is currently poor and could be improved. Future work exploring the impact of intervention timing on effectiveness and whether different psychological approaches are needed to address acute postoperative pain and chronic postoperative pain would be of benefit.PROSPERO registration numberCRD42018095100.

ObjectivesTo explore the experiences of primary care-based professional stakeholders in a dual-sector training programme for foundation pharmacists.MethodsProfessional stakeholders were defined as foundation pharmacists or members of staff working with foundation pharmacists such as general medical or nurse practitioners and administrative staff. Stakeholders were invited to participate via email and through gatekeepers. Participants were asked how they were involved in the training pathway, what their experiences had been and what they hoped for the future. Interviews were audio-recorded, transcribed and thematically analysed using computer software.Key findingsTwenty-eight face-to-face semi-structured interviews were conducted. Five major themes were identified (1) benefits of integration (2) appropriateness of the work (3) perceived impact (4) identity development and (5) training and peer support. These findings outline participants’ experiences of establishing a scope of practice in primary and secondary care settings and developing mechanisms to negotiate non-prescriber status to save general practitioners, practice nurse, community pharmacy and administrator time. Foundation pharmacists were able to develop a professional identity whilst working in each care setting, highlighting the dominance of hospital pharmacy exposure in clinical knowledge acquisition and establishing a community of practice across organisational and geographical boundaries using WhatsApp as a peer support tool.ConclusionsFoundation pharmacists are able to work within their own competencies in two different care settings, developing scopes of practice and contributing clinically to service provision. This work provides evidence that this type of training pathway can offer an appropriate landscape for pharmacy practitioner development. Further work is needed to explore the longitudinal outcomes of the programme.

ISSUE ADDRESSED The aim of this study was to characterise lifestyle and training habits of a large cohort of Australian recreational runners. Understanding the health benefits of recreational running and differentiating between the habits of males and females may allow for the development of gender-specific messaging for promoting recreational running as a form of physical activity. METHODS An online questionnaire was used to collect data from 4720 Australian recreational runners. Data on physical, lifestyle and training characteristics of male and female subgroups were compared using chi-square tests. Multiple logistic regression method was used to assess the effect of running experience on the reported clinically significant weight loss. RESULTS The study cohort was 54.1% female and 45.9% male. Smoking was uncommon among surveyed runners. The most typical weekly running distance in the cohort was 20-40 km, usually distributed by 2-5 running sessions. Significantly more males than females reported running over 40 km per week (29.9% vs 18.9%, P < .001) and running at least six sessions per week (11.5% vs 6.7%, P < .001). The majority (72.9%) of runners had normal BMI, and the cohort reported a lower overweight/obesity rate than the Australian population. The logistic regression model indicated that commencing running may lead to a clinically significant weight loss irrespectively of sex, participation in other sports and injury history. CONCLUSION Recreational running was associated with beneficial health outcomes. Commencement of running is associated with weight loss, and regular running supports healthy weight maintenance. Male and female runners had different running preferences which should be taken into account for physical activity promotion. SO WHAT?: Captured health outcomes associated with running and described sex differences in training patterns may assist in development of physical activity promotion programmes involving recreational running, particularly targeting weight loss and healthy weight maintenance.

The major function of the enzyme human tissue transglutaminase (TG2) is the crosslinking of proteins via a transamidation between the γ-carboxamide of a glutamine and the ε-amino group of a lysine. Overexpression of TG2 can lead to undesirable outcomes and has been linked to conditions such as fibrosis, celiac disease and neurodegenerative diseases. Accordingly, TG2 is a tempting drug target. The most effective TG2 inhibitors to date are small-molecule peptidomimetics featuring electrophilic warheads that irreversibly modify the active site catalytic cysteine (CYS277). In an effort to facilitate the design of such TG2 inhibitors, we undertook a quantum mechanical reaction profiling of the Michael reaction between a set of six acrylamide-based known TG2 inhibitors and the TG2 CYS277. The inhibitors were docked into the active site and the coordinates were refined by MD simulations prior to modelling the covalent modification of the CYS277 thiolate. The results of QM/MM MD umbrella sampling applied to reaction coordinates driving the Michael reaction are presented for two approximations of the Michael reaction: a concerted reaction (simultaneous thiolate attack onto the acrylamide warhead and pronation from the adjacent HIS335) and a two-stage reaction (consecutive thiolate attack and protonation). The two-stage approximation of the Michael reaction gave the better results for the evaluation of acrylamide-based potential TG2 inhibitors in silico. Good correlations were observed between the experimental TG2 IC50 data and the calculated activation energies over the range 0.0061 – 6.3 µM (three orders of magnitude) and we propose that this approach may be used to evaluate acrylamide-based potential TG2 inhibitors.