Parsing digital or analog TCR performance through piconewton forces.

αß T cell receptors (TCRs) principally recognize aberrant peptides bound to major histocompatibility complex molecules (pMHCs) on unhealthy cells, amplifying specificity and sensitivity through physical load placed on the TCR-pMHC bond during immunosurveillance. To understand this mechanobiology, TCRs stimulated by abundantly and sparsely arrayed epitopes (NP366-374/Db and PA224-233/Db, respectively) following in vivo influenza A virus infection were studied with optical tweezers. While certain NP repertoire CD8 T lymphocytes require many ligands for activation, others are digital, needing just few. Conversely, all PA TCRs perform digitally, exhibiting pronounced bond lifetime increases through sustained, energizing volleys of structural transitioning. Optimal digital performance is superior in vivo, correlating with ERK phosphorylation, CD3 loss, and activation marker up-regulation in vitro. Given neoantigen array paucity, digital TCRs are likely critical for immunotherapies.

A qualitative evaluation of a fentanyl patch safer supply program in Vancouver, Canada.

BACKGROUND: The ongoing overdose crisis in Canada has prompted efforts to increase access to a "safer supply" of prescribed alternatives to the unregulated drug supply. While safer supply programs predominantly distribute hydromorphone tablets, the Safer Alternatives for Emergency Response (SAFER) program in Vancouver, Canada offers a range of prescribed alternatives, including fentanyl patches. However, little is known about the effectiveness of fentanyl patches as safer supply. Drawing on the perspectives and experiences of program participants, we sought to qualitatively evaluate the effectiveness of the SAFER fentanyl patch program in meeting its intended aims, including reducing risk of overdose by decreasing reliance on the unregulated drug supply. METHODS: As part of a larger mixed-methods evaluation of SAFER, semi-structured qualitative interviews were conducted with 17 fentanyl patch program participants between February 2022 and April 2023. Thematic analysis of interview data focused on program engagement, experiences, impacts, and challenges. RESULTS: The flexible program structure, including lack of need for daily dispensation, the extended missed dose protocol, and community pharmacy patch distribution fostered engagement and enhanced autonomy. Improved management of withdrawal symptoms and cravings due to steady transdermal dosing led to reduced unregulated drug use and overdose risk. Participants also experienced economic benefits and improvements in overall health and quality of life. However, skin irritation and patch adhesion issues were key barriers to program retention. CONCLUSION: Our findings demonstrate the value of including fentanyl patch safer supply in the substance use continuum of care and offer insights for innovations in delivery of this intervention.

Effect of fractional exhaled nitric oxide (FENO)-based asthma management during pregnancy versus usual care on infant development, temperament, sensory function and autism signs.

Asthma during pregnancy is associated with a range of adverse perinatal outcomes. It is also linked to increased rates of neurodevelopmental conditions in the offspring. We aimed to assess whether fractional exhaled nitric oxide (FENO)-based asthma management during pregnancy improves child developmental and behavioural outcomes compared to usual care. The Breathing for Life Trial was a randomised controlled trial that compared FENO-based asthma management during pregnancy to usual care. Participants were invited to the developmental follow-up, the Breathing for Life Trial - Infant Development study, which followed up infants at 6 weeks, 6 months and 12 months. The primary outcomes were measured in infants at 12 months using the Bayley-III: Cognitive, Language and Motor composite scores. Secondary outcomes included Bayley-III social-emotional and adaptive behaviour scores, autism likelihood and sensory and temperament outcomes. The exposure of interest was the randomised intervention group. Two hundred and twenty-two infants and their 217 participating mothers were recruited to the follow-up; 107 mothers were in the intervention group and 113 were in the control group. There was no evidence of an intervention effect for the primary outcomes: Bayley-III cognitive (mean = 108.9 control, 108.5 intervention, p = 0.93), language (mean = 95.9 control, 95.6 intervention, p = 0.87) and motor composite scores (mean = 97.2 control, 97.9 intervention, p = 0.25). Mean scores for secondary outcomes were also similar among infants born to control and FENO group mothers, with few results reaching p < 0.05. CONCLUSION:  In this sample, FENO-guided asthma treatment during pregnancy did not improve infant developmental outcomes in the first year of life. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: ACTRN12613000202763. WHAT IS KNOWN: • Maternal asthma during pregnancy has been associated with increased rates of neurodevelopmental conditions in offspring, including intellectual disability and autism. WHAT IS NEW: • This is the first study to examine how managing asthma during pregnancy via a FENO-guided algorithm or usual care affects infant developmental and behavioural outcomes. While the results of the study showed no impact of the intervention, and therefore do not support the integration of FENO-based management of asthma in antenatal settings for optimal infant development, they do send a positive message about the implications of active asthma management during pregnancy on infant developmental outcomes.

Landscape fire smoke airway exposure impairs respiratory and cardiac function and worsens experimental asthma.

BACKGROUND: Millions of people are exposed to landscape fire smoke (LFS) globally, and inhalation of LFS particulate matter (PM) is associated with poor respiratory and cardiovascular outcomes. However, how LFS affects respiratory and cardiovascular function is less well understood. OBJECTIVE: We aimed to characterize the pathophysiologic effects of representative LFS airway exposure on respiratory and cardiac function and on asthma outcomes. METHODS: LFS was generated using a customized combustion chamber. In 8-week-old female BALB/c mice, low (25 µg/m3, 24-hour equivalent) or moderate (100 µg/m3, 24-hour equivalent) concentrations of LFS PM (10 µm and below [PM10]) were administered daily for 3 (short-term) and 14 (long-term) days in the presence and absence of experimental asthma. Lung inflammation, gene expression, structural changes, and lung function were assessed. In 8-week-old male C57BL/6 mice, low concentrations of LFS PM10 were administered for 3 days. Cardiac function and gene expression were assessed. RESULTS: Short- and long-term LFS PM10 airway exposure increased airway hyperresponsiveness and induced steroid insensitivity in experimental asthma, independent of significant changes in airway inflammation. Long-term LFS PM10 airway exposure also decreased gas diffusion. Short-term LFS PM10 airway exposure decreased cardiac function and expression of gene changes relating to oxidative stress and cardiovascular pathologies. CONCLUSIONS: We characterized significant detrimental effects of physiologically relevant concentrations and durations of LFS PM10 airway exposure on lung and heart function. Our study provides a platform for assessment of mechanisms that underpin LFS PM10 airway exposure on respiratory and cardiovascular disease outcomes.

Prevalence and associations of provision of nursing home visits and home visits by early-career specialist general practitioners.

OBJECTIVE: To establish prevalence and associations of provision of nursing home visits (NHV) and home visits (HV) by early-career specialist GPs. Of particular interest were associations of rurality with performing NHVs and HVs. METHODS: A cross-sectional study. DESIGN: A questionnaire-based study. SETTING: Australian general practice. PARTICIPANTS: Early-career specialist GPs, practising in Australia, who attained Fellowship between January 2016 and July 2018, inclusive, having completed GP training in NSW, the ACT, Eastern Victoria or Tasmania. MAIN OUTCOME MEASURES: Current provision of NHV and HV. RESULTS: NHV were provided by 34% of participants (59% in rural areas) and HV by 41% of participants (60% in rural areas). Remote, rural or regional practice location, as compared to major-city practice, was strongly associated with performing NHV as an early-career specialist GP; multivariable OR 5.87 (95% CI: 2.73, 12.6), p < 0.001, and with the provision of HV; multivariable OR 3.64 (95% CI: 1.63, 8.11), p = 0.002. Rurality of GP training (prior to attaining Fellowship) was significantly univariably associated with providing NHV and with providing HV as an early-career specialist GP. On multivariable analyses, these were no longer statistically significant. CONCLUSION: Early-career specialist GPs located in regional/remote areas are more likely than their urban colleagues to provide NHV and HV.

Perceptions of the effectiveness of using patient encounter data as an education and reflection tool in general practice training.

Introduction Patient encounter tools provide feedback and potentially reflection on general practitioner (GP) registrars' in-practice learning and may contribute to the formative assessment of clinical competencies. However, little is known about the perceived utility of such tools. Aim To investigate the perceived utility of a patient encounter tool by GP registrars, their supervisors, and medical educators (MEs). Methods General practice registrars, supervisors and MEs from two Australian regional training organisations completed a cross-sectional questionnaire. Registrars rated how Registrar Clinical Encounters in Training (ReCEnT), a patient encounter tool, influenced their reflection on, and change in, clinical practice, learning and training. Supervisors' and MEs' perceptions provided contextual information about understanding their registrars' clinical practice, learning and training needs. Results Questionnaires were completed by 48% of registrars (n = 90), 22% of supervisors (n = 182), and 61% of MEs (n = 62). Most registrars agreed that ReCEnT helped them reflect on their clinical practice (79%), learning needs (69%) and training needs (72%). Many registrars reported changing their clinical practice (54%) and learning approaches (51%). Fewer (37%) agreed that ReCEnT influenced them to change their training plans. Most supervisors (68%) and MEs (82%) agreed ReCEnT reports helped them better understand their registrars' clinical practice. Similarly, most supervisors (63%) and MEs (68%) agreed ReCEnT reports helped them better understand their registrars' learning and training needs. Discussion ReCEnT can prompt self-reflection among registrars, leading to changes in clinical practice, learning approaches and training plans. Reaching its potential as an assessment for learning (as opposed to an assessment of learning) requires effective engagement between registrars, their supervisors and MEs.

Utilisation of in-consultation supervisor assistance in general practice training and personal cost to trainees: a cross-sectional study.

Aim The aim of the study was to establish whether two previously described barriers to effective in-consultation assistance-seeking by general practice (GP) vocational specialist trainees (ie concern about patient impressions of their competence, and discomfort presenting to supervisors in front of patients) influenced the frequency of trainee in-consultation assistance-seeking from their supervisor. Methods This was a cross-sectional study nested in the Registrar Clinical Encounters in Clinical Training ongoing cohort study of Australian GP trainees. Trainee participants completed contemporaneous records of 60 consecutive patient consultations, including whether supervisory assistance was sought. Trainees also completed a cross-sectional survey including items eliciting their beliefs about patient impressions and their own discomfort in seeking in-consultation supervisory assistance. These were factors of interest in multivariable logistic regression analyses; the outcome factor in both regression models was the seeking of in-consultation supervisory assistance. Results In 2018, 778 trainees (778/876, response rate 89%) completed the cross-sectional survey. No association was found between the odds of in-consultation help-seeking and perceived decrease in patient impressions of trainee competence (OR = 1.09; 95% CI: 0.91, 1.31; P = 0.36) or higher comfort presenting outside patients' hearing (OR = 0.9; 95% CI: 0.77, 1.05; P = 0.19). Discussion Contrary to expected utility models of help-seeking, trainees may not consider personal discomfort or impression management to be important enough, compared to patient safety and other considerations, to influence decisions regarding in-consultation help-seeking. Clinical supervisors should, nevertheless, consider the potential personal costs to trainees and maintain trainee self-esteem and confidence by providing in-consultation assistance in front of patients as comfortably and effectively as possible.

Prediction of general practice licensure/certification examination performance by a measure of 'questionable' activities in clinical practice: a retrospective cohort study.

PURPOSE: 'Low-value' clinical care and medical services are 'questionable' activities, being more likely to cause harm than good or with disproportionately low benefit relative to cost. This study examined the predictive ability of the QUestionable In Training Clinical Activities Index (QUIT-CAI) for general practice (GP) registrars' (trainees') performance in Australian GP Fellowship examinations (licensure/certification examinations for independent GP). METHODS: The study was nested in ReCEnT, an ongoing cohort study in which Australian GP registrars document their in-consultation clinical practice. Outcome factors in analyses were individual registrars' scores on the three Fellowship examinations ('AKT', 'KFP', and 'OSCE' examinations) and pass/fail rates during 2012-21. Analyses used univariable and multivariable regression (linear or logistic, as appropriate). The study factor in each analysis was 'QUIT-CAI score percentage'-the percentage of times a registrar performed a QUIT-CAI clinical activity when 'at risk' (i.e. when managing a problem where performing a QUIT-CAI activity was a plausible option). RESULTS: A total of 1265, 1145, and 553 registrars sat Applied Knowledge Test, Key Features Problem, and Objective Structured Clinical Exam examinations, respectively. On multivariable analysis, higher QUIT-CAI score percentages (more questionable activities) were significantly associated with poorer Applied Knowledge Test scores (P = .001), poorer Key Features Problem scores (P = .003), and poorer Objective Structured Clinical Exam scores (P = .005). QUIT-CAI score percentages predicted Royal Australian College of General Practitioner exam failure [odds ratio 1.06 (95% CI 1.00, 1.12) per 1% increase in QUIT-CAI, P = .043]. CONCLUSION: Performing questionable clinical activities predicted poorer performance in the summative Fellowship examinations, thereby validating these examinations as measures of actual clinical performance (by our measure of clinical performance, which is relevant for a licensure/certification examination).

Development of a diagnostic support tool for predicting cervical arterial dissection in primary care.

OBJECTIVES: Cervical arterial dissection (CAD) is an important cause of stroke in young people which may be missed because early features may mimic migraine or a musculoskeletal presentation. The study aimed to develop a diagnostic support tool for early identification of CAD. DESIGN: Retrospective observational study. SETTING: Tertiary hospital. PARTICIPANTS: Radiologically confirmed CAD cases (n = 37), non-CAD stroke cases (n = 20), and healthy controls (n = 100). MAIN OUTCOME MEASURES: The presence of CAD is confirmed with imaging. Predictive variables included risk factors and clinical characteristics of CAD. Variables with a p-value <0.2 included in a multivariable model. Predictive utility of the model is assessed by calculating area underthe ROC curve (AUC). RESULTS: The model including four variables: age 40-55 years (vs < 40), trauma, recent onset headache, and > 2 neurological features, demonstrated excellent discrimination: AUC of 0.953 (95% CI: 0.916, 0.987). A predictive scoring system (total score/7) identified an optimal threshold of ≥ 3 points, with a sensitivity of 87% and specificity of 79%. CONCLUSIONS: The study identified a diagnostic support tool with four variables to predict increased risk of CAD. Validation in a clinical sample is needed to confirm variables and refine descriptors to enable clinicians to efficiently apply the tool.Optimum cutoff scores of ≥ 3/7 points will help identify those in whom CAD should be considered and further investigation instigated. The potential impact of the tool is to improve early recognition of CAD in those with acute headache or neck pain, thereby facilitating more timely medical intervention, preventing inappropriate treatment, and improving patient outcomes.Wordcount: 3195.

Using Genetics to Inform Interventions Related to Sodium and Potassium in Hypertension.

BACKGROUND: Hypertension is a key risk factor for major adverse cardiovascular events but remains difficult to treat in many individuals. Dietary interventions are an effective approach to lower blood pressure (BP) but are not equally effective across all individuals. BP is heritable, and genetics may be a useful tool to overcome treatment response heterogeneity. We investigated whether the genetics of BP could be used to identify individuals with hypertension who may receive a particular benefit from lowering sodium intake and boosting potassium levels. METHODS: In this observational genetic study, we leveraged cross-sectional data from up to 296 475 genotyped individuals drawn from the UK Biobank cohort for whom BP and urinary electrolytes (sodium and potassium), biomarkers of sodium and potassium intake, were measured. Biologically directed genetic scores for BP were constructed specifically among pathways related to sodium and potassium biology (pharmagenic enrichment scores), as well as unannotated genome-wide scores (conventional polygenic scores). We then tested whether there was a gene-by-environment interaction between urinary electrolytes and these genetic scores on BP. RESULTS: Genetic risk and urinary electrolytes both independently correlated with BP. However, urinary sodium was associated with a larger BP increase among individuals with higher genetic risk in sodium- and potassium-related pathways than in those with comparatively lower genetic risk. For example, each SD in urinary sodium was associated with a 1.47-mm Hg increase in systolic BP for those in the top 10% of the distribution of genetic risk in sodium and potassium transport pathways versus a 0.97-mm Hg systolic BP increase in the lowest 10% (P=1.95×10-3). This interaction with urinary sodium remained when considering estimated glomerular filtration rate and indexing sodium to urinary creatinine. There was no strong evidence of an interaction between urinary sodium and a standard genome-wide polygenic score of BP. CONCLUSIONS: The data suggest that genetic risk in sodium and potassium pathways could be used in a precision medicine model to direct interventions more specifically in the management of hypertension. Intervention studies are warranted.

Video versus telephone for telehealth delivery: a cross-sectional study of Australian general practice trainees.

BACKGROUND: Remunerated telehealth consultations were introduced in Australia in 2020 in response to the COVID-19 pandemic. Videoconferencing has advantages over telephone-consulting, including improved diagnostic and decision-making accuracy. However, videoconferencing uptake in Australia has been low. This study aimed to establish prevalence and associations of video versus telephone consultations in Australian general practice (GP) registrars' practice. METHODS: A cross-sectional analysis of data from 2020 to 2021 (three 6-monthly data-collection rounds) from the Registrars Clinical Encounters in Training (ReCEnT) study. GP registrars record details of 60 consecutive consultations every 6-month term, for a total of 3 terms. Univariable and multivariable logistic regression were performed within the Generalized Estimating Equations framework with the outcome video versus telephone. RESULTS: 102,286 consultations were recorded by 1,168 registrars, with 21.4% of consultations performed via telehealth. Of these, telephone accounted for 96.6% (95% CI: 96.3-96.8%) and videoconferencing for 3.4% (95% CI: 3.2-3.7%). Statistically significant associations of using videoconferencing, compared to telephone, included longer consultation duration (OR 1.02, 95% CI: 1.01-1.03 per minute; and mean 14.9 versus 12.8 min), patients aged 0-14 years old (OR 1.29, 95% CI: 1.03-1.62, compared to age 15-34), patients new to the registrar (OR 1.19, 95% CI: 1.04-1.35), part-time registrars (OR 1.84, 95% CI: 1.08-3.15), and areas of less socioeconomic disadvantage (OR 1.27, 95% CI: 1.00-1.62 per decile). CONCLUSIONS: Registrars' telehealth consultations were mostly performed via telephone. Telephone use being associated with socioeconomic disadvantage has health equity implications. Future research should explore barriers to videoconferencing use and strategies to increase its uptake.

Characterization and inhibition of inflammasome responses in severe and non-severe asthma.

BACKGROUND: Increased airway NLRP3 inflammasome-mediated IL-1ß responses may underpin severe neutrophilic asthma. However, whether increased inflammasome activation is unique to severe asthma, is a common feature of immune cells in all inflammatory types of severe asthma, and whether inflammasome activation can be therapeutically targeted in patients, remains unknown. OBJECTIVE: To investigate the activation and inhibition of inflammasome-mediated IL-1ß responses in immune cells from patients with asthma. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from patients with non-severe (n = 59) and severe (n = 36 stable, n = 17 exacerbating) asthma and healthy subjects (n = 39). PBMCs were stimulated with nigericin or lipopolysaccharide (LPS) alone, or in combination (LPS + nigericin), with or without the NLRP3 inhibitor MCC950, and the effects on IL-1ß release were assessed. RESULTS: PBMCs from patients with non-severe or severe asthma produced more IL-1ß in response to nigericin than those from healthy subjects. PBMCs from patients with severe asthma released more IL-1ß in response to LPS + nigericin than those from non-severe asthma. Inflammasome-induced IL-1ß release from PBMCs from patients with severe asthma was not increased during exacerbation compared to when stable. Inflammasome-induced IL-1ß release was not different between male and female, or obese and non-obese patients and correlated with eosinophil and neutrophil numbers in the airways. MCC950 effectively suppressed LPS-, nigericin-, and LPS + nigericin-induced IL-1ß release from PBMCs from all groups. CONCLUSION: An increased ability for inflammasome priming and/or activation is a common feature of systemic immune cells in both severe and non-severe asthma, highlighting inflammasome inhibition as a universal therapy for different subtypes of disease.

Parsing digital or analogue TCR performance through piconewton forces.

αß T-cell receptors (TCRs) recognize aberrant peptides bound to major histocompatibility complex molecules (pMHCs) on unhealthy cells, amplifying specificity and sensitivity through physical load placed on the TCR-pMHC bond during immunosurveillance. To understand this mechanobiology, TCRs stimulated by abundantly and sparsely arrayed epitopes (NP 366-374 /D b and PA 224-233 /D b , respectively) following in vivo influenza A virus infection were studied with optical tweezers. While certain NP repertoire CD8 T lymphocytes require many ligands for activation, others are digital, needing just few. Conversely, all PA TCRs perform digitally, exhibiting pronounced bond lifetime increases through sustained, energizing volleys of structural transitioning. Optimal digital performance is superior in vivo, correlating with ERK phosphorylation, CD3 loss, and activation marker upregulation in vitro . Given neoantigen array paucity, digital TCRs are likely critical for immunotherapies. One Sentence Summary: Quality of ligand recognition in a T-cell repertoire is revealed through application of physical load on clonal T-cell receptor (TCR)-pMHC bonds.

MTHFR C677T and A1298C polymorphism's effect on risk of colorectal cancer in Lynch syndrome.

Lynch syndrome (LS) is characterised by an increased risk of developing colorectal cancer (CRC) and other extracolonic epithelial cancers. It is caused by pathogenic germline variants in DNA mismatch repair (MMR) genes or the EPCAM gene, leading to a less functional DNA MMR system. Individuals diagnosed with LS (LS individuals) have a 10-80% lifetime risk of developing cancer. However, there is considerable variability in the age of cancer onset, which cannot be attributed to the specific MMR gene or variant alone. It is speculated that multiple genetic and environmental factors contribute to this variability, including two single nucleotide polymorphisms (SNPs) in the methylenetetrahydrofolate reductase (MTHFR) gene: C677T (rs1801133) and A1298C (rs1801131). By decreasing MTHFR activity, these SNPs theoretically reduce the silencing of DNA repair genes and increase the availability of nucleotides for DNA synthesis and repair, thereby protecting against early-onset cancer in LS. We investigated the effect of these SNPs on LS disease expression in 2,723 LS individuals from Australia, Poland, Germany, Norway and Spain. The association between age at cancer onset and SNP genotype (risk of cancer) was estimated using Cox regression adjusted for gender, country and affected MMR gene. For A1298C (rs1801131), both the AC and CC genotypes were significantly associated with a reduced risk of developing CRC compared to the AA genotype, but no association was seen for C677T (rs1801133). However, an aggregated effect of protective alleles was seen when combining the alleles from the two SNPs, especially for LS individuals carrying 1 and 2 alleles. For individuals with germline pathogenic variants in MLH1, the CC genotype of A1298C was estimated to reduce the risk of CRC significantly by 39% (HR = 0.61, 95% CI 0.42, 0.89, p = 0.011), while for individuals with pathogenic germline MSH2 variants, the AC genotype (compared to AA) was estimated to reduce the risk of CRC by 26% (HR = 0.66, 95% CI 0.53, 0.83, p = 0.01). In comparison, no association was observed for C677T (rs1801133). In conclusion, our study suggests that combining the MMR gene information with the MTHFR genotype, including the aggregated effect of protective alleles, could be useful in developing an algorithm that estimates the risk of CRC in LS individuals.

Exam prediction and the general Practice Registrar Competency Assessment Grid (GPR-CAG).

BACKGROUND: In GP training, identifying early predictors of poor summative examination performance can be challenging. We aimed to establish whether external clinical teaching visit (ECTV) performance, measured using a validated instrument (GP Registrar Competency Assessment Grid, GPR-CAG) is predictive of Royal Australian College of General Practitioners (RACGP) Fellowship examination performance. METHODS: A retrospective cohort study including GP registrars in New South Wales/Australian Capital Territory with ECTV data recorded during their first training term (GPT1), between 2014 and 2018, who attempted at least one Fellowship examination. Independent variables of interest included the four GPR-CAG factors assessed in GPT1 ('patient-centredness/caring', 'formulating hypotheses/management plans', 'professional responsibilities', 'physical examination skills'). Outcomes of interest included individual scores of the three summative examinations (Applied Knowledge Test (AKT); Key Feature Problem (KFP); and the Objective Structured Clinical Examination (OSCE)) and overall Pass/Fail status. Univariable and multivariable regression analyses were performed. RESULTS: Univariably, there were statistically significant associations (p < 0.01) between all four GPR-CAG factors and all four summative examination outcomes, except for 'formulating hypotheses/management plans' and OSCE score (p = 0.07). On multivariable analysis, each factor was significantly associated (p < 0.05) with at least one exam outcome, and 'physical examination skills' was significantly associated (p < 0.05) with all four exam outcomes. DISCUSSION: ECTV performance, via GPR-CAG scores, is predictive of RACGP Fellowship exam performance. The univariable findings highlight the pragmatic utility of ECTVs in flagging registrars who are at-risk of poor exam performance, facilitating early intervention. The multivariable associations of GPR-CAG scores and examination performance suggest that these scores provide predictive ability beyond that of other known predictors.

'Low-value' clinical care in general practice: a cross-sectional analysis of low-value care in early-career GPs' practice.

Nonevidence-based and 'low-value' clinical care and medical services are 'questionable' clinical activities that are more likely to cause harm than good or whose benefit is disproportionately low compared with their cost. This study sought to establish general practitioner (GP), patient, practice, and in-consultation associations of an index of key nonevidence-based or low-value 'questionable' clinical practices. The study was nested in the Registrar Clinical Encounters in Training study-an ongoing (from 2010) cohort study in which Australian GP registrars (specialist GP trainees) record details of their in-consultation clinical and educational practice 6-monthly. The outcome factor in analyses, performed on Registrar Clinical Encounters in Training data from 2010 to 2020, was the score on the QUestionable In-Training Clinical Activities Index (QUIT-CAI), which incorporates recommendations of the Australian Choosing Wisely campaign. A cross-sectional analysis used negative binomial regression (with the model including an offset for the number of times the registrar was at risk of performing a questionable activity) to establish associations of QUIT-CAI scores. A total of 3206 individual registrars (response rate 89.9%) recorded 406 812 problems/diagnoses where they were at risk of performing a questionable activity. Of these problems/diagnoses, 15 560 (3.8%) involved questionable activities being performed. In multivariable analyses, higher QUIT-CAI scores (more questionable activities) were significantly associated with earlier registrar training terms: incidence rate ratios (IRRs) of 0.91 [95% confidence interval (CI) 0.87, 0.95] and 0.85 (95% CI 0.80, 0.90) for Term 2 and Term 3, respectively, compared to Term 1. Other significant associations of higher scores included the patient being new to the registrar (IRR 1.27; 95% CI 1.12, 1.45), the patient being of non-English-speaking background (IRR 1.24; 95% CI 1.04, 1.47), the practice being in a higher socioeconomic area decile (IRR 1.01; 95% CI 1.00, 1.02), small practice size (IRR 1.05; 95% CI 1.00, 1.10), shorter consultation duration (IRR 0.99 per minute; 95% CI 0.99, 1.00), and fewer problems addressed in the consultation (IRR 0.84; 95% CI 0.79, 0.89) for each additional problem]. Senior registrars' clinical practice entailed less 'questionable' clinical actions than junior registrars' practice. The association of lower QUIT-CAI scores with a measure of greater continuity of care (the patient not being new to the registrar) suggests that continuity should be supported and facilitated during GP training (and in established GPs' practice).

General practice registrars training part-time: a cross-sectional analysis of prevalence and associations.

While GPs are working fewer clinical hours and many GP trainees (registrars) do not foresee themselves working full-time in clinical practice, little is known of the epidemiology of registrars training part-time. We aimed to establish the prevalence of general practice part-time training (PTT), and part-time registrars' characteristics and practice patterns. A cross-sectional analysis was conducted of data from the Registrar Clinical Encounters in Training project, an ongoing cohort study of Australian GP registrars' clinical experiences over 60 consecutive consultations in each of three training terms. Univariable and multivariable logistic regression analyses were conducted with the outcome 'training part-time'. 1790 registrars contributed data for 4,135 registrar-terms and 241,945 clinical encounters. Nine hundred and twenty-two registrar-terms (22%, 95%CI:21%-24%) and 52,339 clinical encounters (22%, 95%CI:21%-22%) involved PTT. Factors associated with PTT were registrar characteristics - female gender, older age, in a later training stage, performing other regular medical work; practice characteristics - working in a higher socioeconomic status area; and patient characteristics - seeing more patients new to the registrar and seeing more patients from a non-English-speaking background. No consultation or consultation action factors were significantly associated with PTT. Registrars, practices, and patient associations have GP training implications. The lack of registrar consultation or consultation action associations suggests there may be limited impact of PTT on patient care.

Absolute cardiovascular risk assessment by Australian early-career general practitioners: a cross-sectional study.

OBJECTIVE: To determine the prevalence and associations of general practice registrars' performing absolute cardio-vascular risk (ACVR) assessment (ACVRa). DESIGN: A cross-sectional study employing data (2017-2018) from the Registrar Clinical Encounters in Training project, an ongoing inception cohort study of Australian GP registrars. The outcome measure was whether an ACVRa was performed. Analyses employed univariable and multivariable regression. Analysis was conducted for all patient problems/diagnoses, then for an 'at-risk' population (specific problems/diagnoses for which ACVRa is indicated). SETTING: Three GP regional training organisations (RTOs) across three Australian states. PARTICIPANTS: GP registrars training within participating RTOs. RESULTS: 1003 registrars (response rate 96.8%) recorded details of 69 105 problems either with Aboriginal and/or Torres Strait patients aged 35 years and older or with non-Indigenous patients aged 45 years and older. Of these problems/diagnoses, 1721 (2.5% (95% CI 2.4% to 2.6%)) involved an ACVRa. An ACVRa was 'plausibly indicated' in 10 384 problems/diagnoses. Of these, 1228 (11.8% (95% CI 11.2% to 12.4%)) involved ACVRa. For 'all problems/diagnoses', on multivariable analysis female gender was associated with reduced odds of ACVRa (OR 0.61 (95% CI 0.54 to 0.68)). There was some evidence for Aboriginal and/or Torres Strait Islander people being more likely to receive ACVRa (OR 1.40 (95% CI 0.94 to 2.08), p=0.10). There were associations with variables related to continuity of care, with reduced odds of ACVRa: if the patient was new to the registrar (OR 0.65 (95% CI 0.57 to 0.75)), new to the practice (OR 0.24 (95% CI 0.15 to 0.38)) or the problem was new (OR 0.68 (95% CI 0.59 to 0.78)); and increased odds if personal follow-up was organised (OR 1.43 (95% CI 1.24 to 1.66)). For 'ACVRa indicated' problems/diagnoses, findings were similar to those for 'all problems/diagnoses'. Association with Aboriginal and/or Torres Strait Islander status, however, was significant at p<0.05 (OR 1.60 (95% CI 1.04 to 2.46)) and association with female gender was attenuated (OR 0.88 (95% CI 0.77 to 1.01)). CONCLUSION: Continuity of care is associated with registrars assessing ACVR, reinforcing the importance of care continuity in general practice. Registrars' assessment of an individual patient's ACVR is targeted to patients with individual risk factors, but this may entail ACVRa underutilisation in female patients and younger age groups.

A Novel, Paresthesia-Free Spinal Cord Stimulation Waveform for Chronic Neuropathic Low Back Pain: Six-Month Results of a Prospective, Single-Arm, Dose-Response Study.

OBJECTIVES: The aim of this prospective, single-blinded, dose-response study was to evaluate the safety and efficacy of a novel, paresthesia-free (subperception) spinal cord stimulation (SCS) waveform designed to target dorsal horn dendrites for the treatment of chronic neuropathic low back pain (LBP). MATERIALS AND METHODS: Twenty-seven participants with chronic neuropathic LBP were implanted with a commercial SCS system after a successful trial of SCS therapy. Devices were programmed to deliver the investigative waveform (100 Hz, 1000 µs, T9/T10 bipole) at descending stimulation perception threshold amplitudes (80%, 60%, 40%). Programs were evaluated at six, ten, and 14 weeks, after which participants selected their preferred program, with more follow-up at 26 weeks (primary outcomes). Participants were blinded to the nature of the programming. Pain score (visual analog scale [VAS]), Brief Pain Inventory (BPI), quality of life (EQ-5D-5L), and health status (36-Item Short Form [SF-36]) were measured at baseline and follow-ups. Responder rate, treatment satisfaction, clinician global impression of change, and adverse events (AEs) also were evaluated. RESULTS: Mean (± SD) baseline VAS was 72.5 ± 11.2 mm. At 26 weeks (n = 26), mean change from baseline in VAS was -51.7 mm (95% CI, -60.7 to -42.7; p < 0.001), with 76.9% of participants reporting ≥50% VAS reduction, and 46.2% reporting ≥80% VAS reduction. BPI, EQ-5D-5L, and SF-36 scores were all statistically significantly improved at 26 weeks (p < 0.001), and 100% of participants were satisfied with their treatment. There were no unanticipated AEs related to the study intervention, device, or procedures. CONCLUSIONS: This novel, paresthesia-free stimulation waveform may be a safe and effective option for patients with chronic neuropathic LBP eligible for SCS therapy and is deliverable by all current commercial SCS systems. CLINICAL TRIAL REGISTRATION: This study is registered on anzctr.org.au with identifier ACTRN12618000647235.

The prevalence and associations of Australian early-career general practitioners' provision of after-hours care.

INTRODUCTION: Access to after-hours care (AHC) is an important aspect of general practice service provision. OBJECTIVE: To establish the prevalence and associations of early-career GPs' provision of AHC. DESIGN: An analysis of data from the New alumni Experiences of Training and independent Unsupervised Practice (NEXT-UP) cross-sectional questionnaire-based study. Participants were early-career GPs (6-month to 2-year post-Fellowship) following the completion of GP vocational training in NSW, the ACT, Victoria or Tasmania. The outcome factor was 'current provision of after-hours care'. Associations of the outcome were established using multivariable logistic regression. FINDINGS: Three hundred and fifty-four early-career GPs participated (response rate 28%). Of these, 322 had responses available for analysis of currently performing AHC. Of these observations, 128 (40%) reported current provision of AHC (55% of rural participants and 32% of urban participants). On multivariable analysis, participants who provided any AHC during training were more likely to be providing AHC (odds ratio (OR) 5.51, [95% confidence interval (CI) 2.80-10.80], p < 0.001). Current rural location and in-training rural experience were strongly associated with currently providing AHC in univariable but not multivariable analysis. DISCUSSION: Early-career GPs who provided AHC during training, compared with those who did not, were more than five times more likely to provide after-hours care in their first 2 years after gaining Fellowship, suggesting participation in AHC during training may have a role in preparing registrars to provide AHC as independent practitioners. CONCLUSION: These findings may inform future GP vocational training policy and practice concerning registrars' provision of AHC during training.