Efgartigimod and Ravulizumab for Treating Acetylcholine Receptor Auto-antibody-Positive (AChR-Ab+) Generalized Myasthenia Gravis: Indirect Treatment Comparison.

INTRODUCTION: Efgartigimod and ravulizumab, both approved for treating acetylcholine receptor auto-antibody-positive (AChR-Ab+) generalized myasthenia gravis (gMG), have not been directly compared. This paper assessed comparative effects of efgartigimod vs. ravulizumab for treating adults with AChR-Ab+ gMG using indirect treatment comparison methods. METHODS: The matching-adjusted indirect comparison used data from two randomized trials of adult men and women. The ADAPT (efgartigimod vs. placebo; individual patient data available) population was reweighted to match the CHAMPION (ravulizumab vs. placebo; index study; aggregate data available) population. The relative effect of efgartigimod versus placebo was estimated in this reweighted population and compared with the observed ravulizumab versus placebo effect to estimate the efgartigimod versus ravulizumab effect. The outcomes were Myasthenia Gravis Activities of Daily Living (MG-ADL), Quantitative Myasthenia Gravis (QMG), and Myasthenia Gravis Quality of Life 15-item-revised scale (MG-QoL15r) assessed as cumulative effect (area under the curve; AUC) over 26 weeks (primary) and change from baseline at 4 weeks and time of best response (week 4 for efgartigimod; week 26 for ravulizumab). RESULTS: For MG-QoL15r, efgartigimod had a statistically significant improvement compared with ravulizumab over 26 weeks [mean difference (95% confidence interval): - 52.6 (- 103.0, - 2.3)], at week 4 [- 4.0 (- 6.6, - 1.4)], and at time of best response [- 3.9 (- 6.5, - 1.3)]. Efgartigimod had a statistically significant improvement over ravulizumab in MG-ADL at week 4 [- 1.9 (- 3.3, - 0.5)] and at time of best response [- 1.4 (- 2.8, 0.0)] and in QMG at week 4 [- 3.2 (- 5.2, - 1.2)] and at time of best response [- 3.0 (- 5.0, - 1.0)]. For AUC over 26 weeks, improvements were not significantly different between efgartigimod and ravulizumab for MG-ADL [- 8.7 (- 36.1, 18.8)] and QMG [- 13.7 (- 50.3, 22.9)]. CONCLUSION: Efgartigimod may provide a faster and greater improvement over 26 weeks in quality of life than ravulizumab in adults with AChR-Ab+ gMG. Efgartigimod showed faster improvements in MG-ADL and QMG than ravulizumab.

Emergency coronary artery bypass surgery after chronic total occlusion percutaneous coronary intervention: Insights from the PROGRESS-CTO registry.

BACKGROUND: Emergency coronary artery bypass surgery (eCABG) is a serious complication of chronic total occlusion (CTO) percutaneous coronary artery intervention (PCI). METHODS: We examined the incidence and outcomes eCABG among 14,512 CTO PCIs performed between 2012 and 2023 in a large multicenter registry. RESULTS: The incidence of eCABG was 0.12% (n = 17). Mean age was 68 ± 6 years and 69% of the patients were men. The most common reason for eCABG was coronary perforation (70.6%). eCABG patients had larger target vessel diameter (3.36 ± 0.50 vs. 2.90 ± 0.52; p = 0.003), were more likely to have moderate/severe calcification (85.7% vs. 45.8%; p = 0.006), side branch at the proximal cap (91.7% vs. 55.4%; p = 0.025), and balloon undilatable lesions (50% vs. 7.4%; p = 0.001) and to have undergone retrograde crossing (64.7% vs. 30.8%, p = 0.006). eCABG cases had lower technical (35.3% vs. 86.7%; p < 0.001) and procedural (35.3% vs. 86.7%; p < 0.001) success and higher in-hospital mortality (35.3% vs. 0.4%; p < 0.001), coronary perforation (70.6% vs. 4.6%; p < 0.001), pericardiocentesis (47.1% vs. 0.8%; p < 0.001), and major bleeding (11.8% vs. 0.5%; p < 0.001). CONCLUSIONS: The incidence of eCABG after CTO PCI was 0.12% and associated with high in-hospital mortality (35%). Coronary perforation was the most common reason for eCABG.

Implementing systematic melanoma risk assessment and risk-tailored surveillance in a skin cancer focussed dermatology clinic: A qualitative study of feasibility and acceptability to patients and clinic staff.

BACKGROUND: International bodies recommend that melanoma risk assessment should be integrated into skin cancer care provision, but evidence to support implementation is lacking. AIM: To explore the acceptability and feasibility of implementing personalised melanoma risk assessment and tailored patient education and skin surveillance within routine clinical care. METHODS: This prospective qualitative implementation study was informed by the Theoretical Framework of Acceptability (TFA). Personalised, systematic melanoma risk assessment was implemented in the dermatology clinic at the Melanoma Institute Australia, Sydney, Australia February-May 2021. Pre- and post-implementation observations and semi-structured interviews with patients and staff were conducted (September 2020-March 2021). Observational notes and interview transcript data were analysed thematically using the TFA as a classifying framework. RESULTS: A total of 37 h of observations were made, and 29 patients and 12 clinic staff were interviewed. We found that the delivery of personalised melanoma risk estimates did not impact on patient flow through the clinic. Dermatologists reported that the personalised risk information enhanced their confidence in assessing patient risk and recommending tailored surveillance schedules. Most patients reported that the risk assessment and tailored information were a beneficial addition to their care. Among patients whose risk deviated from their expectations, some reported feeling worried, confused or mistrust in the risk information, including those at lower risk who were recommended to decrease surveillance frequency. CONCLUSIONS: It is feasible and acceptable to patients and clinic staff to calculate and deliver personalised melanoma risk information and tailored surveillance as part of routine clinical care within dermatology clinics.

PRRSV-2 viral load in critical non-lymphoid tissues is associated with late gestation fetal compromise.

The impact of late gestation PRRSV-2 infection is highly variable within a litter, with a subset of fetuses displaying varying degrees of compromise following infection while others remain viable despite significant systemic viral load. To understand the underlying cause of this variation, we examined the susceptibility, distribution and impact of viral infection within non-lymphoid tissues. Samples of brain, heart, kidney, liver, lung, and skeletal muscle were obtained from fetuses of pregnant gilts at gestation day 86, and the presence and distribution of CD163+ cells within each tissue evaluated via immunohistofluorescence. Equivalent samples were collected from phenotypic extremes representing resistant, resilient and susceptible fetuses at 21 days following infection of pregnant gilts with PRRSV-2 at day 86 of gestation. Viral load and its impact in each tissue was evaluated by a combination of qPCR, in vitro viral recovery, and local expression of IFNG and CD163. Resting populations of CD163+ cells were observed in all six non-lymphoid tissues from healthy day 86 fetuses, though the apparent density and the morphology of positive cells varied between tissue. Viral RNA was detected in all six tissues derived from fetuses previously classified as highly infected, and infectious viral particles successfully recovered. Significantly more viral RNA was detected in heart, brain, lung and skeletal muscle of susceptible fetuses, relative to their viable counterparts. Infection was associated with an increase in the expression of CD163 in brain, kidney and lung. In addition, the presence of virus in each tissue coincided with a significant upregulation in the expression of IFNG, but the scale of this response was not associated with fetal susceptibility. Thus, PRRSV-2 is widely distributed across these susceptible non-lymphoid fetal tissues, and fetal outcome is associated with local viral load in critical fetal organs.

'Getting control of Corona takes many angles': COVID-19 vaccine knowledge, attitudes and beliefs among refugee/immigrant/migrant communities in four US cities.

The objectives of the study were to (i) document refugee, immigrant and migrant (RIM) communities' knowledge, attitudes and beliefs (KABs) related to the Coronavirus disease (COVID-19) vaccine and (ii) identify best practices for developing and disseminating culturally and linguistically responsive health messaging addressing those KABs. Thirteen online focus groups (OFGs) in 10 languages were conducted. Each OFG was conducted in the participants' native language. OFGs were recorded, transcribed, translated and uploaded to qualitative software for coding. A thematic analysis was conducted. Results suggest that while there was some variation between different language groups (e.g. whether religious leaders were seen as trusted sources of information about COVID), there were also important commonalities. Most language groups (i) alluded to hearing about or having gaps in knowledge about COVID-19/the COVID-19 vaccine, (ii) reported hearing negative or conflicting stories about the vaccine and (iii) shared concerns about the negative side effects of the vaccine. There continues to be a need for health messaging in RIM communities that is culturally and linguistically concordant and follows health literacy guidelines. Message content about the COVID-19 vaccine should focus on vaccine importance, effectiveness and safety, should be multimodal and should be primarily delivered by healthcare professionals and community members who have already been vaccinated.

Plasma proteomic analysis on neuropathic pain in idiopathic peripheral neuropathy patients.

BACKGROUND AND AIMS: Why only half of the idiopathic peripheral neuropathy (IPN) patients develop neuropathic pain remains unknown. By conducting a proteomics analysis on IPN patients, we aimed to discover proteins and new pathways that are associated with neuropathic pain. METHODS: We conducted unbiased mass-spectrometry proteomics analysis on blood plasma from 31 IPN patients with severe neuropathic pain and 29 IPN patients with no pain, to investigate protein biomarkers and protein-protein interactions associated with neuropathic pain. Univariate modeling was done with linear mixed modeling (LMM) and corrected for multiple testing. Multivariate modeling was performed using elastic net analysis and validated with internal cross-validation and bootstrapping. RESULTS: In the univariate analysis, 73 proteins showed a p-value <.05 and 12 proteins showed a p-value <.01. None were significant after Benjamini-Hochberg adjustment for multiple testing. Elastic net analysis created a model containing 12 proteins with reasonable discriminatory power to differentiate between painful and painless IPN (false-negative rate 0.10, false-positive rate 0.18, and an area under the curve 0.75). Eight of these 12 proteins were clustered into one interaction network, significantly enriched for the complement and coagulation pathway (Benjamini-Hochberg adjusted p-value = .0057), with complement component 3 (C3) as the central node. Bootstrap validation identified insulin-like growth factor-binding protein 2 (IGFBP2), complement factor H-related protein 4 (CFHR4), and ferritin light chain (FTL), as the most discriminatory proteins of the original 12 identified. INTERPRETATION: This proteomics analysis suggests a role for the complement system in neuropathic pain in IPN.

Systemic azithromycin versus amoxicillin/metronidazole as an adjunct in the treatment of periodontitis: a systematic review and meta-analysis.

BACKGROUND: The use of systemic azithromycin (AZT) and amoxicillin/metronidazole (AMX/MTZ) as adjuncts provided additional clinical and microbiological benefits over subgingival instrumentation alone. However, the superiority of one antibiotic regimen over another has not been proven. Therefore, the aim of this systematic review and meta-analyses was to evaluate the clinical efficacy and safety of subgingival instrumentation (SI) in conjunction with the systemic use of AZT or AMX/MTZ for the treatment of periodontitis from current published literature. METHODS: Electronic databases were searched to identify randomized controlled trials (RCTs), controlled clinical trials, prospective and retrospective human studies that compared the adjunctive use of systemic AZT to AMX/MTZ with SI in the treatment of periodontitis. The eligibility criteria were defined based on the participant (who had periodontitis), intervention (SI with adjunctive use of systemic AZT), comparison (SI with adjunctive use of systemic AMX/MTZ), outcomes (primary outcome: changes in probing pocket). The risk of bias was assessed using the Cochrane Collaboration's Risk of Bias tool. Data were analysed using a statistical software program. RESULTS: Five studies with 151 participants with periodontitis were included in the present review. Of these, 74 participants received adjunctive AZT, while the remaining participants received AMX/MTZ as an adjunct to SI. The adjunctive use of AZT and AMX/MTZ had comparable changes in probing pocket depths at 1-3 months with no statistically significant difference (mean difference (MD) 0.01; 95% CI -0.20 to 0.22; P = 0.94). The adjunctive use of AZT had significantly fewer number of residual sites with probing pocket depths of ≥5 mm at 1-3 months compared to the adjunctive use of AMX/MTZ (MD -3.41; 95% CI -4.73 to -2.10; P < 0.0001). The prevalence rates of adverse events among participants who received AZT and AMX/MTZ were 9.80% and 14.8%, respectively. The meta-analysis showed that the difference between the two groups was not statistically significant (risk ratio 0.69; 95% CI 0.28 to 1.72; P = 0.43). CONCLUSIONS: Within the limitation of this review, there was no superiority between AZT and AMX/MTZ in terms of mean changes in probing pocket depths, clinical attachment level, bleeding on probing at 1-3 months. AZT seem to be associated with less sites with residual probing pocket depths of ≥5 mm at 1-3 months and fewer adverse events compared with AMX/MTZ. © 2023 Australian Dental Association.

Socioeconomic status, lifestyle and risk of incident dementia: a prospective cohort study of 276730 participants.

Healthy lifestyle might alleviate the socioeconomic inequities in health, but the extent of the joint and interactive effects of these two factors on dementia are unclear. This study aimed to detect the joint and interactive associations of socioeconomic status (SES) and lifestyle factors with incident dementia risk, and the underlying brain imaging alterations. Cox proportional hazards analysis was performed to test the joint and interactive associations. Partial correlation analysis was performed to reflect the brain imaging alterations. A total of 276,730 participants with a mean age of 55.9 (±8.0) years old from UK biobank were included. Over 8.5 (±2.6) years of follow-up, 3013 participants were diagnosed with dementia. Participants with high SES and most healthy lifestyle had a significantly lower risk of incident dementia (HR=0.19, 95% CI=0.14 to 0.26, P<2×10-16), Alzheimer's disease (AD, HR=0.19, 95% CI=0.13 to 0.29, P=8.94×10-15), and vascular dementia (HR=0.24, 95% CI=0.12 to 0.48, P=7.57×10-05) compared with participants with low SES and an unhealthy lifestyle. Significant interactions were found between SES and lifestyle on dementia (P=0.002) and AD (P=0.001) risks; the association between lifestyle and dementia was stronger among those of high SES. The combination of high SES and healthy lifestyle was positively associated with higher volumes in brain regions vulnerable to dementia-related atrophy. These findings suggest that SES and lifestyle significantly interact and influence dementia with its related brain structure phenotypes.

"It's not just the medical aspects that are important": A qualitative exploration of first-time parents' experiences of antenatal imaging and their influence on parent-fetal bonding.

INTRODUCTION: Antenatal imaging provides clinical information regarding fetal growth and development. The additional benefit afforded by imaging for expectant parents in developing an emotional connection (bond) to the unborn baby is also acknowledged. However, the relationship between imaging and bonding is not fully understood, particularly where there are differing parental and pregnancy circumstances, for example use of advanced imaging techniques or the prenatal diagnosis of a congenital fetal condition. This study aimed to explore the role of antenatal imaging in enhancing the developing parent-fetal bond in first-time parents. METHODS: A descriptive, qualitative methodology was used. Semi-structured telephone interviews were conducted with first-time expectant parents attending a London hospital for clinical ultrasound (n = 20) or research MRI (n = 8) imaging during pregnancy. The sample included parents receiving specialist antenatal care for a diagnosed fetal cardiac condition (n = 8). Thematic analysis was conducted. RESULTS: The analysis generated three themes: 1) Our baby, our scan too; 2) Destination parenthood; and 3) Being in the dark, then finding the light. These themes highlight the important, but transient role of antenatal imaging in enhancing parent-fetal bonding, as well as the differing care needs of expectant parents. The integral role of healthcare professionals in providing a personalised, supportive, imaging experience to facilitate bonding is also reflected. CONCLUSION: Adopting parent-centred care approaches which involve expectant parents in fetal imaging influences bonding by helping parents to consider the reality of their impending parenthood. Knowledge acquired during scans is used to create an identity for the unborn baby, which parents can develop an emotional connection to. IMPLICATIONS FOR PRACTICE: To optimise the potential for enhanced parent-fetal bonding, care provision in fetal imaging should be tailored to the individual needs of expectant parents.

Ultra-low oxygen, liquid sample cell for in situ synchrotron-based small-wide angle scattering (SAXS-WAXS).

Here, we report the design and successful implementation of an ultra-low oxygen sample cell for use on the SAXS-WAXS (small-wide angle x-ray scattering) beamline I22 at DIAMOND. The rigorous exclusion of oxygen is found to require double jacketing with purge gas throughout the entire system, pipework, pumps, and the sample cell itself. This particularly includes a "double-window" arrangement at the sample location to accommodate the very tight geometrical restrictions of the sample position. The in situ cell design also requires the additional complexity of heating the sample/solution and real-time electrochemical measurements. We demonstrate the successful implementation of this arrangement with real-time in situ characterization of an iron foil corrosion evolving under the "sweet-scale environment," very anoxic conditions common, in particular, commercial situations. The formation of iron carbonate, siderite, rather than iron oxide, indicates that our system is oxygen free down very low levels (<35 ppb at 80 °C).

Safety and Efficacy of Topiramate in Individuals With Cryptogenic Sensory Peripheral Neuropathy With Metabolic Syndrome: The TopCSPN Randomized Clinical Trial.

Importance: Cryptogenic sensory peripheral neuropathy (CSPN) is highly prevalent and often disabling due to neuropathic pain. Metabolic syndrome and its components increase neuropathy risk. Diet and exercise have shown promise but are limited by poor adherence. Objective: To determine whether topiramate can slow decline in intraepidermal nerve fiber density (IENFD) and/or neuropathy-specific quality of life measured using the Norfolk Quality of Life-Diabetic Neuropathy (NQOL-DN) scale. Design, Setting, and Participants: Topiramate as a Disease-Modifying Therapy for CSPN (TopCSPN) was a double-blind, placebo-controlled, randomized clinical trial conducted between February 2018 and October 2021. TopCSPN was performed at 20 sites in the National Institutes of Health-funded Network for Excellence in Neurosciences Clinical Trials (NeuroNEXT). Individuals with CSPN and metabolic syndrome aged 18 to 80 years were screened and randomly assigned by body mass index (<30 vs ≥30), which is calculated as weight in kilograms divided by height in meters squared. Patients were excluded if they had poorly controlled diabetes, prior topiramate treatment, recurrent nephrolithiasis, type 1 diabetes, use of insulin within 3 months before screening, history of foot ulceration, planned bariatric surgery, history of alcohol or drug overuse in the 2 years before screening, family history of a hereditary neuropathy, or an alternative neuropathy cause. Interventions: Participants received topiramate or matched placebo titrated to a maximum-tolerated dose of 100 mg per day. Main Outcomes and Measures: IENFD and NQOL-DN score were co-primary outcome measures. A positive study was defined as efficacy in both or efficacy in one and noninferiority in the other. Results: A total of 211 individuals were screened, and 132 were randomly assigned to treatment groups: 66 in the topiramate group and 66 in the placebo group. Age and sex were similar between groups (topiramate: mean [SD] age, 61 (10) years; 38 male [58%]; placebo: mean [SD] age, 62 (11) years; 44 male [67%]). The difference in change in IENFD and NQOL-DN score was noninferior but not superior in the intention-to-treat (ITT) analysis (IENFD, 0.21 fibers/mm per year; 95% CI, -0.43 to ∞ fibers/mm per year and NQOL-DN score, -1.52 points per year; 95% CI, -∞ to 1.19 points per year). A per-protocol analysis excluding noncompliant participants based on serum topiramate levels and those with major protocol deviations demonstrated superiority in NQOL-DN score (-3.69 points per year; 95% CI, -∞ to -0.73 points per year). Patients treated with topiramate had a mean (SD) annual change in IENFD of 0.56 fibers/mm per year relative to placebo (95% CI, -0.21 to ∞ fibers/mm per year). Although IENFD was stable in the topiramate group compared with a decline consistent with expected natural history, this difference did not demonstrate superiority. Conclusion and Relevance: Topiramate did not slow IENFD decline or affect NQOL-DN score in the primary ITT analysis. Some participants were intolerant of topiramate. NQOL-DN score was superior among those compliant based on serum levels and without major protocol deviations. Trial Registration: ClinicalTrials.gov Identifier: NCT02878798.

Whole-genome sequencing links cases dispersed in time, place, and person while supporting healthcare worker management in an outbreak of Panton-Valentine leucocidin meticillin-resistant Staphylococcus aureus; and a review of literature.

This is a report on an outbreak of Panton-Valentine leucocidin-producing meticillin-resistant Staphylococcus aureus (PVL-MRSA) in an intensive care unit (ICU) during the COVID-19 pandemic that affected seven patients and a member of staff. Six patients were infected over a period of ten months on ICU by the same strain of PVL-MRSA, and a historic case identified outside of the ICU. All cases were linked to a healthcare worker (HCW) who was colonized with the organism. Failed topical decolonization therapy, without systemic antibiotic therapy, resulted in ongoing transmission and one preventable acquisition of PVL-MRSA. The outbreak identifies the support that may be needed for HCWs implicated in outbreaks. It also demonstrates the role of whole-genome sequencing in identifying dispersed and historic cases related to the outbreak, which in turn aids decision-making in outbreak management and HCW support. This report also includes a review of literature of PVL-MRSA-associated outbreaks in healthcare and highlights the need for review of current national guidance in the management of HCWs' decolonization regimen and return-to-work recommendations in such outbreaks.

Progressive drought alters the root exudate metabolome and differentially activates metabolic pathways in cotton (Gossypium hirsutum).

Root exudates comprise various primary and secondary metabolites that are responsive to plant stressors, including drought. As increasing drought episodes are predicted with climate change, identifying shifts in the metabolome profile of drought-induced root exudation is necessary to understand the molecular interactions that govern the relationships between plants, microbiomes, and the environment, which will ultimately aid in developing strategies for sustainable agriculture management. This study utilized an aeroponic system to simulate progressive drought and recovery while non-destructively collecting cotton (Gossypium hirsutum) root exudates. The molecular composition of the collected root exudates was characterized by untargeted metabolomics using Fourier-Transform Ion Cyclotron Resonance Mass Spectrometry (FT-ICR MS) and mapped to the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Over 700 unique drought-induced metabolites were identified throughout the water-deficit phase. Potential KEGG pathways and KEGG modules associated with the biosynthesis of flavonoid compounds, plant hormones (abscisic acid and jasmonic acid), and other secondary metabolites were highly induced under severe drought, but not at the wilting point. Additionally, the associated precursors of these metabolites, such as amino acids (phenylalanine and tyrosine), phenylpropanoids, and carotenoids, were also mapped. The potential biochemical transformations were further calculated using the data generated by FT-ICR MS. Under severe drought stress, the highest number of potential biochemical transformations, including methylation, ethyl addition, and oxidation/hydroxylation, were identified, many of which are known reactions in some of the mapped pathways. With the application of FT-ICR MS, we revealed the dynamics of drought-induced secondary metabolites in root exudates in response to drought, providing valuable information for drought-tolerance strategies in cotton.

Cross-sectional associations between short and mid-term blood pressure variability, cognition, and vascular stiffness in older adults.

Background: High blood pressure variability (BPV), particularly in older age, appears to be an independent risk factor for incident dementia. The current study aimed to investigate the association between different BPV measures (short- and mid-term BPV including circadian patterns) and cognitive functioning as well as vascular stiffness measures to better understand the role that BPV plays in cognitive impairment. Methods: 70 older adults (60-80-year-olds) without dementia completed a cognitive test battery and had their blood pressure (BP) assessed via a 24-hour ambulatory BP monitor (divided into sleep and wake for short-term BPV) and 4-day morning and evening home-based BP monitor (for day-to-day BPV). Arterial stiffness was evaluated via pulse wave analysis and pulse wave velocity (PWV) and cerebrovascular pulsatility was assessed via transcranial doppler sonography of the middle cerebral arteries. Results: High systolic as well as diastolic short- and mid-term BPV were associated with poorer cognitive functioning, independent of the mean BP. Higher short-term BPV was associated with poorer attention and psychomotor speed, whilst day-to-day BPV was negatively linked with executive functioning. Circadian BP patterns (dipping and morning BP surge) showed no significant relationships with cognition after adjusting for covariates. Higher systolic short-term BPV was associated with higher arterial stiffness (PWV) and higher diastolic day-to-day BPV was linked with lower arterial stiffness. No significant associations between BPV measures and cerebrovascular pulsatility were present. Conclusion: High BPV, independently of the mean BP, is associated with lower cognitive performance and increased arterial stiffness in older adults without clinically-relevant cognitive impairment. This highlights the role of systolic and diastolic BPV as a potential early clinical marker for cognitive impairment.

South African Thoracic Society position statement on the management of non-cystic fibrosis bronchiectasis in adults: 2023.

Background: Bronchiectasis is a chronic lung disorder that affects the lives of many South Africans. Post-tuberculosis (TB) bronchiectasis is an important complication of previous pulmonary TB and a common cause of bronchiectasis in South Africa (SA). No previous statements on the management of bronchiectasis in SA have been published. Objectives: To provide a position statement that will act as a template for the management of adult patients with bronchiectasis in SA. Methods: The South African Thoracic Society appointed an editorial committee to compile a position statement on the management of adult non-cystic fibrosis (CF) bronchiectasis in SA. Results: A position statement addressing the management of non-CF bronchiectasis in adults in SA was compiled. This position statement covers the epidemiology, aetiology, diagnosis, investigations and various aspects of management of adult patients with non-CF bronchiectasis in SA. Conclusion: Bronchiectasis has largely been a neglected lung condition, but new research has improved the outlook for patients. Collaboration between interprofessional team members in patient management is important. In SA, more research into the epidemiology of bronchiectasis, especially post-TB bronchiectasis and HIV-associated bronchiectasis, is required. Abstract: The South African Thoracic Society mandated a multidisciplinary team of healthcare providers to compile a position statement on the management of non-cystic fibrosis bronchiectasis in South Africa (SA). International guidelines on the management of bronchiectasis were reviewed and used as a basis from which the current position statement was compiled. This is the first position statement on the management of adult non-cystic fibrosis bronchiectasis in SA. A description of the epidemiology and aetiology of bronchiectasis is provided, as well as guidance on its diagnosis and management. The position statement provides guidance on the management of bronchiectasis to healthcare providers, policymakers and regulatory authorities.

Behavioural susceptibility theory: the role of appetite in genetic susceptibility to obesity in early life.

Excess weight gained during the early years and, in particular, rapid weight gain in the first 2 years of life, are a major risk factors for adult obesity. The growing consensus is that childhood obesity develops from a complex interaction between genetic susceptibility and exposure to an 'obesogenic' environment. Behavioural susceptibility theory (BST) was developed to explain the nature of this gene-environment interaction, and why the 'obesogenic' environment does not affect all children equally. It hypothesizes that inherited variation in appetite, which is present from birth, determines why some infants and children overeat, and others do not, in response to environmental opportunity. That is, those who inherit genetic variants promoting an avid appetite are vulnerable to overeating and developing obesity, while those who are genetically predisposed to have a smaller appetite and lower interest in food are protected from obesity-or even at risk of being underweight. We review the breadth of research to-date that has contributed to the evidence base for BST, focusing on early life, and discuss implications and future directions for research and theory. This article is part of a discussion meeting issue 'Causes of obesity: theories, conjectures and evidence (Part I)'.

A pragmatic digital health informatics based approach for aiding clinical prioritisation and reducing backlog of care: A study in cohort of 4022 people with diabetes.

BACKGROUND AND AIMS: The backlog of care in resource stretched healthcare systems requires innovative approaches to aid clinical prioritisation. Our aim was to develop an informatics tool to identify and prioritise people with diabetes who are likely to deteriorate whilst awaiting an appointment to optimise clinical outcomes and resources. MATERIALS AND METHODS: Using data from electronic health care records we identified 6 risk-factors that could be addressed in 4022 people (52% male, 30% non-Caucasian) with diabetes attending a large university hospital in London. The risk-factors were new clinical events/data occurring since their last routine clinic visit. To validate and compare data-led prioritisation tool to a traditional 'clinical approach' a sample of 450 patients were evaluated. RESULTS: Of the 4022 people, 549 (13.6%) were identified as having one or more risk events/factors. People with risk were more likely to be non-Caucasian and had greater socio-economic deprivation. Taking clinical prioritisation as the gold standard, informatics tool identified high risk patients with a sensitivity of 83% and lower risk patients with a specificity of 81%. An operational pilot pathway over 3 months using this approach demonstrated in 101 high risk people that 40% received interventions/care optimisation to prevent deterioration in health. CONCLUSION: A pragmatic data-driven method identifies people with diabetes at highest need for clinical prioritisation within restricted resources. Health informatics systems such as our can enhance care and improve operational efficiency and better healthcare delivery for people with diabetes.