Race-specific FRAX models are evidence-based and support equitable care: a response to the ASBMR Task Force report on Clinical Algorithms for Fracture Risk.

Task Force on 'Clinical Algorithms for Fracture Risk' commissioned by the American Society for Bone and Mineral Research (ASBMR) Professional Practice Committee has recommended that FRAX® models in the US do not include adjustment for race and ethnicity. This position paper finds that an agnostic model would unfairly discriminate against the Black, Asian and Hispanic communities and recommends the retention of ethnic and race-specific FRAX models for the US, preferably with updated data on fracture and death hazards. In contrast, the use of intervention thresholds based on a fixed bone mineral density unfairly discriminates against the Black, Asian and Hispanic communities in the US. This position of the Working Group on Epidemiology and Quality of Life of the International Osteoporosis Foundation (IOF) is endorsed both by the IOF and the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO).

Right atrial and right ventricular strain: prognostic value depends on the severity of tricuspid regurgitation.

AIMS: Assessing right heart function is challenging, particularly when significant tricuspid regurgitation (TR) is present. Among available echocardiographic techniques for assessment, literatures suggests that strain imaging may be more reliable and less susceptible to loading conditions. Thus, we aimed to assess the validity of RA and RV strain relative to conventional metrics as well as their utility in predicting patient outcomes in TR. METHODS: We studied 262 consecutive patients (mean age 74 ± 11.2 years, 53% male) who underwent same-day echocardiography and right heart catheterization between 2018 and 2023. We compared right heart strain to traditional metrics of RV function and subsequently correlated RA and RV strain to heart failure (HF)-related death or hospitalization, whichever came first. RESULTS: Over a mean follow-up of 34 ± 15 months, there were 103 deaths and HF hospitalizations. Both RA and RV strain were correlated with echocardiographic and invasive measures of right heart function. Across all patients, preserved RA strain was associated with lower risk of adverse outcomes (HR 0.763, 95% CI 0.618-0.943). Similarly, preserved RV strain was correlated with better outcomes, though this was only statistically significant in patients without severe TR or pulmonary hypertension (HR 2.450, 95% CI 1.244-4.825). Moreover, abnormal ratios of RV strain to pulmonary pressures and RV size were significantly correlated with adverse outcomes (p < 0.05 each). CONCLUSION: RA and RV strain are independently correlated with echocardiographic and invasive measures of cardiac function. Moreover, preserved RA and RV strain are likely associated with better clinical outcomes.

Clinical Practice Patterns for Transradial Coronary Artery Catheterisation in Australian and New Zealand: Mixed-Methods Survey and Interview Study.

BACKGROUND: While there has been an increase in the use of the transradial approach when performing percutaneous coronary angiography and intervention, there is evidence of variations in international practice. Ensuring that operators' practices are supported by evidence is important to ensure optimal outcomes. METHOD: Interventional cardiologists and advanced trainees completed a cross-sectional survey followed by semi-structured interviews to map current practices for transradial coronary artery procedures in Australia and New Zealand and explore factors that influence clinical decision-making around procedural practice. RESULTS: The right radial artery was the preferred access site (88%). Over a third (37%) of the participants indicated that they tested the hand circulation pre-procedure. Over a quarter of respondents (28.6%) reported that they would carry out transradial procedures regardless of the patient's coagulation status. Most participants (77.8%) described radial artery spasm in around 10% of transradial procedures performed. Only 62% of participants assessed for radial artery occlusion post-catheterisation. Interview data revealed four themes that guided clinical decision-making, namely (1) Decision-making based on research, (2) Using clinical experience, (3) Being led by their training, and (4) Individual patient factors. CONCLUSIONS: This study has demonstrated that despite clinical guidelines, substantial practice variation exists in transradial coronary artery catheterisation across Australia and New Zealand. The variation in practice and factors impacting clinical decision-making highlight a need for future strategies to optimise evidence translation and implementation across clinical settings.

Predictive value of sarcopenia components for all-cause mortality: findings from population-based cohorts.

BACKGROUND: Low grip strength and gait speed are associated with mortality. However, investigation of the additional mortality risk explained by these measures, over and above other factors, is limited. AIM: We examined whether grip strength and gait speed improve discriminative capacity for mortality over and above more readily obtainable clinical risk factors. METHODS: Participants from the Health, Aging and Body Composition Study, Osteoporotic Fractures in Men Study, and the Hertfordshire Cohort Study were analysed. Appendicular lean mass (ALM) was ascertained using DXA; muscle strength by grip dynamometry; and usual gait speed over 2.4-6 m. Verified deaths were recorded. Associations between sarcopenia components and mortality were examined using Cox regression with cohort as a random effect; discriminative capacity was assessed using Harrell's Concordance Index (C-index). RESULTS: Mean (SD) age of participants (n = 8362) was 73.8(5.1) years; 5231(62.6%) died during a median follow-up time of 13.3 years. Grip strength (hazard ratio (95% CI) per SD decrease: 1.14 (1.10,1.19)) and gait speed (1.21 (1.17,1.26)), but not ALM index (1.01 (0.95,1.06)), were associated with mortality in mutually-adjusted models after accounting for age, sex, BMI, smoking status, alcohol consumption, physical activity, ethnicity, education, history of fractures and falls, femoral neck bone mineral density (BMD), self-rated health, cognitive function and number of comorbidities. However, a model containing only age and sex as exposures gave a C-index (95% CI) of 0.65(0.64,0.66), which only increased to 0.67(0.67,0.68) after inclusion of grip strength and gait speed. CONCLUSIONS: Grip strength and gait speed may generate only modest adjunctive risk information for mortality compared with other more readily obtainable risk factors.

Heterogeneity of right ventricular echocardiographic parameters in systemic lupus erythematosus among four clinical subgroups, as stratified by clinical organ involvement in observational cohort.

BACKGROUND: Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease. Cardiac involvement in SLE is rare but plays an important prognostic role. The degree of cardiac involvement according to SLE subsets defined by non-cardiac manifestations is unknown. The objective of this study was to identify differences in transthoracic echocardiography (TTE) parameters associated with different SLE subgroups. METHODS: One hundred eighty-one patients who fulfilled the 2019 American College of Rheumatology/EULAR classification criteria for SLE and underwent baseline TTE were included in this cross-sectional study. We defined four subsets of SLE based on the predominant clinical manifestations. A multivariate multinomial regression analysis was performed to determine whether TTE parameters differed between groups. RESULTS: Four clinical subsets were defined according to non-cardiac clinical manifestations: group A (n=37 patients) showed features of mixed connective tissue disease, group B (n=76 patients) had primarily cutaneous involvement, group C (n=18) exhibited prominent serositis and group D (n=50) had severe, multi-organ involvement, including notable renal disease. Forty TTE parameters were assessed between groups. Per multivariate multinomial regression analysis, there were statistically significant differences in early diastolic tricuspid annular velocity (RV-Ea, p<0.0001), RV S' wave (p=0.0031) and RV end-diastolic diameter (p=0.0419) between the groups. Group B (primarily cutaneous involvement) had the lowest degree of RV dysfunction. CONCLUSION: When defining clinical phenotypes of SLE based on organ involvement, we found four distinct subgroups which showed notable differences in RV function on TTE. Risk-stratifying patients by clinical phenotype could help better tailor cardiac follow-up in this population.

Bone health, cardiovascular disease, and imaging outcomes in UK Biobank: a causal analysis.

This study examined the association of estimated heel bone mineral density (eBMD, derived from quantitative ultrasound) with: (1) prevalent and incident cardiovascular diseases (CVDs: ischemic heart disease (IHD), myocardial infarction (MI), heart failure (HF), non-ischemic cardiomyopathy (NICM), arrhythmia), (2) mortality (all-cause, CVD, IHD), and (3) cardiovascular magnetic resonance (CMR) measures of left ventricular and atrial structure and function and aortic distensibility, in the UK Biobank. Clinical outcomes were ascertained using health record linkage over 12.3 yr of prospective follow-up. Two-sample Mendelian randomization (MR) was conducted to assess causal associations between BMD and CMR metrics using genetic instrumental variables identified from published genome-wide association studies. The analysis included 485 257 participants (55% women, mean age 56.5 ± 8.1 yr). Higher heel eBMD was associated with lower odds of all prevalent CVDs considered. The greatest magnitude of effect was seen in association with HF and NICM, where 1-SD increase in eBMD was associated with 15% lower odds of HF and 16% lower odds of NICM. Association between eBMD and incident IHD and MI was non-significant; the strongest relationship was with incident HF (SHR: 0.90 [95% CI, 0.89-0.92]). Higher eBMD was associated with a decreased risk in all-cause, CVD, and IHD mortality, in the fully adjusted model. Higher eBMD was associated with greater aortic distensibility; associations with other CMR metrics were null. Higher heel eBMD is linked to reduced risk of a range of prevalent and incident CVD and mortality outcomes. Although observational analyses suggest associations between higher eBMD and greater aortic compliance, MR analysis did not support a causal relationship between genetically predicted BMD and CMR phenotypes. These findings support the notion that bone-cardiovascular associations reflect shared risk factors/mechanisms rather than direct causal pathways.

Medieval DNA from Soqotra points to Eurasian origins of an isolated population at the crossroads of Africa and Arabia.

Soqotra, an island situated at the mouth of the Gulf of Aden in the northwest Indian Ocean between Africa and Arabia, is home to ~60,000 people subsisting through fishing and semi-nomadic pastoralism who speak a Modern South Arabian language. Most of what is known about Soqotri history derives from writings of foreign travellers who provided little detail about local people, and the geographic origins and genetic affinities of early Soqotri people has not yet been investigated directly. Here we report genome-wide data from 39 individuals who lived between ~650 and 1750 CE at six locations across the island and document strong genetic connections between Soqotra and the similarly isolated Hadramawt region of coastal South Arabia that likely reflects a source for the peopling of Soqotra. Medieval Soqotri can be modelled as deriving ~86% of their ancestry from a population such as that found in the Hadramawt today, with the remaining ~14% best proxied by an Iranian-related source with up to 2% ancestry from the Indian sub-continent, possibly reflecting genetic exchanges that occurred along with archaeologically documented trade from these regions. In contrast to all other genotyped populations of the Arabian Peninsula, genome-level analysis of the medieval Soqotri is consistent with no sub-Saharan African admixture dating to the Holocene. The deep ancestry of people from medieval Soqotra and the Hadramawt is also unique in deriving less from early Holocene Levantine farmers and more from groups such as Late Pleistocene hunter-gatherers from the Levant (Natufians) than other mainland Arabians. This attests to migrations by early farmers having less impact in southernmost Arabia and Soqotra and provides compelling evidence that there has not been complete population replacement between the Pleistocene and Holocene throughout the Arabian Peninsula. Medieval Soqotra harboured a small population that showed qualitatively different marriage practices from modern Soqotri, with first-cousin unions occurring significantly less frequently than today.

Transcatheter aortic valve implantation in severe aortic stenosis does not necessarily reverse left ventricular myocardial damage: data of long-term follow-up.

AIMS: Aortic stenosis (AS) is causing myocardial damage and replacement is mainly indicated based on symptoms. Non-invasive estimation of myocardial work (MW) provides a less afterload-dependent too for assessing myocardial function. We sought to look at the impact of transcatheter aortic valve implantation (TAVI) on the myocardium at long-term follow-up and according to current indications. METHODS AND RESULTS: We conducted an observational, cross-sectional, single-centre study. Patients were selected based on the validated indication for a TAVI. Standardized echocardiographies were repeated. A total of 102 patients were included. The mean age was 85 years, 45% were female, 68% had high blood pressure, and 52% had a coronary disease. One-fifth was suffering from low-flow-low-gradient AS. A follow-up was performed at 22 ± 9.5 months after the TAVI. No TAVI dysfunction was observed. Left ventricular (LV) ejection fraction was stable (62 ± 8%), and global longitudinal strain had improved (-14.0 ± 3.7 vs. -16.0 ± 3.6%, P < 0.0001). No improvement of the MW parameters was noticed (LV global work index 2099 ± 692 vs. 2066 ± 706 mmHg%, P = 0.8, LV global constructive 2463 ± 736 vs. 2463 ± 676 mmHg%, P = 0.8). Global wasted work increased [214 (149; 357) vs. 247 (177; 394) mmHg%, P = 0.0008]. CONCLUSION: In a population of severe symptomatic AS patients who had undergone a TAVI, the non-invasive myocardial indices that assess the LV performance at long-term follow-up did not improve. These results are questioning the timing of the intervention and the need for more attention in the pharmacological management of these AS patients.

Phenotyping of heart failure with preserved ejection faction using electronic health records and echocardiography.

Aims: Patients presenting symptoms of heart failure with preserved ejection fraction (HFpEF) are not a homogenous population. Different phenotypes can differ in prognosis and optimal management strategies. We sought to identify phenotypes of HFpEF by using the medical information database from a large university hospital centre using machine learning. Methods and results: We explored the use of clinical variables from electronic health records in addition to echocardiography to identify different phenotypes of patients with HFpEF. The proposed methodology identifies four phenotypic clusters based on both clinical and echocardiographic characteristics, which have differing prognoses (death and cardiovascular hospitalization). Conclusion: This work demonstrated that artificial intelligence-derived phenotypes could be used as a tool for physicians to assess risk and to target therapies that may improve outcomes.

Evolution and prognostic value of left ventricular deformation and myocardial work parameters in transthyretin amyloid cardiomyopathy.

AIMS: Wild-type transthyretin amyloid cardiomyopathy (ATTR-CM) is an increasingly recognized condition. It remains challenging to estimate the extent of disease and the prognosis for most patients. Myocardial work is a sensitive echocardiographic approach that improves the characterization of myocardial damage. We investigate the parameters of myocardial deformation and work in ATTR-CM patients and their changes over time. METHODS AND RESULTS: We analysed clinical, electrocardiographic, biological, and echocardiographic characteristics in 113 patients [median age 82 (77-85), 90.4% male] diagnosed with wild-type ATTR-CM based on international consensus at a single centre. We compared the data at baseline and 18-month follow-up. Thirty-four patients died and 12 were hospitalized for heart failure at a median follow-up of 935 days (interquartile range 691-1159 days). Left ventricular end-diastolic diameter, left atrial strain during reservoir phase (LASRES), left ventricular longitudinal strain, global work index (GWI), global constructive work significantly decreased from baseline to 18 months, while left ventricular wall thickness increased. Left ventricular ejection fraction, right ventricular free wall strain (FWS), global wasted work (GWW), and global work efficiency did not alter significantly. Strain parameters were identified as prognostic on baseline evaluation using a multivariate analysis: GWI, GWW, FWS, and LASRES. They were significantly associated with the risk of death and hospitalization for heart failure. CONCLUSION: Multi-chamber strain assessment may improve the surveillance of patients with ATTR-CM, and myocardial work parameters may improve clinical risk stratification in this population.

Primary mitral regurgitation: Toward a better quantification on left ventricular consequences.

BACKGROUND: Left ventricular end-systolic diameter (LVESD) and ejection fraction (LVEF) are the parameters to look for when discussing repair in asymptomatic patients with a primary mitral regurgitation (PMR). Loading conditions are altering LV-function quantification. LV-myocardial work (LVMW) is a method based on pressure-strain loops. HYPOTHESIS: We sought to evaluate the additive value of the LVMW for predicting clinical events in patients with PMR. METHODS: 103 patients (66% men, median age 57 years) with asymptomatic severe PMR were explored at rest and during an exercise stress echocardiography. LV myocardial global work index (GWI), constructive work (GCW), wasted work (GWW), and work efficiency (GWE) were measured with speckle-tracking echocardiography at rest and low workload. The indication for surgery was based on the heart teams' decision. The median follow-up was 670 days. RESULTS: Clinical events occurred for 50 patients (48.5%) with a median of event-free survival distribution of 289 days. Systolic pulmonary artery pressure (sPAP) at rest was 32.61 ± 8.56 mmHg and did not predict the risk of event like LVEF and LVESD. Changes in, GLS (hazard ratio [HR] 0.55; 95% confidence interval (Cl): 0.36-0.83; p = .005), GWI (HR 1.01; 95% Cl: 1.00-1.02; p = .002) and GCW (HR 1.85; 95% Cl: 1.28-2.68; p = .001) in addition to Left Atrial Volume Index (HR 1.73; 95% CI: 1.28 - 2.33; p < 0,001) were independent predictors of events. CONCLUSION: Changes in myocardial work indices related to low-dose exercise are relevant to best predict PMR patient prognosis It might help to better select patient's candidate for "early-surgery."

Genetic continuity and change among the Indigenous peoples of California.

Before the colonial period, California harboured more language variation than all of Europe, and linguistic and archaeological analyses have led to many hypotheses to explain this diversity1. We report genome-wide data from 79 ancient individuals from California and 40 ancient individuals from Northern Mexico dating to 7,400-200 years before present (BP). Our analyses document long-term genetic continuity between people living on the Northern Channel Islands of California and the adjacent Santa Barbara mainland coast from 7,400 years BP to modern Chumash groups represented by individuals who lived around 200 years BP. The distinctive genetic lineages that characterize present-day and ancient people from Northwest Mexico increased in frequency in Southern and Central California by 5,200 years BP, providing evidence for northward migrations that are candidates for spreading Uto-Aztecan languages before the dispersal of maize agriculture from Mexico2-4. Individuals from Baja California share more alleles with the earliest individual from Central California in the dataset than with later individuals from Central California, potentially reflecting an earlier linguistic substrate, whose impact on local ancestry was diluted by later migrations from inland regions1,5. After 1,600 years BP, ancient individuals from the Channel Islands lived in communities with effective sizes similar to those in pre-agricultural Caribbean and Patagonia, and smaller than those on the California mainland and in sampled regions of Mexico.

The effect of pregnancy vitamin D supplementation on offspring bone mineral density in childhood: a systematic review and meta-analysis.

Systematic review and meta-analysis of the effect of moderate- to high-dose vitamin D supplementation in pregnancy on offspring bone mineralisation found a positive effect of vitamin D supplementation on offspring bone mineral density (BMD) at age 4-6 years, with a smaller effect on bone mineral content. PURPOSE: A systematic review and meta-analysis was performed to assess the effect of pregnancy vitamin D supplementation on offspring bone mineral density (BMD) in childhood. METHODS: A literature search was conducted for published RCTs of antenatal vitamin D supplementation with assessment of offspring BMD or bone mineral content (BMC) by dual-energy X-ray absorptiometry (DXA) using MEDLINE and EMBASE up to 13th July 2022. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Study findings were grouped in two age groups of offspring assessment: neonatal period and early childhood (3-6 years). Random-effects meta-analysis of the effect on BMC/BMD at 3-6 years was performed using RevMan 5.4.1, yielding standardised mean difference (SMD) (95% CI). RESULTS: Five RCTs were identified with offspring assessment of BMD or BMC; 3250 women were randomised within these studies. Risk of bias was low in 2 studies and "of concern" in 3. Supplementation regimes and the control used (3 studies used placebo and 2 used 400 IU/day cholecalciferol) varied, but in all studies the intervention increased maternal 25-hydroxvitamin D status compared to the control group. Two trials assessing BMD in the neonatal period (total n = 690) found no difference between groups, but meta-analysis was not performed as one trial represented 96.4% of those studied at this age. Three trials assessed offspring whole-body-less-head BMD at age 4-6 years. BMD was higher in children born to mothers supplemented with vitamin D [0.16 SD (95% confidence interval 0.05, 0.27), n = 1358] with a smaller effect on BMC [0.07 SD (95% CI - 0.04, 0.19), n = 1351]. CONCLUSIONS: There are few RCTs published to address this question, and these are inconsistent in methodology and findings. However, meta-analysis of three trials suggests moderate- to high-dose vitamin D supplementation in pregnancy might increase offspring BMD in early childhood, but further trials are required to confirm this finding. (Prospero CRD42021288682; no funding received).

Nursing students' attitudes, behaviour, and knowledge toward smoking cessation: Results from a descriptive survey at a regional university.

BACKGROUND: Smoking is the largest single cause of lifestyle-related preventable morbidity and mortality. Nurses form the largest cohort of health professionals and are strategically placed to implement smoking cessation interventions. However their capacity is underutilised, particularly in rural and remote areas in countries such as Australia where the incidence of smoking in is higher than average and access to healthcare is limited. One strategy to address the underutilisation of nurses in smoking cessation interventions is to include training in the university/college nursing curriculum. To effectively implement this training, it is vital to have an in-depth knowledge of student nurses' attitudes towards smoking including the role of healthcare professionals in smoking cessation, their smoking behaviour and that of their peers, and knowledge regarding smoking cessation techniques and resources. OBJECTIVES: Investigate nursing students' attitudes, behaviour, and knowledge towards smoking cessation, determine the impact of demographics and educational experienced on these, and develop recommendations for future research and educational practice. DESIGN: Descriptive survey. PARTICIPANTS: Non-probability sample of undergraduate nursing students (n = 247) from a regional Australian university. RESULTS: Significantly more participants had tried smoking cigarettes than had not (p = 0.026). There were no significant relationships between gender and smoking (p = 0.169) or e-cigarette use (p = 0.200), but a significant relationship was found between age and smoking status where older participants (48-57 years) were more likely to smoke (p < 0.001). Most participants (70 %) were supportive of public health measures to reduce cigarette smoking but felt that they lacked specific knowledge to assist their patients to cease smoking. CONCLUSIONS: Within education there needs to be an emphasis on the central role that nurses play in smoking cessation with a greater focus on training nursing students about smoking cessation strategies and resources. There is also a need to ensure that students know it falls within their duty of care to address smoking cessation with patients.

Entwined African and Asian genetic roots of medieval peoples of the Swahili coast.

The urban peoples of the Swahili coast traded across eastern Africa and the Indian Ocean and were among the first practitioners of Islam among sub-Saharan people1,2. The extent to which these early interactions between Africans and non-Africans were accompanied by genetic exchange remains unknown. Here we report ancient DNA data for 80 individuals from 6 medieval and early modern (AD 1250-1800) coastal towns and an inland town after AD 1650. More than half of the DNA of many of the individuals from coastal towns originates from primarily female ancestors from Africa, with a large proportion-and occasionally more than half-of the DNA coming from Asian ancestors. The Asian ancestry includes components associated with Persia and India, with 80-90% of the Asian DNA originating from Persian men. Peoples of African and Asian origins began to mix by about AD 1000, coinciding with the large-scale adoption of Islam. Before about AD 1500, the Southwest Asian ancestry was mainly Persian-related, consistent with the narrative of the Kilwa Chronicle, the oldest history told by people of the Swahili coast3. After this time, the sources of DNA became increasingly Arabian, consistent with evidence of growing interactions with southern Arabia4. Subsequent interactions with Asian and African people further changed the ancestry of present-day people of the Swahili coast in relation to the medieval individuals whose DNA we sequenced.