Combining bone resorption markers and heel quantitative ultrasound to discriminate between fracture cases and controls

Summary: This nested case-control analysis of a Swiss ambulatory cohort of elderly women assessed the discriminatory power of urinary markers of bone resorption and heel quantitative ultrasound for non-vertebral fractures. The tests all discriminated between cases and controls, but combining the two strategies yielded no additional relevant information. Introduction: Data are limited regarding the combination of bone resorption markers and heel quantitative bone ultrasound (QUS) in the detection of women at risk for fracture. Methods: In a nested case-control analysis, we studied 368 women (mean age 76.2 ± 3.2years), 195 with low-trauma non-vertebral fractures and 173 without, matched for age, BMI, medical center, and follow-up duration, from a prospective study designed to predict fractures. Urinary total pyridinolines (PYD) and deoxypyridinolines (DPD) were measured by high performance liquid chromatography. All women underwent bone evaluations using Achilles+ and Sahara heel QUS. Results: Areas under the receiver operating-characteristic curve (AUC) for discriminative models of the fracture group, with 95% confidence intervals, were 0.62 (0.56-0.68) and 0.59 (0.53-0.65) for PYD and DPD, and 0.64 (0.58-0.69) and 0.65 (0.59-0.71) for Achilles+ and Sahara QUS, respectively. The combination of resorption markers and QUS added no significant discriminatory information to either measurement alone with an AUC of 0.66 (0.60-0.71) for Achilles+ with PYD and 0.68 (0.62-0.73) for Sahara with PYD. Conclusions: Urinary bone resorption markers and QUS are equally discriminatory between non-vertebral fracture patients and controls. However, the combination of bone resorption markers and QUS is not better than either test used alon

Bis-Retinoid A2E Induces an Increase of Basic Fibroblast Growth Factor via Inhibition of Extracellular Signal-Regulated Kinases 1/2 Pathway in Retinal Pigment Epithelium Cells and Facilitates Phagocytosis.

Age-related macular degeneration (ARMD) is the leading cause of vision loss in developed countries. Hallmarks of the disease are well known; indeed, this pathology is characterized by lipofuscin accumulation, is principally composed of lipid-containing residues of lysosomal digestion. The N-retinyl-N-retinylidene ethanolamine (A2E) retinoid which is thought to be a cytotoxic component for RPE is the best-characterized component of lipofuscin so far. Even if no direct correlation between A2E spatial distribution and lipofuscin fluorescence has been established in aged human RPE, modified forms or metabolites of A2E could be involved in ARMD pathology. Mitogen-activated protein kinase (MAPK) pathways have been involved in many pathologies, but not in ARMD. Therefore, we wanted to analyze the effects of A2E on MAPKs in polarized ARPE19 and isolated mouse RPE cells. We showed that long-term exposure of polarized ARPE19 cells to low A2E dose induces a strong decrease of the extracellular signal-regulated kinases' (ERK1/2) activity. In addition, we showed that A2E, via ERK1/2 decrease, induces a significant decrease of the retinal pigment epithelium-specific protein 65 kDa (RPE65) expression in ARPE19 cells and isolated mouse RPE. In the meantime, we showed that the decrease of ERK1/2 activity mediates an increase of basic fibroblast growth factor (bFGF) mRNA expression and secretion that induces an increase in phagocytosis via a paracrine effect. We suggest that the accumulation of deposits coming from outer segments (OS) could be explained by both an increase of bFGF-induced phagocytosis and by the decrease of clearance by A2E. The bFGF angiogenic protein may therefore be an attractive target to treat ARMD

Associations Between Cardiovascular Risk Factors, Inflammation, and Progression of Carotid Atherosclerosis Among Smokers.

The high risk of cardiovascular events in smokers requires adequate control of other cardiovascular risk factors (CVRFs) to curtail atherosclerosis progression. However, it is unclear which CVRFs have the most influence on atherosclerosis progression in smokers. In 260 smokers aged 40-70 included in a smoking cessation trial, we analyzed the association between traditional CVRFs, high-sensitivity C-reactive protein (hs-CRP), smoking cessation and 3-year progression of carotid intima-media thickness (CIMT, assessed by repeated ultrasound measurements) in a longitudinal multivariate model. Participants (mean age 52 years, 47% women) had a mean smoking duration of 32 years with a median daily consumption of 20 cigarettes. Baseline CIMT was 1185 μm (95% confidence interval [CI]: 1082-1287) and increased by 93 μm (95% CI: 25-161) and 108 μm (95% CI: 33-183) after 1 and 3 years, respectively. Age, male sex, daily cigarette consumption, systolic blood pressure (SBP), but neither low-density lipoprotein cholesterol nor hs-CRP, were independently associated with baseline CIMT (all P ≤ .05). Baseline SBP, but neither low-density lipoprotein cholesterol nor hs-CRP, was associated with 3-year atherosclerosis progression (P = .01 at 3 years). The higher the SBP at baseline, the steeper was the CIMT increase over 3-year follow-up. We found an increase of 26 μm per each 10-mmHg raise in SBP at 1 year and an increase of 39 μm per each 10 mmHg raise in SBP at 3 years. Due to insufficient statistical power, we could not exclude an effect of smoking abstinence on CIMT progression. Control of blood pressure may be an important factor to limit atherosclerosis progression in smokers, besides support for smoking cessation. Among 260 smokers aged 40-70 years with a mean smoking duration of 32 years, baseline SBP was associated with atherosclerosis progression over 3 years, as measured by CIMT (P = .01 at 3 years), independently of smoking variables and other CVRFs. The higher the SBP at baseline, the steeper was the CIMT increase over 3-year follow-up. Our findings emphasize the importance of focusing not only on smoking cessation among smokers, but to simultaneously control other CVRFs, particularly blood pressure, in order to prevent future cardiovascular disease

Childhood adversity: A gateway to multimorbidity in older age?

Multimorbidity, or co-occurrence of several chronic diseases, has major consequences in terms of function, quality of life and mortality. Recent advances suggest that the aetiology of multimorbidity includes a life-long process. The purpose of this study was to determine the association between childhood adversity and multimorbidity in community-dwelling older adults, and to investigate variation in participants born immediately before, during and at the end of the Second World War. Participants were 4731 community-dwelling older adults who enrolled in the Lausanne cohort 65+ study (Switzerland) at age 65-70 years in 2004/2009/2014. A baseline questionnaire provided several indicators of childhood adversity including premature birth, food restrictions, child labour, family economic environment, serious illness/accident, and stressful life events. Multimorbidity at age 67-72 years was defined as ≥2 active chronic diseases at the 2-year follow-up questionnaire. All childhood adversity indicators except premature birth were significantly associated with multimorbidity. Odds ratio (OR) ranged from 1.23 (P = 0.034) for poor family economic environment to 1.74 (P < 0.001) for stressful life events. In a multivariable model adjusted for socioeconomic status, health behaviours and stressful life events in adulthood (>16 years), a history of serious illness/accident (OR = 1.45; P < 0.001) and stressful life events (OR = 1.42; P = 0.001) in childhood remained significantly associated with multimorbidity. Comparisons between cohorts indicated substantial variations in the prevalence of childhood adversity indicators but similar associations with multimorbidity. There was an independent association between childhood adversity and multimorbidity after age 65. This study encourages a comprehensive life-course perspective to better understand and potentially prevent multimorbidity

Comparison of the European and U.S. guidelines for lipid-lowering therapy in primary prevention of cardiovascular disease.

Population-wide impacts of new guidelines in the primary prevention of atherosclerotic cardiovascular disease (ASCVD) should be explored in independent cohorts. Assess and compare the lipid-lowering therapy eligibility and predictive classification performance of 2016 and 2021 European Society of Cardiology (ESC), 2019 American Heart Association/American College of Cardiology (AHA/ACC) and 2022U.S. Preventive Services Task Force (USPSTF) guidelines. Participants from the Colaus|PsyCoLaus study, without ASCVD and not taking lipid-lowering therapy at baseline. Derivation of 10-year risk for ASCVD using SCORE1, SCORE2 (including SCORE2-OP) and PCE. Computation of the number of people eligible for lipid-lowering therapy based on each guideline and assessment of discrimination and calibration metrics of the risk models using first incident ASCVD as an outcome. Among 4,092 individuals, 158 (3.9%) experienced an incident ASCVD during a median follow-up of 9 years (IQR, 1.1). Lipid-lowering therapy was recommended or considered in 40.2% (95% CI, 38.2-42.2), 26.4% (24.6-28.2), 28.6% (26.7-30.5) and 22.6% (20.9-24.4) of women and in 62.1% (59.8-64.3), 58.7% (56.4-61.0), 52.6% (50.3-54.9) and 48.4% (46.1-50.7) of men according to 2016 ESC, 2021 ESC, 2019 AHA/ACC and 2022 USPSTF guidelines, respectively. 43.3% and 46.7% of women facing an incident ASCVD were not eligible for lipid-lowering therapy at baseline according to 2021 ESC and 2022 USPSTF, compared to 21.7% and 38.3% using 2016 ESC and 2019 AHA/ACC, respectively. Both 2022 USPSTF and 2021 ESC guidelines particularly reduced lipid-lowering therapy eligibility in women. Nearly half of women who faced an incident ASCVD were not eligible for lipid-lowering therapy

Nicotine Replacement Therapy for Smokers with Acute Aneurysmal Subarachnoid Hemorrhage: An International Survey.

Smoking prevalence is twice as high among patients admitted to hospital because of the acute condition of aneurysmal subarachnoid hemorrhage (aSAH) as in the general population. Smoking cessation may improve the prognosis of aSAH, but nicotine replacement therapy (NRT) administered at the time of aSAH remains controversial because of potential adverse effects such as cerebral vasospasm. We investigated the international practice of NRT use for aSAH among neurosurgeons. The online SurveyMonkey software was used to administer a 15-question, 5-min online questionnaire. An invitation link was sent to those 1425 of 1988 members of the European Association of Neurosurgical Societies (EANS) who agreed to participate in surveys to assess treatment strategies for withdrawal of tobacco smoking during aSAH. Factors contributing to physicians' posture towards NRT were assessed. A total of 158 physicians from 50 nations participated in the survey (response rate 11.1%); 68.4% (108) were affiliated with university hospitals and 67.7% (107) practiced at high-volume neurovascular centers with at least 30 treated aSAH cases per year. Overall, 55.7% (88) of physicians offered NRT to smokers with aSAH, 22.1% (35) offered non-NRT support including non-nicotine medication and counselling, while the remaining 22.1% (35) did not actively support smoking cessation. When smoking was not possible, 42.4% (67) of physicians expected better clinical outcomes when prescribing NRT instead of nicotine deprivation, 36.1% (57) were uncertain, 13.9% (22) assumed unaffected outcomes, and 7.6% (12) assumed worse outcomes. Only 22.8% (36) physicians had access to a local smoking cessation team in their practice, of whom half expected better outcomes with NRT as compared to deprivation. A small majority of the surveyed physicians of the EANS offered NRT to support smoking cessation in hospitalized patients with aSAH. However, less than half believed that NRT could positively impact clinical outcome as compared to deprivation. This survey demonstrated the lack of consensus regarding use of NRT for hospitalized smokers with aSAH

Hospital revascularisation capability and quality of care after an acute coronary syndrome in Switzerland.

BACKGROUND: Patients with acute coronary syndrome (ACS) transferred to regional nonacademic hospitals after percutaneous coronary intervention (PCI) may receive fewer preventive interventions than patients who remain in university hospitals. We aimed at comparing hospitals with and without PCI facilities regarding guidelines-recommended secondary prevention interventions after an ACS. METHODS: We studied patients with ACS admitted to a university hospital with PCI facilities in Switzerland, and either transferred within 48 hours to regional nonacademic hospitals without PCI facilities or directly discharged from the university hospital. We measured prescription rates of evidence-based recommended therapies after ACS including reasons for nonprescription of aspirin, statins, β-blockers, angiotensin converting-enzyme inhibitors (ACEI) / angiotensin II receptor blockers (ARB), along with cardiac rehabilitation attendance and delivery of a smoking cessation intervention. RESULTS: Overall, 720 patients with ACS were enrolled; 541 (75.1%) were discharged from the hospital with PCI facilities, 179 (24.9%) were transferred to hospitals without PCI facilities. Concomitant prescription of aspirin, β-blockers, ACEI/ARB and statins at discharge was similar in hospitals with and without PCI facilities, reaching 83.9% and 85.5%, respectively (p = 0.62). Attendance at cardiac rehabilitation reached 55.5% for the hospital with PCI facilities and 65.7% for hospitals without PCI facilities (p = 0.02). In-hospital smoking cessation interventions were delivered to 70.8% patients exclusively at the hospital with PCI facilities. CONCLUSION: Quality of care for patients with ACS discharged from hospitals without PCI facilities was similar to that of patients directly discharged from the hospital with PCI facilities, except for in-hospital smoking cessation counselling and cardiac rehabilitation attendance

Uptake and efficacy of a systematic intensive smoking cessation intervention using motivational interviewing for smokers hospitalised for an acute coronary syndrome: a multicentre before-after study with parallel group comparisons.

To compare the efficacy of a proactive approach with a reactive approach to offer intensive smoking cessation intervention using motivational interviewing (MI). Before-after comparison in 2 academic hospitals with parallel comparisons in 2 control hospitals. Academic hospitals in Switzerland. Smokers hospitalised for an acute coronary syndrome (ACS). In the intervention hospitals during the intervention phase, a resident physician trained in MI systematically offered counselling to all smokers admitted for ACS, followed by 4 telephone counselling sessions over 2 months by a nurse trained in MI. In the observation phase, the in-hospital intervention was offered only to patients whose clinicians requested a smoking cessation intervention. In the control hospitals, no intensive smoking cessation intervention was offered. The primary outcome was 1 week smoking abstinence (point prevalence) at 12 months. Secondary outcomes were the number of smokers who received the in-hospital smoking cessation intervention and the duration of the intervention. In the intervention centres during the intervention phase, 87% of smokers (N=193/225) received a smoking cessation intervention compared to 22% in the observational phase (p<0.001). Median duration of counselling was 50 min. During the intervention phase, 78% received a phone follow-up for a median total duration of 42 min in 4 sessions. Prescription of nicotine replacement therapy at discharge increased from 18% to 58% in the intervention phase (risk ratio (RR): 3.3 (95% CI 2.4 to 4.3; p≤0.001). Smoking cessation at 12-month increased from 43% to 51% comparing the observation and intervention phases (RR=1.20, 95% CI 0.98 to 1.46; p=0.08; 97% with outcome assessment). In the control hospitals, the RR for quitting was 1.02 (95% CI 0.84 to 1.25; p=0.8, 92% with outcome assessment). A proactive strategy offering intensive smoking cessation intervention based on MI to all smokers hospitalised for ACS significantly increases the uptake of smoking cessation counselling and might increase smoking abstinence at 12 months

Identification and molecular characterisation of Lausanne Institutional Biobank participants with familial hypercholesterolaemia - a proof-of-concept study.

We aimed to identify familial hypercholesterolaemia mutation carriers among participants to the Lausanne Institutional Biobank (BIL). Our experimental workflow was designed as a proof-of-concept demonstration of the resources and services provided by our integrated institutional clinical research support platform. Familial hypercholesterolaemia was used as a model of a relatively common yet often underdiagnosed and inadequately treated Mendelian disease. Clinical and laboratory information was extracted from electronic hospital records. Patients were selected using elevated plasma cholesterol levels (total cholesterol ≥7.5 mM or low-density lipoprotein cholesterol ≥5 mM), premature coronary artery disease status and age (18-60 yr) as main inclusion criteria. LDLR, APOB and PCSK9 were analysed by high-throughput DNA sequencing. The most relevant mutations were confirmed by Sanger sequencing. Of 23 737 patients contacted by the BIL, 17 760 individuals consented to participate and 13 094 wished to be recontacted if there were findings requiring clinical action. Plasma cholesterol records were available for 5111 participants, of whom 94 were selected for genetic screening. Twenty-five of the tested patients presented with premature coronary artery disease while 69 had no such diagnosis. Seven heterozygous carriers of eight rare coding missense variants were identified. Three mutations were pathogenic (APOB p.R3527Q) or likely pathogenic (LDLR p.C27W, LDLR p.P526S) for hypercholesterolaemia, while the others were either benign or of unknown significance. One patient was a double heterozygote for variants APOB p.R3527Q and LDLR p.P526S. This work illustrates how clinical and translational research can benefit from a dedicated platform integrating both a hospital-based biobank and a data support team