Tissue factor pathway inhibitor: a new link among arterial stiffness, pulse pressure, and coagulation in postmenopausal women.

OBJECTIVE: To investigate in women older than 60 whether aortic stiffness or pulse pressure (PP) is associated with selected procoagulant or anticoagulant factors and to examine whether pulsatile stretch influences these factors in human vascular smooth muscle cells (VSMCs) in vitro. METHODS AND RESULTS: Aortic pulse wave velocity (PWV) and carotid PP were studied in 123 apparently healthy postmenopausal women. PWV, PP, von Willebrand factor, and free tissue factor pathway inhibitor (TFPI), but not mean arterial pressure, increased with age. Free TFPI and PWV were positively correlated, even after adjustment for age and PP and other confounding parameters. In vitro, 5% or 10% pulsatile stretch (at 1 Hz) enhanced TFPI synthesis and secretion by VSMCs in a time-independent manner (1 to 48 hours) without changes in protein level of smooth muscle myosin heavy chain. Application of 5% static stretch had no effect. CONCLUSIONS: In postmenopausal women, free TFPI increases as vascular wall function deteriorates and PP increases. These findings are supported by the increase in TFPI synthesized by VSMCs in response to cyclic stress in vitro. They suggest that VSMCs require pulsatility to interfere with the coagulation process and highlight the relevance of plasma free TFPI levels to cardiovascular diseases.

[Home delivered meals: impasse or solution?]. / Portage des repas à domicile: impasse ou solution?

Undernutrition is common in elderly people living at home. A loss of autonomy can lead them to use home help services, such as home delivered meals. However this solution is not always effective and having meals brought to the home seems to aggravate their isolation, as the results of a survey of twenty people showed.

Health-related quality of life in French adolescents and adults: norms for the DUKE Health Profile.

BACKGROUND: The continual monitoring of population health-related quality of life (HRQoL) with validated instruments helps public health agencies assess, protect, and promote population health. This study aimed to determine norms for the French adolescent and adult general population for the Duke Health Profile (DUKE) questionnaire in a large representative community sample. METHODS: We randomly selected 17,733 French people aged 12 to 75 years old in 2 steps, by households and individuals, from the National Health Barometer 2005, a periodic population study by the French National Institute for Prevention and Health Education. Quality of life and other data were collected by computer-assisted telephone interview. RESULTS: Normative data for the French population were analyzed by age, gender and self-reported chronic disease. Globally, function scores (best HRQoL=100) for physical, mental, social, and general health, as well as perceived health and self-esteem, were 72.3 (SEM 0.2), 74.6 (0.2), 66.8 (0.1), 71.3 (0.1), 71.3 (0.3), 76.5 (0.1), respectively. Dysfunction scores (worst HRQoL=100) for anxiety, depression, pain and disability domains were 30.9 (0.1), 27.6 (0.2), 34.3 (0.3), 3.1 (0.1), respectively. CONCLUSION: The French norms for adolescents and adults for the DUKE could be used as a reference for other studies assessing HRQoL, for specific illnesses, in France and for international comparisons.

The Nexus Between Telomere Length and Lymphocyte Count in Seniors Hospitalized With COVID-19.

Profound T-cell lymphopenia is the hallmark of severe coronavirus disease 2019 (COVID-19). T-cell proliferation is telomere length (TL) dependent and telomeres shorten with age. Older COVID-19 patients, we hypothesize, are, therefore, at a higher risk of having TL-dependent lymphopenia. We measured TL by the novel Telomere Shortest Length Assay (TeSLA), and by Southern blotting (SB) of the terminal restriction fragments in peripheral blood mononuclear cells of 17 COVID-19 and 21 non-COVID-19 patients, aged 87 ± 8 (mean ± SD) and 87 ± 9 years, respectively. TeSLA tallies and measures single telomeres, including short telomeres undetected by SB. Such telomeres are relevant to TL-mediated biological processes, including cell viability and senescence. TeSLA yields 2 key metrics: the proportions of telomeres with different lengths (expressed in %) and their mean (TeSLA mTL), (expressed in kb). Lymphocyte count (109/L) was 0.91 ± 0.42 in COVID-19 patients and 1.50 ± 0.50 in non-COVID-19 patients (p < .001). In COVID-19 patients, but not in non-COVID-19 patients, lymphocyte count was inversely correlated with the proportion of telomeres shorter than 2 kb (p = .005) and positively correlated with TeSLA mTL (p = .03). Lymphocyte count was not significantly correlated with SB mTL in either COVID-19 or non-COVID-19 patients. We propose that compromised TL-dependent T-cell proliferative response, driven by short telomere in the TL distribution, contributes to COVID-19 lymphopenia among old adults. We infer that infection with SARS-CoV-2 uncovers the limits of the TL reserves of older persons. Clinical Trials Registration Number: NCT04325646.

A Mechanism for Severity of Disease in Older Patients with COVID-19: The Nexus between Telomere Length and Lymphopenia.

BACKGROUND: Lymphopenia due to a plummeting T-cell count is a major feature of severe COVID-19. T-cell proliferation is telomere length (TL)-dependent and TL shortens with age. Older persons are disproportionally affected by severe COVID-19, and we hypothesized that those with short TL have less capacity to mount an adequate T-cell proliferative response to SARS-CoV-2. This hypothesis predicts that among older patients with COVID-19, shorter telomeres of peripheral blood mononuclear cells (PBMCs) will be associated with a lower lymphocyte count. METHODS: Our sample comprised 17 COVID-19 and 21 non-COVID-19 patients, aged 87(8) (mean(SD)) and 87 (9) years, respectively. We measured TL by the Telomere Shortest Length Assay, a novel method that measures and tallies the short telomeres directly relevant to telomere-mediated biological processes. The primary analysis quantified TL as the proportion of telomeres shorter than 2 kilobases. For comparison, we also quantified TL by Southern blotting, which measures the mean length of telomeres. RESULTS: Lymphocyte count (109/L) was 0.91 (0.42) in COVID-19 patients and 1.50(0.50) in non-COVID-19 patients (P < 0.001). In COVID-19 patients, but not in non-COVID-19 patients, lymphocyte count was inversely correlated with the proportion of telomeres shorter than 2 kilobases (P = 0.005) and positively correlated with the mean of telomeres measured by TeSLA (P = 0.03). Lymphocyte counts showed no statistically significant correlations with Southern blotting results in COVID-19 or non-COVID-19 patients. CONCLUSIONS: These results support the hypothesis that a compromised TL-dependent T-cell proliferative response contributes to lymphopenia and the resulting disproportionate severity of COVID-19 among old adults. We infer that infection with SARS-CoV-2 uncovers the limits of the TL reserves of older persons.

Mechanisms of antiphospholipid-induced thrombosis: effects on the protein C system.

An acquired resistance to activated protein C (APC) has been demonstrated in patients with antiphospholipid antibodies (aPL). Recent studies report interactions between beta2 glycoprotein I (beta2GPI) and prothrombin-binding antibodies and the protein C system. Some aPL in patients recognize one or more conformational epitopes shared by beta2GPI and catalytic domains of APC. Both beta2GPI and anti-prothrombin antibodies are associated with APC resistance. Several clinical studies have focused on an association between aPL and APC resistance, determined by classic activated partial thromboplastin time-based tests. It has been shown in most studies that APC resistance was associated with lupus anticoagulants. APC resistance is also associated with thrombosis, especially venous thromboembolism. Several recent studies have reported a novel integrated approach of coagulation using calibrated automated thrombography. This technique allows an approach of APC sensitivity without interference with lupus anticoagulants. Clinical associations between APC resistance and thromboembolic events have been demonstrated.

Clinical determinants of failure in balance tests in elderly subjects.

We assessed the role of clinical and biological parameters on performance in four balance tests in elderly subjects. An observational study was conducted in the Center for Preventive Medicine of Nancy (France) in 2368 community-living elderly subjects aged 60 and older. Body mass index (BMI), Mini-Mental State Examination (MMSE), clock test, "Health score" and use of psychotropic drugs (UPD) were assessed. Participants performed four balance tests: "one-leg-stand" (OLS), "timed-up-and-go" (TUG), "rise-from-the-floor" (RFF) and "sit-to-stand" (STS). The statistical analysis showed that women were almost twice as likely to fail balance tests as men. In both women and men, the following determinant factors of the performance in balance tests were found: for OLS: age, BMI and health score; for TUG: age, BMI, clock test and health score; for RFF: BMI and health score. In addition, in women other determinant factors were: MMSE for OLS, UPD for TUG, age and clock test for RFF. In men, the clock test and the UPD were also significant determinant factors for OLS. Similar results were found for STS. In conclusion, female sex, overweight, low cognitive status, low self-perception of health and UPD were associated with a higher risk of failure in balance tests.

Improvement of decision-making criteria for the care of elderly cancer patients by general practitioners (Lorraine, France).

OBJECTIVE: The objective of this study was to identify changes in the decision-making criteria of general practitioners (GPs) concerning the care of elderly cancer patients after 1 year of corrective measures for care practices in the Lorraine region, France. MATERIALS AND METHODS: In 2014, a postal mail questionnaire was sent to all GPs in the Lorraine region. This questionnaire was designed to identify GPs' decision-making criteria. It was based on the results of a literature review and on existing guidelines. During 1 year, corrective measures were implemented to improve practices, especially training sessions for physicians and production of specific tools, including a guide to the accepted ideas in geriatric oncology. In 2015, the same questionnaire was resent to all GPs to compare the answers. RESULTS: In 2014, 430 questionnaires were returned out of 2,048 sent, and in 2015, 378 questionnaires were returned out of 2,066 sent. Our results show for the first time that there exists a significant difference in the overall decision criteria between the two survey periods. This difference mainly concerns criteria related to the cancerous diseases. Physicians tend to consider the principal decision criteria to be less important after the training period. GPs express the importance of accessibility to specialists for additional advice in both 2014 and 2015; the distance between the patient's home and an adapted care facility and the interval before care begins are viewed as similarly important. CONCLUSION: Training and information sessions for physicians remain the most important tool for improving care practices. Such training strategies are more effective when carried out at the geographical scale at which the cancer professionals practice, allowing them to exploit their local organizational structure. The analysis of our data makes it possible to further integrate the patient into the care path, which remains a public health issue in terms of cost and organization.

Hypercoagulability resulting from opposite effects of lupus anticoagulants is associated strongly with thrombotic risk.

Interference of antiphospholipid antibodies (aPL) with coagulation was investigated in 40 aPL-patients (24 with thrombosis) using thrombography. Impairment of the activated protein C anticoagulant pathway was partially offset by the genuine anticoagulant effect. The net result, a procoagulant phenotype, was associated with a 7-fold increased risk of thrombosis in aPL-patients.

Decision making affecting care of older people with cancer: a comparison between general practitioners and oncologists in Lorraine.

The main objective of this study is to identify the decision criteria of general practitioners and oncologists in the management of older patients with cancer in Lorraine. The secondary objectives are to identify the difficulties encountered and to propose solutions to improve health path of these patients. 2,995 post mail questionnaires were sent to all general practitioners and oncologists in Lorraine. Some decision criteria differ between general practitioners and oncologists: civilian age and accessibility to a specialized advice for general practitioners; type of cancer, nutritional status, application of best practice recommendations, and multidisciplinary discussion for oncologists. The main difficulties reported are organizational and relate to time interval before specific care beginning, accessibility to a medical specialist, and post-diagnosis such link between primary care and hospital. General practitioners and oncologists mainly agree with the difficulties encountered and the solutions to find, even if some decision criteria differences are highlighted. The training of professionals remains the major lever for improvement of medical practices.

Effect of Multimorbidity on Health-Related Quality of Life in Adults Aged 55 Years or Older: Results from the SU.VI.MAX 2 Cohort.

INTRODUCTION: Multimorbid chronic diseases are usually considered separately in trials. Here, we aimed to describe overall multimorbidity patterns in adults aged 55 years or older and assess their effect on health-related quality of life (HRQoL). METHODS: We used data for 5,647 participants included in the SUpplémentation en VItamines et Minéraux AntioXydants 2 (SU.VI.MAX 2) population-based trial. HRQoL was assessed by the French versions of the Medical Outcome Study Short Form 36 and the Duke Health Profile. An exploratory factor analysis was used to determine multimorbidity patterns, and a multimorbidity score for each resulting pattern was calculated. Adjusted multiple linear regression was used to examine the association between the identified multimorbidity and HRQoL scores by gender and for each age group (55-59, 60-64, 65-69, ≥ 70 years). RESULTS: More than 63% of the sample reported two or more chronic conditions (from 55.8% for those 55-59 years to 74.4% for those ≥ 70 years). Multimorbidity was more common among women than men (67.3% vs 60%). Two different multimorbidity patterns were identified. Pattern A was represented mainly by mental illness and bone impairments. Pattern B was represented mainly by cardiovascular and metabolic disorders. After adjusting for covariates, a high pattern A score was associated with reduced HRQoL for the physical and mental components of each HRQoL questionnaire, and a high pattern B score was associated with reduced HRQoL for only the physical component of each questionnaire. These multimorbidity scores affected HRQoL differently by age group. CONCLUSION: Our study used a novel methodological approach to account for multimorbidity patterns in determining the link with chronic conditions. These multimorbidity scores (counted and weighted) can be used in clinical research to control for the effect of multimorbidity on patients' HRQoL and may be useful for clinical practice. CLINICAL TRIAL REGISTRATION: Clinicaltrial.gov (number NCT00272428).

Initiation of warfarin therapy in elderly medical inpatients: a safe and accurate regimen.

PURPOSE: Elderly patients are at high risk of over-anticoagulation when treated with warfarin, especially during treatment induction. We developed a simple low-dose regimen for starting warfarin therapy in elderly inpatients. The daily maintenance dosage is predicted from the international normalized ratio (INR) measured the day after the third daily intake of a 4-mg dose. We conducted a prospective multicenter study to evaluate the accuracy and safety of this regimen. METHODS: We studied 106 elderly (age >or=70 years) inpatients (mean [+/- SD] age, 85 +/- 6 years; range, 71 to 97 years) who had a target INR of 2.0 to 3.0. Accuracy in predicting the daily maintenance dose from INR value on day 3 was evaluated. RESULTS: The predicted daily maintenance warfarin dose (3.1 +/- 1.6 mg/d) correlated closely with the actual maintenance dose (3.2 +/- 1.7 mg/d; R(2) = 0.84). The predicted dose was equal to the actual dose in 77 patients (73%; 95% confidence interval [CI]: 64% to 81%) and within 1 mg in 101 patients (95%; 95% CI: 91% to 99%). The mean time needed to achieve a therapeutic INR was 6.7 +/- 3.3 days (median, 6.0 days); the mean time needed to achieve the maintenance dose was 9.2 +/- 4.5 days (median, 7.0 days). None of the patients had an INR >4.0 during this period. One fatal bleeding event was recorded in a patient with an INR in the therapeutic range. CONCLUSION: Our warfarin induction regimen was simple, safe, and accurate in predicting the daily maintenance warfarin dose in elderly hospitalized patients.

Low-dose warfarin in atrial fibrillation leads to more thromboembolic events without reducing major bleeding when compared to adjusted-dose--a meta-analysis.

The use of warfarin with a range INR of 2.0-3.0 is recommended in prevention of stroke for nonvalvular atrial fibrillation (AF) patients, in particular those older than 75 years. The risk of bleeding that is associated with this range of INR has led to evaluate lower ranges (low-dose or fixed minidose) in terms of risks and benefits. A meta-analysis of all randomized controlled trials evaluating 'low-intensity' 'minidose' or 'low-dose anticoagulant' treatment for prevention of thromboembolic events in AF was conducted by two independent reviewers. Study quality was evaluated in a blinded fashion. Four original studies were retrieved. Outcome events were determined in various treatment groups: ischemic stroke, systemic embolism, thromboses (ischemic stroke, systemic embolism or myocardial infarction), vascular death, major hemorrhage and hemorrhagic death. Results obtained with a random effects model were expressed as a common relative risk. Adjusted-dose warfarin compared with lower dose warfarin (INR < or = 1.6) in 2108 randomised patients significantly reduced the risk of any thrombosis: Relative risk (RR): 0.50 (95% CI; 0.25 to 0.97). The RR was 0.46 (95%CI; 0.2 to 1.07) for ischemic stroke. Inversely lower dose did not statistically decrease the risk for major hemorrhage compared to adjusted-dose: RR adjusted-dose vs lower dose: 1.23 (95% CI; 0.67-2.27). The RR was 0.97 (95 % CI 0.27-3.54) for hemorrhagic death. Our meta-analysis showed that adjusted-dose compared with low-dose or minidose warfarin therapy (INR < or =1.6) was more effective to prevent ischemic thromboembolic events in patients with atrial fibrillation.

[Antiphospholipid syndrome in nephrology. Kidney damage and practical aspects of the management]. / Le syndrome des antiphospholipides en néphrologie. Atteinte rénale et aspects pratiques de la prise en charge.

The antiphospholipid syndrome is a thrombophilia characterized by the combination of arterial and/or venous thrombotic events or obstetric clinical events, associated with persistent presence of antiphospholipid antibodies. In this syndrome, thromboses may affect all of the vascular tree, renal damage is frequently associated with a specific antiphospholipid syndrome nephropathy. We propose in this review to provide updated recommendations on the management of antiphospholipid syndrome in nephrology. Treatment is based on long-term anticoagulant therapy with or without antiplatelet agents according to clinical events. The use of a conventional nephroprotection must not be forgotten (strict control of blood pressure with drugs blocking the renin-angiotensin-aldosterone system). Catastrophic antiphospholipid syndrome is an extremely severe complication which can threaten the vital prognosis of the patient. This justifies particular surveillance, as well as prevention in high-risk situations. We also illustrate the difficulties of long-term management in these patients, both in dialysis or kidney transplantation.

[What use general practitioners do they tests and scales referred to geriatric?]. / Quelle utilisation les médecins généralistes font-ils des tests et échelles à visée gériatrique ?

JUSTIFICATION: the complexity of the elderly's cares justifies to set up tools of screening, diagnosis and follow-up of multiple pathologies. Numerous tests and scales were elaborated and validated, and are recommended by the Haute autorité de santé (HAS). Are these tools useful and are they adapted to the consultation of general medicine? What are the obstacles to their appropriation by the general practitioners? OBJECTIVE: to determine the frequency of use of a series of twelve tests and scales to geriatric aim by the general practitioners. SECONDARY OBJECTIVE: interests of these tests and obstacles to their use in practice. METHOD: transverse survey by mail way, with a representative sampling of general practitioners of Meurthe-et-Moselle concerning the use of 12 tests or scales validated. RESULTS: 84 general practitioners on 145 requested participated in the survey (rate of answers 58%). The most used tests are the MMSE, the AGGIR, the test of the clock and the test of five words of Dubois (respectively 48, 43, 38 and 36% of regular users). Thirty five percent of the general practitioners never use tests or scales, while 37% use them at least once a month. 85.5% of the trained practitioners use it more frequently. A practitioner on two (51%) considers that these tools are unsuitable for his practice while almost totality of the general practitioners (90%) admits an interest about these tools in the screening, the diagnosis and the follow-up of the geriatric pathologies. The obstacles are essentially connected to the very time-consuming character, to the absence of specific quotation and to the lack of training. CONCLUSION: in the absence of tests and scales conceived by geriatricians and general practitioners, the existing tests although recognized useful are underused by the general practitioners of Meurthe-et-Moselle.

Correlation between peripheral blood pressure and pulse-wave velocity values in the institutionalized elderly persons 80 years of age and older: the PARTAGE study.

BACKGROUND: Carotid-femoral pulse-wave velocity (PWV) provides a comprehensive noninvasive indication of arterial stiffness, and is now established as a strong marker of cardiovascular disease (CVD). The correlation between peripheral blood pressure (BP) and PWV and their respective influences on mortality have been poorly studied in the elderly. Our objective was to analyze this correlation in nursing-home residents over 80 years of age, with the view that the results of this could ultimately be helpful in implementing strategies for the diagnosis and long-term follow-up of CVD and mortality in the very elderly population. METHODS: The Predictive Value of Blood Pressure and Arterial Stiffness in Institutionalized Very Aged Population (PARTAGE) study is a 2-year cohort study of 1,130 subjects living in 72 nursing homes in France and Italy. The correlation between baseline systolic and diastolic blood pressure (SBP and DBP, respectively) and baseline PWV (measured with a PulsePen® tonometer) was studied in 1,071 subjects for whom PWV measurements were available. RESULTS: Correlations between peripheral BP and PWV were significant but weak, with r = 0.24 for self-measured SBP, r = 0.30 for casual SBP, r = 0.11 for self-measured DBP, r = 0.14 for casual DBP, and r = 0.26 for casual pulse pressure (PP). A trend toward a weaker correlation was observed in the older age group for self-measured SBP and in the group with a lower level of activities of daily living (ADL) for self-measured SBP and DBP. CONCLUSIONS: These findings suggest that SBP, DBP, and PWV provide different information in the very elderly. The results of the prospective, longitudinal, long-term PARTAGE study will allow further insight into this and provide additional in-depth information about the respective prognostic value of the measurement of peripheral BP and PWV.

[Place and characteristics of patients older than 85 managed by mobile palliative care team; a retrospective study]. / Place et caractéristiques des patients âgés de 85 ans et plus suivis en équipe mobile de soins palliatifs ; étude rétrospective.

The objectives of this study was to specify the place of the patients older than 85 in the activity of the Mobile health unit of the Hospital of Metz-Thionville, to determine their characteristics and to show possible care differences as compared with younger patients. This is a retrospective study concerning all the patients seen by the Mobile health unit in 2006 and 2007. The patients older than 85 represent 11% of the 652 patients followed by the Unit and 7.8% of the 2.436 consultations on the study period. The older patients have a WHO mean score significantly higher and a Karnofsky mean score significantly lower than the younger subjects. Their survival rate tends to be lower but not significantly. Cancers are less frequent in older patients and they have fewer consultations than younger ones. The older patients present fewer communication problems and less often pain than the younger patients. The prescriptions of non-opioid and opioid analgesics, steroïds or antiepileptic drugs (used as analgesics) are less frequent in the older patients. The results of this study showed some specificities of palliative care in the older patients: we observed a great variety of pathologies and a lower frequency of cancers than in younger patients, various places of care, difficulties to evaluate the symptoms or to treat them due to communication problems especially. If these specificities are real, they do not seem to have important repercussions on following since the group of the patients older than 85 and the one of the younger patients differ only little in terms of survival rate or mean number of consultations.

Mortality and cardiovascular events are best predicted by low central/peripheral pulse pressure amplification but not by high blood pressure levels in elderly nursing home subjects: the PARTAGE (Predictive Values of Blood Pressure and Arterial Stiffness in Institutionalized Very Aged Population) study.

OBJECTIVES: The aim of the longitudinal PARTAGE study was to determine the predictive value of blood pressure (BP) and pulse pressure amplification, a marker of arterial function, for overall mortality (primary endpoint) and major cardiovascular (CV) events, in subjects older than 80 years of age living in a nursing home. BACKGROUND: Assessment of pulse indexes may be important in the evaluation of the CV risk in very elderly frail subjects. METHODS: A total of 1,126 subjects (874 women) who were living in French and Italian nursing homes were enrolled (mean age, 88 ± 5 years). Central (carotid) to peripheral (brachial) pulse pressure amplification (PPA) was calculated with the help of an arterial tonometer. Clinical and 3-day self-measurements of BP were conducted. RESULTS: During the 2-year follow-up, 247 subjects died, and 228 experienced major CV events. The PPA was a predictor of total mortality and major CV events in this population. A 10% increase in PPA was associated with a 24% (p < 0.0003) decrease in total mortality and a 17% (p < 0.01) decrease in major CV events. Systolic BP, diastolic BP, or pulse pressure were either not associated or inversely correlated with total mortality and major CV events. CONCLUSIONS: In very elderly individuals living in nursing homes, low PPA from central to peripheral arteries strongly predicts mortality and adverse effects. Assessment of this parameter could help in risk estimation and improve diagnostic and therapeutic strategies in very old, polymedicated persons. In contrast, high BP is not associated with higher risk of mortality or major CV events in this population. (Predictive Values of Blood Pressure and Arterial Stiffness in Institutionalized Very Aged Population [PARTAGE]; NCT00901355).