Frailty in heart failure according to the presence or absence of wild-type transthyretin cardiac amyloidosis.

AIMS: Wild-type transthyretin cardiac amyloidosis (ATTRwt CA) is a common, underdiagnosed cause of heart failure (HF) in the elderly. Concurrent extracardiac amyloid infiltration might be responsible for a specific frailty phenotype. This study aims to compare the prevalence and characteristics of frailty parameters in HF patients, with or without ATTRwt CA. METHODS: In a comparative cross-sectional study, we prospectively included consecutive HF patients with or without ATTRwt CA (the HF + ATTRwt+ and HF + ATTRwt- groups, respectively) between April 2018 and April 2021. Logistic regression models were used to compare the groups with regard to frailty as assessed using multidimensional geriatric tools. RESULTS: We included 123 patients (68 HF + ATTRwt+ and 55 HF + ATTRwt-). The mean age was 80.9 (standard deviation 6.3) years, 87% were male, 34% had left ventricular systolic dysfunction and 34% were New York Heart Association (NYHA) III. Relative to the HF + ATTRwt- group, patients in the HF + ATTRwt+ group were more likely to have shrinking [odds ratios = 2.9 (95% confidence interval, 1.1 to 1.7), P = 0.03], balance disorders [1.8 (1.1 to 2.8), P = 0.02], memory complaints [2.5, (1.0 to 5.9), P = 0.05] and overactive bladder [1.5 (1.1 to 2.2), P = 0.03], independently of age, sex, NYHA class and diabetes status. The proportion of very frail patients was higher (albeit not significantly) in the HF + ATTRwt+ group than in the HF + ATTRwt- group [2.4 (0.9 to 6.9), P = 0.10]. CONCLUSIONS: ATTRwt CA is associated with a specific frailty phenotype. Patients with ATTRwt CA should be screened for frailty and managed collaboratively by cardiologists and geriatricians, with a view to improving quality of life.

Effectiveness of comprehensive geriatric assessment adapted to primary care when provided by a nurse or a general practitioner: the CEpiA cluster-randomised trial.

BACKGROUND: The benefits of comprehensive geriatric assessment (CGA) are well established for hospital care but less so for primary care. Our primary objective was to assess the effect of two multifaceted interventions based on a CGA adapted for primary care on a composite criterion combining all-cause mortality, emergency department visits, unplanned hospital admissions, and institutionalisation. METHODS: This open-label, pragmatic, three-arm, cluster-randomised controlled trial involved 39 general practices in France. It included 634 patients aged 70 years or over with chronic health conditions and/or an unplanned hospital admission in the past 3 months, between 05/2016 and 08/2018. Interventions were in arm 1: a systematic nurse-led CGA; arm 2: a GP-led CGA, at the GP's discretion; arm 3: standard care. The primary composite endpoint was assessed at 12 months. The secondary endpoints included: components of the composite endpoint, health-related quality of life (Duke Health Profile), functional status (Katz Activities of Daily Living Index) and medications (number) at 12 months. Pairwise comparisons between the experimental groups and the control were tested. The main analysis was performed on the intention-to-treat (ITT) population, after imputing missing information and adjusting for baseline imbalances by mixed effects regressions. RESULTS: For the primary composite outcome, no statistically significant difference was found between arm 1 and the control (adjusted odds ratio [aOR] = 0.81 [95%CI 0.54-1.21], P = 0.31), whereas arm 2 and the control differed significantly (aOR = 0.60 [0.39-0.93], P = 0.022). A statistically lower risk of unplanned hospital admission in arm 2 vs control (aOR = 0.57 [0.36-0.92], P = 0.020)) was observed, while no statistically significant differences were found for the other components and between arm 1 and the control. None of the other secondary endpoints differed between arms. CONCLUSIONS: Our study led in community-dwelling older patients with chronic conditions found no significant effect of a CGA adapted for primary care on mortality, functional independence and quality of life, but suggests that a GP-led CGA may reduce the risk of unplanned hospital admission. Our study demonstrates the feasibility of incorporating CGA into clinical practice and highlights its potential benefits when applied on a case-by-case basis, guided by the GPs who develop the resulting PCP. TRIAL REGISTRATION: NCT02664454.

COVID-19 profiles in general practice: a latent class analysis.

BACKGROUND: General practitioners (GPs) were on the front line of the COVID-19 outbreak. Identifying clinical profiles in COVID-19 might improve patient care and enable closer monitoring of at-risk profiles. OBJECTIVES: To identify COVID-19 profiles in a population of adult primary care patients, and to determine whether the profiles were associated with negative outcomes and persistent symptoms. DESIGN, SETTING AND PARTICIPANTS: In a prospective multicentre study, 44 GPs from multiprofessional primary care practices in the Paris area of France recruited 340 consecutive adult patients (median age: 47 years) with a confirmed diagnosis of COVID-19 during the first two waves of the epidemic. METHOD AND OUTCOME: A latent class (LC) analysis with 11 indicators (clinical signs and symptoms) was performed. The resulting profiles were characterised by a 3-month composite outcome (COVID-19-related hospital admission and/or death) and persistent symptoms three and 6 months after inclusion. RESULTS: We identified six profiles: 'paucisymptomatic' (LC1, 9%), 'anosmia and/or ageusia' (LC2, 12.9%), 'influenza-like syndrome with anosmia and ageusia' (LC3, 15.5%), 'influenza-like syndrome without anosmia or ageusia' (LC4, 24.5%), 'influenza-like syndrome with respiratory impairment' (LC5) and a 'complete form' (LC6, 17.7%). At 3 months, 7.4% of the patients were hospitalised (with higher rates in LC5), and 18% had persistent symptoms (with higher rates in LC5 and LC6). At 6 months, 6.4% of the patients had persistent symptoms, with no differences between LCs. CONCLUSION: Our findings might help GPs to identify patients at risk of persistent COVID-19 symptoms and hospital admission and then set up procedures for closer monitoring.

14-day tailored PCR-guided triple therapy versus 14-day non-Bismuth concomitant quadruple therapy for Helicobacter pylori eradication: A multicenter, open-label randomized noninferiority controlled trial.

BACKGROUND: The systematic use of susceptibility testing and tailored first-line treatment for Helicobacter pylori eradication has yet to be established. AIM: To compare 14-day tailored PCR-guided triple therapy to 14-day non-Bismuth concomitant quadruple therapy for first-line Helicobacter pylori eradication. PATIENTS AND METHODS: We performed a multicenter, parallel-group, randomized noninferiority controlled trial. Naive adult patients with Helicobacter pylori infection were treated with 14-day tailored PCR-guided triple therapy (esomeprazole 40 mg and amoxicillin 1000 mg b.d. plus clarithromycin 500 mg or levofloxacin 500 mg b.d. according to clarithromycin susceptibility) or 14-day non-Bismuth concomitant quadruple therapy (esomeprazole 40 mg, amoxicillin 1000 mg, clarithromycin 500 mg, and metronidazole 500 mg b.d.). The primary endpoint was H. pylori eradication. RESULTS: We screened 991 patients for eligibility and randomized 241 patients. The first-line eradication rate was 99.2% in the tailored PCR-guided group and 95.9% in the control group (ITT population; absolute difference of +3.30%, with a lower bound of CI at -0.68%). Both first-line therapies were well tolerated, with a formally significant difference in favor of the tailored PCR-guided group (61.4% vs. 41.2%, p = 0.003). Economic analyses revealed a lower cost of the tailored PCR-guided arm, with a 92% chance of being jointly more effective and less expensive than the control arm in the ITT population. CONCLUSION: In a country with a high level of clarithromycin resistance, the results of our study demonstrated the noninferiority of 14-day tailored PCR-guided triple therapy as a first-line H. pylori eradication therapy compared to 14-day non-Bismuth quadruple therapy (ClinicalTrials.gov NCT02576236).

Cancer mortality and competing causes of death in older adults with cancer: A prospective, multicentre cohort study (ELCAPA-19).

BACKGROUND: In older patients with cancer, comorbidities compete with cancer for cause of death. The objectives were to evaluate cancer mortality and factors associated, according to metastatic status. METHODS: Between 2007 and 2014, patients with cancer aged ≥70 referred for pre-therapeutic geriatric assessment (GA) were included through the ELCAPA prospective cohort study. The underlying cause of death was defined according to the International Classification of Diseases, 10th Revision. The World Health Organisation definition was used to categorise the cause of death as cancer versus another disease (e.g. cardiovascular disease, infectious disease, etc.) Competing risk models were used. RESULTS: Mean (SD) age of the 1445 included patients was 80.2 (5.8) and 48% were women. Most common tumour sites were colorectal (19%), breast (17%) and urinary (15%); 773 patients (49%) had metastases. After a 34-month median follow-up, 706 cancer deaths were observed among 843 deaths. The 6-month and 3-year cancer mortality rates (95% CI) were 12% (9-15) and 34% (29-38) for non-metastatic patients and 43% (39-47) and 79% (75-82) for metastatic patients, respectively. Dependency in activities of daily living and comorbidities were associated with 6-month and 3-year cancer mortality in non-metastatic (adjusted subhazard ratio [aSHR] = 1.68 [0.99-2.85] and 1.69 [1.16-2.45]; and 1.98 [1.08-3.63] and 3.38 [1.47-7.76], respectively) and metastatic patients (aSHR = 2.81 [2.01-3.93] and 2.95 [2.14-4.07]; and 1.63 [1.18-2.25] and 2.06 [1.39-3.05], respectively). Impaired Timed-Get-Up-and-Go test was associated with 6-month and 3-year cancer mortality in metastatic patients (aSHR = 1.5 [1.06-2.12] and 1.38 [1.06-1.81], respectively). Obesity was negatively associated with 3-year cancer death in non-metastatic (aSHR = 0.53 [0.29-0.97]) and metastatic patients (aSHR = 0.71 [0.51-1.00]). CONCLUSIONS: The majority of older adults with cancer referred for pre-therapeutic GA die from cancer. Geriatric parameters are independently associated with cancer mortality and should be considered for prognosis assessment, decision-making and care.

Initial characteristics and course of disease in patients with suspected COVID-19 managed in general practice: a prospective, multicentre cohort study.

OBJECTIVES: To describe and compare the initial clinical characteristics of a cohort of patients with suspected COVID-19 managed by general practitioners (GPs); to assess whether 3-month persistent symptoms were more frequent among confirmed cases than among no-COVID cases; and to identify factors predictive of persistent symptoms and adverse outcomes among confirmed cases. DESIGN AND SETTING: A comparative, prospective, multicentre cohort study in primary care in the Paris region of France. PARTICIPANTS: 521 patients aged ≥18 with suspected COVID-19 were enrolled between March and May 2020. OUTCOME MEASURES: Initial symptoms, COVID-19 status, persistent symptoms 3 months after inclusion and a composite criterion for potentially COVID-19-related events (hospitalisation, death, emergency department visits). The final COVID-19 status ('confirmed', 'no-COVID' and 'uncertain' cases) was determined by the GP after the receipt of the laboratory test results. RESULTS: 516 patients were analysed; 166 (32.2%) were classified into the 'confirmed COVID' group, 180 (34.9%) into the 'no-COVID' group and 170 (32.9%) in the 'uncertain COVID' group. Confirmed cases were more likely to have persistent symptoms than no-COVID cases (p=0.09); initial fever/feeling feverish and anosmia were independently associated with persistent symptoms. At 3 months, we observed 16 (9.8%) COVID-19-related hospital admissions, 3 (1.8%) intensive care unit admissions, 13 (37.1%) referrals to an emergency department and no death. Age >70 and/or at least one comorbidity (OR 6.53; 95% CI 1.13-37.84; p=0.036), abnormalities in a lung examination (15.39; 95% CI 1.61-146.77; p=0.057) and two or more systemic symptoms (38.61; 95% CI 2.30-647.40; p=0.011) were associated with the composite criterion. CONCLUSIONS: Although most patients with COVID-19 in primary care had mild disease with a benign course, almost one in six had persistent symptoms at 3 months. These symptoms were more frequent in the 'confirmed COVID' group. Our findings need to be confirmed in a prospective study with longer follow-up.

External Validity of Two Scores for Predicting the Risk of Chemotherapy Toxicity Among Older Patients With Solid Tumors: Results From the ELCAPA Prospective Cohort.

BACKGROUND: Severe chemotherapy-related toxicities are frequent among older patients. The Chemotherapy Risk Assessment Scale for High-Age Patients (CRASH) and the Cancer and Aging Research Group Study (CARG) score were both developed to predict these events. PATIENTS AND METHODS: The objective of this study was to evaluate the scores' predictive performance in a prospective cohort, which included patients aged 70 years and older referred for a geriatric assessment prior to chemotherapy for a solid tumor. The main endpoints were grades 3/4/5 toxicities for the CARG score and grades 4/5 hematologic toxicities and grades 3/4/5 non-hematologic toxicities for the CRASH score. RESULTS: A total of 248 patients were included, of which 150 (61%) and 126 (51%) experienced at least one severe adverse event as defined respectively in CARG and CRASH studies. The incidence of adverse events was not significantly greater in the intermediate and high-risk CARG groups than in the low-risk group (odds ratio (OR) [95% CI] = 0.3 [0.1-1.4] (P = .1) and 0.4 [0.1-1.7], respectively). The area under curve (AUC) was 0.55. Similarly, the incidence of severe toxicities was no greater in the intermediate-low, intermediate-high, and high-risk CRASH groups than in the low-risk CRASH group (OR [95%CI] = 1 [0.3-3.6], 1 [0.3-3.4], and 1.5 [0.3-8.1], respectively). The AUC was 0.52. The type of cancer, performance status, comorbidities, body mass index, and MAX2 index were independently associated with grades 3/4/5 toxicities. CONCLUSION: In an external cohort of older patients referred for a pretherapeutic GA, the CARG and CRASH scores were poor predictors of the risk of chemotherapy severe toxicities.

The Relative Contributions of Occupational and Community Risk Factors for COVID-19 among Hospital Workers: The HOP-COVID Cohort Study.

The relative contributions of occupational and community sources of COVID-19 among health-care workers (HCWs) are still subject to debate. In a cohort study at a 2814-bed tertiary medical center (five hospitals) in the Paris area of France, we assessed the proportion of hospital-acquired cases among staff and identified risk factors. Between May 2020 and June 2021, HCWs were invited to complete a questionnaire on their COVID-19 risk factors. RT-PCR and serology test results were retrieved from the virology department. Mixed-effects logistic regression was used to account for clustering by hospital. The prevalence of COVID-19 was 15.6% (n = 213/1369 respondents) overall, 29.7% in the geriatric hospitals, and 56.8% of the infections were hospital-acquired. On multivariable analyses adjusted for COVID-19 incidence and contact in the community, a significantly higher risk was identified for staff providing patient care (especially nursing assistants), staff from radiology/functional assessment units and stretcher services, and staff working on wards with COVID-19 clusters among patients or HCWs. The likelihood of infection was greater in geriatric wards than in intensive care units. The presence of significant occupational risk factors after adjustment for community exposure is suggestive of a high in-hospital risk and emphasizes the need for stronger preventive measures-especially in geriatric settings. Clinicaltrials.gov NCT04386759.

More than a third of middle-aged adults (50-65) have understated executive dysfunction.

OBJECTIVES: Understated executive dysfunction (UED) is predictive of cognitive decline and death. We aimed to assess the prevalence of UED, assessed with the clock-drawing test (CDT) and the Frontal Assessment Battery (FAB) in middle-aged adults and to investigate associated characteristics. METHODS: Cross-sectional analysis of data on 516 community-dwellers aged 50-65, lacking cognitive complaints, who were included prospectively (2010-2017) after a multidimensional geriatric assessment at a "healthy ageing" outpatient clinic. Age- and educational-level-adjusted logistic models were used to assess factors associated with UED. RESULTS: The CDT and FAB were impaired in 27.7% and 14.7% of the participants (median age: 59.7 years). The prevalence [95% confidence interval (CI)] of UED was 36.2% [32.2-40.5%]. After adjustment for age and education, participants with UED were more likely to be obese (odds ratio [95%CI] = 1.89 [1.12-3.19], P = 0.02), and to have a metabolic syndrome (1.98 [1.06-3.72], P = 0.03). CONCLUSION: More than one third of middle-aged adults without cognitive complaints have UED, which was linked to obesity and metabolic syndrome. Cognitive screening tests targeting executive functions might be useful for early detection of UED and the initiation of multidomain interventions improving cognitive performance.

Prescription of benzodiazepines and Z-drugs among older patients in primary care: a French, national, cohort study.

BACKGROUND: In France, general practitioners (GPs) prescribe benzodiazepines and Z-drugs (BZD/ZDs) widely, and especially to older adults. Several characteristics of patients and/or GPs linked to BZD/ZD overprescription have been described in the general population but not among older patients in primary care. OBJECTIVES: To estimate the proportion of GP consultations by patients aged 65 and over that resulted in a BZD/ZD prescription, and determine whether any GP-related factors predicted BZD/ZD overprescription in this setting. METHODS: We analyzed sociodemographic and practice-related GP characteristics, and aggregated data on consultations recorded prospectively by 117 GPs in a database between 2000 and 2010. Next, we used logistic regression models to look for factors potentially associated with BZD/ZD overprescription (defined as an above-median prescription rate). RESULTS: The GPs' mean age at inclusion was 47.4 (7.1), and 87.9% were male. During the study period, the median (95% confidence interval) proportion of consultations with patients aged 65 and over resulting in a BZD/ZD prescription was 21.8% (18.1-26.1) (range per GP: 5-34.1%). In a multivariable analysis, a greater number of chronic disease (OR [95% CI] = 2.10 [1.22-3.64]), a greater number of drugs prescribed per consultation (5.29 [2.72-10.28]), and shorter study participation were independently associated with BZD/ZD overprescription. CONCLUSIONS: BZD/ZD overprescription was associated with a greater chronic disease burden and the number of drugs prescribed per consultation but not with any sociodemographic or practice-related GP characteristics. Targeted actions are needed to help GPs limit their prescription of BZD/ZDs to older patients with multiple comorbidities and polypharmacy.

In France, general practitioners (GPs) prescribe benzodiazepines and Z-drugs (BZD/ZDs) widely, and especially to older adults. Even though BZD/ZDs may not have a favorable risk­benefit ratio in older patients, we lack data on GP-related factors that might influence BZD/ZD overprescription in our population. The objectives of the present study were to (i) estimate the proportion of GP consultations by patients aged 65 and over that resulted in a BZD/ZD prescription and (ii) identify GP-related factors that were predictive of overprescription. To achieve this goal, we analyzed consultation notes registered by 117 GPs in a database curated by the French Society of General Practice between 2000 and 2010. About 22% of consultations by patients aged 65 and over resulted in a BZD/ZD prescription. With regard to the GPs, we did not find any sociodemographic or practice-related characteristics associated with overprescription. A greater chronic disease burden and the number of drug prescriptions (other than BZD/ZDs) per consultation was independently associated with overprescription. Targeted actions are therefore needed to help GPs limit their prescription of BZD/ZDs in older patients with multimorbidity and polypharmacy.

The Prognostic Value of Eight Comorbidity Indices in Older Patients with Cancer: The ELCAPA Cohort Study.

Background: A prognostic assessment is crucial for making cancer treatment decisions in older patients. We assessed the prognostic performance (relative to one-year mortality) of eight comorbidity indices in a cohort of older patients with cancer. Methods: We studied patients with cancer aged ≥70 included in the Elderly Cancer Patient (ELCAPA) cohort between 2007 and 2010. We assessed seven nonspecific indices (Charlson Comorbidity Index (CCI), three modified versions of the CCI, the Elixhauser Comorbidity Index, the Gagne index, and the Cumulative Illness Rating Scale for Geriatrics (CIRS-G)) and the National Cancer Institute Comorbidity Index. Results: Overall, 510 patients were included. Among patients with nonmetastatic cancer, all the comorbidity indices were independently associated with 1-year mortality (adjusted hazard ratios (aHRs) of 1.44 to 2.51 for one standard deviation increment; p < 0.05 for all) and had very good discriminant ability (Harrell's C > 0.8 for the eight indices), but were poorly calibrated. Among patients with metastatic cancer, only the CIRS-G was independently associated with 1-year mortality (aHR (95% confidence interval): 1.26 [1.06−1.50]). Discriminant ability was moderate (0.61 to 0.70) for the subsets of patients with metastatic cancer and colorectal cancer. Conclusion: Comorbidity indices had strong prognostic value and discriminative ability for one-year mortality in older patients with nonmetastatic cancer, although calibration was poor. In older patients with metastatic cancer, only the CIRS-G was predictive of one-year mortality.

Geriatric impairments were directly and indirectly associated with mortality in older patients with cancer: a structural equation analysis.

OBJECTIVES: We assessed the direct and indirect effects between six geriatric domains and 6- and 12-month mortality in older cancer patients. STUDY DESIGN AND SETTING: We included cancer patients aged ≥70 years from the Elderly Cancer Patients cohort, referred for geriatric assessment between 2007 and 2016. We used structural equation modelling to examine the interrelationships between six geriatric domains (function and mobility, nutrition, cognition, mood, comorbidities and polypharmacy, and social support) and the direct and indirect relationships between these domains, the cancer stage, site, and treatment on the one hand and mortality on the other. RESULTS: The analysis included 1,434 patients (mean age: 80 ± 5.6 years; women: 48%; main cancer sites: digestive tract [36.2%], urinary tract and prostate [26.6%], and breast [16.5%]; metastatic cancer: 48%). Direct relationships to 6- and 12-month mortality were identified for functional impairment (standardized coefficient [SC]: 0.37 [P < 0.001] and 0.32 [P < 0.001], respectively), poor nutritional status (SC: 0.11 [P = 0.005] and 0.14 [P = 0.001]), poor social support (SC = 0.07 [P = 0.08] and 0.09 [P = 0.02]), cancer site, stage, and treatment. The effects of comorbidities, cognitive impairment, and depression on mortality were mediated by functional and nutritional status. CONCLUSION: In older cancer patients, functional and nutritional impairments were the strongest direct prognostic geriatric factors for mortality.

Predicting Frailty and Geriatric Interventions in Older Cancer Patients: Performance of Two Screening Tools for Seven Frailty Definitions-ELCAPA Cohort.

Screening tools have been developed to identify patients warranting a complete geriatric assessment (GA). However, GA lacks standardization and does not capture important aspects of geriatric oncology practice. We measured and compared the diagnostic performance of screening tools G8 and modified G8 according to multiple clinically relevant reference standards. We included 1136 cancer patients ≥ 70 years old referred for GA (ELCAPA cohort; median age, 80 years; males, 52%; main locations: digestive (36.3%), breast (16%), and urinary tract (14.8%); metastases, 43.5%). Area under the receiver operating characteristic curve (AUROC) estimates were compared between both tools against: (1) the detection of ≥1 or (2) ≥2 GA impairments, (3) the prescription of ≥1 geriatric intervention and the identification of an unfit profile according to (4) a latent class typology, expert-based classifications from (5) Balducci, (6) the International Society of Geriatric Oncology task force (SIOG), or using (7) a GA frailty index according to the Rockwood accumulation of deficits principle. AUROC values were ≥0.80 for both tools under all tested definitions. They were statistically significantly higher for the modified G8 for six reference standards: ≥1 GA impairment (0.93 vs. 0.89), ≥2 GA impairments (0.90 vs. 0.87), ≥1 geriatric intervention (0.85 vs. 0.81), unfit according to Balducci (0.86 vs. 0.80) and SIOG classifications (0.88 vs. 0.83), and according to the GA frailty index (0.86 vs. 0.84). Our findings demonstrate the robustness of both screening tools against different reference standards, with evidence of better diagnostic performance of the modified G8.

Serum Leptin Levels, Nutritional Status, and the Risk of Healthcare-Associated Infections in Hospitalized Older Adults.

We aimed to determine whether serum leptin levels are predictive of the occurrence of healthcare-associated infections (HAIs) in hospitalized older patients. In a prospective cohort, 232 patients had available data for leptin and were monitored for HAIs for 3 months. Admission data included comorbidities, invasive procedures, the Mini Nutritional Assessment (MNA), BMI, leptin, albumin and C-reactive protein levels, and CD4 and CD8 T-cell counts. Multivariate logistic regression modelling was used to identify predictors of HAIs. Of the 232 patients (median age: 84.8; females: 72.4%), 89 (38.4%) experienced HAIs. The leptin level was associated with the BMI (p < 0.0001) and MNA (p < 0.0001) categories. Women who experienced HAIs had significantly lower leptin levels than those who did not (5.9 µg/L (2.6-17.7) and 11.8 (4.6-26.3), respectively; p = 0.01; odds ratio (OR) (95% confidence interval): 0.67 (0.49-0.90)); no such association was observed for men. In a multivariate analysis of the women, a lower leptin level was significantly associated with HAIs (OR = 0.70 (0.49-0.97)), independently of comorbidities, invasive medical procedures, and immune status. However, leptin was not significantly associated with HAIs after adjustments for malnutrition (p = 0.26) or albuminemia (p = 0.15)-suggesting that in older women, the association between serum leptin levels and subsequent HAIs is mediated by nutritional status.

Diuretic vs. placebo in intermediate-risk acute pulmonary embolism: a randomized clinical trial.

AIMS: The role of diuretics in patients with intermediate-risk pulmonary embolism (PE) is controversial. In this multicentre, double-blind trial, we randomly assigned normotensive patients with intermediate-risk PE to receive either a single 80 mg bolus of furosemide or a placebo. METHODS AND RESULTS: Eligible patients had at least a simplified PE Severity Index (sPESI) ≥1 with right ventricular dysfunction. The primary efficacy endpoint assessed 24 h after randomization included (i) absence of oligo-anuria and (ii) normalization of all sPESI items. Safety outcomes were worsening renal function and major adverse outcomes at 48 hours defined by death, cardiac arrest, mechanical ventilation, or need of catecholamine. A total of 276 patients underwent randomization; 135 were assigned to receive the diuretic, and 141 to receive the placebo. The primary outcome occurred in 68/132 patients (51.5%) in the diuretic and in 49/132 (37.1%) in the placebo group (relative risk = 1.30, 95% confidence interval 1.04-1.61; P = 0.021). Major adverse outcome at 48 h occurred in 1 (0.8%) patients in the diuretic group and 4 patients (2.9%) in the placebo group (P = 0.19). Increase in serum creatinine level was greater in diuretic than placebo group [+4 µM/L (-2; 14) vs. -1 µM/L (-11; 6), P < 0.001]. CONCLUSION: In normotensive patients with intermediate-risk PE, a single bolus of furosemide improved the primary efficacy outcome at 24 h and maintained stable renal function. In the furosemide group, urine output increased, without a demonstrable improvement in heart rate, systolic blood pressure, or arterial oxygenation.ClinicalTrials.gov identifier NCT02268903.

Prognostic Value of Routinely Measured Inflammatory Biomarkers in Older Cancer Patients: Pooled Analysis of Three Cohorts.

BACKGROUND: The prognostic assessment of older cancer patients is complicated by their heterogeneity. We aimed to assess the prognostic value of routine inflammatory biomarkers. METHODS: A pooled analysis of prospective multicenter cohorts of cancer patients aged ≥70 was performed. We measured CRP and albumin, and calculated Glasgow Prognostic Score (GPS) and CRP/albumin ratio. The GPS has three levels (0 = CRP ≤ 10 mg/L, albumin ≥ 35 g/L, i.e., normal values; 1 = one abnormal value; 2 = two abnormal values). One-year mortality was assessed using Cox models. Discriminative power was assessed using Harrell's C index (C) and net reclassification improvement (NRI). RESULTS: Overall, 1800 patients were analyzed (mean age: 79 ± 6; males: 62%; metastases: 38%). The GPS and CRP/albumin ratio were independently associated with mortality in patients not at risk of frailty (hazard ratio [95% confidence interval] = 4.48 [2.03-9.89] for GPS1, 11.64 [4.54-29.81] for GPS2, and 7.15 [3.22-15.90] for CRP/albumin ratio > 0.215) and in patients at risk of frailty (2.45 [1.79-3.34] for GPS1, 3.97 [2.93-5.37] for GPS2, and 2.81 [2.17-3.65] for CRP/albumin ratio > 0.215). The discriminative power of the baseline clinical model (C = 0.82 [0.80-0.83]) was increased by adding GPS (C = 0.84 [0.82-0.85]; NRI events (NRI+) = 10% [2-16]) and CRP/albumin ratio (C = 0.83 [0.82-0.85]; NRI+ = 14% [2-17]). CONCLUSIONS: Routine inflammatory biomarkers add prognostic value to clinical factors in older cancer patients.

Etiological Work-Up for Adults with Bronchiectasis: A Predictive Diagnostic Score for Primary Ciliary Dyskinesia and Cystic Fibrosis.

BACKGROUND: etiological investigations are not done for all adult patients with bronchiectasis because of the availability and interpretation of tests. The aim of the study was to elaborate a score to identify patients at high risk of having cystic fibrosis or primary ciliary dyskinesia (CF/PCD), which require appropriate management. METHODS: diagnostic work-ups were carried out on a French monocenter cohort, and results were subjected to logistic-regression analyses to identify the independent factors associated with CF/PCD diagnosis and, thereby, elaborate a score to validate in a second cohort. RESULTS: among 188 patients, 158 had no obvious diagnosis and were enrolled in the algorithm-construction group. In multivariate analyses, age at symptom onset (8.69 (2.10-35.99); p = 0.003), chronic ENT symptoms or diagnosed sinusitis (10.53 (1.26-87.57); p = 0.03), digestive symptoms or situs inversus (5.10 (1.23-21.14); p = 0.025), and Pseudomonas. aeruginosa and/or Staphylococcus aureus isolated from sputum (11.13 (1.34-92.21); p = 0.02) are associated with CF or PCD. Receiver operating characteristics curve analysis, using a validation group of 167 patients with bronchiectasis, confirmed the score's performance with AUC 0.92 (95% CI: 0.84-0.98). CONCLUSIONS: a clinical score may help identify adult patients with bronchiectasis at higher risk of having CF or PCD.

Frailty in Wild-Type Transthyretin Cardiac Amyloidosis: The Tip of the Iceberg.

ATTRwt-CA occurs in elderly patients and leads to severe heart failure. The disease mechanism involves cardiac and extracardiac infiltration by amyloid fibrils. The objectives of this study are to describe the frailty phenotype in patients with ATTRwt-CA and to assess the associations between frailty parameters, the severity of cardiac involvement, and the course of amyloid disease. We used multidimensional geriatric tools to prospectively assess frailty in patients with ATTRwt-CA consulting (in 2018-2019) in the French National Reference Center for Cardiac Amyloidosis. We included 36 patients (35 males; median age: 82 years (76-86). A third of the patients were categorized as NYHA class III or IV, and 39% had an LVEF below 45%. The median serum NTproBNP was 3188 (1341-8883) pg/mL. The median duration of amyloidosis was 146 months (73-216). The frequency of frailty was 50% and 33% according to the physical frailty phenotype and the Short Emergency Geriatric Assessment questionnaire, respectively. Frailty affected a large number of domains, namely autonomy (69%), balance (58%), muscle weakness (74%), malnutrition (39%), dysexecutive syndrome (72%), and depression (49%). The severity of CA was significantly associated with many frailty parameters independently of age. Balance disorders and poor mobility were also significantly associated with a longer course of amyloid disease. Frailty is frequent in patients with ATTRwt-CA. Some frailty parameters were significantly associated with a longer course of amyloid disease and CA severity. Taking into account frailty in the assessment and management of ATTRwt should improve patients' quality of life.

Several frailty parameters highly prevalent in middle age (50-65) are independent predictors of adverse events.

Although frailty can arise in middle age, very few studies have investigated frailty before 65 years. Our objectives were to assess the prevalence of frailty parameters in middle-aged individuals and probe the association with future adverse events. We performed cross-sectional and longitudinal analyses of community-dwelling individuals aged 50 to 65 (n = 411, median age: 59.0) having undergone a multidomain geriatric assessment (2010-2015) in an outpatient clinic in the greater Paris area of France (SUCCEED cohort). The primary outcome was a composite measure of adverse events (non-accidental falls, fractures, unplanned hospitalizations, death), recorded in 2016/2017. Multivariable logistic regression models were built to identify independent predictors. Six frailty parameters were highly prevalent (> 20%): low activity (40.1%), exhaustion (31.3%), living alone (28.5%), balance impairment (26.8%), weakness (26.7%), and executive dysfunction (23.2%). Female sex (odds ratio: 2.67 [95% confidence interval: 1.17-6.11]), living alone (2.39 [1.32-4.33]), balance impairment (2.09 [1.16-3.78]), executive dysfunction (2.61, [1.18-5.77]), and exhaustion (2.98 [1.65-5.39]) were independent predictors of adverse events. Many frailty parameters are already altered in middle-aged individuals and are predictive of adverse health events. Our findings highlight a possible need for frailty screening and preventive programs targeting middle-aged individuals.

Diagnostic Performance of the 4-Item Geriatric Depression Scale for Depression Screening in Older Patients with Cancer: The ELCAPA Cohort Study.

BACKGROUND: In older patients with cancer, depression is difficult to assess because of its heterogeneous clinical expression. The 4-item version of the Geriatric Depression Scale (GDS-4) is quick and easy to administer but has not been validated in this population. The present study was designed to test the diagnostic performance of the GDS-4 in a French cohort of older patients with cancer before treatment. MATERIALS AND METHODS: Our cross-sectional analysis of data from the Elderly Cancer Patient cohort covered all patients with cancer aged ≥70 years and referred for geriatric assessment at two centers in France between 2007 and 2018. The GDS-4's psychometric properties were evaluated against three different measures of depression: the geriatrician's clinical diagnosis (based on a semistructured interview), the 4th edition of the Diagnostic and Statistical Manual of Mental Disorders, and a cluster analysis. The scale's sensitivity, specificity, positive and negative likelihood ratios, and area under the receiver operating characteristic curve (AUROC) were calculated. RESULTS: In a sample of 2,293 patients (median age, 81 years; women, 46%), the GDS-4's sensitivity and specificity for detecting physician-diagnosed depression were, respectively, 90% and 89%. The positive and negative likelihood ratios were 8.2 and 0.11, and the AUROC was 92%. When considering the subset of patients with data on all measures of depression, the sensitivity and specificity values were, respectively, ≥90% and ≥72%, the positive and negative likelihood ratios were, respectively, ≥3.4 and ≤ 0.11, and the AUROC was ≥91%. CONCLUSION: The GDS-4 appears to be a clinically relevant, easy-to-use tool for routine depression screening in older patients with cancer. IMPLICATIONS FOR PRACTICE: Considering the overlap between symptoms of cancer and symptoms of depression, depression is particularly difficult to assess in older geriatric oncology and is associated with poor outcomes; there is a need for a routine psychological screening. Self-report instruments like the 4-item version of the Geriatric Depression Scale appears to be a clinically relevant, easy-to-use tool for routine depression screening in older patients with cancer. Asking four questions might enable physicians to screen older patients with cancer for depression and then guide them toward further clinical evaluation and appropriate care if required.