Mortality in Elderly Patients Taking Furosemide: Prospective Cohorts Study.

Objectives: Low blood pressure (BP) has been proposed as a risk factor of death in elderly patients. However, this association could be partially accounted for by the deleterious effects of BP-lowering drugs. We analyzed whether these drugs are associated to an increased risk of death in elderly patients taking multiple potential confounders into account. Design: This is a prospective cohort study. Setting and Participants. Probabilistic sample of 772 community-dwelling patients aged >65 years living in Spain, who were appointed for an initial clinical visit and followed up through telephone calls 4, 6, 9, 12, and 60 months afterwards. Methods: At baseline visit, BP was measured using standardized methods, and BP medications and risk factors of death in elderly patients (BMI, oxygen saturation, toxic habits, comorbidity, muscular strength, and functional and cognitive capacity) were collected. During the follow-up, the vital status of patients and the date of death were ascertained. Results: During a median 5-year follow-up, 226 all-cause deaths occurred among the 686 participants included in the analysis. In a Cox regression model that included all the BP drug classes, diuretics and nitrites were significantly associated with mortality (p < 0.005). Within diuretics, furosemide was found to be responsible for the association of the group. In multivariable Cox regression models adjusted for BP and the rest of the mortality risk factors, furosemide remained as the only BP drug that was independently associated with mortality (hazard ratio 2.34; p < 0.01). Conclusions: Furosemide was prospectively associated with increased mortality in older people. If confirmed, this drug should be taken into account by prescribers and considered a confounder in BP studies.

Matched cohort study on the efficacy of tocilizumab in patients with COVID-19.

BACKGROUND: Tocilizumab has been proposed as a treatment for the new disease COVID-19, however, there is not enough scientific evidence to support this treatment. The objective of this study is to analyze whether the use of tocilizumab is associated with respiratory improvement and a shorter time to discharge in patients with COVID-19 and lung involvement. METHODS: Observational study on a cohort of 418 patients, admitted to three county hospitals in Catalonia (Spain). Patients admitted consecutively were included and followed until discharge or up to 30 days of admission. A sub-cohort of patients treated with tocilizumab and a sub-cohort of control patients were identified, matched by a large number of risk factors and clinical variables. Sub-cohorts were also matched by the number of other treatments for COVID-19 that patients received. Increment in SAFI (inspired oxygen fraction / saturation) 48 h after the start of treatment, and time to discharge, were the primary outcomes. Mortality, which was a secondary outcome, was analyzed in the total cohort, by using logistic regression models, adjusted by confounders. RESULTS: There were 96 patients treated with tocilizumab. Of them, 22 patients could be matched with an equivalent number of control patients. The increment in SAFI from baseline to 48 h of treatment, was not significantly different between groups (tocilizumab: -0.04; control: 0.09; p = 0.636). Also, no difference in time to discharge was found between the two sub-cohorts (logrank test: p = 0.472). The logistic regression models, did not show an effect of tocilizumab on mortality (OR 0.99; p = 0.990). CONCLUSIONS: We did not find a clinical benefit associated with the use tocilizumab, in terms of respiratory function at 48 h of treatment, or time to discharge.

Association between COVID-19 prognosis and disease presentation, comorbidities and chronic treatment of hospitalized patients.

IMPORTANCE: The rapid pandemic expansion of the disease caused by the new SARS-CoV-2 virus has compromised health systems worldwide. Knowledge of prognostic factors in affected patients can help optimize care. OBJECTIVE: The objective of this study was to analyze the relationship between the prognosis of COVID-19 and the form of presentation of the disease, the previous pathologies of patients and their chronic treatments. DESIGN, PARTICIPANTS AND LOCATIONS: This was an observational study on a cohort of 418 patients admitted to three regional hospitals in Catalonia (Spain). As primary outcomes, severe disease (need for oxygen therapy via nonrebreather mask or mechanical ventilation) and death were studied. Multivariate binary logistic regression models were performed to study the association between the different factors and the results. RESULTS: Advanced age, male sex and obesity were independent markers of poor prognosis. The most frequent presenting symptom was fever, while dyspnea was associated with severe disease and the presence of cough with greater survival. Low oxygen saturation in the emergency room, elevated CRP in the emergency room and initial radiological involvement were all related to worse prognosis. The presence of eosinophilia (% of eosinophils) was an independent marker of less severe disease. CONCLUSIONS: This study identified the most robust markers of poor prognosis for COVID-19. These results can help to correctly stratify patients at the beginning of hospitalization based on the risk of developing severe disease.

Observational study of azithromycin in hospitalized patients with COVID-19.

BACKGROUND: The rapid spread of the disease caused by the novel SARS-CoV-2 virus has led to the use of multiple therapeutic agents whose efficacy has not been previously demonstrated. The objective of this study was to analyze whether there is an association between the use of azithromycin and the evolution of the pulmonary disease or the time to discharge, in patients hospitalized with COVID-19. METHODS: This was an observational study on a cohort of 418 patients admitted to three regional hospitals in Catalonia, Spain. As primary outcomes, we studied the evolution of SAFI ratio (oxygen saturation/fraction of inspired oxygen) in the first 48 hours of treatment and the time to discharge. The results were compared between patients treated and untreated with the study drug through subcohort analyses matched for multiple clinical and prognostic factors, as well as through analysis of non-matched subcohorts, using Cox multivariate models adjusted for prognostic factors. RESULTS: There were 239 patients treated with azithromycin. Of these, 29 patients treated with azithromycin could be matched with an equivalent number of control patients. In the analysis of these matched subcohorts, SAFI at 48h had no significant changes associated to the use of azithromycin, though azithromycin treatment was associated with a longer time to discharge (10.0 days vs 6.7 days; log rank: p = 0.039). However, in the unmatched cohorts, the increased hospital stay associated to azithromycin use, was no significant after adjustment using Multivariate Cox regression models: hazard ratio 1.45 (IC95%: 0.88-2.41; p = 0.150). This study is limited by its small sample size and its observational nature; despite the strong pairing of the matched subcohorts and the adjustment of the Cox regression for multiple factors, the results may be affected by residual confusion. CONCLUSIONS: We did not find a clinical benefit associated with the use of azithromycin, in terms of lung function 48 hours after treatment or length of hospital stay.

Pain and recurrent falls in the older and oldest-old non-institutionalized population.

BACKGROUND: Recurrent falls represent a priority in geriatric research. In this study we evaluated the influence of pain as a risk factor for recurrent falls (two or more in 1 year) in the older (65-79 years) and oldest-old (80 or more years) non-institutionalized population. METHODS: Prospective cohort study. 772 non-institutionalized individuals with ages of 65 years or older (with overrepresentation of people aged 80 years or older [n = 550]) were included through randomized and multistage sampling, stratified according to gender, geographic area and habitat size. Basal evaluation at participant's home including pain evaluation by Face Pain Scale (FPS, range 0-6) and then telephonic contact every 3 months were performed until complete 12 months. Multivariate analysis by logistic regression (recurrent falls as outcome variable) for each age group (older and oldest-old group) were developed considering pain as a quantitative variable (according to FPS score). Models were adjusted for age, gender, balance, muscle strength, depressive symptoms, cognitive decline, number of drugs and number of drugs with risk of falls. RESULTS: 114 (51.35%) and 286 (52%) participants of older and oldest-old group, respectively, reported pain; and recurrent falls occurred in 6.93% (n = 12) of the older group and 12.06% (n = 51) of the oldest-old group. In the older group, pain was associated with recurrent falls, with an associated odds ratio (OR) of 1.47 (95% CI 1.08-2.00; beta 0.3864) for each unit increase in pain intensity (thus, participants with the most severe pain [FPS 6] had OR of 10.16 regarding to participants without pain [FPS 0]). In the oldest-old group, pain was not associated with recurrent falls. CONCLUSIONS: Pain, a potentially modifiable and highly prevalent symptom, is a risk factor for recurrent falls in the older people (65-79 years). However, we have not been able to demonstrate that this relationship is maintained in the oldest-old population (80 or more years).

The spatial parameters of gait and their association with falls, functional decline and death in older adults: a prospective study.

Association between spatial gait parameters and adverse health outcomes in the elderly has not been sufficiently studied. The goal of this study is to evaluate whether the stride length or the step width predict falls, functional loss and mortality. We conducted a prospective cohort study on a probabilistic sample of 431 noninstitutionalized, older-than-64-years subjects living in Spain, who were followed-up for five years. In the baseline visit, spatial gait parameters were recorded along with several control variables, with special emphasis on known medical conditions, strength, balance and functional and cognitive capacities. In the follow-up calls, vital status, functional status and number of falls from last control were recorded. We found that a normalized-to-height stride length shorter than 0.52 predicted recurrent falls in the next 6 months with 93% sensitivity and 53% specificity (AUC: 0.72), and in the next 12 months with 81% sensitivity and 57% specificity (AUC: 0.67). A normalized stride length <0.5 predicted functional loss at 12 months with a sensitivity of 79.4% and specificity of 65.6% (AUC: 0.75). This predictive capacity remained independent after correcting for the rest of risk factors studied. Step-with was not clearly related to functional loss or falls. Both shorter normalized stride length (OR1.56; AUC: 0.62; p < 0.05) and larger step width (OR1.42; AUC: 0.62; p < 0.05) were associated with risk of death at 60 months; however, none of them remained as independent predictor of death, after correcting for other risk factors. In summary, spatial gait parameters may be risk markers for adverse outcomes in the elderly. Step length is independently associated with functional loss and falls at one year, after correction for numerous known risk factors.

Prevalence and treatment of pain in non-institutionalized very old population: transversal study at national level.

BACKGROUND: In Europe, there is no conclusive data at national level about pain prevalence in non-institutionalized very old population. In USA, it has recently been reported a high prevalence (56 %); however, this data can not be extrapolated to other regions because the known influence of geographical and ethnic differences. Furthermore there are few data on use of treatments for pain in this population. AIMS: To explore prevalence and considered pharmacological treatments for pain in this population. METHODS: Transversal study on 551 participants aged 80 or more living in Spain (non-institutionalized). Probabilistic multistage sampling was carried out, stratified by sex and place of residence. All Spanish regions were considered for recruitment process. Pain (last 4 weeks), intensity (Face Pain Scale), localization and pharmacological treatments were evaluated by in-person interviews. RESULTS: Pain's prevalence was 52.5 % (CI 95 % 48.28-56.80) and 38.5 % experienced pain of at least moderate intensity. The most frequently involved body regions were lower limbs (26.6 %) and dorso-lumbar region (21.9 %). Only 40 % of participants with pain and 43.2 % with moderate or severe pain used analgesics, and paracetamol was less frequently used than non-steroidal anti-inflammatory drugs at any pain intensity. Age was not associated with higher prevalence [odds ratios 0.97 (CI 95 % 0.93-1.02) in females and 0.99 (CI 95 % 0.92-1.06) in males]. CONCLUSIONS: The prevalence of pain in non-institutionalized very old people is high. Pain is probably being undertreated, even moderate or severe pain. Guideline's recommendations are probably not being considered to select the analgesic therapy.

Association with and predictive capacity of self-perceived risk of falling in recurrent falls in older people: a prospective study.

OBJECTIVE: Given the impact of recurrent falls in older people, risk evaluation for falling is an important part of geriatric assessment. Available clinical tools usually do not include patients' self-perceived risk of falling. The objective of this study was to evaluate association with and predictive capacity of self-perceived risk of falling in recurrent falls. METHODS: Prospective cohort study. Patients attending a geriatric outpatients' clinic were recruited (Pfeiffer score <5). A baseline assessment and follow-up over 14 months was scheduled for each patient. Self-perceived risk of falling was assessed through four questions. Association with falls was evaluated through relative risk, survival curves (Kaplan-Meier), and Cox regression (recurrent falls as outcome variables). Predictive capacity was evaluated through sensitivity, specificity, and predictive values. RESULTS: 52 participants answered all 4 questions, and 15 participants (27.2 %) presented recurrent falls. Question 1 (Do you think you may fall in the next few months?) was associated with the occurrence of recurrent falls according to relative risk [3.88 (CI95 %:1.48-10.09)] and survival curves (log Rank, p 0.004). Such relationship is maintained over time. Cox-regression also showed significant difference in relation to the answer for question 1 and recurrent falls [hazard ratio 4.044 (CI: 1.410-11.597); p 0.009]. Sensitivity, specificity, positive and negative predictive values (question 1) were 53.3 % (CI95 %:28.1-78.6), 84.2 % (CI95 %:72.6-95.8), 57.1 % (CI95 %:31.2-83.1), and 82.1 % (CI95 %:70.0-94.1), respectively. CONCLUSIONS: Patients' self-perceived risk of falling is related to recurrent falls amongst people with a high risk of falling and this parameter might be useful in falling risk evaluation.