Statins during Anticoagulation for Emergency Life-Threatening Venous Thromboembolism: A Review.

Venous thromboembolism (VTE) is the leading cause of morbidity and death worldwide, after cancer and cardiovascular diseases. VTE is defined to include pulmonary embolism (PE) and/or deep vein thrombosis (DVT). Approximately 25% of PE patients experience sudden death as an initial symptom of VTE, and between 10% and 30% of patients die within the first month after diagnosis. Currently, the only drugs approved for the treatment of both acute and chronic VTE are vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs). However, their effectiveness is limited due to their associated risk of bleeding. Ideally, therapy should be able to treat VTE and limit the risk of VTE recurrence without increasing the risk of bleeding. Several studies have shown that the use of statins during anticoagulation for VTE reduces the risk of death and VTE recurrence. However, to date, there are conflicting data on the impact of statins during anticoagulation for VTE. A biological protective function of statins during anticoagulation has also been reported. Statins affect D-dimer levels; tissue factor (TF) gene expression; and VIII, VII, and Von Willebrand clotting factors-the major clotting factors they are able to affect. However, the usefulness of statins for the treatment and prevention of VTE is currently under debate, and they should not be substituted for guideline-recommended VTE prophylaxis or anticoagulation treatment. In this review of the literature, we illustrate the advances on this topic, including data on the role of statins in primary VTE prevention and secondary VTE prevention, related biological mechanisms, the risk of bleeding during their use, and their ability to reduce the risk of death.

Implementing a multidisciplinary rapid geriatric observation unit for non-critical older patients referred to hospital: observational study on real-world data.

BACKGROUND: Geriatric rapid observation units may represent an alternative to hospitalization in older patients with non-critical acute illness. AIMS: To describe the characteristics and outcomes of patients admitted to a geriatric observation unit called URGe (Unità Geriatrica Rapida), implemented in an Italian hospital and characterized by multidisciplinary medical staff with geriatric expertise, fast-track access to diagnostic resources, regular use of point-of-care ultrasound and predicted length of stay (LOS) < 72 h. METHODS: The medical records of patients admitted to URGe during a 3-month period (452 subjects, 247 F and 205 M, median age 82 years, IQR 77-87) were retrospectively examined. The primary study endpoint was transferral from URGe to regular wards. Baseline covariates included demographics, comprehensive geriatric assessment, acute illnesses, comorbidities, vital signs and routine laboratory tests. RESULTS: Despite elevated burden of multimorbidity (median number of chronic diseases 4, IQR 2-5) and frailty (median Rockwood Clinical Frailty Scale score 4, IQR 3-6), only 137 patients (30.3%) required transferral from URGe to regular wards. The main factors positively associated with this outcome were Rockwood score, fever, cancer and red cell distribution width (P < 0.05 on multivariate logistic regression model). The rate of complications (mortality, delirium, and falls) during URGe stay was low (0.5%, 7% and 2%, respectively). Overall duration of hospital stay was lower than that of a group of historical controls matched by age, sex, main diagnosis, multimorbidity and frailty. CONCLUSIONS: The URGe model of acute geriatric care is feasible, safe and has the potential of reducing unnecessary hospitalizations of older patients.

The Clinical Significance of Procalcitonin Elevation in Patients over 75 Years Old Admitted for COVID-19 Pneumonia.

AIM: To investigate the clinical significance of procalcitonin (PCT) elevation on hospital admission for coronavirus disease-19 (COVID-19) and its association with mortality in oldest old patients (age > 75 years). METHODS: The clinical records of 1074 patients with chest high-resolution computed-tomography (HRCT) positive for interstitial pneumonia and symptoms compatible for COVID-19, hospitalized in medical wards during the first pandemic wave in a single academic center in Northern Italy, were retrospectively analyzed. All patients had serum PCT testing performed within six hours from admission. Information on COVID-19-related symptoms, comorbidities, drugs, autonomy in daily activities, respiratory exchanges, other routine lab tests, and outcomes were collected. Clinical characteristics were compared across different admission PCT levels and ages. The association of admission PCT with mortality was tested separately in participants aged > 75 and ≤75 years old by stepwise multivariate Cox regression model with forward selection. RESULTS: With increasing classes of PCT levels (<0.05, 0.05-0.49, 0.5-1.99, and ≥2 ng/ml), there was a significant trend (P < 0.0001) towards older age, male gender, wider extension of lung involvement on HRCT, worse respiratory exchanges, and several other laboratory abnormalities. Each incremental PCT class was associated with increased risk of hospital death at multivariate models in subjects older than 75 (hazard ratio for PCT ≥ 2 vs. <0.05 ng/ml: 30.629, 95% confidence interval 4.176-224.645, P = 0.001), but not in subjects aged 75 or younger. CONCLUSIONS: In patients admitted for COVID-19, PCT elevation was associated with several clinical, radiological, and laboratory characteristics of disease severity. However, PCT elevation was strongly associated with hospital mortality only in oldest old subjects (age > 75).

Delirium in COVID-19: epidemiology and clinical correlations in a large group of patients admitted to an academic hospital.

BACKGROUND: Delirium incidence and clinical correlates in coronavirus disease-19 (COVID-19) pneumonia are still poorly investigated. AIM: To describe the epidemiology of delirium in patients hospitalized for suspect COVID-19 pneumonia during the pandemic peak in an academic hospital of Northern Italy, identify its clinical correlations and evaluate the association with mortality. METHODS: The clinical records of 852 patients admitted for suspect COVID-19 pneumonia, defined as respiratory symptoms or fever or certain history of contact with COVID-19 patients, plus chest CT imaging compatible with alveolar-interstitial pneumonia, were retrospectively analyzed. Delirium was defined after careful revision of daily clinical reports in accordance with the Confusion Assessment Method criteria. Data on age, clinical presentation, comorbidities, drugs, baseline lab tests and outcome were collected. The factors associated with delirium, and the association of delirium with mortality, were evaluated through binary logistic regression models. RESULTS: Ninety-four patients (11%) developed delirium during stay. They were older (median age 82, interquartile range, IQR 78-89, vs 75, IQR 63-84, p < 0.001), had more neuropsychiatric comorbidities and worse respiratory exchanges at baseline. At multivariate models, delirium was independently and positively associated with age [odds ratio (OR) 1.093, 95% confidence interval (CI) 1.046-1.143, p < 0.001], use of antipsychotic drugs (OR 4.529, 95% CI 1.204-17.027, p = 0.025), serum urea and lactate-dehydrogenase at admission. Despite a higher mortality in patients with delirium (57% vs 30%), this association was not independent of age and respiratory parameters. CONCLUSIONS: Delirium represents a common complication of COVID-19 and a marker of severe disease course, especially in older patients with neuropsychiatric comorbidity.

Gut Microbiota and Microbiota-Related Metabolites as Possible Biomarkers of Cognitive Aging.

Gut microbiota composition and functionality can influence the pathophysiology of age-related cognitive impairment and dementia, according to a large number of animal studies. The translation of this concept to humans is still uncertain, due to the relatively low number of clinical studies focused on fecal microbiota and large number of environmental factors that influence the microbiota composition. However, the fecal microbiota composition of older patients with dementia is deeply different from that of healthy active controls, conditioning a different metabolic profile. The possible use of fecal microbiota-related parameters and microbiota-derived metabolites as biomarkers of cognitive performance and dementia is critically reviewed in this paper, focusing on the most promising areas of research for the future.

Short-Physical Performance Battery (SPPB) score is associated with falls in older outpatients.

BACKGROUND: The capacity of Short-Physical Performance Battery (SPPB) test to discriminate between fallers and non-fallers is controversial, and has never been compared with fall risk assessment-specific tools, such as Performance-Oriented Mobility Assessment (POMA). AIM: To verify the association of SPPB and POMA scores with falls in older outpatients. METHODS: 451 older subjects (150 males, mean age 82.1 ± 6.8) evaluated in a geriatric outpatient clinic for suspected frailty were enrolled in this cross-sectional study. Self-reported history of falls and medication history were carefully assessed. Each participant underwent comprehensive geriatric assessment, including SPPB, POMA, Geriatric Depression Scale (GDS), mini-mental state examination (MMSE) and mini-nutritional assessment-short form (MNA-SF). Multivariate logistic regression and receiver-operating characteristic (ROC) analyses were performed to determine the factors associated with the status of faller. RESULTS: 245 (54.3%) subjects were identified as fallers. They were older and had lower SPPB and POMA test scores than non-fallers. At ROC analysis, SPPB (AUC 0.676, 95% CI 0.627-0.728, p < 0.001) and POMA (AUC 0.677, 95% CI 0.627-0.726, p < 0.001) scores were both associated with falls. At multivariate logistic regression models, SPPB total score (OR 0.83, 95% CI 0.76-0.92, p < 0.001), POMA total score (OR 0.94, 95% CI 0.91-0.98, p = 0.002) and SPPB balance score alteration (OR 2.88, 95% CI 1.42-5.85, p = 0.004), but not POMA balance subscale score alteration, were independently associated with recorded falls, as also GDS, MMSE and MNA-SF scores. CONCLUSIONS: SPPB total score was independently associated with reported falls in older outpatients, resulting non-inferior to POMA scale. The use of SPPB for fall risk assessment should be implemented.

Molecular and Clinical Issues about the Risk of Venous Thromboembolism in Older Patients: A Focus on Parkinson's Disease and Parkinsonism.

Venous thromboembolism (VTE) is a common and potentially life-threatening condition which includes both deep-vein thrombosis (DVT) and pulmonary embolism (PE). VTE has a significant clinical and epidemiological impact in the elderly, and its incidence increases to more than 1% per year in older patients, suggesting the presence of specific age-related risk factors in this population. Immobilization seems to predominate as the main cause in patients admitted for medical acute illness in medicine wards, and there is evidence of a high risk in older patients with immobilization resulting from advanced forms of Parkinson’s disease (PD), regardless of the presence of an acute medical condition. In this review, we would to discuss the recent evidence on clinical, molecular and epidemiological features of VTE in older frail subjects focusing on patients with PD and parkinsonism. We also discuss some therapeutic issues about the risk prevention and we suggest a thorough comprehensive geriatric assessment that can represent an optimal strategy to identify and prevent the VTE risk in these patients.

The association of serum procalcitonin and high-sensitivity C-reactive protein with pneumonia in elderly multimorbid patients with respiratory symptoms: retrospective cohort study.

BACKGROUND: Serum procalcitonin and high-sensitivity C-reactive protein (hs-CRP) elevations have been associated with pneumonia in adults. Our aim was to establish their diagnostic usefulness in a cohort of hospitalized multimorbid patients ≥65 years old admitted to hospital with acute respiratory symptoms. METHODS: With a retrospective cohort study design, all multimorbid patients ≥65 years-old with acute respiratory symptoms admitted to an internal medicine hospital ward in Italy from January to August 2013 were evaluated. Pneumonia diagnosis, comorbidities expressed through Cumulative Illness Rating Scale (CIRS), setting of living, length of stay, serum hs-CRP and procalcitonin at admission were collected for each patient. Data were analyzed with Mann-Whitney's U test and multivariate Cox logistic regression analysis. A Receiver Operating Characteristic (ROC) curve was used to verify each biomarker's association with pneumonia diagnosis. RESULTS: Four hundred fifty five patients (227 M) were included in the study, of whom 239 with pneumonia (138 M, mean age 80 ± 13) and 216 without pneumonia (89 M, mean age 80 ± 14). After adjustment for age and sex, median levels of hs-CRP were significantly higher in patients with pneumonia (116 mg/L, IQR 46.5-179.0, vs 22.5 mg/dl, IQR 6.9-84.4, p < 0.0001), while procalcitonin median levels were not (0.22 ng/ml IQR 0.12-0.87, vs 0.15 ng/ml, IQR 0.10-0.35, p = 0.08). The ROC analysis showed that, unlike procalcitonin, hs-CRP values were predictive of pneumonia (AUC 0.76, 95% CI 0.72-0.79, p < 0.0001, cut-off value 61 mg/L), even after adjustment for possible confounders including nursing home residence and dementia. Serum hs-CRP levels >61 mg/L were independently associated with a 3.59-fold increased risk of pneumonia (OR 3.59, 95% CI 2.35-5.48, p < 0.0001). CONCLUSION: In elderly multimorbid patients who require hospital admission for respiratory symptoms, serum hs-CRP testing seems to be more useful than procalcitonin for guiding the diagnostic process when clinical suspicion of pneumonia is present. Procalcitonin testing might hence be not recommended in this setting.

Factors associated with delirium in a real-world acute-care setting: analysis considering the interdependence of clinical variables with the frailty syndrome.

PURPOSE: Delirium risk assessment in the acute-care setting generally does not account for frailty. The objective of this retrospective study was to identify factors associated with delirium, considering the interdependency of clinical variables with frailty syndrome in complex older patients. METHODS: The clinical records of 587 participants (248 M, median age 84) were reviewed, collecting clinical, anamnestic and pharmacological data. Frailty syndrome was assessed with the Clinical Frailty Scale (CFS). Delirium was the main study endpoint. The correlations of the considered anamnestic and clinical variables with delirium and its subtypes were investigated selecting only those variables not showing a high overlap with frailty. Correlations associated with a 25% excess of frequency of delirium in comparison with the average of the population were considered as statistically significant. RESULTS: Delirium was detected in 117 (20%) participants. The presence of one among age > 85 years old, CFS > 4 and invasive devices explained 95% of delirium cases. The main factors maximizing delirium incidence at the individual level were dementia, other psychiatric illness, chronic antipsychotic treatment, and invasive devices. The coexistence of three of these parameters was associated with a peak frequency of delirium, ranging from 57 to 61%, mostly hypoactive forms. CONCLUSIONS: In acute-care wards, frailty exhibited a strong association with delirium during hospitalization, while at the individual level, dementia and the use of antipsychotics remained important risk factors. Modern clinical prediction tools for delirium should account for frailty syndrome.

Non-Invasive Ventilation Support during Hospitalization for SARS-CoV-2 and the Risk of Venous Thromboembolism.

Background/Objectives: Although SARS-CoV-2 infection is a significant risk factor for venous thromboembolism (VTE), data on the impact of the use of non-invasive ventilation support (NIVS) to mitigate the risk of VTE during hospitalization are scarce. Methods: Data for 1471 SARS-CoV-2 patients, hospitalized in a single hub during the first pandemic wave, were collected from clinical records, including symptom duration and type, information on lung abnormalities on chest computed tomography (CT), laboratory parameters and the use of NIVS. Determining VTE occurrence during hospital stays was the main endpoint. Results: Patients with VTE (1.8%) had an increased prevalence of obesity (26% vs. 11%), diabetes (41% vs. 21%), higher CHA2DS2VASC score (4, IQR 2-5 vs. 3, IQR 1-4, age- and sex-adjusted, p = 0.021) and cough (65% vs. 44%) and experienced significantly higher rates of NIVS (44% vs. 8%). Using a stepwise multivariate logistic regression model, the prevalence of electrocardiogram abnormalities (odds ratio (OR) 2.722, 95% confidence interval (CI) 1.039-7.133, p = 0.042), cough (OR 3.019, 95% CI 1.265-7.202, p = 0.013), CHA2DS2-VASC score > 3 (OR 3.404, 95% CI 1.362-8.513, p = 0.009) and the use of NIVS (OR 15.530, 95% CI 6.244-38.627, p < 0.001) were independently associated with a risk of VTE during hospitalization. NIVS remained an independent risk factor for VTE even after adjustment for the period of admission within the pandemic wave. Conclusions: Our study suggests that NIVS is a risk factor for VTE during hospitalization in SARS-CoV-2 patients. Future studies should assess the optimal prophylactic strategy against VTE in patients with a SARS-CoV-2 infection candidate to non-invasive ventilatory support.

Reducing unnecessary hospital days to improve quality of care through physician accountability: a cluster randomised trial.

BACKGROUND: Over 20% of hospital bed use is inappropriate, implying a waste of resources and the increase of patient iatrogenic risk. METHODS: This is a cluster, pragmatic, randomised controlled trial, carried out in a large University Hospital of Northern Italy, aiming to evaluate the effect of a strategy to reduce unnecessary hospital days. The primary outcome was the percentage of patient-days compatible with discharge. Among secondary objectives, to describe the strategy's effect in the long-term, as well as on hospital readmissions, considered to be a marker of the quality of hospital care. The 12 medical wards with the longest length of stay participated. Effectiveness was measured at the individual level on 3498 eligible patients during monthly index days. Patients admitted or discharged on index days, or with stay >90 days, were excluded. All ward staff was blinded to the index days, while staff in the control arm and data analysts were blinded to the trial's objectives and interventions. The strategy comprised the distribution to physicians of the list of their patients whose hospital stay was compatible with discharge according to a validated Delay Tool, and of physician length of stay profiles, followed by audits managed autonomously by the physicians of the ward. RESULTS: During the 12 months of data collection, over 50% of patient-days were judged to be compatible with discharge. Delays were mainly due to problems with activities under medical staff control. Multivariate analysis considering clustering showed that the strategy reduced patient-days compatible with discharge by 16% in the intervention vs control group, (OR=0.841; 95% CI, 0.735 to 0.963; P=0.012). Follow-up at 1 year did not yield a statistically significant difference between the percentages of patient-days judged to be compatible with discharge between the two arms (OR=0.818; 95% CI, 0.476 to 1.405; P=0.47). There was no significant difference in 30-day readmission and mortality rates for all eligible patients (N=3498) between the two arms. CONCLUSIONS: Results indicate that a strategy, involving physician direct accountability, can reduce unnecessary hospital days. Relatively simple interventions, like the one assessed in this study, should be implemented in all hospitals with excessive lengths of stay, since unnecessary prolongation may be harmful to patients. TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT01422811.

The possible role of gut microbiota dysbiosis in the pathophysiology of delirium in older persons.

Delirium is a clinical syndrome characterized by an acute change in attention, awareness and cognition with fluctuating course, frequently observed in older patients during hospitalization for acute medical illness or after surgery. Its pathogenesis is multifactorial and still not completely understood, but there is general consensus on the fact that it results from the interaction between an underlying predisposition, such as neurodegenerative diseases, and an acute stressor acting as a trigger, such as infection or anesthesia. Alterations in brain insulin sensitivity and metabolic function, increased blood-brain barrier permeability, neurotransmitter imbalances, abnormal microglial activation and neuroinflammation have all been involved in the pathophysiology of delirium. Interestingly, all these mechanisms can be regulated by the gut microbiota, as demonstrated in experimental studies investigating the microbiota-gut-brain axis in dementia. Aging is also associated with profound changes in gut microbiota composition and functions, which can influence several aspects of disease pathophysiology in the host. This review provides an overview of the emerging evidence linking age-related gut microbiota dysbiosis with delirium, opening new perspectives for the microbiota as a possible target of interventions aimed at delirium prevention and treatment.

Insights from comparison of the clinical presentation and outcomes of patients hospitalized with COVID-19 in an Italian internal medicine ward during first and third wave.

Background: The reasons of variability of clinical presentation of coronavirus disease-19 (COVID-19) across different pandemic waves are not fully understood, and may include individual risk profile, SARS-CoV-2 lineage and seasonal variations of viral spread. The objective of this retrospective study was to compare the characteristics and outcomes of patients admitted with confirmed coronavirus disease-19 (COVID-19) in the same season during the first (March 2020) and the third pandemic wave (March 2021, dominance of SARS-CoV-2 B.1.1.7 lineage) in an internal medicine ward of a large teaching hospital in Italy. Materials and methods: Data of 769 unvaccinated patients (399 from the first and 370 from the third wave) were collected from clinical records, including symptom type and duration, extension of lung abnormalities on chest computed tomography (CT) and PaO2/FiO2 ratio on admission arterial blood gas analysis. Results: Third wave patients were in average younger (median 65, interquartile range [IQR] 55-75, vs. 72, IQR 61-81 years old, p < 0.001), with less comorbidities and better pulmonary (CT visual score median 25, IQR 15-40, vs. 30, IQR 15-50, age- and sex-adjusted p = 0.017) and respiratory involvement (PaO2/FiO2 median 288, IQR 237-338, vs. 233, IQR 121-326 mmHg, age- and sex-adjusted p < 0.001) than first wave patients. Hospital mortality was lower (19% vs. 36%, p < 0.001), but not for subjects over 75 years old (46 vs. 49%). Age, number of chronic illnesses, PCT levels, CT visual score [Odds Ratio (OR) 1.022, 95% confidence interval (CI) 1.009-1.036, p < 0.001] and PaO2/FiO2 (OR 0.991, 95% CI 0.988-0.994, p < 0.001), but not the pandemic wave, were associated with mortality on stepwise multivariate logistic regression analysis. Conclusion: Despite the higher virulence of B.1.1.7 lineage, we detected milder clinical presentation and improved mortality in patients hospitalized during the third COVID-19 wave, with involvement of younger subjects. The reasons of this discrepancy are unclear, but could involve the population effect of vaccination campaigns, that were being conducted primarily in older frail subjects during the third wave.

Dietary habits in women with recurrent idiopathic calcium nephrolithiasis.

BACKGROUND: Nutrition has been widely recognized to influence the risk of kidney stone formation. Therefore the aim of our study was to assess: a) whether usual diet of women with idiopathic calcium nephrolithiasis (ICN) living in Parma (Northern-Italy) is different compared to healthy controls, b) how their diet differs from Italian National guidelines and c) whether it is related to nephrolithiasis clinical course. METHODS: 143 women with recurrent ICN (mean age 43 ± 13 ys) and 170 healthy women (mean age 42 ± 11 ys) were enrolled. All women completed a food frequency questionnaire for the last 60-days and a 3-day dietary diary analysed with a dedicated software. RESULTS: Stone formers showed a higher consumption of sausages, ham, meat and sweets than healthy controls (43.1% vs 11.1%, 29.4% vs 13.9%, 21.6% vs 4.2%, 66.7% vs 18.1%, p < 0.001). The 3-day diary analysis showed an intake of calories, carbohydrates, lipids and non-discretionary sodium about 10% higher than healthy controls (p < 0.001). Finally, after dividing the population into 3 age groups (≤30, 31-40, > 40 years), the differences described above were amplified in the class ≤30 years, where nephrolithiasis presented a more serious course (shorter recurrence interval, greater stone-rate). In this age group the intake of fruit and vegetables was notably lower than guideline recommendations. CONCLUSIONS: We conclude that the usual diet of women with recurrent ICN is different from controls and characterized by low intake of fruits and vegetables and higher consumption of simple sugars and foods with high protein and salt content. This dietary imbalance could play a role in the ICN pathogenesis, especially in younger women.

Defining SARS-CoV-2 breakthrough infection needing hospitalization in mass vaccination era: from disease-centered to patient-centered care.

After the implementation of mass vaccination campaigns, breakthrough infections by SARS-CoV-2 are being increasingly observed worldwide, due to high pervasiveness of viral spread, emergence of novel variants, progressive ease of restrictive measures and waning protection against infection. Although breakthrough infections have generally lower clinical severity than COVID-19 in unvaccinated subjects, a consistent number of patients may still require hospitalization. These patients are generally old, frail and with a high number of comorbidities. Despite COVID-19-related symptoms are generally milder, they may still exhibit complicated clinical course for their intrinsic clinical complexity. The organization of hospital care should thus consider the changing epidemiology of patients admitted with SARS-CoV-2 infection in the post-vaccine era, to improve the quality and appropriateness of care.

Multimorbidity and Frailty Are the Key Characteristics of Patients Hospitalized with COVID-19 Breakthrough Infection during Delta Variant Predominance in Italy: A Retrospective Study.

The aims of this study were to describe the characteristics of patients hospitalized with delta SARS-CoV-2 breakthrough infection, and to identify factors associated with pneumonia on chest Computed Tomography (CT) and mortality. The clinical records of 229 patients (105 F), with a median age of 81 (interquartile range, IQR, 73−88) years old, hospitalized between June and December 2021 after completion of the primary vaccination cycle, were retrospectively analyzed, retrieving data on comorbidities, Clinical Frailty Scale (CFS), clinical presentation and outcomes. Multimorbidity (91.7% with ≥2 chronic illnesses) and frailty (61.6% with CFS ≥ 5) were highly prevalent. CFS (OR 0.678, 95% CI 0.573−0.803, p < 0.001) and hypertension were independently associated with interstitial pneumonia. Mortality was 25.1% and unrelated with age. PaO2/FiO2 on blood gas analysis performed upon admission (OR 0.986, 95% CI 0.977−0.996, p = 0.005), and CFS (OR 1.723, 95% CI 1.152−2.576, p = 0.008) were independently associated with mortality only in subjects < 85 years old. Conversely, serum PCT levels were associated with mortality in subjects ≥ 85 years old (OR 3.088, 95% CI 1.389−6.8628, p = 0.006). In conclusion, hospitalization for COVID-19 breakthrough infection mainly involved geriatric patients, with those aged ≥ 85 more characterized by decompensation of baseline comorbidities rather than typical COVID-19 respiratory symptoms.

Co-Administration of Remdesivir and Azithromycin May Protect against Intensive Care Unit Admission in COVID-19 Pneumonia Requiring Hospitalization: A Real-Life Observational Study.

The benefits of remdesivir treatment, with or without co-administration of antibiotics such as azithromycin, are uncertain in COVID-19 pneumonia. The aim of this retrospective single-center study was to assess the effects of remdesivir, with or without azithromycin, on hospital mortality, intensive care unit (ICU) admission, and need of non-invasive ventilation. The clinical records of the COVID-19 patients hospitalized in an Italian ward in March 2021 were analyzed, and data on comorbidities and clinical, radiological, and laboratory presentation of the disease were collected. Among 394 participants (234 M), 173 received remdesivir (43.9%), including 81 with azithromycin (20.5%). Remdesivir recipients were younger, with less comorbidities, and had better PaO2/FiO2 and clinical outcomes, including reduced mortality, but the differences were not independent of covariates. Rates of ICU transferal were 17%, 9%, and 1% in the no remdesivir, remdesivir without azithromycin, and remdesivir/azithromycin groups, respectively. In a stepwise multivariate logistic regression model, remdesivir/azithromycin co-treatment was independently associated with reduced ICU admission (vs remdesivir alone, OR 0.081, 95% CI 0.008-0.789, p = 0.031; vs no remdesivir, OR 0.060, 95% CI 0.007-0.508, p = 0.010). These data suggest that the therapeutical effect of remdesivir in COVID-19 pneumonia may be potentiated by azithromycin. The association between the two drugs should be further investigated.

Accounting for frailty and multimorbidity when interpreting high-sensitivity troponin I tests in oldest old.

BACKGROUND: Older patients evaluated in Emergency Departments (ED) for suspect Myocardial Infarction (MI) frequently exhibit unspecific elevations of serum high-sensitivity troponin I (hs-TnI), making interpretation particularly challenging for emergency physicians. The aim of this longitudinal study was to identify the interaction of multimorbidity and frailty with hs-TnI levels in older patients seeking emergency care. METHODS: A group of patients aged≥75 with suspected MI was enrolled in our acute geriatric ward immediately after ED visit. Multimorbidity and frailty were measured with Cumulative Illness Rating Scale (CIRS) and Clinical Frailty Scale (CFS), respectively. The association of hs-TnI with MI (main endpoint) was assessed by calculation of the Area Under the Receiver-Operating Characteristic Curve (AUROC), deriving population-specific cut-offs with Youden test. The factors associated with hs-TnI categories, including MI, CFS and CIRS, were determined with stepwise multinomial logistic regression. The association of hs-TnI with 3-month mortality (secondary endpoint) was also investigated with stepwise logistic regression. RESULTS: Among 268 participants (147 F, median age 85, IQR 80-89), hs-TnI elevation was found in 191 cases (71%, median 23 ng/L, IQR 11-65), but MI was present in only 12 cases (4.5%). hs-TnI was significantly associated with MI (AUROC 0.751, 95% CI 0.580-0.922, p = 0.003), with an optimal cut-off of 141 ng/L. hs-TnI levels ≥141 ng/L were significantly associated with CFS (OR 1.58, 95% CI 1.15-2.18, p = 0.005), while levels <141 ng/L were associated with the cardiac subscore of CIRS (OR 1.36, 95% CI 1.07-1.71, p = 0.011). CFS, but not hs-TnI levels, predicted 3-month mortality. CONCLUSIONS: In geriatric patients with suspected MI, frailty and cardiovascular multimorbidity should be carefully considered when interpreting emergency hs-TnI testing.

Trends of COVID-19 Admissions in an Italian Hub during the Pandemic Peak: Large Retrospective Study Focused on Older Subjects.

Older multimorbid frail subjects have been severely involved in the coronavirus disease-19 (COVID-19) pandemic. The aim of this retrospective study is to compare the clinical features and outcomes of patients admitted in different phases of the outbreak in a COVID-19 hospital hub, with a particular focus on age, multimorbidity, and functional dependency. The clinical records of 1264 patients with clinical and radiological features compatible with COVID-19 pneumonia admitted in February-June, 2020, were analyzed, retrieving demographical, clinical, laboratory data, and outcomes. All variables were compared after stratification by the period of admission (first phase: rising slope of pandemic wave; second phase: plateau and falling slope), age, results of the first reverse transcriptase-polymerase chain reaction (RT-PCR) test for detection of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), multimorbidity (≥2 chronic diseases), and presence of disability. Factors independently associated with hospital mortality were determined by multivariate forward-selection logistic regression. Patients admitted during the second phase were older, more frequently multimorbid, disabled, and of female gender. However, on admission they exhibited milder respiratory impairment (PaO2/FiO2 268, IQR 174-361, vs. 238, IQR 126-327 mmHg, p < 0.001) and lower mortality (22% vs. 27%, p < 0.001). Age, respiratory exchanges, positive RT-PCR test, number of chronic diseases (odds ratio (OR) 1.166, 95% confidence interval (CI) 1.036-1.313, p = 0.011), and disability (OR 1.927, 95% CI 1.027-3.618, p = 0.022) were positively associated with mortality, while admission during the second phase exhibited an inverse association (OR 0.427, 95% CI 0.260-0.700, p = 0.001). In conclusion, older multimorbid patients were mainly hospitalized during the second phase of the pandemic wave. The prognosis was strongly influenced by the COVID-19 phenotype and period of admission, not just by age, multimorbidity, and disability.

Reduced mortality in COVID-19 patients treated with colchicine: Results from a retrospective, observational study.

OBJECTIVES: Effective treatments for coronavirus disease 2019 (COVID-19) are urgently needed. We hypothesized that colchicine, by counteracting proinflammatory pathways implicated in the uncontrolled inflammatory response of COVID-19 patients, reduces pulmonary complications, and improves survival. METHODS: This retrospective study included 71 consecutive COVID-19 patients (hospitalized with pneumonia on CT scan or outpatients) who received colchicine and compared with 70 control patients who did not receive colchicine in two serial time periods at the same institution. We used inverse probability of treatment propensity-score weighting to examine differences in mortality, clinical improvement (using a 7-point ordinary scale), and inflammatory markers between the two groups. RESULTS: Amongst the 141 COVID-19 patients (118 [83.7%] hospitalized), 70 (50%) received colchicine. The 21-day crude cumulative mortality was 7.5% in the colchicine group and 28.5% in the control group (P = 0.006; adjusted hazard ratio: 0.24 [95%CI: 0.09 to 0.67]); 21-day clinical improvement occurred in 40.0% of the patients on colchicine and in 26.6% of control patients (adjusted relative improvement rate: 1.80 [95%CI: 1.00 to 3.22]). The strong association between the use of colchicine and reduced mortality was further supported by the diverging linear trends of percent daily change in lymphocyte count (P = 0.018), neutrophil-to-lymphocyte ratio (P = 0.003), and in C-reactive protein levels (P = 0.009). Colchicine was stopped because of transient side effects (diarrhea or skin rashes) in 7% of patients. CONCLUSION: In this retrospective cohort study colchicine was associated with reduced mortality and accelerated recovery in COVID-19 patients. This support the rationale for current larger randomized controlled trials testing the safety/efficacy profile of colchicine in COVID-19 patients.