Resilience is associated with frailty and older age in hospitalised patients.

BACKGROUND: Little is known about resilience in an internal medicine setting. We aimed to assess the relationship between resilience and frailty and other clinical and sociodemographic characteristics in a cohort of prospectively enrolled hospitalised patients. METHODS: In 2017-2019, we consecutively enrolled patients in our internal medicine wards. We selected all patients who filled in the 25-item Connor-Davidson resilience scale (CD-RISC). Mean resilience was evaluated according to baseline demographic (i.e., age, sex, marital and socioeconomic status) and clinical (i.e., Cumulative Illness Rating Scale [CIRS], Edmonton Frail Scale [EFS], Barthel index, Short Blessed test, length of stay [LOS]) data. A multivariable analysis for assessing factors affecting resilience was fitted. RESULTS: Overall, 143 patients (median age 69 years, interquartile range 52-79, 74 females) were included. Resilience was significantly lower in frail (p = 0.010), elderly (p = 0.021), dependent (p = 0.032), and more clinically (p = 0.028) and cognitively compromised patients (p = 0.028), and in those with a low educational status (p = 0.032). No relation between resilience and LOS was noticed (p = 0.597). Frail patients were significantly older (p < 0.001), had a greater disease burden as measured by CIRS comorbidity (p < 0.001) and severity indexes (p < 0.001), were more dependent (p < 0.001), more cognitively impaired (p < 0.001), and displayed a lower educational level (p = 0.011) compared to non-frail patients. At multivariable analysis, frailty (p = 0.022) and dependency (p = 0.031; according to the Barthel index) were associated with lower resilience in the age groups 18-64 and ≥ 65 years, respectively. CONCLUSIONS: Low resilience was associated with frailty and dependency with an age-dependent fashion. Studies assessing the impact of this finding on important health outcomes are needed. TRIAL REGISTRATION: Clinical Complexity in Internal Medicine Wards. San MAtteo Complexity Study (SMAC); NCT03439410 . Registered 01/11/2017.

Comorbidity and multimorbidity in patients with cirrhosis, hospitalised in an internal medicine ward: a monocentric, cross-sectional study.

OBJECTIVES: There are no data regarding the prevalence of comorbidity (ie, additional conditions in reference to an index disease) and multimorbidity (ie, co-occurrence of multiple diseases in which no one holds priority) in patients with liver cirrhosis. We sought to determine the rate and differences between comorbidity and multimorbidity depending on the aetiology of cirrhosis. DESIGN: This is a subanalysis of the San MAtteo Complexity (SMAC) study. We have analysed demographic, clinical characteristics and rate of comorbidity/multimorbidity of patients with liver cirrhosis depending on the aetiology-alcoholic, infectious and non-alcoholic fatty liver disease (NAFLD). A multivariable analysis for factors associated with multimorbidity was fitted. SETTING: Single-centre, cross-sectional study conducted in a tertiary referral, academic, internal medicine ward in northern Italy (November 2017-November 2019). PARTICIPANTS: Data from 1433 patients previously enrolled in the SMAC study were assessed; only those with liver cirrhosis were eventually included. RESULTS: Of the 1433 patients, 172 (median age 79 years, IQR 67-84; 83 females) had liver cirrhosis. Patients with cirrhosis displayed higher median Cumulative Illness Rating Scale (CIRS) comorbidity (4, IQR 3-5; p=0.01) and severity (1.85, IQR 16.-2.0; p<0.001) indexes and lower educational level (103, 59.9%; p=0.003). Patients with alcohol cirrhosis were significantly younger (median 65 years, IQR 56-79) than patients with cirrhosis of other aetiologies (p<0.001) and more commonly males (25, 75.8%). Comorbidity was more prevalent in patients with alcohol cirrhosis (13, 39.4%) and multimorbidity was more prevalent in viral (64, 81.0%) and NAFLD (52, 86.7%) cirrhosis (p=0.015). In a multivariable model for factors associated with multimorbidity, a CIRS comorbidity index >3 (OR 2.81, 95% CI 1.14 to 6.93, p=0.024) and admission related to cirrhosis (OR 0.19, 95% CI 0.07 to 0.54, p=0.002) were the only significant associations. CONCLUSIONS: Comorbidity is more common in alcohol cirrhosis compared with other aetiologies in a hospital, internal medicine setting.

Rate and risk factors of in-hospital and early post-discharge mortality in patients admitted to an internal medicine ward.

BACKGROUND: We sought to quantify in-hospital and early post-discharge mortality rates in hospitalised patients. METHODS: Consecutive adult patients admitted to an internal medicine ward were prospectively enrolled. The rates of in-hospital and 4-month post-discharge mortality and their possible associated sociodemographic and clinical factors (eg Cumulative Illness Rating Scale [CIRS], body mass index [BMI], polypharmacy, Barthel Index) were assessed. RESULTS: 1,451 patients (median age 80 years, IQR 69-86; 53% female) were included. Of these, 93 (6.4%) died in hospital, while 4-month post-discharge mortality was 15.9% (191/1,200). Age and high dependency were associated (p<0.01) with a higher risk of in-hospital (OR 1.04 and 2.15) and 4-month (HR 1.04 and 1.65) mortality, while malnutrition and length of stay were associated (p<0.01) with a higher risk of 4-month mortality (HR 2.13 and 1.59). CONCLUSIONS: Several negative prognostic factors for early mortality were found. Interventions addressing dependency and malnutrition could potentially decrease early post-discharge mortality.

A mid-term follow-up with a lung ultrasonographic score correlates with the severity of COVID-19 acute phase.

Lung ultrasound (LUS) has rapidly emerged in COVID-19 diagnosis and for the follow-up during the acute phase. LUS is not yet used routinely in lung damage follow-up after COVID-19 infection. We investigated the correlation between LUS score, and clinical and laboratory parameters of severity of SARS-COV-2 damage during hospitalization and at follow-up visit. Observational retrospective study including all the patients discharged from the COVID-19 wards, who attended the post-COVID outpatient clinic of the IRCCS Policlinico San Matteo in April-June 2020. 115 patients were enrolled. Follow-up visits with LUS score measurements were at a median of 38 days (IQR 28-48) after discharge. LUS scores were associated with the length of hospitalization (p < 0.001), patients' age (p = 0.036), use of non-invasive ventilation (CPAP p < 0.001 or HFNC p = 0.018), administration of corticosteroids therapy (p = 0.030), and laboratory parameters during the acute phase (WBC p < 0.001, LDH p < 0.001, CRP p < 0.001, D-dimer p = 0.008, IL-6 p = 0.045), and inversely correlated with lymphocyte count (p = 0.007). We found correlation between LUS score and both LDH (p = 0.001) and the antibody anti-SARS-CoV-2 titers (p value = 0.008). Most of these finding were confirmed by dichothomizing the LUS score (≤ 9 or > 9 points). We found a significantly higher LUS score at the follow-up in the patients with persistent dyspnea (7.00, IQR 3.00-11.00) when compared to eupnoeic patients (3.00, IQR 0-7.00 p < 0.001). LUS score at follow-up visit correlates with more severe lung disease. These findings support the hypothesis that ultrasound could be a valid tool in the follow-up medium-term COVID-19 lung damage.

Mid-term follow-up chest CT findings in recovered COVID-19 patients with residual symptoms.

OBJECTIVES: More than a year has passed since the initial outbreak of SARS-CoV-2, which caused many hospitalizations worldwide due to COVID-19 pneumonia and its complications. However, there is still a lack of information detailing short- and long-term outcomes of previously hospitalized patients. The purpose of this study is to analyze the most frequent lung CT findings in recovered COVID-19 patients at mid-term follow-ups. METHODS: A total of 407 consecutive COVID-19 patients who were admitted to the Fondazione IRCCS Policlinico San Matteo, Pavia and discharged between February 27, 2020, and June 26, 2020 were recruited into this study. Out of these patients, a subset of 108 patients who presented with residual asthenia and dyspnea at discharge, altered spirometric data, positive lung ultrasound and positive chest X-ray was subsequently selected, and was scheduled to undergo a mid-term chest CT study, which was evaluated for specific lung alterations and morphological patterns. RESULTS: The most frequently observed lung CT alterations, in order of frequency, were ground-glass opacities (81%), linear opacities (74%), bronchiolectases (64.81%), and reticular opacities (63.88%). The most common morphological pattern was the non-specific interstitial pneumonia pattern (63.88%). Features consistent with pulmonary fibrosis were observed in 32 patients (29.62%). CONCLUSIONS: Our work showed that recovered COVID-19 patients who were hospitalized and who exhibited residual symptoms after discharge had a slow radiological recovery with persistent residual lung alterations. ADVANCES IN KNOWLEDGE: This slow recovery process should be kept in mind when determining the follow-up phases in order to improve the long-term management of patients affected by COVID-19.

Hydroxychloroquine Blood Concentrations Can Be Clinically Relevant Also After Drug Discontinuation.

BACKGROUND AND OBJECTIVE: Hydroxychloroquine was widely used during the severe acute respiratory syndrome coronavirus 2 pandemic as an antiviral drug. Most previous pharmacokinetic/pharmacodynamic studies on hydroxychloroquine were conducted on healthy volunteers or patients receiving long-term therapy. There are no studies on the elimination of hydroxychloroquine after short-term treatments. Hydroxychloroquine is known to have a pro-arrhythmic effect through QT interval prolongation, but data in this setting are not conclusive. Our aims were to estimate the time needed for hydroxychloroquine concentrations (CHCQ) to drop to a safe concentration (500 ng/mL) after a short-term therapeutic cycle and to correlate the corrected QT interval with CHCQ. METHODS: We collected blood samples and electrocardiograms of patients who underwent short-term therapy with hydroxychloroquine during drug intake and after discontinuation. Hydroxychloroquine concentrations were determined by high-performance liquid chromatography-tandem mass spectrometry and analysed with a linear regression model to estimate the elimination time of the drug after its discontinuation. We conducted a multivariate analysis of the corrected QT interval correlation with CHCQ. RESULTS: Our data suggest that short-term hydroxychloroquine courses can generate significant CHCQ persisting above 500 ng/mL up to 16 days after discontinuation of treatment. Corrected QT interval prolongation significantly correlates with CHCQ. CONCLUSIONS: The study confirms the long half-life of hydroxychloroquine and its effect on the corrected QT interval even after short-term courses of the drug. This can inform the clinician using hydroxychloroquine treatments that it would be safer to start or re-initiate treatments with corrected QT interval-prolonging potential 16 days after hydroxychloroquine discontinuation.

Aging underlies heterogeneity between comorbidity and multimorbidity frameworks.

Studies exploring differences between comorbidity (i.e., the co-existence of additional diseases with reference to an index condition) and multimorbidity (i.e., the presence of multiple diseases in which no one holds priority) are lacking. In this single-center, observational study conducted in an academic, internal medicine ward, we aimed to evaluate the prevalence of patients with two or more multiple chronic conditions (MCC), comorbidity, or multimorbidity, correlating them with other patients' characteristics. The three categories were compared to the Cumulative Illness Rating Scale (CIRS) comorbidity index, age, gender, polytherapy, 30-day readmission, in-hospital and 30-day mortalities. Overall, 1394 consecutive patients (median age 80 years, IQR 69-86; F:M ratio 1.16:1) were included. Of these, 1341 (96.2%; median age 78 years, IQR 65-84; F:M ratio 1.17:1) had MCC. Fifty-three patients (3.8%) had no MCC, 286 (20.5%) had comorbidity, and 1055 (75.7%) had multimorbidity, showing a statistically significant (p < 0.001) increasing age trend (median age 38 years vs 71 vs 82, respectively) and increasing mean CIRS comorbidity index (1.53 ± 0.95 vs 2.97 ± 1.43 vs 4.09 ± 1.70, respectively). The CIRS comorbidity index was always higher in multimorbid patients, but only in the subgroups 75-84 years and ≥ 85 years was a significant (p < 0.001) difference (1.24 and 1.36, respectively) noticed. At multivariable analysis, age was always independently associated with in-hospital mortality (p = 0.002), 30-day mortality (p < 0.001), and 30-day readmission (p = 0.037), while comorbidity and multimorbidity were not. We conclude that age determines the most important differences between comorbid and multimorbid patients, as well as major outcomes, in a hospital setting.

Anemia in patients with Covid-19: pathogenesis and clinical significance.

COVID-19 patients typically present with lower airway disease, although involvement of other organ systems is usually the rule. Hematological manifestations such as thrombocytopenia and reduced lymphocyte and eosinophil numbers are highly prevalent in COVID-19 and have prognostic significance. Few data, however, are available about the prevalence and significance of anemia in COVID-19. In an observational study, we investigated the prevalence, pathogenesis and clinical significance of anemia among 206 patients with COVID-19 at the time of their hospitalization in an Internal Medicine unit. The prevalence of anemia was 61% in COVID-19, compared with 45% in a control group of 71 patients with clinical and laboratory findings suggestive of COVID-19, but nasopharyngeal swab tests negative for SARS-CoV-2 RNA (p = 0.022). Mortality was higher in SARS-CoV-2 positive patients. In COVID-19, females had lower hemoglobin concentration than males and a higher prevalence of moderate/severe anemia (25% versus 13%, p = 0.032). In most cases, anemia was mild and due to inflammation, sometimes associated with iron and/or vitamin deficiencies. Determinants of hemoglobin concentration included: erythrocyte sedimentation rate, serum cholinesterase, ferritin and protein concentrations and number of chronic diseases affecting each patient. Hemoglobin concentration was not related to overall survival that was, on the contrary, influenced by red blood cell distribution width, age, lactate dehydrogenase and the ratio of arterial partial oxygen pressure to inspired oxygen fraction. In conclusion, our results highlight anemia as a common manifestation in COVID-19. Although anemia does not directly influence mortality, it usually affects elderly, frail patients and can negatively influence their quality of life.

Clinical complexity and hospital admissions in the December holiday period.

BACKGROUND: Christmas and New Year's holidays are risk factors for hospitalization, but the causes of this "holiday effect" are uncertain. In particular, clinical complexity (CC) has never been assessed in this setting. We therefore sought to determine whether patients admitted to the hospital during the December holiday period had greater CC compared to those admitted during a contiguous non-holiday period. METHODS: This is a prospective, longitudinal study conducted in an academic ward of internal medicine in 2017-2019. Overall, 227 consecutive adult patients were enrolled, including 106 cases (mean age 79.4±12.8 years, 55 females; 15 December-15 January) and 121 controls (mean age 74.3±16.6 years, 56 females; 16 January-16 February). Demographic characteristics, CC, length of stay, and early mortality rate were assessed. Logistic regression analyses for the evaluation of independent correlates of being a holiday case were computed. RESULTS: Cases displayed greater CC (17.7±5.5 vs 15.2±5.9; p = 0.001), with greater impact of socioeconomic (3.51±1.7 vs 2.9±1.7; p = 0.012) and behavioral (2.36±1.6 vs 1.9±1.8; p = 0.01) CC components. Cases were also significantly frailer according to the Edmonton Frail Scale (8.0±2.8 vs 6.4±3.1; p<0.001), whilst having similar disease burden, as measured by the CIRS comorbidity index. Age (OR 1.02; p = 0.039), low income (OR 1.97, 95% CI 1.10-3.55; p = 0.023), and total CC (OR 1.06; p = 0.014) independently correlated with the cases. Also, cases showed a longer length of stay (median 15.5 vs 11 days; p = 0.0016) and higher in-hospital (12 vs 4 events; p = 0.021) and 30-day (14 vs 6 events; p = 0.035) mortality. CONCLUSIONS: Patients hospitalized during the December holiday period had worse health outcomes, and this could be attributable to the grater CC, especially related to socioeconomic (social deprivation, low income) and behavioral factors (inappropriate diet). The evaluation of all CC components could potentially represent a useful tool for a more rational resource allocation over this time of the year.