Treatment of Proximal Femoral Fragility Fractures in Patients with COVID-19 During the SARS-CoV-2 Outbreak in Northern Italy.

BACKGROUND: From February 20 to April 2020, the coronavirus SARS (severe acute respiratory syndrome)-CoV-2 spread in northern Italy, drastically challenging the care capacities of the national health care system. Unprepared for this emergency, hospitals have quickly reformulated paths of assistance in an effort to guarantee treatment for infected patients. Orthopaedic departments have been focused on elderly traumatology, especially the treatment of femoral neck fractures in patients with coronavirus disease-2019 (COVID-19). The purpose of the present study was to evaluate the orthopaedic management strategy for femoral fragility fractures in COVID-19-positive patients with the hypothesis that operative treatment may contribute to the overall stability of the patient. METHODS: Sixteen patients affected by proximal femoral fracture and a recent history of fever, shortness of breath, and desaturation were admitted to the emergency room. Thoracic computed tomography (CT) and oropharyngeal swabs confirmed that they were positive for COVID-19, requiring hospitalization and prophylaxis with low-molecular-weight heparin. RESULTS: Three patients died before surgery because of severe respiratory insufficiency and multiple-organ-failure syndrome. Ten patients underwent surgery on the day after admission, whereas 3 patients had suspended their use of direct thrombin inhibitors and needed surgery to be delayed until the third day after admission. In all patients except 1, we noted an improvement in terms of O2 saturation and assisted respiration. In 9 patients, hemodynamic and respiratory stability was observed at an average of 7 days postoperatively. Four patients who underwent surgical treatment died of respiratory failure on the first day after surgery (1 patient), the third day after surgery (2 patients), or the seventh day after surgery (1 patient). CONCLUSIONS: We noted a stabilization of respiratory parameters in 12 COVID-19-positive patients who underwent surgery treatment of proximal femoral fractures. We believe that in elderly patients with COVID-19 who have proximal femoral fractures, surgery may contribute to the overall stability of the patient, seated mobilization, improvement in physiological ventilation, and general patient comfort in bed. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Association of frailty with outcomes in individuals with COVID-19: A living review and meta-analysis.

BACKGROUND AND OBJECTIVES: Frailty leaves older adults vulnerable to adverse health outcomes. Frailty assessment is recommended by multiple COVID-19 guidelines to inform care and resource allocation. We aimed to identify, describe, and synthesize studies reporting the association of frailty with outcomes (informed by the Institute for Healthcare Improvement's Triple Aim [health, resource use, and experience]) in individuals with COVID-19. DESIGN: Systematic review and meta-analysis. SETTING: Studies reporting associations between frailty and outcomes in the setting of COVID-19 diagnosis. PARTICIPANTS: Adults with COVID-19. MEASUREMENTS: Following review of titles, abstracts and full text, we included 52 studies that contained 118,373 participants with COVID-19. Risk of bias was assessed using the Quality in Prognostic studies tool. Our primary outcome was mortality, secondary outcomes included delirium, intensive care unit admission, need for ventilation and discharge location. Where appropriate, random-effects meta-analysis was used to pool adjusted and unadjusted effect measures by frailty instrument. RESULTS: The Clinical Frailty Scale (CFS) was the most used frailty instrument. Mortality was reported in 37 studies. After confounder adjustment, frailty identified using the CFS was significantly associated with mortality in COVID-19 positive patients (odds ratio 1.79, 95% confidence interval [CI] 1.49-2.14; hazard ratio 1.87, 95% CI 1.33-2.61). On an unadjusted basis, frailty identified using the CFS was significantly associated with increased odds of delirium and reduced odds of intensive care unit admission. Results were generally consistent using other frailty instruments. Patient-reported, cost and experience outcomes were rarely reported. CONCLUSION: Frailty is associated with a substantial increase in mortality risk in COVID-19 patients, even after adjustment. Delirium risk is also increased. Frailty assessment may help to guide prognosis and individualized care planning, but data relating frailty status to patient-reported outcomes are urgently needed to provide a more comprehensive overview of outcomes relevant to older adults.

Older adults with SARS-CoV-2 infection: Utility of the clinical frailty scale to predict mortality.

The objective of this study was to identify predictive factors of mortality in older adults with coronavirus disease 2019 (COVID-19), including the level of clinical frailty by using the clinical frailty scale (CFS). We analyzed medical records of all patients aged of 75 and older with a confirmed diagnosis of COVID-19 hospitalized in our Hospital between March 3 and April 25, 2020. Standardized variables were prospectively collected, and standardized care were provided to all patients. One hundred and eighty-six patients were included (mean 85.3 ± 5.78 year). The all cause 30-day mortality was 30% (56/186). At admission, dead patients were more dyspneic (57% vs. 38%, p = .014), had more often an oxygen saturation less than 94% (70% vs. 47%, p < .01) and had more often a heart rate faster than 90/min (70% vs. 42%, p < .001). Mortality increased in parallel with CFS score (p = .051) (20 deaths (36%) in 7-9 category). In multivariate analysis, CFS score (odds ratio [OR] = 1.49; confidence interval [CI] 95%, 1.01-2.19; p = .046), age (OR = 1.15; CI 95%, 1.01-1.31; p = .034), and dyspnea (OR = 5.37; CI 95%, 1.33-21.68; p = .018) were associated with all-cause 30-day mortality. It is necessary to integrate the assessment of frailty to determine care management plan of older patients with COVID-19, rather than the only restrictive criterion of age.

The impact of frailty on survival in elderly intensive care patients with COVID-19: the COVIP study.

BACKGROUND: The COVID-19 pandemic has led highly developed healthcare systems to the brink of collapse due to the large numbers of patients being admitted into hospitals. One of the potential prognostic indicators in patients with COVID-19 is frailty. The degree of frailty could be used to assist both the triage into intensive care, and decisions regarding treatment limitations. Our study sought to determine the interaction of frailty and age in elderly COVID-19 ICU patients. METHODS: A prospective multicentre study of COVID-19 patients ≥ 70 years admitted to intensive care in 138 ICUs from 28 countries was conducted. The primary endpoint was 30-day mortality. Frailty was assessed using the clinical frailty scale. Additionally, comorbidities, management strategies and treatment limitations were recorded. RESULTS: The study included 1346 patients (28% female) with a median age of 75 years (IQR 72-78, range 70-96), 16.3% were older than 80 years, and 21% of the patients were frail. The overall survival at 30 days was 59% (95% CI 56-62), with 66% (63-69) in fit, 53% (47-61) in vulnerable and 41% (35-47) in frail patients (p < 0.001). In frail patients, there was no difference in 30-day survival between different age categories. Frailty was linked to an increased use of treatment limitations and less use of mechanical ventilation. In a model controlling for age, disease severity, sex, treatment limitations and comorbidities, frailty was independently associated with lower survival. CONCLUSION: Frailty provides relevant prognostic information in elderly COVID-19 patients in addition to age and comorbidities. Trial registration Clinicaltrials.gov: NCT04321265 , registered 19 March 2020.

Clinical Characteristics and Outcomes of Patients with COVID-19 Infection: The Results of the SARS-RAS Study of the Italian Society of Hypertension.

The COVID-19 infection has rapidly spread around the world and a second wave is sweeping in many countries. Different clinical and epidemiological aspects characterize the disease and their understanding is necessary to better face the management of the pandemic in progress. The Italian society of arterial hypertension with the SARS-RAS study has contributed significantly to the knowledge of the interaction between inhibition of the renin-angiotensin system and COVID-19 infection. Furthermore, the study results help to understand some of the main aspects related to mortality and morbidity deriving from the infection through a multicentre analysis throughout the national territory.

Vitamin D Supplementation Associated to Better Survival in Hospitalized Frail Elderly COVID-19 Patients: The GERIA-COVID Quasi-Experimental Study.

BACKGROUND: The objective of this quasi-experimental study was to determine whether bolus vitamin D supplementation taken either regularly over the preceding year or after the diagnosis of COVID-19 was effective in improving survival among hospitalized frail elderly COVID-19 patients. METHODS: Seventy-seven patients consecutively hospitalized for COVID-19 in a geriatric unit were included. Intervention groups were participants regularly supplemented with vitamin D over the preceding year (Group 1), and those supplemented with vitamin D after COVID-19 diagnosis (Group 2). The comparator group involved participants having received no vitamin D supplements (Group 3). Outcomes were 14-day mortality and highest (worst) score on the ordinal scale for clinical improvement (OSCI) measured during COVID-19 acute phase. Potential confounders were age, gender, functional abilities, undernutrition, cancer, hypertension, cardiomyopathy, glycated hemoglobin, number of acute health issues at admission, hospital use of antibiotics, corticosteroids, and pharmacological treatments of respiratory disorders. RESULTS: The three groups (n = 77; mean ± SD, 88 ± 5years; 49% women) were similar at baseline (except for woman proportion, p = 0.02), as were the treatments used for COVID-19. In Group 1 (n = 29), 93.1% of COVID-19 participants survived at day 14, compared to 81.2% survivors in Group 2 (n = 16) (p = 0.33) and 68.7% survivors in Group 3 (n = 32) (p = 0.02). While considering Group 3 as reference (hazard ratio (HR) = 1), the fully-adjusted HR for 14-day mortality was HR = 0.07 (p = 0.017) for Group 1 and HR = 0.37 (p = 0.28) for Group 2. Group 1 had longer survival time than Group 3 (log-rank p = 0.015), although there was no difference between Groups 2 and 3 (log-rank p = 0.32). Group 1, but not Group 2 (p = 0.40), was associated with lower risk of OSCI score ≥5 compared to Group 3 (odds ratio = 0.08, p= 0.03). CONCLUSIONS: Regular bolus vitamin D supplementation was associated with less severe COVID-19 and better survival in frail elderly.

Characteristics and outcomes of patients with COVID-19 at a district general hospital in Surrey, UK.

BACKGROUND: This retrospective cohort study aims to define the clinical findings and outcomes of every patient admitted to a district general hospital in Surrey with COVID-19 in March 2020, providing a snapshot of the first wave of infection in the UK. This study is the first detailed insight into the impact of frailty markers on patient outcomes and provides the infection rate among healthcare workers. METHODS: Data were obtained from medical records. Outcome measures were level of oxygen therapy, discharge and death. Patients were followed up until 21 April 2020. RESULTS: 108 patients were included. 34 (31%) died in hospital or were discharged for palliative care. 43% of patients aged over 65 died. The commonest comorbidities were hypertension (49; 45%) and diabetes (25; 23%). Patients who died were older (mean difference ±SEM, 13.76±3.12 years; p<0.0001) with a higher NEWS2 score (median 6, IQR 2.5-7.5 vs median 2, IQR 2-6) and worse renal function (median differences: urea 2.7 mmol/L, p<0.01; creatinine 4 µmol/L, p<0.05; eGFR 14 mL/min, p<0.05) on admission compared with survivors. Frailty markers were identified as risk factors for death. Clinical Frailty Scale (CFS) was higher in patients over 65 who died than in survivors (median 5, IQR 4-6 vs 3.5, IQR 2-5; p<0.01). Troponin and creatine kinase levels were higher in patients who died than in those who recovered (p<0.0001). Lymphopenia was common (median 0.8, IQR 0.6-1.2; p<0.005). Every patient with heart failure died (8). 26 (24%) were treated with continuous positive airway pressure (CPAP; median 3 days, IQR 2-7.3) and 9 (8%) were intubated (median 14 days, IQR 7-21). All patients who died after discharge (4; 6%) were care home residents. 276 of 699 hospital staff tested were positive for COVID-19. CONCLUSIONS: This study identifies older patients with frailty as being particularly vulnerable and reinforces government policy to protect this group at all costs.

Frailty Combined with Loneliness or Social Isolation: An Elevated Risk for Mortality in Later Life.

BACKGROUND/OBJECTIVES: Frailty, loneliness, and social isolation are all associated with adverse outcomes in older adults, but little is known about their combined impact on mortality. DESIGN: Prospective cohort study. SETTING: The Longitudinal Aging Study Amsterdam. PARTICIPANTS: Community-dwelling older adults aged 65 and older (n = 1,427). MEASUREMENTS: Frailty was measured with the frailty phenotype (Fried criteria). Loneliness was assessed with the De Jong Gierveld Loneliness Scale. Social isolation was operationalized using information on partner status, social support, and network size. Two categorical variables were created, for each possible combination regarding frailty and loneliness (FL) and frailty and social isolation (FS), respectively. Mortality was monitored over a period of 22 years (1995-2017). Survival curves and Cox proportional hazard models were used to study the effects of the FL and FS combinations on mortality. Analyses were adjusted for sociodemographic factors, depression, chronic diseases, and smoking. RESULTS: Frailty prevalence was 13%, and 5.9% of the sample were frail and lonely, and 6.2% frail and socially isolated. In fully adjusted models, older adults who were only frail had a higher risk of mortality compared with people without any of the conditions (hazard ratio [HR] range = 1.40-1.48; P < .01). However, the highest risk of mortality was observed in people with a combined presence of frailty and loneliness or social isolation (HRFL = 1.83; 95% confidence interval [CI] = 1.42-2.37; HRFS = 1.77; 95% CI = 1.36-2.30). Sensitivity analyses using a frailty index based on the deficit accumulation approach instead of the frailty phenotype showed similar results, confirming the robustness of our findings. CONCLUSION: Frail older adults are at increased risk of mortality, but this risk is even higher for those who are also lonely or socially isolated. To optimize well-being and health outcomes in physically frail older adults, targeted interventions focusing on both subjective and objective social vulnerability are needed.

Outcomes from COVID-19 across the range of frailty: excess mortality in fitter older people.

PURPOSE: Our aim was to quantify the mortality from COVID-19 and identify any interactions with frailty and other demographic factors. METHODS: Hospitalised patients aged ≥ 70 were included, comparing COVID-19 cases with non-COVID-19 controls admitted over the same period. Frailty was prospectively measured and mortality ascertained through linkage with national and local statutory reports. RESULTS: In 217 COVID-19 cases and 160 controls, older age and South Asian ethnicity, though not socioeconomic position, were associated with higher mortality. For frailty, differences in effect size were evident between cases (HR 1.02, 95% CI 0.93-1.12) and controls (HR 1.99, 95% CI 1.46-2.72), with an interaction term (HR 0.51, 95% CI 0.37-0.71) in multivariable models. CONCLUSIONS: Our findings suggest that (1) frailty is not a good discriminator of prognosis in COVID-19 and (2) pathways to mortality may differ in fitter compared with frailer older patients.

Frailty and Mortality in Hospitalized Older Adults With COVID-19: Retrospective Observational Study.

OBJECTIVES: To determine the association between frailty and short-term mortality in older adults hospitalized for coronavirus disease 2019 (COVID-19). DESIGN: Retrospective single-center observational study. SETTING AND PARTICIPANTS: Eighty-one patients with COVID-19 confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR), at the Geriatrics department of a general hospital in Belgium. MEASUREMENTS: Frailty was graded according to the Rockwood Clinical Frailty Scale (CFS). Demographic, biochemical, and radiologic variables, comorbidities, symptoms, and treatment were extracted from electronic medical records. RESULTS: Participants (N = 48 women, 59%) had a median age of 85 years (range 65-97 years) and a median CFS score of 7 (range 2-9); 42 (52%) were long-term care residents. Within 6 weeks, 18 patients died. Mortality was significantly but weakly associated with age (Spearman r = 0.241, P = .03) and CFS score (r = 0.282, P = .011), baseline lactate dehydrogenase (LDH; r = 0.301, P = .009), lymphocyte count (r = -0.262, P = .02), and RT-PCR cycle threshold (Ct, r = -0.285, P = .015). Mortality was not associated with long-term care residence, dementia, delirium, or polypharmacy. In multivariable logistic regression analyses, CFS, LDH, and RT-PCR Ct (but not age) remained independently associated with mortality. Both age and frailty had poor specificity to predict survival. A multivariable model combining age, CFS, LDH, and viral load significantly predicted survival. CONCLUSIONS AND IMPLICATIONS: Although their prognosis is worse, even the oldest and most severely frail patients may benefit from hospitalization for COVID-19, if sufficient resources are available.

SARS-CoV-2, testosterone and frailty in males (PROTEGGIMI): A multidimensional research project.

Preliminary published data depict a much greater prevalence of males with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) referred for intensive care unit admission and severe sequelae in several countries. In this context, males seem to not only be more susceptible to the infection compared to female subjects, at least in Western countries, but their case fatality rate attributable to SARS-CoV-2 infection is also highest. Therefore, we may speculate that the different hormonal milieu could have a more profound pathophysiological role in association with SARS-CoV-2, with endogenous testosterone leaving men more prone to develop more serious complications related to the SARS-CoV-2 infection. Another option is that SARS-CoV-2 infection per se causes an acute stage of male hypogonadism, the depletion of androgenic action triggering serious or an even fatal course of the disease. Therefore, we strongly advocate the development of a prospective multidimensional andrological translational research project in men, which we called the PROTEGGIMI study. In this Opinion Article, we will not only highlight novel research activity in this area but also invite other researchers and learned scientific societies to join us in our efforts to understand an important and very newly discovered gap in knowledge, which may have serious implications for the lives of millions of men.