The association of non-severe COVID-19 infection and progression to frailty among robust older veterans.

BACKGROUND: Studies have shown that frailty was increased in hospitalized COVID-19 patients. However, it is not clear whether non-severe COVID-19 increases the risk for pre-frailty and frailty development. Our study aimed to determine the risk of developing frailty and pre-frailty in robust veterans who contracted non-severe COVID-19. METHODS: We conducted a retrospective cohort study to assess the association of SARS-CoV-2 infection with the development of pre-frailty and frailty status among robust U.S. veterans using VA COVID-19 Shared Data Resource. We included patients 55 years and older who had at least one SARS-CoV-2 testing between March 15, 2020, and November 30, 2020, had been active patients in the past 12 months, and had a VA frailty index of zero (robust status) at the time of testing. Cox proportional hazard model was used to assess the association between COVID-19 infection and developing frailty or pre-frailty and frailty. We also assessed the association by patients' age groups, sex, and race. FINDINGS: We identified 82070 veterans mean age 68.3 ± 7.8, 74738 (91.1%) male, 53899 (65.7%) white, 7557 (9.2%) with mild COVID-19 infection. Over the follow up period of 36 months, testing positive for COVID-19 was associated with a 66% increase in the hazard of becoming frail (adjusted HR = 1.66, 95%CI: 1.32-2.08), and a 68% increase in the hazard of becoming pre-frail (adjusted HR = 1.68, 95%CI: 1.45-1.94). Among male patients, mild COVID-19 infection was associated with a 54% increase in the hazard of becoming frail (adjusted HR = 1.54, 95% CI: 1.21-1.96), while among female patients there was a 330% increase (adjusted HR = 4.30, 95% CI: 2.13-8.64). CONCLUSIONS AND RELEVANCE: Non-severe COVID-19 infection that occurred in robust older adults increased the risk of developing frailty. Further multi-center prospective cohort studies evaluating the mechanism of action and clinical trials of treatment options for post-COVID frailty are indicated in Veterans to support clinical care.

Frailty training among healthcare professionals.

As the population ages worldwide, frailty becomes more prevalent, leading to a higher risk of poor outcomes. Therefore, there is an increased need to educate healthcare providers in the areas of frailty screening, assessment, and treatment. In our review of the current state of frailty education worldwide we showed that, with the exception of a few European countries, education of clinicians on frailty screening, assessment, and treatment is inadequate. Interprofessional team competencies, quality measures and clinical guidelines that require screening, assessment and management of frailty are needed to propel frailty education forward. It is evident that there is much-needed collaboration between high-, mid-, and low-income countries to reach consensus and create worldwide recommendations for frailty education.

Association of Frailty and Cardiopulmonary Resuscitation Outcomes in Older U.S. Veterans.

Objectives: Determine the association between frailty and immediate survival of cardiopulmonary resuscitation (CPR) in older Veterans. Secondary outcomes: compare in-hospital mortality, duration of resuscitation efforts, hospital and intensive care unit (ICU) length of stay, neurologic outcomes, and discharge disposition between frail and non-frail Veterans. Methods: Retrospective cohort study including Veterans 50 years and older, who were "Full Code" and had in-hospital cardiac arrest between 7/1/2017 and 6/30/2020, at the Miami VAMC. Frailty Index for the VA (VA-FI) was used to determine frailty status. Immediate Survival was determined by return of spontaneous circulation (ROSC) and in-hospital mortality was determined by all-cause mortality. We compared outcomes between frail and non-frail Veterans using chi-square test. After adjusting for age, gender, race, and previous hospitalizations, we used multivariate binomial logistic regression with 95% confidence intervals to analyze the relationship between immediate survival and frailty, and in-hospital mortality and frailty. Results: 91% Veterans were non-Hispanic, 49% Caucasian, 96% male, mean age 70.7 ± 8.5 years, 73% frail and 27% non-frail. Seventy-six (65.5%) Veterans had ROSC, without difference by frailty status (P = .891). There was no difference based on frailty status of in-hospital mortality, discharge disposition, or neurologic outcomes. Frail and non-frail Veterans had resuscitation efforts lasting the same amount of time. Conclusions and Implications: CPR outcomes were not different depending on frailty status in our Veteran population. With these results, we cannot use frailty - as measured by the VA-FI - as a prognosticator of CPR outcomes in Veterans.

Frailty as a risk factor for post-acute sequelae of COVID-19 among US veterans during the Delta and Omicron waves.

BACKGROUND: Older populations have suffered the highest rates of SARS-CoV-2 infection and associated complications, including Post-Acute Sequelae of SARS-CoV-2 infection (PASC). Frailty is a geriatric syndrome that often coexists with COVID-19 infection. The vulnerability to stressors caused by multisystemic dysfunction that characterizes frailty may predispose older adults to develop PASC. METHODS: Retrospective cohort study using the VA COVID-19 Shared Data Resource to identify US veterans testing positive for SARS-CoV-2 between July 2021 and February 2022, without prior positive tests and who were alive 30 days after infection. Frailty was calculated using a 31-item VA Frailty Index generated from electronic health records. We categorized Veterans into robust (FI ≤ 0.10), prefrail (FI: >0.10- < 0.21), and frail (FI ≥ 0.21). We assessed the association between frailty and PASC and vaccination and PASC using Cox survival model, adjusting for covariates. RESULTS: We identified 245,857 COVID-19-positive veterans surviving 30 days after infection. The mean age was 57.5 ± 16.5 years; 87.2% were males, 68.1% were white, and 9.0% were Hispanic. Almost half of the sample (48.9%) were classified as robust, while 28.3% were pre-frail and 22.7% were frail; 99,886 (40.6%) were fully vaccinated, and 33,516 (13.6%) received booster doses. Over a median follow-up of 143 days (IQR = 101), 23,890 (9.7%) patients developed PASC. Within 6 months after infection, frailty and pre-frailty were associated with a 41% (adjusted HR [aHR]:1.40 (95% CI: 1.35-1.47) and 15% (aHR: 1.17 (95% CI: 1.11-1.19) increase in the risk of PASC compared with the robust, respectively. Vaccination and booster doses before infection were associated with a 27% (aHR: 0.73 (95% CI: 0.71-0.75) and 33% (aHR: 0.66 (95% CI: 0.63-0.69) reduction in the risk of developing PASC, respectively. CONCLUSIONS: Frailty was associated with an increased risk of developing PASC. Vaccination was associated with a decreased risk of PASC, further reduced by booster doses. Early recognition of frailty in patients with COVID-19 may assist in the early identification and management of PASC.

COVID-19 mRNA vaccine effectiveness against hospitalisation and death in veterans according to frailty status during the SARS-CoV-2 delta (B.1.617.2) variant surge in the USA: a retrospective cohort study.

Background: Studies have shown that COVID-19 vaccination is effective at preventing infection and death in older populations. However, whether vaccination effectiveness is reduced in patients with frailty is unclear. We aimed to compare vaccine effectiveness against hospitalisation and death after COVID-19 during the surge of the delta (B.1.617.2) variant of SARS-CoV-2 according to patients' frailty status. Methods: In this retrospective cohort study, we used data derived from the US Veterans Health Administration (VHA) facilities and the US Department of Veterans Affairs (VA) COVID-19 Shared Data Resource, which contains information from the VA National Surveillance Tool, death certificates, and National Cemetery Administration. We included veterans aged 19 years or older who tested positive for SARS-CoV-2 using RT-PCR or antigen tests between July 25 and Sept 30, 2021, with no record of a previous positive test. Deaths were identified through VHA facilities, death certificates, and National Cemetery Administration data available from VA databases. We also retrieved data including sociodemographic characteristics, medical conditions diagnosed at baseline, frailty score, and vaccination information. The primary outcomes were COVID-19-associated hospitalisations and all-cause deaths at 30 days from testing positive for SARS-CoV-2. The odds ratio (OR) for COVID-19-associated hospitalisation and hazard ratio (HR) for death of vaccinated patients compared with the unvaccinated patients were estimated according to frailty categories of robust, pre-frail, or frail. Vaccine effectiveness was estimated as 1 minus the OR for COVID-19-associated hospitalisation, and 1 minus the HR for death. Findings: We identified 57 784 veterans (mean age 57·5 years [SD 16·7], 50 642 [87·6%] males, and 40 743 [70·5%] White people), of whom 28 497 (49·3%) were categorised as robust, 16 737 (29·0%) as pre-frail, and 12 550 (21·7%) as frail. There were 2577 all-cause deaths (676 [26·2%] in the vaccinated group and 1901 [73·8%] in the unvaccinated group), and 7857 COVID-19-associated hospitalisations (2749 [35·0%] in the vaccinated group and 5108 [65·0%] in the unvaccinated group) within 30 days of a positive SARS-CoV-2 test. Vaccine effectiveness against COVID-19-associated hospitalisation within 30 days of a positive SARS-CoV-2 test was 65% (95% CI 61-69) in the robust group, 54% (48-58) in the pre-frail group, and 36% (30-42) in the frail group. By 30 days of a positive SARS-CoV-2 test, the vaccine effectiveness for all-cause death was 79% (95% CI 74-84) in the robust group, 79% (75-83) in the pre-frail group, and 68% (63-71) in the frail group. Interpretation: Compared with non-frail patients (pre-frail and robust), those with frailty had lower levels of vaccination protection against COVID-19-associated hospitalisation and all-cause death. Future studies investigating COVID-19 vaccine effectiveness should incorporate frailty assessments and actively recruit older adults with frailty. Funding: Miami VA Healthcare System Geriatric Research Education and Clinical Center.

Can three-dimensional high-resolution anorectal manometry detect anal sphincter defects in patients with faecal incontinence?

AIM: Endoanal ultrasound (EAUS) is the gold standard for detecting anal sphincter defects in patients with faecal incontinence (FI), while anorectal manometry evaluates sphincter function. Three-dimensional high-resolution anorectal manometry (3D HRAM) is a newer modality with the potential to assess both sphincter function and anatomy. The purpose of the present study was to compare 3D HRAM with 3D EAUS for the detection of anal sphincter defects in patients with FI. METHOD: A linkage analysis was performed between the 3D HRAM and 3D EAUS databases of a tertiary referral centre to identify patients with FI who underwent both 3D EAUS and 3D HRAM. With 3D HRAM, a defect was defined as any pressure measurement below 25 mmHg at rest with at least 18° of continuous expansion. The 3D HRAM findings were compared with those of 3D EAUS. RESULTS: The study cohort included 39 patients with a mean age of 64.7 ± 15.2 years (SD); and 31 (79%) were female. Eight (21%) patients had an anal sphincter defect on EAUS with a median size of 93° (range 40°-136°). Fourteen (36%) had a defect shown by 3D HRAM with a median size of 144° (36°-180°). The sensitivity, specificity and positive and negative predictive values of 3D HRAM in detecting a sphincter defect were 75%, 74%, 43% and 92%, respectively. CONCLUSION: With a negative predictive value of 92%, 3D HRAM may be a useful screening method for ruling out a sphincter defect in patients with FI, thereby avoiding both EAUS and manometry in selected patients.

Hyperoxic exposure in humans. Effects of 50 percent oxygen on alveolar macrophage leukotriene B4 synthesis.

The pathogenesis of oxygen toxicity remains unknown but may involve leukocyte mediated injury. The effects of hyperoxia on several lower respiratory tract parameters were examined in bronchoalveolar lavage fluid of normal nonsmoking subjects who inhaled a fractional inspired oxygen concentration of 50 percent (mean exposure: 44 h). Evidence that 50 percent O2 produced oxidative stress in the lung included recovery of fluorescent products of lipid peroxidation and partial oxidation of alpha 1-antitrypsin in BAL fluid obtained after O2 exposure. To examine whether alveolar macrophage-derived leukotriene B4 may be generated in response to 50 percent O2, AM were isolated from O2-exposed subjects and compared with AM recovered from subjects breathing room air. Leukotriene B4 levels were elevated in supernatants from both unstimulated and arachidonic acid-stimulated AM obtained from hyperoxia-exposed subjects. In hyperoxia-exposed individuals, LTB4 levels were also elevated in extracted BAL fluid. The percentage of BAL neutrophils was also significantly increased after O2 exposure (2.8 +/- 0.6 vs 1.2 +/- 0.4 percent, p = 0.05). We conclude that an FIO2 of 50 percent inhaled for 44 h is associated with enhanced oxidative stress, stimulation of AM to release LTB4, and a small but significantly increased percentage of neutrophils recovered in BAL fluid.