Presentation, management, and outcomes of older compared to younger adults with hospital-acquired bloodstream infections in the intensive care unit: a multicenter cohort study.

PURPOSE: Older adults admitted to the intensive care unit (ICU) usually have fair baseline functional capacity, yet their age and frailty may compromise their management. We compared the characteristics and management of older (≥ 75 years) versus younger adults hospitalized in ICU with hospital-acquired bloodstream infection (HA-BSI). METHODS: Nested cohort study within the EUROBACT-2 database, a multinational prospective cohort study including adults (≥ 18 years) hospitalized in the ICU during 2019-2021. We compared older versus younger adults in terms of infection characteristics (clinical signs and symptoms, source, and microbiological data), management (imaging, source control, antimicrobial therapy), and outcomes (28-day mortality and hospital discharge). RESULTS: Among 2111 individuals hospitalized in 219 ICUs with HA-BSI, 563 (27%) were ≥ 75 years old. Compared to younger patients, these individuals had higher comorbidity score and lower functional capacity; presented more often with a pulmonary, urinary, or unknown HA-BSI source; and had lower heart rate, blood pressure and temperature at presentation. Pathogens and resistance rates were similar in both groups. Differences in management included mainly lower rates of effective source control achievement among aged individuals. Older adults also had significantly higher day-28 mortality (50% versus 34%, p < 0.001), and lower rates of discharge from hospital (12% versus 20%, p < 0.001) by this time. CONCLUSIONS: Older adults with HA-BSI hospitalized in ICU have different baseline characteristics and source of infection compared to younger patients. Management of older adults differs mainly by lower probability to achieve source control. This should be targeted to improve outcomes among older ICU patients.

Active screening cultures to reduce infections caused by carbapenem-resistant Acinetobacter baumannii: a systematic review and meta-analysis.

BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CRAB) has emerged as a significant healthcare-associated infection carrying substantial mortality. We aimed to assess the clinical impact of active screening cultures for CRAB. METHODS: A systematic review and meta-analysis, aiming to answer two questions: 1. Does screening vs no screening improve clinical outcomes? 2. Does positive screening ("CRAB carrier") predict CRAB infections? We searched MEDLINE, Cochrane library, Web of Science, and conferences, until January 2024, comparative studies reporting clinical outcomes (mortality, invasive CRAB infections). RESULTS: Of 5,407 screened publications, 9 studies (10,865 individuals) were included for study question #2. Invasive CRAB infection rate was significantly higher among CRAB carriers (odds ratio [OR] 11.14, 95% confidence interval [CI] 4.95-25.05, with substantial heterogeneity stemming from size rather than direction of the effect). Negative predictive value (NPV) of non-carriage for invasive infection was 97%. CRAB bloodstream infections rate was significantly higher among carriers (OR 16.23, 95% CI 2.9-110.08). No significant difference was demonstrated between the two groups CRAB ventilator-associated pneumonia, length of stay, and mortality. Only one study reported outcomes for the screening vs no screening (study question #1). CONCLUSIONS: Data to support active CRAB screening are scarce regarding its clinical benefit for patients. Positively screened patients are at significantly higher risk for invasive CRAB infections, with high NPV for non-carriage. This did not translate to reduced mortality.

Humoral response superiority of the monovalent XBB.1.5 over the bivalent BA.1 and BA.5 mRNA COVID-19 vaccines.

JN.1, the dominating SARS-CoV-2 variant, is antigenically distinct from ancestral BA.1, BA.5 and XBB.1.5 variants, raising concern about effectiveness of updated COVID-19 vaccines. Here, we compared the neutralizing antibody response against JN.1, 1-month after receipt of the three available Moderna mRNA vaccines. Sera obtained from 37, 30 and 30 XBB.1.5, BA.1 and BA.4-5 -vaccine recipients, respectively, were tested for anti-RBD IgG and for JN-1 specific neutralizing antibody levels. Geometric mean fold rise (GMFR) in JN.1 specific neutralizing titers was 27 (95 % CI: 17-43.1), 10.1 (95 % CI: 6.48-15.7) and 8.77 (95 % CI: 5.69-13.5) following XBB.1.5, BA.1 and BA.4-5 vaccines, respectively, translating into a 64 % lower adjusted response (geometric mean ratio [GMR] = 0.36, 95 % CI: 0.21-0.6) in the BA.1 arm, and a 75 % lower response (GMR = 0.25, 95 % CI: 0.15-0.43) in the BA.4-5 arm. This suggests that XBB.1.5 vaccination will most likely, result in improved effectiveness against JN.1 compared with other COVID-19 vaccines.

SARS-CoV-2 IgG Levels as Predictors of XBB Variant Neutralization, Israel, 2022- and 2023.

Although a vaccine against SARS-CoV-2 Omicron-XBB.1.5 variant is available worldwide and recent infection is protective, the lack of recorded infection data highlights the need to assess variant-specific antibody neutralization levels. We analyzed IgG levels against receptor-binding domain-specific SARS-CoV-2 ancestral strain as a correlate for high neutralizing titers against XBB variants.

One-year follow-up of COVID-19 recoverees with impaired pulmonary function: A prospective cohort study.

Decreased diffusion capacity for carbon monoxide (DLCO) is the most prevalent pulmonary testing abnormality among COVID-19 recoverees. We prospectively followed 51 individuals with impaired DLCO at an average of ∼3 months following COVID-19 and re-examined them at one year. At follow-up, mean DLCO increased from 68.0 % to 72.6 % (p = 0.002); while 33 % of the cohort experienced a clinically significant rise (>10 points) in DLCO, only 29 % normalized their values. While DLCO change did not correlate with symptoms, lack of improvement was more prevalent among individuals with obesity. Regardless of COVID-19 severity, a substantial proportion continued to exhibit DLCO impairment at 1-year.

Sink-traps are a major source for carbapenemase-producing Enterobacteriaceae transmission.

OBJECTIVE: We studied the extent of carbapenemase-producing Enterobacteriaceae (CPE) sink contamination and transmission to patients in a nonoutbreak setting. METHODS: During 2017-2019, 592 patient-room sinks were sampled in 34 departments. Patient weekly rectal swab CPE surveillance was universally performed. Repeated sink sampling was conducted in 9 departments. Isolates from patients and sinks were characterized using pulsed-field gel electrophoresis (PFGE), and pairs of high resemblance were sequenced by Oxford Nanopore and Illumina. Hybrid assembly was used to fully assemble plasmids, which are shared between paired isolates. RESULTS: In total, 144 (24%) of 592 CPE-contaminated sinks were detected in 25 of 34 departments. Repeated sampling (n = 7,123) revealed that 52%-100% were contaminated at least once during the sampling period. Persistent contamination for >1 year by a dominant strain was common. During the study period, 318 patients acquired CPE. The most common species were Klebsiella pneumoniae, Escherichia coli, and Enterobacter spp. In 127 (40%) patients, a contaminated sink was the suspected source of CPE acquisition. For 20 cases with an identical sink-patient strain, temporal relation suggested sink-to-patient transmission. Hybrid assembly of specific sink-patient isolates revealed that shared plasmids were structurally identical, and SNP differences between shared pairs, along with signatures for potential recombination events, suggests recent sharing of the plasmids. CONCLUSIONS: CPE-contaminated sinks are an important source of transmission to patients. Although traditionally person-to-person transmission has been considered the main route of CPE transmission, these data suggest a change in paradigm that may influence strategies of preventing CPE dissemination.

Immunogenicity and Safety of Modified Vaccinia Ankara (MVA) Vaccine-A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Prevention of mpox has become an important public health interest. We aimed to evaluate the safety and immunogenicity of the Modified Vaccinia Ankara (MVA) vaccine. We conducted a systematic review and meta-analysis of randomized-controlled trials (RCTs) comparing MVA versus no intervention, placebo, or another vaccine. Outcomes included safety and immunogenicity outcomes. We also performed a systematic review of RCTs evaluating various MVA regimens. Fifteen publications were included in the quantitative meta-analysis. All but one (ACAM2000) compared MVA with placebo. We found that cardiovascular adverse events following two MVA doses were significantly more common compared to placebo (relative risk [RR] 4.07, 95% confidence interval [CI] 1.10-15.10), though serious adverse events (SAEs) were not significantly different. Following a single MVA dose, no difference was demonstrated in any adverse event outcomes. Seroconversion rates were significantly higher compared with placebo after a single or two doses. None of the RCTs evaluated clinical effectiveness in preventing mpox. This meta-analysis provides reassuring results concerning the immunogenicity and safety of MVA. Further studies are needed to confirm the immunogenicity of a single dose and its clinical effectiveness. A single vaccine dose may be considered according to vaccine availability, with preference for two doses.

Screening for Latent Tuberculosis Infection in Solid Organ Transplant Recipients to Predict Active Disease: A Systematic Review and Meta-Analysis of Diagnostic Studies.

Background: This is a systematic review and meta-analysis of diagnostic test accuracy studies to assess the predictive value of both tuberculin skin test (TST) and interferon-gamma release assays (IGRA) for active tuberculosis (TB) among solid organ transplantation (SOT) recipients. Methods: Medline, Embase, and the CENTRAL databases were searched from 1946 until June 30, 2022. Two independent assessors extracted data from studies. Sensitivity analyses were performed to investigate the effect of studies with high or low risk of bias. Methodological quality of each publication was assessed using QUADAS-2. Results: A total of 43 studies (36 403 patients) with patients who were screened for latent TB infection (LTBI) and who underwent SOT were included: 18 were comparative and 25 noncomparative (19 TST, 6 QuantiFERON-TB Gold In-Tube [QFT-GIT]). For IGRA tests taken together, positive predictive value (PPV) and negative predictive value (NPV) were 1.2% and 99.6%, respectively. For TST, PPV was 2.13% and NPV was 95.5%. Overall, PPV is higher when TB burden is higher, regardless of test type, although still low in absolute terms. Incidence of active TB was similar between studies using LTBI prophylaxis (mean incidence 1.22%; 95% confidence interval [CI], .2179-2.221) and those not using prophylaxis (mean incidence 1.045%; 95% CI, 0.2731-1.817; P = .7717). Strengths of this study include the large number of studies available from multiple different countries; limitations include absence of gold standard for diagnosis of latent TB and low incidence of active TB. Conclusions: We found both TST and IGRA had a low PPV and high NPV for the development of active TB posttransplant. Further studies are needed to better understand how to prevent active TB in the SOT population.

Retracted publications in infectious diseases and clinical microbiology literature: an analysis using the retraction watch database.

OBJECTIVES: We aimed to examine the rate and characteristics of retracted articles in infectious diseases and clinical microbiology. METHODS: Using the Retraction Watch Database, we conducted a cross-sectional study for retracted publications categorized as 'Infectious Disease' or 'Microbiology' until June 30 2022. We included publications for which citation information was available through the Web of Science database. Study characteristics, retraction trends and number of citations before and after the retraction year were analysed. RESULTS: Overall, 1004 retracted publications were included, retracted between August 1968 and June 2022. The number of retractions climbed through the years, peaking in 2020-2021. A total of 614 retractions originated from USA, China, and India, of total 183 736 PubMed publications from these countries. Overall, 378 (38%) were retracted because of errors; 182 (18%) because of plagiarism; and 142 (14%) because of falsification/fabrication. Specific reasons included 'concerns/issues about data' (158, 16%); 'duplication of image' (127, 13%); and 'unreliable results' (116, 12%). Of the 347 retractions during 2020 to June 2022, 91 (26%) were COVID-19 related. Fifty of 895 (5.6%) first authors had two retracted papers, and 14 (1.6%) had ≥2 retractions. Of 824 publications cited at least once, 466 (57%) were cited more often after retraction. DISCUSSION: Retractions of infectious diseases and clinical microbiology publications are increasing. Concerning reasons such as plagiarism, falsification/fabrication and errors are not uncommon. Nonetheless, these publications continue to be commonly cited after being retracted.

Real-life experience with remdesivir for treatment of COVID-19 among older adults: a multicentre retrospective study.

INTRODUCTION: The effect of remdesivir on COVID-19 mortality remains conflicting. Elderly individuals are at risk for poor COVID-19 outcomes. We aimed to assess the effect of remdesivir on COVID-19 mortality among elderly individuals, using real-world data. METHODS: Retrospective multinational cohort of individuals aged ≥65 years, hospitalized with COVID-19 in six medical centres between January 2020 and May 2021. Associations with in-hospital mortality were evaluated using a multivariable logistic regression model with propensity score adjustment for remdesivir therapy and while implementing generalized estimating equations to control for centre effect. Sensitivity analysis was performed by stratification according to the degree of respiratory support. RESULTS: Of 3010 individuals included, 2788 individuals required either oxygen supplementation or non-invasive/invasive mechanical ventilation, 489 (16%) were treated with remdesivir, and 836 (28%) died. Median age was 77 (IQR 70-84) years and 42% were women. Remdesivir was the only therapeutic intervention associated with decreased mortality [adjusted OR (aOR) 0.49, 95% CI 0.37-0.66, P < 0.001]. This protective effect was shown for individuals requiring oxygen support and non-invasive mechanical ventilation, while no association was found among individuals necessitating invasive mechanical ventilation.Risk factors for mortality included invasive ventilation (aOR 5.18, 95% CI 2.46-10.91, P < 0.001), higher serum creatinine (aOR 1.25, 95% CI 1.09-1.43, P = 0.001) and dyspnoea (aOR 1.40, 95% CI 1.07-1.84, P = 0.015) on presentation, and other non-modifiable factors, such as comorbidities. CONCLUSIONS: Among elderly individuals hospitalized with COVID-19, remdesivir carries survival benefit for those with moderate to severe disease. Its role among individuals with critical illness should be further assessed.

A Longitudinal Assessment of the Natural Change in Haemoglobin, Haematocrit, and Mean Corpuscular Volume with Age.

INTRODUCTION: We aimed to assess the natural annual trends in the levels of haemoglobin, haematocrit, and mean corpuscular volume (MCV) in a population of adults, together with the influence of different clinical parameters on these trends. METHODS: A retrospective analysis was carried out on data from a large cohort of subjects attending a screening centre in Israel. For each subject, the yearly average change of haemoglobin, haematocrit, and MCV was calculated. Statistical analysis was performed for the whole cohort and for different subgroups. RESULTS: The study included 3,551 subjects. The average annual rates of decline were found to be -0.0550 g/dL (95% confidence interval [CI] -0.0590 g/dL to -0.0503 g/dL) and -0.097% (95% CI -0.112% to -0.083%) for haemoglobin and haematocrit, respectively. An average annual increase in the MCV level by 0.184 fL (95% CI 0.168 fL-0.200 fL) was found. Among men, the rate of decline in haemoglobin was found to be twice as high compared with women -0.06 g/dL versus -0.03 g/dL, respectively (p = 0.0063). In a multivariate analysis, gender remained the only parameter significantly associated with the annual decline of haemoglobin (p = 0.0001). CONCLUSION: An annual average decrease in the levels of haemoglobin and haematocrit together with an annual increase in MCV was found. These changes were more prominent in men.

Assessment of Exercise Capacity of Individuals with Long COVID: A Cross-sectional Study.

BACKGROUND: Clinical investigations of long-term effects of coronavirus disease 2019 (COVID-19) are rarely translated to objective findings. OBJECTIVES: To assess the functional capacity of individuals reported on deconditioning that hampered their return to their pre-COVID routine. METHODS: Assessment included the 6-minute walk test (6MWT) and the 30-second sit-to-stand test (30-STST). We compared the expected and observed scores using the Wilcoxon signed-rank test. Predictors of test scores were identified using linear regression models. RESULTS: We included 49 individuals, of whom 38 (77.6%) were recovering from mild COVID-19. Twenty-seven (55.1%) individuals had a 6MWT score lower than 80% of expected. The average 6MWT scores were 129.5 ± 121.2 meters and 12.2 ± 5.0 repeats lower than expected scores, respectively (P < 0.001 for both). The 6MWT score was 107.3 meters lower for individuals with severe COVID-19 (P = 0.013) and rose by 2.7 meters per each 1% increase in the diffusing capacity of carbon monoxide (P = 0.007). The 30-STST score was 3.0 repeats lower for individuals who reported moderate to severe myalgia (P = 0.038). CONCLUSIONS: Individuals with long COVID who report on deconditioning exhibit significantly decreased physical capacity, even following mild acute illness. Risk factors include severe COVID-19 and impaired diffusing capacity or myalgia during recovery.

Outcomes of octogenarians and nonagenarians with Pseudomonas aeruginosa bacteremia: a multicenter retrospective study.

BACKGROUND: P. aeruginosa bacteremia is a common and severe infection carrying high mortality in older adults. We aimed to evaluate outcomes of P. aeruginosa bacteremia among old adults (≥ 80 years). METHODS: We included the 464/2394 (19%) older adults from a retrospective multinational (9 countries, 25 centers) cohort study of individuals hospitalized with P. aeruginosa bacteremia. Bivariate and multivariable logistic regression models were used to evaluate risk factors for 30-day mortality among older adults. RESULTS: Among 464 adults aged ≥ 80 years, the mean age was 84.61 (SD 3.98) years, and 274 (59%) were men. Compared to younger patients, ≥ 80 years adults had lower Charlson score; were less likely to have nosocomial acquisition; and more likely to have urinary source. Thirty-day mortality was 30%, versus 27% among patients 65-79 years (n = 894) and 25% among patients < 65 years (n = 1036). Multivariate analysis for predictors of mortality among patients ≥ 80 years, demonstrated higher SOFA score (odds ratio [OR] 1.36, 95% confidence interval [CI] 1.23-1.51, p < 0.001), corticosteroid therapy (OR 3.15, 95% CI: 1.24-8.01, p = 0.016) and hospital acquired P. aeruginosa bacteremia (OR 2.30, 95% CI: 1.33-3.98, p = 0.003) as predictors. Appropriate empirical therapy within 24 h, type of definitive anti-pseudomonal drug, and type of regimen (monotherapy or combination) were not associated with 30-day mortality. CONCLUSIONS: In older adults with P. aeruginosa bacteremia, background conditions, place of acquisition, and disease severity are associated with mortality, rather than the antimicrobial regimen. In this regard, preventive efforts and early diagnosis before organ failure develops might be beneficial for improving outcomes.

Predictors of survival in elderly patients with coronavirus disease 2019 admitted to the hospital: derivation and validation of the FLAMINCOV score.

OBJECTIVE: To identify predictors of 30-day survival in elderly patients with coronavirus disease 2019 (COVID-19). METHODS: Retrospective cohort study including patients with COVID-19 aged ≥65 years hospitalized in six European sites (January 2020 to May 2021). Data on demographics, comorbidities, clinical characteristics, and outcomes were collected. A predictive score (FLAMINCOV) was developed using logistic regression. Regression coefficients were used to calculate the score. External validation was performed in a cohort including elderly patients from a major COVID-19 centre in Israel. Discrimination was evaluated using the area under the receiver operating characteristic curve (AUC) in the derivation and validation cohorts. Survival risk groups based on the score were derived and applied to the validation cohort. RESULTS: Among 3010 patients included in the derivation cohort, 30-day survival was 74.5% (2242/3010). The intensive care unit admission rate was 7.6% (228/3010). The model predicting survival included independent functional status (OR, 4.87; 95% CI, 3.93-6.03), a oxygen saturation to fraction of inspired oxygen (SpO2/FiO2) ratio of >235 (OR, 3.75; 95% CI, 3.04-4.63), a C-reactive protein level of <14 mg/dL (OR, 2.41; 95% CI, 1.91-3.04), a creatinine level of <1.3 (OR, 2.02; 95% CI, 1.62-2.52) mg/dL, and absence of fever (OR, 1.34; 95% CI, 1.09-1.66). The score was validated in 1174 patients. The FLAMINCOV score ranges from 0 to 15 and showed good discrimination in the derivation (AUC, 0.79; 95% CI, 0.77-0.81; p < 0.001) and validation cohorts (AUC, 0.79; 95% CI, 0.76-0.81; p < 0.001). Thirty-day survival ranged from 39.4% (203/515) to 95.3% (634/665) across four risk groups according to score quartiles in the derivation cohort. Similar proportions were observed in the validation set. DISCUSSION: The FLAMINCOV score identifying elderly with higher or lower chances of survival may allow better triage and management, including intensive care unit admission/exclusion.

Characteristics of long-COVID among older adults: a cross-sectional study.

OBJECTIVES: To describe long-COVID symptoms among older adults and to assess the risk factors for two common long-COVID symptoms: fatigue and dyspnea. METHODS: This is a multicenter, prospective cohort study conducted in Israel, Switzerland, Spain, and Italy. Individuals were included at least 30 days after their COVID-19 diagnosis. We compared long-COVID symptoms between elderly (aged >65 years) and younger individuals (aged 18-65 years) and conducted univariate and multivariable analyses for the predictors of long-COVID fatigue and dyspnea. RESULTS: A total of 2333 individuals were evaluated at an average of 5 months (146 days [95% confidence interval 142-150]) after COVID-19 onset. The mean age was 51 years, and 20.5% were aged >65 years. Older adults were more likely to be symptomatic, with the most common symptoms being fatigue (38%) and dyspnea (30%); they were more likely to complain of cough and arthralgia and have abnormal chest imaging and pulmonary function tests. Independent risk factors for long-COVID fatigue and dyspnea included female gender, obesity, and closer proximity to COVID-19 diagnosis; older age was not an independent predictor. CONCLUSION: Older individuals with long-COVID have different persisting symptoms, with more pronounced pulmonary impairment. Women and individuals with obesity are at risk. Further research is warranted to investigate the natural history of long-COVID among the elderly population and to assess possible interventions aimed at promoting rehabilitation and well-being.

Assessment of Adult Patients with Long COVID Manifestations Suspected as Cardiovascular: A Single-Center Experience.

Background: Persistent symptoms affect a subset of coronavirus disease 2019 (COVID-19) survivors. Some of these may be cardiovascular (CV)-related. Objective: To assess the burden of objective CV morbidity among, and to explore the short-term course experienced by, COVID-19 patients with post-infectious symptomatology suspected as CV. Methods: This was a single-center, retrospective analysis of consecutive adult patients with new-onset symptoms believed to be CV following recovery from COVID-19, who had been assessed at a dedicated 'Cardio'-COVID clinic between June 2020 and June 2021. All participants were followed for 1 year for symptomatic course and the occurrence of new CV diagnoses and major adverse cardiovascular events (MACE). Results: A total of 96 patients (median age 54 (IQR, 44-64) years, 52 (54%) females) were included in the final analysis. Initial visits occurred within a median of 142 days after the diagnosis of acute COVID. Nearly all (99%) patients experienced a symptomatic acute illness, which was graded as severe in 26 (27%) cases according to the National Institutes of Health (NIH) criteria. Long-COVID symptoms included mainly dyspnea and fatigue. While the initial work-up was mostly normal, 45% of the 11 cardiac magnetic resonance studies performed revealed pathologies. New CV diagnoses were made in nine (9%) patients and mainly included myocarditis that later resolved. An abnormal spirometry was the only variable associated with these. No MACE were recorded. Fifty-two (54%) participants felt that their symptoms improved. No association was found between CV morbidity and symptomatic course. Conclusions: In our experience, long-COVID symptoms of presumed CV origin signified actual CV disease in a minority of patients who, irrespective of the final diagnosis, faced a fair 1-year prognosis.

Immune Response to Third Dose BNT162b2 COVID-19 Vaccine Among Kidney Transplant Recipients-A Prospective Study.

Immune response to two SARS-CoV-2 mRNA vaccine doses among kidney transplant recipients (KTRs) is limited. We aimed to evaluate humoral and cellular response to a third BNT162b2 dose. In this prospective study, 190 KTRs were evaluated before and ∼3 weeks after the third vaccine dose. The primary outcomes were anti-spike antibody level >4160 AU/ml (neutralization-associated cutoff) and any seropositivity. Univariate and multivariate analyses were conducted to identify variables associated with antibody response. T-cell response was evaluated in a subset of participants. Results were compared to a control group of 56 healthcare workers. Among KTRs, we found a seropositivity rate of 70% (133/190) after the third dose (37%, 70/190, after the second vaccine dose); and 27% (52/190) achieved levels above 4160 AU/ml after the third dose, compared to 93% of controls. Variables associated with antibody response included higher antibody levels after the second dose (odds ratio [OR] 30.8 per log AU/ml, 95% confidence interval [CI]11-86.4, p < 0.001); and discontinuation of antimetabolite prior to vaccination (OR 9.1,95% CI 1.8-46.5, p = 0.008). T-cell response was demonstrated in 13% (7/53). In conclusion, third dose BNT162b2 improved immune response among KTRs, however 30% still remained seronegative. Pre-vaccination temporary immunosuppression reduction improved antibody response.

Effectiveness and safety of colistin among older adults: a systematic review and meta-analysis.

OBJECTIVES: Limited data are available to guide colistin use in older adults (>65 years old). We aimed to assess the effectiveness and safety of colistin in this population. METHODS: Systematic review and meta-analysis of original data from randomized control trials, cohort studies and case-control studies assessing colistin regimens with various comparisons for any infection. Original data were obtained from corresponding authors of original studies. The primary outcome was all-cause 1 month mortality; secondary outcomes included clinical and microbiological outcomes and adverse events, including acute kidney injury. Two independent reviewers screened citations, extracted data and assessed risk of bias. ORs with 95% CIs were pooled. RESULTS: We included 38 publications (41 comparisons) reporting 2857 elderly individuals: 29 studies compared a colistin-based regimen versus another regimen (comparison 1) and 10 compared colistin monotherapy versus colistin combination (comparison 2). No significant difference in 1 month mortality was demonstrated between colistin and comparator (comparison 1, OR 1.13, 95% CI 0.80-1.60; comparison 2, OR 0.99, 95% CI 0.78-1.27). Clinical failure was significantly more likely with colistin-based therapy versus comparator (OR 1.52, 95% CI 1.13-2.06). Acute kidney injury was also significantly more common with colistin-based combinations versus other drugs (OR 3.81, 95% CI 2.14-6.77). CONCLUSIONS: For older adults, colistin-based therapy resulted in no mortality difference, compared with other regimens, for any infection. Clinical failure and acute kidney injury were significantly more common with colistin-based regimens. Close renal function monitoring is needed while using colistin in older adults.

Risk Factors and Multidimensional Assessment of Long Coronavirus Disease Fatigue: A Nested Case-Control Study.

BACKGROUND: Fatigue is the most prevalent and debilitating long-COVID (coronavirus disease) symptom; however, risk factors and pathophysiology of this condition remain unknown. We assessed risk factors for long-COVID fatigue and explored its possible pathophysiology. METHODS: This was a nested case-control study in a COVID recovery clinic. Individuals with (cases) and without (controls) significant fatigue were included. We performed a multidimensional assessment evaluating various parameters, including pulmonary function tests and cardiopulmonary exercise testing, and implemented multivariable logistic regression to assess risk factors for significant long-COVID fatigue. RESULTS: A total of 141 individuals were included. The mean age was 47 (SD: 13) years; 115 (82%) were recovering from mild coronavirus disease 2019 (COVID-19). Mean time for evaluation was 8 months following COVID-19. Sixty-six (47%) individuals were classified with significant long-COVID fatigue. They had a significantly higher number of children, lower proportion of hypothyroidism, higher proportion of sore throat during acute illness, higher proportions of long-COVID symptoms, and of physical limitation in daily activities. Individuals with long-COVID fatigue also had poorer sleep quality and higher degree of depression. They had significantly lower heart rate [153.52 (22.64) vs 163.52 (18.53); P = .038] and oxygen consumption per kilogram [27.69 (7.52) vs 30.71 (7.52); P = .036] at peak exercise. The 2 independent risk factors for fatigue identified in multivariable analysis were peak exercise heart rate (OR: .79 per 10 beats/minute; 95% CI: .65-.96; P = .019) and long-COVID memory impairment (OR: 3.76; 95% CI: 1.57-9.01; P = .003). CONCLUSIONS: Long-COVID fatigue may be related to autonomic dysfunction, impaired cognition, and decreased mood. This may suggest a limbic-vagal pathophysiology. CLINICAL TRIALS REGISTRATION: NCT04851561.