The impact of removing gastric residual volume monitoring and enteral nutrition rate titration in adults receiving mechanical ventilation

BackgroundMonitoring gastric residual volume (GRV) and titrating enteral nutrition (EN) towards goal rate are common practices in the intensive care unit (ICU) despite limited supportive evidence. We investigated the effect of removal of GRV monitoring and commencing EN at goal rate had on EN provision in mechanically ventilated ICU patients.MethodsWe conducted a single-centre, pre-post implementation study, in a 10-bed ICU comprising 181 patients with ventilation ≥48 h and given EN within 24 h of intubation. EN adequacy, expressed as the proportion of patients receiving ≥90% of the prescribed volume during the first 24 h of feeding, was compared before and after implementation. Secondary outcomes included EN adequacy over entire ICU stay; incidence of gastrointestinal intolerance in terms of vomiting, abdominal distension, and GRV >200 ml; prokinetic use; onset of a ventilator-associated condition; ventilation duration; length of stay; and mortality.ResultsAfter intervention, the proportion of patients meeting ≥90% of their prescribed EN volume within the first 24 h of feeding increased by 38.1% (pre: 46.4%, 95% confidence interval [CI]: 36.7–56.3; post: 84.5%, 95% CI: 75.8–91.2; p < 0.001). Over their entire ICU stay, the proportion of patients meeting ≥90% of their prescribed EN volume increased by 21.4% (pre: 61.9%, 95% CI: 52.0–71.1; post: 83.3%, 95% CI: 74.4–90.2; p = 0.001). Gastrointestinal intolerance reduced by 34.0% (pre: 80.4%, 95% CI: 71.8–87.5; post: 46.4%, 95% CI: 36.0–57.1; p < 0.001) and fewer prescribed prokinetic agents (pre: 57.7%, 95% CI: 47.8–67.3; post: 23.8%, 95% CI: 15.6–33.6; p < 0.001).ConclusionsRemoval of GRV monitoring and commencing EN at goal resulted in significantly increased EN provision during the first 24 h of feeding and entire ICU stay with reduced prokinetic use and gastrointestinal complications.     

Antiretroviral therapy improves neurocognitive impairment in people living with HIV? A meta-analysis

ObjectivesAlthough effective antiretroviral therapy (ART) has been used for more than two decades, HIV-associated neurocognitive disorder remains prevalent. Thus, whether ART can improve neurocognitive impairment is controversial. This review aims to explore the effects of ART on cognitive impairment in people living with HIV (PLWH).MethodsA systematic literature search was conducted in eight databases (PubMed, Embase, Web of Science, Cochrane Library, CNKI, VIP, China Biology Medicine disc, and WanFang) to identify studies that compare cognitive function between study groups who are administered and not administered ART. We searched for articles published up to April 2019. Article evaluation and data extraction were independently conducted by two reviewers.ResultsSixteen articles (6,694 participants)—14 cross-sectional studies and 2 cohort studies—were included in this meta-analysis. The cross-sectional studies demonstrated that ART group did not perform better than the non-ART group (OR = 1.16; 95% CI, 1.03–1.30). However, the cohort studies reported a significant improvement in cognitive function at three months (OR = 4.01; 95% CI, 2.35–6.85) and six months (OR = 9.24; 95% CI, 1.71–49.96) after ART initiation compared with the baseline data. No significant cognitive improvement was found in participants younger than 55 years old, but the two cross-sectional studies showed that ART may improve cognitive function in PLWH under 65 years old with poor physical condition and immune status.ConclusionsART could improve cognitive function in PLWH with poor physical condition and immune status, but it does not considerably improve cognition in the entire PLWH population.     

Persistence Among Patients with Crohn Disease Previously Treated with an Anti-tumor Necrosis Factor Inhibitor and Switching or Cycling to Another Biologic Agent

PurposeNonresponse to an anti–tumor necrosis factor (TNF) agent in patients with Crohn disease (CD) is often managed by either a switch to a different class of biologic (ie, ustekinumab, vedolizumab) or by cycling to another anti-TNF agent (ie, adalimumab, infliximab, certolizumab pegol). Persistence after a switch to a different biologic class or after cycling within the anti-TNF class was assessed in patients with nonresponse to an anti-TNF agent.MethodsAdults with CD who discontinued from an anti-TNF agent and either switched to a different class of biologic (ie, anti-interleukin/integrin; the switching cohort) or cycled within the anti-TNF class (the cycling cohort) between September 23, 2016, and August 1, 2019, were selected from a commercial database. The index date was defined as the date of the first claim of the subsequent-line biologic (index biologic) after an anti-TNF. The switching and cycling cohorts were balanced with regard to baseline characteristics, using inverse probability of treatment weights–average treatment effect (IPTW-ATE). Persistence with the index biologic was defined as consistent use with no gaps of >120 days (ustekinumab, vedolizumab, infliximab) or of >60 days (adalimumab, certolizumab pegol) in biologic supply. Composite end points were persistence while being corticosteroid-free (defined as no use of corticosteroids with ≥14 days of supply after day 90 post-index) and persistence while on monotherapy (no immunomodulators/nonindex biologics). Weighted Kaplan-Meier and Cox models were used to assess outcomes at 12 months post-index.FindingsThere were 444 patients in the weighted switching cohort (mean age, 40.4 years; 56.3% female) and 441 in the weighted cycling cohort (mean age, 39.5 years; 58.4% female). At 12 months post-index, the rate of persistence with the index biologic was 75.7% in the switching cohort compared to 67.5% in the cycling cohort (log-rank P = 0.023); the rate of persistence while on monotherapy was 58.2% compared to 44.2%, respectively (log-rank P < 0.001). The rate of persistence was 44% greater in the switching compared to that in the cycling cohort (hazard ratio [HR] = 1.44; 95% CI, 1.11–1.88; P = 0.007); the rate of persistence while on monotherapy was 56% greater in the switching cohort (HR = 1.56; 95% CI, 1.28–1.90; P < 0.001). The between-cohort difference in persistence while being corticosteroid-free was not statistically significant (HR = 1.08; 95% CI, 0.89–1.32; P = 0.426).ImplicationsPatients with CD who switched to a different biologic class were more persistent than were patients who cycled to another anti-TNF agent. These findings may be useful for physicians when considering the treatment of patients who have experienced nonresponse or loss of response to the first-line anti-TNF agent.     

Multiple comorbidities increase the risk of death from invasive pneumococcal disease under the age of 65 years

IntroductionRisk factors for death from invasive pneumococcal disease (IPD) have not been clearly established in patients aged under 65 years. We aimed to evaluate contributions of host and bacterial factors to the risk of death from IPD in patients aged under 65 years in Japan.MethodsIn this prospective, observational, multicenter cohort study, patients with IPD (n = 581) aged 6–64 years were enrolled between 2010 and 2017. We investigated the role of host and bacterial factors in 28-day mortality.ResultsThe mortality rate increased from 3.4% to 6.2% in patients aged 6–44 years to 15.5%–19.5% in those aged 45–64 years. Multivariable analysis identified the following risk factors for mortality: age 45–64 years (hazard ratio [HR], 3.4; 95% confidence interval [CI], 1.6–6.8, p = 0.001), bacteremia with unknown focus (HR, 2.0; 95% CI, 1.1–3.7, p = 0.024), meningitis (HR, 2.1; 95% CI, 1.1–4.0, p = 0.019), underlying multiple non-immunocompromising conditions (HR, 2.6; 95% CI, 1.1–7.4, p = 0.023), and immunocompromising conditions related to malignancy (HR, 2.4; 95% CI, 1.0–5.2, p = 0.039). Pneumococcal serotype was not associated with poor outcomes.ConclusionsHost factors, including age of 45–64 years and underlying multiple non-immunocompromising conditions, are important for the prognosis of IPD. Our results will contribute to the development of targeted pneumococcal vaccination strategies in Japan.     

Meta-analysis of the Efficacy and Tolerability of Immune Checkpoint Inhibitors Combined With Chemotherapy in First-line Treatment of Small Cell Lung Cancer

PurposeThe present study was conducted to evaluate the efficacy and tolerability of using an immune checkpoint inhibitor (ICI; programmed cell death protein 1/ligand 1 [PD-1/PD-L1] inhibitor or cytotoxic T-lymphocyte antigen [CTLA]-4 inhibitor) combined with chemotherapy in the first-line treatment of small cell lung cancer.MethodsPotential articles and studies were identified using Web of Science, Cochrane Library, and ClinicalTrials.gov. The end points included overall survival, progression-free survival, objective response rate, and adverse events. Significant heterogeneity was represented by a P value (P_h) of <0.05 or an I² value of ≥50%, and the random-effects model was applied for pooled analysis. Otherwise, the fixed-effects model was used. Subgroup analysis was performed based on the type of ICI. Potential publication bias was evaluated via funnel plot and the Egger test.FindingsFive eligible articles were included. Both overall survival (hazard ratio [HR] = 0.83; 95% CI, 0.75–0.91; P < 0.001) and progression-free survival (HR = 0.80; 95% CI, 0.73–0.86; P < 0.001) were significantly prolonged by joint ICI + chemotherapy treatment. Additionally, the rates of tolerable grade ≥3 adverse events were similar between the ICI combination regimens and conventional chemotherapy (relative risk = 1.05; 95% CI, 0.98–1.12; P = 0.17). Subanalysis demonstrated that patient survival and objective response rate were more efficiently improved with a combination of anti–PD-1/PD-L1, but not anti–CTLA-4, + chemotherapy.ImplicationsBased on data from the available literature, clinical efficacy (as measured by patient survival and objective response rate) was improved with a combination of anti–PD-1/PD-L1 + chemotherapy as first-line treatment compared with chemotherapy alone in patients with small cell lung cancer.     

Endothelium-associated biomarkers mid-regional proadrenomedullin and C-terminal proendothelin-1 have good ability to predict 28-day mortality in critically ill patients with SARS-CoV-2 pneumonia: A prospective cohort study

PurposeWe assessed the ability of mid-regional proadrenomedullin (MR-proADM) and C-terminal proendothelin-1 (CT-proET-1) to predict 28-day mortality in critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia.MethodsBiomarkers were collected during the first seven days in this prospective observational cohort study. We investigated the relationship between biomarkers and mortality in a multivariable Cox regression model adjusted for age and SOFA score.ResultsIn 105 critically ill patients with confirmed SARS-CoV-2 pneumonia 28-day mortality was 28.6%. MR-proADM and CT-proET-1 were significantly higher in 28-day non-survivors at baseline and over time. ROC curves revealed high accuracy to identify non-survivors for baseline MR-proADM and CT-proET-1, AUC 0.84, (95% CI 0.76–0.92), p < 0.001 and 0.79, (95% CI 0.69–0.89), p < 0.001, respectively. The AUC for prediction of 28-day mortality for MR-proADM and CT-proET-1 remained high over time. MR-proADM ≥1.57 nmol/L and CT-proET-1 ≥ 111 pmol/L at baseline were significant predictors for 28-day mortality (HR 6.80, 95% CI 3.12–14.84, p < 0.001 and HR 3.72, 95% CI 1.71–8.08, p 0.01).ConclusionBaseline and serial MR-proADM and CT-proET-1 had good ability to predict 28-day mortality in critically ill patients with SARS-CoV-2 pneumonia.Trial registrationNEDERLANDS TRIAL REGISTER, NL8460.     

Risk of Acute Kidney Injury Associated With Medication Administration in the Emergency Department

BackgroundPatients who develop acute kidney injury (AKI) have a 2-fold increased risk for major adverse events within 1 year. An estimated 19–26% of all cases of hospital-acquired AKI may be attributable to drug-induced kidney disease (DIKD). Patients evaluated in the emergency department (ED) are often prescribed potentially nephrotoxic drugs, yet the role of ED prescribing in DIKD is unknown.ObjectiveWe sought to measure the association between ED medication administration and development of AKI.MethodsThis was a retrospective 5-year cohort analysis at a single center. Patients with a serum creatinine measurement at presentation in the ED and 24–168 h later were included. Outcome was incidence of AKI as defined by Kidney Disease Improving Global Outcomes criteria in the 7 days after ED evaluation. Medication administration risk was estimated using Cox proportional hazards model.ResultsThere were 46,965 ED encounters by 30,407 patients included in the study, of which 6461 (13.8%) patients met the criteria for AKI. For hospitalized patients, administration of a potentially nephrotoxic medication was associated with increased risk of AKI (hazard ratio [HR] 1.30 [95% confidence interval {CI} 1.20–1.41]). Diuretics were associated with the largest risk of AKI (HR 1.64 [95% CI 1.52–1.78]), followed by angiotensin-converting enzyme inhibitors (HR 1.39 [95% CI 1.26–1.54]) and antibiotics (HR 1.13 [95% CI 1.05–1.22]). For discharged patients, administration of antibiotics was strongly associated with increased risk of AKI (HR 3.19 [95% CI 1.08–9.43]).ConclusionED administration of potentially nephrotoxic medications was associated with an increased risk of AKI in the following 7 days. Diuretics, angiotensin-converting enzyme inhibitors, and antibiotics were independently associated with increased risk of AKI. Nephroprotective practices in the ED may mitigate kidney injury and long-term adverse outcomes.     

Identifying patients with symptoms suspicious for COVID-19 at elevated risk of adverse events: The COVAS score

ObjectiveDevelop and validate a risk score using variables available during an Emergency Department (ED) encounter to predict adverse events among patients with suspected COVID-19.MethodsA retrospective cohort study of adult visits for suspected COVID-19 between March 1 – April 30, 2020 at 15 EDs in Southern California. The primary outcomes were death or respiratory decompensation within 7-days. We used least absolute shrinkage and selection operator (LASSO) models and logistic regression to derive a risk score. We report metrics for derivation and validation cohorts, and subgroups with pneumonia or COVID-19 diagnoses.Results26,600 ED encounters were included and 1079 experienced an adverse event. Five categories (comorbidities, obesity/BMI ≥ 40, vital signs, age and sex) were included in the final score. The area under the curve (AUC) in the derivation cohort was 0.891 (95% CI, 0.880–0.901); similar performance was observed in the validation cohort (AUC = 0.895, 95% CI, 0.874–0.916). Sensitivity ranging from 100% (Score 0) to 41.7% (Score of ≥15) and specificity from 13.9% (score 0) to 96.8% (score ≥ 15). In the subgroups with pneumonia (n = 3252) the AUCs were 0.780 (derivation, 95% CI 0.759–0.801) and 0.832 (validation, 95% CI 0.794–0.870), while for COVID-19 diagnoses (n = 2059) the AUCs were 0.867 (95% CI 0.843–0.892) and 0.837 (95% CI 0.774–0.899) respectively.ConclusionPhysicians evaluating ED patients with pneumonia, COVID-19, or symptoms suspicious for COVID-19 can apply the COVAS score to assist with decisions to hospitalize or discharge patients during the SARS CoV-2 pandemic.     

Use of comedications and potential drug-drug interactions in people living with HIV in China

BackgroundBecause people living with HIV (PLWH) are ageing, they will inevitably develop non-communicable diseases (NCDs) and the number of non-HIV medications will increase. Drug-drug interactions(DDIs) will become an ever-increasing issue. However, little is known about this important issue in Chinese PLWH. This study aimed to investigate the prevalence and risk factors of DDIs among PLWH in China.MethodsChinese PLWH aged ≥18 years were enrolled prospectively from October 2018 to April 2019 and after informed consent was obtained, they were ask to fill out a questionnaire about comorbidity and co-medications. Potential DDIs were identified using the University of Liverpool HIV Drug Interaction Checker.ResultsA total of 1804 questionnaires were included. Antiretroviral drugs (ARVs) that most frequently were prescribed were lamivudine (96.18%), efavirenz(64.64%) and tenofovir(60.62%). 16.96% of the participations reported current co-infection with HIV and14.69% reported NCDs. 263(14.57%) participations reported they had used co-medications in the past six months while 186(10.31%) reported they were taking co-medications. Age≥50 years (p < 0.001), living in developed areas(p < 0.001) and lower CD4 cell count(p = 0.045) were independently associated with the use of co-medications. Potential DDIs were identified in 54 (19.15%) persons using co-medications. Age≥50 [OR = 2.272(1.241–4.158)], PLWH with NCDs[OR = 2.889(1.509–5.532)] and usage of protease inhibitors[OR = 2.538(1.250–5.156)] were independently associated with the potential DDIs.ConclusionThe prevalence of the use of co-medications and potential DDIs among Chinese PLWH are low. Older age, NCDs and use of PIs were risk factors for the potential of developing DDIs. With the aging of PLWH, co-medications and DDIs in China warrants more attention.     

Association Between the Overall Risk of Prostate Cancer and Use of Calcium Channel Blockers: A Systematic Review and Meta-analysis

PurposeAlthough calcium channel blockers (CCBs) are now commonly prescribed to treat hypertension as a first-line drug therapy, their impact on prostate cancer (PCa) is unclear. This systematic review and meta-analysis was conducted to determine the association between CCB use and the overall risk of PCa.MethodsPubMed, EMBASE, and Cochrane were searched up to December 26, 2019, stratified according to statistical method of outcome [odd ratios (ORs), relative ratios (RRs), hazard ratios (HRs)] and cumulative duration of CCB use. The quality assessment of included studies was evaluated by using the Newcastle–Ottawa Scale. Fixed effects models were used to study the association between CCB use and the risk of PCa. Between-study heterogeneity was quantified by using Cochran's Q-statistic and I² statistics. Sensitivity analysis was performed by excluding the studies one by one, and publication bias was analyzed by using funnel plots.FindingsNineteen studies with 1,418,407 patients were identified for inclusion in the meta-analysis, which was based on the comparison of cohort studies, nested case–control studies, and case–control studies. Pooled estimates showed a RR of 1.08 (95% CI, 1.05–1.11; P < 0.00001) and a HR of 1.07 (95% CI, 1.02–1.13; P = 0.008) for association between CCB use and the risk of PCa. In addition, the results of subgroup analysis showed that CCB users of <5 years had an 8% increased overall risk of PCa (RR, 1.08; 95% CI, 1.04–1.12; P = 0.0001), and CCB users of 5–10 years had a 13% increased overall risk of PCa (RR, 1.13; 95% CI, 1.04–1.23; P = 0.003).ImplicationsCCB use had a tendency to increase the overall risk of PCa, and cumulative duration of CCB use might also be positively correlated with the overall risk of PCa.     

Single versus multiple doses of Tocilizumab in critically ill patients with coronavirus disease 2019 (COVID-19): A two-center,retrospective cohort study

PurposeTo evaluate the effectiveness and safety of the optimal tocilizumab dosing regimen.MethodsA two-center, retrospective cohort study, for COVID19 critically ill patients admitted to the intensive care units (ICUs). We included critically ill patients aged 18 years or older who received tocilizumab during ICU stay. Patients were divided into two groups based on the number of the received tocilizumab doses. The primary outcome was the in-hospital and 30-day mortality. Propensity score (PS) matching was used (1:1 ratio) based on the selected criteria.ResultsA total of 298 patients were included in the study; 70.4% (210 patients) received a single dose of tocilizumab. After adjusting for possible confounders, the 30-day mortality (HR 0.79 95% CI 0.43–1.45 P = 0.44) and in-hospital mortality (HR 0.81; 95% CI 0.46–1.49; P = 0.53) were not significantly different between the two groups. On the flip side, patients who received multiple doses had higher pneumonia odds than a single dose (OR 3.81; 95% CI 1.79–8.12 P = 0.0005).ConclusionRepeating tocilizumab doses were not associated with a mortality benefit in COVID-19 critically ill patients, but it was associated with higher odds of pneumonia compared to a single dose.     

Risk of incident bleeding after acute kidney injury: A retrospective cohort study

PurposeEnd-stage kidney disease (ESKD) causes bleeding diathesis; however, whether these findings are extrapolable to acute kidney injury (AKI) remains uncertain. We assessed whether AKI is associated with an increased risk of bleeding.MethodsSingle-center retrospective cohort study, excluding readmissions, admissions <24 h, ESKD or kidney transplants. The primary outcome was the development of incident bleeding analyzed by multivariate time-dependent Cox models.ResultsIn 1001 patients, bleeding occurred in 48% of AKI and 57% of non-AKI patients (p = .007). To identify predictors of incident bleeding, we excluded patients who bled before ICU (n = 488). In bleeding-free patients (n = 513), we observed a trend toward higher risks of bleeding in AKI (22% vs. 16%, p = .06), and a higher risk of bleeding in AKI-requiring dialysis (38% vs. 17%, p = .01). Cirrhosis, AKI-requiring dialysis, anticoagulation, and coronary artery disease were associated with bleeding (HR 3.67, 95%CI:1.33–10.25; HR 2.82, 95%CI:1.26–6.32; HR 2.34, 95%CI:1.45–3.80; and HR 1.84, 95%CI:1.06–3.20, respectively), while SOFA score and sepsis had a protective association (HR 0.92 95%CI:0.84–0.99 and HR 0.55, 95%CI:0.34–0.91, respectively). Incident bleeding was not associated with mortality.ConclusionsAKI-requiring dialysis was associated with incident bleeding, independent of anticoagulant administration. Studies are needed to better understand how AKI affects coagulation and clinical outcomes.     

Factors associated with a persistent delirium in the intensive care unit: A retrospective cohort study

PurposeTo explore differences between ICU patients with persistent delirium (PD), non-persistent delirium (NPD) and no delirium (ND), and to determine factors associated with PD.Materials and methodsRetrospective cohort study including all ICU adults admitted for ≥12 h (January 2015–February 2020), assessable for delirium and followed during their entire hospitalization. PD was defined as ≥14 days of delirium. Factors associated with PD were determined using multivariable logistic regression analysis.ResultsOut of 10,295 patients, 3138 (30.5%) had delirium, and 284 (2.8%) had PD. As compared to NPD (n = 2854, 27.7%) and ND (n = 7157, 69.5%), PD patients were older, sicker, more physically restrained, longer comatose and mechanically ventilated, had a longer ICU and hospital stay, more ICU readmissions and a higher mortality rate.Factors associated with PD were age (adjusted odds ratio [aOR] 1.03; 95% confidence interval [CI] 1.02–1.04); emergency surgical (aOR 1.84; 95%CI 1.26–2.68) and medical (aOR 1.57; 95%CI 1.12–2.21) referral, mean Sequential Organ Failure Assessment (SOFA) score before delirium onset (aOR 1.18; 95%CI 1.13–1.24) and use of physical restraints (aOR 5.02; 95%CI 3.09–8.15).ConclusionsPatients with persistent delirium differ in several characteristics and had worse short-term outcomes. Physical restraints were the most strongly associated with PD.     

Association between habitual hot spring bathing and depression in Japanese older adults: A retrospective study in Beppu

ObjectivesThermal therapy is used to manage various psychological diseases, such as depression. We investigated the relationship between hot spring bathing and depression in older adults using questionnaire responses.Design and SettingWe comprehensively evaluated the preventive effects of long-term hot spring bathing in 10429 adults aged ≥ 65 years in Beppu, Japan, by conducting a questionnaire study on the prevalence of depression (n = 219).Main outcome measuresOdds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a multivariable logistic regression model for history of depression.ResultsA separate multivariable logistic regression model for inference showed that female sex (OR, 1.56; 95 % CI, 1.17–2.08; p = 0.002), arrhythmia (OR, 1.73; 95 % CI, 1.18–2.52; p = 0.004), hyperlipidemia (OR, 1.63; 95 % CI, 1.14–2.32; p = 0.006), renal disease (OR, 2.26; 95 % CI, 1.36–3.75; p = 0.001), collagen disease (OR, 2.72; 95 % CI, 1.48–5.02; p = 0.001), allergy (OR, 1.97; 95 % CI, 1.27–3.04; p = 0.002), and habitual daily hot spring bathing (OR, 0.63; 95 % CI, 0.41–0.94; p = 0.027) were independently significantly associated with a history of depression.ConclusionsWe found an inverse relationship between habitual daily hot spring bathing and history of depression. Prospective randomized controlled trials on habitual daily hot spring bathing as a treatment for depression are warranted to investigate whether the use of hot springs can provide relief to those with psychiatric and mental health disorders.     

Treatment Outcome of Bacteremia Due to Non–Carbapenemase-producing Carbapenem-Resistant Klebsiella pneumoniae Bacteremia: Role of Carbapenem Combination Therapy

PurposeInfections caused by carbapenemase-producing Klebsiella pneumoniae are emerging causes of morbidity and mortality worldwide. Optimal treatment for non–carbapenemase-producing carbapenem-resistant K pneumoniae (nCP-CRKP) bacteremia remains undefined. The goal of this study was to assess the clinical outcome, predictors of mortality, and therapeutic strategy of carbapenems for nCP-CRKP bacteremia.MethodsA retrospective study of monomicrobial bacteremia caused by nCP-CRKP, at a medical center between 2010 and 2015 was conducted. CRKP which was defined as a minimum inhibitory concentration (MIC) of ≥ 2 for ertapenem or ≥ 4 mg/L for meropenem, or imipenem. Multiplex polymerase chain was applied to detect carbapenemase genes. The patients definitively treated with combination therapy were compared with monotherapy using a propensity score–matched analysis to assess therapeutic effectiveness. The primary end point was the 30-day crude mortality and clinical prognostic factors were assessed.FindingsOverall 171 patients met criteria were eligible for the study and their overall 30-day mortality rate was 38.6%. The multivariate logistic regression analysis showed that combination therapy was associated with a lower 30-day mortality rate (adjusted odds ratio [aOR], 0.11; 95% CI, 0.03–0.43; P = 0.001) and less clinical (aOR, 0.21; 95% CI, 0.08–0.58; P = 0.003) and microbiologic (aOR, 0.36; 95% CI, 0.19–0.71; P = 0.003) failure. However, the 30-day mortality rate in the cases infected by a pathogen with a meropenem MIC ≤8 mg/L receiving carbapenem-containing or carbapenem-sparing combination regimens was similar (15 of 58 [25.9%] vs 5 of 20 [23.3%]; P = 1.0).ImplicationsCombination therapy, regardless of carbapenem-containing or carbapenem-sparing, with one or more active agents improved survival more than monotherapy and was more effective in patients with critical illness. (Clin Ther. 2020; 42:XXX–XXX) © 2020 Elsevier HS Journals, Inc.     

Clinical and Cancer-Related Predictors for Venous Thromboembolism in Cancer Patients Presenting to the Emergency Department

BackgroundThe accurate detection of cancer-associated venous thromboembolism (VTE) can avoid unnecessary diagnostic imaging or laboratory tests.ObjectiveWe sought to determine clinical and cancer-related risk factors of VTE that can be used as predictors for oncology patients presenting to the emergency department (ED) with suspected VTE.MethodsWe retrospectively analyzed all consecutive patients who presented with suspicion of VTE to The University of Texas MD Anderson Cancer Center ED between January 1, 2009, and January 1, 2013. Logistic regression models were used to identify risk factors that were associated with VTE. The ability of these factors to predict VTE was externally validated using a second cohort of patients who presented to King Hussein Cancer Center ED between January 1, 2009, and January 1, 2016.ResultsCancer-related covariates associated with the occurrence of VTE were high-risk cancer type (odds ratio [OR] 3.64 [95% confidence interval {CI} 2.37–5.60], p < 0.001), presentation within 6 months of the cancer diagnosis (OR 1.92 [95% CI 1.62–2.28], p < 0.001), active cancer (OR 1.35 [95% CI 1.10–1.65], p = 0.003), advanced stage (OR 1.40 [95% CI 1.01–1.94], p = 0.044), and the presence of brain metastasis (OR 1.73 [95% CI 1.32–2.27], p < 0.001). When combined, these factors along with other clinical factors showed high prediction performance for VTE in the external validation cohort.ConclusionsCancer risk group, presentation within 6 months of cancer diagnosis, active and advanced cancer, and the presence of brain metastases along with other related clinical factors can be used to predict VTE in patients with cancer presenting to the ED.     

Prevalence and impact of frailty on mortality in elderly ICU patients: a prospective,multicenter, observational study

Purpose

Frailty is a recent concept used for evaluating elderly individuals. Our study determined the prevalence of frailty in intensive care unit (ICU) patients and its impact on the rate of mortality.

Methods

A multicenter, prospective, observational study performed in four ICUs in France included 196 patients aged ≥65 years hospitalized for >24 h during a 6-month study period. Frailty was determined using the frailty phenotype (FP) and the clinical frailty score (CFS). The patients were separated as follows: FP score <3 or ≥3 and CFS <5 or ≥5.

Results

Frailty was observed in 41 and 23 % of patients on the basis of an FP score ≥3 and a CFS ≥5, respectively. At admission to the ICU, the Simplified Acute Physiology Score II (SAPS II) and Sequential Organ Failure Assessment (SOFA) scores did not differ between the frail and nonfrail patients. In the multivariate analysis, the risk factors for ICU mortality were FP score ≥3 [hazard ratio (HR), 3.3; 95 % confidence interval (CI), 1.6–6.6; p < 0.001], male gender (HR, 2.4; 95 % CI, 1.1–5.3; p = 0.026), cardiac arrest before admission (HR, 2.8; 95 % CI, 1.1–7.4; p = 0.036), SAPS II score ≥46 (HR, 2.6; 95 % CI, 1.2–5.3; p = 0.011), and brain injury before admission (HR, 3.5; 95 % CI, 1.6–7.7; p = 0.002). The risk factors for 6-month mortality were a CFS ≥5 (HR, 2.4; 95 % CI, 1.49–3.87; p < 0.001) and a SOFA score ≥7 (HR, 2.2; 95 % CI, 1.35–3.64; p = 0.002). An increased CFS was associated with significant incremental hospital and 6-month mortalities.

Conclusions

Frailty is a frequent occurrence and is independently associated with increased ICU and 6-month mortalities. Notably, the CFS predicts outcomes more effectively than the commonly used ICU illness scores.