The effect of higher-intensity dosing of anticoagulation on the clinical outcomes in hospitalized patients with COVID-19: A meta-analysis of randomized controlled trials

ObjectiveWe aimed to perform a meta-analysis to summarize the overall evidence from randomized controlled trials related to higher-intensity anticoagulation in hospitalized patients with COVID-19.MethodsA systematic literature search was performed in electronic databases to identify randomized controlled trials comparing the clinical outcomes between intermediate/ therapeutic anticoagulation and prophylactic anticoagulation. Meta-analyses with random-effects models were used to estimate the pooled odds ratio (OR) for outcomes of interest at a 95% confidence interval (CI).ResultsEight randomized controlled trials were included, with a total of 5405 hospitalized patients with COVID-19. The meta-analysis revealed no statistically significant difference in the odds of mortality (pooled OR = 0.92; 95% CI 0.71–1.19) but a statistically significant reduction in the odds of development of thrombotic events (pooled OR = 0.55; 95% CI 0.42–0.72), and significantly increased odds of development of major bleeding (pooled OR = 1.81; 95% CI 1.20–2.72) with the use of intermediate/therapeutic anticoagulation, relative to prophylactic anticoagulation. Subgroup analysis in patients with a severe course of COVID-19 observed a statistically significant reduction in the odds of development of thrombotic events (pooled OR = 0.66; 95% CI 0.45–0.98) but no significant difference in the odds of development of major bleeding events (pooled OR = 1.37; 95% CI 0.74–2.56), with the use of intermediate/therapeutic anticoagulation, relative to prophylactic anticoagulation.ConclusionThere could be net clinical benefits with higher-intensity dosing of anticoagulation relative to prophylactic-dosing of anticoagulation among hospitalized patients with severe COVID-19.     

Intensive care patients receiving vasoactive medications: A retrospective cohort study

BackgroundVasoactive medications are high-risk drugs commonly used in intensive care units (ICUs), which have wide variations in clinical management.ObjectivesThe aim of this study was to describe the patient population, treatment, and clinical characteristics of patients who did and did not receive vasoactive medications while in the ICU and to develop a predictive tool to identify patients needing vasoactive medications.MethodsA retrospective cohort study of patients admitted to a level three tertiary referral ICU over a 12-month period from October 2018 to September 2019 was undertaken. Data from electronic medical records were analysed to describe patient characteristics in an adult ICU. Chi square and Mann–Whitney U tests were used to analyse data relating to patients who did and did not receive vasoactive medications. Univariate analysis and Pearson's r² were used to determine inclusion in multivariable logistic regression.ResultsOf 1276 patients in the cohort, 40% (512/1276) received a vasoactive medication for haemodynamic support, with 84% (428/512) receiving noradrenaline. Older patients (odds ratio [OR] = 1.02; 95% confidence interval [CI] = 1.01–1.02; p < 0.001) with higher Acute Physiology and Chronic Health Evaluation (APACHE) III scores (OR = 1.04; 95% CI = 1.03–1.04; p < 0.001) were more likely to receive vasoactive medications than those not treated with vasoactive medications during an intensive care admission. A model developed using multivariable analysis predicted that patients admitted with sepsis (OR = 2.43; 95% CI = 1.43–4.12; p = 0.001) or shock (OR = 4.05; 95% CI = 2.68–6.10; p < 0.001) and managed on mechanical ventilation (OR = 3.76; 95% CI = 2.81–5.02; p < 0.001) were more likely to receive vasoactive medications.ConclusionsMechanically ventilated patients admitted to intensive care for sepsis and shock with higher APACHE III scores were more likely to receive vasoactive medications. Predictors identified in the multivariable model can be used to direct resources to patients most at risk of receiving vasoactive medications.     

Care and treatments related to intensive care unit–acquired muscle weakness: A cohort study

BackgroundIntensive care unit–acquired muscle weakness (ICUAW) has an incidence of 40–46%. Early mobilisation is known to be a protective factor.ObjectiveThe aim of the study was to identify the incidence of ICUAW in Spain and to evaluate variables likely to contribute to the development of ICUAW.MethodsA 4-month, prospective observational multicentre cohort study was conducted on patients receiving invasive mechanical ventilation for at least 48 h. Data were collected from ICU day 3 until ICU discharge. The primary outcome was presence of ICUAW (diagnosed using the Medical Research Council [MRC] scale). The secondary outcome was nurse–patient ratio, physiotherapist availability, analgesia, sedation and delirium management, glycaemic control, and daily level of mobility during the ICU stay as per the ICU Mobility Scale. A logistic regression model was constructed based exclusively on days 3–5 of the ICU stay.ResultsThe data of 642 patients were analysed from 80 ICUs, accounting for 35% of all ICUs in Spain. The incidence of ICUAW was 58% (275 of 474 patients; 95% confidence interval [CI] [53–62]). The predictors for ICUAW were older age (odds ratio [OR] = 1.01; 95% CI [1.00–1.03]) and more days with renal replacement therapy (OR = 1.01; 95% CI [1.00–1.02]). The protective factors for ICUAW were male gender (OR = 0.58; 95% CI [0.38–0.89]), higher Barthel Index (showing prehospital functional independence) (OR = 0.97; 95% CI [0.95–0.99]), more days of being awake and cooperative (defined by a feasible MRC assessment) (OR = 0.98; 95% CI [0.97–0.99]), presence of delirium (OR = 0.98; 95% CI [0.97–0.99]), and more days with active mobilisation (ICU Mobility Scale ≥ 4) (OR = 0.98; 95% CI [0.97–0.99]).ConclusionsThe risk factors for ICUAW were functional dependence before admission, female gender, older age, and more days on renal replacement therapy. The protective factors for ICUAW were feasibility of MRC assessment, the presence of delirium, and being actively mobilised during the first 5 days in the ICU.     

Clinical predictors of prophylaxis use prior to the onset of acute venous thromboembolism in hospitalized patients SWIss Venous ThromboEmbolism Registry (SWIVTER)

Summary. Background: We investigated clinical predictors of appropriate prophylaxis prior to the onset of venous thromboembolism (VTE). Methods: In 14 Swiss hospitals, 567 consecutive patients (306 medical, 261 surgical) with acute VTE and hospitalization < 30 days prior to the VTE event were enrolled. Results: Prophylaxis was used in 329 (58%) patients within 30 days prior to the VTE event. Among the medical patients, 146 (48%) received prophylaxis, and among the surgical patients, 183 (70%) received prophylaxis (P < 0.001). The indication for prophylaxis was present in 262 (86%) medical patients and in 217 (83%) surgical patients. Among the patients with an indication for prophylaxis, 135 (52%) of the medical patients and 165 (76%) of the surgical patients received prophylaxis (P < 0.001). Admission to the intensive care unit [odds ratio (OR) 3.28, 95% confidence interval (CI) 1.94–5.57], recent surgery (OR 2.28, 95% CI  1.51–3.44), bed rest > 3 days (OR 2.12, 95% CI  1.45–3.09), obesity (OR 2.01, 95% CI  1.03–3.90), prior deep vein thrombosis (OR 1.71, 95% CI  1.31–2.24) and prior pulmonary embolism (OR 1.54, 95% CI  1.05–2.26) were independent predictors of prophylaxis. In contrast, cancer (OR 1.06, 95% CI  0.89–1.25), age (OR 0.99, 95% CI  0.98–1.01), acute heart failure (OR 1.13, 95% CI  0.79–1.63) and acute respiratory failure (OR 1.19, 95% CI  0.89–1.59) were not predictive of prophylaxis. Conclusions: Although an indication for prophylaxis was present in most patients who suffered acute VTE, almost half did not receive any form of prophylaxis. Future efforts should focus on the improvement of prophylaxis for hospitalized patients, particularly in patients with cancer, acute heart or respiratory failure, and in the elderly.     

French ICU's health care workers have a poor knowledge of the cost of the devices they use for patient care: A prospective multicentric study

PurposeICU patient's care may require the use of onerous devices, which contributes to make this department one of the most expensive in the hospital. It seemed us relevant to assess healthcare workers' (HCWs) knowledge of the cost of the devices daily used in ICU.Materials and methodsAn anonymous questionnaire was administered on a voluntary basis to HCWs of 3 ICUs.Measurements and main resultsCost estimations were expressed as percentage of the real cost; an estimation was considered correct if it was ±50% of the true price. 107 HCWs (66 physicians and 41 nurses and nurse aids) answered the survey. Only 29% of estimations were within 50% of the real cost. The prices of the cheapest devices were overestimated, while the costs of the most expensive ones were underestimated. In multivariate analysis, cost less than50 euros [OR = 3.2; CI 95%(1.6–6.3)], professional experience <10 years [OR = 1.5; CI 95%(1.1–2.1)], being a medical student [OR = 2.0; CI 95%(1.3–3.0)], and working in a university affiliated hospital [OR = 0.6; CI 95%(0.4–0.9)] were associated with an incorrect estimation.ConclusionsICU's HCWs have a poor knowledge of the price of devices they regularly use for the care of their patients.     

Association between prehospital prognostic factors and out-of-hospital cardiac arrest: Effect of rural–urban disparities

BackgroundOut-of-hospital cardiac arrest (OHCA) is associated with a poor prognosis and a highly variable survival rate. Few studies have focused on outcomes in rural and urban groups while also evaluating underlying diseases and prehospital factors for OHCAs.ObjectiveTo investigate the relationship between the patient's underlying disease and outcomes of OHCAs in urban areas versus those in rural areas.MethodsWe reviewed the emergency medical service (EMS) database for information on OHCA patients treated between January 2015 and December 2019, and collected data on pre-hospital factors, underlying diseases, and outcomes of OHCAs. Univariate and multivariate logistic regression analyses were used to evaluate the prognostic factors for OHCA.ResultsData from 4225 OHCAs were analysed. EMS response time was shorter and the rate of attendance by EMS paramedics was higher in urban areas (p < 0.001 for both). Urban area was a prognostic factor for >24-h survival (odds ratio [OR] = 1.437, 95% confidence interval [CI]: 1.179–1.761). Age (OR = 0.986, 95% CI: 0.979–0.993). EMS response time (OR = 0.854, 95% CI: 0.811–0.898), cardiac arrest location (OR = 2.187, 95% CI: 1.707–2.795), attendance by paramedics (OR = 1.867, 95% CI: 1.483–2.347), and prehospital defibrillation (OR = 2.771, 95% CI: 2.154–3.556) were independent risk factors for survival to hospital discharge, although the influence of an urban area was not significant (OR = 1.211, 95% CI: 0.918–1.584).ConclusionsCompared with rural areas, OHCA in urban areas are associated with a higher 24-h survival rate. Shorter EMS response time and a higher probability of being attended by paramedics were noted in urban areas. Although shorter EMS response time, younger age, public location, defibrillation by an automated external defibrillator, and attendance by Emergency Medical Technician-paramedics were associated with a higher rate of survival to hospital discharge, urban area was not an independent prognostic factor for survival to hospital discharge in OHCA patients.     

Use of Antidepressants and the Risk of Upper Gastrointestinal Tract Bleeding: A Case-control Study

PurposeTo investigate the association between the use of antidepressants and the risk of upper gastrointestinal tract bleeding (UGIB).MethodsA Case-control study was conducted in a Brazilian hospital complex. Cases were defined as patients with a diagnosis of UGIB and controls as patients admitted for reasons unrelated to gastrointestinal bleeding, gastric concerns, or complications associated with low-dose aspirin (LDA) or nonsteroidal anti-inflammatory drugs (NSAIDs) use. Sociodemographic and clinical data, comorbidities, drug therapy in use (long-term use and self-medication), and lifestyle habits were recorded through face-to-face interviews. Two groups were defined: use of antidepressants in general and use of antidepressants according to their affinity for serotonin transporters. The presence of synergism between the concomitant use of antidepressants and LDA or NSAIDs on the risk of UGIB was also explored.FindingsA total of 906 participants were recruited (200 in the case group and 706 in the control group). The use of antidepressants was not associated with the risk of UGIB (odds ratio [OR] = 1.503; 95% CI, 0.78–2.88) or the use of antidepressants with high affinity for serotonin receptors (OR = 1.983; 95% CI, 0.81–4.85). An increased risk of UGIB was observed in concomitant users of antidepressants and LDA (OR = 5.489; 95% CI, 1.60–18.81) or NSAIDs (OR = 18.286; 95% CI, 3.18–105.29). Despite the lack of significance, the use of antidepressants appears to be a positive modifier of UGIB risk in LDA and NSAID users.ImplicationsThese findings indicate an increased risk of UGIB in concomitant users of antidepressants and LDA or NSAIDs, suggesting the need to monitor antidepressant users, especially those most likely to develop UGIB. In addition, further studies with larger sample sizes are needed to confirm these findings.     

Gender-based differences of copeptin alone or combined with troponin for early rule-out of non-ST-elevation myocardial infarction

BackgroundLittle is known about the role of gender in the dual biomarker strategy using copeptin and troponin for the early rule-out of non-ST-elevation myocardial infarction (NSTEMI). We aimed to evaluate gender-based differences on copeptin levels, combined negative predictive value (NPV) and predictors of copeptin elevation at admission.MethodsBiomarkers were measured in 852 adult patients presenting to the emergency department with chest pain and suspected NSTEMI. Logistic regression analyses on predictors of copeptin elevation were evaluated by gender.ResultsOverall, 362 women (42.5%) and 490 men (57.5%) were included. Copeptin levels were higher in men (median 7.36 pmol/L vs. 4.8 pmol/L; P < .001). Men had a similar NPV (100%) as women (99.6%, CI: 98.8–100) using the dual biomarker rule-out strategy and when compared to troponin alone (men, NPV = 98.7%, CI: 97.5–99.8; and women, NPV = 98.7%, CI: 97.5–100). Multivariate logistic regression showed positive association of male gender with copeptin elevation (OR = 2.37; CI: 1.61–3.49; P < .001). In men, diastolic blood pressure was a negative predictor of copeptin elevation (OR = 0.98, 95% CI: 0.96–0.99), while positive predictors were current MI (OR = 2.16, 95% CI: 1.19–3.91), chronic renal insufficiency (OR = 3.58, 95% CI: 1.33–9.62), and atrial fibrillation (OR = 2.56, 95% CI: 1.23–5.32), respectively (all P < .05). In women, current MI (OR = 2.98, CI: 1.23–7.24), atrial fibrillation (OR = 2.90, CI: 1.26–6.70) and syncope-like events (OR = 7.56, CI: 2.26–25.30) were significant predictors of copeptin elevation.ConclusionsMen with suspected NSTEMI have higher copeptin levels. The dual biomarker rule-out strategy has a similar performance in both male and female patients. Certain predictors of copeptin elevation are gender-specific.     

Risk factors for post–intensive care syndrome: A systematic review and meta-analysis

ObjectiveThe objective of this study was to identify the risk factors for each area of post–intensive care syndrome (PICS) and to determine their effect size.Review method usedThis study used systematic review and meta-analysis.Data sourcesPubMed, CINAHL, EMBASE, PsycINFO, and Cochrane Library were searched.Review methodsEighty-nine studies were selected for the review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The PICS areas and risk factors reported in the individual studies were reviewed and categorised. We used the Newcastle–Ottawa Scale to evaluate the quality of studies. The effect size of each risk factor was calculated as odds ratio (OR).ResultsThere were 33 mental health studies, 15 cognitive impairment studies, 32 physical impairment studies, eight studies on two areas, and one study on all three areas. Sixty risk factors were identified, including 33 personal and 27 intensive care unit (ICU)–related factors. Significant risk factors for mental health included female sex (odds ratio [OR] = 3.37, 95% confidence interval [CI]: 1.12–10.17), previous mental health problems (OR = 9.45, 95% CI: 2.08–42.90), and negative ICU experience (OR = 2.59, 95% CI: 2.04–3.28). The only significant risk factor for cognitive impairment was delirium (OR = 2.85, 95% CI: 1.10–7.38). Significant risk factors for physical impairment included older age (OR = 2.19, 95% CI: 1.11–4.33), female sex (OR = 1.96, 95% CI: 1.32–2.91), and high disease severity (OR = 2.54, 95% CI: 1.76–3.66).ConclusionsAlthough PICS is a multidimensional concept, each area has been studied separately. Significant risk factors for PICS included older age, female sex, previous mental health problems, disease severity, negative ICU experience, and delirium. To prevent PICS, the multidisciplinary team should pay attention to modifiable risk factors such as delirium and patients’ ICU experience.     

Frequency of Advanced Cardiac Life Support Medication Use and Association With Survival During In-hospital Cardiac Arrest

PurposeCardiopulmonary resuscitation is common in the United States, with >200,000 people experiencing an in-hospital cardiac arrest (IHCA) annually. Recent medication shortages have raised the question of the frequency and type of medication used during cardiac arrest resuscitation. We sought to determine the frequency and quantity of medications used during IHCA.MethodsThis retrospective, single-center, medical record review was performed at a large, urban teaching hospital. Adults ≥18 years old who had an IHCA with confirmed loss of pulse between January 2017 and March 2018 were identified. A standardized data collection tool was used to extract data from the electronic medical record. The primary outcome was the frequency and quantity of medications used during the IHCA. Secondary outcomes included median time to defibrillation and frequency of sodium bicarbonate use, including among patients with end-stage renal disease (ESRD).FindingsCriteria were met for 181 IHCA events. Demographic characteristics were 71% black, 17% white, mean age of 65 years, and 46% women. Epinephrine was given in 86.7% of the arrests, with a mean cumulative dose of 4.2 mg. Sodium bicarbonate was given in 63.5% of the arrests, with a mean cumulative dose of 9.0 g (1.9 amps). Amiodarone was given in 30.9% of the arrests, with a mean cumulative dose of 311.8 mg. Median time to defibrillation was 2 min (interquartile range, 1–4 min). Preexisting ESRD was present in 24.8% of patients, of whom 71.1% received sodium bicarbonate. Sodium bicarbonate administration was associated with a lower likelihood of survival to discharge (odds ratio [OR] = 0.27; 95% CI, 0.11–0.66) as well as a lower rate of return to spontaneous circulation (ROSC) (OR = 0.35; 95% CI, 0.13–0.95). Magnesium administration was associated with a lower rate of ROSC (OR = 0.39; 95% CI, 0.15–0.98). Of note, in patients with preexisting ESRD, no medications were significantly associated with a change in likelihood of survival to discharge or rate of ROSC. In patients without preexisting ESRD, magnesium was associated with a lower rate of ROSC (OR = 0.23; 95% CI, 0.08–0.77).ImplicationsWe found that in a hospital with established rapid response and code blue teams, numerous medications that are not recommended for routine use in cardiac arrest are still administered at significant frequencies. Furthermore, substantial amounts of drugs with known recent shortage are used in IHCA. Inc.     

Seroprevalence of Helicobacter pylori in human immunodeficiency virus-infected patients in a tertiary care hospital in Busan,South Korea

IntroductionHuman immunodeficiency virus (HIV) infection management has recently become more successful. While the life expectancy of HIV-infected patients increased, the prevalence of non-acquired immunodeficiency syndrome-defining cancers, such as gastric cancer, also increased. Helicobacter pylori is associated with gastric cancer, the most common cancer and the fourth leading cause of cancer-related deaths in South Korea, which has the highest incidence of chronic gastric mucosa inflammation. Here, the seroprevalence and risk factors of H. pylori infection in Korean HIV-infected patients were evaluated.MethodsThree hundred HIV-infected patients attending the Outpatient Department of Pusan National University Hospital were prospectively enrolled from October 2018 to February 2019. Socio-demographic information was evaluated using questionnaires, and the serological status of H. pylori infection was analyzed for anti-H. pylori IgG antibodies.ResultsThe overall seropositivity of H. pylori was 32.7%, and 254 patients (84.7%) were male. The risk factors significantly associated with H. pylori seropositivity were: age of 40–49 years (odds ratio [OR] = 5.00; 95% confidence interval [CI] 1.30–19.17), age of 50–59 years (OR = 3.93; 95% CI 1.05–14.73), CD4 cell counts of 350–500/μL (OR = 4.23; 95% CI 1.53–11.65), CD4 cell counts ≥500/μL (OR = 2.78; 95% CI 1.15–6.72), and a weekly average alcohol consumption of at least one alcoholic beverage (OR = 1.78; 95% CI 1.05–2.99).ConclusionsThe seroprevalence of H. pylori is significantly associated with alcohol consumption, high CD4 cell count, and the age group of 40–59 years.     

Implementation of a hospital-wide multidisciplinary blunt chest injury care bundle (ChIP): Fidelity of delivery evaluation

BackgroundIneffective intervention for patients with blunt chest wall injury results in high rates of morbidity and mortality. To address this, a blunt chest injury care bundle protocol (ChIP) was developed, and a multifaceted plan was implemented using the Behaviour Change Wheel.ObjectiveThe purpose of this study was to evaluate the reach, fidelity, and dose of the ChIP intervention to discern if it was activated and delivered to patients as intended at two regional Australian hospitals.MethodsThis is a pretest and post-test implementation evaluation study. The proportion of ChIP activations and adherence to ChIP components received by eligible patients were compared before and after intervention over a 4-year period. Sample medians were compared using the nonparametric median test, with 95% confidence intervals. Differences in proportions for categorical data were compared using the two-sample z-test.Results/FindingsOver the 19-month postimplementation period, 97.1% (n = 440) of eligible patients received ChIP (reach). The median activation time was 134 min; there was no difference in time to activation between business hours and after-hours; time to activation was not associated with comorbidities and injury severity score. Compared with the preimplementation group, the postimplementation group were more likely to receive evidence-based treatments (dose), including high-flow nasal cannula use (odds ratio [OR] = 6.8 [95% confidence interval {CI} = 4.8–9.6]), incentive spirometry in the emergency department (OR = 7.5, [95% CI = 3.2–17.6]), regular analgesia (OR = 2.4 [95% CI = 1.5–3.8]), regional analgesia (OR = 2.8 [95% CI = 1.5–5.3]), patient-controlled analgesia (OR = 1.8 [95% CI = 1.3–2.4]), and multiple specialist team reviews, e.g., surgical review (OR = 9.9 [95% CI = 6.1–16.1]).ConclusionsHigh fidelity of delivery was achieved and sustained over 19 months for implementation of a complex intervention in the acute context through a robust implementation plan based on theoretical frameworks. There were significant and sustained improvements in care practices known to result in better patient outcomes. Findings from this evaluation can inform future implementation programs such as ChIP and other multidisciplinary interventions in an emergency or acute care context.     

Utilization of the electrocardiogram in the pediatric emergency department

ObjectiveReview pediatric electrocardiogram (ECG) result severity classification and describe the utilization of ECG testing, and rate of clinically significant results, in the pediatric emergency department (PED).MethodsThis was a review of patients ≤18 years who had an ECG performed in a tertiary children's hospital PED 2005–2017. Using established guidelines and expert consultation, ECG results were categorized: Class 0 = normal, Class I = mild abnormality (no cardiology follow-up), Class II = moderate abnormality (cardiology follow-up), Class III = severe abnormality (immediate intervention). Chi-square tests were used to examine differences between patients with clinically insignificant (Class 0/I) and clinically significant (Class II/III) results. Multivariable regression was used to examine factors associated with clinically significant results.Results16,147 unique PED encounters with ECG performed were included for analysis. The most common ECG indications were chest pain (32.5%), syncope (22.0%), arrhythmia (11.8%), toxicology/ingestion (9.4%), and seizure (5.7%). Overall, 12.7% (n = 2056) of ECGs had clinically significant (Class II/III) results, and only 2.0% (n = 325) had severe abnormality (Class III) that would require immediate intervention or cardiologist input. Factors associated with increased odds of clinically significant ECG were age ≤ 1 year (OR = 1.20, 95% CI: 1.02–1.41), male (OR = 1.33, 95% CI: 1.20–1.46), and indications of arrhythmia (OR = 1.84, 95% CI: 1.59–2.13), cardiac (OR = 2.57, 95% CI: 1.99–3.31), blank indication (OR = 1.52, 95% CI: 1.17–1.98), and electrolyte abnormality (OR = 1.42, 95% CI: 1.03–1.95).ConclusionsIn this study, we provided a valuable review of ECG result severity classification in the pediatric population. We found that chest pain and syncope represented over half of all ECGs performed. We found that clinically significant results are rare in the pediatric population at 12.7% of all ECGs performed, and very few (2.0%) have severe abnormalities that would require immediate intervention. Those with increased odds of a clinically significant ECG include young patients ≤1 year of age, male patients, and certain ECG indications.     

Liquid Formulation of Gemcitabine Increases Venous Pain in Patients With Cancer: A Retrospective Study

PurposeVenous pain induced by peripheral intravenous infusion of gemcitabine has remained an unresolved issue in clinical practice. This study aimed to identify differences between gemcitabine formulations as well as risk factors associated with gemcitabine-induced venous pain in patients with cancer.MethodsWe retrospectively analyzed data from consecutive patients with cancer who had received chemotherapy including a lyophilized or liquid formulation of gemcitabine diluted with 5% glucose solution via a peripheral vein. The study was conducted at Ehime University Hospital using electronic medical records dated between January 2015 and July 2017. The primary end point was the prevalence of venous pain at the administration site during gemcitabine infusion, classified as injection site reaction of grade ≥2 according to the Common Terminology Criteria for Adverse Events, version 4.0. A multivariate logistic regression analysis with generalized estimating equations for longitudinal data was used to identify risk factors for venous pain during all courses of gemcitabine treatment.FindingsA total of 1150 treatment courses in 141 Japanese patients were evaluated in this study. Venous pain occurred in 115 courses (10.0%) and in 49 patients (34.8%). The multivariate logistic regression analysis with generalized estimating equations revealed that a dose increase of gemcitabine and use of the liquid formulation of gemcitabine were significantly associated with an increased risk for venous pain (dose increase, adjusted odds ratio [OR] = 1.25; 95% CI, 1.11–1.40 [P < 0.001]; and liquid formulation, adjusted OR = 12.43, 95% CI, 5.61–27.51 [P < 0.001]), whereas age, course number of gemcitabine, and use of the soft-back product of 5% glucose solution were significantly associated with a reduced risk for venous pain (age, adjusted OR = 0.75; 95% CI, 0.57–0.98 [P = 0.037]; course number, adjusted OR = 0.96; 95% CI, 0.92–0.99 [P = 0.023]; and soft back, adjusted OR = 0.39; 95% CI, 0.21–0.74 [P = 0.004]).ImplicationsThe use of the liquid formulation of gemcitabine was associated with a significant increase in the frequency of gemcitabine-induced venous pain despite dilution with 5% glucose solution compared to that with the lyophilized formulation. The lyophilized formulation of gemcitabine should hence be used in peripheral intravenous infusion for the treatment of patients with cancer.     

Predicting bacteremia caused by Streptococcus anginosus group: A new scoring method

BackgroundViridans group streptococci (VGS) are the most common causative organisms of infective endocarditis. Among VGS, the Streptococcus anginosus group (SAG) is often associated with abscess formation, and delayed diagnosis leads to increased morbidity and mortality. This study aims to examine the factors associated with SAG bacteremia and develop a predictive scoring method.MethodsThis single-center retrospective case-control study of patients with VGS bacteremia compared the background and clinical characteristics between the SAG and non-SAG groups. The univariate analysis used the χ² test and t-test. The multivariate analysis was conducted using logistic regression.ResultsOut of 161 patients, 95 had SAG and 66 had non-SAG bacteremia. Age >63 years: 2 points (odds ratio [OR] = 3.52, 95% confidence interval [CI]: 1.64–7.54); solid tumor: 2 points (OR = 4.44, 95% CI: 1.42–6.77); C-reactive protein >7.61 mg/dL: 3 points (OR = 5.40, 95% CI: 2.49–11.72), and white blood cell count >8550/μL: 2 points (OR = 2.76, 95% CI: 1.29–2.91) were found to be independently associated with SAG bacteremia. After totaling the above variables and adding 1 point for diabetes mellitus, the area under the receiver operating curve was 0.81 (95% CI: 0.74–0.88). The sensitivity and specificity were 51% and 88%, respectively, at a cut-off of 6 points.ConclusionsIn patients with VGS bacteremia, a score of 6 points or higher using this method predicts SAG with high specificity.     

Risk factors of multidrug-resistant bacteria infection in patients with ventilator-associated pneumonia: A systematic review and meta-analysis

BackgroundMultidrug-resistant (MDR) bacteria-induced VAP often has high lethality. We present this systematic review and meta-analysis to assess the risk factors for MDR bacterial infection in patients with VAP.MethodsPubMed, EMBASE, Web of Science, and Cochrane Library were searched for studies regarding MDR bacterial infection in VAP patients, from Jan 1996 to Aug 2022. Study selection, data extraction, and quality assessment of included studies were conducted by two reviewers independently, and potential risk factors for MDR bacterial infection were identified.ResultsMeta-analysis showed that the score of the Acute Physiology and Chronic Health Evaluation II (APACHE-II) [OR = 1.009, 95% (CI 0.732, 1.287)], Simplified Acute Physiology Score II (SAPS-II) [OR = 2.805, 95%CI (0.854, 4.755)], length of hospital-stay before VAP onset (days) [OR = 2.639, 95%CI (0.387, 4.892)], in-ICU duration [OR = 3.958, 95%CI (0.894, 7.021)], Charlson index [OR = 1.000, 95%CI (0.889, 1.111)], overall hospital-stay [OR = 20.742, 95%CI (18.894, 22.591)], Medication of Quinolones [OR = 2.017, 95%CI (1.339, 3.038)], medication of carbapenems [OR = 3.527, 95%CI (2.476, 5.024)], combination of more than 2 prior antibiotics [OR = 3.181, 95%CI (2.102, 4.812)], and prior use of antibiotics [OR 2.971, 95%CI (2.001, 4.412)] were independent risk factors of MDR bacterial infection in VAP patients. Diabetes and mechanical ventilation duration before VAP onset showed no association with risk for MDR bacterial infection.ConclusionsThis study has identified 10 risk factors associated with MDR bacterial infection in VAP patients. Identification of these factors would be able to facilitate the treatment and prevention of MDR bacterial infection in clinical practice.     

Colchicine administration for percutaneous coronary intervention: A meta-analysis of randomized controlled trials

IntroductionThe efficacy of colchicine administration in patients undergoing percutaneous coronary intervention (PCI) remains controversial. We conduct a systematic review and meta-analysis to explore the influence of colchicine administration versus placebo on treatment efficacy for PCI.MethodsWe search PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through June 2020 for randomized controlled trials (RCTs) assessing the effect of colchicine administration versus placebo in patients with PCI. This meta-analysis is performed using the random-effect model.ResultsFive RCTs involving 5526 patients are included in the meta-analysis. Overall, compared with control group for myocardial infarction patients undergoing PCI, colchicine intervention can significantly reduce major adverse cardiovascular events (OR = 0.78; 95% CI = 0.62 to 0.97; P = 0.02), but reveals no obvious impact on mortality (OR = 0.89; 95% CI = 0.60 to 1.32; P = 0.57), myocardial infarction (OR = 0.88; 95% CI = 0.67 to 1.17; P = 0.39), serious adverse events (OR = 0.71; 95% CI = 0.31 to 1.61; P = 0.41), or restenosis (OR = 1.02; 95% CI = 0.63 to 1.64; P = 0.95).ConclusionsColchicine treatment may be effective to reduce major adverse cardiovascular events in patients undergoing PCI.     

Effectiveness of polymyxin B-immobilized hemoperfusion against sepsis and septic shock: A systematic review and meta-analysis

PurposeTo evaluate the efficacy and safety of Polymyxin B-immobilized hemoperfusion (PMX-HP) against sepsis or septic shock.MethodsWe searched databases (PubMed, EMBASE and Cochrane Library) to identify eligible randomized controlled trials (RCTs). The primary outcomes we included in this review were mortality at the longest follow-up available and serious adverse events associated with treatments. We used the Cochrane risk of bias assessment tool to evaluate risk of bias. Trial Sequential Analysis (TSA) was performed to assess the conclusion reached in our research.ResultsThirteen studies including 1163 patients were identified. Use of PMX-HP could reduce overall mortality [relative risk (RR) 0.68, 95% confidence interval (CI) 0.51–0.91, P = 0.01]. An interesting finding was that the mortality of patients in Acute Physiology and Chronic Health Evaluation (APACHE II) scores <25 group (RR 0.64, 95% CI 0.52–0.78, P < 0.0001) and sepsis group (RR 0.48, 95% CI 0.32–0.72, P = 0.0003) significantly decreased after PMX-HP treatment. The result also showed that PMX-HP could reduce endotoxin levels [Standardized mean difference (SMD) -1.53, 95% CI -2.92– -0.13, P = 0.03] and improve mean arterial pressure (SMD 1.07, 95% CI 0.14–2.01, P = 0.02). Serious adverse events between the PMX-HP group and standard therapy group were not significantly different (RR 2.16, 95% CI 0.97–4.80, I² = 0%, P = 0.06). However, TSA did not provide conclusive evidence and more high quality RCTs were required.ConclusionUsing PMX-HP to treat patients with less severe sepsis can reduce overall mortality and is safe. Treatment efficacy may benefit from the reduction of endotoxin level and the improvement of hemodynamics. More high quality RCTs are required to further evaluate the clinical role of PMX-HP against severe sepsis or septic shock.     

Risk of major bleeding associated with aspirin use in non-surgical critically ill patients receiving therapeutic anticoagulation

BackgroundWe aimed to evaluate the risk of major bleeding in non-surgical critically ill patients who received aspirin in conjunction with therapeutic anticoagulation (concomitant therapy) compared to those who received therapeutic anticoagulation alone.MethodsThis is a retrospective cohort study of critically ill patients initiated on therapeutic anticoagulation at a large academic medical center from 2007 to 2016. The exposure of interest was aspirin therapy during anticoagulation. The primary outcome was the incidence of major bleeding during hospitalization. Secondary outcomes included in-hospital mortality, hospital free days, and new myocardial infarction or stroke.Results5507 (73.2%) patients received anticoagulation alone and 2014 (26.8%) received concomitant therapy; major bleeding occurred in 19.0% and 22.2%, respectively. There was no increased risk of major bleeding [OR 1.10 (95% CI: 0.93–1.30); p = .27] or mortality [OR 0.93 (95% CI: 0.77–1.11); p = .43] with concomitant therapy. Patients receiving concomitant therapy had fewer hospital-free days (mean decrease of 0.73 [1.36, 0.09]; p = .03) and were more likely to experience new myocardial infarction or stroke [OR 2.61 (95% CI: 1.72–3.98); p < .001].ConclusionsIn non-surgical critically ill patients receiving therapeutic anticoagulation, concomitant use of aspirin was not associated with an increased risk of bleeding or in-hospital mortality.