Openness Personality Trait Associated With Benefit From a Nonpharmacological Breathlessness Intervention in People With Intrathoracic Cancer: An Exploratory Analysis

ContextBreathlessness is common in people with lung cancer. Nonpharmacological breathlessness interventions reduce distress because of and increase mastery over breathlessness.ObjectivesIdentify patient characteristics associated with response to breathlessness interventions.MethodsExploratory secondary trial data analysis. Response defined as a one-point improvement in 0–10 Numerical Rating Scale of worst breathlessness/last 24 hours (response—worst) or a 0.5-point improvement in the Chronic Respiratory Questionnaire (CRQ) mastery (response—mastery) at four weeks. Univariable regression explored relationships with plausible demographic, clinical, and psychological variables followed by multivariable regression for associated (P < 0.05) variables.ResultsAbout 158 participants with intrathoracic cancer (mean age 69.4 [SD 9.35] years; 40% women) were randomized to one or three breathlessness training sessions. About 91 participants had evaluable data for response—worst and 107 for response—mastery. In the univariable analyses, the personality trait openness was associated with response—worst (odds ratio [OR] 1.99 [95% CI 1.08–3.67]; P = 0.028) and response—mastery (OR 1.84 [95% CI 1.04–3.23]; P = 0.035). Higher CRQ—fatigue (OR 0.61 [95% CI 0.41–0.91]; P = 0.015), CRQ—emotion (OR 0.68 [95% CI 0.47–0.96]; P = 0.030), and worse CRQ—mastery (OR 0.61 [95% CI 0.42–0.88]; P = 0.008), and the presence of metastases and fatigue were associated with reduced odds of response—mastery. In the adjusted response—mastery model, only openness remained (OR 1.73 [95% CI 0.95–3.15]; P = 0.072).ConclusionWorse baseline health, worse breathlessness mastery, but not severity, and openness were associated with a better odds of response. Breathlessness services must be easy to access, and patients should be encouraged and supported to attend.     

Risk of diabetes with fibrates and statins: a pharmacoepidemiological study in VigiBase®

In contrast to statins, the risk of diabetes with fibrates was not clearly studied. This study investigates a putative signal of diabetes associated with the use of fibrates using the World Health Organization (WHO) global individual case safety reports database, VigiBase^®. We included all reports registered until the 31st December 2017 in VigiBase^® to measure the risk of reporting ‘hyperglycemia or new onset of diabetes’ (SMQ term) compared with all other reports [as a reporting odds ratio (ROR 95% CI)] for fibrates, statins, and the combination fibrates + statins. The likelihood that diabetes resulted from statin–fibrate interaction was also estimated. According to the interaction additive model, a ROR value for coexposure exceeding the sum of the RORs estimated for each individual class of drug supports a potential drug–drug interaction (DDI). To assess the stability of our results, we performed several sensitivity analyses, according to outcome definition and after exclusion of putative competitive (hyperglycemic) drugs. We included 19 149 patients exposed to fibrates (without statins), 177 323 to statins (without fibrates) and 3 247 to statins plus fibrates. In contrast to statins (ROR = 1.75, 95% CI 1.72–1.78), no association was found for fibrates (ROR = 0.76, 95% CI 0.71–0.82). The ROR value was lower for the combination statins plus fibrates (ROR = 1.46, 95% CI 1.28–1.67). Similar trends were found in sensitivity analyses. This study, performed in the real conditions of use, failed to find a signal of diabetes with fibrates. It strengths the association previously described with statin without any evidence for a statin–fibrate DDI.     

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.     

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.     

Pharmacologic Prophylaxis of Stress Ulcer in Non-ICU Patients: A Systematic Review and Network Meta-analysis of Randomized Controlled Trials

PurposeAcid-suppressive medications are widely used in non–intensive care unit (non-ICU) patients for stress ulcer (SU) prophylaxis. However, SU prophylaxis in this population is still controversial. The purpose of this study was to systematically evaluate the efficacy and tolerability of these agents for SU prophylaxis in non-ICU patients.MethodsElectronic databases including Cochrane, ClinicalTrials.gov, Ovid-Medline, Embase, Chinese CNKI, and Wanfang Data were systematically searched on July 10, 2019, for randomized controlled trials (RCTs) that evaluated acid-suppressive medications in non-ICU patients. Network meta-analysis and pairwise meta-analysis were performed to calculate odds ratios (ORs) and 95% CIs. A random-effects model was used for generating pooled estimates. The primary outcome was occurrence of SU bleeding, and the adverse drug events (ADEs) were described as the secondary outcome.FindingsA total of 17 RCTs involving 1985 patients were eligible. Meta-analysis results indicated that the occurrence of SU bleeding was significantly decreased with all acid-suppressive medications compared with placebos (gastric mucosa protectants, OR = 0.29 [95% CI, 0.14–0.61]; H2-receptor antagonists, OR = 0.3 [95% CI, 0.18–0.50]; proton pump inhibitors [PPIs]: OR = 0.08 [95% CI, 0.04–0.16]). The occurrence of SU bleeding was significantly decreased with PPIs compared with gastric mucosa protectants (OR = 0.29; 95% CI, 0.12–0.72) and H2-receptor antagonists (OR = 0.28; 95% CI, 0.16–0.48). There was no significant difference between any 2 classes of PPIs on SU bleeding or any 2 acid-suppressive medications on ADEs.ImplicationsPPIs could significantly decrease SU bleeding risk without increasing ADEs than other acid-suppressive medications for SU prophylaxis in non-ICU patients. However, RCTs of high quality were required to confirm the findings of this investigation.     

Comparative Prevalence of Acute Kidney Injury in Chinese Patients Receiving Vancomycin with Concurrent β-Lactam Antibiotics: A Retrospective Cohort Study

PurposeThe combination of vancomycin and piperacillin/tazobactam (VAN + PTZ) provides a broad spectrum of activity against multiple pathogens. However, a major issue in previous research concerned significant nephrotoxicity associated with this drug combination, and most studies have been conducted in American and European countries, with no similar data available from China. Therefore, this study evaluated the nephrotoxic effects of VAN + PTZ in a large-scale Chinese cohort to determine the prevalence of acute kidney injury (AKI) in this population by comparing PTZ and vancomycin monotherapies and the combined use of vancomycin and β-lactam antibiotics.MethodsThis retrospective cohort study identified adult patients who received vancomycin either as monotherapy or in combination with PTZ or carbapenem (VAN + CAR) for at least 48 hours at Jiangsu Province Hospital from January 1, 2017, to December 31, 2018. Patients were also evaluated for the development of AKI, defined according to the Kidney Disease Improving Global Outcome criteria. Duration of vancomycin exposure, steady-state trough vancomycin concentrations, and other risk factors for AKI were assessed. A Bayesian network meta-analysis was conducted to validate our results and comparatively evaluate the nephrotoxicity of β-lactam antibiotics in combination with vancomycin.FindingsIn all, 752 patients were included in the present study. The prevalence of AKI was higher in the VAN + PTZ group than in the VAN and VAN + CAR groups (15.2% vs 4.0% and 6.0%, respectively). After adjustment for confounding factors, VAN + PTZ was still related to AKI (odds ratio [OR] = 4.37; 95% CI, 1.65–11.59; P = 0.003). The network meta-analysis indicated that VAN + PTZ was associated with a significantly higher risk for AKI than was VAN (OR = 3.23; 95% CI, 2.50–4.35), PTZ (OR = 2.86; 95% CI, 1.92–4.12), VAN + cefepime (FEP) (OR = 2.37; 95% CI, 1.80–3.19), or VAN + CAR (OR = 2.28; 95% CI, 1.64–3.21). However, there was no significant difference with respect to AKI prevalence among the VAN, PTZ, VAN + FEP, and VAN + CAR groups.ImplicationsThe prevalence of AKI was higher with VAN + PTZ therapy than with VAN or PTZ monotherapy or with the concurrent use of VAN and FEP or CAR in our study. Clinicians should adequately assess renal function and consider this differential risk for nephrotoxicity when choosing empiric antibiotics in hospitalized patients to minimize the rates of AKI.     

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.     

Should age be incorporated into the adult triage algorithm in the emergency department?

ObjectiveTo compare resource utilization and mortality between older and younger adult patients with similar ED chief complaints and ESI triage levels.MethodsThis was an observational study of consecutive adult patients (age ≥ 40) who presented to an academic ED over a 1-year period with chest pain, abdominal pain, altered mental status, generalized weakness, or headache. Patients were categorized into 40–64, 65–79, and ≥ 80-year old groups. Mortality and utilization outcomes were compared between age groups through logistic regression models or Cox proportional hazards adjusting for ESI level and chief complaint. Odds ratios (OR) and hazard ratios (HR) were calculated with 95% confidence intervals (CI).ResultsA total of 9798 ED visits were included. As compared to younger adults (age 40–64), older adults, independently of ESI level and chief complaint, had higher ED laboratory use (OR 1.46 [CI 1.29, 1.66] for age 65–80; OR 1.33 [CI 1.15, 1.55] for age ≥ 80), ED radiology use (OR 1.40 [CI 1.26, 1.56]; OR 1.48 [CI 1.30, 1.69]), hospital admission (OR 1.56 [CI 1.42, 1.72]; OR 1.97 [CI 1.75, 2.21]), and ICU admission (OR 1.38 [CI 1.15, 1.65]; OR 1.23 [CI 0.99, 1.52]). Despite similar ESI and chief complaint, patients age 65–79 and ≥ 80 had higher 30-day mortality rates (HR 1.87 [CI 1.39 to 2.51] and 2.47 [CI 1.81 to 3.37], respectively).ConclusionsOlder adults with similar chief complaints and ESI levels than younger adults, have significantly higher ED resource use, hospitalization rates, and mortality.     

Short-term Evidence in Adults of Anorexigenic Drugs Acting in the Central Nervous System: A Meta-Analysis

PurposeObesity is a chronic clinical condition that is considered one of the most serious health problems in the world because it can cause other chronic metabolic disorders. A meta-analysis was conducted to evaluate the safety and efficacy of 4 central-acting drugs, all approved in Brazil's market for weight loss.MethodsPubMed, EMBASE, and Cochrane library databases were searched from inception until January 2018 to retrieve randomized controlled trials comparing sibutramine, diethylpropion, mazindol, and fenproporex versus placebo in overweight or obese patients. Language was not a restriction for the database searches. We extracted and combined data from studies that reported adverse drug events and weight change. A random effects meta-analytic model was applied in all calculations. The Cochrane Collaboration tool was used to assess the quality and bias of all included studies. Quality of evidence was assessed by using the Grading of Recommendations, Assessment, Development, and Evaluation criteria.FindingsFifty-three studies were included, with a total of 16,903 patients with a median follow-up of 12 weeks (2–260 weeks). The appetite suppressants showed a significant weight loss compared with placebo (mean difference [MD], −4.70 kg; 95% CI, −5.25 to −4.15; I² = 100%; 43 studies). There was an increased total number of adverse events, dry mouth, constipation, insomnia, dizziness, and tachycardia reported in the intervention group (risk ratio [RR], 1.06; 95% CI, 1.01 to 1.10; I² = 20% [22 studies]; RR, 2.08; 95% CI, 1.76 to 2.47; I² = 34% [25 studies]; RR, 2.31; 95% CI, 1.88 to 2.84; I² = 0% [25 studies]; RR, 1.84; 95% CI, 1.40 to 2.39; I² = 0% [17 studies]; RR, 1.78; 95% CI, 1.24 to 2.58; I² = 0% [13 studies]; and RR, 2.01; 95% CI, 1.42 to 2.86; I² = 0% [10 studies], respectively). Sibutramine showed a significant increase in heart rate and mean diastolic pressure compared with placebo (MD, 4.17 beats/min [95% CI, 3.60 to 4.74; I² = 99%; 23 studies]; MD, 1.68 mm Hg [95% CI, 1.29 to 2.07; I² = 98%; 22 studies]).ImplicationsThese drugs are effective for weight loss in overweight and obese patients; however, they increase the risk of adverse events. In fact, the evidence is of low quality, the data availability of studied agents (especially for cardiovascular outcomes) are limited, and the studies are of short duration. PROSPERO identifier: CRD42018091083.     

Adverse events and practice variability associated with paediatric endotracheal suction: An observational study

ObjectiveThe objective of this study was to determine the incidence of endotracheal tube (ETT) suction–related adverse events (AEs) and to examine associations between AEs and patient and suction characteristics. Secondary objectives were to describe ETT suction practices in an Australian paediatric intensive care unit (PICU).MethodsA prospective, observational study was undertaken in a mixed cardiac and general PICU. Children were eligible for inclusion if they were intubated and mechanically ventilated. Data on patient and suction variables (indication for ETT suction, number of suction episodes per mechanical ventilation episode, indication for normal saline instillation [NSI] and NSI dose) including potential predictive variables (age, Paediatric Index of Mortality 3 [PIM3], NSI, positive end-expiratory pressure, and hyperoxygenation) were collected. The main outcome variable was a composite measure of any AE.Main resultsA total of 955 suction episodes were recorded in 100 children. AEs occurred in 211 (22%) ETT suctions. Suction-related AEs were not associated with age, diagnostic category, or index of mortality score. Desaturation was the most common AE (180 suctions; 19%), with 69% of desaturation events requiring clinician intervention. Univariate logistic regression showed the odds of desaturation decreased as the internal diameter of the ETT increased (odds ratio [OR]: 0.59; 95% confidence interval [CI]: 0.37–0.95; p = 0.028). Multivariable modelling revealed NSI was significantly associated with an increased risk of desaturation (adjusted OR [aOR]: 3.23; 95% CI: 1.99–5.40; p < 0.001) and the occurrence of an AE (aOR: 2.76; 95% CI: 1.74–4.37; p < 0.001). Presuction increases in fraction of inspired oxygen (FiO₂) was significantly associated with an increased risk of experiencing an AE (aOR: 2.0; 95% CI: 1.27–3.15; p = 0.003).ConclusionsETT suction–related AEs are common and associated with NSI and the requirement for pre-suction increases in FiO₂. Clinical trial data are needed to identify high-risk patient groups and to develop interventions which optimise practice and reduce the occurrence of ETT suction–related AEs.     

The Effect of Music on Pain in the Adult Intensive Care Unit: A Systematic Review of Randomized Controlled Trials

ContextMultimodal analgesic approaches are recommended for intensive care unit (ICU) pain management. Although music is known to reduce pain in acute and chronic care settings, less is known about its effectiveness in the adult ICU.ObjectivesDetermine the effects of music interventions on pain in the adult ICU, compared with standard care or noise reduction.MethodsThis review was registered on PROSPERO (CRD42018106889). Databases were searched for randomized controlled trials of music interventions in the adult ICU, with the search terms [“music*” and (“critical care” or “intensive care”)]. Pain scores (i.e., self-report rating scales or behavioral scores) were the main outcomes of this review. Data were analyzed using a DerSimonian-Laird random-effects method with standardized mean difference (SMD) of pain scores. Statistical heterogeneity was determined as I² > 50% and explored via subgroup analyses and meta-regression.ResultsEighteen randomized controlled trials with a total of 1173 participants (60% males; mean age 60 years) were identified. Ten of these studies were included in the meta-analysis based on risk of bias assessment (n = 706). Music was efficacious in reducing pain (SMD −0.63 [95% CI −1.02, −0.24; n = 10]; I² = 87%). Music interventions of 20–30 minutes were associated with a larger decrease in pain scores (SMD −0.66 [95% CI −0.94, −0.37; n = 5]; I² = 30%) compared with interventions of less than 20 minutes (SMD 0.10 [95% CI −0.10, 0.29; n = 4]; I² = 0%). On a 0–10 scale, 20–30 minutes of music resulted in an average decrease in pain scores of 1.06 points (95% CI −1.56, −0.56).ConclusionMusic interventions of 20–30 minutes are efficacious to reduce pain in adult ICU patients able to self-report.     

Optimal trough concentration of voriconazole with therapeutic drug monitoring in children: A systematic review and meta-analysis

ObjectivesThis systematic review and meta-analysis was designed to determine the optimal trough concentration of voriconazole for children with invasive fungal infections (IFIs).MethodsWe searched electronic databases (PubMed, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov and Japana Centra Revuo Medicina) for clinical studies describing the voriconazole trough concentration. We used stepwise cut-off values of 1.0–2.0 mg/L for efficacy and 3.0–6.0 mg/L for safety. The efficacy outcomes were treatment success and all-cause mortality, and the safety outcomes were hepatotoxicity, neurotoxicity and all-cause adverse events.ResultsNine studies involving 211 patients were included in the analysis. The probability of treatment success against IFIs was significantly increased at cut-off values of ≥1.0 mg/L (odds ratio [OR] = 2.65, 95% confidence interval [CI] = 1.20–5.87). Our analysis did not find any relationship between the trough concentration and survival. Concerning safety, the occurrence of any outcomes did not significantly differ according to the voriconazole trough concentrations at any cut-off value. However, in a subgroup analysis of Asian study locations, a significantly higher risk of hepatotoxicity was demonstrated at voriconazole trough cut-off values ≥ 3.0 mg/L (OR = 8.40, 95% CI = 1.36–51.92). Although a significant correlation between the voriconazole concentration and hepatotoxicity was evident in regression curve analysis, (y = 0.1198e^0.2298x), no correlation was demonstrated for neurotoxicity (y = 0.3913e^?0.008x).ConclusionOur findings suggest that the optimal trough concentration for increasing clinical success and minimizing hepatotoxicity during voriconazole therapy in children with IFIs, particularly for Asian populations, is 1.0–3.0 mg/L.     

Impact of the pre-illness lipid profile on sepsis mortality

PurposeTo determine if baseline lipid levels contribute to the relationship between lipid levels during sepsis and outcomes.Materials and methodsWe conducted a retrospective cohort study at a tertiary-care academic medical center. Multivariable logistic regression models were used to adjust for confounders. Both Systemic Inflammatory Response Syndrome (SIRS) and Sequential Organ Failure Assessment (SOFA) score-based definitions of sepsis were analyzed.Measurements and main resultsAfter adjusting for patient characteristics and severity of illness, baseline values for both low density lipoprotein (LDL) cholesterol and triglycerides were associated with mortality (LDL cholesterol odds ratio [OR] 0.44, 95% confidence interval [CI] 0.23–0.84, p = .013; triglyceride OR 0.54, 95% CI 0.37–0.78, p = .001) using a SIRS based definition of sepsis. An interaction existed between these two variables, which resulted in increased mortality with higher baseline low density lipoprotein (LDL) cholesterol values for individuals with triglycerides below 208 mg/dL and the opposite direction of association above this level (interaction OR 1.48, 95% CI 1.02–2.16, p = .039). When using a SOFA score-based definition, only triglycerides remained associated with the mortality (OR 0.55, 95% CI 0.35–0.86, p = .008).ConclusionsBaseline lipid values, particularly triglyceride concentrations, are associated with hospital mortality in septic patients.     

Health Care Cost in Patients With Schizophrenia Treated With Brexpiprazole Versus Other Oral Atypical Antipsychotic Therapy

PurposeBrexpiprazole is an oral atypical antipsychotic (OAA) for the treatment of schizophrenia (SCZ). This study compared all-cause and psychiatric inpatient hospitalization and medical costs in adult patients with SCZ newly treated with brexpiprazole versus other US Food and Drug Administration–approved OAAs in a real-world setting.MethodsThis retrospective cohort study analyzed data from: (1) the IBM MarketScan Commercial and Medicare Supplemental databases, and the MarketScan Multi-State Medicaid database; and (2) the de-identified Optum Clinformatics Datamart. Adult patients were identified if they had SCZ and initiated either brexpiprazole or another OAA during the study identification period (July 1, 2015, to September 30, 2016, for MarketScan Commercial and Medicare Supplemental and for Optum; July 1, 2015, to June 30, 2016, for MarketScan Multi-State Medicaid) and had ≥12 months of continuous enrollment before (baseline) and after (follow-up) the first treatment date. Linear regression analyses were performed to test associations between treatment groups (brexpiprazole vs another OAA) and costs (total and medical); negative binomial regression models were used to estimate number of hospitalizations per year, adjusting for baseline characteristics and medication adherence to index treatment during the 12-month follow-up.FindingsThe final study sample consisted of 6254 patients with SCZ: 176 initiated brexpiprazole; 391, ziprasidone; 453, paliperidone; 523, lurasidone; 786, aripiprazole; 1234, quetiapine; 1264, olanzapine; and 1427, risperidone. Controlling for baseline characteristics and medication adherence, the adjusted number of hospitalizations (both all-cause and psychiatric), all-cause total costs, and all-cause medical costs did not differ across groups. Brexpiprazole users had the lowest mean psychiatric costs among all OAA users ($12,013; 95% bootstrap CI, 7488–16,538). Compared with brexpiprazole users, paliperidone (incidence rate ratio [95% CI], 1.52 [1.05–2.19]; P = 0.027) and quetiapine (incidence rate ratio [95% CI], 1.47 [1.04–2.07]; P = 0.029) users had more psychiatric hospitalizations per year. Paliperidone had higher psychiatric costs than brexpiprazole (total, $32,066 [95% bootstrap CI, 28,779–35,353] vs $23,851 [18,907–28,795]; medical, $19,343 [16,294–22,392] vs $12,013 [7488–16,538]). Psychiatric medical costs were also $6744 higher in olanzapine users (95% bootstrap CI, 1694–11,795; P = 0.009) than in brexpiprazole users.ImplicationsPatients with SCZ treated with brexpiprazole had fewer psychiatric hospitalizations and lower psychiatric costs than those treated with paliperidone. Differences in the number of all-cause hospitalizations and medical costs among treatments were not statistically significant. Although treatment decisions are driven by a number of factors (eg, clinical circumstances and drug costs), choice of OAA may affect health care costs.     

Effect of the Renin-Angiotensin System Inhibitors on Inflammatory Markers: A Systematic Review and Meta-analysis of Randomized Controlled Trials

ObjectiveTo synthesize more conclusive evidence on the anti-inflammatory effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs).MethodsPubMed, Scopus, and Embase were searched from inception until March 1, 2021. We included randomized controlled trials (RCTs) that assessed the effect of ACEIs or ARBs, compared with placebo, on any of the following markers: C-reactive protein (CRP), interleukin 6 (IL-6), or tumor necrosis factor α (TNF-α). Mean changes in the levels of these markers were pooled as a weighted mean difference (WMD) with a 95% CI.ResultsThirty-two RCTs (n=3489 patients) were included in the final analysis. Overall pooled analysis suggested that ACEIs significantly reduced plasma levels of CRP (WMD, ?0.54 [95% CI, ?0.88 to ?0.21]; P=.002; I²=96%), IL-6 (WMD, ?0.84 [95% CI, ?1.03 to ?0.64]; P<.001; I²=0%), and TNF-α (WMD, ?12.75 [95% CI, ?17.20 to ?8.29]; P<.001; I²=99%). Moreover, ARBs showed a significant reduction only in IL-6 (WMD, ?1.34 [95% CI, ?2.65 to ?0.04]; P=.04; I²=85%) and did not significantly affect CRP (P=.15) or TNF-α (P=.97) levels. The lowering effect of ACEIs on CRP levels remained significant with enalapril (P=.006) and perindopril (P=.01) as well as with a treatment duration of less than 24 weeks (WMD, -0.67 [95% CI, ?1.07 to -0.27]; P=.001; I²=94%) and in patients with coronary artery disease (WMD, ?0.75 [95% CI, ?1.17 to ?0.33]; P<.001; I²=96%).ConclusionBased on this meta-analysis, ACEIs showed a beneficial lowering effect on CRP, IL-6, and TNF-α, whereas ARBs were effective as a class in reduction of IL-6 only.     

Initiation of breast-feeding practice and associated factors among mothers who have infants less than 12 months of age in Debre Tabor Town,North West Ethiopia, 2021: A multicenter community-based cross-sectional study

Introductioninitiation of breastfeeding is crucial in preventing newborn deaths and influences childhood nutrition. There was limited updated evidence regarding early initiation of breast-feeding practice and associated factors among the target population in the study area.ObjectiveTo assess initiation of breastfeeding practice and its associated factors among mothers who have infants less than six months of age in, North West Ethiopia, 2020.MethodsThe Community based quantitative cross-sectional study was conducted among 405 respondents in the stud area, then data would be entered and analyzed by using SPSS version 20 statistical packages. Bivariate and multivariable logistic regression model analysis would be done. Odds ratio with 95% confidence was computed to determine the level of significance-value less than 0.05 considered as significant.ResultThis study showed that 94.7% of mothers in Debre Tabor Town practiced initiation of breastfeeding for their infants within the Less Than 12 Months of age. In multivariable analysis I n f a n t S e x, Female [AOR (95% CI) = 0.068 (0.002, 1.659), and Age of Mother 20–24 years [AOR (95% CI) = 2.33 (0.030, 17.12)], 25–29 years ((AOR = 8.20 [(95% CI: 12.212, 22.189]), and 30–34 years (AOR = 4.48 [95% CI: 0.463, 15.478], Assists (Attend) during delivery, Doctor (AOR = 0.644 [95% CI: 0.041, 10.138]) and Encourage BF by religious father (AOR = 6.669 [(95% CI: 4.27, 8.895]) were remained significantly associated with the outcome variable with at 95% CI and P- value of <0.05.Conclusionand Recommendation: The prevalence of EIBF among mother-infant pairs of less than 12 months in debre tabor town, Northwest, Ethiopia, was found to be high as compared to national and global infant and young child feeding guidelines. However; it shows improvement as compared with some previous studies in Ethiopia. I n f a n t s e x, age of mother, assists during delivery, and encourage BF by religious father were factors associated with outcome in the stud area.     

Development and validation of a short version of the French Hand Function Sort questionnaire in vocational rehabilitation

BackgroundThe Hand Function Sort (HFS) is a pictorial self-administered questionnaire with 62 items. It is a valid and reliable scale focused on the physical function of the upper limbs. It is used to predict the return to work.ObjectivesWe aimed to develop and validate a short version of the French version of the HFS (HFS-F) to simplify its use in clinical practice.MethodsWe included patients with upper-limb chronic pain hospitalised for vocational rehabilitation from 2012 to 2019. Vocational rehabilitation aims to improve the autonomy of patients to regain their previous working capacity. The 62 items of the HFS-F were analysed in terms of patient and expert assessments, floor/ceiling effect, item-to-total correlation, principal component analysis, and Rasch analysis. A short HFS-F was developed. Thereafter, we assessed its internal consistency, test–retest reliability, criterion validity with the full-length HFS-F, construct validity with different scales (Disabilities of the Arm, Shoulder, and Hand [DASH]; Brief Pain Inventory [BPI]; Hospital Anxiety and Depression [HAD]), standard error of measurement (SEM), and minimal detectable change (MDC).ResultsSix experts were consulted, 34 patients were interviewed, and 629 questionnaires were analysed. Among the items, 25 were selected after the final round with the six experts. The internal consistency and test–retest reliability were excellent (Cronbach α = 0.95, intraclass correlation coefficient = 0.92, 95% confidence interval [95% CI] 0.87 to 0.95). The correlation coefficient between scores of the short and full-length HFS-F was 0.841 (95% CI: 0.752 to 0.897, P < 10–4), and those between the short HFS-F score and the DASH, BPI, HAD-Anxiety, and HAD-Depression scores were ?0.816 (95% CI: ?0.714 to ?0.881, P < 10–4), ?0.529 (95% CI: ?0.338 to ?0.674, P < 10–4), ?0.451 (95% CI: ?0.244 to 0.614, P = 0.0001), and ?0.360 (95% CI: ?0.140 to ?0.542, P = 0.0018), respectively. The SEM and MDC values were estimated at 6/100 and 17/100, respectively.ConclusionsA short version of the HFS-F was developed and validated. We named this questionnaire the 25 HFS-F.     

Reactogenicity following two doses of the BNT162b2 mRNA COVID-19 vaccine: Real-world evidence from healthcare workers in Japan

As the first authorized COVID-19 vaccine in Japan, the BNT162b2 mRNA COVID-19 vaccine is utilized for mass vaccination. Although efficacy has been proved, real-world evidence on reactogenicity in Japanese personnel is needed to prepare the public. Healthcare workers in a large academic hospital in Japan received two doses of the Pfizer-BioNTech vaccine from March 17 to May 19, 2021. Online questionnaires were distributed to registered recipients following each dose, from day 0 through day 8. Primary outcomes are the frequency of reactogenicity including local and systemic reactions. Length of absence from work was also analyzed. Most recipients self-reported reactogenicity after the first dose (97.3%; n = 3254; mean age [36.4]) and after the second dose (97.2%; n = 3165; mean age [36.5]). Systemic reactions following the second dose were substantially higher than the first dose, especially for fever (OR, 27.38; 95% CI, [22.00–34.06]; p < 0.001), chills (OR, 16.49; 95% CI, [13.53–20.11]; p < 0.001), joint pain (OR, 8.49; 95% CI, [7.21–9.99]; p < 0.001), fatigue (OR, 7.18; 95% CI, [6.43–8.02]; p < 0.001) and headache (OR, 5.43; 95% CI, [4.80–6.14]; p < 0.001). Reactogenicity was more commonly seen in young, female groups. 19.3% of participants took days off from work after the second dose (2.2% after the first dose), with 4.7% absent for more than two days. Although most participants reported reactogenicity, severe cases were limited. This study provides real-world evidence for the general population and organizations to prepare for BNT162b2 mRNA COVID-19 vaccination in Japan and other countries in the region.     

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.     

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.