A cumulative Bayesian network meta-analysis on the comparative efficacy of pharmacotherapies for mania over the last 40 years.

RATIONALE: Mania (or manic episodes) is a common symptom of bipolar disorder and is frequently accompanied by hyperactivity and delusions; given the cost and resources available, there is a paucity of evidence for direct comparison of different drugs. OBJECTIVES: We aimed to provide evidence-based recommendations on the efficacy of overall currently used pharmacological treatments for patients with acute bipolar mania. METHOD: We conducted a systematic review and network meta-analysis (NMA) using a Bayesian network frame. We searched the primary literature databases without language restrictions until Dec 18, 2021, for reports of randomized controlled trials (RCTs) of suspected antimanic drugs used as monotherapy for patients with acute bipolar mania, with the primary outcomes being efficacy (mean difference (MD), standardized mean difference (SMD) in the change of mania score). RESULTS: Eighty-seven studies were included in which 18,724 manic participants (mean age = 34.6 years, with 50.36% males) were allocated at random to one of 25 active medication drug therapies or placebo, resulting in 87 direct comparisons on 192 data points. Tamoxifen (- 22·00 [- 26·00 to - 18·00]) had the best efficacy over the placebo. Meanwhile, risperidone (- 6·60 [- 8·40 to - 4·90]) was substantially more effective than placebo in treating acute mania. Carbamazepine, haloperidol, ziprasidone, cariprazine, olanzapine, quetiapine, aripiprazole, lithium, paliperidone, asenapine, and divalproex were noticeably more effective than placebo. CONCLUSIONS: Overall, tamoxifen appears to be the most effective of the currently known pharmaceutical therapy available to treat acute mania or manic episodes; however, this conclusion is restricted by the scale of RCTs conducted, and risperidone was found to be the most effective medication among antipsychotics. Carbamazepine, haloperidol, ziprasidone, cariprazine, olanzapine, quetiapine, aripiprazole, lithium, paliperidone, asenapine, and divalproex were noticeably effective in treating acute mania or manic episodes.

Transesophageal echocardiography instead or in addition to transthoracic echocardiography in evaluating haemodynamic problems in intubated critically ill patients.

BACKGROUND: Transesophageal echocardiography (TEE) performed by intensivists is increasingly used in critically ill patients. However, TEE is usually not the preferred monitoring tool, especially when transthoracic echocardiography (TTE) appears to have addressed the clinical problems. As a result, it remains largely unknown whether TEE is a clinically valuable replacement or supplement for TTE as a primary tool in evaluating haemodynamic problems in critically ill surgical patients. The purpose of this study was to assess the diagnostic and therapeutic value of TEE instead or in addition to TTE in critically ill surgical patients with hemodynamic instability. METHODS: A prospective observational study was conducted. A total of 68 consecutive patients were enrolled from December 2016 to February 2018. TEE was routinely performed in addition to TTE, and the imaging data from TTE and TEE were successively disclosed to two different primary physicians, who reported any resulting changes in management. The two physicians were required to reach a consensus if there was any disagreement. The results of the additional TEE examination were compared with the clinical findings and TTE information. The image quality of TTE views was classified as a good (score 2), suboptimal (score 1) or poor view (score 0). According to the scores of TTE images, the patients were divided into two groups: patients with adequate TTE views (score ≥6) and inadequate TTE views (score <6). RESULTS: The results of additional TEE examination were classified into four categories. TEE failed to provide additional information about the initial diagnosis and therapy (class 1) in 26 patients (38.2%). Of the remaining 42 patients (61.8%), TEE instead or in addition to TTE revealed new findings or led to significant changes in therapy, as TTE supplied inadequate information. TEE used in addition to TTE led to a new diagnosis without therapeutic implications (class 2) in 11 patients (16.2%) and made a major clinical contribution leading to a therapeutic change (class 3) in 23 patients (33.8%). TEE used instead of TTE determined the diagnosis and therapy in 8 patients (11.8%) whose haemodynamic problems could not be addressed by TTE (class 4). In total, TEE had critical therapeutic benefits (class 3 and 4) that was not provided by TTE in 31 patients (45.6%). Of particular concern was that TEE had a higher proportion of therapeutic benefits to patients with inadequate TTE views than those with adequate TTE views (54.3% vs. 27.3%, P=0.036). CONCLUSIONS: TEE as a feasible clinical tool is useful for critically ill surgical patients with hemodynamic instability, especially for the patients with inadequate TTE views. TEE instead or in addition to TTE could provide valuable information for diagnosis, which may bring significant therapeutic benefits.

Does Respiratory Variation in Inferior Vena Cava Diameter Predict Fluid Responsiveness in Mechanically Ventilated Patients? A Systematic Review and Meta-analysis.

BACKGROUND: We performed a systematic review and meta-analysis of studies investigating the diagnostic accuracy of respiratory variation in inferior vena cava diameter (ΔIVC) for predicting fluid responsiveness in patients receiving mechanical ventilation. METHODS: MEDLINE, EMBASE, the Cochrane Library, and Web of Science were screened from inception to February 2017. The meta-analysis assessed the pooled sensitivity, specificity, diagnostic odds ratio, and area under the receiver operating characteristic curve. In addition, heterogeneity and subgroup analyses were performed. RESULTS: A total of 12 studies involving 753 patients were included. Significant heterogeneity existed among the studies, and meta-regression indicated that ventilator settings were the main sources of heterogeneity. Subgroup analysis indicated that ΔIVC exhibited better diagnostic performance in the group of patients ventilated with tidal volume (TV) ≥8 mL/kg and positive end-expiratory pressure (PEEP) ≤5 cm H2O than in the group ventilated with TV <8 mL/kg or PEEP >5 cm H2O, as demonstrated by higher sensitivity (0.80 vs 0.66; P = .02), specificity (0.94 vs 0.68; P < .001), diagnostic odds ratio (68 vs 4; P < .001), and area under the receiver operating characteristic curve (0.88 vs 0.70; P < .001). The best ΔIVC threshold for predicting fluid responsiveness was 16% ± 2% in the group of TV ≥8 mL/kg and PEEP ≤5 cm H2O, whereas in the group of TV <8 mL/kg or PEEP >5 cm H2O, this threshold was 14% ± 5%. CONCLUSIONS: ΔIVC shows limited ability for predicting fluid responsiveness in distinct ventilator settings. In patients with TV ≥8 mL/kg and PEEP ≤5 cm H2O, ΔIVC was an accurate predictor of fluid responsiveness, while in patients with TV <8 mL/kg or PEEP >5 cm H2O, ΔIVC was a poor predictor. Thus, intensivists must be cautious when using ΔIVC.

miR­23a downregulation modulates the inflammatory response by targeting ATG12­mediated autophagy.

Autophagy, part of the innate immune defense mechanisms, is activated during the initial phase of septic insult. Previous studies indicated that micro (mi)RNAs are additionally involved in the host response to sepsis; however, the association between miRNAs and autophagy during this process is not fully understood. To study the role of miRNA (miR)­23a in autophagy initiated by sepsis, macrophages treated with lipopolysaccharides, in addition to blood samples from patients, were evaluated for miR­23a expression levels. Cell viability, inflammatory mediators and autophagic markers were investigated following overexpression or inhibition of miR­23a. The results suggested that miR­23a was suppressed subsequent to septic insult, promoting autophagy and suppressing a hyper inflammatory response, leading to enhanced cell viability. A luciferase assay and western blot analysis confirmed ubiquitin­like protein ATG12 to be the target of miR­23a. The present study revealed that the downregulation of miR­23a regulates an inflammatory response during septic insult via autophagy promotion.

Effect of Systolic Cardiac Function on Passive Leg Raising for Predicting Fluid Responsiveness: A Prospective Observational Study.

BACKGROUND: Passive leg raising (PLR) represents a "self-volume expansion (VE)" that could predict fluid responsiveness, but the influence of systolic cardiac function on PLR has seldom been reported. This study aimed to investigate whether systolic cardiac function, estimated by the global ejection fraction (GEF) from transpulmonary-thermodilution, could influence the diagnostic value of PLR. METHODS: This prospective, observational study was carried out in the surgical Intensive Care Unit of the First Affiliated Hospital of Sun Yat-sen University from December 2013 to July 2015. Seventy-eight mechanically ventilated patients considered for VE were prospectively included and divided into a low-GEF (<20%) and a near-normal-GEF (≥20%) group. Within each group, baseline hemodynamics, after PLR and after VE (250 ml 5% albumin over 30 min), were recorded. PLR-induced hemodynamic changes (PLR-Δ) were calculated. Fluid responders were defined by a 15% increase of stroke volume (SV) after VE. RESULTS: Twenty-five out of 38 patients were responders in the GEF <20% group, compared to 26 out of 40 patients in the GEF ≥20% group. The thresholds of PLR-ΔSV and PLR-Δ cardiac output (PLR-ΔCO) for predicting fluid responsiveness were higher in the GEF ≥20% group than in the GEF <20% group (ΔSV: 12% vs. 8%; ΔCO: 7% vs. 6%), with increased sensitivity (ΔSV: 92% vs. 92%; ΔCO: 81% vs. 80%) and specificity (ΔSV: 86% vs. 70%; ΔCO: 86% vs. 77%), respectively. PLR-Δ heart rate could predict fluid responsiveness in the GEF ≥20% group with a threshold value of -5% (sensitivity 65%, specificity 93%) but could not in the GEF <20% group. The pressure index changes were poor predictors. CONCLUSIONS: In the critically ill patients on mechanical ventilation, the diagnostic value of PLR for predicting fluid responsiveness depends on cardiac systolic function. Thus, cardiac systolic function must be considered when using PLR. TRIAL REGISTRATION: Chinese Clinical Trial Register, ChiCTR-OCH-13004027; http://www.chictr.org.cn/showproj.aspx?proj=5540.