Hospital Clínic de Barcelona
  • Barcelona, Catalonia, Spain
Recent publications
Background : Time between Emergency Department (ED) and ST-segment elevation acute myocardial infarction (STEMI) activation time is a good indicator of ED quality. STEMI delays are of particular importance in some subgroups, such as women and the elderly. Objective : To determine the association of sex and age with activation time in STEMI patients admitted to the ED. Methods : An observational retrospective study was conducted including all patients admitted to the ED activated as a STEMI. The main variable was activation time. To evaluate the independent predictors of activation time, a multivariate logistic regression analysis was carried out, variables were sex, age, sex and age combined, chest pain, ST elevation in the electrocardiogram, and first medical contact (FMC) at the hospital's ED. Results : A total of 330 patients were included. They were classified by sex: 23.9% (78) women and 76.1% (249) men; and age: 51.1% (167) <65 yo and 48.9% (160) ≥65 yo. Women and elderly patients exhibited a more atypical presentation. Multivariate analysis shows that showed that elderly age (OR=1.976 95%; CI=1.257–3.104; p = 0.003) and FMC prior to attending the ED (OR=1.762; 95% CI=1.117–2.779; p = 0.015) were associated with a longer activation time. Women older than 65 years old showed the longest activation time. Conclusion : STEMI delays are longer in women and the elderly with atypical presentation. Age ≥65 and FMC outside the ED were associated with an increase in the activation time. This highlights the need to develop strategies to improve activation time for these specific patient groups.
Objective To evaluate the association between early postoperative hypoventilation in the last hour of the post-anesthesia care unit (PACU) stay and hypoventilation during the rest of the first 48 postoperative hours in the surgical ward. Design Sub-analysis of a clinical trial. Setting PACU and surgical wards of a single medical center. Patients Adults having abdominal surgery under general anesthesia. Interventions Monitoring with a respiratory volume monitor from admission to PACU until the earlier of 48 h after surgery or discharge. Measurements The exposure was having at least one low minute-ventilation (MV) event during the last hour of PACU stay, defined as MV lower than 40% the predicted value lasting at least 1 min. The primary outcome was low MV events lasting at least 2 min during the rest of the first 48 postoperative hours, while in the surgical ward. The secondary outcome was the rate of low MV events per monitored hour. Main results Data of 292 patients were analyzed, of which 20 (6.8%) patients had a low MV event in PACU. Low MV events in the surgical ward were found in 81 (28%) patients. All patients who had low MV events in PACU had events again in the ward, while 61/272 (22%) had an event in the ward but not in PACU. The incidence rate of low MV events per hour was 24 (95% CI: 13, 46) among patients having an event in the PACU, and 2 (1, 4) among those who did not. Conclusions In adults recovering from abdominal surgery, events of hypoventilation during the first postoperative hour are associated with similar events during the rest of the first 48 postoperative hours, with positive predictive value approaching 100%. Sixty-one patients had ward hypoventilation that was not preceded by hypoventilation in PACU.
Resumen El sangrado uterino anormal (SUA) es una de las patologías ginecológicas más comunes en mujeres en edad reproductiva. El sistema de clasificación de la Federación Internacional de Ginecología y Obstetricia (PALM-COEIN) armoniza las definiciones de los síntomas de hemorragia normal y anormal y clasifica las posibles causas subyacentes en causas estructurales y no estructurales. El objetivo de este manuscrito es revisar el diagnóstico radiológico de cada una de las causas estructurales de sangrado uterino anormal, examinar las indicaciones de las técnicas de radiología vascular intervencionista en el manejo del SUA y conocer el procedimiento de embolización de arterias uterinas, así como sus posibles complicaciones y contraindicaciones.
Autoinflammatory disorders is a group of inherited disorders characterized by recurrent episodes of fever and inflammation, in the absence of infections, neoplasia, or autoimmunity. These disorders have in common a dysregulated inflammatory response and among them, inflammasome-related autoinflammatory disorders or inflammasomopathies are a consequence of inappropriate activation of inflammasomes with the consequent overproduction of cytokines of the IL-1 family. However, other autoinflammatory disorders are type I interferonopathies, deficiency of ADA2, disorders associated with aberrant TNF or NF-κB signaling, and inflammatory actinopathies, in which some of them the inflammasome could be activated. These disorders are treated with anticytokines biological drugs, but novel small molecules targeting inflammasomes are promising new therapeutic approaches.
Background The EDCTP-TDR Clinical Research and Development Fellowship (CRDF) scheme has offered one-year clinical research training placements for early- and mid-career researchers from LMIC since 1999. Objective Using the results of a 2018 external evaluation of the CRDF, the current article aims to identify the principal benefits for the main stakeholders of the CRDF scheme as well as the main barriers to accessing these benefits. Method Data analysis was derived from an external evaluation of the CRDF scheme. Based on a logical framework approach, data for the external evaluation was collected through document review, interviews, focus groups, and questionnaires collected from the main stakeholder groups. The evaluation was structured along six main themes: relevance, effectiveness, efficiency, impact, sustainability, and equity. Results The current paper focuses on the expected benefits, unexpected benefits, and barriers to enjoying benefits of the scheme for key stakeholders. Discussion Expected benefits were aligned with the development of clinical research competencies, which is the objective of the scheme. Unexpected benefits centred on transferable professional skills in scientific leadership and knowledge translation. Barriers mainly were found around engagement with home institutions and the return and reintegration of fellows following the training period. Conclusions and Recommendations Recommendations include further engagement with and support for home institutions and developing a formal framework for the development of transferable professional competencies, including leadership and knowledge transfer competencies.
Background When genes responsible for normal embryonic development are abnormally expressed in adults, it can lead to tumor development. This can suggest that the same mechanism that controls embryonic differentiation can also control tumor differentiation. We hypothesize that the malignant phenotype of lung cancer cells could acquire benign characteristics when in contact with an embryonic lung microenvironment. We cultured two lung cancer cell lines in embryonic lung mesenchyme-conditioned medium and evaluated morphological, functional and molecular changes. Methods The human embryonic mesenchymal lung-conditioned medium (hEML-CM) was obtained by culturing lung cells from embryos in the pseudoglandular stage of development. The NSCLC cell lines A549 and H1299 we cultured in the hEML-CM and in a tumor-conditioned medium. Morphological changes were analyzed with optical and transmission electron microscopy. To evaluate the functional effect of conditioned medium in tumor cells, we analyzed cell proliferation, migration, colony formation capacity in 2D and 3D and in vivo tumor growth capacity. The expression of the pluripotency genes OSKM, the adenocarcinoma marker NKX2-1, the lung surfactant proteins SFTP, the myofibroblast marker MYH and DNMT3A/3B was analyzed with qRT-PCR and the presence of the myofibroblast markers vimentin and α-SMA with immunofluorescence. Transcriptomic analysis was performed using Affymetrix arrays. Results The A549 and H1299 cells cultured in hEML-CM lost their epithelial morphology, acquired mesodermal characteristics, and decreased proliferation, migration, and colony formation capacity in 2D and 3D, as well as reduced its capacity to growth in vivo. The expression of OSKM, NKX2-1 and SFTP decreased, while that of DNMT3A/3B, vimentin, α-SMA and MYH increased. Distant matrix analysis based on transcriptomic profile showed that conditioned cells were closer to myoblast and human lung fibroblast than to normal epithelial immortalized lung cells. A total of 1631 for A549 and 866 for H1299 differentially expressed genes between control and conditioned cells were identified. Conclusions To the best of our knowledge, this is the first study to report that stimuli from the embryonic lung can modulate the malignant phenotype of lung cancer cells, control their growth capacity and activate their differentiation into myofibroblasts. These findings could lead to new strategies for lung cancer management.
Background Non-invasive oxygenation strategies have a prominent role in the treatment of acute hypoxemic respiratory failure during the coronavirus disease 2019 (COVID-19). While the efficacy of these therapies has been studied in hospitalized patients with COVID-19, the clinical outcomes associated with oxygen masks, high-flow oxygen therapy by nasal cannula and non-invasive mechanical ventilation in critically ill intensive care unit (ICU) patients remain unclear. Methods In this retrospective study, we used the best of nine covariate balancing algorithms on all baseline covariates in critically ill COVID-19 patients supported with > 10 L of supplemental oxygen at one of the 26 participating ICUs in Catalonia, Spain, between March 14 and April 15, 2020. Results Of the 1093 non-invasively oxygenated patients at ICU admission treated with one of the three stand-alone non-invasive oxygenation strategies, 897 (82%) required endotracheal intubation and 310 (28%) died during the ICU stay. High-flow oxygen therapy by nasal cannula ( n = 439) and non-invasive mechanical ventilation ( n = 101) were associated with a lower rate of endotracheal intubation (70% and 88%, respectively) than oxygen masks ( n = 553 and 91% intubated), p < 0.001. Compared to oxygen masks, high-flow oxygen therapy by nasal cannula was associated with lower ICU mortality (hazard ratio 0.75 [95% CI 0.58–0.98), and the hazard ratio for ICU mortality was 1.21 [95% CI 0.80–1.83] for non-invasive mechanical ventilation. Conclusion In critically ill COVID-19 ICU patients and, in the absence of conclusive data, high-flow oxygen therapy by nasal cannula may be the approach of choice as the primary non-invasive oxygenation support strategy.
Background The extracellular volume (ECV) and intracellular volume (ICV) estimated by bioimpedance analysis (BIA) deviates markedly from the textbook volumes of 20% and 40% of the body weight (BW). We estimated the transcellular exchange of water by calculating solute equilibriums after fluid challenges to examine whether the BIA or the textbook volumes are likely to be most correct. Methods Data was retrieved from 8 healthy male volunteers who received 25 mL/kg of Ringer’s solution or 3–5 mL/kg of hypertonic (7.5%) saline over 30 min after the ECV and ICV had been estimated by BIA. The exchange of water between the ECV and the ICV was calculated according to a sodium equation and an osmolality equation. Simulations were performed, where deviating body fluid volumes were applied. Results The mean ECV measured with BIA was 24.9% of BW ( p < 0.05 versus the “textbook” volume). Mean ICV measured with BIA was 22.3% of BW ( p < 0.05). The sodium and osmolality equations correlated closely with respect to the translocation of water across the cell membrane ( r ² = 0.86). By applying the “textbook” ECV, the sodium equation indicated that Ringer’s solution exchanged negligible amounts of water, while hypertonic saline withdrew 1.4 L from the ICV to the ECV. By contrast, applying the BIA-derived ECV to the sodium equation implied that 3 L of water would be translocated from the ECV to the ICV once hypertonic saline was administered. Conclusion The “textbook” ECV and ICV volumes but not the BIA-derived volumes were consistent with the fluid shifts obtained by two solute equations.
First-episode psychosis (FEP) patients show structural brain abnormalities at the first episode. Whether the cortical changes that follow a FEP are progressive and whether age at onset modulates these changes remains unclear. This is a multicenter MRI study in a deeply phenotyped sample of 74 FEP patients with a wide age range at onset (15–35 years) and 64 neurotypical healthy controls (HC). All participants underwent two MRI scans with a 2-year follow-up interval. We computed the longitudinal percentage of change (PC) for cortical thickness (CT), surface area (CSA) and volume (CV) for frontal, temporal, parietal and occipital lobes. We used general linear models to assess group differences in PC as a function of age at FEP. We conducted post-hoc analyses for metrics where PC differed as a function of age at onset. We found a significant age-by-diagnosis interaction effect for PC of temporal lobe CT ( d = 0.54; p = 002). In a post-hoc-analysis, adolescent-onset (≤19 y) FEP showed more severe longitudinal cortical thinning in the temporal lobe than adolescent HC. We did not find this difference in adult-onset FEP compared to adult HC. Our study suggests that, in individuals with psychosis, CT changes that follow the FEP are dependent on the age at first episode, with those with an earlier onset showing more pronounced cortical thinning in the temporal lobe.
Neuroinflammation, in which activated microglia are involved, appears to contribute to the development of Parkinson’s disease (PD). However, the role of microglial activation and the mechanisms governing this process remain uncertain. We focused on one inhibitory mechanism involved in the control of microglial activation, the microglia inhibitory receptor CD200R1, and its ligand CD200, mainly expressed by neurons. The human CD200R1 gene encodes two membrane-associated and two soluble protein isoforms and the human CD200 gene encodes full-length proteins (CD200full) but also truncated (CD200tr) proteins which act as CD200R1 antagonists. Little is known about their expression in the human brain under pathological conditions. We used human peripheral blood monocytes and monocyte-derived microglia-like cells from control subjects to characterize the expression of the CD200R1 mRNA variants, which showed stimulus-specific responses. We provide evidence of increased CD200R1 (mRNA variants and protein isoforms) and CD200 expression (CD200tr mRNA) in brain tissue of PD patients, mainly in the hippocampus, as well as increased CD200 expression (CD200full and CD200tr mRNAs) in iPSCs-derived dopaminergic neurons generated from skin fibroblasts of PD patients. Our results suggest that CD200-CD200R1 signalling is altered in PD, which may affect the microglial function and constitute a potential target in therapeutic strategies for PD.
Background The detection of coinfections is important to initiate appropriate antimicrobial therapy. Molecular diagnostic testing identifies pathogens at a greater rate than conventional microbiology. We assessed both bacterial coinfections identified via culture or the BioFire® FilmArray® Pneumonia Panel (FA-PNEU) in patients infected with SARS-CoV-2 in the ICU and the concordance between these techniques. Methods This was a prospective study of patients with SARS-CoV-2 who were hospitalized for no more than 48 h and on mechanical ventilation for no longer than 24 h in 8 ICUs in Medellín, Colombia. We studied mini-bronchoalveolar lavage or endotracheal aspirate samples processed via conventional culture and the FA-PNEU. Coinfection was defined as the identification of a respiratory pathogen using the FA-PNEU or cultures. Serum samples of leukocytes, C-reactive protein, and procalcitonin were taken on the first day of intubation. We analyzed the empirical antibiotics and the changes in antibiotic management according to the results of the FA-PNEUM and cultures. Results Of 110 patients whose samples underwent both methods, FA-PNEU- and culture-positive samples comprised 24.54% versus 17.27%, respectively. Eighteen samples were positive in both techniques, 82 were negative, 1 was culture-positive with a negative FA-PNEU result, and 9 were FA-PNEU-positive with negative culture. The two bacteria most frequently detected by the FA-PNEU were Staphylococcus aureus (37.5%) and Streptococcus agalactiae (20%), and those detected by culture were Staphylococcus aureus (34.78%) and Klebsiella pneumoniae (26.08%). The overall concordance was 90.1%, and when stratified by microorganism, it was between 92.7 and 100%. The positive predictive value (PPV) was between 50 and 100% and were lower for Enterobacter cloacae and Staphylococcus aureus . The negative predictive value (NPV) was high (between 99.1 and 100%); MecA/C/MREJ had a specificity of 94.55% and an NPV of 100%. The inflammatory response tests showed no significant differences between patients whose samples were positive and negative for both techniques. Sixty-one patients (55.45%) received at least one dose of empirical antibiotics. Conclusions The overall concordance was 90.1%, and it was between 92.7% and 100% when stratified by microorganisms. The positive predictive value was between 50 and 100%, with a very high NPV.
Economic evaluations of public health interventions to prevent malaria should consider the adoption of wider perspectives and the inclusion of non-health impacts, particularly economic development outcomes, such as education. This is especially relevant in malaria elimination settings and in the context of the current SARS-CoV-2 pandemic.
Purpose Despite the benefits of mechanical ventilation, its use in critically ill patients is associated with complications and had led to the growth of noninvasive techniques. We assessed the effect of early intubation (first 8 h after vasopressor start) in septic shock patients, as compared to non-early intubated subjects (unexposed), regarding in-hospital mortality, intensive care and hospital length of stay. Methods This study involves secondary analysis of a multicenter prospective study. To adjust for baseline differences in potential confounders, propensity score matching was carried out. In-hospital mortality was analyzed in a time-to-event fashion, while length of stay was assessed as a median difference using bootstrapping. Results A total of 735 patients (137 intubated in the first 8 h) were evaluated. Propensity score matching identified 78 pairs with similar severity and characteristics on admission. Intubation was used in all patients in the early intubation group and in 27 (35%) subjects beyond 8 h in the unexposed group. Mortality occurred in 35 (45%) and in 26 (33%) subjects in the early intubation and unexposed groups (hazard ratio 1.44 95% CI 0.86–2.39, p = 0.16). ICU and hospital length of stay were not different among groups [9 vs. 5 (95% CI 1 to 7) and 14 vs. 16 (95% CI − 7 to 8) days]. All sensitivity analyses confirmed the robustness of our findings. Conclusions An early approach to invasive mechanical ventilation did not improve outcomes in this matched cohort of patients. The limited number of patients included in these analyses out the total number included in the study may limit generalizability of these findings. Trial registration NCT02780466. Registered on May 19, 2016.
Background Transthyretin amyloidosis (ATTR amyloidosis) is a rare, life-threatening disease caused by the accumulation of variant or wild-type (ATTRwt amyloidosis) transthyretin amyloid fibrils in the heart, peripheral nerves, and other tissues and organs. Methods Established in 2007, the Transthyretin Amyloidosis Outcomes Survey (THAOS) is the largest ongoing, global, longitudinal observational study of patients with ATTR amyloidosis, including both inherited and wild-type disease, and asymptomatic carriers of pathogenic TTR mutations. This descriptive analysis examines baseline characteristics of symptomatic patients and asymptomatic gene carriers enrolled in THAOS since its inception in 2007 (data cutoff: August 1, 2021). Results This analysis included 3779 symptomatic patients and 1830 asymptomatic gene carriers. Symptomatic patients were predominantly male (71.4%) and had a mean (standard deviation [SD]) age of symptom onset of 56.3 (17.8) years. Val30Met was the most common genotype in symptomatic patients in South America (80.9%), Europe (55.4%), and Asia (50.5%), and more patients had early- versus late-onset disease in these regions. The majority of symptomatic patients in North America (58.8%) had ATTRwt amyloidosis. The overall distribution of phenotypes in symptomatic patients was predominantly cardiac (40.7%), predominantly neurologic (40.1%), mixed (16.6%), and no phenotype (2.5%). In asymptomatic gene carriers, mean (SD) age at enrollment was 42.4 (15.7) years, 42.4% were male, and 73.2% carried the Val30Met mutation. Conclusions This 14-year global overview of THAOS in over 5000 patients represents the largest analysis of ATTR amyloidosis to date and highlights the genotypic and phenotypic heterogeneity of the disease. ClinicalTrials.gov Identifier : NCT00628745.
Venous thrombo-embolic (VTE) disease is a common cause of complications in patients with cancer and is the second most common cause of death in oncology patients other than the malignant disease. Whilst symptomatic VTE comprises the majority of such presentations to an emergency department (ED), incidental pulmonary embolism (IPE) is an increasingly frequent reason for attendance. Many studies report that the consequences of IPE do not differ significantly from those with symptomatic presentations and thus most guidelines recommend using the same approach. The complexity of treatment in cancer patients due to increased prevalence of co-morbidities, higher risk of bleeding, abnormal platelet and renal function, greater risk of VTE recurrence, and medications with the risk of anticoagulant interaction are consistent across patients with symptomatic and IPE. One of the initial challenges of the management of IPE is the design of a pathway that provides both patients and clinicians with a seamless journey from the radiological diagnosis of IPE to their initial clinical workup and management. Increased access to ambulatory care has successfully reduced ED utilisation and improved clinical outcomes in high-risk non-oncological populations, such as those with IPE. In this clinical review, we consider IPE management, its workup, the conundrums it may present for emergency physicians and the need to consider emergency ambulatory care for this growing cohort of patients.
Background The World Health Organization (WHO) risk assessment algorithm for vertical transmission of HIV (VT) assumes the availability of maternal viral load (VL) result at delivery and early viral control 4 weeks after initiating antiretroviral treatment (ART). However, in many low-and-middle-income countries, VL is often unavailable and mothers’ ART adherence may be suboptimal. We evaluate the inclusion of the mothers’ self-reported adherence into the established WHO-algorithm to identify infants eligible for enhanced post-natal prophylaxis when mothers’ VL result is not available at delivery. Methods We used data from infants with perinatal HIV infection and their mothers enrolled from May-2018 to May-2020 in Mozambique, South Africa, and Mali. We retrospectively compared the performance of the WHO-algorithm with a modified algorithm which included mothers’ adherence as an additional factor. Infants were considered at high risk if born from mothers without a VL result in the 4 weeks before delivery and with adherence <90%. Results At delivery, 143/184(78%) women with HIV knew their status and were on ART. Only 17(12%) obtained a VL result within 4 weeks before delivery, and 13/17(76%) of them had VL ≥1000 copies/ml. From 126 women on ART without a recent VL result, 99(79%) had been on ART for over 4 weeks. 45/99(45%) women reported suboptimal (< 90%) adherence. A total of 81/184(44%) infants were classified as high risk of VT as per the WHO-algorithm. The modified algorithm including self-adherence disclosure identified 126/184(68%) high risk infants. Conclusions In the absence of a VL result, mothers’ self-reported adherence at delivery increases the number of identified infants eligible to receive enhanced post-natal prophylaxis.
The use of digital technology is increasing rapidly across surgical specialities, yet there is no consensus for the term ‘digital surgery’. This is critical as digital health technologies present technical, governance, and legal challenges which are unique to the surgeon and surgical patient. We aim to define the term digital surgery and the ethical issues surrounding its clinical application, and to identify barriers and research goals for future practice. 38 international experts, across the fields of surgery, AI, industry, law, ethics and policy, participated in a four-round Delphi exercise. Issues were generated by an expert panel and public panel through a scoping questionnaire around key themes identified from the literature and voted upon in two subsequent questionnaire rounds. Consensus was defined if >70% of the panel deemed the statement important and <30% unimportant. A final online meeting was held to discuss consensus statements. The definition of digital surgery as the use of technology for the enhancement of preoperative planning, surgical performance, therapeutic support, or training, to improve outcomes and reduce harm achieved 100% consensus agreement. We highlight key ethical issues concerning data, privacy, confidentiality and public trust, consent, law, litigation and liability, and commercial partnerships within digital surgery and identify barriers and research goals for future practice. Developers and users of digital surgery must not only have an awareness of the ethical issues surrounding digital applications in healthcare, but also the ethical considerations unique to digital surgery. Future research into these issues must involve all digital surgery stakeholders including patients.
Background The development of liver cirrhosis is usually an asymptomatic process until late stages when complications occur. The potential reversibility of the disease is dependent on early diagnosis of liver fibrosis and timely targeted treatment. Recently, the use of non-invasive tools has been suggested for screening of liver fibrosis, especially in subjects with risk factors for chronic liver disease. Nevertheless, large population-based studies with cost-effectiveness analyses are still lacking to support the widespread use of such tools. The aim of this study is to investigate whether non-invasive liver stiffness measurement in the general population is useful to identify subjects with asymptomatic, advanced chronic liver disease. Methods This study aims to include 30,000 subjects from eight European countries. Subjects from the general population aged ≥ 40 years without known liver disease will be invited to participate in the study either through phone calls/letters or through their primary care center. In the first study visit, subjects will undergo bloodwork as well as hepatic fat quantification and liver stiffness measurement (LSM) by vibration-controlled transient elastography. If LSM is ≥ 8 kPa and/or if ALT levels are ≥1.5 x upper limit of normal, subjects will be referred to hospital for further evaluation and consideration of liver biopsy. The primary outcome is the percentage of subjects with LSM ≥ 8kPa. In addition, a health economic evaluation will be performed to assess the cost-effectiveness and budget impact of such an intervention. The project is funded by the European Commission H2020 program. Discussion This study comes at an especially important time, as the burden of chronic liver diseases is expected to increase in the coming years. There is consequently an urgent need to change our current approach, from diagnosing the disease late when the impact of interventions may be limited to diagnosing the disease earlier, when the patient is asymptomatic and free of complications, and the disease potentially reversible. Ultimately, the LiverScreen study will serve as a basis from which diagnostic pathways can be developed and adapted to the specific socio-economic and healthcare conditions in each country. Trial registration This study is registered on Clinicaltrials.gov ( NCT03789825 ).
Background Acute mania is a psychiatric emergency requiring rapid management. However, randomised controlled trials (RCTs) have shown considerable individual differences in treatment effects on manic symptoms with antimanic drugs. Methods We searched the MEDLINE, CENTRAL, EMBASE, PsycINFO, and ClinicalTrials.gov to identify RCTs without language restrictions from inception to April 19, 2022. We included double-blind RCTs of oral antimanic monotherapy versus placebo in adult patients. The primary outcome was variability in improvement of manic symptoms (assessed using the coefficient of variation ratio [CVR]). The secondary outcomes were overall improvement of manic symptoms and acceptability (i.e., discontinuation for any reason). The pooled effects of outcomes were calculated by random-effects meta-analyses using restricted maximum likelihood methods. The quality of the included studies was assessed using the Cochrane Risk of Bias (ROB) Assessment Tool. This study was registered with OSF (DOI:10.17605/OSF.IO/G4JNY). Findings We included 39 RCTs (N=12150; mean age=39·9 years, interquartile range [IQR]=38·7-41·1; mean proportion of female=48·6%, IQR=42·3%-52·3%) and investigated 14 antimanic drugs. We found that eight antimanic drugs compared to placebo were associated with lower CVRs (95% confidence interval [CI]; I²), including risperidone (0·51; 0·37-0·70; 0%), haloperidol (0·54; 0·44-0·67; 4%), olanzapine (0·59; 0·44-0·79; 47%), ziprasidone (0·61; 0·53-0·71; 0%), lithium (0·63; 0·52-0·76; 0%), quetiapine (0·65; 0·48-0·87; 2%), aripiprazole (0·68; 0·56-0·84; 25%), and cariprazine (0·70; 0·49-0·99; 28%). There were nine antimanic drugs associated with greater efficacy than placebo, including risperidone (reported as standardised mean difference; 95% CI; I²: 0·64; 0·31-0·97; 15%), haloperidol (0·57; 0·29-0·85; 64%), cariprazine (0·51; 0·24-0·78; 0%), olanzapine (0·44; 0·30-0·58; 0%), lithium (0·42; 0·29-0·55; 0%), ziprasidone (0·42; 0·26-0·58; 0%), quetiapine (0·40; 0·13-0·67; 0%), asenapine (0·40; 0·13-0·67; 0%), and aripiprazole (0·32; 0·14-0·49; 53%). Ziprasidone (reported as risk ratio; 95% CI; I²: 0·83; 0·79-0·89; 0%) and olanzapine (0·63; 0·49-0·80; 35%) were associated with better acceptability relative to placebo. Among the 39 RCTs, none had a high ROB. Interpretation We demonstrated that eight antimanic drugs were associated with lower variability and better efficacy than placebo, suggesting that these antimanic drugs were associated with more homogenous and predictable improvements of manic symptoms in patients with acute mania. Funding The study was supported by from the Ministry of Science and Technology (MOST-110-2314-B-016-035, MOST-111-2314-B-016-054), Medical Affairs Bureau (MND-MAB-D-111102), and Tri-service General Hospital (TSGH-E-111229).
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Antoni Sisó Almirall
  • Servicio de Medicina Interna General
Carme Font
  • Servicio de Oncología
Christian Manzardo
  • Servicio de Enfermedades Infecciosas
Jose Inciarte
  • Servicio de Reumatología
Elena Arbelo
  • Servicio de Cardiología
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