Searching for bridges between psychopathology and real-world functioning in first-episode psychosis: A network analysis from the OPTiMiSE trial

BackgroundNetwork analysis has been used to explore the interplay between psychopathology and functioning in psychosis, but no study has used dedicated statistical techniques to focus on the bridge symptoms connecting these domains. The current study aims to estimate the network of depressive, negative, and positive symptoms, general psychopathology, and real-world functioning in people with first-episode schizophrenia or schizophreniform disorder, focusing on bridge nodes.MethodsBaseline data from the OPTiMiSE trial were analyzed. The sample included 446 participants (age 40.0 ± 10.9 years, 70% males). The network was estimated with a Gaussian graphical model, using scores on individual items of the positive and negative syndrome scale (PANSS), the Calgary depression scale for schizophrenia, and the personal and social performance scale. Stability, strength centrality, expected influence (EI), predictability, and bridge centrality statistics were computed. The top 20% scoring nodes on bridge strength were selected as bridge nodes.ResultsNodes from different rating scales assessing similar psychopathological and functioning constructs tended to cluster together in the estimated network. The most central nodes (EI) were Delusions, Emotional Withdrawal, Depression, and Depressed Mood. Bridge nodes included Depression, Conceptual Disorganization, Active Social Avoidance, Delusions, Stereotyped Thinking, Poor Impulse Control, Guilty Feelings, Unusual Thought Content, and Hostility. Most of the bridge nodes belonged to the general psychopathology subscale of the PANSS. Depression (G6) was the bridge node with the highest value.ConclusionsThe current study provides novel insights for understanding the complex phenotype of psychotic disorders and the mechanisms underlying the development and maintenance of comorbidity and functional impairment after psychosis onset.     

Baixa Concordância entre a Classificação da NYHA e as Variáveis do Teste de Exercício Cardiopulmonar em Pacientes com Insuficiência Cardíaca e Fração de Ejeção Reduzida

BackgroundThe New York Heart Association (NYHA) functional classification is the most commonly used classification system for heart failure (HF), whereas cardiopulmonary exercise testing (CPET) is the gold standard for functional status evaluation in HF.ObjectiveThis study aimed to analyze correlation and concordance between NYHA classes and CPET variables.MethodsHF patients with clinical indication for CPET and ejection fraction (EF) < 50% were selected. Correlation (Spearman coefficient) and concordance (kappa) between NYHA classification and CPET-based classifications were analyzed. A p < 0.05 was accepted as significant.ResultsIn total, 244 patients were included. Mean age was 56 ± 14 years, and mean EF was 35.5% ± 10%. Distribution of patients according to NYHA classification was 31.2%% class I, 48.3% class II, 19.2% class III, and 1.3% class IV. Correlation (r) between NYHA and Weber classes was 0.489 (p < 0.001), and concordance was 0.231 (p < 0.001). Correlation (r) between NYHA and ventilatory classes (minute ventilation/carbon dioxide production [VE/VCO₂] slope) was 0.218 (p < 0.001), and concordance was 0.002 (p = 0.959). Spearman correlation between NYHA and CPET score classes was 0.223 (p = 0.004), and kappa concordance was 0.027 (p = 0.606).ConclusionThere was a moderate association between NYHA and Weber classes, although concordance was low. Ventilatory (VE/VCO₂slope) and CPET score classes had a weak association and a low concordance with NYHA classes.     

Evaluation of Reduced Susceptibility to Quaternary Ammonium Compounds and Bisbiguanides in Clinical Isolates and Laboratory-Generated Mutants of Staphylococcus aureus

The MICs and minimum bactericidal concentrations (MBCs) for the biocides benzalkonium chloride and chlorhexidine were determined against 1,602 clinical isolates of Staphylococcus aureus. Both compounds showed unimodal MIC and MBC distributions (2 and 4 or 8 mg/liter, respectively) with no apparent subpopulation with reduced susceptibility. To investigate further, all isolates were screened for qac genes, and 39 of these also had the promoter region of the NorA multidrug-resistant (MDR) efflux pump sequenced. The presence of qacA, qacB, qacC, and qacG genes increased the mode MIC, but not MBC, to benzalkonium chloride, while only qacA and qacB increased the chlorhexidine mode MIC. Isolates with a wild-type norA promoter or mutations in the norA promoter had similar biocide MIC distributions; notably, not all clinical isolates with norA mutations were resistant to fluoroquinolones. In vitro efflux mutants could be readily selected with ethidium bromide and acriflavine. Multiple passages were necessary to select mutants with biocides, but these mutants showed phenotypes comparable to those of mutants selected by dyes. All mutants showed changes in the promoter region of norA, but these were distinct from this region of the clinical isolates. Still, none of the in vitro mutants displayed fitness defects in a killing assay in Galleria mellonella larvae. In conclusion, our data provide an in-depth comparative overview on efflux in S. aureus mutants and clinical isolates, showing also that plasmid-encoded efflux pumps did not affect bactericidal activity of biocides. In addition, current in vitro tests appear not to be suitable for predicting levels of resistance that are clinically relevant.     

Biliary Complications in Orthotopic Liver Transplantation Using Choledochocholedochostomy with a T-tube

Despite significant advances in orthotopic liver transplantation (OLT), biliary tract reconstruction is still a major source of complications. Choledochocholedochostomy with a T-tube used to be the standard procedure for biliary reconstruction after OLT. However, many centers currently avoid use of the T-tube because of the high incidence of complications. Our aim was to study the biliary complications occurring at our center when end-to-end choledochocholedochostomy (EE-CC) over a T-tube was used as the standard procedure for biliary reconstruction. A retrospective review was conducted of all patients who underwent liver transplantation from February 1, 1996, to April 30, 2010. Only patients requiring any therapy to treat biliary complications were considered, whereas those with concomitant hepatic artery complications were excluded. The study cohort consisted of 743 patients who had EE-CC with a T-tube.Of these, 73 patients (9.8%) experienced any biliary complication. Anastomotic strictures occurred in 17 patients (2.3%), and non-anastomotic strictures in 2 (0.3%). Fifteen patients with anastomotic strictures were successfully treated by dilatation and stenting. Bile leakage was diagnosed in 39 patients (5.2%). Leakage occurred at the anastomosis in 15 patients (2%), and at the exit site of the T-tube in 24 patients (3.2%). Tube opening was the only treatment used in 30 patients with bile leakage (76.9%). Seven patients experienced leaks after elective T-tube removal (1%). Overall, repeat surgery to manage biliary complications was needed in 9 patients (1.2%). The mortality rate from biliary complications was 0.13%. In conclusion, EE-CC with a T-tube was followed by a low incidence of biliary complications. The complication rate after elective T-tube removal and the repeat surgery rate were extremely low. These results might challenge the current trend to avoid T-tube stenting in OLT.     

25 hydroxyvitamin D serum levels influence adequate response to bisphosphonate treatment in postmenopausal osteoporosis

It remains unclear whether vitamin D sufficiency optimizes response to bisphosphonate (BP) treatment in postmenopausal osteoporosis. We evaluated the role and possible mechanisms of vitamin D in adequate response to standard BP treatment for postmenopausal osteoporosis.MethodsWe included 120 postmenopausal osteoporotic women (aged 68 ± 8 years) receiving BP (alendronate or risedronate) at their annual follow-up, performing complete anamnesis, including treatment adherence, use of vitamin D supplements, and previous falls and fractures during the last year. We analyzed the evolution of bone mineral density (BMD) during this period and serum PTH and 25 hydroxyvitamin D (25(OH)D) and urinary NTx levels. Patients were classified as inadequate responders to antiosteoporotic treatment based on BMD loss > 2% and/or the presence of fragility fractures during the last year.ResultsThirty percent of patients showed inadequate response to BP treatment, with significantly lower levels of 25(OH)D (22.4 ± 1.3 vs. 26.6 ± 0.3 ng/ml, p = 0.01), a higher frequency of 25(OH)D levels < 30 ng/ml (91% vs. 69%, p = 0.019) and higher urinary NTx values (42.2 ± 3.9 vs. 30.9 ± 2.3 nM/mM, p = 0.01). Patients with 25(OH)D > 30 ng/ml had a greater significant increase in lumbar BMD than women with values < 30 ng/ml (3.6% vs. 0.8%, p < 0.05). The probability of inadequate response was 4-fold higher in patients with 25(OH)D < 30 (OR, 4.42; 95% CI, 1.22–15.97, p = 0.02).ConclusionsInadequate response to BP treatment is frequent in postmenopausal women with osteoporosis as is vitamin D insufficiency, despite vitamin D supplementation. Maintenance of 25(OH)D levels > 30 ng/ml is especially indicated for adequate response to BP treatment.     

Disease Progression in the Contralateral Carotid Artery after Endarterectomy

Our objectives were to establish the incidence and progression of stenotic lesions in the contralateral carotid artery (CCA) after endarterectomy, to identify subpopulations of patients at risk of contralateral disease progression, and to evaluate the efficacy of duplex scanning surveillance at detecting these lesions. We performed a prospective study on 180 patients in whom the CCA to the operated artery was healthy or showed <70% stenosis. All patients had completed a clinical and hemodynamic follow-up program, including duplex scanning of both carotids, with sessions 3 and 6 months after surgery and then every semester until 2 years. Thereafter, examinations were scheduled according to the severity of stenosis. Mean follow-up time was 26.2 months (range 1.6-67.6). Disease progression was observed in 26 lesions (15%), nine of which (5.5%) progressed to severe stenosis (SS). Kaplan-Meier event-free rates of any disease progression were 89%, 88%, 82%, and 79% for 1, 2, 3, and 4 years, respectively. Event-free rates of progression to SS were 98%, 96%, 93%, and 90.6%, respectively, for 1, 2, 3, and 4 years. The risk of progression to SS was five times higher for stenoses that were moderate at the start of the study (p = 0.025). Severe contralateral stenoses were more common and appeared later during follow-up than ipsilateral restenoses. Progression of contralateral stenotic lesions is not uncommon and is essentially related to the presence of a moderate lesion at the start of follow-up. Indeed, moderate stenosis is a risk factor for progression to SS, which appears later and more frequently than ipsilateral restenosis. It therefore seems that patients with a moderate contralateral lesion would benefit from long-term duplex ultrasound surveillance.